POLYMERIC SUSPENSIONS AND COMPOSITIONS COMPRISING THEM FOR VACCINATING POULTRY

Abstract

The present invention relates to a ready-to-dilute polymeric suspension comprising between 1 and 15% by weight of a thickening agent, between 0.5 and 8% by weight of at least one suspending agent, between 1 and 10% by weight of water, and at least 60% by weight of a non-aqueous vehicle, relative to the total weight of the suspension. The invention also relates to a composition comprising such a suspension and a therapeutic agent.

Description

Title of the invention: POLYMERIC SUSPENSIONS AND COMPOSITIONS COMPRISING THEM FOR VACCINATING POULTRY

[0001] Object and invention

[0002] The present invention relates to the veterinary field, and more particularly to the field of poultry vaccination with compositions comprising polymeric suspensions enabling the delivery of a therapeutic agent.

[0003] Technological background of the invention

[0004] Poultry farming requires the administration of therapeutic agents to treat and protect individuals against various diseases. Numerous therapeutic agents are used in poultry farming and vaccination to stimulate the immune system and develop protective and lasting adaptive immunity against the infectious agent of a particular disease. Such therapeutic agents can be derived from living organisms, but also include vitamins, minerals, and electrolytes.

[0005] Various systems and devices for delivering a therapeutic agent and vaccinating poultry have been developed. For example, vaccines can be administered at the hatchery by injection when the hatchlings are being transferred from the incubator to the holding or transport trays. Vaccines can also be administered once the hatchlings are established in their brooding areas in the form of aqueous suspensions sprayed onto the feed or added to the drinking water.

[0006] Vaccines can also be administered and sprayed in the form of a soft gel to treat hatchlings. Preferably, these gels have a sticky consistency that promotes the availability of the gel pellets or droplets for consumption by the hatchlings, preventing them from rolling feathers to the ground. For example, WO 2011 / 011873 describes a powder mixture comprising 25% by weight of maltodextrin, 67% carrageenan, 4% carboxymethylcellulose, and 4% xanthan gum. A powder mixture marketed under the Cevagel® brand corresponds to a mixture comprising 84% by weight of maltodextrin, 10% carrageenan, and 6% sodium carboxymethylcellulose.

[0007] These powder mixtures are generally suspended in water to form a fluid, soft, and sticky gel comprising a therapeutic agent, and are then administered to newborns in the form of beads or sprayed droplets using a dispensing device such as, for example, that described in application WO 2005 / 099617. In particular, this type of device is capable The system distributes a predetermined volume of gel from a reservoir, via an arrangement of collecting nozzles, to the newborn chicks. The gel is dispensed as a plurality of small beads or droplets containing the therapeutic agent, which are easily ingested by the chicks. These gel beads or droplets retain their moisture content to maintain the viability and / or efficacy of the therapeutic agent within the soft gel during distribution and consumption. They also help prevent moisture loss and minimize potential wetting of the birds.

[0008] However, these gels adapted to this type of administration require ingredients with particular properties in order to guarantee the formation of beads or droplets that are stable and easily consumable by newborns for effective vaccination of poultry.

[0009] There therefore remains a need to develop new ready-to-dilute polymeric suspensions that can be used in vaccine compositions. Furthermore, in light of evolving regulatory standards and increasingly competitive economic and industrial conditions, the development of non-toxic products that are easy to produce for poultry farming remains a key objective. Summary of the invention

[0010] In this context, the inventors have provided new ready-to-dilute polymeric suspensions for preparing veterinary compositions intended for use in poultry vaccination. The polymeric suspensions according to the invention have, among other advantages, the use of non-toxic ingredients and a small amount of polymers, and are prepared using a simple and economical process. Furthermore, the veterinary compositions, preferably in gel form, comprising a polymeric suspension according to the invention after dilution in water, have a viscosity of approximately 100-300 mPas, which is particularly well-suited for the formation of stable beads or droplets.

[0011] The present invention therefore relates to a ready-to-dilute polymeric suspension comprising:

[0012] - between 1 and 15% by weight of a thickening agent,

[0013] - between 0.5 and 8% by weight of at least one suspending agent,

[0014] - between 1 and 10% by weight of water, and

[0015] - at least 60% by weight of a non-aqueous vehicle,

[0016] in relation to the total weight of the suspension.

[0017] More specifically, the ready-to-dilute polymeric suspension according to the invention comprises:

[0018] - between 5 and 15% by weight of a thickening agent,

[0019] - between 2 and 6% by weight of at least one suspending agent,

[0020] - between 2 and 10% by weight of water, and

[0021] - at least 60% by weight of a non-aqueous vehicle,

[0022] in relation to the total weight of the suspension.

[0023] More specifically, the ready-to-dilute polymeric suspension according to the invention comprises:

[0024] - between 8 and 13% by weight of a thickening agent,

[0025] - between 2 and 4% by weight of at least one suspending agent,

[0026] - between 2 and 8% by weight of water, and

[0027] - at least 75% by weight of a non-aqueous vehicle,

[0028] in relation to the total weight of the suspension.

[0029] According to a particular embodiment of the invention, the ready-to-dilute polymeric suspension according to the invention further comprises at least one additional excipient, preferably a coloring agent. Preferably, this additional excipient has a proportion of between 0.01 and 5% by weight, preferably between 0.01 and 2% by weight, relative to the total weight of the composition.

[0030] According to one aspect, the thickening agent is a polysaccharide, preferably selected from cellulose or its derivatives, alginic acid or its derivatives, hyaluronic acid or its derivatives, xanthan gum, guar gum, pullulan gum, and pectin. Preferably, the polysaccharide is selected from sodium alginate, sodium hyaluronate, sodium carboxymethylcellulose, methylcellulose, and hydroxypropyl methylcellulose, preferably sodium carboxymethylcellulose. According to a preferred embodiment, the thickening agent is carboxymethylcellulose.

[0031] According to one aspect, said at least one suspending agent is selected from sodium chloride, polyethylene glycol having a molar mass greater than 1000 g / mol, glycerides, polyacrylamides, polyacrylic acid copolymers, polyvinyl alcohols, polyvinylpyrrolidones, waxes, and silicones. Preferably, said at least one suspending agent is selected from sodium chloride and a glyceride. Even more preferably, said at least one suspending agent is selected from sodium chloride and a mixture of glyceryl mono- and distearate and glyceryl mono- and dipalmitate.

[0032] According to one aspect, the non-aqueous vehicle comprises polyols, polyalkylene glycols, polyglycerin, and triacetin. In particular, the non-aqueous vehicle comprises polyethylene glycol having a molar mass of less than 1000 g / mol, propylene glycol, glycerol, and / or sorbitol. Preferably, the non-aqueous vehicle comprises propylene glycol.

[0033] A preferred object of the invention is a ready-to-dilute polymeric suspension comprising:

[0034] - between 8 and 13% by weight, preferably about 11% by weight of carboxy methyl Icellulo se,

[0035] - between 2 and 4% by weight, preferably about 3% by weight of a mixture of mono- and glycerol distearate and glycerol mono- and dipalmitate,

[0036] - between 0.1 and 1% by weight, preferably about 0.5% by weight of chloride sodium,

[0037] - between 2 and 8% by weight, preferably about 6% by weight of water,

[0038] - between 0.01 and 1% by weight, preferably about 0.3 or about 0.4% by weight of a coloring agent, preferably the disodium salt of α-[(N-ethyl-sulfo-3-benzylamino)-4-phenyl]-α-(N-ethyl-sulfo-3-benzylamino-4)-cyclohexadiene-2,5-ylidene) toluenesulfonic acid, and

[0039] - propylene glycol qsp,

[0040] in relation to the total weight of the suspension.

[0041] Preferably, the ready-to-dilute polymeric suspension as described in this application is sterile.

[0042] Another object of the invention relates to a composition comprising a ready-to-dilute polymeric suspension as defined in this application, and a therapeutic agent. Preferably, the composition is an oral composition. Even more preferably, the composition is a gel.

[0043] According to one aspect, the therapeutic agent is chosen from:

[0044] a) a living organism selected from the group consisting of hemorrhagic enteritis virus, infectious bursitis virus, Newcastle disease virus, salmonella, infectious bronchitis, infectious laryngotracheitis, Mycoplasma sp., a pneumovirus, coccidiosis, and a competitive exclusion product, such as probiotics, lactobacilli or bacillus species,

[0045] b) vitamins,

[0046] c) minerals, and

[0047] d) electrolytes.

[0048] Preferably, the therapeutic agent comprises oocysts of Eimeria acervulina, Eimeria maxima, Eimeria tenella, Eimeria necatrix, Eimeria brunetti, Eimeria adenoid.es, and Eimeria meleagremitis.

[0049] Another object of the invention is a composition as defined in the present application intended for use in the treatment of a viral, bacterial, or parasitic infection in poultry, particularly in newborns.

[0050] An additional object of the invention is a kit for vaccinating poultry comprising in a first compartment (a) a polymeric suspension ready to be diluted according to the invention, and in a second compartment (b) a therapeutic agent. Detailed description of the invention

[0051] Polymer suspension

[0052] The present invention provides a ready-to-dilute polymeric suspension comprising:

[0053] - between 1 and 15% by weight of a thickening agent,

[0054] - between 0.5 and 8% by weight of at least one suspending agent,

[0055] - between 1 and 10% by weight of water, and

[0056] - at least 60% by weight of a non-aqueous vehicle,

[0057] in relation to the total weight of the suspension.

[0058] According to the invention, the polymeric suspension is ready to be diluted. By "ready-to-dilute suspension" is meant a suspension that can be directly and simply diluted in a liquid medium, preferably water, to form a reconstituted product. Preferably, no step other than a dilution step is required to form the reconstituted product from the suspension according to the invention.

[0059] According to a particular embodiment of the invention, the ready-to-dilute polymeric suspension comprises:

[0060] - between 5 and 15% by weight of a thickening agent,

[0061] - between 2 and 6% by weight of at least one suspending agent,

[0062] - between 2 and 10% by weight of water, and

[0063] - at least 60% by weight of a non-aqueous vehicle,

[0064] in relation to the total weight of the suspension.

[0065] Preferably, the ready-to-dilute polymeric suspension comprises:

[0066] - between 8 and 13% by weight of a thickening agent,

[0067] - between 2 and 4% by weight of at least one suspending agent,

[0068] - between 2 and 8% by weight of water, and

[0069] - at least 75% by weight of a non-aqueous vehicle,

[0070] in relation to the total weight of the suspension.

[0071] According to a particular embodiment of the invention, the thickening agent is a polysaccharide. Examples of polysaccharides include, but are not limited to, cellulose or its derivatives, alginic acid or its derivatives, hyaluronic acid or its derivatives, natural gums such as xanthan gum, guar gum, and pullulan gum, and pectin. In a particular embodiment, the thickening agent is selected from cellulose or its derivatives, alginic acid or its derivatives, hyaluronic acid or its derivatives, xanthan gum, guar gum, pullulan gum, and pectin. In a preferred embodiment, the thickening agent is selected from sodium alginate, sodium hyaluronate, sodium carboxymethylcellulose, methylcellulose, and hydroxypropyl methylcellulose, preferably sodium carboxymethylcellulose. (Sodium CMC). In particular, the thickening agent has a weight proportion of between 1 and 15%, between 5 and 15%, or between 8 and 13% in the suspension, relative to its total weight. The thickening agent, in particular sodium carboxymethylcellulose, present in such proportions allows the formation of stable beads or droplets after dilution in water.

[0072] According to the invention, the polymeric suspension comprises at least one suspending agent. This suspending agent facilitates, in particular, the homogenization of the suspension. According to a particular embodiment of the invention, the at least one suspending agent is selected from sodium chloride, polyethylene glycol having a molar mass greater than 1000 g / mol, glycerides, polyacrylamides, polyacrylic acid copolymers, polyvinyl alcohols, polyvinylpyrrolidones, waxes, and silicones. Preferably, the at least one suspending agent is selected from sodium chloride and a glyceride, preferably a mixture of glyceryl mono- and distearate and glyceryl mono- and dipalmitate. According to a more particular embodiment, the polymeric suspension comprises two suspending agents. Preferably, the polymeric suspension comprises sodium chloride and a glyceride.Preferably, the polymeric suspension comprises sodium chloride and a mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate. A mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate may be the commercial product Geleol Mono & Diglyceride NF from Gattefossé. In particular, at least one suspending agent has a weight proportion of between 0.5 and 8%, between 2 and 6%, or between 2 and 4% in the suspension relative to its total weight.

[0073] In a particular embodiment, the non-aqueous vehicle comprises polyols, polyalkylene glycols, polyglycerin, and triacetin. In a more particular embodiment, the non-aqueous vehicle comprises polyethylene glycol having a molar mass of less than 1000 g / mol, propylene glycol, glycerol, and / or sorbitol. Preferably, the non-aqueous vehicle is propylene glycol. In particular, the non-aqueous vehicle has a weight proportion of at least 60%, at least 65%, at least 70%, or at least 75% in the suspension, relative to its total weight.

[0074] According to one embodiment, the ready-to-dilute polymeric suspension further comprises at least one additional excipient. Such excipients may be coloring agents, buffering agents, salts, palatability enhancers, or nutrients such as vitamins. In particular, the at least one additional excipient has a weight proportion of between 0.01 and 5%, between 0.01 and 4%, between 0.01 and 3%, or between 0.01 and 2% of the suspension relative to its total weight.

[0075] According to a particular mode, the suspension further comprises a coloring agent. One coloring agent is the disodium salt of α-[(N-ethyl-sulfo-3-benzylamino)-4-phenyl]-α-(N-ethyl-sulfo-3-benzylamino-4)-cyclohexadiene-2,5-ylidene)-2-toluenesulfonic acid, more commonly known as "Brilliant Blue". Specifically, the coloring agent has a weight proportion of between 0.01 and 5%, between 0.01 and 4%, between 0.01 and 3%, or between 0.01 and 2% of the suspension relative to its total weight. Preferably, the coloring agent, and in particular the disodium salt of α-[(N-ethyl-sulfo-3-benzylamino)-4-phenyl]-α-(N-ethyl-sulfo-3-benzylamino-4)-cyclohexadiene-2,5-ylidene) toluenesulfonic-2 acid, has a weight proportion between 0.01 and 1%, or better still about 0.3 or about 0.4% in the suspension relative to its total weight.

[0076] A preferred object of the invention is a ready-to-dilute polymeric suspension comprising:

[0077] - between 8 and 13% by weight of carboxymethylcellulose,

[0078] - between 2 and 4% by weight of a mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate,

[0079] - between 0.1 and 1% by weight of sodium chloride,

[0080] - between 2 and 8% by weight of water,

[0081] - between 0.01 and 1% by weight of a coloring agent, preferably the disodium salt of α-[(N-ethyl-sulfo-3-benzylamino)-4-phenyl]-α-(N-ethyl-sulfo-3-benzylamino-4)-cyclohexadiene-2,5-ylidene) toluenesulfonic acid, and

[0082] - propylene glycol qsp,

[0083] in relation to the total weight of the suspension.

[0084] An even more preferred object of the invention is a polymeric suspension, preferably sterile, ready to be diluted, comprising:

[0085] - approximately 11% by weight of carboxymethylcellulose,

[0086] - approximately 3% by weight of a mixture of glycerol mono- and distearate and mono- and glycerol dipalmitate,

[0087] - approximately 0.5% by weight of sodium chloride,

[0088] - approximately 6% by weight of water,

[0089] - approximately 0.3 or approximately 0.4% by weight of a coloring agent, preferably salt disodium α-[(N-ethyl-sulfo-3-benzylamino)-4-phenyl]-α-(N-ethyl-sulfo-3-benzylamino-4)-cyclohexadiene-2,5-ylidene) toluenesulfonic-2, and

[0090] - propylene glycol qsp,

[0091] in relation to the total weight of the suspension.

[0092] The terms "about" and "around" will be understood by a person skilled in the art and They may vary to some extent depending on the context in which they are used. If some uses of these terms are not clear to a person skilled in the art Depending on the context, "about" or "around" means plus or minus 20%, preferably plus or minus 10% of the particular term.

[0093] The sterile, ready-to-dilute polymeric suspensions according to the invention can be prepared using a simple, economical process, and therefore well-suited to industrial scale. For example, the various ingredients, namely the suspending agent(s) and the thickening agent, are dissolved in water and the non-aqueous vehicle and heated to temperatures above 50 °C, preferably above 70 °C.

[0094] An object of the invention relates to a process for preparing a ready-to-dilute polymeric suspension comprising the following steps:

[0095] a) dissolution of a suspending agent, preferably sodium chloride in water;

[0096] b) dispersion of a thickening agent, preferably sodium carboxymethylcellulose, in a non-aqueous vehicle, preferably propylene glycol followed by the addition of a suspending agent, preferably a mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate, then heating to a temperature around 100 °C,

[0097] c) combining the mixture from step a) with the mixture from step b) at a temperature around 100 °C,

[0098] d) adding a coloring agent, preferably the disodium salt of α-[(N-ethyl-sulfo-3-benzylamino)-4-phenyl]-α-(N-ethyl-sulfo-3-benzylamino-4)-cyclohexadiene-2,5-ylidene) toluenesulfonic acid, to the mixture of step c) at a temperature around 100 °C, and

[0099] f) cooling to 25 °C and recovery of the polymeric suspension ready to be diluted.

[0100] According to a particular aspect of the invention, the ready-to-dilute polymeric suspensions are sterile. "Sterile suspension" means a suspension for which a sterilization step has been carried out. The sterilization step corresponds to step e) in the process for preparing a sterile ready-to-dilute polymeric suspension, as described below. Sterilization steps or means known to those skilled in the art include, for example, sterilization by heating, sterilization by radiation, sterilization with nitrogen dioxide, sterilization with ethylene oxide, and sterilization by steam (autoclave). Preferably, the ready-to-dilute polymeric suspensions according to the invention are rendered sterile by a heating sterilization step.According to a specific method, the sterilization by heating step is carried out at a temperature between 100 and 150 °C, between 105 and 140 °C, between 115 and 130 °C, preferably at a temperature of about 120 or 121 °C. According to a specific method, the sterilization by heating step is carried out for 10 to 120 minutes, 20 to 100 minutes, 30 to 90 minutes, preferably for about 60 minutes.

[0101] An object of the invention also relates to a process for preparing a sterile polymeric suspension ready for dilution, comprising the following steps:

[0102] a) dissolution of a suspending agent, preferably sodium chloride in water;

[0103] b) dispersion of a thickening agent, preferably sodium carboxymethylcellulose, in a non-aqueous vehicle, preferably propylene glycol followed by the addition of a suspending agent, preferably a mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate, then heating to a temperature around 100 °C,

[0104] c) combining the mixture from step a) with the mixture from step b) at a temperature around 100 °C,

[0105] d) adding a coloring agent, preferably the disodium salt of α-[(N-ethyl-sulfo-3-benzylamino)-4-phenyl]-α-(N-ethyl-sulfo-3-benzylamino-4)-cyclohexadiene-2,5-ylidene) toluenesulfonic-2 acid, into the mixture of step c) at a temperature around 100 °C,

[0106] e) heating the mixture from step d) to a temperature of approximately 121 °C for approximately 60 minutes; and

[0107] f) cooling to 25 °C and recovery of the polymeric suspension ready to be diluted.

[0108] Composition

[0109] The present invention also provides a composition comprising a polymeric suspension as described in this application, and a therapeutic agent.

[0110] As described above, the polymeric suspensions of the invention can be diluted in water and form a composition, also referred to as the reconstituted product in this application.

[0111] An object of the invention therefore relates to a composition comprising a sterile polymeric suspension ready to be diluted as described in the present application and water.

[0112] Another object of the invention also relates to a composition comprising a sterile polymeric suspension ready to be diluted as described in the present application, water and a therapeutic agent.

[0113] The term "therapeutic agent" means any agent, compound, molecule, or drug having a biological or therapeutic effect on a subject. A therapeutic agent is, for example, a living organism, a vitamin, a mineral, and electrolytes.

[0114] In particular, a therapeutic agent is a living organism selected from the group consisting of hemorrhagic enteritis virus, infectious bursitis virus, Newcastle disease virus, salmonella, infectious bronchitis, infectious laryngotracheitis, Mycoplasma sp., a pneumovirus, coccidiosis, and a competitive exclusion product, such as probiotics, lactobacilli or bacillus species. More specifically, the therapeutic agent comprises oocysts of Eimeria acervulina, Eimeria maxima, Eimeria tenella, Eimeria necatrix, Eimeria brunetti, Eimeria adenoides, and Eimeria meleagremitis.

[0115] Generally, the compositions according to the invention can be prepared by mixing a ready-to-dilute polymeric suspension, preferably sterile, in water and adding the therapeutic agent.

[0116] An object of the invention therefore relates to a process for preparing a composition comprising the following steps:

[0117] al) adding a quantity of water to a blender,

[0118] a2) gradual addition to the mixer of a ready-to-dilute polymeric suspension such as described in this application, and leave under agitation,

[0119] a3) Gradual addition of the therapeutic agent to the blender, and leave under agitation, And

[0120] a4) retrieval of the composition.

[0121] The compositions of the invention prepared according to such a process can be obtained in the form of a homogeneous opaque solution, in particular a gel. Such a composition has viscous properties particularly well suited for the formation of beads or droplets with a suitable device comprising a reservoir and an arrangement of collecting nozzles. In particular, the composition has a viscosity of between 100 and 300 millipascals per second (mPas), preferably between 100 and 200 mPas. Such a device is described, in particular, in international application WO 2005 / 099617. The Desvac Spray & Gel vaccination machine may also be cited.

[0122] Preferably, the compositions according to the invention are intended to be administered orally.

[0123] One object of the invention therefore relates to an oral composition as described in this application. A further object of the invention relates to an oral composition as described in this application in the form of a gel.

[0124] Another object of the invention relates to a composition as described in this application for use in the treatment of a viral, bacterial, or parasitic infection. The invention also relates to a composition as described in this application for its use in the treatment of a viral, bacterial, or parasitic infection.

[0125] In the context of the present invention, the terms "treatment" and "treat" broadly refer to the improvement, prophylaxis, or cure of a disease or disorder or clinical sign associated with the disease, in this case a viral, bacterial, or parasitic infection. "Treatment of an infection" refers to the improvement, prophylaxis, or cure of a disease or disorder, or a clinical sign associated with the disease, in this case a viral, bacterial, or parasitic infection. "Viral, bacterial, or parasitic" also refers to control, that is, the eradication, elimination, or reduction of the parasite(s) responsible for such an infection in a non-human mammal, particularly poultry.

[0126] In one particular sense, these expressions include the curative treatment of a non-human mammal against a viral, bacterial, or parasitic infection. "Curative treatment" means treatment that cures a non-human mammal of a viral, bacterial, or parasitic infection. In another particular sense, these expressions include the preventive treatment of a non-human mammal against a viral, bacterial, or parasitic infection. In one aspect, preventive treatment means treatment administered before the non-human mammal has been exposed to or has come into contact with the agent causing or leading to the viral, bacterial, or parasitic infection. Preventive treatment therefore reduces the risk to the non-human mammal of developing a viral, bacterial, or parasitic infection.The terms "treatment" and / or "prevention" can thus also refer to the protection of a non-human mammal against a viral, bacterial, or parasitic infection, or at least one of its associated disorders. In a second sense, preventive treatment also refers to treatment administered to a non-human mammal suffering from a viral, bacterial, or parasitic infection. Treatment administered to an infected individual can control the parasite(s) causing the viral or bacterial infection in its environment and reduce the risk of infection and contamination in surrounding healthy individuals, thereby helping to limit the spread of the infection.

[0127] In particular, the compositions of the invention are veterinary compositions. They are preferably intended to be administered to poultry, in particular to newborns or chicks.

[0128] Another object of the invention relates to a composition as described in the present application intended to be used or for use in the treatment of a viral, bacterial, or parasitic infection in poultry, in particular in newborns.

[0129] An object of the invention relates to the use of a sterile, ready-to-dilute polymeric suspension as described in this application for the manufacture of a composition for the treatment of a viral, bacterial, or parasitic infection in poultry, particularly in newborns.

[0130] An object of the invention also relates to a method of treating a viral, bacterial, or parasitic infection in poultry, particularly in newborns, comprising administering an effective amount of a composition according to the invention.

[0131] Viral infections include, for example, infectious bronchitis, Gumboro disease, Newcastle disease, and infectious laryngotracheitis,

[0132] Bacterial infections include, for example, coryza, salmonellosis, Escherichia coli, and necrotizing enteritis.

[0133] Parasitic infections include, for example, coccidiosis.

[0134] An additional object of the invention relates to a Kit for vaccinating poultry comprising in a first compartment (a) a ready-to-dilute polymeric suspension as described in the present application, and in a second compartment (b) a therapeutic agent.

[0135] Other aspects and advantages of the invention will become apparent from the following examples, which should be considered illustrative and not limiting. Examples

[0136] 1. Preparation of a ready-to-dilute polymeric suspension according to the invention

[0137] Polymer suspension:

[0138] [Tables 1] Steps Ingredients Description Parameters Mixture A Sodium chloride: 1.1g Purified water Solubilization of sodium chloride in water Agitation: 200-300 rpm for 20 min. Mixture B Propylene glycol: 92.4 g Sodium carboxymethylcellulose: 23.7 g Dispersion of sodium carboxymethylcellulose in the propylene glycol fraction and heating to 90 °C Agitation: 200-300 rpm for 30 min at 90 °C Geleol Mono- and Diglycerides: 6.5 g Addition of mono- and diglycerides to the PG / sodium carboxymethylcellulose mixture and heating to 100 °C Agitation: 600-1200 rpm for 30 min at 100 °C Propylene glycol: 77.8 g Addition of PG to the mixture Agitation: 600-1200 rpm for 20 min at 100 °C Mixture C Mixture A Mixture B Addition of mixture A to mixture B Agitation: 600-1200 rpm for 15 min at 100 °C Final Mixture Brilliant Blue: 0.6 g Add the dye to mixture C. Agitation: 600-1200 rpm for 15 min at 100 °C. Sterilization (optional) Heat the final mixture to 121 °C. Agitation: 600-1200 rpm for 60 min at 121 °C. Cooling Cool the final mixture to 25 °C. Agitation: 600-1200 rpm at 25 °C. Filling (optional for storage) Fill a 250 mL bottle with the suspension by continuously mixing. Agitation: 600-1200 rpm. Volume: 200 mL Examples of suspensions

[0139]

[0140]

[0141]

[0142]

[0143] The suspensions described below are prepared according to the process described above. The quantities of ingredients have been adjusted, and the percentages of ingredients in the suspensions below are expressed by weight relative to the total weight of the suspension. Suspension A: Sodium CMC 11.0% - Geleol Mono & Diglyceride NF 3.0% - Water 6.0% - Sodium chloride 0.5% - Brilliant Blue 0.3% - Propylene glycol qs 100% Suspension B: Sodium CMC 10.0 - 12.0% PEG 4000 5.0 - 8.0% Water 4.0 - 8.0% - Sodium chloride 0.5% - Brilliant Blue 0.3% - Propylene glycol qs 100% Suspension C: Sodium CMC 10.0 - 12.0% - Povidone K90 3.0 - 5.0% Water 4.0 - 8.0%

[0144]

[0145]

[0146]

[0147]

[0148]

[0149]

[0150]

[0151] - Sodium chloride 0.5% - Propylene glycol qs 100% Suspension D: Sodium CMC 10.0 - 12.0% - Compritol 888 ATO 3.0 - 5.0% Water 4.0 - 8.0% - Sodium chloride 0.5% - Propylene glycol qs 100% Suspension E: Sodium CMC 10.0 - 12.0% - Geleol Mono & Diglyceride NF 1.0 - 3.0% Water 4.0 - 8.0% - Sodium chloride 0.5% - Propylene glycol qs 100% 2. Reconstitution process A composition according to the invention in the form of a gel (reconstituted product - Gel NF)) was prepared according to the process described below. 4.8 liters of water were added to a blender. 200 mL of polymeric suspension A were then gradually added to the blender. The mixture was then blended for at least 5 minutes until a homogeneous composition was achieved. 3. Physicochemical properties Physicochemical studies on the viscosity, contact angle, and pH of the composition in gel form obtained by the reconstitution process described above were carried out and compared with existing products Cevagel®, the gel described in WO 2011 / 011873, and the solvents Paracox (carminic acid (red color E120), xanthan gum (E415), sodium chloride, and for injectable preparations) and Hipramune T (Brilliant Blue (E 133), AC Red (E 129), vanillin, montanide IMS. [Tables 2] Ingredients Gel NF (Inv ention) Cevagel® Gel WO 201 1 / 011873 Sodium carboxymethylcellulose 11% 84% 4% Carrageenan - 10% 67% Maltodextrin - 6% 25% Geleol Mono & Diglyceride NF 3% - - Water 6% - Sodium chloride 0.5% - Blue pigment (Brilliant Blue) 0.3% - Propylene glycol q.s. 100% - Xanthan gum 4%

[0152] The percentages in Table 2 are expressed as weight relative to the total weight of the product.

[0153] 3.1. Viscosity

[0154] The viscosity of the products was measured using a Brookfield Dv Next viscometer and a "Small Sample Adapter" on a 9 mL sample at a rotation speed of 150 revolutions per minute and an ambient temperature of 20°C.

[0155] [Tables3] NF Gel (Inv ention) Cevagel® Gel WO2011 / 011873 Paracox Hipramun eT Viscosity (mPa.s) 120-192 90-138 230 235 -

[0156] The NF gel according to the invention has a viscosity between 120-192 mPa.s suitable for the formation of well-adhered beads or droplets, just like the Cevagel® product. The WO 2011 / 011873 and Paracox gels have a very high viscosity and preclude their use in a vaccination machine, such as the Desvac Spray & Gel vaccination machine.

[0157] 3.2. Contact angle

[0158] The contact angle of the products was measured in order to evaluate the resistance of the drop according to its wettability as well as its surface tension.

[0159] Equipment: Goniometer for measuring contact angle

[0160] Drop method

[0161] Average of values ​​over 6 measurements

[0162] [Tables4] Gel NF (Inv ention) Cevagel® Gel WO2011 / 011873 Paracox Hipramun etT Contact angle (°) 65.2+1.3 65.0 + 0.5 - 67.9 + 0.9 -

[0163] 3.3. pH

[0164] The pH of the products was measured using a pH meter to assess its neutrality in order to comply with specifications.

[0165] 10 mL sample

[0166] [Tables5] Gel NF (Inv ention) Cevagel® Gel WO2011 / 011873 Paracox Hipramun eT PH 6.8-7.5 7.0-9.5 9.4 - -

[0167] The NF gel according to the invention and the Cevagel® product has a neutral pH in accordance with a product intended to be ingested by chicks.

[0168] 4. Tests on vaccination equipment

[0169] Tests were carried out on the Desvac vaccination equipment: Spray & Gel on the NF gel according to the invention and the Cevagel® product to evaluate the continuity of the spray and the size of the droplets on a plexiglass support, allowing to validate their use.

[0170] Equipment: Desvac Spray & Gel Vaccination Machine

[0171] Batch size: preparation of a 5L solution

[0172] Pressure: 2.5 Bars

[0173] Needle: 18G .033X.25 green 50P (Nordson EFD)

[0174] Support: plexiglass plate

[0175] Smaller droplets and a continuous flow without dripping were observed for the NF Gel according to the invention compared to the Cevagel® product.

[0176] 5. Preparation of a composition according to the invention

[0177] A composition according to the invention comprising cryptosporidium oocysts was prepared according to the following process:

[0178] 4.8 liters of water were added to a blender. 200 mL of polymeric suspension A were then gradually added to the blender. The mixture was then stirred for at least 5 minutes until a homogeneous composition was achieved. Finally, 200 mL of a solution containing Cryptosporidium oocysts was gradually added to the mixture while stirring.

[0179] 6. Biological study

[0180] A preliminary study was implemented to verify the effectiveness of the composition prepared in point 5 above in comparison with the Cevagel® product.

[0181] Three groups of 10 chicks were placed in cages. The composition according to the invention and the Cevagel® product were then distributed to two groups, with the third group serving as the control, using a Desvac Spray & Gel Vaccination machine. Fecal evaluation of the oocysts was measured between 5 and 8 days after product distribution.

[0182] [Tableauxô] Gel NF (Inv ention) Cevagel® Oocyst per chick 889779 1057387

[0183] The results in Table 6 show an effectiveness for the composition of the invention comparable to the Cevagel® product.

Claims

Demands

1. Ready-to-dilute polymeric suspension comprising: - between 1 and 15% by weight of a thickening agent, - between 0.5 and 8% by weight of at least one suspending agent, - between 1 and 10% by weight of water, and - at least 60% by weight of a non-aqueous vehicle, relative to the total weight of the suspension.

2. Suspension according to claim 1, wherein the suspension comprises: - between 5 and 15% by weight of a thickening agent, - between 2 and 6% by weight of at least one suspending agent, - between 2 and 10% by weight of water, and - at least 60% by weight of a non-aqueous vehicle, relative to the total weight of the suspension.

3. Suspension according to claim 1 or 2, wherein the suspension comprises: - between 8 and 13% by weight of a thickening agent, - between 2 and 4% by weight of at least one suspending agent, - between 2 and 8% by weight of water, and - at least 75% by weight of a non-aqueous vehicle, relative to the total weight of the suspension.

4. Suspension according to any one of claims 1 to 3, wherein the suspension further comprises at least one additional excipient, preferably a coloring agent.

5. Suspension according to claim 4, wherein said excipient has a proportion of between 0.01 and 5% by weight, preferably between 0.01 and 2% by weight, relative to the total weight of the composition.

6. Suspension according to any one of claims 1 to 5, wherein the thickening agent is a polysaccharide, preferably selected from cellulose or its derivatives, and alginic acid or its derivatives, hyaluronic acid or its derivatives, xanthan gum, guar gum, pullulan gum, and pectin.

7. Suspension according to claim 6, wherein the polysaccharide is selected from sodium alginate, sodium hyaluronate, sodium carboxymethylcellulose, the methylcellulose, and hydroxypropylmethylcellulose, preferably sodium carboxymethylcellulose.

8. Suspension according to any one of claims 1 to 7, wherein said at least one suspending agent is selected from sodium chloride, polyethylene glycol having a molar mass greater than 1000 g / mol, glycerides, polyacrylamides, polyacrylic acid copolymers, polyvinyl alcohols, polyvinylpyrrolidones, waxes, and silicones.

9. Suspension according to claim 8, wherein at least one suspending agent is selected from sodium chloride and a glyceride, preferably a mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate.

10. Suspension according to any one of claims 1 to 9, wherein the non-aqueous vehicle comprises polyols, polyalkylene glycols, polyglycerin, and triacetin, preferably polyethylene glycol having a molar mass of less than 1000 g / mol, propylene glycol, glycerol, and / or sorbitol, even more preferably propylene glycol.

11. A suspension according to any one of claims 1 to 10, comprising: - between 8 and 13% by weight, preferably about 11% by weight, of carboxymethylcellulose, - between 2 and 4% by weight, preferably about 3% by weight, of a mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate, - between 0.1 and 1% by weight, preferably about 0.5% by weight, of sodium chloride, - between 2 and 8% by weight, preferably about 6% by weight, of water, - between 0.01 and 1% by weight, preferably about 0.3 or about 0.4% by weight, of a coloring agent, preferably the disodium salt of acid a-[(N-ethyl-sulfo-3-benzylamino)-4-phenyl]-a-(N-ethyl-sulfo-3-benzylamino-4)-cyclohexadiene-2,5-ylidene) toluenesulfonic-2, and - propylene glycol qsp, relative to the total weight of the suspension.

12. Suspension according to any one of claims 1 to 11, wherein the suspension is sterile.

13. Composition comprising a polymeric suspension according to any one of claims 1 to 12, and a therapeutic agent.

14. Composition according to claim 13, wherein the composition is an oral composition, preferably a gel.

15. Composition according to claim 13 or 14, wherein the therapeutic agent is selected from: a) a live organism selected from the group consisting of hemorrhagic enteritis virus, infectious bursitis virus, Newcastle disease virus, salmonella, infectious bronchitis, infectious laryngotracheitis, Mycoplasma sp., a pneumovirus, coccidiosis, and a competitive exclusion product, such as probiotics, lactobacilli or bacillus species, b) vitamins, c) minerals, and d) electrolytes.

16. Composition according to any one of claims 13 to 15, wherein the therapeutic agent comprises oocysts of Eimeria acervulina, Eimeria maxima, Eimeria tenella, Eimeria necatrix, Eimeria brunetti, Eimeria adenoides, and Eimeria meleagremitis.

17. Composition according to any one of claims 13 to 16, intended for use in the treatment of viral, bacterial, or parasitic infection in poultry, particularly in newborns.

18. Kit for vaccinating poultry comprising in a first compartment (a) a polymeric suspension ready to be diluted according to any one of claims 1 to 12, and in a second compartment (b) a therapeutic agent according to claim 15 or 16.