Veterinary composition for controlling iron deficiency in non-human mammals and its use

Abstract

The present invention relates to veterinary compositions comprising an iron complex and a water-soluble polymer as the only active ingredients. The present invention further relates to the use of such compositions for controlling iron deficiency and / or anemic conditions in non-human mammals.

Description

Technical Field

[0001] The present invention belongs to the field of veterinary medicine and relates to a preparation containing iron. The present invention further relates to the use of such a preparation for controlling iron deficiency and / or anemia conditions in non-human mammals.

Background Art

[0002] Newborn animals are prone to anemia caused by iron deficiency in the short period after birth. They are born with very little iron accumulation and receive too little iron from breast milk to ensure good growth. For example, in the pig industry, piglets are born with limited iron stores and, if born in the wild, depend on dietary supplementation from iron-containing soil. Indoors, pigs have no access to iron sources other than pig milk (iron-deficient) until they start eating feeding diets. Piglets are born with normal levels of hemoglobin in the blood of 12 - 13 g / 100 mL, which rapidly decreases to 6 - 7 g / 100 mL by 10 - 14 days of age. Iron deficiency results in a decrease in the level of hemoglobin in red blood cells (anemia), a decrease in the oxygen-carrying capacity in the body, an increased susceptibility to diseases, and a decrease or poor development of body weight. Severe iron deficiency anemia can sometimes lead to the death of young pigs.

[0003] Therefore, in order to overcome iron deficiency, it is necessary to give additional iron to newborn piglets. In this context, a whole series of quite different iron preparations, differing both in the type of iron compound and the mode of application, are commercially available for preventing iron deficiency anemia.

[0004] For example, Pharmacosmos and Ark Animal Care Ltd. offer an injectable solution containing iron(III) dextran, which is Uniferon (registered trademark and commercialized under the trademarks of Anaemex®. Ceva Sante Animale, SerumWerk, and Labiana provide injectable solutions containing a colloidal aqueous solution of beta-oxyhydroxyferric acid and dextran glucoheptonic acid (Gleptoferron, commercialized under the trademarks of Gleptosil®, Ursoferran®, and Gleptoferron 200 Labiana).

[0005] However, with the increasing number of offspring (in high-fertility sows) and the rapid growth of piglets, the above-mentioned commercially available preparations administered to piglets do not always meet farmers' expectations and cannot be hindered by their overall effectiveness in preventing anemia in piglets. Therefore, some iron suppliers recommend increasing the administration rate and / or administering a second injection before or at weaning. Increasing the administration rate is limited by the potential toxicity of iron in young animals. A second injection is labor-intensive and less effective. This is due to the fact that the hemodynamic activity of orally or intravenously administered iron decreases with age. Therefore, it is generally recommended to treat animals within the first three days of birth.

[0006] Therefore, the need remains today to develop new iron formulations with improved efficacy for controlling iron deficiency and / or anemia in non-human mammals. [Overview of the project]

[0007] In this context, the present inventors propose a veterinary composition comprising an iron complex combined with a water-soluble polymer.

[0008] Therefore, the present invention relates to a veterinary composition comprising an iron complex and a water-soluble polymer as the sole active ingredient.

[0009] In certain embodiments, the water-soluble polymer is selected from polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyacrylamide, N-(2-hydroxypropyl)methacrylamide, divinyl ether-maleic anhydride, polyoxazoline, polyphosphate, polyphosphazene, and mixtures thereof, and is preferably polyvinylpyrrolidone.

[0010] In certain embodiments, the water-soluble polymer has a concentration of 1 to 100 mg / mL, preferably 5 to 70 mg / mL, more preferably 7 to 60 mg / mL, and even more preferably 10 to 50 mg / mL.

[0011] In further specific embodiments, the veterinary composition further comprises an organic solvent, preferably at a concentration of 1 to 20 mg / mL, more preferably 5 to 10 mg / mL, and even more preferably 5 to 8 mg / mL.

[0012] In further specific embodiments, the veterinary composition further comprises a pharmaceutically acceptable salt and / or a surfactant having more than 8 HLB.

[0013] In preferred embodiments, the pharmaceutically acceptable salt has a concentration of 1 to 100 mg / mL, preferably 5 to 70 mg / mL, and more preferably 10 to 50 mg / mL.

[0014] In a further preferred embodiment, the surfactant having an HLB greater than 8 has a concentration of 0.01 to 10 mg / mL, preferably 0.5 to 8 mg / mL, and more preferably 1 to 5 mg / mL.

[0015] In a further preferred embodiment, the iron complex is selected from iron(2+)carboxylic acid complexes, iron(3+)carboxylic acid complexes, iron(2+) chelate complexes with amino acids, iron(3+) chelate complexes with amino acids, polynuclear iron(3+) polysaccharide complexes, and mixtures thereof.

[0016] In preferred embodiments, the polynuclear iron(3+) polysaccharide complex is selected from aqueous colloidal solutions of beta-oxyhydroxyhydroxydioxide and dextran glucoheptonic acid, iron(III) dextran, and iron(III) hydroxypolymaltose, and is preferably an aqueous colloidal solution of beta-oxyhydroxyhydroxydioxide and dextran glucoheptonic acid.

[0017] In a more preferred embodiment, the concentration of iron supplied as an iron complex is 50 to 300 mg / mL of iron element, preferably 100 to 200 mg / mL, and more preferably 120 to 150 mg / mL.

[0018] A further object of the present invention is a veterinary composition disclosed herein for use in controlling iron deficiency and / or anemia in non-human mammals.

[0019] In preferred embodiments, the non-human mammal is a pig, sheep, cattle, dog, or cat, preferably a piglet.

[0020] In a further preferred embodiment, the composition for use is administered by injection, preferably by intramuscular injection. [Modes for carrying out the invention]

[0021] The inventors provide a veterinary composition comprising an iron complex as the sole active ingredient and a water-soluble polymer. The presence of an effective amount of the water-soluble polymer in the composition can increase blood efficacy and improve the tissue distribution of the iron complex in non-human mammals. Therefore, the composition of the present invention can exhibit improved efficacy in controlling iron deficiency and / or anemia in non-human mammals compared to iron preparations currently in use. The composition of the present invention can also be well-tolerated and can improve weight development in non-human mammals.

[0022] composition Therefore, the present invention provides a veterinary composition comprising an iron complex and a water-soluble polymer as the sole active ingredient.

[0023] According to the present invention, the iron complex is the sole active ingredient. Therefore, the compositions of the present invention do not contain further active ingredients such as triazines, antibiotics, insecticides, endectides, anti-inflammatory agents, and anti-infective agents such as vitamins.

[0024] As used herein, “iron complex” includes any form of iron(2+) or 3(+) complex. In certain embodiments, the iron complex is selected from iron(2+) carboxylic acid complexes, iron(3+) carboxylic acid complexes, iron(2+) chelate complexes with amino acids, iron(3+) chelate complexes with amino acids, polynuclear iron(3+) polysaccharide complexes, and mixtures thereof.

[0025] Iron(2+) or -(3+) carboxylic acid complexes, and iron(2+) or -(3+) chelate complexes with amino acids, are complexed in a chelate-like manner. They form relatively stable iron complexes that are only partially decomposed into ions by stomach acid. Examples of iron(2+) carboxylic acid complexes that may be described include, but are not limited to, iron(II) lactate, iron(II) gluconate, or iron(II) fumarate, or their hydrates. Examples of iron(3+) carboxylic acid complexes include, for example, iron(III) citrate, iron ammonium(III) citrate, or their hydrates. Examples of iron(2+) chelate complexes with amino acids include iron(II) bisglycinate, iron(II) methionate, and their hydrates.

[0026] Polynuclear iron(3+) polysaccharide complexes exist in oligomeric or polymeric form and are associated in their coordination spheres as complexes with one or more of the above-mentioned oligomeric and polymeric carbohydrate compounds, such as hydroxide ions (OH) -) is understood to mean a complex of iron(III) ions with an aqueous base (H2O) and oxygen (O). Thus, the polynuclear iron(III) polysaccharide complex also includes polynuclear iron(III) hydroxide polysaccharide complexes and polynuclear iron(III) oxyhydroxide polysaccharide complexes. Examples of the polynuclear iron(III) polysaccharide complex include, but are not limited to, a polynuclear beta-FeO(OH) core complex, a polynuclear iron(III) polysaccharide complex compound containing a polymeric carbohydrate compound associated at free coordination sites, such as iron dextran(III), glucoheptonate of iron(III) dextran, iron(III) isomaltoside, iron(III) carboxymaltose, iron(III) hydroxypolymaltose, iron(III) sucrose, or iron(III) oligosaccharide.

[0027] In a preferred embodiment, the polynuclear iron(III) polysaccharide complex of the composition of the present invention is selected from an aqueous colloidal solution of beta-ferric oxyhydroxide and dextran glucoheptonate, iron(III) dextran, and iron(III) hydroxypolymaltose. In a more preferred embodiment, the polynuclear iron(III) polysaccharide complex is an aqueous colloidal solution of beta-ferric oxyhydroxide and dextran glucoheptonate (Gleptoferron, commercialized under the trademarks Gleptosil® or Ursoferran®). In an even more preferred embodiment, the polynuclear iron(III) polysaccharide complex is ferric hydroxide having a low molecular weight dextran such as a product commercialized under the trademark Uniferon® or Dexafer®, or ferric hydroxide having a high molecular weight dextran such as a product commercialized under the trademark Ferroforte®.

[0028] In certain embodiments, the concentration of iron supplied from the iron complexes disclosed herein is from 50 to 300 mg / mL of iron element, preferably from 100 to 200 mg / mL, more preferably from 120 to 150 mg / mL. In a more preferred embodiment, the concentration of iron supplied as the iron complex is an amount of about 50, 100, 133, 133.3, 133.4, 133.5, 150, 200, 250, 300 mg of iron element per 1 mL of the composition. In an even more preferred embodiment, the concentration of iron supplied as the iron complex is an amount of about 133.4 mg of iron element per 1 mL of the composition or about 200 mg of iron element per 1.5 mL of the composition.

[0029] According to the present invention, the concentration of iron supplied as or in the form of an iron complex in the composition corresponds to the concentration of the iron element. Thus, it is well understood that the concentration of the iron complex in the composition can vary depending on the nature of the complex. One skilled in the art can readily adapt the concentration of the iron complex by knowing the concentration of the iron element added to the composition.

[0030] A water-soluble polymer is a natural or synthetic substance that dissolves, disperses, or swells in water and thus modifies the physical properties of an aqueous system in the form of gelling, thickening, or emulsifying / stabilizing. It has repeating units or blocks of units that form polymer chains with hydrophilic groups incorporated into the backbone of the polymer chains or that replace the polymer chains.

[0031] Preferred water-soluble polymers of the present invention are selected from polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyacrylamide, N-(2-hydroxypropyl)methacrylamide, divinyl ether-maleic anhydride, polyoxazoline, polyphosphate, polyphosphazene, and mixtures thereof. In a more preferred embodiment, the water-soluble polymer is polyvinylpyrrolidone (povidone).

[0032] In certain embodiments, the water-soluble polymers disclosed herein have a concentration of 1 to 100 mg / mL, preferably 5 to 70 mg / mL, more preferably 7 to 60 mg / mL, and even more preferably 10 to 50 mg / mL. In more preferred embodiments, the water-soluble polymer is present in an amount of about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, or 55 mg per 1 mL of composition. In even more preferred embodiments, the water-soluble polymer is present in an amount of about 10 or 50 mg per 1 mL of composition, or about 15 or 75 mg per 1.5 mL of composition.

[0033] Preferred compositions according to the present invention, -50 to 300 mg / mL, preferably 100 to 200 mg / mL, more preferably 120 to 150 mg / mL, the concentration of iron element supplied as the sole active ingredient disclosed herein, A veterinary composition comprising a concentration of a water-soluble polymer disclosed herein, ranging from -1 to 100 mg / mL, preferably 5 to 70 mg / mL, preferably 7 to 60 mg / mL, and more preferably 10 to 50 mg / mL.

[0034] A more preferred composition according to the present invention is: -The iron complex supplied as the sole active ingredient disclosed herein has a concentration of approximately 133.4 mg / mL of elemental iron, - A veterinary composition containing polyvinylpyrrolidone at a concentration of approximately 10 or 50 mg / mL.

[0035] The term "approximately" can be understood by those skilled in the art and may vary to some extent depending on the context in which it is used. Depending on the context, if some uses of this term are not clear to those skilled in the art, "approximately" means plus or minus 20%, preferably plus or minus 10%, of a particular term.

[0036] As disclosed herein, the range "X to Y" or "X~Y" includes the terms "X" and "Y".

[0037] In further specific embodiments, the veterinary composition comprises an iron complex disclosed herein as the sole active ingredient and a water-soluble polymer disclosed herein, wherein the weight ratio of the iron element supplied as the iron complex to the water-soluble polymer is set to 0.5 to 300, preferably 1.5 to 40, 2 to 20, 2.4 to 15, more preferably 2.7 to 13.3, and even more preferably about 2.7 or about 13.3.

[0038] In further specific embodiments, the veterinary compositions disclosed herein further comprise an organic solvent. Preferably, the organic solvent is selected from methanol, ethanol, butanol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, glycerol, phenol, benzyl alcohol, phenylethanol, phenoxyethanol, ethyl acetate, butylbenzoate benzyl acetate, ethyl oleate, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, dipropylene glycol monomethyl ether, acetone, methyl ethyl ketone, glycerol formal, 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane, N-methylpyrrolidone, 2-pyrrolidone, N,N-dimethylacetamide, glycoflurol, dimethyl-isosorbitol, lauroglycol, propylene carbonate, octyldodecanol, dimethylformamide, and mixtures thereof. More preferably, the organic solvent is phenol.

[0039] In preferred embodiments, the organic solvent is concentrated at a concentration of 1 to 20 mg / mL, preferably 5 to 10 mg / mL, and more preferably 5 to 8 mg / mL. In more preferred embodiments, the organic solvent is contained in an amount of about 6.4 mg per 1 mL of composition or about 9.6 mg per 1.5 mL of composition.

[0040] Preferred compositions according to the present invention, -The iron complex supplied as the sole active ingredient disclosed herein is an element of iron at a concentration of 50-300 mg / mL, preferably 100-200 mg / mL, more preferably 120-150 mg / mL, -A water-soluble polymer disclosed herein in a concentration of 1 to 100 mg / mL, preferably 5 to 70 mg / mL, preferably 7 to 60 mg / mL, more preferably 10 to 50 mg / mL, -A veterinary composition comprising an organic solvent disclosed herein at a concentration of 1 to 20 mg / mL, preferably 5 to 10 mg / mL, more preferably 5 to 8 mg / mL.

[0041] A more preferred composition according to the present invention is: -The iron complex, supplied as the sole active ingredient disclosed herein, is iron element at a concentration of approximately 133.4 mg / mL, -Polyvinylpyrrolidone at a concentration of approximately 10 or 50 mg / mL, -A veterinary composition containing phenol at a concentration of approximately 6.4 mg / mL.

[0042] Further excipients The veterinary composition of the present invention may further comprise at least one excipient, such as a pharmaceutically acceptable salt and / or surfactant, in particular a surfactant having more than 8 HLB.

[0043] Accordingly, the object of the present invention is a veterinary composition disclosed herein, further comprising a pharmaceutically acceptable salt and / or a surfactant having an HLB of more than 8.

[0044] In a preferred embodiment, the veterinary composition of the present invention further comprises a pharmaceutically acceptable salt.

[0045] As used herein, “pharmaceutically acceptable salt” includes both organic and inorganic salts. Typical examples of organic salts include, for example, formate, acetate, trichloroacetate, propionate, benzoate, gluconate, carbonate, citrate, cinnamate, fumarate, maleate, and methanesulfonate. Typical examples of inorganic salts include, for example, hydrochloride, hydrobromide, iodate, ammonium, sulfonate, and phosphate. In certain embodiments of the present invention, pharmaceutically acceptable salts include any water-soluble agent that provides ionic strength.

[0046] In preferred embodiments, pharmaceutically acceptable salts are selected from calcium gluconate, calcium phosphate, calcium chloride, calcium sulfate, calcium carbonate, magnesium gluconate, magnesium phosphate, magnesium chloride, magnesium sulfate, magnesium carbonate, potassium phosphate, potassium gluconate, potassium chloride, potassium sulfate, potassium carbonate, sodium gluconate, sodium chloride, sodium carbonate, sodium lactate, sodium propionate, sodium phosphate, sodium citrate, sodium sulfate, ammonium chloride, ammonium carbonate, and mixtures thereof. In more preferred embodiments, the pharmaceutically acceptable salt is sodium chloride.

[0047] In certain embodiments, the pharmaceutically acceptable salts disclosed herein have a concentration of 1 to 100 mg / mL. In certain embodiments, the pharmaceutically acceptable salts disclosed herein have a concentration of 5 to 70 mg / mL, preferably 7 to 60 mg / mL, and more preferably 10 to 50 mg / mL. In more preferred embodiments, the pharmaceutically acceptable salt is in an amount of about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, or 55 mg per 1 mL of composition. In even more preferred embodiments, the pharmaceutically acceptable salt is in an amount of about 10 or 50 mg per 1 mL of composition, or about 15 or 75 mg per 1.5 mL of composition.

[0048] Preferred compositions according to the present invention, -The iron complex supplied as the sole active ingredient disclosed herein is an element of iron at a concentration of 50-300 mg / mL, preferably 100-200 mg / mL, more preferably 120-150 mg / mL, -A water-soluble polymer disclosed herein in a concentration of 1 to 100 mg / mL, preferably 5 to 70 mg / mL, preferably 7 to 60 mg / mL, more preferably 10 to 50 mg / mL, - An organic solvent disclosed herein at a concentration of 1 to 20 mg / mL, preferably 5 to 10 mg / mL, more preferably 5 to 8 mg / mL, -A veterinary composition comprising a pharmaceutically acceptable salt disclosed herein in a concentration of 1 to 100 mg / mL, preferably 5 to 70 mg / mL, more preferably 10 to 50 mg / mL.

[0049] A more preferred composition according to the present invention is: -The iron complex, supplied as the sole active ingredient disclosed herein, is iron element at a concentration of approximately 133.4 mg / mL, -Polyvinylpyrrolidone at a concentration of approximately 10 or 50 mg / mL, -Phenol at a concentration of approximately 6.4 mg / mL, - A veterinary composition containing sodium chloride at a concentration of approximately 10 or 50 mg / mL.

[0050] It is understood that the above-mentioned pharmaceutically acceptable concentrations or amounts of salt correspond to the concentrations or amounts added to prepare the compositions of the present invention. In other words, such concentrations or amounts are free from impurities that may be obtained during the process of preparing the iron complex and can be recovered in the original raw materials.

[0051] In a further preferred embodiment, the veterinary composition of the present invention further comprises a surfactant having an HLB of 8 or more.

[0052] The term "surfactant" refers to a substance that modifies the surface tension of a liquid, particularly water. A surfactant molecule can be described as having a hydrophobic chain (affinity for non-polar solvents) linked to a hydrophilic chain (affinity for polar solvents). Therefore, surfactants exhibit antagonistic properties; when mixed with water, the hydrophobic portion rejects molecules on the surface, while the hydrophilic portion tends to penetrate the liquid.

[0053] HLB (Hydrophilic-Lipophilic Balance) is used to determine the hydrophilic or hydrophobic dominance of a surfactant. The HLB value was proposed in 1949 by Griffin (Griffin WC, Surface-Active Classification of Agents by HLB, Newspaper of the Society of Cosmetic Chemists 1(1949):31). This method quantifies the existing balance between the hydrophilic and lipophilic parts of a surfactant molecule, allowing for the determination of a reference point related to its solubility in water. Its scale ranges from 0 to 40, with higher HLB values ​​indicating greater solubility in water. In 1957, Davies proposed a method based on calculating the value based on the chemical groups of the molecule. The advantage of this method is that it takes into account the effects of stronger and weaker hydrophilic groups. According to Davies' method, the following equation holds:

number

[0054] The preferred surfactants of the present invention are surfactants having an HLB greater than 8, more preferably in the range of 8 to 40, and more preferably in the range of 8 to 30. In preferred embodiments, the surfactant having an HLB greater than 8 is selected from polyethylene castor oil, polyoxyethylene alkyl ethers, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearic acid, sodium lauryl sulfate, sodium doxate, cetrimide, phospholipids, cetylpyridinium chloride, and mixtures thereof. In more preferred embodiments, the surfactant having an HLB greater than 8 is sodium doxate.

[0055] In certain embodiments, the surfactant having an HLB greater than 8 disclosed herein is at a concentration of 0.01 to 10 mg / mL, preferably 0.5 to 8 mg / mL, and more preferably 1 to 5 mg / mL. In more preferred embodiments, the surfactant having an HLB greater than 8 is in an amount of about 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, or 5.5 mg per 1 mL of composition. In even more preferred embodiments, the surfactant having an HLB greater than 8 is in an amount of about 1 or 5 mg per 1 mL of composition, or about 1.5 or 7.5 mg per 1.5 mL of composition.

[0056] Preferred compositions according to the present invention, -The iron complex supplied as the sole active ingredient disclosed herein is an element of iron at a concentration of 50-300 mg / mL, preferably 100-200 mg / mL, more preferably 120-150 mg / mL, -A water-soluble polymer disclosed herein in a concentration of 1 to 100 mg / mL, preferably 5 to 70 mg / mL, preferably 7 to 60 mg / mL, more preferably 10 to 50 mg / mL, - An organic solvent disclosed herein at a concentration of 1 to 20 mg / mL, preferably 5 to 10 mg / mL, more preferably 5 to 8 mg / mL, -A veterinary composition comprising a surfactant having an HLB greater than 8 as disclosed herein, in a concentration of 0.01 to 10 mg / mL, preferably 0.5 to 8 mg / mL, more preferably 1 to 5 mg / mL.

[0057] A more preferred composition according to the present invention is: -The iron complex, supplied as the sole active ingredient disclosed herein, is iron element at a concentration of approximately 133.4 mg / mL, -Polyvinylpyrrolidone at a concentration of approximately 10 or 50 mg / mL, -Phenol at a concentration of approximately 6.4 mg / mL, - A veterinary composition containing doxate sodium at a concentration of approximately 1 or 5 mg / mL.

[0058] Further preferred compositions according to the present invention are: -The iron complex supplied as the sole active ingredient disclosed herein is an element of iron at a concentration of 50-300 mg / mL, preferably 100-200 mg / mL, more preferably 120-150 mg / mL, -A water-soluble polymer disclosed herein in a concentration of 1 to 100 mg / mL, preferably 5 to 70 mg / mL, preferably 7 to 60 mg / mL, more preferably 10 to 50 mg / mL, - An organic solvent disclosed herein at a concentration of 1 to 20 mg / mL, preferably 5 to 10 mg / mL, more preferably 5 to 8 mg / mL, -A pharmaceutically acceptable salt disclosed herein in a concentration of 1 to 100 mg / mL, preferably 5 to 70 mg / mL, more preferably 10 to 50 mg / mL, -A veterinary composition comprising a surfactant having an HLB greater than 8 as disclosed herein, in a concentration of 0.01 to 10 mg / mL, preferably 0.5 to 8 mg / mL, more preferably 1 to 5 mg / mL.

[0059] Further preferred compositions according to the present invention are: -The iron complex, supplied as the sole active ingredient disclosed herein, is iron element at a concentration of approximately 133.4 mg / mL, -Polyvinylpyrrolidone at a concentration of approximately 10 or 50 mg / mL, -Phenol at a concentration of approximately 6.4 mg / mL, -Sodium chloride at a concentration of approximately 10 or 50 mg / mL, - A veterinary composition containing doxate sodium at a concentration of approximately 1 or 5 mg / mL.

[0060] The veterinary compositions of the present invention as defined herein may also comprise at least one further excipient, such as an antifoaming agent. Non-limiting examples of antifoaming agents include soy lecithin, sorbitan esters, polyol esters, silicone emulsions, simethicone emulsions, propylene glycol monolaurate, propylene glycol monocaprylate, glyceryl monooleate, phospholipids, lauroyl polyoxylglycerides, linoleyl polyoxylglycerides, oleoyl polyoxylglycerides, or polyoxyethylene alkyl ethers. Preferred antifoaming agents are sorbitan monooleate, propylene glycol monolaurate, and simethicone emulsion. In more preferred embodiments, the antifoaming agent is typically a simethicone emulsion containing about 25–35% by weight of simethicone USP. In specific examples, simethicone emulsions include the following components: polydimethylsiloxane, octamethylcyclotetrasiloxane, methylcellulose, decamethylcyclopentasiloxane, methylated silica, and sorbic acid.

[0061] The compositions of the present invention disclosed herein may be prepared by any method known to those skilled in the art. For example, a composition may be prepared by providing an iron complex, a water-soluble polymer, an organic solvent, any pharmaceutically acceptable salt, any surfactant having an HLB greater than 8, and an appropriate amount of water for mixing the components in a suitable container. The compositions of the present invention may be prepared in advance and stored in any suitable container (such as a flask or bottle). Alternatively, the composition may be prepared on the spot, for example, by mixing the components immediately before administration.

[0062] Applicable The compositions of the present invention disclosed herein may be used, in particular, for the prevention and / or treatment of any non-human mammal suffering from iron deficiency and anemia.

[0063] Therefore, the object of the present invention is a composition disclosed herein, which is used to control iron deficiency and / or anemia in non-human mammals.

[0064] A further object of the present invention is a method for controlling iron deficiency and / or anemia in a non-human mammal, comprising administering an effective amount of the composition disclosed herein to the non-human mammal.

[0065] A further object of the present invention is the use of the veterinary compositions disclosed herein for the manufacture of drugs for controlling iron deficiency and / or anemia in non-human mammals.

[0066] As used herein, the expressions “control iron deficiency and / or anemia” and “control iron deficiency and / or anemia” include the prevention and / or treatment of iron deficiency and / or anemia in non-human mammals. In embodiments, iron deficiency and / or anemia is controlled by iron intake in iron-dependent non-human mammals. In further embodiments, iron intake corrects spontaneous iron deficiency in non-human mammals.

[0067] As used herein, the terms “treatment” and “control” include, in particular, prophylactic treatment of iron deficiency and / or anemic conditions in non-human mammals. Prophylactic treatment of a disease in a non-human mammal means treatment performed before the non-human mammal becomes anemic and / or before the onset of symptoms or in the early stages of the onset of the disease, in particular a disease associated with anemia or iron deficiency.

[0068] The term “treatment” also includes the alleviation of symptoms, as well as the delay, reduction, or cure of diseases associated with anemia or iron deficiency. The term “treatment” also includes the improvement of the welfare of the non-human mammal being treated, thereby enabling satisfactory growth. It also includes increased meat production.

[0069] As used herein, “iron deficiency-related diseases” are known to those skilled in the art. Examples of “iron deficiency-related diseases” include, but are not limited to, anemia, infections such as coscidomycosis, and inflammatory diseases.

[0070] As used herein, “effective dose” preferably refers to the dose of the composition of the present invention that produces a clinical benefit in the non-human mammal being treated. In particular, the effective dose is an amount sufficient to control iron deficiency and reduce and / or treat anemia.

[0071] The compositions of the present invention can be formulated as solutions or suspensions, or in any form suitable for oral or parenteral administration. The compositions of the present invention are preferably administered by oral or parenteral routes, preferably by parenteral routes.

[0072] More specifically, the compositions of the present invention may be administered parenterally by injection (e.g., intramuscular, subcutaneous, intravenous, etc.), in various dosage forms and by infusion or implantation in formulations, or via suitable delivery devices or implants.

[0073] The preferred route of administration of the composition of the present invention is by injection. Intramuscular administration is the most preferred route.

[0074] The compositions of the present invention may be administered by injection using technologies and / or devices known in the art. In this regard, injections such as intramuscular injections may be performed with syringes, guns, microneedle injection devices, needleless injection devices, pulse devices, etc. In preferred embodiments, injections are performed with needle injectors or syringes. In other specific embodiments, injections are performed with needleless injection devices such as pulse needleless systems, more specifically with spring-actuated, battery-powered, or compressed gas-powered devices. Specific examples of needleless technologies are described, for example, in WO2006 / 058426, WO2007 / 140610, or WO2009 / 111794. Preferred needleless injection devices for use in the present invention are the AcuShot® needleless technologies described in International Patent Applications WO2006 / 058426 and WO2007 / 140610. Intramuscular injections may be performed in any muscle.

[0075] The composition of the present invention is more preferably administered by a single injection.

[0076] Therefore, a particular object of the present invention lies in the veterinary compositions for use disclosed herein, which are administered by injection, preferably intramuscular injection, and more preferably by single injection.

[0077] A further specific object of the present invention lies in a method for controlling iron deficiency and / or anemia in a non-human mammal, comprising intramuscular injection of an effective amount of the veterinary composition disclosed herein into the non-human mammal.

[0078] The present invention can be used with any non-human mammal, including pigs, sheep, cattle, dogs, or cats, preferably livestock, breeding animals, companion animals, and laboratory animals. Examples of livestock and breeding animals include mammals such as cattle, horses, sheep, pigs, goats, camels, buffalo, donkeys, rabbits, fallow deer, reindeer, and fur-bearing animals such as minks, chinchillas, or raccoons. Examples of companion animals include horses, dogs, and cats. Examples of laboratory and experimental animals include mice, rats, guinea pigs, or golden hamsters. Of all species, subspecies, and breeds, particular emphasis may be placed on pigs, cattle, sheep, and dogs. This can be used with adult or young animals such as neonates to 10 days old non-human mammals.

[0079] A preferred object of the present invention is a veterinary composition for use disclosed herein, wherein the non-human mammal is a pig, sheep, cattle, dog, or cat, preferably a pig.

[0080] The present invention is particularly suitable for treating newborn piglets and young piglets within 3 days of birth, typically weighing between 0.40 and 5 kg. More specifically, there is no need to dilute the composition or fatten the animals for preparation in order to treat such a population.

[0081] A preferred embodiment of the present invention is a veterinary composition disclosed herein for use in controlling iron deficiency and / or anemia in piglets, wherein 1.5 mL of the composition is administered to the piglet by a single intramuscular injection.

Claims

1. A veterinary composition for use in controlling iron deficiency and / or anemia in non-human mammals, comprising an aqueous colloidal solution of beta-oxyhydroxydic acid and dextran glucoheptonic acid as the sole active ingredients, and polyvinylpyrrolidone.

2. The veterinary composition according to claim 1, wherein polyvinylpyrrolidone is present at a concentration of 1 to 100 mg / mL.

3. The veterinary composition according to claim 1 or 2, further comprising an organic solvent selected from methanol, ethanol, butanol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, glycerol, phenol, benzyl alcohol, phenylethanol, phenoxyethanol, ethyl acetate, butyl benzoate benzyl acetate, ethyl oleate, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, dipropylene glycol monomethyl ether, acetone, methyl ethyl ketone, glycerol formal, 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane, N-methyl-pyrrolidone, 2-pyrrolidone, N,N-dimethylacetamide, glycoflurol, dimethyl-isosorbitol, lauroglycol, propylene carbonate, octyldodecanol, dimethylformamide, and mixtures thereof.

4. The veterinary composition according to claim 3, wherein the organic solvent has a concentration of 1 to 20 mg / mL.

5. A veterinary composition according to any one of claims 1 to 4, further comprising a pharmaceutically acceptable salt and / or a surfactant having an HLB greater than 8.

6. The veterinary composition according to claim 5, wherein the pharmaceutically acceptable salt is selected from calcium gluconate, calcium phosphate, calcium chloride, calcium sulfate, calcium carbonate, magnesium gluconate, magnesium phosphate, magnesium chloride, magnesium sulfate, magnesium carbonate, potassium phosphate, potassium gluconate, potassium chloride, potassium sulfate, potassium carbonate, sodium gluconate, sodium chloride, sodium carbonate, sodium lactate, sodium propionate, sodium phosphate, sodium citrate, sodium sulfate, ammonium chloride, and ammonium carbonate, and mixtures thereof.

7. The veterinary composition according to claim 5 or 6, wherein the pharmaceutically acceptable salt has a concentration of 1 to 100 mg / mL.

8. The veterinary composition according to claim 5, wherein the surfactant having an HLB of 8 or more is selected from polyethylene castor oil, polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene stearate, sodium lauryl sulfate, phospholipids, and mixtures thereof.

9. The veterinary composition according to claim 5 or 8, wherein the surfactant having an HLB greater than 8 is present in a concentration of 0.01 to 10 mg / mL.

10. The veterinary composition according to any one of claims 1 to 9, wherein the iron supplied as an aqueous colloidal solution of beta-oxyhydric acid ferric and dextran glucoheptonic acid has an iron element concentration of 50 to 300 mg / mL.

11. Iron element is supplied as an aqueous colloidal solution of beta-oxyhydric acid ferric and dextran glucoheptonic acid as the sole active ingredients, at a concentration of approximately 133.4 mg / mL, Polyvinylpyrrolidone at a concentration of approximately 10 mg / mL, Phenol at a concentration of approximately 6.4 mg / mL, A veterinary composition according to any one of claims 1 to 10, comprising:

12. The veterinary composition according to any one of claims 1 to 11, wherein the non-human mammal is a pig, sheep, cattle, dog, or cat.

13. The veterinary composition according to any one of claims 1 to 12, wherein the composition is administered by injection.

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