Use of ammonium ferric citrate and organic acid complex thereof in preparation of drug for preventing and treating diseases in animals

Abstract

The present invention belongs to the technical field of veterinary pharmaceuticals, and specifically to the use of ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof in the preparation of a drug for preventing or treating a disease in animals. The ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof, and the pharmaceutical composition comprising the ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof provided by the present invention exhibit significant growth-inhibitory activity against intestinal coccidia in animals, diarrhoea viruses in animals, and pathogenic bacteria to which animals are susceptible, and have therapeutic efficacy against diseases caused by their infections.

Description

[0001] USE OF AMMONIUM FERRIC CITRATE AND ORGANIC ACID COMPEEX THEREOF IN PREPARATION OF DRUG FOR PREVENTING AND TREATING DISEASES IN ANIMAES

[0002] Technical Field

[0003] The present invention relates to the technical field of veterinary pharmaceuticals, and specifically to the use of ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof in the preparation of a drug for preventing or treating a disease in animals. The present invention further relates to a pharmaceutical composition comprising ammonium ferric citrate or an organic acid complex thereof or a salt of the organic acid complex thereof.

[0004] Background Art

[0005] Animal diseases such as diarrhoea and respiratory diseases in animals are prevalent health issues in the animal breeding industry. They not only affect animal survival rates and growth development but also significantly reduce feed conversion efficiency, leading to substantial economic losses for the industry. According to the 2022 annual report of the Ministry of Agriculture and Rural Affairs of the People's Republic of China, the direct nation-wide economic losses caused by diseases in animals exceed 100 billion CNY annually. Based on etiological classification, the pathogens causing diseases in animals are mainly divided into four major types: viruses, bacteria, parasites, and environmental factors. Current prevention and control strategies primarily involve the use of vaccines and antiviral drugs. However, pathogenic viruses often have complex genotypes, vaccine efficacy in terms of prevention and control is not ideal and costs are high. For some viruses like porcine transmissible gastroenteritis virus, no effective vaccine is available, leaving sole reliance on single control measures like isolation and disinfection. In the process of the use of antiviral drugs, it has been found that traditional antiviral drugs are ineffective against viral diarrhoea in pigs and easily lead to drug resistance. Some small-molecule drugs showing viral inhibitory effects in vitro and in short-term animal experiments only have a single mechanism of action and lack broad-spectrum and long-lasting efficacy. Given the characteristics of rapid viral mutation andprevalent mixed infections, there is an urgent need to develop novel antiviral compounds.

[0006] Summary of the Invention

[0007] Based on this, the present invention provides the use of ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof in the preparation of a drug for preventing or treating a disease in animals, and also provides a pharmaceutical composition comprising ammonium ferric citrate or an organic acid complex thereof or a salt of the organic acid complex thereof.

[0008] In order to achieve the objects of the present invention, the following technical solutions are adopted:

[0009] The present invention relates to the use of ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof in the preparation of a drug for preventing or treating a disease in animals.

[0010] The ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof serve as a drug for preventing or treating a disease in animals, wherein the therapeutically effective amount of the active ingredient of the drug, i.e. ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof, calculated as Fe, is 20-1,000 ppm.

[0011] In some technical solutions, the disease in animals is mastitis in dairy cows. In some technical solutions, the disease in animals is blue ear disease in pigs caused by an infection with porcine reproductive and respiratory syndrome virus.

[0012] In some technical solutions, the disease in animals is diarrhoea in animals. Further, the diarrhoea in animals is bacterial infectious diarrhoea in animals, viral infectious diarrhoea in animals, or coccidial infectious diarrhoea in animals.

[0013] Specifically, the viral infectious diarrhoea in animals is diarrhoea in pigs caused by an infection with porcine rotavirus, porcine epidemic diarrhoea virus, and porcine transmissible gastroenteritis virus.

[0014] Specifically, the coccidial infectious diarrhoea is diarrhoea in animals caused by an infection with Eimeria maxima, Eimeria mitis, Eimeria tenella, Eimeria necatrix, Eimeria acervulina, Eimeria auburnensis, Eimeria bovis, Eimeria zuernii, Eimeria debliecki, Eimeria stiedai, Eimeria perforans, Eimeria canis, and Eimeria brunetti.The animals are livestock, poultry, and pets. The livestock are preferably pigs, cattle, sheep, and rabbits. The poultry are preferably broilers, layers, ducks, meat pigeons, geese, and quails. The pets are preferably dogs or cats.

[0015] Further, the animals are young livestock, poultry, and pets.

[0016] In some technical solutions, the organic acid complex of ammonium ferric citrate comprises ammonium ferric citrate and an organic acid, wherein 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.

[0017] Further, the organic acid is fumaric acid or maleic acid.

[0018] In some technical solutions, the organic acid complex of ammonium ferric citrate is a sodium salt of the organic acid complex of ammonium ferric citrate.

[0019] The present invention further relates to a pharmaceutical composition for preventing or treating a disease in animals, comprising a therapeutically effective amount, calculated as Fe, of 20-1,000 ppm of ammonium ferric citrate or an organic acid complex thereof or a salt of the organic acid complex thereof, and a pharmaceutically acceptable auxiliary material.

[0020] Further, the pharmaceutical composition further comprises an additional therapeutic drug.

[0021] The present invention further provides a method for preventing or treating a disease in animals, the method comprising administering to the animals ammonium ferric citrate or an organic acid complex thereof or a salt of the organic acid complex thereof; or administering to the animals a pharmaceutical composition comprising ammonium ferric citrate or an organic acid complex thereof or a salt of the organic acid complex thereof. The therapeutically effective amount of ammonium ferric citrate or the organic acid complex thereof or the salt of the organic acid complex thereof, calculated as Fe, is 20-1,000 ppm.

[0022] Specifically, the animals applicable to the method are livestock, poultry, and pets at various growth stages, preferably young livestock, poultry, and pets.

[0023] Experiments have confirmed that the ammonium ferric citrate or the organic acid complex thereof or the salt of the organic acid complex thereof provided by the present invention exhibit significant inhibitory effects on the growth and / or proliferation of bacteria to which animals are susceptible, animal viruses, and animal coccidia, possess broad-spectrum disease-resistant efficacy, and can be applied in the treatment or prevention of common diseases in livestock, poultry, and pets, thusproviding a safe and effective drug for preventing and treating animal diseases in animal breeding.

[0024] The foregoing content is merely a summary of certain aspects of the present invention, but is not limited to these aspects. The content involved above and in other aspects will be described more specifically and completely below.

[0025] Detailed Description of the Invention

[0026] The following detailed description is intended to enable those skilled in the art to implement different embodiments. The present invention intends to cover all alternative, modified and equivalent technical solutions, which are all included within the scope of the present invention as defined by the claims. Additionally, for clarity, some technical features of the present invention are described in multiple independent embodiments, respectively, but they may also be provided in combination or in the form of any suitable sub-combination in a single embodiment.

[0027] Ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof involved in the present invention Ammonium ferric citrate, also known as ammonium iron(III) citrate, citric acid iron ammonium and ferric(III) ammonium citrate, is an iron-red solid powder with an iron (Fe) content of 20%-22% and a market price of approximately 50-115 CNY / kg. Ammonium ferric citrate is a double salt of ferric citrate and ammonium citrate, i.e. an organic non-heme iron complex or iron salt composed of naturally occurring substances (iron with citric acid and ammonia). In foods or drugs, ammonium ferric citrate is used as an iron source in the treatment of elemental iron deficiency, is used as a food additive in the fortification of bread nutrition or is used as a dietary iron supplement, and is used as an anti-caking agent in the production of products containing a compounded sweetener and in the production of table salt. In the field of animal breeding, ammonium ferric citrate is used to alleviate the generation of H2S in rumen and as a non-heme iron source required for animal nutrition. Ammonium ferric citrate is one of the components in culture media for bacterial or viral cultivation.

[0028] A method for preparing an organic acid complex of ammonium ferric citrate comprises the following steps of:

[0029] (1) dissolving an organic acid in a solvent to obtain a solution of the organic acid;(2) dissolving ammonium ferric citrate in a solvent to obtain a solution of the ammonium ferric citrate;

[0030] (3) adding the solution of the ammonium ferric citrate to the solution of the organic acid to obtain a reaction solution, and stirring the reaction solution at 25°C-60°C for 1-4 h;

[0031] (4) stirring the reaction solution obtained in step (3) at room temperature for 4-15 h; and

[0032] (5) filtering the reaction solution obtained in step (4), and concentrating and drying the resulting filtrate to obtain the organic acid complex of ammonium ferric citrate comprising ammonium ferric citrate and the organic acid,

[0033] wherein the organic acid is an organic acid or acidic amino acid acceptable in pharmacy, foods and feeds, 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 solvents in step (1) and step (2) are solvents capable of solvating ammonium ferric citrate and the organic acid, and are selected from water, methanol, ethanol, an aqueous methanol solution, or an aqueous ethanol solution.

[0034] In some particular embodiments, the molar ratio of the ammonium ferric citrate to the organic acid in the preparation method is 1 : 1-3 : 1; preferably, the molar ratio of the ammonium ferric citrate to the organic acid is 2 : 1; more preferably, the organic acid is fumaric acid or maleic acid.

[0035] In some particular embodiments, in order to obtain an organic acid complex of ammonium ferric citrate or a salt thereof having a higher chemical purity and a lower impurity content, the preparation for the organic acid complex of ammonium ferric citrate or the salt thereof provided in the present invention further comprises: concentrating and drying the filtrate obtained in step (5) in the above-mentioned preparation method to obtain an organic acid complex of ammonium ferric citrate comprising the ammonium ferric citrate and the organic acid, and subjecting the complex to slurrying treatment in methanol, ethanol, an aqueous methanol solution or an aqueous ethanol solution to further remove impurities.

[0036] In some embodiments, in order to improve the solubility or effective utilization in an organism, the organic acid complex of ammonium ferric citrate can be prepared into a salt by a chemical synthesis method. Provided is a method for preparing a saltof the organic acid complex of ammonium ferric citrate, comprising the following steps:

[0037] (1) dissolving an organic acid salt in a solvent to obtain a solution of the organic acid salt;

[0038] (2) dissolving ammonium ferric citrate in a solvent to obtain a solution of the ammonium ferric citrate;

[0039] (3) adding the solution of the ammonium ferric citrate to the solution of the organic acid salt to obtain a reaction solution, and stirring the reaction solution for 1-4 h while heating;

[0040] (4) stirring the reaction solution obtained in step (3) at room temperature for 4-15 h; and

[0041] (5) filtering the reaction solution obtained in step (4), and concentrating and drying the resulting filtrate to obtain the salt of the organic acid complex of ammonium ferric citrate comprising the ammonium ferric citrate and the organic acid salt,

[0042] wherein the organic acid salt is an organic acid salt or an acidic amino acid salt acceptable in pharmacy, foods and feeds, 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, aspartic acid or y-aminobutyric acid; and the solvents in step (1) and step (2) are solvents capable of solvating the ammonium ferric citrate and the organic acid salt, and are independently selected from water, methanol, ethanol, an aqueous methanol solution, or an aqueous ethanol solution. Preferably, the heating is performed at 25°C-60°C.

[0043] In some particular embodiments, the organic acid salt is a sodium salt of the organic acid, the product obtained by the above-mentioned method for preparing a salt of an organic acid complex of ammonium ferric citrate is a sodium salt of the organic acid complex of ammonium ferric citrate, and the molar ratio of the sodium ions to the organic acid in the sodium salt of the organic acid is 1 : 1-1 : 2. For example, taking fumaric acid as an example, the sodium salt of fumaric acid may include monosodium fumarate and disodium fumarate.

[0044] In some embodiments, the organic acid complex of ammonium ferric citrate and the salt thereof obtained by the above-mentioned preparation method further comprise at least one solvent capable of solvating ammonium ferric citrate, theorganic acid and a salt of the organic acid, wherein the solvent is selected from water, methanol, ethanol, or a combination thereof.

[0045] In some embodiments, the present invention provides an organic acid complex of ammonium ferric citrate, wherein the organic acid is selected from fumaric acid or maleic acid.

[0046] Fumaric acid is trans-butenedioic acid. Maleic acid is cis-butenedioic acid, which has the same molecular formula, same molecular weight, and same number of carboxyl groups as fumaric acid, and can be used as a substitute for fumaric acid in the preparation of an organic acid complex of ammonium ferric citrate.

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

[0048] In a particular embodiment, the organic acid complex of ammonium ferric citrate provided in the present invention comprises ammonium ferric citrate and fumaric acid, and a method for preparing the organic acid complex of ammonium ferric citrate comprises the following steps:

[0049] (1) dissolving fumaric acid in water to obtain a solution of fumaric acid;

[0050] (2) dissolving ammonium ferric citrate in water to obtain a solution of ammonium ferric citrate;

[0051] (3) adding the solution of ammonium ferric citrate to the solution of fumaric acid to obtain a reaction solution, and stirring the reaction solution at 50°C for 1-4 h;

[0052] (4) stirring the reaction solution obtained in step (3) at room temperature for 4-15 h; and

[0053] (5) filtering the reaction solution obtained in step (4), and concentrating and drying the resulting filtrate to obtain a fumaric acid complex of ammonium ferric citrate comprising ammonium ferric citrate and fumaric acid.

[0054] In some embodiments, in the above-mentioned method for preparing a fumaric acid complex of ammonium ferric citrate, the molar ratio of the ammonium ferric citrate to the fumaric acid is from 1 : 1 to 3 : 1, and the content of elements in the provided fumaric acid complex of ammonium ferric citrate is: C 23.8%-25.82%, H 4.09%-4.29%, N 5.74%-6.19%, O 45.12%-48.84%, andFe 16.13%-18.8%.

[0055] Further, the fumaric acid complex of ammonium ferric citrate provided in the present invention further comprises a certain amount of water.In a particular embodiment, in the above-mentioned method for preparing a fumaric acid complex of ammonium ferric citrate, the molar ratio of the ammonium ferric citrate to the fumaric acid is 2 : 1, and the content of elements in the provided fumaric acid complex of ammonium ferric citrate is: C 25.82%, H 4.09%, N 6.19%, and Fe 18.8%.

[0056] In some preparation schemes, the sodium salt of fumaric acid complex of ammonium ferric citrate provided in the present invention is prepared by the above-mentioned method, wherein step (1) of the preparation method involves dissolving sodium fumarate in water to obtain a solution of sodium fumarate.

[0057] In some particular preparation schemes, the sodium fumarate is monosodium fumarate, and the salt of the fumaric acid complex of ammonium ferric citrate is ammonium ferric citrate-monosodium fumarate.

[0058] In some particular preparation schemes, the sodium fumarate is disodium fumarate, and the salt of the fumaric acid complex of ammonium ferric citrate is ammonium ferric ci trate-di sodium fumarate.

[0059] Bioavailability studies on ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof involved in the present invention

[0060] The experiments for studying the bioavailability of the ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof provided by the present invention include: studies on pharmacokinetic characteristics; experiments for studying the inhibitory effects of a feed additive or feed comprising the ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof as main active ingredients against intestinal coccidia, porcine anti-blue ear virus, porcine diarrhoea viruses, and bacteria.

[0061] In the present invention, "inhibition" means a relative decrease in a designated activity in specific response, in the presence of the aforementioned ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof.

[0062] In studies on molecular integrity in animals, ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof demonstrated prominent stability in gastrointestinal tract and could reach theintestinal tract through the stomach in their intact form to exert their medicinal effects.

[0063] In anticoccidial study experiments, the intestinal coccidia include, but are not limited to, Eimeria maxima, Eimeria mitis, Eimeria tenella, Eimeria necatrix, Eimeria acervulina, Eimeria auburnensis, Eimeria bovis, Eimeria zuernii, Eimeria debliecki, Eimeria stiedai, Eimeria perforans, Eimeria canis, and Eimeria brunetti. The infection with these intestinal coccidia causes intestinal discomfort in animals, including but not limited to bloody feces and diarrhoea in animals.

[0064] Further, the intestinal coccidia are preferably Eimeria necatrix, Eimeria acervulina, and Eimeria tenella.

[0065] In anticoccidial study experiments, the intestinal coccidia include, but are not limited to, intestinal coccidia of the genera Isospora, Cryptosporidium, Sarcocystis, Toxoplasma, Neospora, Hammondia, and Besnoitia.

[0066] In experiments for studying anti -diarrhoea in pigs, the causes of the diarrhoea in pigs include, but are not limited to, porcine diarrhoea virus infection and / or transmission, coccidial infection, bacterial infection, and physiological stress reactions. The porcine diarrhoea virus includes, but is not limited to, porcine rotavirus, porcine transmissible gastroenteritis virus, and porcine epidemic diarrhoea virus.

[0067] In experiments for studying anti-blue ear virus in pigs, the porcine blue ear virus, also known as porcine reproductive and respiratory syndrome virus, causes clinical symptoms in infected and diseased pigs including but not limited to abortion in late pregnancy, stillbirths or weak piglets, premature or delayed farrowing, anorexia, fever, poor mammary gland development, and reduced milk production in sows; also including but not limited to dyspnea, death, eyelid edema, conjunctivitis, and even diarrhoea in diseased pigs; also including but not limited to coughing, sneezing, fever, arthritis or meningitis caused by secondary bacterial infections; also including but not limited to reduced semen quality of boar, decreased sperm motility, and even infertility in boars, thereby leading to diseases such as pulmonary inflammation, lymph node enlargement or haemorrhage, myocarditis, and pericardial effusion in diseased pigs.

[0068] In experiments for evaluating the therapeutic effect on mastitis in dairy cows, the mastitis in dairy cows is mammary gland inflammation caused by an infection with bacteria such as Staphylococcus aureus and Escherichia coli, characterized bysymptoms such as udder swelling and redness, udder pain, and abnormal milk quality.

[0069] Research results indicate that the ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof exhibit significant growth-inhibitory activity against intestinal coccidia, porcine blue ear virus, porcine diarrhoea virus, and bacteria. Furthermore, the ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof can also significantly improve growth performance in animals, specifically manifested as increased growth rate (weight gain) and improved feed conversion rate (reduced feed conversion ratio). Studies of drug metabolism also find that the residual components of ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof after metabolism in animals contain no antibiotics, and the Fe ion concentration is below 0.5 ppm, complying with food safety standards. These findings provide important basis for the ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof as and / or in the preparation of a safe and effective drug for preventing or treating a disease in animals.

[0070] Pharmaceutical composition involved in the present invention

[0071] A pharmaceutical composition comprising ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof and a pharmaceutically acceptable auxiliary material, wherein the amount of the ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof in the composition can effectively control the status of disease in animals.

[0072] The term “composition” involved in the present invention refers to a collection of compounds, which collection comprises one or more compounds that are used as the active ingredients.

[0073] In the present invention, the term “comprise” is an open-ended expression that encompasses both the content explicitly indicated in the present invention and the content from other aspects.

[0074] The pharmaceutically acceptable auxiliary material is a pharmaceutically acceptable carrier, auxiliary agent, diluent, excipient, vehicle, dispersant, suspending agent, surfactant, isotonic agent, thickening agent, emulsifier, preservative, solid adhesive or lubricant, or a combination thereof.The "carrier" involved in the present invention refers to a pharmaceutically acceptable substance that has the ability to carry active ingredients and improve their dispersibility, and exhibits good chemical stability and adsorbability. The auxiliary material involved in the present invention includes, but is not limited to, an ion exchanger, aluminum stearate, lecithin, serum protein, a buffer substance such as phosphate, glycine, sorbic acid, potassium sorbate, a mixture of glycerides of saturated vegetable fatty acids, water, a salt, an electrolyte, protamine sulphate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, a zinc salt, colloidal silicon, magnesium trisilicate, polyvinylpyrrolidone, polyacrylate, wax, lanolin, sugar, starch, cellulose and derivatives thereof, gum acacia powder, malt, gelatin, and talc powder; an auxiliary material such as cocoa butter and suppository wax; an oil such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, com oil, and soybean oil; a diol compound, such as propylene glycol and polyethylene glycol; an ester such as ethyl oleate, ethyl laurate, and agar; a buffer agent such as magnesium hydroxide and aluminum hydroxide; alginic acid, ethanol, a phosphate buffer solution, a lubricant such as sodium laurate, a colorant, a coating material, a sweetener, a flavouring agent, a perfume, a preservative, and an antioxidant.

[0075] The auxiliary agent is a wetting agent that induces the inherent viscosity of a substance, an adhesive that binds substances together, a disintegrating agent that breaks the entire sheet of a substance into many fine particles, a retention aid that reduces the friction between particles, or an anti-sticking agent that prevents materials from adhesion, and includes, but not limited to, magnesium stearate, talc powder, vegetable oil, magnesium lauryl sulphate, starch, starch slurry, water, inorganic salts, dextrin, powdered sugar, etc.

[0076] The “vehicle” involved in the present invention refers to a solvent required for dissolving or dispersing a solid, and includes, but not limited to, water, ethanol, glycerol, etc.

[0077] In some embodiments, the pharmaceutical composition further comprises one or more therapeutic agents.

[0078] The therapeutic agents include, but are not limited to, antimicrobial drugs, anticoccidial drugs, antiviral drugs, anthelmintics and health enhancers, veterinary antibiotics, or Chinese herbal medicines, or feed additives.Specifically, the feed additives include, but are not limited to, a premixed veterinary drug that has the functions of preventing animal diseases and promoting animal growth and can be mixed with a carrier or diluent and added to feeds for long-term use.

[0079] Use of ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof, and their pharmaceutical composition involved in the present invention

[0080] Based on bioavailability study results of the aforementioned ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof, the present invention provides the use of ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof, and a pharmaceutical composition comprising ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof, in the preparation of a drug for preventing or treating a disease in animals, especially for preventing or treating a disease in animals caused by viral, bacterial, or coccidial transmission or infection, demonstrating significant therapeutic effects.

[0081] The "prevent or treat" involved in the present invention refers to a method of reducing animal health risk by delaying and / or preventing the complete or partial onset, recurrence, or transmission of a disorder, disease, or condition, or by preventing an animal from developing a disorder, disease, or condition, or by reducing the risk of an animal developing a disorder, disease, or condition.

[0082] In some embodiments, the "treat" refers to ameliorating the disease or condition (i.e., slowing or stopping or alleviating the development of the disease or at least one of the clinical symptoms thereof) by means of administering to a diseased animal a therapeutic dose of the drug provided by the present invention.

[0083] In some other embodiments, the "treat" refers to palliating and / or ameliorating at least one clinical parameter by means of administering to a diseased animal a therapeutic dose of the drug provided by the present invention.

[0084] In some other embodiments, the "treat" refers to modulating the disease or condition either physically (e.g., stabilization of a perceptible symptom) or physiologically (e.g., stabilization of a physical parameter), or both, by means of administering to a diseased animal a therapeutic dose of the drug provided by the present invention.In some other embodiments, the "treat" refers to preventing or delaying the onset, occurrence or worsening of the disease or condition by means of administering to a diseased animal a therapeutic dose of the drug provided by the present invention.

[0085] The term "therapeutic dose" refers to an amount of a compound which, when administered to a diseased animal for treating a disease, is sufficient to provide a treatment effect on such a disease and may vary with the compound, the disease, the severity, and the condition, age, weight and gender of the animal to be treated.

[0086] In some specific embodiments, the drug provided by the present invention is used to prevent or treat a disease such as bloody feces caused by coccidial infection in poultry. At a therapeutic dose of 20-1,000 ppm, the drug can effectively control the occurrence of bloody feces in poultry, inhibit the growth of cocci dia in poultry, and simultaneously effectively promote weight gain in poultry. The pharmacologically active ingredients of the drug are the ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof provided by the present invention.

[0087] The poultry are preferably broilers, layers, ducks, meat pigeons, geese, and quails, and further preferably young broilers, layers, ducks, meat pigeons, geese, and quails.

[0088] The coccidia are intestinal coccidia, including but not limited to, Eimeria maxima, Eimeria mitis, Eimeria tenella, Eimeria necatrix, Eimeria acervulina, Eimeria auburnensis, Eimeria bovis, Eimeria zuernii, Eimeria debliecki, Eimeria stiedai, Eimeria perforans, Eimeria canis, Eimeria brunetti, and intestinal coccidia of the genera Isospora, Cryptosporidium, Sarcocystis, Toxoplasma, Neospora, Hammondia, and Besnoitia. The infection with these intestinal coccidia causes intestinal discomfort in animals, including but not limited to bloody feces and diarrhoea in animals. Further, the intestinal coccidia are preferably Eimeria necatrix, Eimeria acervulina, and Eimeria tenella.

[0089] In some specific embodiments, the drug provided by the present invention is used to prevent or treat livestock diseases such as diarrhoea, fever, and mastitis caused by coccidial infection, diarrhoea virus infection, bacterial infection, or porcine blue ear virus infection, or mixed infections thereof in livestock. At a therapeutic dose of 250-1,000 ppm, the drug can effectively control the diarrhoea rate in livestock, while increasing feed intake in livestock, promoting weight gain inanimals, and reducing feed conversion ratio to improve feed conversion rate. The pharmacologically active ingredients of the drug are the ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof provided by the present invention.

[0090] Further, the drug provided by the present invention, when used to prevent or treat livestock diseases caused by coccidial infection, diarrhoea virus infection, bacterial infection, or porcine blue ear virus infection, or mixed infections thereof in livestock, can effectively reduce the viral load in animals, achieving a viral load decrease rate of 61%-84%.

[0091] Further, the drug provided by the present invention, when used to prevent or treat livestock diseases caused by coccidial infection, diarrhoea virus infection, bacterial infection, or porcine blue ear virus infection, or mixed infections thereof in livestock, can effectively eliminate bacteria at the infection site in animals, with an elimination rate of 79%-93%. The efficacy is similar or equivalent to that of standard antibiotic treatment, and no antibiotic residues are found in the animals. The metabolite residues comply with the requirements of food safety standards, ensuring the production quality of food-producing animals.

[0092] The livestock are preferably pigs, cattle, sheep, and rabbits, and further preferably piglets, calves, lambs, and young rabbits.

[0093] The coccidia are intestinal coccidia, including but not limited to, Eimeria maxima, Eimeria mitis, Eimeria tenella, Eimeria necatrix, Eimeria acervulina, Eimeria auburnensis, Eimeria bovis, Eimeria zuernii, Eimeria debliecki, Eimeria stiedai, Eimeria perforans, Eimeria canis, Eimeria brunetti, and intestinal coccidia of the genera Isospora, Cryptosporidium, Sarcocystis, Toxoplasma, Neospora, Hammondia, and Besnoitia. The infection with these intestinal coccidia causes intestinal discomfort in animals, including but not limited to bloody feces and diarrhoea in animals.

[0094] Method for preventing or treating a disease in animals involved in the present invention

[0095] The present invention further provides a method for preventing or treating a disease in animals, effectively preventing or treating a disease in animals caused by viral, bacterial, or coccidial transmission or infection. The method comprises administering to animals a drug involved in the present invention, wherein the pharmacologically active ingredient of the drug comprises ammonium ferric citrateor an organic acid complex thereof or a salt of the organic acid complex thereof, or a pharmaceutical composition comprising ammonium ferric citrate or an organic acid complex thereof or a salt of the organic acid complex thereof. The therapeutically effective amount of ammonium ferric citrate or the organic acid complex thereof or the salt of the organic acid complex thereof, calculated as Fe, is 20-1,000 ppm.

[0096] Specifically, the animals applicable to the method are livestock, poultry, and pets at various growth stages, preferably young livestock, poultry, and pets.

[0097] The following describes a method of using the drug involved in the present invention. A method of using the drug in the treatment of a disease in animals comprises administering to a diseased animal a therapeutic dose of ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof, or a pharmaceutical composition comprising a therapeutic dose of ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof. The pharmaceutical composition of the present invention may be manufactured according to those conventional methods disclosed in the art. The pharmaceutical composition is in a particular target dosage form suitable for therapeutic purposes. The ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof is administered in admixture with a suitable pharmaceutical diluent, excipient, carrier, etc. selected in accordance with administration form and conventional pharmaceutical practice, e.g., administered in an oral dosage form via a suitable carrier.

[0098] The pharmaceutical composition is used in the treatment of a disease in animals. The oral dosage form includes, but is not limited to, enteric-coated oral dosage forms of tablets, pills or capsules. The oral dosage form containing the pharmaceutical composition of the present invention is administered to a diseased animal via drenching, drinking water or in admixture with a feed by a breeder or a veterinarian.

[0099] The dosage regimen of the drug designed by the present invention will vary depending on a variety of known factors, such as the pharmacokinetic characteristics and mode, and route of administration of a particular reagent; the type, age, and body weight of a diseased animal; the nature and extent of a symptom; the type of parallel treatment; the frequency of medication in treatment; and the route of administration and the desired therapeutic effect. A veterinarian can make a decision and prescribean effective amount of a drug to prevent, restrain, alleviate, or slow the development of the symptom of a disease.

[0100] Based on the pharmacokinetic study results of ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof provided by the present invention and the physicochemical properties of the compounds themselves, the drug involved in the present invention can be in the form of tablets, pulvis, powders, aqueous solutions, or injections. Routes of administration include, but are not limited to, intramuscular injection, intravenous injection, aerosolization, and cavity administration. The cavity administration includes but is not limited to intramammary injection and intrauterine injection.

[0101] The pharmaceutical composition of the present invention is prepared into a unit dosage form according to a preparation formula, to reduce the dosage and ensure the uniformity of dosage units. Each unit dose of a preparation suitable for administration may contain from 1 mg to 100 mg of ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof. In these dosage forms, the weight of the active ingredient generally accounts for 0.5%-95% of the total weight of the composition.

[0102] The above-mentioned "unit dose" refers to a physically discrete unit of a drug required for an appropriate treatment in an organism.

[0103] Detailed Description of Embodiments

[0104] In order to make the purposes, technical solutions and advantages of the present invention clearer, the technical solutions of the present invention are further illustrated in detail below by way of examples. It should be understood that the specific examples described herein are merely used to explain the present invention, but are not intended to limit the present invention.

[0105] Example 1 Study on molecular integrity of ammonium ferric citrate and a fumaric acid complex thereof in animals

[0106] To evaluate the effective concentration maintenance capacity, molecular structure stability, and gastrointestinal degradation characteristics of ammonium ferric citrate and a fumaric acid complex thereof in animals, 40 healthy adult outbred experimental rats were selected and randomly divided into 4 treatment groups, with equal numbers of males and females. Among them, the first treatment group received ammonium ferric citrate at a single oral dose of 50 mg / kg, the second treatmentgroup received an fumaric acid complex of ammonium ferric citrate at a single oral dose of 50 mg / kg, the third treatment group received ammonium ferric citrate at an intravenous injection of 10 mg / kg, and the fourth treatment group received a fumaric acid complex of ammonium ferric citrate at an intravenous injection of 10 mg / kg. Plasma was collected from each treatment group at 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose. Digestive fluids at different time points within 0-8 hours were collected via catheterization, and feces were collected segmentally over 0-24 hours. High-performance liquid chromatography coupled with mass spectrometry (HPLC-MS / MS, quantification limit 0.1 pg / ml) was used to detect the concentration of the ammonium ferric citrate and the fumaric acid complex thereof. LC-MS was used to analyse the integrity of ammonium ferric citrate and the fumaric acid complex thereof in plasma / digestive fluids, and ultraviolet spectroscopy (UV) was used to detect the iron ion dissociation rate. Experimental results showed that intact molecules of ammonium ferric citrate and the fumaric acid complex thereof were detected 6 hours post-dose, and only 2.3% of the drug in the original form was excreted in feces within 24 hours.

[0107] Example 2 Inhibitory effects of different types of feed additives against Eimeria tenella in broilers

[0108] One-day-old fast-growing yellow-feathered broilers were raised in a coccidia-free environment. At 18 days of age, after microscopic examination confirmed the absence of coccidial oocysts in feces, they were grouped for the experiment. Weak or overweight chicks were culled, and healthy chicks with individual weight differences within 20 g were selected and divided into 13 groups, with 50 experimental chicks per group. Groups 1 and 2 were the unmedicated unchallenged control group and the coccidia-infected unmedicated control group, respectively. Groups 3-13 were experimental groups supplemented with different types of feed additives. On the day of experiment grouping, different feed additives were added to the feed according to Table 1, respectively. During the experiment, feed and water were provided ad libitum. Except for Group 1, 72 hours after the start of the experiment, 2.5 x 105sporulated oocysts of Eimeria tenella were administrated by gavage via ingluvies to each experimental broiler in each experimental group. On day 5 after challenge for infection, bloody feces scores were recorded for each experimental group. The experiment was ended on day 7 after challenge for infection.The relative weight gain rate (%), survival rate (%), and bloody feces score during the experiment were counted.

[0109] Bloody feces score: 0 points, no bloody feces; 1 point, less than 25% of feces with blood; 2 points, 25%-50% of feces with blood; 3 points, 50%-75% of feces with blood; 4 points, more than 75% of feces with blood.

[0110] Relative weight gain rate (%): The body weight of each broiler was measured at the beginning and end of the experiment, respectively, and the average weight gain and relative weight gain rate were calculated. Relative weight gain rate = (Average weight gain of experimental group / Average weight gain of uninfected unmedicated control group) x 100%.

[0111] Mortality: the number of dead broilers in each group was recorded, causes of death were determined via necropsy, and survival rate was calculated. Survival rate = (Total number of broilers in the experimental group - Number of broilers dead because of coccidial infection during the experiment) / Total number of broilers in experimental group x 100%.

[0112] Experimental results showed that feed additives comprising ammonium ferric citrate or a fumaric acid complex thereof or a salt of the fumaric acid complex thereof as main ingredients all exhibited varying degrees of inhibitory activity against Eimeria tenella. By comprehensively evaluating the three indicators of survival rate, bloody feces score, and relative weight gain rate, it was found that when the usage dosage of the main ingredient in the feed additive reached 250 ppm or above, the inhibitory activity against coccidia was the most significant. Compared to the unmedicated unchallenged control group, the growth rate of the experimental broilers increased significantly with increasing usage dosage of the feed additive.

[0113] Table 1 Inhibitory effects of different types of feed additives against Eimeria tenella in broilers

[0114] Survival Bloody Relative weight Main ingredient of feed Dosage

[0115] Group rate feces gain rate additive (ppm)

[0116] score

[0117] 1 - - 100% 0 100% 2 - - 70% 4 56.2% 3 Ammonium ferric citrate 20 100% 3 78.7% 4 Ammonium ferric citrate 100 100% 2 85.3 5 Ammonium ferric citrate 250 100% 1 95.5%6 Ammonium ferric citrate 500 100% 1 105.9% 7 Ammonium ferric citrate 1,000 100% 0 131.8% Fumaric acid complex of 100 100% 2 87.2%8

[0118] ammonium ferric citrate

[0119] Fumaric acid complex of 500 100% 1 99.4%9

[0120] ammonium ferric citrate

[0121] Fumaric acid complex of 1,000 100% 0 133.4%10

[0122] ammonium ferric citrate

[0123] Ammonium ferric citrate- 100 100% 2 83.7% 11

[0124] monosodium fumarate

[0125] Ammonium ferric citrate- 500 100% 1 97.9% 12

[0126] monosodium fumarate

[0127] Ammonium ferric citrate- 1,000 100% 0 127.5% 13

[0128] monosodium fumarate

[0129] Example 2 Inhibitory effects of different types of feed additives against Eimeria acervulina in broilers

[0130] One-day-old fast-growing yellow-feathered broilers were raised in a coccidia-free environment. At 18 days of age, after microscopic examination confirmed the absence of coccidial oocysts in feces, they were grouped for the experiment. Weak or overweight chicks were culled, and healthy chicks with individual weight differences within 20 g were selected and divided into 5 groups, with 50 experimental chicks per group. Groups 1 and 2 were the unmedicated unchallenged control group and the coccidia-infected unmedicated control group, respectively. Groups 3-5 were experimental groups supplemented with different types of feed additives. On the day of experiment grouping, different feed additives to be tested were added to the feed according to Table 2, respectively. During the experiment, feed was provided ad libitum. Except for Group 1, 72 hours after the start of the experiment, 4.0 * 105sporulated oocysts of Eimeria acervulina were administrated by gavage via ingluvies to each experimental broiler in each experimental group. The experiment was ended on day 7 after challenge for infection. The relative weight gain rate (%), survival rate (%), and feed conversion ratio during the experiment were counted. Experimental results showed that feed additives comprising ammonium ferric citrate, an fumaric acid complex of ammonium ferric citrate, or ammonium ferric citrate-monosodium fumarate as main ingredients, respectively, all had significant inhibitory activity against Eimeria acervulina. Bycomprehensively evaluating the three indicators of survival rate, relative weight gain rate, and feed conversion ratio, it was found that under the same addition dosage (1,000 ppm), the anticoccidial activities of these three feed additives were comparable. Compared to the unmedicated unchallenged control group, the experimental broilers not only showed improved growth rates but also significantly improved feed conversion rates, which was specifically manifested as a significant decrease in the feed conversion ratio.

[0131] Table 2 Inhibitory effects of different types of feed additives against Eimeria acervulina in broilers

[0132] Relative Feed Main ingredient of feed Dosage Survival

[0133] Group weight gain conversion additive (ppm) rate

[0134] rate ratio 1 - - 100% 100% 2.151 2 - - 100% 48.6% 3.078 3 Ammonium ferric citrate 1,000 100% 137.4% 2.047 Fumaric acid complex of 1,000 100% 140.1% 1.936 4

[0135] ammonium ferric citrate

[0136] Ammonium ferric citrate- 1,000 100% 133.6% 2.063 5

[0137] monosodium fumarate

[0138] Example 3 Inhibitory effects of different types of feed additives against Eimeria necatrix in broilers

[0139] One-day-old fast-growing yellow-feathered broilers were raised in a coccidia-free environment. At 18 days of age, after microscopic examination confirmed the absence of coccidial oocysts in feces, they were grouped for the experiment. Weak or overweight chicks were culled, and healthy chicks with individual weight differences within 20 g were selected and divided into 11 groups, with 50 experimental chicks per group. Groups 1 and 2 were the unmedicated unchallenged control group and the coccidia-infected unmedicated control group, respectively. Groups 3-11 were experimental groups supplemented with different types of feed additives. On the day of experiment grouping, different feed additives to be tested were added to the feed according to Table 3, respectively. During the experiment, feed was provided ad libitum. Except for Group 1, 72 hours after the start of the experiment, 1.0 * 105sporulated oocysts of Eimeria necatrix were administrated by gavage via ingluvies to each experimental broiler in each experimental group. On day 5 after challenge for infection, bloody feces scores were recorded for eachexperimental group. The experiment was ended on day 7 after challenge for infection. The relative weight gain rate (%), survival rate (%), and bloody feces score during the experiment were counted (the same as in Example 1).

[0140] Experimental results showed that feed additives comprising ammonium ferric citrate or a fumaric acid complex thereof or a salt of the fumaric acid complex thereof as main ingredients all exhibited varying degrees of inhibitory activity against Eimeria necatrix. By comprehensively evaluating the three indicators of survival rate, bloody feces score, and relative weight gain rate, it was found that when the usage dosage of the main ingredient in the feed additive reached 500 ppm or above, the inhibitory activity against Eimeria necatrix in broilers was the strongest. Compared to the unmedicated unchallenged experimental group, the growth rate of the experimental broilers was significantly improved (Table 3).

[0141] Table 3 Inhibitory effects of different types of feed additives against Eimeria necatrix in broilers

[0142] Survival Bloody Relative weight Main ingredient of feed Dosage

[0143] Group rate feces gain rate additive (ppm)

[0144] score

[0145] 1 - - 100% 0 100% 2 - . 58% 4 60.9% 3 Ammonium ferric citrate 100 100% 1 99.3% 4 Ammonium ferric citrate 500 100% 0 129.5% 5 Ammonium ferric citrate 1,000 100% 0 134.1% Fumaric acid complex of 100 100% 1 98.4% 6

[0146] ammonium ferric citrate

[0147] Fumaric acid complex of 500 100% 0 131.7% 7

[0148] ammonium ferric citrate

[0149] Fumaric acid complex of 1,000 100% 0 141.6% 8

[0150] ammonium ferric citrate

[0151] Ammonium ferric citrate- 100 100% 2 79.7% 9

[0152] monosodium fumarate

[0153] Ammonium ferric citrate- 500 100% 1 96.8% 10

[0154] monosodium fumarate

[0155] Ammonium ferric citrate- 1,000 100% 0 130.1% 11

[0156] monosodium fumarate

[0157] Example 4 Evaluation of therapeutic effect of ammonium ferric citrate and a complex thereof on porcine blue ear virus infectionFrom a population of fattening pigs confirmed positive for porcine blue ear virus, 60 pigs with similar body weights were selected and randomly divided into 6 treatment groups, with 10 pigs per group. The treatment scheme for each treatment group is shown in Table 4, including interventions with different doses of ammonium ferric citrate and a fumaric acid complex thereof (calculated as Fe, 250-1,000 ppm). Each treatment group was experimented on the same feeding management conditions. The test drugs were continuously administered in admixture with a feed for 10 days. Blood samples were collected from the experimental pigs in each group at pre-dose (day 0) and on day 10 post-dose. The quantitative PCR method was used to detect the porcine blue ear virus load in the blood, and changes in viral load at post-dose were calculated. Detection results showed that compared to pre-dose, the porcine blue ear virus load in each treatment group decreased significantly. Among them, the high-dose group (1,000 ppm Fe) showed better viral inhibitory effects than the low-dose group (250 ppm Fe). It can be seen that, within the usage dosage range of 250-1,000 ppm calculated as Fe, ammonium ferric citrate or the fumaric acid complex thereof exhibited significant anti-porcine blue ear virus activity.

[0158] Table 4 Study on therapeutic effect of ammonium ferric citrate and a complex thereof on porcine blue ear virus infection

[0159] Dosage Viral load decrease rate pre-dose vs Group Test drug

[0160] (ppm) post-dose

[0161] 1 Ammonium ferric citrate 250 61%

[0162] 2 Ammonium ferric citrate 500 72%

[0163] 3 Ammonium ferric citrate 1,000 80%

[0164] Fumaric acid complex of 68%

[0165] 4 250

[0166] ammonium ferric citrate

[0167] Fumaric acid complex of 77%

[0168] 5 500

[0169] ammonium ferric citrate

[0170] Fumaric acid complex of 1,000 84%

[0171] 6

[0172] ammonium ferric citrate

[0173] Example 5 Effects of different types of feed additives on growth performance and diarrhoea in piglets

[0174] One hundred and eighty of 45-day-old Duroc x Landrace x Yorkshire heterozygous lean piglets with similar weights were randomly divided into 9 treatment groups, with 2 replicates per group and 10 piglets per replicate (half maleand half female). The specific grouping was as shown in Table 5. Pigsty and utensils were disinfected before the experiment. In the experimental period, the animals were held in separate pens in the same pigsty under the same raising and management conditions. During the experiment, the experimental piglets had free access to food and water. Group 1 was the blank control group, and provided with nursery feeds only. Groups 2-3 were positive control groups fed zinc oxide and chlortetracycline, respectively. Groups 4-9 were experimental groups fed nursery feeds containing different addition amounts of ammonium ferric citrate or a fumaric acid complex of ammonium ferric citrate, respectively. No additional antioxidant ingredients and growth promoters were added to each experimental group throughout the raising process. The experimental period was 28 days, and the growth performance of the experimental piglets was recorded. The average daily feed intake (ADFI, g / d*the number of piglets), average daily gain (ADG, g / d*the number of piglets), feed conversion ratio (FCR) and diarrhoea rate of the experimental piglets were expressed as “mean values”, as shown in Table 4.

[0175] Feed conversion ratio (FCR) = average daily feed intake / average daily gain; Weight gain rate = (experimental group ADG - control group ADG) / control group ADG * 100%;

[0176] Feed intake increase rate = (experimental group ADFI - control group ADFI) / control group ADFI * 100%;

[0177] Feed conversion ratio decrease rate = (control group FCR - experimental group FCR) / control group FCR * 100%;

[0178] Diarrhoea ameliorating rate = (diarrhoea rate of experimental group - diarrhoea rate of control group) / diarrhoea rate of control group * 100%.Table 5 Effect of fumaric acid complex of ammonium ferric citrate on growth performance of piglets

[0179]

[0180] From the above-mentioned experimental results, it could be seen that the experimental groups provided with the nursery feeds containing ammonium ferric citrate or the fumaric acid complex thereof had obvious effects on improving the feed intake, average daily gain, feed conversion ratio and diarrhoea rate of the experimental piglets compared to those in the blank control group.

[0181] The experimental piglets provided with the nursery feeds containing ammonium ferric citrate had an increase of 12.54%-15.49% in the feed intake, an increase of 21 ,94%-30.83% in the body weight, a feed conversion ratio decrease rate of 8.08%-12.12%, and a decrease of 22.54%-68.57% in the diarrhoea rate.

[0182] The experimental piglets provided with the nursery feeds containing the fumaric acid complex of ammonium ferric citrate had an increase of 15.49%- 18.31% in the feed intake, an increase of 25.00%-33.89% in the body weight, a feed conversion ratio decrease rate of 13.85%- 18.08%, and a decrease of 36.55%-74.47% in the diarrhoea rate.

[0183] From the experimental results in Table 5, compared to the positive control groups, 500-1,000 ppm of ammonium ferric citrate or the fumaric acid complex thereof had effects similar to zinc oxide in controlling the diarrhoea rate in experimental piglets, and showed better animal breeding effects in terms of feed intake, weight gain, and feed conversion rate. Furthermore, when the usage dosage of ammonium ferric citrate or the fumaric acid complex thereof reached 250 ppm or above, it could achieve the application effects of chlortetracycline in animal breeding.

[0184] Example 6 Evaluation of therapeutic effect of ammonium ferric citrate and a complex thereof on diarrhoea caused by a mixed infection with porcine rotavirus and coccidia

[0185] Faecal samples from weaned piglets with severe diarrhoea were tested by RT-qPCR and microscopic examination, confirming positive for rotavirus (identified by RT-qPCR) and coccidia (identified by microscopic examination). Forty weaned piglets with diarrhoea and similar body weights were selected and randomly divided into 4 treatment groups (as shown in Table 6). Group 1 was the blank control group (no medication), and groups 2-4 were treatment groups with medication. Under the same feeding conditions, each treatment group was fed the drugs shown in Table 6 in admixture with a feed for 10 consecutive days. The administration dosage was calculated as Fe. Changes in the diarrhoea rate pre-dose vs post-dose were recordedand calculated. Experimental results showed that compared to the unmedicated control group, ammonium ferric citrate and the complex thereof had significant inhibitory effects on the growth of both porcine rotavirus and coccidia. The diarrhoea rates in diseased piglets receiving drug treatment decreased by 70%-90%, and diarrhoea symptoms were effectively controlled.

[0186] Table 6 Study on therapeutic effect of ammonium ferric citrate and a complex thereof on diarrhoea caused by a mixed infection in pigs Diarrhoea Diarrhoea Decrease Dosage rate before rate after rate of Group Test drug

[0187] (ppm) treatment treatment diarrhoea rate 1 - - 100% 100% 0 2 Ammonium ferric citrate 500 100% 30% 70% 3 Ammonium ferric citrate 1,000 100% 20% 80% Fumaric acid complex of 100% 10% 90% 4 1,000

[0188] ammonium ferric citrate

[0189] Example 7 Evaluation of effect of ammonium ferric citrate in treating mastitis in dairy cows

[0190] Fifty dairy cows with clinical mastitis, without other secondary infections in the mammary gland, were selected and randomly divided into 5 treatment groups. The treatment scheme for each treatment group is shown in Table 7. Group 1 was the negative control group, receiving physiological saline infusion treatment. Group 2 was the positive control group, receiving ceftiofur sodium treatment. Groups 3-5 received treatment with ammonium ferric citrate or a fumaric acid complex thereof. Each group of dairy cows was infused with 10 mL of solution according to the infusion operation method and the respective group's treatment method, once daily for 3 consecutive days. The udder was massaged after infusion, and milking was prohibited for 6 hours. Udder swelling and redness, pain, and milk character scores in dairy cows were recorded (0-3 points, 0 = normal), and the cure rate was calculated. Milk samples were taken before the experiment (day 0) and after the experiment ended (day 4). Somatic cell count (SCC) was determined by flow cytometry. The concentrations of Staphylococcus aureus and Escherichia coli were determined through bacterial culture, and the bacterial elimination rate was calculated after treatment. Antibiotic residues were detected by ELISA method (threshold: < 0.01 ppm). Free iron ion concentration was detected by HPLC-MS.Results are shown in Table 7. Experiment results showed that compared to the negative and positive control groups, ammonium ferric citrate and the fumaric acid complex thereof could effectively treat mastitis in dairy cows, with a cure rate of 73.2%-86.1%. Results of metabolite residues in dairy cow's milk after treatment showed no antibiotic residues, and Fe ion concentration was within safe threshold limits, complying with food safety standards.

[0191] Table 7 Study on effect of ammonium ferric citrate in treating mastitis in dairy cows

[0192] SCC Bacterial Treatment Cure rate

[0193] Group Metabolite residues decrease elimination method (72h)

[0194] rate rate ELISA negative

[0195] Physiological

[0196] 1 Fe ion concentration < 6.7% 12% 10% saline infusion

[0197] 0.5 ppm

[0198] ELISA positive

[0199] Ceftiofur

[0200] 2 Fe ion concentration < 80.0% 65% 85%

[0201] sodium

[0202] 0.5 ppm

[0203] 2% ammonium

[0204] ELISA negative

[0205] ferric citrate

[0206] 3 Fe ion concentration < 73.2% 57% 79%

[0207] solution

[0208] 0.5 ppm

[0209] infusion

[0210] 5% ammonium

[0211] ELISA negative

[0212] ferric citrate

[0213] 4 Fe ion concentration < 85.7% 70% 91%

[0214] solution

[0215] 0.5 ppm

[0216] infusion

[0217] Infusion of a

[0218] solution with

[0219] ELISA negative

[0220] 5% fumaric

[0221] 5 Fe ion concentration < 86.1% 72% 93% acid complex

[0222] 0.5 ppm

[0223] of ammonium

[0224] ferric citrate

Claims

CLAIMS1. Ammonium ferric citrate and an organic acid complex thereof or a salt of the organic acid complex thereof for use in the preparation of a drug for preventing or treating a disease in animals.

2. The use according to claim 1, characterized in that the disease in animals is mastitis in dairy cows.

3. The use according to claim 1, characterized in that the disease in animals is diarrhoea in animals.

4. The use according to claim 3, characterized in that the disease in animals is bacterial infectious diarrhoea in animals, viral infectious diarrhoea in animals, or coccidial infectious diarrhoea in animals.

5. The use according to claim 4, characterized in that the viral infectious diarrhoea in animals is diarrhoea in pigs caused by an infection with porcine rotavirus, porcine epidemic diarrhoea virus, and porcine transmissible gastroenteritis virus.

6. The use according to claim 4, characterized in that the coccidial infectious diarrhoea in animals is diarrhoea in animals caused by an infection with Eimeria maxima, Eimeria mitis, Eimeria tenella, Eimeria necatrix, Eimeria acervulina, Eimeria auburnensis, Eimeria bovis, Eimeria zuernii, Eimeria debliecki, Eimeria stiedai, Eimeria perforans, Eimeria canis, and Eimeria brunetti.

7. The use according to claim 1, characterized in that the animals are livestock; preferably pigs, cattle, sheep, and rabbits.

8. The use according to claim 1, characterized in that the animals are poultry; preferably broilers, layers, ducks, meat pigeons, geese, and quails.

9. The use according to claim 1, characterized in that the animals are pets; preferably, the pets are dogs or cats.

10. The use according to claim 1, characterized in that the disease in animals is blue ear disease in pigs caused by an infection with porcine reproductive and respiratory syndrome virus (PRRSV).

11. The use according to claim 1, characterized in that the organic acid complex comprises ammonium ferric citrate and an organic acid, wherein 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; preferably, the organic acid is fumaric acid or maleic acid.

12. The use according to claim 1, characterized in that the salt of the organic acid complex of ammonium ferric citrate is a sodium salt of the organic acid complex of ammonium ferric citrate.

13. The use according to claim 1, characterized in that a usage dosage of the ammonium ferric citrate and the organic acid complex thereof or the salt of the organic acid complex thereof, calculated as Fe, is 20-1,000 ppm.

14. A pharmaceutical composition, characterized in that the pharmaceutical composition comprises ammonium ferric citrate or an organic acid complex thereof or a salt of the organic acid complex thereof, and a pharmaceutically acceptable auxiliary material.

15. The pharmaceutical composition according to claim 14, characterized in that the pharmaceutical composition further comprises an additional therapeutic drug.

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