Veterinary soft chewing product and manufacturing method thereof

Abstract

A soft chewing product (1) for oral administration has at least one pair of score marks (5, 6) configured to facilitate dividing the product into dose blocks (1a, 1b), the force required to divide the product (1) into dose blocks (1a, 1b) along the at least one pair of score marks (5, 6) being between 10 N and 60 N, and the mass loss during dividing the product (1) into dose blocks (1a, 1b) being less than 0.5%.

Description

Technical Field

[0001] The present invention relates to products in the form of soft chews, in particular soft chews, which can be easily divided into several dosage pieces by applying moderate manual force. More specifically, the subject of the invention is such products for veterinary use, in particular for dogs and cats, and methods for their manufacture. Background Art

[0002] In the veterinary field, the oral route is the simplest and most convenient method of administering pharmaceutical agents to animals, at least for their owners. A variety of dosage forms have been developed for the oral route, including solid dosage forms, of which tablets are the most common.

[0003] Hard tablets and chewable tablets are made from conventional dusty, granular and powdered materials. Their dry, gritty texture often makes them unappealing to many animals. In addition, hard chewable tablets break in the animal's mouth during chewing, and often parts of the tablet fall out of the animal's mouth. Compliance with the dosage is thus compromised.

[0004] On the contrary, soft chewable products have a soft texture, a pleasant mouthfeel and a suitable taste for animals, and they are generally easily accepted by animals. In addition, soft chewable tablets are moist, and when chewed by animals, soft chewable tablets maintain sufficient cohesion and they do not break, which is in sharp contrast to hard tablets and chewable tablets.

[0005] Most commonly, soft chewable products are unit doses of defined form and weight, comprising the same amount of active substance. They are almost exclusively obtained by compressing, moulding or extruding a paste containing the active substance.

[0006] Since the amount of active substance to be administered varies from subject to subject, in particular according to the subject's weight, animal health companies have developed products of different sizes intended for use over a more or less wide range of weights. For example, some veterinary products are sold as tablets intended for dogs weighing between 20 kg and 40 kg. Administration of a tablet to a 20 kg dog may result in an overdose and cause adverse reactions, whereas administration of the same tablet to a 40 kg dog may result in an underdose and compromise the efficacy of the treatment.

[0007] However, having products in lower weight ranges is limited by practical and economic considerations, such as the need to multiply the number of production cycles and the number of product presentations for the same product but different dosage strengths.

[0008] Products made from soft, divisible chewable compositions have been described in the prior art. US20140141055 describes the possibility of adding a cross score or score mark on one side of a soft chew made by molded scoring. US2020360290 describes a "soft tablet" with score marks that divide the tablet into up to 4 dosage pieces.

[0009] Furthermore, the introduction of score marks facing each other on opposite sides of hard tablets to facilitate their segmentation has been described in the prior art. However, soft chews and hard tablets differ significantly in their rheological properties: solid tablets are designed to be hard, brittle and resistant to crushing, whereas soft chews have a soft (ductile), deformable and plastic texture.

[0010] It is known that the way a material breaks (or fractures) into two or more parts under stress is different, depending on whether it is a brittle material or a deformable material. For brittle materials such as tablets, the fracture occurs by a mechanism called brittle fracture: when stress is applied to the material, the material does not deform, and the fracture occurs when the applied stress reaches the maximum value (limiting resistance) that it can resist. This fracture is the result of the formation of so-called unstable cracks and their spontaneous and extremely fast expansion. The fracture surface is usually clean. Reducing the thickness of the tablet with a score mark provides a predetermined weak point, which reduces the limiting resistance and allows the formation of cracks with less stress. By inserting a second score mark opposite to the first score mark, a predetermined fracture path is generated, which guides the direction of the crack during expansion. The essentially clean fracture surface then extends from one groove to another.

[0011] For deformable materials, such as soft chews, failure occurs through a mechanism called ductile failure: unlike brittle materials, the material deforms under stress but does not fail when the ultimate resistance is reached. Failure occurs when the material reaches its plastic limit. The material does not actually break, but rather tears due to the formation of stable cracks, which do not propagate spontaneously but instead propagate under the action of additional stress. The fracture surface is often irregular due to the deformation the material undergoes before failure. For ductile products, such as soft chews, score marks can facilitate segmentation by reducing the stress required to initiate a crack. However, once a crack has started, it will not propagate spontaneously. Summary of the invention

[0012] The object of the present invention is to solve the problems associated with the divisibility of prior art soft chewable products by improving the accuracy of the division and the accuracy of the dose obtained after division, while reducing the risk of contamination of the user by the active ingredients contained in the soft chewable composition.

[0013] It has been found that by careful selection of the rheological properties of the product and the arrangement of the score marks on the product, the soft chewable product can be more easily divided into dosage pieces.

[0014] Thus, the present invention proposes a soft chewable product for oral administration, comprising a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent, the soft chewable product having a pair of score marks facing each other on opposite sides of the product, the strength required to divide the product into dose pieces along the pair of score marks is preferably between 10 N and 60 N, and the mass loss during the division of the product into dose pieces is less than 0.5%. Preferably, the cumulative depth of the two score marks is greater than 10% of the thickness of the product.

[0015] "Soft chewable product" refers to a dimensionally stable pharmaceutical dosage unit having a flexible and elastic (ductile) texture. Soft chewable products have a higher moisture content than conventional tablets or chewable tablets. Unlike chewable tablets or hard tablets, soft chewable products can be deformed without breaking. In other words, if it falls, it will not break, but will eventually deform. In the present invention, preferably, the soft chewable product is a soft chew for animals (such as dogs and cats).

[0016] Due to the physical properties of the soft chewable product according to the invention, such as the configuration of the score marks, uniform separation of the product along said score marks is facilitated by simply applying a moderate force. The risk of contamination of the person separating the products is also limited. It is also possible to obtain a half, a quarter, a sixth or an eighth or any fraction of a product, with a controlled amount of active substance per portion, by adjusting the number of score marks.

[0017] In order to provide a soft chew product that can be easily split without loss of quality, other properties of the soft chew product such as hardness and friability should be considered because they affect the texture of the soft chew and have an impact on the mass loss during the splitting of the soft chew product. The friability of a soft chew refers to its tendency to break or crack easily when subjected to pressure or handling. It is a measure of the structural integrity and resistance to crushing of the soft chew. The lower the friability, the less likely the soft chew product is to break or crack, while the higher the friability, the more prone to breaking or disintegration.

[0018] In other words, the object of the present invention is to provide a soft chewable product that can be divided, if necessary, into two or more portions comprising a defined and reproducible amount of a substance. The division of the product allows the amount of substance to be administered to be easily adjusted according to the dose and / or body weight of the subject. The score marks configured to facilitate the division of the product into dosing pieces can define product portions of different sizes and weights or product portions of the same size and weight.

[0019] Since any fraction or multiple of fractions of the entire product can be administered, when the product is divisible into 8 dosage pieces, for example 1 / 8, 2 / 8, 3 / 8, 4 / 8, 5 / 8, 6 / 8, 7 / 8 or 8 / 8 can be administered, the product according to the invention has, among other advantages, the following advantages:

[0020] - The same product can administer a precise amount of substance to subjects with widely varying weights. For example, if each dose of the product contains the amount of substance to be administered per 10 kg of subject weight, a 30 kg subject will receive 3 / 8 of the product and a 70 kg subject will receive 7 / 8 of the product. This avoids overdosing or underdosing subjects.

[0021] - When the dose needs to be divided into several doses, the same product can be divided into several doses for consecutive administration. For example, when the product is administered twice a day, the product can be cut in half and each dose block can be taken at a specified time of the day.

[0022] - When it is difficult for the subject to swallow a single dose of the product, the same product can be administered multiple times. For example, when the subject is an elderly person or a child, the product can be cut into smaller dose pieces that are easier for the subject to swallow.

[0023] - The same product can be administered to several subjects at the same time. This is the case when several subjects have to receive the same treatment at the same time, for example in a hospital, clinic or veterinary clinic.

[0024] It should also be noted that the product according to the invention makes it possible to increase the exchange surface of the undivided product, thanks to the presence of the score mark or scores used. Such a configuration promotes the diffusion of the composition in the body and therefore its therapeutic effect when the product is used without being divided.

[0025] Another advantage is that the same product can be used in multiple doses, which enables the use of less packaging. For example, in the case where the product is administered twice a day, the product can be packaged in a single blister, rather than in two blisters.

[0026] The features according to the invention can be implemented independently of one another or in all technically possible combinations and form many variants of the invention:

[0027] - the force required to separate the product along the score mark is between 20N and 55N,

[0028] - the mass loss during segmentation is less than 0.1% of the total mass of the product,

[0029] - Score marks with V-shaped sections,

[0030] - at least one score mark extends parallel to the larger dimension of the product,

[0031] - the product is formed by extrusion, pressing or moulding,

[0032] - the cutting start point is set on at least one scoring mark,

[0033] - the product has a firmness between 10 N and 300 N, preferably between 10 N and 150 N, more preferably between 30 N and 80 N,

[0034] - the product has a brittleness of less than 1%, preferably less than 0.5%, more preferably less than 0.2%,

[0035] - the depth of each score mark occurring in pairs and facing each other on opposite sides is, independently of one another, between 1 / 20 and 4 / 10 of the thickness of the product,

[0036] - the cumulative depth of the two score marks of the same pair of said one or more pairs is greater than 20%, preferably greater than 30%, more preferably greater than 40%, and in a particular embodiment greater than 50%,

[0037] - both score marks of the same pair of said one or more pairs have the same depth, the depth of each score mark being between 5% and 45%, preferably between 10% and 45%, and more preferably between 25% and 35% of the thickness of the product,

[0038] a score mark, referred to as the first score mark, extending parallel, in particular parallel to a larger dimension of the product,

[0039] - All said score marks extend parallel to the longest dimension of the product

[0040] - as a variant, some other score marks, called additional score marks, extend transversely to the greatest dimension of the product,

[0041] - the score mark or pairs of score marks form a grid on the surface of the product,

[0042] - the score marks are configured to allow the product to be divided into four, six or eight dose blocks,

[0043] - The score marks are configured to allow for division into equal doses,

[0044] - the product has a cylindrical, elliptical, oblong or rectangular and / or parallelepiped form,

[0045] - the product has a base and projections extending from the base and separated by score marks,

[0046] - the base has a substantially rectangular cross-section,

[0047] - the product has a mass of 100 mg to 20 g,

[0048] - the pharmaceutical, veterinary or nutritional active substance is evenly distributed in the product,

[0049] - said product further comprises an excipient,

[0050] - the product is intended for use as a medicament to be administered to a subject, for human or veterinary use,

[0051] - the product is intended to be administered in several doses, in particular for a single and identical treatment,

[0052] - the product is intended to be administered at defined and / or regular intervals, each dose providing the subject to be treated with an effective amount of the pharmaceutically, veterinary or nutritionally active substance until the next dose is administered,

[0053] - the dosage of the product is intended to be administered several times a day, several days a week and / or several days a month,

[0054] - the product is intended for administration to elderly subjects or pediatric subjects,

[0055] - the product is intended for use on non-human mammals, preferably pets, and

[0056] - The product is intended for use on dogs or cats, preferably dogs.

[0057] The present invention also proposes a method for producing a shaped soft chew product as described above.

[0058] Preferably, the method comprises the following steps:

[0059] (a) obtaining a composition, and

[0060] (b) shaping the composition to obtain a shaped soft chew product.

[0061] According to a first embodiment, the shaping of the composition is carried out by pressing or moulding, the at least one score mark being hollowed out in step (b), in particular by means of a mould of suitable shape.

[0062] According to another embodiment, shaping is carried out by extrusion and, in step (b), the at least one score mark is hollowed out, in particular by means of a suitably shaped die. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] The invention will be better understood and other objects, details, features and advantages thereof will emerge more clearly from the following detailed explanatory description of at least one embodiment of the invention, by way of purely illustrative and non-limiting example, with reference to the accompanying schematic drawings, which include:

[0064] Figure 1 Schematically shows a perspective view of a first embodiment of a product according to the invention;

[0065] Figure 2 schematically shows a perspective view of a second embodiment of a product according to the invention;

[0066] Figure 3 schematically shows a perspective view of a third embodiment of a product according to the invention;

[0067] Figure 4 Schematically shows the Figure 1 A front view of a first test performed on a product;

[0068] Figure 5 Schematically shows the Figure 1 a front view of a second test performed on a product of; and

[0069] Figure 6 The soft chew is shown to have a high degree of brittleness after attempting to separate it by hand.

[0070] In the drawings, the same reference numerals correspond to the same or similar elements. DETAILED DESCRIPTION

[0071] The present invention relates to a soft chewable product 1 for oral administration, comprising a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent, wherein the product 1 has a pair of score marks 5, 6 facing each other on opposite sides 3a, 3b of the product, and the pair of score marks 5, 6 are configured to divide the product into dosage pieces 1a, 1b, the cumulative depth of the pair of score marks 5, 6 is greater than 10% of the thickness of the product 1, and the mass loss during the division of the product 1 into the dosage pieces 1a, 1b is less than 0.5%.

[0072] like Figures 1 to 3 As shown, the present invention provides a soft chewable product 1 for oral administration. The product has at least one score mark 5, 6 configured to facilitate the division of the product into doses 1a, 1b, 1c, 1d.

[0073] The latter is shown before separation. To carry out the separation of the product 1, the user can grasp two different areas of the product with one of his hands between the thumb and the index finger. He will then separate them along at least one score mark 5, 6.

[0074] According to the invention, in order to obtain a controlled and uniform manual division of the product, the product has score marks 5, 6 configured such that the force required to divide the product into dose pieces along said score marks 5, 6 is between 10 N and 60 N and the mass loss when dividing the product into dose pieces is less than 0.5%. Thanks to these characteristics, each dose piece comprises a controlled amount of substance. In addition, the risk of contamination by the user is reduced.

[0075] The soft chewable products according to the invention are characterized by their flexible (ductile) texture, softness and sensitivity to elastic deformation. The products according to the invention are also characterized by their texture, in particular the hardness of the product, which is preferably between 10 N and 300 N. Unlike solid tablets (e.g. chewable tablets and hard tablets), the products according to the invention can be deformed without breaking.

[0076] Unlike tablets, soft chews are pliable, and they lack the structural integrity required for clean separation; they tend to deform and stretch rather than break cleanly.

[0077] The hardness corresponds to the force required to obtain a given deformation of the product.

[0078] like Figure 4 As shown, in the present invention, hardness is measured in a texture analyzer, particularly TAXT2i (Stable MicroSystems) at a temperature between 18°C ​​and 25°C using a spherical probe with a diameter of 8 mm, and the parameters are as follows:

[0079] Suppression in test mode;

[0080] Pre-test speed 1.00 mm / s;

[0081] Test speed 1.00 mm / s;

[0082] After the test, the speed is 10.00 mm / s;

[0083] Target mode distance;

[0084] Distance 2.00mm;

[0085] trigger type automatic(force);

[0086] Release force 0.5N; and

[0087] Points per second: 25.

[0088] For example, these parameters are implemented directly in the texture analyzer software.

[0089] Briefly, the product 1 used as the test sample is placed on a flat base / surface 10 and a spherical probe 12 is lowered at a predetermined speed to a position 2 mm into the sample. The sample 1 is deformed by the probe 12 and the resistance offered by the sample is recorded, corresponding to the force required to penetrate 2 mm. The measured resistance expressed in Newtons (N) corresponds to the hardness of the product. The sample 1 is tested at a distance from the score marks 5, 6.

[0090] Advantageously, the product according to the invention has a hardness between 10 N and 150 N, preferably between 30 N and 80 N.

[0091] The composition of the product according to the invention can vary in large proportions. Suitable compositions for obtaining products having textural characteristics are described, for example, in applications WO2005 / 01 3714, WO2022 / 049149, WO2021 / 180603, WO2016 / 073347, WO2009 / 064859, WO2014 / 079825, WO2007 / 067582, WO2020 / 172232, WO2021 / 013825, WO2013 / 119442, WO2013 / 150052, WO2021 / 046296, WO2019 / 021191, WO2014 / 141223 and WO2012 / 049156.

[0092] The soft chewable product according to the invention comprises a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent.

[0093] As used herein, a "humectant" is a substance that has the effect of maintaining the softness of the soft chew during the shelf life of the product. Preferably, the humectant is selected from the group consisting of propylene glycol; triacetin; vinyl alcohol; neo-agarobiose; sugar polyols such as glycerol, sorbitol, xylitol and maltitol; polymeric polyols such as polydextrose; caprylic / capric triglyceride; propylene glycol dicaprylate / dicaprate; medium chain triglycerides sold under the trademark Miglyol, especially Miglyol 812 or 814; vegetable oils; or mixtures thereof.

[0094] As used herein, a "forming agent" is a substance that provides texture to a soft chew product.

[0095] Preferably, the shaping agent is selected from the group consisting of polyvinyl pyrrolidone; cross-linked polyvinyl pyrrolidone; various grades of polyethylene glycol including PEG 3350, PEG 4000, PEG 6000 and PEG 8000; copolymers of vinyl pyrrolidone and vinyl acetate; polypropylene glycol; polyethylene glycol-polypropylene glycol copolymer (poloxamer); microcrystalline wax; cetyl alcohol; polysaccharides; hydroxypropyl methylcellulose; poly(meth)acrylates; polyalkyl(meth)acrylates; and mixtures thereof.

[0096] Preferably, the soft chewable product further comprises a filler (or diluent).

[0097] As used herein, "filler" refers to a food product that contains significant amounts of starch and / or starch-like substances.

[0098] Preferably, the filler is selected from the group consisting of starch, such as corn starch, rice starch or potato starch; sucrose; confectioner's sugar; lactose including anhydrous lactose, hydrated lactose, spray-dried lactose; dextrin; dextran; mannitol; soy meal; soy protein powder; microcrystalline cellulose; silicified microcrystalline cellulose; calcium phosphate; crystalline maltose; maltodextrin; and mixtures thereof. More preferably, the filler is selected from the group consisting of corn starch, lactose, microcrystalline cellulose, confectioner's sugar and mixtures thereof.

[0099] Preferably, the soft chewable product further comprises a flavoring agent.

[0100] As used herein, "flavoring agent" means an inactive ingredient that induces pets to eat the veterinary dosage form of the present invention. The flavoring agent used in the dosage form of the present invention can take the form of a dry powder flavoring agent, a non-powder flavoring agent, or as a system using both dry powder and non-powder flavoring agents.

[0101] Flavoring agents include chicken, turkey, beef, pork, mutton, fish, eggs, cheese, seafood, vegetables and plant matter, yeast (e.g., brewer's yeast), yeast extracts and mixtures thereof. Natural meat flavoring agents can be obtained from meat, meat products, organ meats, yeast extracts, plant matter and mixtures thereof. For example, oral veterinary composition drugs may include flavoring agents based on animal products (such as dried meat or powdered meat and meat parts such as beef, pork, chicken, turkey, fish and mutton, organ meats such as liver and kidney, meat meal, bone meal and ground bone); and animal-derived foods such as casein, milk (which may include dry forms and low-fat forms, such as dry skim milk), yogurt, gelatin, cheese and eggs (collectively referred to as "flavoring agents of animal origin") may be used. The flavoring agent of non-animal origin comprises essential oil, oleoresin, essence or extract, protein hydrolyzate, distillate or any baking, heating or enzymolysis product, it contains the flavoring component of any other edible part of spice, fruit or fruit juice, vegetable or vegetable juice, edible yeast (active and inactive), herb, bark, bud, root, leaf or plant.Practitioners in this field can easily determine the type and amount of flavoring agent.More preferably, flavoring agent is selected from the group consisting of flavoring agent based on animal product (such as dried meat or powdered meat and meat part such as beef, pork, chicken, turkey, fish and mutton, organ meat such as liver and kidney, meat meal, bone meal and ground bone) and flavoring agent based on non-animal product (such as yeast, yeast extract and glutamate).The most preferred flavoring agent is chicken (or poultry) liver powder, yeast, yeast extract and their mixture.

[0102] In a preferred embodiment, the soft chewable product comprises:

[0103] - pharmaceutical, veterinary or nutritional active substances;

[0104] a humectant selected from the group consisting of propylene glycol; triacetin; vinyl alcohol; neoagarobiose; sugar polyols such as glycerol, sorbitol, xylitol and maltitol; polymeric polyols such as polydextrose; caprylic / capric triglyceride; propylene glycol dicaprylate / dicaprate; medium chain triglycerides sold under the trademark Miglyol, especially Miglyol 812 or 814; vegetable oils; or mixtures thereof;

[0105] - a shaping agent selected from the group consisting of polyvinyl pyrrolidone; cross-linked polyvinyl pyrrolidone; various grades of polyethylene glycol including PEG 3350, PEG 4000, PEG 6000 and PEG 8000; copolymers of vinyl pyrrolidone and vinyl acetate; polypropylene glycol; polyethylene glycol-polypropylene glycol copolymers (poloxamers); microcrystalline wax; cetyl alcohol; polysaccharides; hydroxypropyl methylcellulose; poly(meth)acrylates; polyalkyl(meth)acrylates; and mixtures thereof;

[0106] - a filler selected from the group consisting of starch, such as corn starch, rice starch or potato starch; sucrose; confectioner's sugar; lactose including anhydrous lactose, hydrated lactose, spray-dried lactose; dextrin; dextran; mannitol; soy meal; soy protein powder; microcrystalline cellulose; silicified microcrystalline cellulose; calcium phosphate; crystalline maltose; maltodextrin; and mixtures thereof; and

[0107] - a flavoring selected from the group consisting of: animal product based flavorings, such as dried or powdered meat and meat parts such as beef, pork, chicken, turkey, fish and lamb, organ meats such as liver and kidney, meat meal, bone meal and ground bone; and non-animal product based flavorings, such as essential oils, oleoresins, essences or extracts, protein hydrolysates, distillates or any product of roasting, heating or enzymatic hydrolysis, any product containing flavoring ingredients derived from spices, fruits or fruit juices, vegetables or vegetable juices, edible yeasts (active and inactive), herbs, barks, buds, roots, leaves or any other edible part of a plant; and mixtures thereof.

[0108] It is worth noting that, based on the total weight of the soft chew product, the soft chew product includes:

[0109] - 0.01% to 30%, preferably 0.1% to 20%, more preferably 5% to 15% of pharmaceutical, veterinary or nutritional active substances;

[0110] - 5% to 40%, preferably 10% to 30%, more preferably 10% to 20% of a humectant, preferably selected from the group consisting of: propylene glycol; triacetin; vinyl alcohol; neoagarobiose; sugar polyols such as glycerol, sorbitol, xylitol and maltitol; polymeric polyols such as polydextrose; caprylic / capric triglyceride; propylene glycol dicaprylate / dicaprate; medium chain triglycerides sold under the trademark Miglyol, especially Miglyol 812 or 814; vegetable oils; or mixtures thereof;

[0111] -1% to 40%, preferably 1% to 20%, more preferably 10% to 20% of a shaping agent, which is preferably selected from the group consisting of: polyvinyl pyrrolidone; cross-linked polyvinyl pyrrolidone; various grades of polyethylene glycol including PEG 3350, PEG 4000, PEG 6000 and PEG 8000; copolymers of vinyl pyrrolidone and vinyl acetate; polypropylene glycol; polyethylene glycol-polypropylene glycol copolymer (poloxamer); microcrystalline wax; cetyl alcohol; polysaccharides; hydroxypropyl methylcellulose; poly(meth)acrylates; polyalkyl (meth)acrylates; and mixtures thereof;

[0112] - 10% to 60%, preferably 15% to 45%, more preferably 15% to 35% of a filler, which is preferably selected from the group consisting of starch, such as corn starch, rice starch or potato starch; sucrose; confectioner's sugar; lactose including anhydrous lactose, hydrated lactose, spray-dried lactose; dextrin; dextran; mannitol; soy meal; soy protein powder; microcrystalline cellulose; silicified microcrystalline cellulose; calcium phosphate; crystalline maltose; maltodextrin; and mixtures thereof;

[0113] - 10% to 50%, preferably 10% to 35%, more preferably 15% to 35% of a flavoring agent, the flavoring agent is preferably selected from the group consisting of: animal product based flavoring agents, such as dried or powdered meat and meat parts such as beef, pork, chicken, turkey, fish and lamb, organ meats such as liver and kidney, meat meal, bone meal and ground bone; and non-animal product based flavoring agents, such as essential oils, oleoresins, essences or extracts, protein hydrolysates, distillates, or any product of roasting, heating or enzymatic hydrolysis, which contains flavoring ingredients derived from spices, fruits or fruit juices, vegetables or vegetable juices, edible yeast (active and inactive), herbs, barks, buds, roots, leaves or any other edible part of plants; and mixtures thereof; the flavoring agent is more preferably selected from chicken (or poultry) liver powder, yeast, yeast extract, and mixtures thereof.

[0114] - 0.1% to 20%, preferably 1% to 15%, more preferably 5% to 15% of a disintegrant, preferably selected from the group consisting of sodium starch glycolate, crospovidone, cross-linked carboxymethylcellulose and mixtures thereof.

[0115] The soft chewable product as described above may include at least one additional excipient selected from the group consisting of a lubricant, a glidant, a surfactant and a dye.

[0116] As a non-limiting example, a soft chewable product including a pharmaceutical, veterinary or nutritional active according to the present invention may include the following ingredients, by weight of the total weight of the product:

[0117] - 1% to 20% of a shaping agent, preferably selected from the group consisting of polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone, various grades of polyethylene glycol including PEG 3350, PEG 4000, PEG 6000 and PEG 8000, copolymers of vinylpyrrolidone and vinyl acetate, polypropylene glycol, polyethylene glycol-polypropylene glycol copolymers (poloxamers), microcrystalline wax, cetyl alcohol, polysaccharides, hydroxypropylmethylcellulose, poly(meth)acrylates, polyalkyl(meth)acrylates, and mixtures thereof;

[0118] -15% to 35% filler, such as microcrystalline cellulose, starch, or a mixture of these two fillers;

[0119] -10% to 20% humectant, such as polyethylene glycol, glycerin, or a mixture of these two humectants;

[0120] - 15% to 35% of at least one palatable agent, such as poultry liver powder or a flavoring agent of non-animal origin sold by DianaPetfood;

[0121] -5% to 15% disintegrant, such as croscarmellose sodium; and

[0122] - Optional excipients selected from antioxidants, lubricants and flavorings.

[0123] The configuration of the score mark can be selected in a variety of ways, as long as it is configured to allow the product to be divided into dosage blocks. For example, a product with two orthogonal score marks on opposing surfaces will not be considered to have a configuration that facilitates the division of the product into dosage blocks.

[0124] Preferably, the score marks are hollowed through the thickness of the product. The thickness of the product refers to the dimension extending perpendicular to the plane of the main lower or upper face of the product in an oblong, cubic or parallelepiped structure, or in the case of a cylindrical or elliptical product with the longest dimension. In the present invention, when referring to a fraction or part of the thickness, it refers to the thickness at the location where the pair of score marks are hollowed.

[0125] According to the invention, the product can be divided into two parts, for example, by applying a pulling force on each side of at least one score mark. If other score marks are present, the product can also be divided into smaller parts by pulling along these score marks again. Thus, a desired, for example identical, number of parts is obtained.

[0126] According to the invention, the force used to separate the product can be tension (pulling each sub-portion of the product away from each other, or pulling a single portion in the length direction of the score mark) or pressure (pressing one portion with the hand or fingers while the other portion is held in the other hand).

[0127] like Figure 5 As shown, within the meaning of the present invention, the force required to separate the product along at least one score mark is between 10 N and 60 N, which should be understood as the force measured on a texture analyzer, in particular a TA XT2i (Stable Micro Systems) at a temperature between 18° C. and 25° C. using a 2 cm diameter cylindrical probe, with the following parameters:

[0128] Suppression in test mode;

[0129] Pre-test speed 1.00 mm / s;

[0130] Test speed 10.00 mm / s;

[0131] After the test, the speed is 10.00 mm / s;

[0132] Target mode distance;

[0133] Distance 5.00mm;

[0134] Trigger Type Automatic (Force); and

[0135] Release force 0.5N.

[0136] For example, these parameters are implemented directly in the texture analyzer software.

[0137] In short, the first half of the product was fixed in the jig 20, and the cylindrical probe 22 was lowered just above the product 1 serving as a sample (1 mm), and then lowered a distance of 5 mm at a predetermined speed of 10 mm / sec.

[0138] The cylindrical probe 22 applies pressure to the second half of the product until it separates. The product is placed in the fixture 20 so that the separation of the sample produced by the test occurs along at least one score mark 5, 6. The resistance offered by the sample (the force required to separate the sample) is recorded. The measured resistance expressed in N corresponds to the separation force.

[0139] Advantageously, the score markings on the product are configured such that the force required to divide the product into dosage pieces is between 20N and 55N, or even between 24N and 52N.

[0140] Advantageously, the composition of the product and / or the score mark of the product is configured so that the mass loss during separation is less than, in particular strictly less than 0.4%, preferably 0.3%, more preferably 0.2%, even more preferably less than 0.1% of the total mass of the product.

[0141] In order to minimize mass loss during division, the product composition according to the present invention provides a friability of less than 0.5%, and preferably less than 0.2%, determined according to the method of European Pharmacopoeia Chapter 2.9.7 (Friability of uncoated tablets).

[0142] The score marks may be provided with, for example, a circular, square or rectangular cross section, such that the width of the score marks is constant over their depth. Score marks with a U or V cross section are particularly suitable.

[0143] When the notch mark has a V-section, such as Figures 1 to 3 As shown, the V-section has an opening angle between 40° and 120°, advantageously between 60° and 100°, and preferably equal to 80°+ / -5°. A V-section is to be understood as a section plane along a plane perpendicular to the major dimension of the product.

[0144] According to a first aspect, not shown, the product has a score mark arranged on a single surface of the product, preferably in the thickness of the product. In this configuration, the score mark has a depth greater than 20%, advantageously greater than 25%, and preferably greater than 50% of the thickness of the product. Advantageously, the cumulative depth of the score mark is less than 90% of the thickness of the product. Beyond such a depth, the product is too fragile and there is a risk of separation into several dosage pieces during storage or when the product is removed from its packaging without being intentionally divided.

[0145] According to a preferred aspect of the present invention, Figures 1 to 3 As shown, the product has at least one pair of score marks 5, 6, which face each other on opposite faces 3, 4 of the product. In this configuration, the cumulative depth of the two score marks is preferably greater than 20%, more preferably greater than 30%, even more preferably greater than 40%, and in a particular embodiment greater than 50%. The cumulative depth of the score marks is less than 90% of the thickness of the product. Beyond such a depth, the product is too fragile and there is a risk of separation into several dose blocks during storage or when the product is taken out of its packaging without intentional segmentation. Advantageously, the cumulative depth of the score marks 5, 6 or a pair of score marks is less than 70% of the thickness of the product.

[0146] In this configuration, the score marks 5, 6 facing each other may have the same depth as each other or different depths from each other.

[0147] According to one embodiment, each score mark differs from the relative score mark in depth by between 5% and 80%, the cumulative depth of the two score marks 5, 6 being greater than 10%, greater than 20%, more preferably greater than 30%, even more preferably greater than 40%, and in a specific embodiment greater than 50% and less than 90%, advantageously less than 70%.

[0148] According to another advantageous embodiment, corresponding to the embodiment shown, the score marks 5, 6 facing each other have the same depth, for example between 5% and 45% of the product thickness, advantageously between 10% and 35%, preferably between 25% and 35%, the cumulative depth of the two score marks being greater than 10%, greater than 20%, more preferably greater than 30%, even more preferably greater than 40%, and in a specific embodiment greater than 50%, and less than 90%, advantageously less than 70%.

[0149] When the product according to the invention is intended to be divided into two parts, the product has a single score mark hollowed out on a single surface of the product, or as Figure 1 As shown, a pair of score marks 5, 6 are positioned relative to each other and fixed on opposite sides 3, 4 of the product.

[0150] The score mark or the pair of score marks facing each other may cut into the thickness of the product to define two identical parts, such as Figure 1 Alternatively, they may be two different parts.

[0151] The choice of the configuration of the score marks facing each other will depend on the desired division and the dose of the substance to be administered, in particular the active substance. For an active substance administered in two identical doses, the score marks or score marks 5, 6 facing each other will be configured to define two identical portions of the product. For an active substance administered in a first dose representing 1 / 3 of the total amount of active substance and a second dose representing 2 / 3 of the total amount of active substance, the score marks or score marks facing each other will be configured to define two portions representing 1 / 3 and 2 / 3 of the product, respectively.

[0152] like Figure 2 and Figure 3 As shown, when the product according to the present invention is intended to be divided into two or more parts, in addition to the first score mark or the pair of score mark parts facing each other, the product also has at least one other score mark hollowed out on a single surface of the product, or as shown in Figure 2 and Figure 3 As shown, another pair of score marks are positioned facing each other on opposite sides of the product, the score mark or score mark pair being configured to allow the product to be divided into multiple dosage pieces.

[0153] The score mark pairs can be configured to allow the product to be divided into as many portions or dosage pieces as desired.

[0154] As shown in the figure, the pair of score marks are cut into the same surface or multiple surfaces of the product.

[0155] Pairs of notch marks can be dug in parallel directions, e.g. Figure 3 As shown, and / or a pair of notch marks are dug out in the transverse direction, such as Figure 2 shown.

[0156] Score marks may define the same dose (such as Figure 3 One third of the products, or Figure 2 a quarter product), or even different doses (such as a half product and two quarter products).

[0157] According to a first variant, the depth of the score marks is the same whether they are the same pair of score marks and / or all score marks.

[0158] As a variation, additional score marks or score mark pairs may be provided that are of a different depth than the first score mark or first score mark pair to facilitate separation of the product according to one of the score marks. For example, a first deeper score mark or score mark pair may be provided to allow the product to be divided into two halves, and other score marks or score mark pairs of shallower depths may be used to divide each half into smaller portions.

[0159] The three-dimensional form of the product according to the invention can be very diverse. It can be a combination of superimposed cylinders, triangles, etc. Preferably, the product has an elongated cylindrical, elliptical, oblong, parallelepiped or cuboid form.

[0160] exist Figure 1 In the embodiment, it has the form of two parallel cylinders, each cylinder corresponding to one of the dosage blocks 1a, 1b and connected to the other cylinder by a pair of notched marks 5, 6. Figure 2 In the embodiment of the invention, it has a generally parallelepipedal form with slightly rounded edges. It forms four rectangular doses connected by pairs of orthogonal notch marks 5, 6. Figure 3 In the embodiment of the invention, it has the form of three parallel cylinders, each cylinder corresponding to one of the dosage blocks 1a, 1b, 1c and connected to another of the cylinders by one of the pairs of score marks 5,6.

[0161] The product according to the invention advantageously has a mass between 100 mg and 20 g, in particular between about 100 mg and about 10 g, even more in particular between 500 mg and 7 g. In illustrative embodiments, the product has a mass of 700 mg, 3.5 g and 6.5 g.

[0162] The product of the invention is intended for administration to all types of subjects, human and non-human. Advantageously, the product according to the invention is intended for use in non-human mammals.

[0163] Thus, the shaped soft chewable products according to the present invention may be formulated in the form of appetizing bites or soft chewable tablets.

[0164] The shaped soft chew products according to the present invention are particularly suitable for administration to companion animals, particularly dogs, cats and ferrets.

[0165] According to an advantageous embodiment, the shaped soft chewable product is intended for use with subjects who have difficulty ingesting large amounts of medication, such as elderly or pediatric subjects.

[0166] The products according to the invention can be used for the administration of all types of substances, in particular pharmaceutically or veterinary active substances or nutritional substances.

[0167] Thus, the product of the present invention comprises at least one nutritional substance or at least one pharmaceutically active substance uniformly distributed in the product.

[0168] In one embodiment, the active substance is a pharmaceutical active ingredient, in particular selected from anesthetics, corticosteroids, NSAIDs, antibiotics, antiemetics, antithyroid agents, anthelmintics, parasiticides, appetite stimulants, antihistamines, antipruritics, histamine blockers, antifungals, antiprotozoals, anthelmintics, antidepressants or steroids, or any combination of two or more of these.

[0169] The NSAID may be selected from meloxicam, carprofen, naproxen, tolfenamic acid and meclofenamic acid, flunixin and indomethacin.

[0170] The anthelmintic may be selected from: macrolides such as abamectin, moxidectin, avermectin, ivermectin, selamectin or cydectin, milbemycin; benzimidazoles such as mebendazole, fenbendazole, oxfendazole, albendazole, thiabendazole or thiabendazole; imidazothiazoles such as levamisole or pyrantel; salicylanilides such as closantel or niclosamide; praziquantel or epsipantel.

[0171] The antibiotic can be selected from penicillins, aminopenicillins (e.g., amoxicillin, ampicillin, hetacillin), cephalosporins (e.g., cefuroxime, ceftiofur), quinolones (e.g., ciprofloxacin, enrofloxacin, difloxacin, orbifloxacin, marbofloxacin); chloramphenicols (e.g., chloramphenicol, thiamphenicol, florfenicol); tetracyclines (e.g., chlortetracycline, tetracycline, oxytetracycline, doxycycline, minocycline); macrolides (e.g., erythromycin, tylosin, tilicosin, clarithromycin, azithromycin, tulathromycin); lincosamides (e.g., lincomycin, clindamycin); aminoglycosides (e.g., gentamicin, amikacin, kanamycin, apramycin, tobramycin, neomycin, dihydrostreptomycin, paromomycin).

[0172] The antiemetic may be selected from maropitant and aprepitant.

[0173] The parasiticide may be selected from: organochlorines; organophosphates; carbamates; amidines; pyrethrins and synthetic pyrethroids; benzoylureas; analogs of juvenile hormone; macrolides; neonicotinoids; phenylpyrazoles; spinosomal, such as spinosad; isoxazolines, such as fluralaner; afoxolaner; sarolaner; and lotilaner.

[0174] The anti-cancer drug is a JAK-1 inhibitor, particularly selected from oclacitinib, molotinib, tofacitinib and ruxolitinib.

[0175] Within the meaning of the present invention, a nutrient refers to an ingredient whose purpose is to help or maintain the health of a target animal. For example, a nutrient can provide nutritional benefits to a target animal. Nutrients include, but are not limited to, vitamins, minerals, plant extracts, and combinations thereof.

[0176] Vitamins include, for example, vitamin A, vitamin E, vitamin B12, vitamin B3, d-pantothenic acid (vitamin B5), folic acid, vitamin B6, vitamin B1, vitamin D3, vitamin C, vitamin B2, and provitamins (such as beta-carotene or panthenol).

[0177] Minerals include potassium, sodium, manganese, zinc, iron, calcium, copper, cobalt, iodine, chloride and selenium. The minerals may be in the form of a suitable salt.

[0178] Other nutrients that may be considered include: lecithin; phosphatidylserine; antioxidants such as Pycnogenol, Ginkgo biloba extract, Bacopa extract, Huperzine A, omega-3 polyunsaturated fatty acids (such as DHA, 1EPA); flavonoids or plant extracts containing flavonoids such as blueberry or maqui berry, anthocyanins, flavan-3-ols, epigallocatechin gallate (ECGC) and proanthocyanidins, isoflavones such as puerarin and genistein and flavonols (e.g., rutin and troxerutin); cytochrome C; monosodium glutamate; N-acetylcysteine; zinc methionine; biotin; L-carnitine; phytoceramides; prebiotics; probiotics; postbiotics, casein phosphopeptides, L-theanine or green tea extract, ashwaganda and fish protein hydrolysate.

[0179] In a specific embodiment, the nutrient is selected from the group consisting of: eggshell membrane; krill meal or krill oil, astaxanthin or a source of astaxanthin, such as seaweed, yeast, salmon, trout, krill, shrimp and crayfish; boswellia serrata; hyaluronic acid or a salt thereof; and vitamin D3. Preferably, the nutrient is a mixture of at least 2, at least 3 or at least 4 nutrients selected from the group consisting of eggshell membrane, krill meal, astaxanthin or a source of astaxanthin (such as seaweed, yeast, salmon, trout, krill meal or krill oil, shrimp and crayfish), boswellia serrata, hyaluronic acid or a salt thereof, and vitamin D3. Even more preferably, the nutrient is a mixture of eggshell membrane, krill meal or krill oil, astaxanthin, boswellia serrata and hyaluronic acid or a salt thereof.

[0180] The pharmaceutical, veterinary or nutritional active substance may be present in the product in any amount as required to achieve the desired therapeutic effect or health benefit. Advantageously, the pharmaceutical, veterinary or nutritional active substance is present at a level of 0.1% to 20% of the total mass of the product, preferably at a level of 1% to 10%.

[0181] Of particular note are soft chewable products according to the present invention wherein the active substance is meloxicam.

[0182] The present invention also proposes a method for making a shaped soft chewable product for oral administration as described above.

[0183] The method comprises, for example, the following steps:

[0184] (a) obtaining a composition comprising a pharmaceutically, veterinary or nutritionally active substance and inactive ingredients (such as excipients); and

[0185] (b) shaping the composition to obtain said product.

[0186] The product according to the invention can advantageously be manufactured by extrusion, moulding or compression of the composition.

[0187] The present invention therefore relates to a method for manufacturing a shaped soft chewable product for oral administration, the soft chewable product comprising a pharmaceutical, veterinary or nutritional active substance, as well as a humectant and a shaping agent, wherein the product has a pair of score marks facing each other on opposite surfaces of the product and configured to divide the product into dosage pieces, the cumulative depth of the pair of score marks being greater than 10% of the thickness of the product, and the cumulative depth of the two score marks being less than 90% of the thickness of the product, and the mass loss during the division of the product (1) into dosage pieces (1a, 1b) being less than 0.5%.

[0188] In more detail, the method comprises, for example, the following steps:

[0189] a) mixing the pharmaceutical, veterinary or nutritional active substance with a humectant and a shaping agent and optionally inactive ingredients such as excipients to prepare the composition; and

[0190] c) moulding, compressing or extruding the composition under conditions suitable for obtaining a soft chewable product, in particular temperature and pressure, hollowing out said pair of score marks in the product by means of a die during compression or moulding or by means of a compression mould during extrusion.

[0191] In one embodiment, the invention relates to a method for manufacturing a product as defined above, wherein the product is formed by extruding the composition, the at least one score mark 5, 6 being hollowed into the product by a die of the extruder.

[0192] According to this embodiment, the pharmaceutical, veterinary or nutritional active substances and inactive ingredients (such as excipients) are introduced into the hopper of the extruder, advantageously after the mixing step. The composition is then pushed through the extruder under suitable conditions so that the extrudate has the desired structural characteristics, such as a hardness between 10 N and 300 N and a brittleness of less than 1 roar until it leaves the extruder. At the exit of the extruder, a die of suitable shape forms the pair of score marks 5, 6 in the extrudate.

[0193] The extrudate in which at least one score mark is hollowed out is cut into portions of desired length in a direction transverse to the length of the extrudate, each portion thus obtained representing a product according to the invention.

[0194] It is preferred that the pair of score marks extend over the larger dimension of the product as this avoids excessively high cutting frequencies of the extrudate, thereby allowing for better uniformity of quality across the product.

[0195] The present invention therefore relates to a method for preparing a shaped soft chewable product for oral administration as described above by extrusion, comprising the steps of:

[0196] (a) optionally obtaining in a mixer a composition of a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent and optionally inactive ingredients such as excipients;

[0197] (b) introducing a pharmaceutical, veterinary or nutritional substance, a humectant and a shaping agent and inactive ingredients such as excipients into the hopper of an extruder to obtain said composition, or introducing said composition previously formed in step (a) into the hopper of an extruder;

[0198] (c) extruding the composition under suitable conditions to obtain an extrudate;

[0199] (d) hollowing the score mark pair through a die of an extruder;

[0200] (e) cutting the extrudate to obtain a shaped soft chewable product for oral administration; and

[0201] (f) optionally, packaging the product.

[0202] When the product has multiple score marks or multiple score mark pairs in parallel directions, these score marks can be formed directly on the product using a stamp of appropriate shape. The stamp will then be used, wherein the desired number of score marks or score mark pairs are made on the product.

[0203] When the product has at least one score mark or score mark pair (referred to as an additional score mark) in a direction transverse to the other score marks or score mark pairs (referred to as first score marks), additional steps are required to form the additional score mark or additional score mark pair.

[0204] The additional score mark or additional score mark pair may be formed on the product by any means. According to one embodiment, the additional score mark or score mark pair is formed on the product by molding or by pressing.

[0205] In this embodiment, the extruded product is introduced into a device such as a tablet press, Formax F6 manufactured by Formax Corporation. TM Type forming machine, U.S. Patent No. 3,486,186, 3,887,964, 3,952,478, 4,054,967, 4,097,961, 4,182,003, 4,334,339, 4,338,702, 4,343,068, 4,356,595, 4,372,008, 4,535,505, 4,597,135, 4,608,731, 4,622,717, 4,697 ,308, 4,768,941, 4,780,931, 4,818,446, 4,821,376, 4,872,241, 4,975,039, 4,996,743, 5,021,025, 5,022,888, 5,655,436 and 5,980,228, or the machine described in patent EP2922526; the product is then pressed or molded to form an additional score mark or score mark pair.

[0206] The present invention therefore relates to a process for preparing a shaped soft chewable product for oral administration as described above by extrusion, comprising the steps of:

[0207] (a) optionally obtaining in a mixer a composition of a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent and optionally inactive ingredients such as excipients;

[0208] (b) introducing the pharmaceutical, veterinary or nutritional active substance, the humectant and the shaping agent and optionally the inactive ingredients (such as excipients) into the hopper of the extruder to obtain the composition, or, alternatively, introducing the composition previously formed in step (a) into the hopper of the extruder;

[0209] (c) extruding the composition and hollowing out the score marks through a die of the extruder;

[0210] (d) cutting the extrudate;

[0211] (e) forming an additional score mark or score mark pair on the product score, preferably by pressing or molding, under conditions suitable to obtain a soft chewable product; and

[0212] (f) optionally, packaging the product.

[0213] In another embodiment, the invention relates to a process for manufacturing a product as defined above, wherein the score markings are formed in the product by moulding or compression, without prior extrusion.

[0214] According to this embodiment, the mixture containing the active substance of the composition and the excipients is introduced into a mixer, and the obtained composition (in the form of a paste) is then subjected to a compression or molding step in an apparatus such as a tablet press, Formax F6 manufactured by Formax Corporation. TM Molding machine, U.S. Patent Nos. 3,486,186, 3,887,964, 3,952,478, 4,054,967, 4,097,961, 4,182,003, 4,334,339, 4,338,702, 4,343,068, 4,356,595, 4,372,008, 4,535,505, 4,597,135, 4,608,731, 4,622,717, 4,6 97,308, 4,768,941, 4,780,931, 4,818,446, 4,821,376, 4,872,241, 4,975,039, 4,996,743, 5,021,025, 5,022,888, 5,655,436 and 5,980,228, or the machine described in patent EP2922526; using a mold of appropriate shape to form the score mark or score mark pairs.

[0215] The method makes it possible to manufacture a product having a score mark pair and an additional score mark or score mark pair in a single step by using a suitable die or punch, regardless of the direction of the additional score mark, in particular in a direction parallel to the first score mark or score mark pair and / or in a direction transverse to the first score mark or score mark pair.

[0216] Therefore, the present invention relates to a process for preparing a shaped soft chewable product for oral administration as described above, comprising the steps of:

[0217] (a) optionally obtaining in a mixer a composition of a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent and optionally inactive ingredients such as excipients;

[0218] (b) introducing a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent and optionally inactive ingredients (excipients) to obtain a composition, or introducing the composition obtained in step (a) into a container connected to a compression or molding machine;

[0219] (c) compressing or molding the composition under suitable conditions to obtain a soft chewable product, hollowing out the score mark pairs in the product through the mold; and

[0220] (d) optionally, packaging the product.

[0221] According to this embodiment, the pharmaceutical, veterinary or nutritional active substance, humectant and forming agent and optional inactive ingredients (excipients) are preferably mixed in a mixer before the compression or molding step to ensure a uniform distribution of the pharmaceutical, veterinary or nutritional active substance in the composition.

[0222] The present invention also relates in particular to a soft chewable product for oral administration as described above for use as a medicament.

[0223] According to an advantageous aspect of the invention, the product is intended to be administered in the form of doses to several subjects simultaneously and / or in the form of consecutive doses to the same subject.

[0224] Most pharmaceutical, veterinary or nutritional active substances are administered in a dose determined according to the subject's body weight. Since the product according to the invention can be divided into several parts, the amount of pharmaceutical active substance can be adjusted exactly according to the body weight of the subject to be treated.

[0225] Within the meaning of the present invention, "dose" means the portion of a product that is capable of achieving the desired therapeutic effect in the subject to be treated. Therefore, the term "portion" and the term "dose" are interchangeable in this application.

[0226] The effective dose of the pharmaceutically, veterinary or nutritionally active substance corresponds to the amount recommended by the practitioner, which is generally known in the literature and / or is determined by a person skilled in the art on the basis of his general knowledge or by carrying out preliminary or clinical tests.

[0227] Advantageously, the invention relates to a product as defined above, containing an active substance, in particular a veterinary active substance, in particular intended for use in pets such as dogs, cats or ferrets, for use as a medicament as described below.

[0228] More generally, the present invention relates to a soft chewable product for oral administration as described above, comprising a pharmaceutical, veterinary or nutritional active substance, for use as a medicament, the soft chewable product having a pair of score marks configured to facilitate the division of the product into dosing pieces, the strength required to divide the product into dosing pieces preferably being between 10 N and 60 N, and the mass loss during the division of the product into dosing pieces being less than 0.5%.

[0229] Advantageously, the dosage of the product is intended to provide the subject to be treated with an effective amount of the pharmaceutically, veterinarily or nutraceutically active substance until the next time the pharmaceutically, veterinarily or nutraceutically active substance is administered to the subject.

[0230] The possibility of adjusting the amount of product according to the body weight of the subject to be treated reduces the risk of overdose. In addition, since the division of the product is carried out without loss of mass, the amount of product administered is precise and there is no underdose due to the division of the product. For example, the same product can administer a precise amount of active substance to subjects with very different body weights. For example, if each portion of the product contains an effective amount of active substance for 10 kg of subject weight, a 30 kg subject will receive 3 / 8 of the product and a 70 kg subject will receive 7 / 8 of the product. This avoids overdose or underdose of the subject.

[0231] According to one aspect of the invention, the product is intended to be administered in several doses at defined intervals, each dose providing the subject to be treated with an effective amount of the pharmaceutically, veterinary or nutritionally active substance until the administration of the next dose.

[0232] When the dose needs to be divided into several doses, the same product can be administered in several consecutive doses. For example, when the product is administered twice a day, the product can be cut in half and each dose can be taken at a specified time of the day.

[0233] The same product can also be administered in several consecutive doses when it is difficult for the subject to swallow the entire product, for example when the subject is an elderly subject or a pediatric subject. Since the product can be divided into smaller and therefore easier to swallow doses, this helps to ensure that the treatment is carried out completely without underdosing due to division of the product.

[0234] Thus, the product is optionally intended to be administered to elderly or pediatric subjects in several doses as a single treatment.

[0235] Preferably, the product is intended for companion animals, particularly dogs or cats. In one embodiment, the product comprises a nutritionally active substance.

[0236] The present invention particularly relates to a soft chewable product as described above for use as a medicament, wherein an effective dose of the product is sequentially administered to an animal in need thereof.

[0237] In a particular embodiment, the invention relates to a soft chewable product as described above for use as a medicament, wherein the product is divided into dosage pieces and each dose is administered at defined intervals.

[0238] "Defined interval" refers to the time period corresponding to the dosimetry of the drug. For example, the interval can be a few hours (e.g., 4 hours, 6 hours, 12 hours, or 24 hours), a few days (e.g., 2 days, 3 days, 7 days), or a few weeks (e.g., 2 weeks, 3 weeks, or 4 weeks).

[0239] Preferably, the product is divided into two equal doses, the second dose being administered within 24 hours of the first dose.In a particular embodiment, the invention relates to a soft chewable product as described above for use as a medicament, wherein the product is administered once daily in two doses.

[0240] The present invention also relates to a method of treating a pathology or condition in a patient, comprising the steps of:

[0241] (1) providing a soft chewable product 1 comprising a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent, wherein the product 1 has a pair of score marks 5, 6 facing each other on opposite sides 3a, 3b of the product;

[0242] (2) dividing the soft chewable product 1 into individual dosage pieces along the score marks, the dosage pieces being suitable for the patient, in particular his / her weight;

[0243] (3) Single dose blocks are administered repeatedly at defined intervals based on the recommended treatment regimen for the pathology.

[0244] The present invention also relates to a method for treating a subject for a pathology, the method comprising administering to the subject a dose of a soft chewable product for oral administration, the soft chewable product comprising a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent, the product having a pair of scored marks configured to facilitate dividing the product into dosage blocks, the force required to divide the product into doses being between 10 N and 60 N, and the mass loss when dividing the product into dosage blocks being less than 0.5%, the dosage blocks providing an effective amount of the pharmaceutical, veterinary or nutritional active substance to the subject to be treated until the next administration of the pharmaceutical, veterinary or nutritional active substance.

[0245] The present invention further relates to a method for treating a subject for a pathology, the method comprising administering to the subject several consecutive doses of a soft chewable product for oral administration, the soft chewable product comprising a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent, the product having a pair of scored marks configured to facilitate the division of the product into dosage pieces, the force required to divide the product into dosage pieces being between 10 N and 60 N, and the mass loss during the division of the product into dosage pieces being less than 0.5%, providing the subject to be treated with an effective amount of the pharmaceutical, veterinary or nutritional active substance at each administration until the next dose is administered.

[0246] The invention further relates to the use of a soft chewable product for oral administration in the manufacture of a medicament intended for the treatment of a subject with a pathology, the soft chewable product comprising a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent, the product having a pair of score marks configured to facilitate the division of the product into dosing pieces, wherein the force required to divide the product into dosing pieces is between 10 N and 60 N and the mass loss during the division of the product into dosing pieces is less than 0.5%.

[0247] The invention further relates to the use of a soft chewable product for oral administration in the manufacture of a medicament intended for the treatment of a subject for a pathology, the soft chewable product comprising a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent, the product having a pair of score marks configured to facilitate the division of the product into dosing pieces, the force required to divide the product into dosing pieces being between 10 N and 60 N, and the mass loss during the division of the product into dosing pieces being less than 0.5%, the product being administered to the subject in several dosing pieces.

[0248] The invention further relates to the use of a soft chewable product for oral administration in the manufacture of a medicament intended for the treatment of a subject for a pathology, the soft chewable product comprising a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent, the product having a pair of score marks configured to facilitate the division of the product into dosage pieces, the force required to divide the product into dosage pieces being between 10 N and 60 N, and the mass loss during the division of the product into dosage pieces being less than 0.5%, the product being administered to the subject in several dosage pieces and providing an effective amount of the pharmaceutical, veterinary or nutritional active substance per day until the administration of the next dose.

[0249] The present invention further relates to a treatment regimen wherein the soft chewable product as described above is administered in equal doses at regular intervals.

[0250] The present invention relates in particular to a soft chewable product 1 for oral administration, comprising a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent, said product 1 comprising a pair of score marks 5, 6 facing each other on opposite faces 3a, 3b of the product and configured to divide the product 1 into dosage pieces 1a, 1b, the force required to divide the product 1 into dosage pieces 1a, 1b along said score mark pair 5, 6 being preferably between 10 N and 60 N, and the mass loss during the division of the product 1 into dosage pieces 1a, 1b being less than 0.5%.

[0251] Preferably, in said product 1, the cumulative depth of the two score marks 5, 6 is greater than 20%, preferably greater than 30%, even more preferably greater than 40%, in a particular embodiment greater than 50% of the thickness of the product 1, and the cumulative depth of the two score marks 5, 6 is less than 90%, advantageously less than 70% of the thickness of the product 1. More preferably, the two score marks 5, 6 have the same depth, each of the score marks 5, 6 having a depth between 10% and 45%, advantageously between 25% and 35%, of the thickness of the product 1.

[0252] In one embodiment, the nick marks 5, 6 comprise cleavage primers.

[0253] Preferably, the product has a brittleness of less than 0.5%, more preferably less than 0.2%.

[0254] Preferably, the product comprises:

[0255] - pharmaceutical, veterinary or nutritional active substances;

[0256] a humectant selected from the group consisting of propylene glycol, triacetin, vinyl alcohol, neo-agarobiose, sugar polyols such as glycerol, sorbitol, xylitol and maltitol, polymeric polyols such as polydextrose, caprylic / capric triglyceride, propylene glycol dicaprylate / dicaprate, medium chain triglycerides sold under the trademark Miglyol, especially Miglyol 812 or 814, vegetable oils, or mixtures thereof; and

[0257] - a shaping agent selected from the group consisting of polyvinyl pyrrolidone, cross-linked polyvinyl pyrrolidone, various grades of polyethylene glycol including PEG 3350, PEG 4000, PEG 6000 and PEG 8000, copolymers of vinyl pyrrolidone and vinyl acetate, polypropylene glycol, polyethylene glycol-polypropylene glycol copolymers (poloxamers), microcrystalline wax, cetyl alcohol, polysaccharides, hydroxypropyl methylcellulose, poly(meth)acrylates, polyalkyl(meth)acrylates, and mixtures thereof.

[0258] Preferably, the product further comprises:

[0259] - a filler, which is preferably selected from the group consisting of starch such as corn starch, rice starch or potato starch, sucrose, confectioner's sugar, lactose including anhydrous lactose, hydrated lactose, spray-dried lactose, dextrin, dextran, mannitol, soy meal, soy protein powder, microcrystalline cellulose, silicified microcrystalline cellulose, calcium phosphate, crystalline maltose, maltodextrin, and mixtures thereof; and

[0260] - a flavoring agent, which is preferably selected from the group consisting of: flavoring agents based on animal products, such as dried or powdered meat and meat parts such as beef, pork, chicken, turkey, fish and lamb, organ meats such as liver and kidney, meat meal, bone meal and ground bone; and, flavoring agents based on non-animal products, such as essential oils, oleoresins, essences or extracts, protein hydrolysates, distillates or any product of roasting, heating or enzymatic hydrolysis, which contains flavoring ingredients derived from spices, fruits or fruit juices, vegetables or vegetable juices, edible yeasts (active and inactive), herbs, barks, buds, roots, leaves or any other edible part of plants; and mixtures thereof.

[0261] Preferably, the product further comprises an excipient.

[0262] Preferably, the product is for use as a medicament, for human or veterinary use.

[0263] Preferably, the product is intended for use in elderly subjects or pediatric subjects.

[0264] Preferably, the product is intended for use in dogs or cats, preferably dogs.

[0265] Preferably, the product is manufactured by extrusion.

[0266] Preferably, the product is prepared by the following method:

[0267] (a) optionally obtaining a composition of a pharmaceutical, veterinary or nutritional active substance and inactive ingredients (such as excipients) in a mixer;

[0268] (b) introducing the pharmaceutically, veterinary or nutritionally active substance and inactive ingredients such as excipients into the hopper of an extruder to obtain said composition, or introducing said composition previously formed in step (a) into the hopper of an extruder;

[0269] (c) extruding the composition under suitable conditions to obtain an extrudate;

[0270] (d) hollowing the score mark pair through a die of an extruder;

[0271] (e) cutting the extrudate to obtain a shaped soft chewable product for oral administration; and

[0272] (f) Optionally, packaging the product.

[0273] Example - Characterization of the product according to the invention:

[0274] The products tested have the following composition (mass percentage relative to the total mass):

[0275] About 3%-5% active ingredients, 4%-6% microcrystalline cellulose, 4%-6% powdered sugar, 4%-6% polyethylene glycol 3350, 15%-25% native corn starch, 5%-15% croscarmellose sodium, 25%-35% flavoring, 0.1%-5% sodium chloride, 1%-10% purified water, 5%-20% glycerin, 1%-10% soybean oil, 0.001%-1% antioxidants and preservatives.

[0276] Example 1.1 - Hardness of the product

[0277] The hardness of the product was determined according to the method described above.

[0278] The average value measured was 65N.

[0279] Example 1.2 - Brittleness

[0280] The friability of the product was measured according to the method of European Pharmacopoeia Chapter 2.9.7 (Friability of uncoated tablets) using 12 divisible product halves. The results are reported in Table 1. The friability is expressed as mass loss in %.

[0281]

[0282] Table 1

[0283] Example 1.3 - Secability: Tension and mass loss

[0284] The tension was measured according to the method described above.

[0285] After weighing each product, about 700 mg, about 3.5 g and about 6.5 g (6 each) samples were tested. The results are given in Table 2.

[0286] 700mg 3.5g 6.5g Minimum strength 21.96 28.88 44.26 Maximum Strength 27.37 39.98 61.98 Average Strength 24.13 36.25 51.81 Standard Deviation 1.97 4.59 6.77

[0287] Table 2

[0288] After the split test, the product halves were weighed again to assess the mass loss after splitting. The results are given in Table 3:

[0289]

[0290]

[0291] Table 3

[0292] It can be seen that each of the samples tested had a value in accordance with the hardness specified for the product of the invention. Furthermore, the presence of at least one score mark, in relation to the force required to separate the product along the score mark or scores, allowed the separation of the product with very low mass loss, according to the value specified for the product of the invention.

[0293] Example 1.4 - Comparison between a soft chew having one score-mark and a soft chew having a pair of score-marks facing each other on opposite sides (3a, 3b) of the product.

[0294] These products were either soft chews with a single score-mark on one face or soft chews with a pair of score marks facing each other on opposite faces of the product. The score mark or scores had the same depth, with a cumulative depth of 20% of the thickness of the soft chew. The formulations of both types of soft chews were identical.

[0295] The purpose of this example is to evaluate the impact of introducing a second score mark on the opposite side of the product to the first score mark.

[0296] Two parameters were evaluated: mass loss and segmentation accuracy. To this end, 30 soft chews of each type (one score mark or two score marks) were weighed individually. These 30 soft chews were then manually separated along the score-marks by three different users (10 soft chews per user). Each half of the soft chews was weighed and used for statistical evaluation.

[0297] The mass loss was not significantly different for the two types of soft chews and was less than 0.01% in both cases based on the total weight of the soft chews.

[0298] There was a significant difference in the weight of the soft chews when split in half. The results are shown in the table below:

[0299]

[0300]

[0301] It can be seen that the mass difference between the two halves of the soft chew with one score mark is higher than the soft chew with a pair of score marks.

[0302] Thus, the presence of a pair of score marks facilitates dividing the soft chew into two identical dosage pieces.

[0303] The percent mass differences between doses were also statistically different: when two score marks were present, the dose difference between doses of the soft chew was 2 ± 1.5% and when only one score mark was present, the dose difference was 5.9 ± 3.5%. This suggests that the risk of overdose or underdose is higher when only one score mark is present on the soft chew.

[0304] Example 1.5—Comparison between soft chews without a pair of score marks on opposite sides of products of different crispness.

[0305] The product is approximately 3.5g of soft chews with varying degrees of crispness, no score markings, and a hardness of approximately 60N.

[0306] The purpose of this example was to evaluate the effect of the brittleness of soft chews on the ease and accuracy of segmentation under real life conditions. To this end, 20 pieces of each type of soft chew were weighed individually. These 20 soft chews were then split by hand by two different users (10 soft chews per user). During this test, it was quickly discovered that soft chews with high brittleness, while acceptable for use as a whole, were unacceptable for use in multiple doses.

[0307] In fact, in almost all cases, soft chews break in the user's hand due to finger pressure applied to the product or break along the score mark when tearing the two dose pieces apart, resulting in unacceptable mass loss and uneven division of the dose. [ Figure 6 ] shows a soft chew with high brittleness after trying to separate the soft chew into two parts by hand. As can be seen from the figure, the soft chew broke once divided, and several pieces were observed. Therefore, the quality loss was unacceptable. In one case (right picture), the soft chew even broke into three large pieces, and other small pieces also broke apart.

[0308] Thus, the low brittleness of the soft chews facilitates clean and even separation of the soft chews.

Claims

1. A soft chewable product (1) for oral administration, comprising a pharmaceutical, veterinary or nutritional active substance, a humectant and a shaping agent, in, The product (1) has at least one pair of score marks (5, 6), which face each other on opposite sides (3a, 3b) of the product and are configured to divide the product into dosage blocks (1a, 1b), the cumulative depth of the pair of score marks (5, 6) is greater than 10% of the thickness of the product (1), and the mass loss during the division of the product (1) into dosage blocks (1a, 1b) is less than 0.5%.

2. The soft chewable product (1) according to claim 1, wherein: The cumulative depth of the two score marks (5, 6) is greater than 20% of the thickness of the product (1), preferably greater than 30%, more preferably greater than 40%, and the cumulative depth of the two score marks (5, 6) is less than 90% of the thickness of the product (1); preferably less than 70% of the thickness of the product (1).

3. The soft chewable product (1) according to claim 2, wherein: The two score marks (5, 6) have the same depth, each of the score marks (5, 6) having a depth of 10% to 45%, advantageously 25% to 35% of the thickness of the product (1).

4. The soft chewable product (1) according to any one of the preceding claims, having a friability of less than 0.5%, preferably less than 0.2%.

5. A soft chewable product (1) according to any one of the preceding claims, wherein - the humectant is selected from the group consisting of propylene glycol; triacetin; vinyl alcohol; neoagarobiose; sugar polyols such as glycerol, sorbitol, xylitol and maltitol; polymeric polyols such as polydextrose; caprylic / capric triglyceride; propylene glycol dicaprylate / dicaprate; medium chain triglycerides sold under the trademark Miglyol, especially Miglyol 812 or 814; vegetable oils; or mixtures thereof; and - The forming agent is selected from the group consisting of: polyvinyl pyrrolidone; cross-linked polyvinyl pyrrolidone; various grades of polyethylene glycol including PEG3350, PEG 4000, PEG 6000 and PEG 8000; copolymers of vinyl pyrrolidone and vinyl acetate; polypropylene glycol; polyethylene glycol-polypropylene glycol copolymer (poloxamer); microcrystalline wax; cetyl alcohol; polysaccharides; hydroxypropyl methylcellulose; poly(meth)acrylates; polyalkyl(meth)acrylates; and mixtures thereof.

6. The soft chewable product (1) according to any one of claims 1 to 5, further comprising: - a filler, preferably selected from the group consisting of starch, such as corn starch, rice starch or potato starch; sucrose; fructose; lactose including anhydrous lactose, hydrated lactose, spray-dried lactose; dextrin; dextran; mannitol; soy meal; soy protein powder; microcrystalline cellulose; silicified microcrystalline cellulose; calcium phosphate; crystalline maltose; maltodextrin; and mixtures thereof; and - a flavoring agent, which is preferably selected from the group consisting of: flavoring agents based on animal products, such as dried or powdered meat and meat parts such as beef, pork, chicken, turkey, fish and lamb, organ meats such as liver and kidney, meat meal, bone meal and ground bone; and flavoring agents based on non-animal products, such as essential oils, oleoresins, essences or extracts, protein hydrolysates, distillates or any other product of roasting, heating or enzymatic hydrolysis, the any other product containing flavoring ingredients derived from spices, fruits or fruit juices, vegetables or vegetable juices, edible yeasts (active and inactive), herbs, barks, buds, roots, leaves or any other edible part of plants; and mixtures thereof.

7. The soft chewable product (1) according to any one of claims 1 to 6, for use in medicine.

8. The soft chewable product (1) for use thereof according to claim 7, wherein: The product is divided into dosage pieces to administer the appropriate amount of the pharmaceutical, veterinary or nutritional active substance to the subject to be treated.

9. The soft chewable product (1) for use thereof according to claim 7, wherein: The appropriate amount of the pharmaceutically, veterinary or nutritionally active substance is administered at defined intervals.

10. A soft chew product (1) for use as described in any one of claims 7 to 9 for dogs or cats, preferably dogs.

11. A soft chewable product (1) for use as described in claim 10, wherein: The active substance is a nutrient.

12. A method for preparing a soft chewable product according to any one of claims 1 to 6, comprising the steps of: (a) obtaining a composition comprising: - active substances for pharmaceutical, veterinary or nutritional use; - a humectant, preferably selected from the group consisting of propylene glycol; triacetin; vinyl alcohol; neoagarobiose; sugar polyols such as glycerol, sorbitol, xylitol and maltitol; polymeric polyols such as polydextrose; caprylic / capric triglyceride; propylene glycol dicaprylate / dicaprate; medium chain triglycerides; vegetable oils; or mixtures thereof; and - a shaping agent, which is preferably selected from the group consisting of: polyvinyl pyrrolidone; cross-linked polyvinyl pyrrolidone; various grades of polyethylene glycol including PEG 3350, PEG 4000, PEG 6000 and PEG 8000; copolymers of vinyl pyrrolidone and vinyl acetate; polypropylene glycol; polyethylene glycol-polypropylene glycol copolymers (poloxamers); microcrystalline wax; cetyl alcohol; polysaccharides; hydroxypropyl methylcellulose; poly(meth)acrylates; polyalkyl(meth)acrylates; and mixtures thereof; (b) shaping the composition to obtain the product having scored markings.

13. The method according to claim 12, wherein: The shaping of the composition is carried out by pressing or moulding, and in step (b) the score marks (5, 6) are hollowed out.

14. The method according to claim 12, wherein: The shaping is performed by extrusion, and in step (b) the score marks (5, 6) are hollowed out by a die, the die having a shape suitable for hollowing out the score marks.

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