Polymer suspensions and compositions comprising same for vaccinating poultry

Abstract

The present invention relates to a ready-to-dilute polymer suspension comprising between 1 and 15% by weight of a thickening agent, between 0.5 and 8% by weight of at least one suspension 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

[0001] POLYMERIC SUSPENSIONS AND COMPOSITIONS COMPRISING THEM

[0002] TO VACCINATE POULTRY

[0003] Object of the invention

[0004] 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.

[0005] Technological background of the invention

[0006] Poultry farming requires the administration of therapeutic agents to treat and protect birds 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, as well as vitamins, minerals, and electrolytes.

[0007] Various systems and devices for delivering therapeutic agents 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 as aqueous suspensions sprayed onto the feed or added to the drinking water.

[0008] Vaccines can also be administered and sprayed as a soft gel to treat hatchlings. Preferably, these gels have a sticky consistency that makes the gel pellets or droplets more readily available to the hatchlings for consumption, 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 brand name Cevagel® corresponds to a mixture comprising 84% by weight of maltodextrin, 10% carrageenan, and 6% sodium carboxymethylcellulose.

[0009] These powder mixtures are generally suspended in water to form a fluid, soft, and sticky gel containing a therapeutic agent, which is 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 of dispensing a predetermined volume of gel, from a reservoir and through an arrangement of collecting nozzles, to the newborns. The gel is dispensed as a plurality of small beads or droplets containing the therapeutic agent, which can be easily ingested by the newborns. The gel beads or droplets retain their moisture content to maintain the viability and / or efficacy of the therapeutic agent contained in the soft gel during dispensing and consumption of the soft gel.They also help to prevent moisture from escaping and to minimize the potential for birds to get wet.

[0010] However, these gels adapted for 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 poultry vaccination.

[0011] The need to develop new ready-to-dilute polymeric suspensions for use in vaccine formulations remains. Furthermore, given evolving regulatory standards and increasingly competitive economic and industrial landscapes, the development of non-toxic and easy-to-produce products for poultry farming remains a key objective.

[0012] Summary of the Invention In this context, the inventors have provided novel ready-to-dilute polymeric suspensions for preparing veterinary compositions intended for use in poultry vaccination. The polymeric suspensions according to the invention offer, among other advantages, the use of non-toxic ingredients and a low quantity 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, exhibit a viscosity of approximately 100-300 mPas, which is particularly well-suited for the formation of stable beads or droplets.

[0013] The present invention therefore relates to a ready-to-dilute polymeric suspension comprising:

[0014] - between 1 and 15% by weight of a thickening agent,

[0015] - between 0.5 and 8% by weight of at least one suspending agent,

[0016] - between 1 and 10% by weight of water, and

[0017] - at least 60% by weight of a non-aqueous vehicle, relative to the total weight of the suspension.

[0018] More specifically, the ready-to-dilute polymeric suspension according to the invention comprises:

[0019] - between 5 and 15% by weight of a thickening agent,

[0020] - between 2 and 6% by weight of at least one suspending agent,

[0021] - between 2 and 10% water by weight, and

[0022] - at least 60% by weight of a non-aqueous vehicle, relative 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% water by weight, and

[0027] - at least 75% by weight of a non-aqueous vehicle, relative to the total weight of the suspension.

[0028] 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.

[0029] 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.

[0030] In one application, 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. In a preferred application, the thickening agent is carboxymethylcellulose.

[0031] 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. A preferred object of the invention is a ready-to-dilute polymeric suspension comprising:

[0032] - between 8 and 13% by weight, preferably around 11% by weight of carboxymethylcellulose,

[0033] - between 2 and 4% by weight, preferably about 3% by weight of a mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate,

[0034] - between 0.1 and 1% by weight, preferably about 0.5% by weight of sodium chloride,

[0035] - between 2 and 8% by weight, preferably around 6% by weight of water,

[0036] - 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)-2-toluenesulfonic acid, and

[0037] - propylene glycol qsp, relative to the total weight of the suspension.

[0038] Preferably, the ready-to-dilute polymeric suspension as described in this application is sterile.

[0039] 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.

[0040] According to one aspect, 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. Preferably, the therapeutic agent comprises oocysts of Eimeria acervidina, Eimeria maxima, Eimeria lenella, Eimeria necalrix, Eimeria brune, Eimeria adenoides, and Eimeria meleagremitis.

[0041] Another object of the invention is a composition as defined in the present application intended for use in the treatment of viral, bacterial, or parasitic infection in poultry, particularly in newborns.

[0042] 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.

[0043] Detailed description of the invention

[0044] The present invention provides a ready-to-dilute polymeric suspension comprising:

[0045] - between 1 and 15% by weight of a thickening agent,

[0046] - between 0.5 and 8% by weight of at least one suspending agent,

[0047] - between 1 and 10% by weight of water, and

[0048] - at least 60% by weight of a non-aqueous vehicle, relative to the total weight of the suspension.

[0049] According to the invention, the polymeric suspension is ready to be diluted. "Ready to be diluted suspension" means a suspension that can be directly and simply diluted in a liquid medium, preferably water, to form a reconstituted product. Preferably, no steps other than a dilution step are required to form the reconstituted product from the suspension according to the invention.

[0050] According to a particular embodiment of the invention, the ready-to-dilute polymeric suspension comprises:

[0051] - between 5 and 15% by weight of a thickening agent, - between 2 and 6% by weight of at least one suspending agent,

[0052] - between 2 and 10% water by weight, and

[0053] - at least 60% by weight of a non-aqueous vehicle, relative to the total weight of the suspension.

[0054] Preferably, the ready-to-dilute polymeric suspension comprises:

[0055] - between 8 and 13% by weight of a thickening agent,

[0056] - between 2 and 4% by weight of at least one suspending agent,

[0057] - between 2 and 8% water by weight, and

[0058] - at least 75% by weight of a non-aqueous vehicle, relative to the total weight of the suspension.

[0059] 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).Specifically, the thickening agent is present at a weight proportion of between 1 and 15%, between 5 and 15%, or between 8 and 13% of the suspension, relative to its total weight. The thickening agent, particularly sodium carboxymethylcellulose, in such proportions allows for the formation of stable beads or droplets after dilution in water.

[0060] According to the invention, the polymeric suspension comprises at least one suspending agent. This suspending agent facilitates, in particular, the homogenization of the suspension. In 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. In 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. Specifically, at least one suspending agent has a weight proportion of between 0.5 and 8%, between 2 and 6%, or between 2 and 4% of the suspension relative to its total weight.

[0061] According to another preferred method, the polymeric suspension comprises a mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate.

[0062] A preferred object of the invention is a ready-to-dilute polymeric suspension comprising:

[0063] - between 1 and 15%, preferably between 5 and 15%, and even more preferably between 8 and 13% by weight of a thickening agent,

[0064] - between 0.5 and 8%, preferably between 2 and 6%, and even more preferably between 2 and 4% by weight of a mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate,

[0065] - between 1 and 10%, preferably between 2 and 10%, and even more preferably between 2 and 8% by weight of water, and

[0066] - at least 60%, preferably at least 78% by weight of a non-aqueous vehicle, relative to the total weight of the suspension.

[0067] In a particular configuration, the non-aqueous vehicle comprises polyols, polyalkylene glycols, polyglycerin, and triacetin. In a more particular configuration, 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.

[0068] In 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.

[0069] In a specific manner, the suspension also includes a coloring agent. A coloring agent is, in particular, the disodium salt of α-[(N-ethyl-3-sulfo-benzylamino)-4-phenyl]-α-(N-ethyl-3-sulfo-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.

[0070] A preferred object of the invention is a ready-to-dilute polymeric suspension comprising:

[0071] - between 8 and 13% by weight of carboxymethylcellulose,

[0072] - between 2 and 4% by weight of a mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate,

[0073] - between 0.1 and 1% by weight of sodium chloride,

[0074] - between 2 and 8% by weight of water, - 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

[0075] - propylene glycol qsp, relative to the total weight of the suspension.

[0076] An even more preferred object of the invention is a polymeric suspension, preferably sterile, ready to be diluted, comprising:

[0077] - approximately 11% by weight of carboxymethylcellulose,

[0078] - approximately 3% by weight of a mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate,

[0079] - approximately 0.5% by weight of sodium chloride,

[0080] - approximately 6% water by weight,

[0081] - approximately 0.3 or approximately 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

[0082] - propylene glycol qsp, relative to the total weight of the suspension.

[0083] The terms "approximately" and "around" will be understood by a person skilled in the art and 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, "approximately" or "around" means plus or minus 20%, preferably plus or minus 10% of the particular term.

[0084] The sterile, ready-to-dilute polymeric suspensions according to the invention can be prepared using a simple, economical process, and therefore one well-suited to industrial scale. For example, the various ingredients, namely the suspending agent(s) and the thickening agent, are dissolved in water and a non-aqueous vehicle and heated to temperatures above 50 °C, preferably above 70 °C. One object of the invention relates to a process for preparing a ready-to-dilute polymeric suspension comprising the following steps: a) dissolving a suspending agent, preferably sodium chloride, in water;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; c) Assembly of the mixture from step a) with the mixture from step b) at a temperature around 100 °C; d) Addition 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)2-toluenesulfonic acid, to the mixture from step c) at a temperature around 100 °C; and f) Cooling to 25 °C and recovery of the ready polymeric suspension to be diluted.

[0085] According to a particular aspect of the invention, 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. In a particular embodiment, the heating sterilization step is carried out at a temperature between 100 and 150 °C, between 105 and 140 °C, or between 115 and 130 °C.preferably at a temperature of about 120 or 121 °C. According to a particular method, the sterilization step by heating is carried out for 10 to 120 minutes, 20 to 100 minutes, 30 to 90 minutes, preferably for about 60 minutes. An object of the invention also relates to a process for preparing a sterile polymeric suspension ready for dilution comprising the following steps: a) dissolving a suspending agent, preferably sodium chloride, in water; 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, c) assembly of the mixture from step a) with the mixture from step b) at a temperature around 100 °C, d) addition 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) 2-toluenesulfonic acid, in the mixture of step c) at a temperature around 100 °C, e) heating of the mixture of step d) at a temperature of about 121 °C for about 60 minutes; and f) cooling to 25 °C and recovery of the polymeric suspension ready for dilution.

[0086] The present invention also provides a composition comprising a polymeric suspension as described in this application, and a therapeutic agent. As described above, the polymeric suspensions of the invention can be diluted in water to form a composition, also referred to as the reconstituted product in this application.

[0087] One object of the invention relates to a composition comprising a sterile, ready-to-dilute polymeric suspension as described in this application and water. Another object of the invention also relates to a composition comprising a sterile, ready-to-dilute polymeric suspension as described in this application, water, and a therapeutic agent.

[0088] The term "therapeutic agent" refers to any agent, compound, molecule, or drug that has a biological or therapeutic effect on a subject. Examples of therapeutic agents include living organisms, vitamins, minerals, and electrolytes.

[0089] Specifically, a therapeutic agent is 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. More particularly, the therapeutic agent includes oocysts of Eimeria acervulina, Eimeria maxima, Eimeria lenella, Eimeria necalrix, Eimeria brune, Eimeria adenoides, and Eimeria meleagremitis.

[0090] In general, 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.

[0091] An object of the invention therefore relates to a process for preparing a composition comprising the following steps: a1) adding a quantity of water into a mixer, a2) progressively adding into the mixer a ready-to-dilute polymeric suspension as described in the present application, and leaving under agitation, a3) progressively adding the therapeutic agent into the mixer, and leaving under agitation, and a4) recovering the composition.

[0092] 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 exhibits 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.

[0093] Preferably, the compositions according to the invention are intended to be administered orally.

[0094] One object of the invention 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.

[0095] 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.

[0096] 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 a viral, bacterial, or parasitic infection" also includes the control, that is, the eradication, elimination, or reduction of the parasite(s) responsible for such an infection in a non-human mammal, particularly poultry.

[0097] In one particular sense, these terms include the curative treatment of a non-human mammal against a viral, bacterial, or parasitic infection. "Curative treatment" refers to treatment that cures a non-human mammal of a viral, bacterial, or parasitic infection. In another particular sense, these terms include the preventive treatment of a non-human mammal against a viral, bacterial, or parasitic infection. In one sense, preventive treatment refers to 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 of the non-human mammal 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 of 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.

[0098] In particular, the compositions of the invention are veterinary compositions. They are preferably intended for administration to poultry, especially newborns or chicks.

[0099] 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, particularly in newborns.

[0100] One 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.

[0101] 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.

[0102] Viral infections include, for example, infectious bronchitis, Gumboro disease, Newcastle disease, and infectious laryngotracheitis.

[0103] Examples of bacterial infections include coryza, salmonellosis, Escherichia coli, and necrotizing enteritis.

[0104] Parasitic infections include, for example, coccidiosis.

[0105] 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.

[0106] Other aspects and advantages of the invention will become apparent from the following examples, which should be considered illustrative and not limiting.

[0107] Examples

[0108] 1. Preparation of a ready-to-dilute polymeric suspension according to the invention

[0109] Polymer suspension:

[0110] [Table 1]

[0111] Examples of Suspensions 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:

[0112] Sodium CMC 11.0%

[0113] Geleol Mono & Diglyceride NF 3.0% - Water 6.0%

[0114] Sodium chloride 0.5%

[0115] Brilliant Blue 0.3%

[0116] - Propylene glycol qs 100%

[0117] Suspension B:

[0118] Sodium CMC 10.0 - 12.0%

[0119] - PEG 4000 5.0 - 8.0%

[0120] - Water 4.0 - 8.0%

[0121] Sodium chloride 0.5%

[0122] Brilliant Blue 0.3%

[0123] - Propylene glycol qs 100%

[0124] Suspension C:

[0125] Sodium CMC 10.0 - 12.0%

[0126] Povidone K90 3.0 - 5.0%

[0127] - Water 4.0 - 8.0%

[0128] Sodium chloride 0.5%

[0129] - Propylene glycol qs 100%

[0130] Suspension D:

[0131] Sodium CMC 10.0 - 12.0%

[0132] Compritol 888 ATO 3.0 - 5.0%

[0133] - Water 4.0 - 8.0%

[0134] Sodium chloride 0.5%

[0135] - Propylene glycol qs 100%

[0136] Suspension E:

[0137] Sodium CMC 10.0 - 12.0%

[0138] Geleol Mono & Diglyceride NF 1.0 - 3.0%

[0139] - Water 4.0 - 8.0%

[0140] Sodium chloride 0.5% - Propylene glycol Qs 100%

[0141] 2. Reconstitution process

[0142] A composition according to the invention in the form of a gel (reconstituted product - Gel NF)) was prepared according to the process described below.

[0143] 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.

[0144] 3. Physicochemical properties

[0145] 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.

[0146] [Table 2]

[0147] The percentages in Table 2 are expressed as a percentage of the total weight of the product. 3.1. Viscosity

[0148] 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.

[0149] [Table 3]

[0150] The NF gel according to the invention has a viscosity between 120 and 192 mPa·s, suitable for forming well-adhered beads or droplets, just like the Cevagel® product. The WO 2011 / 011873 and Paracox gels have very high viscosity and cannot be used in a vaccination machine, such as the Desvac Spray & Gel vaccination machine.

[0151] 3.2. Contact angle

[0152] The contact angle of the products was measured in order to evaluate the droplet's resistance according to its wettability and surface tension.

[0153] Equipment: Goniometer for measuring contact angle; Drop test method

[0154] Average of values ​​over 6 measurements

[0155] [Table 4]

[0156] 3.3. pH

[0157] The pH of the products was measured using a pH meter to assess its neutrality in order to comply with specifications.

[0158] 10 mL sample [Table 5]

[0159] 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.

[0160] 4. Tests on vaccination equipment

[0161] Tests were carried out on Desvac's 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.

[0162] Equipment: Desvac Spray & Gel Vaccination Machine

[0163] Batch size: preparation of a 5L solution. Pressure: 2.5 bar.

[0164] Needle: 18G .033X.25 green 50P (Nordson EFD)

[0165] Support: plexiglass plate

[0166] Smaller droplets and a continuous flow without dripping were observed for the NF Gel according to the invention compared to the Cevagel® product.

[0167] 5. Preparation of a composition according to the invention

[0168] A composition according to the invention comprising cryptosporidium oocysts was prepared according to the following process:

[0169] 4.8 liters of water were added to a blender. 200 mL of polymeric suspension A was then gradually added to the blender. The mixture was then blended 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. 6. Biological Study

[0170] A preliminary study was implemented to verify the effectiveness of the composition prepared in point 5 above in comparison with the Cevagel® product.

[0171] Three groups of 10 chicks were placed in cages. The composition according to the invention and the Cevagel® product were then administered 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 administration.

[0172] [Table 6]

[0173] The results in Table 6 show an effectiveness for the composition of the invention comparable to the Cevagel® product.

[0174] 7. Biological study (continued)

[0175] An efficacy study was set up to confirm the results of the preliminary study.

[0176] Three groups of chicks were placed in cages. The composition according to the invention, prepared according to the process described in point 5, was administered to them using a Desvac Spray & Gel vaccination machine, either with the Immucox 3 vaccine (Eimeria Acervulina-Maxima-Tenella oocyst-based vaccine), or with the Immucox 5 vaccine (Eimeria Acervulina-Brunetti-Maxima-Necatrix-Tenella oocyst-based vaccine), or without vaccine to serve as a placebo control group. The three groups were challenged with ImL of a composition corresponding to one of the challenges described in Table 7 30 days after vaccine administration. [Table 7]

[0177] A lesion score study was then conducted for each group to verify the efficacy of the vaccines with the composition according to the invention. These trials revealed that:

[0178] - The Immucox 3 vaccine is effective against coccidiosis diseases caused by Eimeria acervulina, Eimeria maxima and Eimeria tenella when administered via the composition according to the invention.

[0179] The Immucox 3 vaccine is effective against coccidiosis diseases caused by Eimeria Brunetti, Eimeria necatrix, Eimeria acervulina, Eimeria maxima and

[0180] Eimeria tenella, when administered via the composition according to the invention, has not been shown to have any adverse effects following administration of these vaccines via the composition according to the invention.

[0181] The results of the tests demonstrate that the composition according to the invention is an effective vector for the oral administration of vaccines.

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% water by weight, 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% water by weight, 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 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.

7. Suspension according to claim 6, wherein at least one suspending agent is selected from sodium chloride and a glyceride.

8. Suspension according to any one of claims 1 to 7, wherein said at least one suspending agent is a mixture of glycerol mono- and distearate and glycerol mono- and dipalmitate.

9. Suspension according to any one of claims 1 to 6, 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.

10. Suspension according to claim 9, wherein the polysaccharide is selected from sodium alginate, sodium hyaluronate, sodium carboxymethylcellulose, methylcellulose, and hydroxypropylmethylcellulose, preferably sodium carboxymethylcellulose.

11. Suspension according to any one of claims 1 to 10, 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.

12. Suspension according to any one of claims 1 to 11, comprising: - between 8 and 13% by weight, preferably around 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 around 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 α-[(N-ethyl-sulfo-3-benzylamino)-4-phenyl]-α-(N-ethyl-sulfo-3-benzylamino-4)-cyclohexadiene-2,5-ylidene)-2-toluenesulfonic acid, and - propylene glycol qsp, relative to the total weight of the suspension.

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

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

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

16. Composition according to claim 14 or 15, 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.

17. Composition according to any one of claims 14 to 16, wherein the therapeutic agent comprises oocysts of Eimeria acervulina, Eimeria maxima, Eimeria lenella, Eimeria necalrix, Eimeria bruneUi, Eimeria adenoides, and Eimeria meleagremitis.

18. A composition according to any one of claims 14 to 17, intended for use in the treatment of viral, bacterial, or parasitic infections in poultry, particularly in newborns.

19. A poultry vaccination kit comprising in a first compartment (a) a ready-to-dilute polymeric suspension according to any one of claims 1 to 13, and in a second compartment (b) a therapeutic agent according to claim 16 or 17.

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