Veterinary oral medicinal composition

Abstract

The present invention relates to the field of medicinal products, in particular veterinary medicinal products, administered orally and intended for the prevention and / or treatment of chronic or progressive veterinary diseases in individuals suffering from such diseases, in particular animals.

Description

[0001] DESCRIPTION

[0002] TITLE OF THE INVENTION: Veterinary oral medicated composition The present invention relates to the field of medicinal products, in particular veterinary medicinal products, administered orally and intended for the prevention and / or treatment of chronic or progressive veterinary diseases in individuals suffering from these diseases, in particular animals.

[0003] More specifically, the present invention relates to a veterinary oral medicated composition in the form of a high-quality complete feed meeting the standards defined by Regulation (EU) 2020 / 354 (so-called PARNUT feeds) and comprising at least one active ingredient, specifically intended for the prevention and / or treatment of chronic or progressive diseases in domestic animals. The particular formulation of this composition allows for improved therapeutic efficacy thanks to the specific composition of the complete feed and the controlled delivery of appropriate active ingredients.

[0004] Administering medication to animals and ensuring compliance with veterinary treatments raises several difficulties that must be overcome:

[0005] - the adaptation of pharmaceutical forms (tablets, liquids, injections) to the different species and their anatomical and physiological particularities, the resolution of difficulties related to the behavior of animals (refusal to take medication, risk of injury to the animal and the owner) and the reconciliation of the time and budget constraints of owners with the requirements of treatments; to this necessity may be added that of feeding sick animals or even maintaining their weight.

[0006] - adherence (and therefore acceptance) which has significant consequences on the effectiveness of treatments and the health of animals and which requires strict adherence to treatment protocols prescribed by veterinarians; it is also important to minimize side effects.

[0007] - even the public health challenges aimed at preventing the development of antibiotic resistance linked to inappropriate use of medicines in animals.

[0008] - Preserving these foods, especially once the container is opened, is another difficulty to overcome.

[0009] This issue highlights the need for new forms of medicines or a comprehensive, multidisciplinary approach involving veterinarians, pet owners, researchers, and public health authorities to ensure the responsible and effective use of medicines in animals. To address all these problems, the Applicant has developed a medicinal product consisting of a veterinary oral composition combining at least one active ingredient that complies with veterinary medicinal product regulations and a complete feed that meets the regulatory requirements for feeds for specific nutritional purposes (PARNUT). This feed is referred to as the dietary food matrix in the following.Advantageously, the active ingredient is incorporated at a dose that allows for a reduced food intake of at least 50%, or 10% to 50%, compared to the active dose of the active ingredient in oral tablet form, due to the product's pharmacokinetics. Dietary drug compositions have already been developed in the past; for example, document EP2988608 proposes a combination of kibble and benazepril.

[0010] In continuing its developments, the Applicant was able to unexpectedly demonstrate that by specifically selecting a complete feed meeting the standards of European Regulation 2020 / 354 (feeds for specific nutritional purposes, also known as PARNUT) and using it as a formulation ingredient in a veterinary composition also containing a therapeutic active ingredient, the resulting composition, which is a medicinal product, leads, even in animals suffering from advanced stages of a chronic disease, to a therapeutic efficacy superior to the administration of any complete feed or feed adapted to the pathology and the active ingredient, while providing essential advantages for the treatment of animals suffering from different stages of a chronic disease, in particular progressive chronic disease: better treatment compliance through high acceptance by the animal,Ease of administration for the owner or breeder, maintenance of health, and improved product preservation.

[0011] The present invention thus relates to a veterinary oral medicated composition, in the form of a complete feed intended for the treatment or prevention of a chronic or progressive disease in a domestic animal, comprising:

[0012] - a food matrix consisting of an animal feed meeting the standards of European regulation (EU) 2020 / 354 (animal feed for specific nutritional purposes, also known as PARNUT);

[0013] - at least one active medicinal ingredient, selected according to the targeted pathology, incorporated into the food matrix;

[0014] - said composition being adapted for controlled twice-daily intake, allowing optimized administration of the active ingredient in accordance with the pharmacological needs of the animal; - said composition being in the form of kibble and / or wet food;

[0015] - said composition being compliant with both PARNUT veterinary regulations and the requirements for placing on the market an oral veterinary medicinal product.

[0016] Pharmacological need means providing a response to all the needs of an animal suffering from a chronic and / or progressive disease, that is to say its nutritional and therapeutic treatment needs.

[0017] The present invention also relates to a veterinary oral medicated composition, in the form of a complete feed intended for the treatment or prevention of a chronic or progressive disease in a domestic animal, comprising:

[0018] - a food matrix consisting of an animal feed meeting the standards of European Regulation (EU) 2020 / 354 (animal feed for specific nutritional purposes, also known as PARNUT),

[0019] - at least one active medicinal ingredient, selected according to the targeted pathology, incorporated into the food matrix,

[0020] characterized in that,

[0021] - said composition being adapted to a controlled twice-daily intake, allowing optimized administration of the active ingredient in accordance with the pharmacological needs of the animal;

[0022] - said composition being in the form of kibble and / or wet food;

[0023] - said composition being compliant with both PARNUT veterinary regulations and the requirements for placing on the market an oral veterinary medicinal product.

[0024] The present invention further relates to a veterinary oral medicated composition, in the form of a complete feed intended for the treatment or prevention of a chronic or progressive disease in a domestic animal, comprising:

[0025] - a food matrix consisting of an animal feed meeting the standards of European regulation 2020 / 354 (animal feed for specific nutritional purposes, also known as PARNUT);

[0026] - at least one active medicinal ingredient, selected according to the targeted pathology, incorporated into the food matrix;

[0027] - said composition being adapted for controlled twice-daily intake, allowing optimized administration of the active ingredient in accordance with the animal's needs; - said composition being in the form of kibble and / or wet food; - said composition being compliant with both PARNUT veterinary regulations and the requirements for placing an oral veterinary medicinal product on the market.

[0028] In general, the invention relates to a veterinary medicinal product consisting of a PARNUT and a veterinary medicinal product.

[0029] According to one aspect, the invention relates to a veterinary oral medicated composition, in the form of a complete feed for the treatment or prevention of a chronic or progressive disease in a domestic animal, comprising:

[0030] - a food matrix consisting of an animal feed meeting the standards of European regulation 2020 / 354 (animal feed for specific nutritional purposes, also known as PARNUT);

[0031] - at least one active medicinal ingredient, selected according to the targeted pathology, incorporated into the food matrix;

[0032] - said composition being adapted to a controlled twice-daily intake, allowing optimized administration of the active ingredient in accordance with the pharmacological needs of the animal;

[0033] - said composition being in the form of kibble and / or wet food;

[0034] - said composition being compliant with both PARNUT veterinary regulations and the requirements for placing on the market an oral veterinary medicinal product.

[0035] The present invention also relates to:

[0036] a veterinary oral medicated composition in the form of a complete feed for use in the treatment or prevention of a chronic or progressive disease in a domestic animal, comprising a food matrix and at least one active medicinal ingredient selected according to said chronic or progressive disease, characterized in that:

[0037] - said food matrix meets the standards of European regulation 2020 / 354 known as PARNUT (foods for specific nutritional purposes) for said chronic or progressive disease;

[0038] - said composition complies with both PARNUT veterinary regulations and the requirements for placing an oral veterinary medicinal product on the market;

[0039] - said active ingredient is incorporated homogeneously into said food matrix so that samples of said composition of the same weight comprise the same quantity of active ingredient; - said composition is intended for administration at least twice daily controlled by the owner consisting of making available weighed or measured portions of the daily ration;

[0040] - Ingestion of said composition ensures a smoothing of plasma exposure of the active ingredient by maintaining a constant effective concentration; in other words, ingestion of the composition according to the invention produces a plasma concentration of active ingredient which is sufficient to be therapeutically effective and which is more spread out over time;

[0041] which allows a therapeutic efficacy equivalent or greater than the separate administration of the active ingredient once a day in the form of an oral tablet and a suitable food, even when the dose of active ingredient actually ingested per day is reduced by 10% to 50% compared to the recommended dose in said form of oral tablet.

[0042] Or, alternatively:

[0043] a veterinary oral medicated composition in the form of a complete feed for use in the treatment or prevention of a chronic or progressive disease in a domestic animal, comprising a food matrix and at least one active medicinal ingredient selected according to said chronic or progressive disease, characterized in that:

[0044] - said food matrix meets the standards of European regulation 2020 / 354 known as PARNUT (foods for specific nutritional purposes) for said chronic or progressive disease;

[0045] - said composition complies with both PARNUT veterinary regulations and the requirements for placing an oral veterinary medicinal product on the market;

[0046] - said active ingredient is incorporated homogeneously into said food matrix so that samples of said composition of the same weight comprise the same quantity of active ingredient;

[0047] - said composition is intended for administration at least twice daily, controlled by the owner, consisting of the administration of the quantity of complete feed corresponding to the prescribed dose of medication;

[0048] - Ingestion of said composition ensures better stability of plasma concentrations of the active ingredient, allowing for a constant therapeutic effect throughout the day;

[0049] which allows a therapeutic efficacy equivalent or greater than the separate administration of the active ingredient once a day in the form of an oral tablet and a suitable food, even when the dose of active ingredient actually ingested per day is reduced by 10% to 50% compared to the recommended dose in the said form of oral tablet.

[0050] According to a particular embodiment, the veterinary oral medicated composition is used for the treatment of a chronic disease in a domestic animal suffering from an eating disorder chosen from anorexia, dysorexia or hyporexia; in particular, this embodiment is characterized in that the homogeneous distribution of the active ingredient in the matrix ensures the maintenance of effective plasma exposure by pharmacokinetic smoothing even when partial consumption of the daily ration is reduced up to 50% of the recommended dose, the reduction of the daily ration can be between 10 and 50%, in the order of 20%, 30%, or even 40%.

[0051] According to a particular embodiment, the veterinary oral medicated composition is used for the treatment of renal failure, congestive heart failure, cancer, diabetes, obesity or hypertension.

[0052] In particular, the use may target a cat suffering from chronic renal failure and the active ingredient is benazepril or one of its salts.

[0053] According to this embodiment, the food matrix is ​​adapted to the stage of the disease and: - for a cat at stage 1, the matrix comprises a protein content > 30% and approximately 0.6% phosphorus; for example, it may be composition A described below;

[0054] - for a cat at stage 2, said matrix comprises a protein content > 35% and approximately 0.55% phosphorus; for example, it may be composition B described below;

[0055] - for a cat at stage 3 or 4, said matrix comprises about 30% protein, about 0.5% phosphorus and bentonite; for example, it may be composition C described below.

[0056] According to this embodiment, the actual daily dose of benazepril ingested is between 0.25 and 0.5 mg per kg of body weight.

[0057] According to another embodiment, the active ingredient is oclacitinib for the treatment of osteoarthritis or dermatological disorders.

[0058] According to yet another embodiment, the active ingredient is an SGLT-2 inhibitor, preferably velagliflozin, for the treatment of diabetes.

[0059] The composition according to the invention may be in the form of kibble comprising an external lipid coating, or in the form of a wet food such as a pâté, terrine, or mince. The present invention also relates to a veterinary medicinal product in the form of a complete feed comprising a solid food matrix and at least one incorporated active ingredient, characterized in that:

[0060] - said matrix meets the requirements of European Regulation (EU) 2020 / 354;

[0061] - said active ingredient is distributed homogeneously on the surface or within the matrix; - said incorporation is carried out at a temperature below 40°C;

[0062] - said structure ensures stability of the active ingredient for at least 30 days at 25°C and is protected against thermal and oxidative degradation.

[0063] The present invention further relates to the manufacturing process of said veterinary medicinal product, comprising the steps of:

[0064] - preparation of a food matrix;

[0065] - preparation of a therapeutic premix in which at least one active ingredient is homogenized in a suitable carrier;

[0066] - homogeneous incorporation of the premix into the matrix at a temperature below 40°C;

[0067] - shaping the composition to meet both PARNUT veterinary regulations and the requirements for placing an oral veterinary medicinal product on the market and packaging it, optionally under nitrogen.

[0068] Unlike existing commercial solutions that rely on the separate administration of the drug and the feed, the invention proposes integrating the active ingredient into a dietary food matrix called PARNUT, specifically designed to optimize therapeutic efficacy while ensuring optimal acceptability and compliance. In addition to offering improved therapeutic efficacy, this holistic approach allows for precise control of the pharmacokinetic parameters of the active ingredient, taking into account the specific pathophysiology of the sick animal and its nutritional needs. The invention thus differs from prior solutions that are limited to supplemented feeds without pharmacological optimization or, conversely, to medications without considering the animals' dietary and behavioral constraints.

[0069] The invention proposes, according to a main aspect, a new pharmaceutical form of a drug for the treatment of an individual suffering from a chronic disease, this new pharmaceutical form comprising a food matrix, which may be in the form of a food core, and a coating, said coating comprising the drug, and the food matrix comprising a regulatory dietary composition specifically designed to provide a therapeutic benefit to the individual suffering from the chronic or progressive disease.

[0070] Food matrix

[0071] By food matrix, we mean a dietetic food matrix used in the present invention which is an animal feed intended for particular nutritional objectives, adapted to the specific physiopathological needs of said animal and meets the regulatory requirements of veterinary PARNUTs, defined by Regulation (EU) 2020 / 354 (version in force on the day of filing of the present invention and associated documents such as the document: https: / / europeanpetfood.org / wp-content / uploads / 2024 / 09 / FEDIAF-Nutritional-Guidelines_2024.pdf?_gl=l*lezm08f*_ga*MTcwMDQxMDA4MS4xNzQ0OTczNTQ3*_ga _TKE2BL8C8W*MTc0NDk3MzU0Ny4xLjAuMTc0NDk3MzU0Ny4wLjAuMA.

[0072] A PARNUT is designed to meet the specific nutritional needs of animals suffering from pathologies and requiring adapted dietary management.

[0073] The general technical effect of these PARNUTS is defined as follows:

[0074] "Feeds intended for a specific nutritional purpose, including meeting the specific nutritional needs of animals whose assimilation, absorption, or metabolism is, or is at risk of being, temporarily or irreversibly disrupted, and which, as a result, may benefit from the ingestion of animal feed appropriate to their condition."

[0075] This regulatory category requires rigorous selection of nutrients and nutritional adaptation according to target diseases, such as chronic kidney failure, osteoarthritis or cardiovascular diseases.

[0076] By integrating these regulatory constraints from the design stage, the invention's composition goes beyond simply being a delivery vehicle for the active ingredient, providing genuine therapeutic support and benefits. The dietary food matrix formulated within the invention's composition improves the animal's overall condition by simultaneously influencing disease progression and drug bioavailability, thus ensuring a dual therapeutic and nutritional action.

[0077] The dietary food matrix may include proteins, carbohydrate-containing substances, including starch-containing substances, fiber-containing substances, fats, minerals, and vitamins, in the form of mixtures or combinations of at least two of these components. Protein-containing substances include meat and meat products from chicken, lamb or mutton, turkey, beef, goat, and fish. Meat products include lungs, kidneys, livers, stomachs, and intestines.

[0078] Starch-containing substances include those derived from cereals, particularly those derived from maize, wheat, rice, oats, or sorghum. Fibre-containing substances include fructo-oligosaccharides, beet pulp, mannan-oligosaccharides, oat fibre, citrus pulp, carboxymethyl cellulose, as well as gums such as gum arabic, guar gum, or apple or tomato pomace, and mixtures or combinations thereof.

[0079] Fats include fats of animal origin and fats of vegetable origin.

[0080] Animal fats include those derived from chicken, turkey, pork, beef, or fish, as well as mixtures or combinations thereof. Preferably, animal fats include those derived from chicken, turkey, duck, pork, beef, or fish, as well as mixtures or combinations thereof. Animal fats also include fish oils.

[0081] Vegetable fats include vegetable oils such as corn oil, soybean oil, cottonseed oil, palm oil, coconut oil, as well as mixtures and combinations thereof.

[0082] Mineral substances include sodium selenite, monosodium phosphate, calcium carbonate, potassium chloride, ferrous sulfate, zinc oxide, manganese sulfate, copper sulfate, manganese oxide, potassium iodide, cobalt carbonate, as well as mixtures and combinations thereof.

[0083] Vitamins include choline chloride, vitamin E, ascorbic acid, vitamin A acetate, calcium pantothenate, pantothenic acid, biotin, thiamine mononitrate, vitamin B12, niacin, riboflavin, inositol, pyridoxine hydrochloride, vitamin D3, folic acid, vitamin C, and mixtures and combinations thereof.

[0084] The dietary food matrix may also include amino acids such as methionine, leucine, lysine, tryptophan, arginine, cysteine, aspartic acid, taurine, as well as mixtures and combinations thereof. The dietary food matrix may include additional substances such as antioxidants, stabilizers, binders, thickeners, flavor enhancers, flavorings, preservatives, fillers, emulsifiers, sweeteners, buffers, colors, gelling agents, and humectants.

[0085] Emulsifying and / or gelling agents include gelatin, cellulose ethers, starch, starch esters, starch ethers, and modified starches. Starch includes ungelatinized starch, fully gelatinized starch, and partially gelatinized starch, as well as mixtures or combinations thereof. Partially or fully gelatinized starch may be in the form of pre-gelatinized starch, which is hydrated at the time of use. Advantageously, the dietary food matrix may also include additional substances such as carotenoids, polyphenols, fatty acids, probiotics, or prebiotics.

[0086] The dietary food matrix may also include a palatability agent (hereinafter referred to as a palatability agent), for example, to make the composition according to the invention more palatable than a composition according to the invention without a palatability agent. A person skilled in the art will be able to select a palatability agent appropriate to the target animal and will ensure that the palatability agent does not compromise compliance with the conditions laid down by EU Regulation 2020 / 354 and that the dietary food matrix containing the palatability agent is indeed a PARNUT feed.

[0087] The dietary food matrix may also include an ingredient intended to mask the taste, in particular, of the active medicinal ingredient(s) added to it.

[0088] The dietary food matrix has the particularity of being adapted according to one or more nutritional parameters selected from: protein intake, lipid intake, omega 6 / omega 3 ratio, phosphorus intake, fermentable fibers, quantity of antioxidants, carbohydrate intake, according to the pathologies associated with the drug with which the food matrices are combined.

[0089] According to an embodiment of a veterinary oral medicated composition according to the invention, the quality and quantity of nutritional substances in the dietary food matrix are adapted to the specific physiology of animals affected by renal failure at a specific stage, in particular cats suffering from renal failure, and more particularly cats suffering from renal failure at a specific stage, 1, 2, 3 or 4. According to this embodiment, the dietary food matrix is ​​such that it contains at least the following essential ingredients: - a source(s) of protein;

[0090] - calcium;

[0091] - phosphorus;

[0092] - potassium;

[0093] - sodium;

[0094] - essential fatty acids; and

[0095] where phosphorus is at a level less than or equal to 6.5 g / kg of complete animal feed at 12% moisture and protein is at a level less than or equal to 320 g / kg of complete animal feed at 12% moisture.

[0096] According to this embodiment, the dietary food matrix preferably has one of the following compositions:

[0097] In this document, unless otherwise stated, the ingredient contents of the dietary food matrix are expressed as a percentage by weight relative to the total weight of said dietary food matrix. Whenever a measurement is expressed as a percentage by weight, it refers to the total weight of the dietary food matrix.

[0098] Composition A includes, in particular:

[0099] - A protein content of more than 30% by weight (for example 38%) to maintain muscle mass;

[0100] - An omega 3 content of approximately 1.5% by weight, including docosahexaenoic acid (DHA) (around 0.4%) which acts on the inflammatory cascade;

[0101] - chondroprotective agents (eggshell membrane + chondroitin sulfate + chitosan) to support the joints;

[0102] - vitamins including vitamin E to manage oxidative processes;

[0103] - A phosphorus level of around 0.6% to maintain kidney function;

[0104] - Phosphorus chelators (chitosan + calcium carbonate) to reduce its bioavailability.

[0105] A composition B, with, in relation to composition A,

[0106] - a protein level 15% lower than that of composition A. A protein level of at least 35% is nevertheless necessary to preserve muscle mass,

[0107] - a phosphorus content of 0.55% by weight and chitosan, calcium carbonate, phosphorus chelators that reduce its bioavailability,

[0108] - Chondroprotective agents: eggshell membrane, chondroitin sulfate, and chitosan. - A calcium content to achieve a Ca / P ratio of 1.8, to help combat secondary hyperparathyroidism.

[0109] - a high energy density of 412 kcal / 100 g,

[0110] - a fat content of 20%,

[0111] - an appetizing,

[0112] Composition B may include 26% carbohydrates.

[0113] or,

[0114] A composition C,

[0115] - with a protein level 15% lower than that of composition B, i.e., a protein level of 30% by weight sufficient to preserve muscle mass,

[0116] - a phosphorus level of 0.5%, reduced by 10% compared to composition B,

[0117] - a calcium content to obtain a Ca / P ratio of 2,

[0118] - Bentonite to reduce the risk of digestive ulcers related to uremia,

[0119] - Calcium carbonate (alkalizing agent) to combat metabolic acidosis, - an energy density of 415 kcal / 100 g, of which 21% by weight is fat,

[0120] - an appetizing,

[0121] where the proteins can be of animal or vegetable origin, derived from dehydrated pork protein, hydrolyzed pork and poultry protein, hydrolyzed fish protein, peas, broad bean pods, rice,

[0122] The fats can be fish oil,

[0123] The fibers can be derived from dehydrated beet pulp, psyllium fibers (Plantago psyllium [L.] spp.),

[0124] Hydrolyzed crustaceans are a source of chitosan.

[0125] Examples of joint supports include eggshell membranes and chondroitin sulfate.

[0126] and where the ingredients: inactivated Lactobacillus acidophilus, brewer's yeast (inactivated), fructo-oligosaccharides, vitamins such as vitamin A (17000 IU / kg), vitamin D3 (1700 IU / kg), vitamin E (610 IU / kg), metals such as copper [copper(II) sulfate pentahydrate] (12 mg / kg), zinc [zinc sulfate monohydrate] (110 mg / kg), iodine [calcium iodate] (0.4 mg / kg), amino acids such as taurine (2460 mg / kg), L-carnitine (540 mg / kg) and bentonite (5 g / kg) may also be present in the composition according to the invention.

[0127] An example of analytical components is as described below (% expressed by weight relative to the total weight of PARNUT) (composition A): [Table 1]

[0128] protein 38.0%

[0129] fats 16.5%

[0130] 6.5% fiber

[0131] ash 7.5%

[0132] Calcium 0.9%

[0133] Phosphorus 0.6%

[0134] Humidity 5.5%

[0135] Potassium 0.8%

[0136] Manganese 14.0 mg / kg

[0137] Methionine 1.0%

[0138] Another example (composition B) includes (% expressed by weight relative to the total weight of the PARNUT):

[0139] [Table 2]

[0140] Fat content (%): 20

[0141] Fiber / cellulose (%): 3.5

[0142] Phosphorus (%): 0.55

[0143] Omega 6 (%): 3

[0144] Humidity (%): 5.5

[0145]

[0146] Omega 3 (%): 1.5

[0147] Carbohydrates (%): 28.5

[0148]

[0149] Inorganic matter / 7.5

[0150] Crude ash (%): Protein (%): 35

[0151] Calcium (%): 1

[0152] Yet another example (composition C) includes (% expressed by weight relative to the total weight of the PARNUT):

[0153] Protein 30%, fat 21%, carbohydrates 33%, crude fiber 3.5%, starch 28%, minerals 7%, moisture 5.5%, calcium 1%, phosphorus 0.5%, sodium 0.4%, potassium 0.8%, Omega-3 essential fatty acids 1.5%, Omega-6 essential fatty acids 3.2%, DHA 0.4%. Other ingredients may include:

[0154] [Table 3]

[0155] protein 38.0% by weight

[0156] fats 16.5% by weight

[0157] fiber 6.5% by weight

[0158] ash 7.5% by weight

[0159] calcium 0.9% by weight

[0160] phosphorus 0.6% by weight

[0161] moisture 5.5% by weight

[0162] potassium 0.8% by weight

[0163] manganese 14.0 mg / kg by weight

[0164] methionine 1% by weight

[0165] sodium 0.4% by weight

[0166] Omega-3 fatty acids 1.5% by weight

[0167] Omega 6 fatty acids 2.5% by weight

[0168] starch 21.0% by weight

[0169] metabolizable energy 3840.0 kcal / kg

[0170] Nitrogen-free extract 26.0% by weight, acid 0.4% by weight

[0171] doco s ahexaenoic

[0172] vitamin E (total) 500.0 lE / kg

[0173] vitamin A (17000 IU / kg), vitamin D3 (1700 IU / kg), vitamin E (610 IU / kg), copper [copper (II) sulfate pentahydrate] (12 mg / kg), zinc [zinc sulfate monohydrate] (110 mg / kg), iodine [calcium iodate] (0.4 mg / kg), taurine (2460 mg / kg), L-carmitine (540 mg / kg), bentonite (5g / kg).

[0174] Yet another composition according to the invention may include:

[0175] [Table 4]

[0176] protein 35.0%

[0177] fats 9.0%

[0178] fibers 0.8%

[0179] ash 2.0%

[0180] calcium 0.28%

[0181] phosphorus 0.15%

[0182] humidity 76.0%

[0183] potassium 0.28%

[0184] manganese 5.0 mg / kg

[0185] methionine 0.3%

[0186] sodium 0.2%

[0187] omega-3 fatty acids 1.0%

[0188] omega-6 fatty acids 2.5%

[0189] starch 0.4%

[0190] Metabolizable energy 124.0 kcal / 100 g

[0191] nitrogen-free extract 1.2% acid 0.3%

[0192] doco s ahexaenoic

[0193] vitamin E (total) 150.0 lE / kg

[0194] vitamin D3 (300 IU / kg), copper [copper(II) sulfate pentahydrate] (1.5 mg / kg), manganese [manganese sulfate monohydrate] (1.5 mg / kg), zinc [zinc sulfate monohydrate] (31 mg / kg), iodine [calcium iodate] (1 mg / kg), bentonite (1 g / kg).

[0195] Yet another composition according to the invention may include:

[0196] [Table 5]

[0197] protein 30.0%

[0198] fats 21.0%

[0199] fibers 3.5%

[0200] ash 7.0%

[0201] calcium 1.0%

[0202] phosphorus 0.5%

[0203] humidity 5.5%

[0204] potassium 0.8%

[0205] manganese 12.0 mg / kg

[0206] methionine 0.5%

[0207] sodium 0.4%

[0208] omega-3 fatty acids 1.5%

[0209] omega-6 fatty acids 3.2%

[0210] starch 28.0%

[0211] Metabolizable energy 415.0 kcal / 100 g

[0212] nitrogen-free extract 33.0%

[0213] docosahexaenoic acid 0.4% vitamin E (total) 500.0 lE / kg

[0214] vitamin A (17000 IU / kg), vitamin D3 (1700 IU / kg), vitamin E (610 mg / kg), copper [copper(II) sulfate pentahydrate] (12 mg / kg), zinc [zinc sulfate monohydrate] (110 mg / kg), iodine [potassium iodide] (0.4 mg / kg), taurine (2460 mg / kg), L-camitine (540 mg / kg), bentonite (5 g / kg), antioxidants.

[0215] According to this embodiment, benazepril or one of its salts such as benazeprilate ((3S)-3-[[(lS)-(l-carboxy-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-lH-l-benzazepine-l-acetic acid) will be added as the preferred active ingredient to these dietary food matrices.

[0216] The choice of dietary food matrix can be made according to the stage of renal failure; these different stages are defined as follows:

[0217] 1. In stage 1, kidney function retains more than a third of its capacity. This is referred to as early or incipient disease; at this stage, no functional abnormalities are detectable. 2. In stage 2, kidney function retains a quarter of its capacity, the disease becomes established, and metabolic disorders appear.

[0218] 3. At stage 3, the disease worsens, kidney function decreases significantly and significant azotemia (presence of nitrogenous waste in the blood) appears, leading to the appearance of marked symptoms;

[0219] 4. In stage 4, or the terminal stage, the disease is severe. Kidney function decreases below 10%, and clinical signs are significant, generally leading to death. Specifically, formula A is preferred for cats with stage 1 malnutrition, formula B is preferred for cats with stage 2 malnutrition, and formula C for cats with stage 3 or 4 malnutrition.

[0220] In another embodiment, oclacitinib is a combination drug with a parnut adapted to the disease treated by oclacitinib, i.e., enabling the reduction of inflammation and allergies or the reduction of intolerances to certain nutrients (see Table 9 below). In another embodiment of a veterinary oral composition according to the invention, the quality and quantity of nutrients in the dietary food matrix are adapted to the specific physiology of animals, particularly dogs, affected by osteoarthritis. In this embodiment, the dietary food matrix contains omega-3 fatty acids, eicosapentaenoic acid, and vitamin E, with a total omega-3 fatty acid content of at least 29 g / kg and an eicosapentaenoic acid content of at least 3.3 g per kg of complete animal feed at 12% moisture.

[0221] An example of a dietary food matrix suitable for this embodiment includes: - a protein content of 35 to 40% by weight, including hydrolyzed proteins,

[0222] - a fat content of 5 to 10% by weight, including a total of omega-3 fatty acids of at least 29 g / kg of complete animal feed at 12% moisture and an eicosapentaenoic acid content of at least 3.3 g / kg of complete animal feed at 12% moisture, - a carbohydrate content of 25 to 30% by weight,

[0223] - a fiber content of 10 to 15% by weight,

[0224] - Vitamin E of the order of 570 IU / kg of complete animal feed at 12% moisture, - an palatable agent.

[0225] According to this method of implementation, an anti-inflammatory (a selective NSAID) and / or a chondroprotective agent (for example, glucosamine and hyaluronic acid) should preferably be added to this dietary food matrix.

[0226] According to another embodiment of a veterinary oral composition according to the invention, the quality and quantity of nutritional substances in the dietary food matrix is ​​adapted to the specific physiology of animals, in particular dogs, affected by dermatological disorders.

[0227] According to this embodiment, the dietary food matrix is ​​such that it contains linoleic acid at a level of at least 18.5 g / kg of complete animal feed at 12% moisture and the sum of eicosapentaenoic acid and docosahexaenoic acid represents at least 0.39 g / kg of complete animal feed at 12% moisture.

[0228] According to this embodiment, oclacitinib is preferably added to a dietary food matrix designed to maintain the integrity of the dermis and mucous membranes, comprising:

[0229] Linoleic acid at a content greater than or equal to 12.3 g per kg and sum of eicosapentaenoic acid and docosahexaenoic acid at a content greater than or equal to 2.9 g per kg of complete animal feed at 12% moisture,

[0230] Or

[0231] Linoleic acid at a content greater than or equal to 18.5 g per kg and sum of eicosapentaenoic acid and docosahexaenoic acid at a content greater than or equal to 0.39 g per kg of complete animal feed at 12% moisture,

[0232] or Linoleic acid at a content greater than or equal to 18.5 g per kg and sum of eicosapentaenoic acid and docosahexaenoic acid at a content greater than or equal to 0.09 g per kg of complete animal feed at 12% moisture.

[0233] According to another embodiment of a veterinary oral composition according to the invention, the quality and quantity of nutritional substances in the dietary food matrix is ​​adapted to the specific physiology of animals, in particular dogs and cats, affected by diabetes.

[0234] According to this embodiment, the dietary food matrix is ​​such that it contains total sugars (monosaccharides and disaccharides) at a level of less than 62 g / kg of complete animal feed at 12% moisture.

[0235] Preferably, the amount of carbohydrates is less than 15% by weight, preferably from 5% to 1% by weight or less than 2% by weight or 1% by weight.

[0236] According to this embodiment, the dietary food matrix is ​​such that it contains:

[0237] - a protein content of 40 to 50% by weight, including hydrolyzed proteins,

[0238] - a fat content of 3 to 6% by weight,

[0239] - a carbohydrate content of 1% to 15% by weight, representing total sugars (monosaccharides and disaccharides) at a level of less than 62 g / kg of complete animal feed at 12% moisture,

[0240] - a fiber content of 15 to 25% by weight,

[0241] - an appetizing,

[0242] as well as fructo-oligosaccharides, chitosamine, chondroitin sulfate and minerals and vitamins.

[0243] According to this embodiment, an antidiabetic such as a blood glucose inhibitor (metformin), a sodium / glucose cotransporter 2 (SLGT2) inhibitor (empagliflozin, dapagliflozin, canagliflozin) or a dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin, saxagliptin, vildagliptin, linagliptin) will preferably be added to this dietary food matrix.

[0244] According to another embodiment of a veterinary oral composition according to the invention, the quality and quantity of nutritional substances in the dietary food matrix are adapted to the specific physiology of animals, in particular dogs and cats, suffering from excess weight. According to this embodiment, the dietary food matrix is ​​such that it provides a metabolizable energy of less than 350 kcal / kg of complete animal feed at 12% moisture or 560 kcal / kg of complete animal feed at 85% moisture.

[0245] According to this embodiment, the dietary food matrix is ​​such that it contains, in particular:

[0246] - a protein content of 40 to 55% by weight, including hydrolyzed proteins,

[0247] - a fat content of 4 to 8% by weight, or 4 to 12% by weight,

[0248] - a carbohydrate content of less than 15% by weight, preferably less than 10% by weight, or even less than 5% by weight, more advantageously less than 4% by weight, or less than 3% by weight or less than 2% by weight or equal to 1% by weight,

[0249] - a fiber content of 10 to 20% by weight,

[0250] - an appetizing,

[0251] as well as fructo-oligosaccharides, chitosamine, chondroitin sulfate, and minerals and vitamins,

[0252] representing a metabolizable energy of less than 350 kcal / kg of complete animal feed at 12% moisture or 250 kcal / kg of complete animal feed at 85% moisture.

[0253] According to this embodiment, the dietary food matrix is ​​such that it can contain:

[0254] [Table 6]

[0255] protein 44.0%

[0256] fats 12.0%

[0257] fibers 11.5%

[0258] ash 8.5%

[0259] carbohydrates 18.5%

[0260] starch 12.0%

[0261] metabolizable energy 342.0 kcal

[0262] total sugars 1.4%

[0263] Vitamin A (17,000 IU / kg), vitamin D3 (1,700 IU / kg), copper (12 mg / kg), zinc (110 mg / kg), iodine (0.4 mg / kg), taurine (2,460 mg / kg), L-carnitine (540 mg / kg), bentonite (5 g / kg). Antioxidants. Another example of a dietary food matrix for weight loss could be:

[0264] [Table 7]

[0265] protein 44.0%

[0266] fats 12.0%

[0267] fibers 11.5%

[0268] ash 8.5%

[0269] Carbohydrates 18.5%

[0270] Starch 12.0%

[0271] metabolizable energy 342.0 kcal

[0272] total sugars 1.4%

[0273] Vitamin A (20,000 IU / kg), vitamin D3 (2,000 IU / kg), vitamin E (700 mg / kg), vitamin K3 (0.25 mg / kg), vitamin B1 (13 mg / kg), vitamin B2 (9 mg / kg), vitamin B3 (130 mg / kg), vitamin B5 (17.4 mg / kg), vitamin B6 (9.1 mg / kg), vitamin B8 (0.18 mg / kg), vitamin B9 (2.2 mg / kg), vitamin B 12 (0.055 mg / kg), copper (14 mg / kg), choline (2,100 mg / kg), taurine (2,900 mg / kg), iodine (0.45 mg / kg), zinc (130 mg / kg), bentonite (5 g / kg), lactobacillus acidophilus (7 mg / kg), chitosan (800 mg / kg), L-carnitine (540 mg / kg), sulfate chondroitin (440 mg / kg).

[0274] Another example of a dietary food matrix for weight loss could be:

[0275] [Table 8]

[0276] protein 44.0%

[0277] fats 11.0%

[0278] fibers 13.0%

[0279] Calcium 1.3%

[0280] Phosphorus 0.9%

[0281] Magnesium 0.08%

[0282] Humidity 5.5% Potassium 0.7%

[0283] Minerals 8.5%

[0284] Sodium 0.9%

[0285] omega-3 fatty acids 0.7%

[0286] omega-6 fatty acids 2.0%

[0287] starch 12.5%

[0288] metabolizable energy 331.0 kcal

[0289] total sugars 1.0%

[0290] Vitamin A (20,000 IU / kg), vitamin D3 (2,000 IU / kg), vitamin E (700 mg / kg), vitamin K3 (0.25 mg / kg), vitamin B1 (13 mg / kg), vitamin B2 (9 mg / kg), vitamin B3 (130 mg / kg), vitamin B5 (17.4 mg / kg), vitamin B6 (9.1 mg / kg), vitamin B8 (0.18 mg / kg), vitamin B9 (2.2 mg / kg), vitamin B 12 (0.055 mg / kg), copper (14 mg / kg), choline (2,100 mg / kg), taurine (2,900 mg / kg), iodine (0.45 mg / kg), zinc (130 mg / kg), bentonite (5 g / kg), lactobacillus acidophilus (7 mg / kg), chitosan (800 mg / kg), L-carnitine (540 mg / kg), sulfate chondroitin (440 mg / kg).

[0291] Depending on the needs of the animal whose excess weight is to be regulated, a matrix according to the invention could comprise:

[0292] - Glucagon-like peptide-1 (GLP-1) analogs. GLP-1 slows gastric emptying (which leads to a decrease in the rate of glucose absorption in the intestines) and increases the feeling of satiety (the feeling of having eaten enough) by acting on the brain areas that control food intake. These analogs include, but are not limited to, semaglutide and liraglutide. These compounds show promising potential for the treatment of obesity in animals.

[0293] - Antidiabetic drugs of the sodium-glucose cotransporter 2 (SGLT2) inhibitor type, or gliflozins. These substances reduce blood glucose levels by inhibiting renal glucose reabsorption. Examples include velagliflozin and bexagliflozin. In particular, velagliflozin is a new active substance authorized in veterinary medicine under the brand name SENVELGO®, indicated for reducing hyperglycemia in cats with non-insulin-dependent diabetes mellitus. According to another embodiment of a veterinary oral composition according to the invention, the quality and quantity of nutritional substances in the dietary food matrix are adapted to the specific physiology of animals with cancer.

[0294] According to one perspective, a dietary food matrix supporting cancer treatment may include, in addition to an anti-cancer agent:

[0295] Protein: 27% to 41% by weight

[0296] Fat content: 23% to 36% by weight

[0297] Carbohydrates from 23% to 20% by weight

[0298] Arginine from 1.8% to 5% by weight

[0299] Omega-6 from 2.1%

[0300] EPA+DHA from 0.3%

[0301] DHA more than 1% by weight or from 1% to 2.2%

[0302] Vitamin E from 100 to 500 mg / kg by weight

[0303] For illustrative purposes, the anti-cancer agent formulated in the appropriate dietary matrix (pamut) may be chosen from:

[0304] - Chlorambucil: an alkylating agent often used to treat chronic small cell lymphoma and other types of cancer.

[0305] - Cyclophosphamide: an alkylating agent used in various chemotherapy protocols for different types of cancer, including lymphoma and multiple myeloma.

[0306] - Lomustine: nitrosourea used in particular to treat mast cell tumors and certain types of brain tumors.

[0307] - Toceranib phosphate: tyrosine kinase inhibitor specifically approved for the treatment of recurrent or unresectable grade II or III cutaneous mast cell tumors in dogs.

[0308] - Masitinib mesylate: tyrosine kinase inhibitor used for the treatment of unresectable grade 2 or 3 mast cell tumors in dogs.

[0309] - Prednisolone and other corticosteroids: Although not strictly chemotherapeutic agents, corticosteroids are often used orally in the treatment of certain cancers, such as lymphoma, due to their anti-inflammatory and lympholytic properties.

[0310] - Metronomic chemotherapy: This involves the frequent administration of low doses of oral chemotherapy agents (such as cyclophosphamide, chlorambucil, or melphalan) on a continuous basis. This approach aims to inhibit angiogenesis and achieve a long-term antitumor effect with fewer acute side effects.

[0311] According to yet another embodiment of a veterinary oral composition according to the invention, the quality and quantity of nutritional substances in the dietary food matrix is ​​adapted to the specific physiology of animals affected by a bacterial infection and requiring the administration of an antibiotic.

[0312] According to this embodiment, the dietary food matrix supporting anti-infective treatment may, for example, include, in addition to an antibiotic, one or more probiotics such as stabilizers of the intestinal flora referred to in Annex I of Regulation (EC) No 1831 / 2003.

[0313] Advantageously, the dietary food matrix of the veterinary oral medicated composition according to the invention represents 75% to 99%, or even 75% to 95% by weight, relative to the total weight of said composition.

[0314] A dietary food matrix conforming to the Pamut regulations according to the invention, which can be combined with an active ingredient preventing and / or treating renal insufficiency, may comprise high-quality protein and phosphorus < 5 g / kg or 6.5 g / kg of complete animal feed at 12% moisture, crude protein in an amount < 220 g / kg or 320 g / kg of complete animal feed at 12% moisture, calcium, phosphorus, potassium, sodium, optionally essential fatty acids, and optionally lanthanum carbonate octahydrate. These specifications are intended for an adult dog or cat only, and a minimum protein digestibility of 85% is recommended.

[0315] According to one embodiment, the dietary feed matrix conforming to the pamut regulation intended for an equine, intended to be combined with an active ingredient preventing and / or treating renal failure, according to the invention comprises a reduced protein content: < 106 g of crude protein per kg of feed at 12% moisture, a sodium content of 2 g / 100 kg of body weight per day, an added eicosapentaenoic acid and docosahexaenoic acid content > 0.2 g / kg of body weight per day, highly digestible and highly palatable starch, Calcium, Phosphorus, Potassium, Magnesium, Sodium, provided that the daily ration guarantees an energy intake of > 0.62 MJ / kg of body weight per day, and does not contain more than 50 mg of calcium / kg of dry matter per day.

[0316] To reduce or prevent the formation of oxalate stones, a PARNUT-compliant dietary food matrix used according to the invention must include a low calcium content, a low vitamin D IU content, and include at least one urine-alkalinizing substance such as potassium citrate or sodium bicarbonate, and include Phosphorus, Sodium, Magnesium, Potassium, Chlorides, Sulfur, and Hydroxyproline.

[0317] The low calcium or vitamin D content is as defined in the current PARNUTS Regulation and its annexes (https: / / europeanpetfood.org / wp-content / uploads / 2024 / 09 / FEDIAF-Nutritional-Guidelines_2024.pdf?_gl=1*1ezm08f*_ga*MTcwMDQxMDA4MS4xNzQOOTczNTQ3*_ga_TKE2BL8C8W*MTc0NDk3MzU0Ny4xLjAuMTc0NDk3MzU0Ny4wLjAuMA). A dietary food matrix conforming to the PARNUT Regulation for the preparation of a composition according to the invention, which can be combined with an active ingredient against diabetes, comprises a quantity of total sugars (monosaccharides and disaccharides) < 62 g / kg of complete animal feed at 12% moisture, fructose (if added), and... essential fatty acids (if added), source(s) of short chain and medium chain fatty acids (if added).

[0318] A dietary food matrix conforming to the Pamut regulation for the preparation of a composition according to the invention may also be combined with several active ingredients provided that the specifications of the PARNUT are compatible with each of the active ingredients.

[0319] Depending on the specific chronic or progressive disease being treated, the qualified professional will be able to formulate the dietary matrix according to the requirements of EU Regulation 2020 / 354, which are detailed in Table 9 below, taking into account that:

[0320] A person in the field will know, for example, that in animal feed, digestibility is a criterion that defines the degree to which organic matter is digested by an animal.

[0321] Digestibility measurement (difference between feed intake (I) and fecal output (O)) is performed using techniques well-known to those skilled in the art, depending on the animal being fed. High-quality proteins are defined as proteins that provide all the essential amino acids (EAAs) that are assimilated by the body.

[0322] Crude protein is calculated in animal feed, as mineral nitrogen x 6.25 (the assumption is that the protein in typical animal feed contains on average 16% nitrogen). [Table 9]

[0323] Objective Nutritional characteristics Species Essential nutrients present Other essential nutritional characteristics Animal or (does not exclude the presence of others)

[0324] particular category of nutrients subject to

[0325] animals must comply with all conditions

[0326] PARNUT)

[0327] High-quality protein support for dogs — Protein source(s) Recommended digestibility of renal function: phosphorus < 5 g / kg of feed — Calcium: protein: minimum 85%. Recommended for animals with renal function at 12%

[0328] — Phosphorus

[0329] chronic renal insufficiency of moisture and crude protein <

[0330] 220 g / kg of complete feed for — Potassium

[0331] animals at 12% moisture — Sodium

[0332] — Essential fatty acids (if added)

[0333] Decreased absorption in dogs — Protein source(s)

[0334] phosphorus through the addition of adults — Calcium

[0335] lanthanum carbonate octahydrate

[0336] — Phosphorus

[0337] — Potassium

[0338] — Sodium

[0339] — Essential fatty acids (if added)

[0340] — Lanthanum carbonate octahydrate

[0341] High-quality protein for cats — Protein source(s) Recommended digestibility of phosphorus < 6.5 g / kg of food — Calcium 12% complete animal food — Phosphorus

[0342] humidity

[0343] — Potassium

[0344] crude protein < 320 g / kg

[0345] — Sodium

[0346] complete animal feed

[0347] 12% moisture — Essential fatty acids (if added)

[0348]

[0349] Presence of lanthanum carbonate in cats — Source(s) of protein

[0350] Calcium octahydrate for adult weight loss — Calcium

[0351] phosphorus absorption

[0352] — Phosphorus

[0353] — Potassium

[0354] — Sodium

[0355] — Essential fatty acids (if added)

[0356] — Lanthanum carbonate octahydrate

[0357] High energy density Equidae — Source(s) of protein and energy The ration should ensure an intake exceeding 8.8 MJ / kg of feed for — Calcium in energy of > 0.62 MJ / kg of animals at 12% moisture.

[0358] — Phosphorus body weight per day.

[0359] Highly digestible sources of starch and

[0360] — Potassium The ration should not contain very appetizing things.

[0361] — Magnesium more than 50 mg of calcium / kg of Reduced protein content: < 106 g dry matter per day.

[0362] of crude protein per kg of food — Sodium

[0363] for animals at 12% moisture. — Sum of eicosapentaenoic acid

[0364] Sodium content: 2 g / 100 kg of docosahexaenoic acid

[0365] body weight per day.

[0366] High acid content

[0367] eicosapentaenoic acid

[0368] Added docosahexaenoic acid: >

[0369] 0.2 g / kg of body weight per day.

[0370] Reduced Calcium, Low Phosphorus for Dogs

[0371] Vitamin D content formation and properties in cats — Calcium

[0372] oxalate stones from urine alkalinization

[0373] — Sodium

[0374] — Magnesium

[0375] — Potassium

[0376] — Chlorides

[0377] — Sulfur

[0378] — Vitamin D (total)

[0379]

[0380] — Hydroxyproline

[0381] — Substances that alkalize urine

[0382] Regulation of Total Sugars (monosaccharides) and Dogs and — Source(s) of carbohydrates

[0383] Glucose (disaccharide) intake < 62 g / kg of cat food — Possible carbohydrate treatment

[0384] (Diabetes mellitus) complete for animals at 12%

[0385] — Starch

[0386] humidity

[0387] — Total sugars

[0388] — Fructose (if added)

[0389] — Essential fatty acids (if added)

[0390] — Source(s) of chain fatty acids

[0391] short and medium chain (if added)

[0392] Reduction of Selected and Limited Number of Dogs and — Protein Sources, including the

[0393] Intolerances to protein source(s) in cats; possible treatment (if added)

[0394] certain ingredients and / or — Source(s) of carbohydrates, including the

[0395] and nutrients

[0396] Source(s) of hydrolyzed proteins, possible treatment (if added)

[0397] and / or — Essential fatty acids (if added)

[0398] Source(s) of carbohydrates

[0399] selected

[0400] Reduction of Urine Alkalinizing Properties in Dogs — Sulfur Amino Acids (Total) “Advise your veterinarian or nutritionist: for complete animal feed with alkalinizing properties,

[0401] — Sodium

[0402] 12% moisture content in the feed should be formulated — Potassium

[0403] or in such a way as to achieve a pH — Urinary chlorides > 7.

[0404] Proteins chosen to limit the

[0405] Cystine and cysteine ​​content (p. — Urine alkalizing substances (if

[0406] e.g. casein, pea protein, added)

[0407] soy protein) and crude protein

[0408] < 220 g / kg of complete feed for

[0409] animals at 12% humidity

[0410] Highly digestible ingredients suitable for dogs

[0411]

[0412] Recovery of an energy density > 3520 kcal — Sources of highly digestible ingredients 1. Apparent nutritional digestibility, and crude protein > 250 g / kg and, where applicable, their recommended dry matter processing > complete animal convalescence feed

[0413] — Energy value 80% or organic matter > 12% moisture

[0414] 85%.

[0415] Highly digestible ingredients suitable for cats

[0416] an energy density > 3520 kcal

[0417] and crude protein > 270 g / kg

[0418] complete animal feed

[0419] 12% humidity

[0420] Reduction of Crude Protein < 130 g / kg Dogs — Protein Source(s)

[0421] complete animal feed training

[0422] urate calculations at 12% humidity

[0423] Or

[0424] Crude protein < 220 g / kg

[0425] complete animal feed

[0426] 12% humidity

[0427] and selected protein sources

[0428] Crude protein < 317 g / kg Cats

[0429] complete animal feed

[0430] 12% humidity

[0431] Dissolution of the Undersaturation Properties of Dogs and — Phosphorus

[0432] Struvite stones, urine allowing dissolution in cats — Calcium

[0433] struvite calculations

[0434] — Sodium

[0435] and / or

[0436] — Magnesium

[0437] Urine acidifying properties

[0438] — Potassium

[0439] And

[0440] — Chloride

[0441] Magnesium < 1.8 g / kg of food

[0442] — Sulfur

[0443] complete pet food at 12%

[0444] humidity

[0445]

[0446] Reduction of Complete Food for Dogs and — Phosphorus

[0447] formation of subsaturation or cat properties — Calcium

[0448] recurrent urine metastasis

[0449] — Sodium

[0450] struvite calculations to reduce formation

[0451] struvite calculations — Magnesium

[0452] and / or — Potassium

[0453] Urine acidifying properties — Chloride

[0454] and — Sulfur

[0455] Magnesium < 1.8 g / kg of food

[0456] complete pet food at 12%

[0457] humidity.

[0458] Compensation for highly digestible food: Dogs and cats — Sources of highly digestible ingredients, maldigestion, apparent digestibility, and, where appropriate, their treatment — low-digestive pet food

[0459] fiber content [crude fiber <

[0460] 44 g / kg of complete feed for

[0461] animals at 12% humidity]:

[0462] - crude protein > 85%

[0463] - crude fat > 90%

[0464] Or

[0465] - fortified animal feed

[0466] in fiber [crude fiber > 44 g / kg

[0467] complete animal feed

[0468] 12% humidity]:

[0469] - crude protein > 80%

[0470] - crude fat > 80%

[0471] Reduction of the risk of malabsorption in highly digestible foods: Dogs and cats — Sources of highly digestible ingredients

[0472] - low-sodium animal feed

[0473] intestinal fiber content [crude fiber < — Potassium

[0474]

[0475] 44 g / kg of complete feed for

[0476] animals at 12% humidity]:

[0477] - crude protein > 85%

[0478] - crude fat > 90%

[0479] Or

[0480] - fortified animal feed

[0481] in fiber [crude fiber > 44 g / kg

[0482] complete animal feed

[0483] 12% humidity]:

[0484] - crude protein > 80%

[0485] - crude fat > 80%

[0486] And

[0487] Sodium > 1.8 g / kg of food

[0488] complete pet food at 12%

[0489] humidity

[0490] And

[0491] Potassium > 5 g / kg of feed

[0492] complete pet food at 12%

[0493] humidity

[0494] Increased Electrolyte Reduction: Dogs and — Sodium

[0495] Risk of sodium > 1.8% in cats — Potassium

[0496] malabsorption

[0497] - potassium > 0.6% — Source(s) of carbohydrates

[0498] acute intestinal

[0499] And

[0500] Highly digestible carbohydrates:

[0501] - > 32%

[0502] Support for dogs and cats with a fat content < 110 g / kg — Crude fat “Low in fat content” complete food with 12% fat

[0503] lipids in case of humidity

[0504] hyperlipidemia

[0505]

[0506] Support for "Moderate Protein Content": Dogs and cats — Protein source(s) "Moderate protein content, liver function, crude protein < 279 g / kg — Copper (total) selected and highly digestible" in the case of complete pet food with — Sodium

[0507] 12% humidity deficiency for dogs

[0508] hepatic

[0509] crude protein < 370 g / kg

[0510] complete animal feed review

[0511] 12% humidity for cats

[0512] And

[0513] Selected protein sources

[0514] And

[0515] Recommended digestibility of

[0516] dietary protein > 85%

[0517] Low in protein, but Equines — Sources of protein and fiber

[0518] High-quality proteins and — highly digestible carbohydrates and, in the case

[0519] highly digestible carbohydrates, if applicable, their processing

[0520] — Methionine

[0521] — Choline

[0522] — Content of n-3 fatty acids (if added)

[0523] Support for Reduced Sodium Content: Dogs and — Magnesium

[0524] Cardiac function sodium < 2.6 g per kg of cat food — Potassium

[0525] in full at 12% moisture — Sodium

[0526] of inadequacy

[0527] heart

[0528] chronic

[0529] Reduction of Metabolizable Energy < 3060 Dogs — Energy Value

[0530] excess weight kcal / kg of complete feed for

[0531] animals at 12% humidity

[0532] Or

[0533]

[0534] Metabolizable energy < 560 kcal / kg

[0535] complete animal feed

[0536] 85% humidity

[0537] Metabolizable energy < 3,190 Cats

[0538] kcal / kg of complete feed for

[0539] animals at 12% humidity

[0540] Or

[0541] Metabolizable energy < 580 kcal / kg

[0542] complete animal feed

[0543] 85% humidity

[0544] Linoleic acid support > 12.3 g per kg and Dogs and — Linoleic acid “High linoleic acid content dermal function sum of acid cats — Sum of eicosapentaenoic acid as well as in acid in case of eicosapentaenoic acid and docosahexaenoic acid eicosapentaenoic acid (EPA) and in dermatosis and docosahexaenoic acid > 2.9 g per kg docosahexaenoic acid (DHA) hair loss of complete feed for animals with added”

[0545] 12% humidity

[0546] Linoleic acid > 18.5 g per kg and Dogs

[0547] sum of acid

[0548] eicosapentaenoic acid and acid

[0549] docosahexaenoic > 0.39 g per kg

[0550] complete animal feed

[0551] 12% humidity

[0552] Linoleic acid > 18.5 g per kg and Cats

[0553] sum of acid

[0554] eicosapentaenoic acid and acid

[0555] docosahexaenoic > 0.09 g per kg

[0556] complete animal feed

[0557] 12% humidity

[0558] Total Omega-3 Fatty Acids Support > Dogs — Omega-3 Fatty Acids (Total)

[0559] metabolism of 29 g per kg and acid — Eicosapentaenoic acid (total)

[0560] eicosapentaenoic > 3.3 g per kg

[0561] — Vitamin E (total)

[0562]

[0563] joints in the case of complete animal feed

[0564] osteoarthritis, 12% humidity and

[0565] Appropriate levels of vitamin E

[0566] Total omega-3 fatty acids > Cats — Omega-3 fatty acids (total)

[0567] 10.6 g / kg of complete feed for — Docosahexaenoic acid (total)

[0568] animals at 12% moisture and acid

[0569] — Methionine (total)

[0570] docosahexaenoic > 2.5 g / kg

[0571] of complete animal feed with — Manganese (total)

[0572] 12% moisture and — Vitamin E (total)

[0573] Increased levels of methionine and

[0574] manganese

[0575] Appropriate levels of vitamin E

[0576] Reduced copper content: copper < Dogs Copper (total)

[0577] accumulation 8.8 mg / kg of complete feed at 12%

[0578] liverwort, copper, moisture

[0579] Reduced iodine content: iodine < Total iodine

[0580] iodine content of 0.26 mg / kg of complete feed to

[0581] food for 12% moisture

[0582] animals in case

[0583] of hyperthyroidism

[0584] Support in 1 to 3 g of hydrolyzed bovine casein Dogs Hydrolyzed bovine casein at the

[0585] stressful situations, with trypsin per kg of food trypsin

[0586] which will result in a total humidity of 12%

[0587] a decrease in

[0588] behavior

[0589] partner

[0590] Support for estrus and reproduction - High selenium content and Mammals Name and total quantity of each trace element and vitamin E per kg added is permitted. Administration as a bolus preparation is permitted. A bolus may contain up to 20% iron in a 12% moisture content: 50 mg for pigs, inert, non-bioavailable form.

[0591] 35 mg for rabbits and 88 mg to increase its density.

[0592]

[0593] dogs, cats and mink; minimum vitamin E content per

[0594] animal and per day: 100 mg for the

[0595] sheep, 300 mg for cattle and

[0596] 1100 mg for horses

[0597] Or

[0598] - high vitamin A content

[0599] and / or vitamin D and / or content

[0600] minimum beta-carotene of 300 mg

[0601] per animal and per day.

[0602] Complementary foods for

[0603] animals may contain

[0604] selenium, vitamin A and the

[0605] vitamin D in a concentration

[0606] greater than 100 times the content

[0607] maximum set for food

[0608] complete pet outfits.

[0609] - High vitamin A content in birds. Name and total quantity of each added vitamin A and / or vitamin D trace element and vitamin.

[0610] - high selenium content

[0611] and / or zinc and / or minimum content of

[0612] vitamin E of 40 mg / kg of food

[0613] Complete at 12% humidity.

[0614] Complementary foods for

[0615] animals may contain

[0616] selenium, zinc, vitamin A

[0617] and vitamin D in a

[0618] concentration greater than 100 times

[0619] the maximum content set for the

[0620] complete animal feed.

[0621]

[0622] Support for high zinc content. Horses, — Zinc (total) Administration as a bolus for hoof regeneration is permitted in animals that may contain zinc. Complementary feeds for ruminants and pigs — Methionine (total)

[0623] — Biotin (if added) ruminants. A bolus may contain up to 20% of iron in a non-bioavailable, inert form, in order to increase its density. This is 100 times the maximum bioavailable content set for complete feeds for animals.

[0624] Prevention of nutritional imbalances: The dietetic feed has the following minimum nutritional requirements for ruminants: Name and total quantity of additives. Administration in the form of a bolus is permitted in complete diets at 12% moisture and / or may contain up to 20% iron. The dietetic feed has the following minimum requirements: Pigs - selenium: 0.1 mg / kg of feed. Rabbits and pigs. A bolus may contain up to 20% iron.

[0625] - Zinc: 15 mg / kg of complete feed in a non-bioavailable form at 12% moisture and / or inert form, to increase its density. - Copper: 2 mg / kg of complete feed

[0626] at 12% humidity for sheep

[0627] and 5 mg / kg of complete feed at

[0628] 12% humidity for the others

[0629] species and / or

[0630] - vitamin A: 2000 IU / kg of food

[0631] complete at 12% moisture and / or

[0632] - vitamin D: 400 IU / kg of food

[0633] complete at 12% moisture and / or

[0634] - vitamin E: 35 mg / kg of food

[0635] complete at 12% humidity for the

[0636] poultry, 10 mg / kg of feed

[0637] complete at 12% humidity for the

[0638] Ruminants, 40 mg / kg of feed

[0639] complete at 12% humidity for the

[0640] rabbits and 20 mg / kg of feed

[0641] complete at 12% humidity for the

[0642] pigs

[0643] Complementary foods for

[0644]

[0645] Animals may contain selenium, zinc, copper, and other minerals.

[0646] vitamin A and vitamin D in

[0647] a concentration greater than 100

[0648] times the maximum content set for

[0649] Complete animal feed.

[0650] Weaning support: Minimum intakes as follows: Mammals - selenium: 0.1 mg / kg of feed

[0651] complete at 12% moisture and / or

[0652] - zinc: 15 mg / kg of complete food at

[0653] 12% humidity and / or

[0654] - copper: 2 mg / kg of complete feed

[0655] 12% humidity for sheep

[0656] and 5 mg / kg of complete feed at

[0657] 12% humidity for the others

[0658] species and / or

[0659] - iodine: 0.2 mg / kg of complete food at

[0660] 12% humidity and / or

[0661] - manganese: 20 mg / kg of food

[0662] complete at 12% moisture and / or

[0663] - vitamin A: 1500 IU / kg of food

[0664] complete at 12% moisture and / or

[0665] - vitamin D: 400 IU / kg of food

[0666] complete at 12% moisture and / or

[0667] - vitamin E: 100 mg / kg of food

[0668] complete at 12% humidity for the

[0669] calves and 50 mg / kg of feed

[0670] complete at 12% humidity for the

[0671] lambs, kids and piglets.

[0672] Complementary foods for

[0673] animals may contain

[0674] selenium, zinc, copper, and

[0675]

[0676] iodine, manganese, vitamin A and vitamin D in a

[0677] concentration greater than 100 times

[0678] the maximum content set for the

[0679] complete animal feed.

[0680] Support for the - Minimum intake of Mammalian compounds Name and total quantity of additives

[0681] zinc regeneration through dietary foods and nutritional poultry, if necessary

[0682] skin and corresponding to 20 mg / kg of food

[0683] complete hair and skin at 12% humidity and

[0684] - High content of: copper and / or iodine

[0685] and / or selenium and / or

[0686] vitamin B6 and / or vitamin E and / or

[0687] vitamin A and / or

[0688] methionine and / or cystine and / or

[0689] minimum intake of 0.4 mg of biotin

[0690] per kg of complete feed for

[0691] animals at 12% humidity for the

[0692] ruminants.

[0693] Complementary foods for

[0694] Animals may contain zinc.

[0695] copper, iodine, selenium and

[0696] vitamin A in a

[0697] concentration greater than 100 times

[0698] the maximum content set for the

[0699] complete animal feed.

[0700] Stabilization of the - Primarily electrolytes: Calves, piglets, - Sodium Recommended quantities of sodium, potassium and chlorides per liter of solution - Potassium

[0701] electrolytes and buffering capacity in the case of lambs,

[0702] — Ready-to-use chlorides for water in order to prepare liquid feed: for a minimum of 60 kids and their diet:

[0703] facilitate the — Source(s) of carbohydrates

[0704] mmol per liter of ready-to-use foal potion

[0705] Sodium: 1.7 g - 3.5 g. For digestive purposes, use in food. — Bicarbonates and / or citrates (if added)

[0706] Physiological potassium: 0.4 g - 2 g

[0707] - Easily digestible carbohydrates

[0708] chlorides: 1 g - 2.8 g

[0709]

[0710] Reduction of high magnesium content, Ruminants — Starch. Administration as a bolus is permitted. A bolus may cause tetany (hypomagnesemia).

[0711] Moderate protein content and — Magnesium, containing up to 20% iron in a non-bioavailable, inert form, low potassium content — Sodium

[0712] in order to increase its density.

[0713] — Potassium

[0714] Reduction of the risk of acidosis in very low carbohydrate ruminants — Starch. Administration as a bolus is permitted. A bolus may contain up to 20% iron in a non-bioavailable, inert form to increase its density. Low carbohydrate content, high potent fermentable starches — Sugars (total).

[0715] Reduction of Low Phosphorus and Calcium Content in Ruminants

[0716] Magnesium kidney stone risk, properties — Phosphorus

[0717] urinary acidification

[0718] — Sodium

[0719] — Magnesium

[0720] — Potassium

[0721] — Chlorides

[0722] — Sulfur

[0723] — Substances that acidify urine

[0724] Prolonged intake of high content of: Ruminants — Name and total quantity of each trace element - trace elements and / or having a trace element, vitamin, provitamin A bolus is permitted. A bolus may be administered as a trace element, vitamin, provitamin B3, and / or vitamins and substances with similar effects.

[0725] - vitamins, provitamins and rumen contain up to 20% iron in animals

[0726] Chemically well-defined substances with similar effects are added. The inert, non-bioavailable form is functional grass.

[0727] chemically well defined. — Daily release rate to increase its density.

[0728] each trace element and / or vitamin

[0729] Supplementary foods

[0730] if a bolus is used.

[0731] pet supplies may contain

[0732] — Maximum release time

[0733] additives in a concentration

[0734] continuous trace element or

[0735] greater than 100 times the content

[0736] vitamin if a bolus is used.

[0737] maximum set for food

[0738] complete pet supplies

[0739]

[0740] Reduction of Low Cation / Anion Ratio in Cows — Calcium

[0741] Risk of fever. For the total ration: dairy — Phosphorus

[0742] vitular and

[0743] - Minimal acidification by — Magnesium

[0744] hypocalcemia

[0745] subclinical animal feed targeting — Sodium

[0746] Specific nutritional objective: — Potassium

[0747] 100 mEq / kg dry matter

[0748] — Chlorides

[0749] - Target: Range between

[0750] negative values ​​of BACA and — Sulfur

[0751] BACA values ​​< 100

[0752] (mEq / kg of dry matter)

[0753] Or

[0754] Zeolite (sodium aluminosilicate): Sodium aluminosilicate should not exceed a daily dose of 250 to 500 g or 500 g of sodium aluminosilicate per animal.

[0755] Supply of raw materials for Calcium

[0756] non-animal feed

[0757] rumen-degradable, rich in

[0758] phytic acid (> 6%) and having a

[0759] calcium content < 0.2%, for

[0760] reach a minimum of 28 g and a

[0761] maximum of 32 g of calcium

[0762] available per cow and per day.

[0763] Or

[0764] High calcium content under — Calcium Administration as a bolus is permitted. A bolus may contain up to 20% iron under the inert, non-bioavailable form of calcium sources — Calcium sources availability: calcium chloride and / or calcium sulfate and / or calcium carbonate to increase its density.

[0765] calcium propionate and / or

[0766]

[0767] calcium formate and / or "any other source of calcium having a

[0768] similar effect

[0769] Minimum calcium intake

[0770] from one of these sources or

[0771] a combination of these

[0772] 50 g per cow per day

[0773] Or

[0774] Minimum calcium intake — Calcium administration in the form of calcium pidolate — Calcium pidolate bolus is permitted. A bolus may contain up to 20% iron in a non-bioavailable or inert form, to increase its density.

[0775] Solanum leaf flour — Glaucous Solanum leaf flour. Administration in the form of glaucous flour allowing for release — 1,25- bolus content is authorized. A daily bolus of 38 to 46 pg of 1,25-dihydroxycholecalciferol glycoside may contain up to 20% iron in its non-bioavailable, inert dihydroxycholecalciferol glycoside form.

[0776] — Crude cellulose

[0777] per day in order to increase its density.

[0778] — Magnesium

[0779] Or

[0780] — Crude fats

[0781] — Starch

[0782] — Vitamin D3 (total) as

[0783] cholecalciferol

[0784] 1,25-Dihydroxycholecalciferol Cows — 1,25-Dihydroxycholecalciferol Glycosylated 1,25-Dihydroxycholecalciferol from Solanum extract Dairy glycosylated from Solanum extract Glycosylated from Solanum extract From Solanum extract Glaucophyllum glaucophyllum extract should be administered daily at a rate of 15-80 pg of — Vitamin D3 (total) as a single, oral bolus dose, with a daily administration of:

[0785] — at least 60 g of calcium per cow in the week preceding the

[0786]

[0787] calving, and 84 g per cow until the end of the third week of lactation;

[0788] — at least 18 g of magnesium per cow the week before calving, and 26 g per cow until the end of the third week of lactation.

[0789] "The bolus can only be administered once during the pre-calving period (from the ninth day before calving to immediately before calving). Calcium and magnesium should be administered daily at the following levels:"

[0790] — at least 60 g of calcium per cow the week before calving, and 84 g per cow until the end of the third week of lactation;

[0791] — at least 18 g of magnesium per cow the week before calving, and 26 g per cow until the end of the third week of lactation.

[0792] Reduction of - Minimum intake of propane- 1,2- Cows — Propane- 1,2-diol, if added. Administration in the form of risk of ketosis ( 20 ) diol or propylene glycol: dairy, — Propionates in the form of bolus salts is permitted. A bolus may contain up to 20% iron in a non-bioavailable inert form, if added in a non-bioavailable inert form, - 250 g / day for dairy cows and ewes, and sodium or calcium salts, if added to increase its density.

[0793] Or

[0794]

[0795] - Minimum intake of propionates

[0796] (calcium or sodium salts):

[0797] - 110 g / day for dairy cows

[0798] - 22 g / day for ewes or

[0799] goats

[0800] Or

[0801] - Minimum combined intake of

[0802] propane-1,2-diol and propionates (salts

[0803] of sodium or calcium) provided

[0804] that:

[0805] - The combination of propane-1,2-diol and propionates for the

[0806] dairy cows is such that the

[0807] propionates 0.44 x propane-1,2-diol

[0808] > 110 g / day

[0809] - The combination of propane-1,2-diol and propionates for the

[0810] sheep or goats is such that the

[0811] propionates 0.44 x propane-1,2-diol

[0812] > 22 g / day

[0813] Mitigation of – High magnesium content Pigs — Magnesium

[0814] reactions to stress and / or — Highly digestible ingredients and, where applicable, their treatment

[0815] — n-3 fatty acid content (if added) Reduction of intestinal transit-stimulating ingredients Sows intestinal transit-stimulating ingredients risk of intestinal

[0816] constipation

[0817] Compensation for high iron compound content in piglets and total iron.

[0818] Iron deficiency allowed, classified in the group of non-calves

[0819] functional postnatal compounds of oligosevered

[0820] elements belonging to the category

[0821]

[0822] nutritional additives, as referred to in Annex I of Regulation (EC)

[0823] No. 1831 / 2003.

[0824] Complementary foods for

[0825] animals may contain iron

[0826] in a concentration greater than

[0827] 100 times the maximum set content

[0828] for whole foods

[0829] animals.

[0830] Compensation for Low Saturated Fatty Acid Content in Poultry, with — Percentage of saturated fatty acids due to malabsorption and high vitamin content, excluding the ratio of total fat-soluble fatty acids in geese and — Vitamin A (total)

[0831] pigeons

[0832] — Vitamin D (total)

[0833] — Vitamin E (total)

[0834] — Vitamin K (total)

[0835] Reduction of Low Energy Levels and Hens — Energy Value (calculated according to the EC method)

[0836] of metabolizable steatosis from lipids — Percentage of hepatic metabolizable energy with high fatty acid content from polyunsaturated lipids

[0837] — Polyunsaturated fatty acid content, Support for Equine Nutrition, High selenium content — Vitamin E (total)

[0838] preparation with a minimum of 50 mg of vitamin E — Selenium (total)

[0839] athletic effort and per kg of complete feed at 12%

[0840] moisture recovery.

[0841] This one: Complementary foods for

[0842] animals can contain

[0843] selenium compounds in a

[0844] concentration greater than 100 times

[0845] the maximum content set for the

[0846] complete animal feed.

[0847]

[0848] Compensation for electrolyte loss: Must contain sodium chloride. Equines — Sodium. Should contain sodium chloride — Chlorides

[0849] in cases of high potassium levels.

[0850] — Potassium for sweating. Low levels of magnesium, in

[0851] — Calcium

[0852] calcium and phosphorus

[0853] — Magnesium. The addition of other electrolytes (salts)

[0854] is optional. — Phosphorus Support of Starch and sugar: no more than 20% Equines — Starch metabolism of available energy. — Sugar energy and Crude fat: more than — Crude fat function 20% of available energy.

[0855] muscle pain in case of — Vitamin E (total) At least 350 IU of vitamin E per

[0856] of rhabdomyolysis kg of complete feed at 12%

[0857] humidity

[0858] Compensation for - Starch content to provide < 1 g Equines — Starch

[0859] Digestive disorders per kg of body weight per meal (< — Chronic crude fat of the fat 0.5 g per kg of body weight per

[0860] intestine meal, in case of diarrhea)

[0861] - Processed cereal grains

[0862] means of treatment

[0863] hydrothermal processes, such as extrusion,

[0864] micronization, expansion or the

[0865] flaking, to improve the

[0866] digestion of starch in the intestine

[0867] hail

[0868] - Additional vitamin intake

[0869] water-soluble and in adequate quantities

[0870] in minerals / electrolytes

[0871] - Additional oil supply in

[0872] the absence of diarrhea

[0873]

[0874] Compensation for - Highly digestible fibers Equines — Raw materials for animal feed

[0875] the inadequacy - Sources of high-quality animal protein that are highly digestible and, in the case

[0876] Chronic high levels of lysine > 4.3% of protein, if applicable, their treatment

[0877] function of crudes — Total sugars and starch

[0878] the small intestine

[0879] - Total sugars and starch reaching — Protein sources

[0880] a maximum of 0.5 g per kg of weight

[0881] body per meal

[0882] - Processed cereal grains

[0883] means of treatment

[0884] hydrothermal processes, such as extrusion,

[0885] micronization, expansion or the

[0886] flaking, to improve the

[0887] prececal digestion

[0888] Stabilization of animal feed additives, intestinal flora stabilizer species or

[0889] digestion of the functional group of animal microorganisms

[0890] physiological stabilizers of the intestinal flora for

[0891] referred to in Annex I of Regulation (EC) which

[0892] No. 1831 / 2003 or, pending stabilizer

[0893] the culmination of the flora procedure

[0894] reauthorization provided for in Article 10 intestinal

[0895] of Regulation (EC) No 1831 / 2003, or micro-additives for animal feed organism

[0896] of the group of microorganisms. is authorized

[0897]

[0898] Table 9 - Guidelines for formulating a dietary food matrix according to the disorder and the animal for which it is intended (extract from EU Regulation 2020 / 354) The invention relates to a veterinary medicated oral composition, in the form of a complete feed for the treatment and / or prevention of a disease in a domestic animal, comprising:

[0899] - a food matrix consisting of an animal feed meeting the standards of European regulation 2020 / 354 (animal feed for specific nutritional purposes, also known as PARNUT);

[0900] - at least one active medicinal ingredient, selected according to the targeted pathology, incorporated into the food matrix;

[0901] - said composition being adapted for controlled twice-daily intake, allowing optimized administration of the active ingredient in accordance with the animal's needs; - said composition being in the form of kibble and / or wet food;

[0902] - said composition being compliant with both PARNUT veterinary regulations and the requirements for placing on the market an oral veterinary medicinal product;

[0903] The illness may be frequent and / or recurrent; the illness may be chronic and / or progressive. A chronic illness is defined as a health condition that develops over a long period, generally more than three months, continuously or recurrently, often with a gradual progression that does not resolve spontaneously and is rarely completely curable by treatment. A chronic illness requires prolonged management, including regular medical care, monitoring, and often lifestyle modifications.

[0904] From a medical perspective, a chronic disease is typically associated with persistent physiological alterations (e.g., organ or systemic dysfunction); stable or evolving biological markers over time; increased risks of long-term complications; and a need for long-term treatments (medication, rehabilitation, specialized follow-up).

[0905] A progressive disease is defined as a health condition characterized by progression over time, with a gradual worsening of symptoms, lesions, or dysfunction of an organ or system. A progressive disease requires regular monitoring, therapeutic adjustments, and sometimes strategies to slow its progression (neuroprotective, anti-inflammatory, immunomodulatory, etc.).

[0906] The invention relates, according to one aspect, to a new galenic form of a medicinal active ingredient comprising a food meeting the definition of a PARNUT and at least one veterinary medicinal active ingredient.

[0907] The use of a food matrix conforming to the PARNUT regulation for the manufacture of a veterinary medicinal product is an object of the present invention. The invention relates, according to one aspect, to the use of a food matrix conforming to the PARNUT regulation for the manufacture of a medicinal product used in the treatment of an animal suffering from a chronic and / or progressive disease.

[0908] The invention relates, according to one aspect, to the use of a food matrix conforming to the PARNUT regulation for the manufacture of a medicinal product used in the treatment of an animal suffering from a frequent and / or recurring disease.

[0909] The invention relates, in one aspect, to the use of a feed matrix conforming to the PARNUT regulation for the manufacture of a medicinal product used in the treatment of an animal suffering from a chronic and / or progressive disease, and administered at least twice a day. The invention also relates, in another aspect, to the use of a feed meeting the definition of a PARNUT for the manufacture of a medicinal product, or even for the manufacture of a medicinal product used in the treatment of an animal suffering from a chronic and / or progressive disease, administered at least twice a day.

[0910] A key feature of the invention lies in the synergy between the nutritional structure of the dietary food matrix and the pharmacokinetic behavior of the active ingredient. Unlike existing compositions where the active ingredient is simply incorporated into a lipid coating or randomly dispersed, the invention proposes a specific interaction between the dietary food matrix and the active ingredient, enabling:

[0911] - Adjustment of the drug release profile according to the pathology being treated. - Optimization of intestinal absorption, thanks to homogeneous distribution and adaptation of the lipid vehicle.

[0912] - Modulation of adverse effects, by reducing peak plasma concentrations or by improving digestive tolerance.

[0913] This synergy helps to ensure a more stable and prolonged therapeutic effect, thus reducing inter-individual variability and offering better predictability of clinical results (and / or adverse effects).

[0914] In particular, this synergy allows the product to remain stable for more than 30 days at 25°C.

[0915] Active ingredient

[0916] Depending on the chronic or progressive disease to be treated, the active ingredient(s) are chosen from among: - Antihypertensives: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), renin inhibitors. - Antiproteinurics: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), spironolactone, finerenone, advantageously benazepril or one of its salts such as benazeprilat ((3S)-3-[[(1S)-(l-carboxy-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid); - Anti-inflammatories: selective and non-steroidal anti-inflammatory drugs (NSAIDs) selective, phosphodiesterase 4 (PDE4) inhibitors, recombinant anti-inflammatory cytokines.- Analgesics: opioids (buprenorphine, tramadol), gabapentinoids (gabapentin, pregabalin), sodium channel blockers, NMDA receptor antagonists (N-methyl-D-aspartate receptor).

[0917] - Chondroprotective and joint modulators: glucosamine, chondroitin sulfate, diacerein, hyaluronic acid, bioactive collagen peptides, pentosan polysulfate sodium. - Immunomodulators: cyclosporine, mycophenolate mofetil, oclacitinib, monoclonal antibodies directed against pro-inflammatory cytokines (e.g., anti-interleukin (IL)-31, anti-IL-4 / -13).

[0918] - Nephroprotective agents: specific antioxidants (astaxanthin, polyphenols, vitamin E, S-adenosylmethionine), regulators of phosphorus metabolism (lanthanum, sevelamer), activators of the NRF2 factor (transcription factor "nuclear factor erythroid-2-related factor 2"),

[0919] - Cardiovascular drugs: beta-blockers, calcium channel blockers, neprilysin inhibitors.

[0920] - Gastroprotective agents: proton pump inhibitors (omeprazole, pantoprazole), histamine H2 receptor antagonists (famotidine, ranitidine), sucralfate, misoprostol. - Metabolic and endocrine agents: parathyroid hormone analogues, GLP-1 agonists, biguanides (metformin), thiazolidinediones.

[0921] Specifically, glucagon-like peptide-1 (GLP-1) analogs. GLP-1 slows gastric emptying (which leads to a decrease in the rate of glucose absorption in the intestines) and increases the feeling of satiety (the sensation of having eaten enough) by acting on brain areas that control food intake. These analogs include, but are not limited to, semaglutide and liraglutide. These compounds show promising potential for the treatment of obesity in animals.

[0922] - Antimicrobials: broad-spectrum or targeted antibiotics (fluoroquinolones, aminoglycosides, beta-lactams, macrolides), antifungals, antivirals. - Neuroprotective and cognitive modulators: acetylcholinesterase inhibitors, phospholipid precursors, N-methyl-D-aspartate (NMDA) receptor antagonists, neuronal antioxidants.

[0923] - antidiabetics such as a blood glucose inhibitor (metformin), an SLGT2 inhibitor (empagliflozin, dapagliflozin, canagliflozin) or a DPP-4 inhibitor (sitagliptin, saxagliptin, vildagliptin, linagliptin).

[0924] Antidiabetic drugs are sodium-glucose cotransporter 2 (SGLT2) inhibitors, also known as gliflozins. These substances reduce blood glucose levels by inhibiting renal glucose reabsorption. Examples include velagliflozin and bexagliflozin. Velagliflozin, in particular, is a new active substance authorized for veterinary use under the brand name SENVELGO®, indicated for reducing hyperglycemia in cats with type 2 diabetes mellitus.

[0925] - medications to reduce excess weight: semaglutide, exenatide, dulaglutide, liraglutide, tirzepatide, or even mitratapide and dirlotapide;

[0926] - medications that increase weight: capromorelin,

[0927] - anti-cancer agents:

[0928] - Chlorambucil: an alkylating agent often used to treat chronic small cell lymphoma and other types of cancer.

[0929] - Cyclophosphamide: an alkylating agent used in various chemotherapy protocols for different types of cancer, including lymphoma and multiple myeloma. - Lomustine: a nitrosourea used primarily to treat mast cell tumors and certain types of brain tumors.

[0930] - Toceranib phosphate: tyrosine kinase inhibitor specifically approved for the treatment of recurrent or unresectable grade II or III cutaneous mast cell tumors in dogs.

[0931] - Masitinib mesylate: tyrosine kinase inhibitor used for the treatment of unresectable grade 2 or 3 mast cell tumors in dogs.

[0932] - Prednisolone and other corticosteroids: Although not strictly chemotherapeutic agents, corticosteroids are often used orally in the treatment of certain cancers, such as lymphoma, due to their anti-inflammatory and lympholytic properties.

[0933] - Metronomic chemotherapy: This involves the frequent administration of low doses of oral chemotherapy agents (such as cyclophosphamide, chlorambucil, or melphalan) on a continuous basis. This approach aims to inhibit angiogenesis and achieve a long-term anti-tumor effect with fewer acute side effects.

[0934] Although parasitic infestations are not considered chronic or progressive diseases, the animal's environment often results in frequent contact with parasites, requiring the owner or breeder to administer frequent and repeated treatments. In this context, the veterinary oral composition according to the invention may advantageously comprise one or more antiparasitic active ingredients.

[0935] The flexibility in the choice of active ingredients allows the composition to be adapted to the specific needs of each patient, depending on their clinical condition and the pathology to be treated. According to a preferred embodiment of the invention, the active ingredient(s) are chosen from among antihypertensives, antiproteinurics, anti-inflammatories, anticancer agents, analgesics, chondroprotective agents, immunomodulators, antidiabetics, and nephroprotective agents.

[0936] According to a particular embodiment of the invention, the active ingredient is benazepril or a pharmaceutically acceptable salt thereof, and the veterinary oral composition is intended for the reduction of proteinuria associated with chronic kidney disease (CKD) in cats, in particular chronic kidney disease of stage 1 or higher than stage 1 disease, stage 2, or stage 3.

[0937] The amount of active ingredient to be incorporated into the veterinary oral composition is readily determined by a person skilled in the art, taking into account the usual diet of the animal being treated and the dose of active ingredient to be administered. Given the superior therapeutic efficacy of the veterinary oral composition according to the invention, this daily dose, administered to an animal at least twice a day, preferably twice a day, can be reduced by 10 to 50% by weight, depending on the active ingredient, compared to the recommended dose of said active ingredient.

[0938] It has indeed been demonstrated that the composition according to the invention is a pharmaceutical form that reduces the effective amount of active ingredient that must be ingested to produce the desired therapeutic effect. This effect is particularly advantageous for sick animals, which often have a reduced appetite.

[0939] Furthermore, the amount of active ingredient incorporated into the veterinary oral composition according to the invention significantly reduces the risk of side effects due to said active ingredient. The active ingredient(s) formulated in the veterinary oral composition are incorporated into said composition in such a way that they are homogeneously distributed throughout the composition. This homogeneity means that samples of the veterinary oral composition of the same weight contain the same amount of active ingredient. This result is achieved by implementing a particular process for preparing the veterinary oral compositions according to the invention, which is detailed below.

[0940] According to one aspect, the active ingredient(s) formulated in the veterinary oral composition may be incorporated into the coating of said composition in such a way that they are distributed homogeneously around the entire composition.

[0941] This result can be achieved by coating the food matrix particles (kibble for example) with a layer that includes the active ingredient.

[0942] The composition according to the invention is characterized in that it complies both with the PARNUT veterinary regulations and with the requirements for placing on the market an oral veterinary medicinal product.

[0943] In particular, the requirements for placing an oral veterinary medicinal product on the market may be regulatory.

[0944] For the sake of clarity, conforming to the PARNUT veterinary regulations means that the composition according to the invention meets the requirements, or corresponds to the defined criteria, or fulfills the conditions set, or is in accordance with the requirements of the PARNUT regulations, as specified in European Regulation 2020 / 354 of the date of filing of the present invention.

[0945] According to one embodiment, the galenic form of composition according to the invention is a dry food in the form of kibble.

[0946] In particular, the pet food containing a pharmaceutical active ingredient according to the invention is such that the active ingredient is stable for a prolonged period under storage conditions at 25°C and is protected against thermal and oxidative degradation during the manufacturing and storage process.

[0947] According to this embodiment, the kibble may include an external coating, in particular a lipid coating, which allows for modulating palatability and improving the absorption of the active ingredient while ensuring its stability.

[0948] According to another embodiment, the galenic form of the composition according to the invention is a moist food in the form of a paste, terrine, soup or mince.

[0949] First and second therapeutic uses The present invention further relates to the veterinary oral composition according to the invention for its use as a medicinal product.

[0950] It also relates to the veterinary oral composition according to the invention for its use for the prevention and / or treatment of a chronic or progressive disease in a companion or farm animal.

[0951] Pets or farm animals include mammals, such as dogs, cats, sheep, cattle, pigs, equines, birds, and fish.

[0952] Preferably, the animal is a cat or a dog.

[0953] According to a particular embodiment, the animal to be treated has an eating disorder such as anorexia, dysorexia or hyporexia, and does not eat enough, that is to say it consumes reduced quantities of food compared to normal needs and recommended doses, these quantities can be reduced from 10% to 50%, or in the order of 20%, 30%, 40% or even 50%.

[0954] Chronic or progressive diseases include, in particular:

[0955] Diseases affecting the musculoskeletal system:

[0956] - Osteoarthritis: Dogs, cats, horses, cattle, and other mammals.

[0957] - Arthritis: Dogs, cats, cattle, and other animals.

[0958] - Hip / elbow dysplasia: Dogs (especially large breeds).

[0959] Diseases affecting the renal system:

[0960] - Chronic kidney disease (CKD): Cats, dogs, and other older animals.

[0961] - Chronic glomerulonephritis: Dogs and cats.

[0962] Diseases affecting the cardiovascular system:

[0963] - Cardiomyopathy: Cats (hypertrophic cardiomyopathy), dogs (dilated cardiomyopathy), horses.

[0964] - Chronic mitral valve disease: Dogs (especially small breeds).

[0965] - Congestive heart failure: Dogs and cats.

[0966] Endocrine diseases:

[0967] - Diabetes mellitus: Cats, dogs, horses.

[0968] - Hyperthyroidism: Cats.

[0969] - Hypothyroidism: Dogs.

[0970] - Cushing's disease (hyperadrenocorticism): Dogs, horses.

[0971] Respiratory diseases:

[0972] - Feline asthma: Cats. - Chronic bronchitis: Dogs.

[0973] - Bovine respiratory diseases (bovine respiratory complex): Cattle.

[0974] - Emphysema (horses): Horses.

[0975] Skin diseases:

[0976] - Atopic dermatitis: Dogs and cats.

[0977] - Seborrheic dermatitis: Dogs and cats.

[0978] - skin disease caused by parasites

[0979] Neurological diseases:

[0980] - Epilepsy: Dogs and cats.

[0981] - Chronic wasting disease (CWD): Cervids (deer, elk, etc.).

[0982] - Cognitive dysfunction syndrome (older dog / cat): Older dogs and cats.

[0983] Digestive diseases:

[0984] - Chronic inflammatory bowel diseases (IBD): Dogs and cats.

[0985] - Chronic pancreatitis: Dogs and cats.

[0986] Chronic infectious diseases:

[0987] - Feline leukemia (FeLV): Cats.

[0988] - Feline immunodeficiency virus (FIV): Cats.

[0989] - Feline infectious peritonitis (FIP): Cats.

[0990] Other chronic diseases:

[0991] - Overweight and obesity: dogs and cats.

[0992] - Cancer: All animals.

[0993] - recurrent parasitic infestations by endo- and / or ectoparasites.

[0994] According to a preferred embodiment, the chronic disease is chosen from renal failure, congestive heart failure, cancer, diabetes, obesity, hypertension, or any other renal or cardiovascular pathology.

[0995] According to a particular embodiment, the veterinary oral composition is formulated so that it can be administered twice a day.

[0996] Indeed, one of the major problems with veterinary treatments lies in the variability of medication intake by domestic animals.

[0997] The invention addresses this challenge by optimizing the oral veterinary medicinal composition to improve the pharmacokinetics of the active ingredient, allowing for more efficient absorption in the digestive tract compared to conventional administration in tablet or liquid form orally, whether taken with or without food. The invention thus makes it possible to offer controlled twice-daily administration, perfectly adapted to the natural feeding behavior of dogs and cats.

[0998] Controlled bi-daily administration is defined as administration twice a day, preferably at intervals of 4, 6, 8 to 12 hours.

[0999] Controlled bi-daily administration is understood to mean administration twice a day, preferably twice a day at 12-hour intervals, and controlled by the owner of the animal who ensures that the animal has eaten the dose corresponding to at least half of the necessary dose of the composition according to the invention to obtain a therapeutic effect at each feeding, i.e. for example 11.71 g of benazepril divided by 2, for the composition according to the invention comprising benazepril and for a cat.

[1000] According to one aspect, the interval between the two administrations can be reduced to less than 4 hours, and / or the number of administrations greater than twice daily, provided that the administrations are carried out by the owner of the animal (in particular for a cat) and that the minimum quantity of food corresponds to the dose of medicine prescribed by the veterinarian, i.e. for example 11.71 g of benazepril per day for the composition according to the invention comprising benazepril.

[1001] In particular, twice-daily administration ensures that the animal receives enough medication to treat itself without being under- or over-dosed (reducing the risk of side effects) while maintaining its weight. Unlike conventional medication forms (tablets, suspensions) which require the animal to take the medication with (forced) intervention from its owner (by gavage), and whose pharmacokinetics are often adapted for a single administration, the twice-daily approach, especially with a 12-hour interval, guarantees:

[1002] - Improved stability of plasma concentrations of the active ingredient.

[1003] - A reduction in the risk of underdosing or overdosing, particularly in animals in a fragile state.

[1004] - Improved compliance through feeding associated with the animal's usual eating behavior.

[1005] - a reduction by at least half of the dose ingested at one time,

[1006] - no additional side effects.

[1007] This characteristic is particularly advantageous for chronic conditions requiring a constant therapeutic effect throughout the day, such as chronic renal failure. Surprisingly, fractionating the administration allows for a more constant and, above all, sufficient plasma concentration of the active ingredient to be achieved and maintained to treat the animal; it thus acts like a slow infusion without requiring the inconvenience of inserting an injection device such as a catheter.

[1008] Thus, according to a preferred embodiment, the invention relates to the veterinary oral composition according to the invention for its use in reducing proteinuria associated with chronic kidney disease in cats, in particular for the treatment of chronic renal failure in cats, stage 1 or higher than stage 1 of the disease, i.e., stage 2 or stage 3, and is characterized in that it comprises benazepril. According to this embodiment, the cat may also suffer from anorexia.

[1009] According to this embodiment, which aims at the prevention and / or treatment of renal failure in cats, the daily dose of benazepril is reduced by 10%, 20%, 30%, 40%, or 50% compared to the recommended dose for Fortekor®, which is between 0.5 and 1 mg / kg of body weight per day. Thus, the daily dose of benazepril per kg of body weight provided by the oral medicated composition according to the invention can be reduced to between 0.25 and 0.5 mg and is preferably administered in two doses throughout the day. More specifically, the experimental portion details the superiority of the veterinary oral medicated composition of the invention:

[1010] Advantageously, the veterinary oral medicinal composition of the invention is palatable even to sick animals, which accept to ingest it without constraint (without forced gavage) on a daily basis in sufficient quantity for the active ingredient to have sufficient bioavailability to prevent and / or treat a chronic disease.

[1011] In the specific case of chronic renal failure, comparative pharmacokinetic and pharmacodynamic (PK / PD) studies have demonstrated that the veterinary oral drug composition according to the invention allows an inhibition of angiotensin-converting enzyme (ACE) at least equivalent, and under certain conditions, superior to that obtained with conventional administration in tablet form (Fortekor®), at an equivalent dose.

[1012] Proven effect:

[1013] Pharmacodynamic analysis indicates that the FACE (Angiotensin-Converting Enzyme) inhibition profile obtained with the composition according to the invention comprising benazepril is superior to that of Fortekor®, particularly in animals with chronic renal failure. PK / PD modeling shows that the stability of the therapeutic effect is improved, especially in the event of variations in food intake, thus ensuring better overall disease control.

[1014] Unlike conventional tablet forms, the dietary food matrix of the composition according to the invention plays an active role in modulating the release of the active ingredient, thus optimizing pharmacokinetic exposure and reducing inter-individual fluctuations.

[1015] These results confirm that the integrated nutrition-pharmacokinetic approach implemented in the invention ensures optimal therapeutic efficacy, while improving adherence and tolerance of treatment in domestic animals.

[1016] Furthermore, the veterinary oral medicated composition of the invention provides therapeutic robustness in case of partial administration:

[1017] A major clinical advantage of the invention lies in its therapeutic robustness, even in the event of partial consumption of the ration. This is essential because anorexia is a common problem in sick animals, particularly cats with chronic kidney disease (CKD). In this context, the veterinary oral medicated composition of the invention ensures:

[1018] - A homogeneous distribution of the active ingredient throughout the day, guaranteeing a minimum effectiveness even if the animal only consumes part of its ration.

[1019] - Enhanced clinical safety, limiting the risk of critical underdosing.

[1020] This point is a strong argument for veterinarians, who have to manage patients whose food intake is irregular.

[1021] Therapeutic flexibility: the invention allows the formulation to be adapted to the individual needs of patients:

[1022] - the choice of the dietary food matrix (PARNUT) is adjusted to the stages of the disease (for example, the composition of the dietary food matrix can be adjusted at each stage of renal failure).

[1023] - Dietary food matrix can be presented in different solid or wet galenic forms (kibble, pâté, terrine...).

[1024] - The veterinary oral medicated composition of the invention can also incorporate several active ingredients allowing the prevention and / or treatment of several chronic or progressive diseases. In conclusion, the present invention offers an integrated therapeutic and nutritional solution, combining pharmacokinetic optimization, regulatory compliance, clinical efficacy and improved adherence.

[1025] Process

[1026] The invention proposes an innovative and optimized method of incorporating the active ingredient via a therapeutic premix integrated into a pre-prepared food matrix.

[1027] A drug premix (also called a therapeutic premix) is one or more active ingredients such as those mentioned above, mixed with one or more carriers acceptable for oral administration.

[1028] This medicated premix can be:

[1029] - mixed directly into the kibble with a specific lipid layer (example: benazepril incorporated via an oily mixture) or

[1030] - pre-dispersed in an acceptable lipid, organic or mineral vector, before being integrated into the food matrix.

[1031] This approach ensures optimal homogeneity, guaranteeing that each administered portion contains a precise and reproducible amount of active ingredient.

[1032] The composition according to the invention can be obtained by a manufacturing process validated according to pharmaceutical quality standards, including a step of preparing a homogenized drug premix before incorporation into the food matrix.

[1033] According to one embodiment, the process for manufacturing a veterinary oral medicated composition in the form of a complete feed intended for the treatment or prevention of a chronic or progressive disease in a domestic animal comprises the following steps:

[1034] - Submit a food matrix adapted to the specific pathophysiological needs of the affected animal, said matrix respecting the PARNUT criteria;

[1035] - Prepare a therapeutic premix, in which at least one active medicinal ingredient is homogenized in a suitable support or acceptable vector;

[1036] - Incorporate the therapeutic premix homogeneously into the food matrix, either directly during the manufacture of the matrix, or by a subsequent addition phase; - Formulation of the veterinary oral composition;

[1037] - Condition the composition, optionally under nitrogen, in a form allowing controlled twice-daily administration, so as to guarantee a release kinetics adapted to the therapeutic needs of the animal; This process guarantees the stability of the composition for at least 12 months at room temperature.

[1038] According to a particular embodiment, the veterinary oral composition in galenic form of complete food is in the form of kibble.

[1039] In a specific formulation, the complete veterinary oral food composition is presented as a wet food such as a pâté, terrine, or soup. The manufacture of such animal feed is well known to professionals who can adjust the content of each ingredient to comply with the requirements of EU Regulation 2020 / 354 on animal feed.

[1040] According to a particular embodiment, the process is characterized in that the medicated premix is ​​homogeneously mixed with the food matrix conforming to the PARNUT regulation, using a method that ensures uniform distribution of the active ingredient on the surface and / or within the dietary food matrix. This can be measured by analyzing the quantity of medication in several batches of compositions according to the invention. For example, the process can be characterized in that the mixture is then coated with a layer of fat or oil that serves as a support for the fixation and optimization of the absorption of the active ingredient.

[1041] The added fat or oil may be selected from vegetable oils, animal fats, medium-chain triglycerides, or edible waxes, and the medicated premix may contain benazepril or one of its pharmaceutically acceptable salts.

[1042] As an illustration, the process implemented for the incorporation of the active ingredient(s) can be as described in patents EP2899608 and EP2988609.

[1043] In particular, the addition of the active ingredient(s) to the dietary food matrix can be done at a temperature such that it does not lead to the degradation of the active ingredient(s); this temperature is therefore preferably below 40°C, for example cold or at room temperature (15-25°C).

[1044] EXAMPLES

[1045]

[1046] oral veterinary treatment of kidney failure

[1047]

[1048] in cats

[1049]

[1050] The composition includes benazepril, which is an angiotensin-converting enzyme (ACE) inhibitor, incorporated into a PARNUT-compliant food matrix adapted to the needs of cats with CKD, the composition of which is:

[1051] Composition 1: [Table 10]

[1052] protein 38.0% by weight

[1053] fats 16.5% by weight

[1054] fiber 6.5% by weight

[1055] ash 7.5% by weight

[1056] calcium 0.9% by weight

[1057] phosphorus 0.6% by weight

[1058] moisture 5.5% by weight

[1059] potassium 0.8% by weight

[1060] manganese 14.0 mg / kg by weight

[1061] methionine 1% by weight

[1062] sodium 0.4% by weight

[1063] Omega-3 fatty acids 1.5% by weight

[1064] Omega 6 fatty acids 2.5% by weight

[1065] starch 21.0% by weight

[1066] metabolizable energy 3840.0 kcal / kg

[1067] nitrogen-free extract 26.0% by weight

[1068] acid 0.4% by weight

[1069] doco s ahexaenoic

[1070] vitamin E (total) 500.0 lE / kg

[1071] vitamin A (17000 IU / kg), vitamin D3 (1700 IU / kg), vitamin E (610 IU / kg), copper [copper (II) sulfate pentahydrate] (12 mg / kg), zinc [zinc sulfate monohydrate] (110 mg / kg), iodine [calcium iodate] (0.4 mg / kg), taurine (2460 mg / kg), L-carnitine (540 mg / kg), bentonite (5g / kg).

[1072] Composition 2: [Table 11]

[1073] protein 35.0%

[1074] fats 9.0%

[1075] fibers 0.8%

[1076] ash 2.0%

[1077] calcium 0.28%

[1078] phosphorus 0.15%

[1079] humidity 76.0%

[1080] potassium 0.28%

[1081] manganese 5.0 mg / kg

[1082] methionine 0.3%

[1083] sodium 0.2%

[1084] omega-3 fatty acids 1.0%

[1085] omega-6 fatty acids 2.5%

[1086] starch 0.4%

[1087] Metabolizable energy 124.0 kcal / 100 g

[1088] nitrogen-free extract 1.2%

[1089] acid 0.3%

[1090] doco s ahexaenoic

[1091] vitamin E (total) 150.0 lE / kg

[1092] vitamin D3 (300 IU / kg), copper [copper(II) sulfate pentahydrate] (1.5 mg / kg), manganese [manganese sulfate monohydrate] (1.5 mg / kg), zinc [zinc sulfate monohydrate] (31 mg / kg), iodine [calcium iodate] (1 mg / kg), bentonite (1 g / kg).

[1093] Composition 3:

[1094] [Table 12] Protein 30.0%

[1095] fats 21.0%

[1096] fibers 3.5%

[1097] ash 7.0%

[1098] calcium 1.0%

[1099] phosphorus 0.5%

[1100] humidity 5.5%

[1101] potassium 0.8%

[1102] manganese 12.0 mg / kg

[1103] methionine 0.5%

[1104] sodium 0.4%

[1105] omega-3 fatty acids 1.5%

[1106] omega-6 fatty acids 3.2%

[1107] starch 28.0%

[1108] Metabolizable energy 415.0 kcal / 100 g

[1109] nitrogen-free extract 33.0%

[1110] docosahexaenoic acid 0.4%

[1111] vitamin E (total) 500.0 lE / kg

[1112] vitamin A (17000 IU / kg), vitamin D3 (1700 IU / kg), vitamin E (610 mg / kg), copper [copper(II) sulfate pentahydrate] (12 mg / kg), zinc [zinc sulfate monohydrate] (110 mg / kg), iodine [potassium iodide] (0.4 mg / kg), taurine (2460 mg / kg), L-camitine (540 mg / kg), bentonite (5 g / kg), antioxidants.

[1113] A premix is ​​prepared from benazepril hydrochloride (6.25 mg equivalent to 5.76 mg of benazepril) and an acceptable vector.

[1114] The benazepril contained in the premix is ​​introduced at a concentration of 72 mg / kg of the final product. Example 2: Veterinary oral composition for the treatment of osteoarthritis in dogs (NSAIDs + chondroprotective agents)

[1115] The composition includes a selective anti-inflammatory (NSAID), at a dose ranging from 0.01 to 50 mg / kg, preferably between 0.1 and 10 mg / kg, (multiple trials) depending on the active ingredient and which will in fact be reduced by at least 25% by weight compared to the dose prescribed by conventional oral route so that the plasma level of the drug is constant for 24 hours, after twice-daily administration) and a chondroprotective agent (glucosamine + hyaluronic acid), integrated into a food matrix rich in omega-3 fatty acids to optimize the anti-inflammatory effect and protect articular cartilage.

[1116] [Table 13]

[1117] protein 39%

[1118] Lipids, including omega-3 (5%) 14%

[1119] carbohydrates 28%

[1120] Fiber 16%

[1121] Chitosamine 0.15%

[1122] Minerals including sodium and potassium 2.30%

[1123] Vitamins

[1124]

[1125] 0.55%

[1126] Example 3: Veterinary oral composition for the treatment of immune disorders (oclacitinib)

[1127] Olacitinib, an immunomodulator targeting inflammatory reactions associated with atopic dermatitis, is incorporated at a dose ranging from 0.2 mg / kg to 20 mg / kg depending on the extent of the dermatitis (several trials) into a food matrix promoting its absorption and ensuring controlled release.

[1128] [Table 14]

[1129] Humidity 9%

[1130] Protein 34%

[1131] Animal / vegetable protein ratio 92 / 08

[1132] Fat content 18%

[1133] Mineral matter 7.5%

[1134] Crude cellulose 5%

[1135] ENA * 26.5%

[1136]

[1137] Starch 20% Calcium 1.3% Phosphorus 0.9% Sodium 0.4% Methionine + Cysteine ​​1.3% Phenylalanine + Tyrosine 2.1% Omega-6 3% Omega-3 1.1% EPA + DHA 0.5% LA + GLA 2.7%

[1138] 375 EM** calculated

[1139] kcal / 100g

[1140] EM** measured in vivo.

[1141] kcal / 100g

[1142] * Nitrogen-Free Extract: Assimilable carbohydrates ** Metabolizable energy

[1143]

[1144] [Table 15]

[1145] Bentonite 0.5% Pasteurized Lactobacillus acidophilus 7 mg / kg L-carnitine 330 mg / kg Vitamin A 1 1,000 lU / kg Vitamin D3 I 1001U / kg Vitamin E 570 mg / kg Vitamin BI 3.8 mg / kg Vitamin B 2 1 1 mg / kg

[1146]

[1147] Vitamin B3 30 mg / kg

[1148] Vitamin B 5 26 mg / kg Vitamin B6 3 mg / kg Vitamin B 9 0.48 mg / kg Vitamin B 12 0.062 mg / kg Choline 740 mg / kg Taurine 1,500 mg / kg Copper 15 mg / kg Iodine 1.1 mg / kg Zinc 120 mg / kg

[1149]

[1150] Example 4: Process for manufacturing a veterinary oral medicinal composition, in the form of a complete feed intended for the treatment or prevention of a chronic or progressive disease in a domestic animal

[1151] An example of a method for manufacturing a composition according to the invention may include the following steps:

[1152] - Provide a food matrix adapted to the specific pathophysiological needs of the animal, said matrix respecting the PARNUT criteria;

[1153] - Prepare a therapeutic premix, in which at least one active medicinal ingredient is homogenized in a suitable support;

[1154] - Incorporate the therapeutic premix homogeneously into the food matrix, either directly during the manufacture of the matrix, or by a subsequent addition phase, for example by coating;

[1155] - Formatting the veterinary oral composition;

[1156] - To package the composition in a form allowing controlled twice-daily administration, so as to guarantee a release kinetics adapted to the therapeutic needs of the animal.

[1157] Packaging adapted for twice-daily distribution of the composition according to the invention, allowing treatment for at least one month, has been produced. For example, shaping the veterinary oral composition according to the invention (or medicated PARNUT) means preparing medicated PARNUT kibble of sizes adapted to the animals for which the medicine is intended.

[1158] Or, by shaping the veterinary oral composition according to the invention, we mean the preparation of pâtés, minces, soups from the product obtained at the incorporation stage, as long as the final product meets the definition of a medicated PARNUT.

[1159] Example 5: Evaluation of the stability of a composition according to the invention

[1160] This study consisted of evaluating the impact of freeze / thaw cycles on the quality of a veterinary oral medicated composition according to example 1 in the form of extruded kibble (with the dietary food matrices 2 and 3 of example 1) at 72 mg / kg of benazepril.

[1161] These two products, previously stored for four months at room temperature, were subjected to a series of temperature changes: freezing and thawing. The impact on product quality was assessed by verifying product conformity in terms of benazepril content. Heat treatment cycle:

[1162] 2 days at -20°C

[1163] 2 days at room temperature (15 to 20°C)

[1164] 3 days at -20°C

[1165] 2 days at room temperature (15 to 20°C)

[1166] 2 days at -20°C

[1167] 3 days at room temperature (15 to 20°C)

[1168] The products obtained after heat treatment are analyzed by checking their visual appearance and by measuring the benazepril hydrochloride content by UHPLC-UV.

[1169] These measurements are also carried out on the same products after manufacture or stored for 3 months at 25°C and 60% humidity.

[1170] Results :

[1171] For both formulations, exposure to freeze / thaw cycles did not affect product conformity in terms of appearance and benazepril HCl content. Benazepril HCl levels were equivalent between each batch stored for 4 months at room temperature exposed to freeze / thaw cycles and the same batch stored for 3 months at 25°C / 60% RH.

[1172] These results confirm the excellent stability of the veterinary oral medicated compositions of the invention. These results are unexpected since they concern food combined with a drug, and demonstrate that the use of a PARNUT for the manufacture of a drug does not affect the stability of a drug combined with the PARNUT.

[1173]

[1174] 6: of the composition according to the invention

[1175]

[1176] in cats exhibiting symptoms of kidney failure at various stages (from 1 to 3)

[1177] The objective of this study is to evaluate the palatability of a veterinary oral medicinal composition according to the invention by cats with renal insufficiency.

[1178] The study was conducted in 11 veterinary clinics between May and August and not during the autumn, a period during which animals tend to increase their food intake in preparation for winter.

[1179] To be eligible, the cats were diagnosed with chronic kidney failure and the stage of the disease was determined according to veterinary medicine criteria.

[1180] 1. In stage 1, kidney function retains more than one-third of its capacity. This is referred to as early or incipient disease; at this stage, no functional abnormalities are detectable. 2. In stage 2, kidney function retains one-quarter of its capacity; the disease becomes established, and metabolic disturbances appear.

[1181] 3. In stage 3, the disease worsens, kidney function decreases significantly and significant azotemia (presence of nitrogenous waste in the blood) appears, leading to the appearance of marked symptoms.

[1182] 4. In stage 4, or terminal stage, the disease is severe. Kidney function capacity decreases below 10% and clinical signs are significant, usually leading to death.

[1183] The disease occurs when the kidneys are unable to maintain the body's internal balance. A number of abnormalities then appear: elevated urea and creatinine levels, disruption of calcium and phosphate metabolism, and cardiac problems. The animals recruited for the study were privately owned cats of various breeds and sexes. A total of 70 cats were included according to specific inclusion and exclusion criteria, including only one cat per household with no other animals.

[1184] The cats were fed for one month prior to the start of the study with a CKD cat diet food prescribed by a veterinarian.

[1185] The products tested:

[1186] The composition according to the invention (dietary food matrix of composition 3 according to example 1) at room temperature (25°C). The food matrix of composition 3 according to example 1 at room temperature (25°C) without active ingredient

[1187] A control group + Fortekor®?

[1188] The food is given orally once or twice a day, always at the same time - morning, noon or evening - or morning and evening.

[1189] Each day, the cat's daily ration is weighed using a scale.

[1190] The following treatments are prohibited during the study:

[1191] - vaccination

[1192] - deworming

[1193] - any product having an effect on the animal's appetite, except those used in the treatment of symptoms of chronic renal failure.

[1194] Measurements taken during the study:

[1195] - Weighing the cat

[1196] - Identification of adverse events,

[1197] - blood sample for proteinuria (creatinine, urea and serum SDMA)

[1198] - urine sample (creatinine and urinary proteins)

[1199] - measurement of urine density using a refractometer.

[1200] Various clinical parameters are also observed.

[1201] Statistics: T-test

[1202] Results :

[1203] The average consumption of kibble without active ingredients was measured at 11.71 g / kg of cat weight. No statistically significant difference was measured between the control group and the PARNUT group, or the group produced according to the invention, with regard to the amount of food ingested.

[1204] Remarkably, cats treated with the product according to the invention maintained their weight without significant adverse effects, or significantly different from those observed in animals treated with Fortekor®, or PARNUT without benazepril.

[1205] Table of side effects across all treatments: Summary of adverse effects by preferred term (safety population)

[1206] [Table 16] Total (n=26) VedDRA N events N (%) subjects ANYAEs 38 17 (65.4%) Vomiting 21 13 (50.0%) Anorexia 4 4 (15.4%) Polydipsia 4 3 (11.5%) Death 1 (3.8%) Epistaxis 1 1 (3.8%) Hair change 1 1 (3.8%) Hypertherapeutic disorders 1 1 (3.8%) Musculoskeletal disorders n 1 1 (3.8%) Skin lesion no. 1 1 (3.8%) Drowsiness 2 1 (3.8%)

[1207]

[1208] Weight loss 1 (3.8%)

[1209] Seventeen cats (65.4%) experienced 38 adverse events during the study. The most frequent adverse events were vomiting (21 events), anorexia (4 events), and polydipsia (4 events). Ten cats (50.0%) suffered from vomiting, four cats (15.4%) from anorexia, and three cats (11.5%) from polydipsia. Cats fed by their owners twice daily ate more and more consistently than cats in the other groups.

[1210] The primary criterion was comparing the amount of the cats' usual kibble consumed with the amount of the new tested kibble consumed. The results showed no difference in kibble consumption, remarkably even in cats with CKD (chronic kidney disease), whose appetite is impaired.

[1211] The average daily food intake per week between weeks 3 and 6 (with the tested kibble) was greater than 9 g / kg of body weight. This amount has been described as the minimum dietary intake to meet the caloric requirements of a neutered cat based on the metabolizable energy of the tested food. Therefore, a large majority of the CKD cat population will consume enough of the tested food.

[1212] It has also been observed that the amount of kibble consumed can vary from day to day in some cats. Over the weeks, the cats ate the same amount of kibble, but they may eat more on some days and less on others. Consequently, cats may eat less than 9 g / kg of body weight on some days. This may be related to nausea, which is a common symptom of CKD and can cause dysorexia. Furthermore, in this study, food was served only once a day, which could be responsible for decreased palatability due to air oxidation at the end of the day, especially for cats with CKD, who are known to be picky eaters. In addition, a significant number of cats in this study had outdoor access.Since it was not possible to assess whether they had access to other types of food outside (either other cat food or hunted prey), it must also be taken into account that food intake was lower on some days.

[1213] Body weight was one of the secondary criteria. During the study, the cat's weight did not show any significant difference over the 4 weeks of follow-up.

[1214] Several laboratory parameters were used to monitor CKD: blood urea nitrogen (BUN), blood creatinine, blood symmetric dimethylarginine (SDMA), urine specific gravity, and urine protein / creatinine ratio (UP / C ratio). None of these showed statistically significant changes after 4 weeks of using the test feed.

[1215] In conclusion, it has been shown that the PARNUT-compliant food matrix tested on cats with chronic kidney disease is well accepted, with the cats consuming at least 9 g / kg of body weight per day on average for several weeks, with some daily variation. The tested food is also very well tolerated by cats with chronic kidney disease.

[1216] Example 7: Comparative study of the administration of a composition according to the invention and the commercial drug Fortekor®

[1217] A multicenter, blinded, controlled, randomized, block, field study of pharmacokinetic data (i) of a veterinary oral composition according to the invention, prepared as described in Example 1, and (ii) of the commercial drug Fortekor® was conducted. This study aims to evaluate the efficacy and safety of a composition of the invention (Example 1, Dietary Matrix 3 with benazeril) compared to the reference product (Fortekor®) over 180 days.

[1218] Summary of study characteristics:

[1219] - Reference: Fortekor® Flavour 5mg tablet (benazepril hydrochloride).

[1220] - Test: composition 3 of example 1, dosed at 72mg benazepril hydrochloride / kg of composition.

[1221] 106 cats (mean age 12 years) suffering from chronic kidney disease (CKD) at different stages (23% at stage 1, 61% at stage 2 and 17% at stage 3) were recruited and divided into two groups: 70 cats received the composition according to the invention (IVP group) and 36 cats received Fortekor® (CP group) and were fed with the dietary food matrix 3 of example 1 (without benazepril). Prior to the study, the cats were fed with the dietary food matrix used for the manufacture of composition 3 of example 1 (without benazepril).

[1222] From day 0 of the study, each group of cats receives one of two diets:

[1223] - For the test group: 6.9g of test composition / kg of body weight per day; and

[1224] - For the Fortekor® group: 6.9g of dietary food matrix 3 (without benazepril) / kg of body weight per day and 0.5 mg of benazepril / kg of body weight per day.

[1225] The following parameters are observed throughout the study:

[1226] - Exposure to benazepril in the blood (PK parameter);

[1227] - ACE activity in the blood (Pharmacodynamic parameter);

[1228] - changes in body weight;

[1229] - body condition index;

[1230] - quality of life;

[1231] - blood and urine renal parameters (urea, creatinine, SDMA, urine protein-creatinine ratio (UPC ratio), urine specific gravity);

[1232] - IRIS stadium; and

[1233] - blood pressure.

[1234] Results :

[1235] [Table 17]

[1236] median product administered measurements

[1237] Area under the curve of the Fortekor® 5315

[1238] Plasma content of benazepril (PK) according to the invention 4946

[1239] Delta % -6.96 Efficacy (PD) Fortekor® 2.12

[1240] Composition according to 2.61 of the invention

[1241] Delta % 23

[1242]

[1243] Data observed in 106 cats with chronic renal failure show an average daily intake of 0.71 mg / kg body weight of benazepril with the Fortekor® diet and 0.57 mg / kg body weight of benazepril with the composition of Example 1. These data show that the composition according to the invention has a FACE inhibitory effect and efficacy superior to that of Fortekor®, even if the average dose received of benazepril is lower.

[1244] These results surprisingly show that when the veterinary oral medicated composition which combines benazepril and the dietary food matrix produces effects superior to the separate administration of the active ingredient and the dietary food matrix; this is all the more surprising as the average dose of benazepril ingested in the case of the composition according to the invention is much lower (0.57 mg / kg body weight per day) than that for the Fortekor® diet (0.71 mg / kg body weight per day).

[1245] Furthermore, administration of the composition according to the invention does not adversely affect the clinical parameters, which are statistically identical between the two groups:

[1246] Blood and urine parameters (renal function, i.e., blood creatinine, urea, SDMA, IRIS staging (the stage of chronic kidney disease can be defined according to the recommendations of the International Renal Interest Society (IRIS). Stage 1 to 4 is based on the degree of renal dysfunction assessed by serum creatinine concentration); urine protein / creatinine ratio; urine specific gravity) remained stable during the study; the same was true for blood pressure, quality of life, weight, and body condition index. This study also demonstrated that administration of the composition according to the invention does not lead to more adverse effects than Fortekor®.

[1247] These results therefore show that the formulation according to the invention guarantees stable absorption and improved efficacy compared to administration in tablet form without compromising safety.

Claims

1. CLAIMS 1. Veterinary oral medicated composition in galenic form as a complete feed for use in the treatment or prevention of a chronic or progressive disease in a domestic animal, comprising a food matrix and at least one active medicative principle selected according to said chronic or progressive disease, characterized in that: - said food matrix meets the standards of European Regulation 2020 / 354 known as PARNUT (foods for specific nutritional purposes) for said chronic or progressive disease; - said composition complies with both PARNUT veterinary regulations and the marketing requirements for an oral veterinary medicinal product; - said active ingredient is homogeneously incorporated into said feed matrix so that samples of said composition of the same weight contain the same quantity of active ingredient; - said composition is intended for administration at least twice daily, controlled by the owner, consisting of administering the quantity of complete feed corresponding to the prescribed dose of medicine; - ingestion of said composition ensures better stability of plasma concentrations of the active ingredient, allowing for a constant therapeutic effect throughout the day;which allows for a therapeutic efficacy equivalent to or greater than the separate administration of the active ingredient once a day in the form of an oral tablet and a suitable food, even when the dose of active ingredient actually ingested per day is reduced by 10% to 50% compared to the recommended dose in said oral tablet form.

2. Veterinary oral medicated composition according to claim 1, for use in the treatment of a chronic disease in a domestic animal suffering from an eating disorder selected from anorexia, dysorexia or hyporexia.

3. Veterinary medicinal product in the form of a complete feed comprising a solid feed matrix and at least one incorporated active ingredient, characterized in that: - said matrix meets the requirements of European Regulation (EU) 2020 / 354; - said active ingredient is distributed homogeneously on the surface or within the matrix; - said incorporation is carried out at a temperature below 40°C; - said structure ensures the stability of the active ingredient for at least 30 days at 25°C and is protected against thermal and oxidative degradation.

4. A method for manufacturing a veterinary medicinal product according to claim 3, comprising the steps of: - preparing a food matrix; - preparing a therapeutic premix in which at least one active ingredient is homogenized in a suitable carrier; - homogeneously incorporating the premix into the matrix at a temperature below 40°C; - shaping the composition to meet both PARNUT veterinary regulations and the requirements for placing an oral veterinary medicinal product on the market and packaging it, optionally under nitrogen.

5. Composition for its use according to any one of claims 1 or 2, characterized in that the chronic disease is selected from renal failure, congestive heart failure, cancer, diabetes, obesity or hypertension.

6. Composition for its use according to claim 5, characterized in that the animal is a cat suffering from chronic renal failure and the active ingredient is benazepril or one of its salts.

7. Composition for use according to claim 6, characterized in that said food matrix is ​​adapted to the stage of the disease and: - for a cat in stage 1, said matrix comprises a protein content > 30% and approximately 0.6% phosphorus; - for a cat in stage 2, said matrix comprises a protein content > 35% and approximately 0.55% phosphorus; - for a cat in stage 3 or 4, said matrix comprises approximately 30% protein, approximately 0.5% phosphorus, and bentonite.

8. Composition for use according to claim 6, characterized in that the daily dose of benazepril actually ingested is between 0.25 and 0.5 mg per kg of body weight.

9. Composition for its use according to claim 1 or 2, characterized in that the active ingredient is oclacitinib for the treatment of osteoarthritis or dermatological disorders.

10. Composition for its use according to claim 1 or 2, characterized in that the active ingredient is an SGLT-2 inhibitor, preferably velagliflozin, for the treatment of diabetes.

11. Composition according to any one of claims 1 to 2 or 5 to 9, characterized in that it is presented in the form of kibble comprising an external lipid coating, or in the form of wet food such as a pâté, terrine or mince.

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