Composition comprising hydrolysed alpha-s1-casein and fish protein hydrolysate

Abstract

The present invention relates to a new composition comprising hydrolysed alpha-s1-casein and a fish protein hydrolysate, to the method for producing said composition and to the use of the composition in a food supplement, in solid or liquid form, for domestic animals, in particular for cats and dogs. The compositions according to the invention are also intended to be administered orally in order to help the animal, preferably domestic animal, in particular dog or cat, to overcome situations which cause anxiety disorders, in particular separation-related problems, and to regain well-adjusted behaviour. The present invention has for example applications in the veterinary field, more particularly in the field of veterinary food supplements or of snacks, treats or bites for pets, in particular for dogs or cats.

Description

[0001] DESCRIPTION

[0002] TITLE OF THE INVENTION: COMPOSITION COMPRISING HYDROLYZED ALPHA-S1-CASEIN AND A FISH PROTEIN HYDROLYZATE

[0003] Technical field

[0004] The present invention relates to a novel composition comprising hydrolyzed alpha-s1-casein and a fish protein hydrolyzate, its manufacturing process and the use of the composition in a food supplement, in solid or liquid form, for domestic animals, in particular for cats and dogs.

[0005] The compositions according to the invention are further intended to be administered orally to help the domestic animal, in particular the dog or the cat, to overcome situations generating anxiety disorders, in particular disorders linked to separation, and to regain balanced behavior.

[0006] The present invention finds applications, for example, in the veterinary field, more particularly in the field of veterinary food supplements or snacks, treats or bites for pets, in particular for dogs or cats.

[0007] State of the art

[0008] Food supplement compositions based on milk protein hydrolyzate, called hydrolyzed alpha-s1-casein, are known. The effectiveness of hydrolyzed alpha-s1-casein in helping to overcome anxiety disorders has been proven by various clinical studies (CRSSA, 2002) [1],

[0009] Any changes in the animal's environment, such as new people in their surroundings, lactation periods, weaning or even a trip, fireworks or any other change in the animal's habits can generate anxiety disorders in the animal. All these stressful situations can most often be overcome by the animal by administering compositions containing hydrolyzed alpha-s1-casein.

[0010] Hydrolyzed alpha-s1-casein containing a bioactive peptide with relaxing properties, alpha-casozepine, was discovered by the company INGREDIA®. Hydrolyzed alpha-s1-casein was first identified in human babies, observing that freshly ingested milk provided newborns with calm and serenity. The baby's enzymatic system allows the natural release of alpha-casozepine, which causes this state during digestion. After research, it was possible to reproduce the baby's digestive mechanism, notably by using the digestive enzyme "trypsin", which made it possible to isolate, from casein, a milk protein hydrolyzate containing the bioactive peptide alpha-casozepine.

[0011] Thus, there are now a variety of commercial products, both for humans and animals, comprising hydrolyzed alpha-s1-casein. The compositions of the prior art are generally solid oral forms. They are found, for example, in the form of capsules, tablets or even powders.

[0012] There are also compositions based on hydrolyzate of fish, mollusc and / or crustacean proteins used in pharmaceutical and / or nutritional applications

[0013] Separation anxiety is one of the behavioral manifestations that pets may frequently face. It is a disorder that refers to any unwanted behavior and significant emotional distress that a domestic animal (preferably a dog or cat) exhibits when separated from its owner, or more broadly from members of its household. Unwanted behaviors include, for example, destruction, vocalizations, and / or inappropriate eliminations. More specifically, these disorders are observed in dogs and cats (Radosta et al, 2017) [5]. Furthermore, pharmaceutical and / or nutritional applications based on hydrolyzed alpha-s1-casein or hydrolyzed proteins from fish, mollusks, and / or crustaceans may be insufficient to prevent or limit separation anxiety.

[0014] Different, more severe treatments exist for the treatment of this type of disorder, however, they are mostly based on medications such as antidepressants like fluoxetine or clomipramine, substances which can have side effects (Landsberg et al, 2008, 2013, Sherman et al 2008) [2-4],

[0015] There is therefore a real need today to provide effective alternative compositions to these antidepressant-based compositions.

[0016] It is to the applicant's credit to have developed a palatable composition intended to be administered orally to animals, preferably to cats or dogs, comprising hydrolyzed alpha-s1-casein and a specific fish protein hydrolyzate, making it possible to overcome the drawbacks of the prior art, without needing to resort to treatment based on antidepressants.

[0017] Statement of the invention

[0018] The present invention thus relates to a new composition comprising:

[0019] - an alpha-s1-casein hydrolyzate,

[0020] - a fish protein hydrolyzate, the peptide distribution of the fish protein hydrolyzate being:

[0021] • at least 2% by mass, relative to the total mass of peptides in the hydrolyzate, of peptides with a molecular weight strictly greater than 10 kDa,

[0022] • from 25 to 80% by mass, relative to the total mass of peptides in the hydrolyzate, of peptides with a molecular weight strictly greater than 1.5 kDa and less than or equal to 10 kDa,

[0023] • from 15 to 70% by mass, relative to the total mass of peptides in the hydrolyzate, of peptides with a molecular weight strictly less than 1.5 kDa.

[0024] In particular, the composition according to the invention may be in the form of a solid or liquid oral composition, preferably solid, powdery or non-powdery. The composition according to the invention may thus be in solid or liquid form, preferably in the form of a treat, a snack, a bite, a powder, a tablet or a capsule containing powder or granules.

[0025] It is to the applicant's credit to have developed a composition comprising an alpha-s1-casein hydrolysate and a fish protein hydrolysate as described above, making it possible to prevent, regulate and / or treat, in animals, preferably domestic animals (such as dogs, cats and / or other pets), (anxiety) disorders such as discomfort and emotional distress, in particular in response to stressful factors and / or at least one behavioural disorder, such as one or more undesirable behaviours linked to separation from its owner.

[0026] Surprisingly, the new combination according to the invention significantly increases the duration of action (thanks to the association of metabotropic and ionotropic action) as well as the responder rate. In particular, the combined action on GABA A and B receptors has a synergistic effect on the duration of action.

[0027] Advantageously, the composition according to the invention is stable, in particular the hydrolyzed alpha-s1-casein and the fish protein hydrolyzate which are stable for a period of at least 6 months, preferably at least 9 months or at least 12 months, and even more preferably at least 18 months.

[0028] Thus a first object of the invention is a new composition comprising:

[0029] - an alpha-s1-casein hydrolyzate,

[0030] - a fish protein hydrolyzate, the peptide distribution of the fish protein hydrolyzate being:

[0031] • at least 2% by mass, relative to the total mass of peptides in the hydrolyzate, of peptides with a molecular weight strictly greater than 10 kDa,

[0032] • from 25 to 80% by mass, relative to the total mass of peptides in the hydrolyzate, of peptides with a molecular weight strictly greater than 1.5 kDa and less than or equal to 10 kDa,

[0033] • from 15 to 70% by mass, relative to the total mass of peptides in the hydrolyzate, of peptides with a molecular weight strictly less than 1.5 kDa.

[0034] Definitions

[0035] Alpha-s1-casein is a milk protein consisting of 199 amino acid residues. Its tryptic hydrolysis releases alpha-casozepine, a bioactive peptide with relaxant and anxiolytic properties, acting like benzodiazepines. Hydrolyzed alpha-s1-casein is also called alpha-s1-casein tryptic hydrolysate (or alpha-s1-casein hydrolysate).

[0036] Hydrolyzed alpha-s1-casein contains, among other things, the following formula 1 alpha-casozepine:

[0037] Formula 1

[0038] Advantageously, hydrolyzed alpha-s1-casein is derived from milk.

[0039] In particular, it is a tryptic hydrolysate of milk protein or tryptic hydrolysate of alpha-s1-casein. It is titrated in a-casozepine, a marker of the activity of the product, but which is not 100% responsible for it (the other peptides present in the hydrolysate also have activity).

[0040] Advantageously, in the composition according to the invention, the concentration of alpha-s1-casein hydrolyzate is within a range from 1% to 70% by mass, preferably from 1 to 60%, more preferably from 10% to 50% or even from 15 to 50%, relative to the total mass of the composition.

[0041] Advantageously, the alpha-s1-casein hydrolyzate can be a milk protein hydrolyzate.

[0042] The term "fish protein hydrolyzate" means a purified marine peptide obtained by enzymatic hydrolysis and whose peptide distribution is: o at least 2% by mass, relative to the total mass of peptides in the hydrolyzate, of peptides with a molecular weight strictly greater than 10 kDa, o from 25 to 80% by mass, relative to the total mass of peptides in the hydrolyzate, of peptides with a molecular weight strictly greater than 1.5 kDa and less than or equal to 10 kDa, o from 15 to 70% by mass, relative to the total mass of peptides in the hydrolyzate, of peptides with a molecular weight strictly less than 1.5 kDa.

[0043] Advantageously, the fish protein hydrolysate may be obtained from fish having no more than 1% lipid. The fish are preferably from the gadidae family or the pleuronectidae family. They may thus be lean fish (also called white fish) from the North Atlantic seas, preferably chosen from gadidae and / or pleuronectidae. Preferably, the fish protein hydrolysate may be obtained from cod (Gadus morhua), pollock (Pollachius virens), haddock (Melanogrammus aeglefinus) and / or plaice (Pleuronectes platessa). Advantageously, the fish protein hydrolysate may comprise at least 80% protein relative to the total mass of the hydrolysate. Fish protein hydrolysate may include lipids and minerals (ash).For example, fish protein hydrolysate may have a protein / moisture / ash mass percentage distribution of >80 / <5 / <15, respectively. Lipids typically represent less than 0.5% of the hydrolysate mass.

[0044] Advantageously, in the composition according to the invention, the concentration of fish protein hydrolyzate in the composition is within a range from 5% to 20% by mass relative to the total mass of the composition, preferably from 10% to 15%.

[0045] A mass ratio of alpha-s1-casein hydrolyzate / fish protein hydrolyzate is defined. Said mass ratio can be in a range from 3 / 1 to 2 / 1, and is preferably equal to 2.5 / 1.

[0046] Advantageously, the composition according to the invention may further comprise one or more excipients (or additives). Preferably, the excipients (or additives) are chosen from texturizing agents, texturizing agents, fillers (or diluents), oils, chelating agents, colorants, preservatives, antioxidants, flavorings, and mixtures thereof.

[0047] A "texturizing agent" is an additive or ingredient that improves the presentation and hold of a composition to make it more attractive. A texturizing agent gives the composition consistency while ensuring the overall stability. It can be hydrophilic or hydrophobic. Hydrophobicity is the property of chemical groups that are repellent to water. These are non-polar groups that do not form hydrogen bonds with water. Conversely, hydrophilicity characterizes chemical groups that have an affinity for water. These are ionized (polar) groups that can form hydrogen bonds with water. The hydrophilic or hydrophobic properties of molecules play an important role in self-assembly phenomena in liquid media. Amphiphilic molecules have both a hydrophobic group and a hydrophilic group. Hydrophilic compounds are soluble in water but not in fatty substances.Conversely, hydrophobic compounds are soluble in fatty substances and insoluble in water. They are sometimes called lipophilic.

[0048] Advantageously, in the composition according to the invention, the concentration of texturizing agent is between 1% and 10% by mass, preferably 1% to 5% by mass, relative to the total mass of the composition.

[0049] Advantageously, the texturizing agent may be selected from the group comprising glycerol derivatives, for example glycerin, polyols, for example xylitol, sorbitol, polyethylene glycol, propylene glycol or polypropylene glycol, alcohols, for example cetyl alcohol, glycerol esters of fatty acids, for example glycerol monostearate and acetylated glycerides, diacetyl monoglyceride, acetic esters of monoglycerides and diglycerides, lipid surfactants, for example sorbitan esters, glycerol monooleate, or lipids, for example linolein, magnesium stearate and mixtures thereof. Preferably, the texturizing agent is magnesium stearate.

[0050] A "bulking agent" or "diluent" is an additive or ingredient that increases the volume of a composition. A bulking agent is used to add volume to the food preparation.

[0051] Advantageously, in the composition according to the invention, the concentration of filler (or diluent) is between 5% and 80% by mass, preferably 25% to 75% by mass, relative to the total mass of the composition.

[0052] Advantageously, the bulking agent (or diluent) may be chosen from the group comprising lactose, maltodextrin, starch derivatives, for example pregelatinized starch or flours (rye flour, oat flour), cellulose derivatives, for example cellulose fiber or microcrystalline cellulose, sorbitol, mannitol, sodium lactate, waxes and maltitol and mixtures thereof. Preferably, the at least one bulking agent or diluent is chosen from maltodextrin, lactose, mannitol, pregelatinized starch, rye flour, cellulose fiber, microcrystalline cellulose and mixtures thereof, and preferably from maltodextrin, lactose, mannitol, microcrystalline cellulose and mixtures thereof.

[0053] The term "vegetable oil" means a fatty substance extracted from an oilseed plant, that is to say a plant whose seeds, nuts or fruits contain lipids.

[0054] “Synthetic oil” means an oil obtained by chemical synthesis (for example by a polymerization, esterification or alkylation process) of components such as olefins, aromatic compounds, alcohols, or acids.

[0055] Mineral oil means an oil extracted from crude oil by refining (e.g., edible paraffin).

[0056] Advantageously, in the composition according to the invention, the oil concentration is between 1% and 20% by mass, preferably 3% to 7% by mass, relative to the total mass of the composition.

[0057] Advantageously, the oil can be chosen from vegetable, synthetic or mineral oil.

[0058] Advantageously, the oil may be selected from the group comprising castor oil, soybean oil, rapeseed oil, peanut oil, coconut oil, avocado oil, borage oil, camelina oil, safflower oil, hemp oil, wheat germ oil, jojoba oil, linseed oil, macadamia oil, neem oil, nigella oil, hazelnut oil, walnut oil, olive oil, evening primrose oil, pumpkin seed oil, grape seed oil, perilla oil, sesame oil and sunflower oil and mixtures thereof. Preferably, the oil is selected from the group consisting of soybean oil, rapeseed oil, sunflower oil or olive oil. A "synthetic, semi-synthetic or natural plant flavouring" means any product or substance intended to be added to foodstuffs to give them an odour, a taste, or an odour and a taste ((EC) No 1334 / 2008 on flavourings and certain food ingredients with flavouring properties). Flavourings do not have any nutritional qualities, but nevertheless play an essential role.Synthetic flavors are produced synthetically from chemicals. Their chemical structure and physicochemical properties are identical to those of flavors found in nature. Flavors that do not occur in nature may be a chemical modification of a natural flavor (addition of a chemical group, replacement of one atom with another: this improves the properties). Synthetic flavors are classified into 3 categories (artificial flavors, processed flavors, and smoke flavors). A natural plant flavor is obtained from plant raw materials but also through physicochemical means (from essential oils, for example). A natural flavor from an aromatic source must contain at least 90% of this aromatic source and 10% natural products. The finished product therefore gives an entirely natural flavor.This term refers to the fact that it is a biological substance but which has, however, undergone a limited number of transformations (distillation, roasting, cold extraction, fermentation, enzymatic reactions, enfleurage).

[0059] Advantageously, in the composition according to the invention, the concentration of synthetic, semi-synthetic or natural plant-based aroma is between 5% and 40% by mass, preferably 10% to 30% by mass, relative to the total mass of the composition.

[0060] Advantageously, the synthetic, semi-synthetic or natural plant-based flavoring, not comprising amino acids or proteins of animal origin, can be chosen from the group comprising yeasts, synthetic flavorings such as, for example, bacon, beef, chicken, meat, veal or turkey liver, chicken liver, beef liver, alone or in combination.

[0061] An "antioxidant" is a substance that reduces or prevents the oxidation of other chemical substances present in the composition.

[0062] Advantageously, in the composition according to the invention, the concentration of antioxidant is between 0.1% and 5% by mass, preferably from 0.2% to 1% by mass, relative to the total mass of the composition.

[0063] Advantageously, the antioxidant may be chosen from the group comprising vitamin C, sodium ascorbate, calcium ascorbate, potassium ascorbate, ascorbyl palmitate, ascorbyl stearate, vitamin E and its derivatives such as alpha tocopherol, D-alpha-tocopherol, DL-alpha-tocopherol, gamma tocopherol and delta tocopherol, sodium lactate, potassium lactate, calcium lactate, disodium ethylenediaminetetraacetate, oxystearin, thiodipropionic acid, propyl gallate, octyl gallate, dodecyl gallate, ethyl gallate, guaiac resin, erythorbic acid, sodium erythorbate, potassium erythorbate, calcium erythorbate, butylhydroxyanisole, butylhydroxytoluene, ethoxyquin, sodium orthophosphate, monosodium orthophosphate, disodium orthophosphate, trisodium orthophosphate, potassium orthophosphate, monopotassium orthophosphate, dipotassium orthophosphate,tripotassium orthophosphate, calcium dinatrium EDTA, tin chloride, hexylresorcinol, anoxomer, dilauryl thiodipropionate, distearyl thiodipropionate, sodium thiosulfate, sodium or potassium disulfite, glucose oxidase, and mixtures thereof. Preferably, the antioxidant is selected from the group consisting of tocopherol and its derivatives (alpha tocopherol, D-alpha tocopherol, DL-alpha tocopherol, gamma tocopherol or delta tocopherol), butylhydroxytoluene, propyl gallate and sodium ascorbate.,

[0064] A "preservative" is a substance that prolongs the shelf life of foodstuffs by protecting them from deterioration caused by microorganisms and / or protects them against the growth of pathogenic microorganisms ((EC) No. 1333 / 2008 on food additives). A distinction is made between organic preservatives and inorganic or mineral preservatives.

[0065] Advantageously, in the composition according to the invention, the concentration of preservative, preferably of antimicrobial preservative, is between 0.05% to 1% by mass, preferably 0.1% to 0.5% by mass, relative to the total mass of the composition.

[0066] Advantageously, the preservative may be selected from the group comprising acetic acid, potassium diacetate, potassium acetate, potassium diacetate, sodium hydrogen diacetate, sodium acetate, sodium diacetate, calcium acetate, carbon dioxide, sorbic acid, sodium sorbate, potassium sorbate, calcium sorbate, benzoic acid, sodium benzoate, potassium benzoate, calcium benzoate, ethylparaben, sodium ethylparaben, propylparaben, methylparaben, sodium methylparaben, sulfur dioxide, sodium sulfite, potassium sulfite, calcium sulfite, calcium hydrogen sulfite, potassium hydrogen sulfite, nisin, pimaricin, hexamethylin tetramine, dimethyl dicarbonate, potassium nitrite, potassium nitrite, sodium, potassium nitrate, dehydroacetic acid, sodium dehydroacetate, propionic acid, sodium propionate,calcium propionate, potassium propionate, boric acid, borax, sodium propylparaben, heptyl parahydroxybenzoate, ethyl lauryl arginate, lecithin citrate, phytic acid and mixtures thereof. Preferably, the preservative is an antimicrobial preservative and is selected from the group consisting of potassium sorbate and benzoic acid derivatives.,

[0067] Advantageously, the composition according to the invention may further comprise at least one colorant.

[0068] Advantageously, in the composition according to the invention, the concentration of colorant is between 0.1% and 5% by mass, relative to the total mass of the composition.

[0069] Advantageously, the colorant may be chosen from the group of food colorants. Preferably, the colorant is a caramel colorant.

[0070] Advantageously, the composition according to the invention may further comprise at least one chelating agent or any other excipient which may impact the texture and stability of the composition.

[0071] According to a variant of the invention, the composition according to the invention comprises:

[0072] - from 1% to 60% by mass, preferably 10 to 50%, of an alpha-s1-casein hydrolyzate,

[0073] - from 1% to 30% by mass, preferably 5 to 20%, of fish protein hydrolyzate as defined above,

[0074] - from 10% to 80% by mass of at least one bulking agent, preferably chosen from lactose, microcrystalline cellulose, maltodextrin and mannitol,

[0075] - from 1% to 10% by mass of at least one texturizing agent, preferably magnesium stearate, the sum of the quantities in percentage (%) being equal to 100%.

[0076] Advantageously, the composition according to the invention may be in solid or liquid form, preferably solid, in the form of powder, granules, tablets or capsules comprising powder or granules.

[0077] Advantageously, in solid form, the composition according to the invention may comprise water, preferably less than 10% water, or even less than 5%, relative to the total mass of the composition. Advantageously, in liquid form, the invention may comprise water, preferably at least 50% water, or even more than 80%, relative to the total mass of the composition.

[0078] The invention also relates to a capsule comprising a composition according to the invention, preferably in the form of powder or granules.

[0079] The invention also relates to a process or method for preparing the composition according to the invention.

[0080] Advantageously, the process or method for manufacturing a solid composition according to the invention comprises the steps: a) Mixing in a paddle or ribbon mixer or in a mixer by turning the hydrolyzed alpha-s1-casein, the fish protein hydrolyzate, and any excipients (e.g., bulking agent), until a homogeneous powder is obtained, b) Adding any texturizing agents and mixing, at room temperature, until a homogeneous powder is obtained, c) Extrusion of the homogeneous powder obtained in step b) and obtaining snacks, bites or treats, d) Compression of the homogeneous powder obtained in step b) and obtaining a tablet or e) Placing the homogeneous powder obtained in step b into a capsule.

[0081] Steps c), d) and e) are alternative steps, and are not implemented in the same process. The process can thus be implemented according to the ordered succession of steps abc, abd or abe.

[0082] Advantageously, step a) is carried out at room temperature, i.e. a temperature in the range from 15 to 25°C. Preferably, step b) is carried out under identical temperature conditions.

[0083] Steps b) and c) can be carried out in a mixer equipped with blades of the deflocculating propeller or marine propeller type, for extrusion. The composition according to the invention is intended to be administered orally.

[0084] The invention also relates to a food supplement comprising a composition according to the invention. The food supplement may be chosen from veterinary food supplements, in the form of a treat, a snack, a bite, a powder, a tablet or a capsule containing powder or granules, for domestic animals, for example dogs and / or cats.

[0085] The invention also comprises a use of a combination of alpha-s1-casein hydrolyzate and fish protein hydrolyzate in a food supplement, solid or liquid, preferably solid. The alpha-s1-casein hydrolyzate and the fish protein hydrolyzate are as defined above. Preferably, the mass ratio of alpha-s1-casein hydrolyzate / fish protein hydrolyzate is in a range from 3 / 1 to 2 / 1, and is preferably equal to 2.5 / 1.

[0086] Advantageously, in the use according to the invention, the food supplement comprises at least one excipient (or additive) chosen from texturizing agents, bulking agents (or diluents), oils, chelating agents, colorants, preservatives, antioxidants, flavorings, and mixtures thereof.

[0087] Advantageously, the food supplement, solid or liquid, is a treat, a snack or a bite for animals, preferably domestic animals, even more preferably for cats or dogs.

[0088] The invention also relates to a composition according to the invention intended to be administered orally to animals, preferably domestic animals, in particular cats or dogs.

[0089] Thus, the invention also relates to a composition according to the invention for its use in helping the animal, preferably domestic, in particular the dog or the cat, to overcome situations generating stress and to regain balanced behavior, for its use in the management and / or prevention of anxiety disorders in the animal, preferably domestic, in particular the dog or the cat.

[0090] The invention further relates to a use of a composition according to the invention for preventing or alleviating anxiety disorders in animals, preferably in cats or dogs.

[0091] Other advantages may still become apparent to those skilled in the art upon reading the examples below, illustrated by the attached figures, given for illustrative and non-limiting purposes.

[0092] EXAMPLES

[0093] EXAMPLE 1: Methods for manufacturing compositions according to the invention

[0094] The example compositions are made from the following compounds:

[0095] - Alpha-s1 -hydrolyzed casein (Lactium®),

[0096] - Fish protein hydrolyzate,

[0097] - Magnesium Stearate,

[0098] - Lactose,

[0099] - Maltodextrin,

[0100] - Microcrystalline cellulose, and

[0101] - Mannitol.

[0102] The following Table 1 gives the composition of the protein part of fish protein hydrolysate:

[0103] [Table 1]

[0104] Table 1: Peptide distribution of fish protein hydrolysate This distribution was measured using the LC-SEC UV analysis method (size exclusion chromatography). A 200A 15*7.8mm*1.7pm column was used. The separation was carried out during a 20 min isocratic LC method at 0.850 pl / min of a buffer consisting of 0.05 Sodium phosphate and 0.075 Sodium chloride at pH = 7.2. The fish protein hydrolysate is derived from a mixture of cod (Gadus morhua), pollock (Pollachius virens), haddock (Melanogrammus aeglefinus) and / or plaice (Pleuronectes platessa). Fish protein hydrolysate has a respective protein / moisture / ash mass percentage distribution of >80 / <5 / >15. Lipids represent less than 0.5% of the mass of the hydrolysate.

[0105] The respective protein, moisture and ash contents are measured respectively according to standards NF V 04-407, NF V 04-401 and NF V 04-404.

[0106] Preparation of the powder mixture: a) In a mixer by inversion, the bulking agent(s) (e.g. lactose, cellulose, maltodextrin, mannitol), the alpha-s1 - hydrolyzed casein, the fish protein hydrolyzate are successively added at room temperature, then mixed.

[0107] The resulting powder mixture is homogeneous and free of agglomerates.

[0108] Lubrication of the powder mixture: b) In a suitable container, the previously obtained powder mixture and the texturizing agent (i.e. magnesium stearate) are mixed, at room temperature, using an inversion mixer. Stirring is maintained until a homogeneous powder is obtained.

[0109] Capsule filling

[0110] The homogeneous mixture obtained is introduced into a capsule filler to be packaged into capsules of 75, 225 or 450mg of Lactium®.

[0111] We obtain composition 1: [Table 2]

[0112] Table 2: composition 1

[0113] EXAMPLE 2: Compositions according to the invention

[0114] Compositions 2 to 11 were prepared according to the method of Example 1: [Table 3]

[0115] Table 3: composition 2 to 11

[0116] EXAMPLE 3: Assessment of separation disorders in cats A test to assess separation disorders with the animal's owner was conducted on 100 cats of different weights and breeds. Each cat was administered two capsules of composition 9, each containing 75 mg of Lactium®, once a day for 30 days (from day 1 to day 30).

[0117] The experimentation and more particularly the characterization of the measured disorders are carried out based on Radosta [5]. The said behavioral disorders linked to the separation of the animal from its owners assessed are as follows:

[0118] - Constant meowing;

[0119] - Excessive licking;

[0120] - Scratching and destruction; - Urinating in inappropriate places;

[0121] - Urine marking;

[0122] - Defecation. The study was carried out in two phases:

[0123] Phase 1 (at JO): assessment of the frequency of occurrence of separation-related disorders in the animal over 24 hours by the owner according to one of the following criteria:

[0124] - Not assigned (N),

[0125] - From time to time (D),

[0126] - Often (S),

[0127] - All the time (T).

[0128] Phase 2 (at D15 and D30): measurement of the improvement of the animal's disorders over 24 hours depending on whether the owner observes:

[0129] - No improvement (-),

[0130] - An average improvement (+),

[0131] - A good improvement (++),

[0132] - An excellent improvement (+++).

[0133] The results obtained in phase 1 are presented in table 4 below:

[0134] [Table 4]

[0135] Table 4: Results of the assessment of separation-related disorders in cats (t = JO).

[0136] The results obtained in phase 2 are presented in tables 5 and 6 below:

[0137] [Table 5]

[0138] Table 5: Percentage of individuals by behavior observed at t = D15 for 24 hours.

[0139] [Table 6]

[0140] Table 6: Percentage of individuals by behavior observed at t = D30 for 24 hours.

[0141] For an average of 90% of cats, an improvement in the disorders was observed.

[0142] In addition, an increase in this improvement is observed at D30 compared to D15. For example, for the constant meowing disorder, a 95% improvement is observed at D30 compared to 87% at D30.

[0143] Thus, composition 9 allows an improvement in the disorders related to the separation of the cat from its owner at D15 and D30. Surprisingly, an increase in the improvement of the disorders is noted as the treatment time increases. No negative effects on behavior were observed.

[0144] EXAMPLE 4: Assessment of separation disorders in dogs

[0145] A test to assess separation-related disorders from the pet owner was conducted on 300 dogs of different weights and breeds. Each dog was administered once a day: - two capsules of composition 9, each containing 75 mg of Lactium® for dogs weighing between 5 and 10 kg,

[0146] - one capsule of composition 1 each comprising 225mg Lactium® for dogs weighing 10 to 15kg, one capsule of composition 7 each comprising 450mg of Lactium® for dogs weighing 15 to 30kg and two capsules for dogs weighing 30 to 60kg, for 30 days (from D1 to D30).

[0147] The experimentation and more particularly the characterization of the measured disorders are carried out by drawing inspiration from Radosta [5],

[0148] The following behavioral disorders related to separation from the animal were assessed:

[0149] - Constant monitoring of the owner by the animal,

[0150] - Anxious behavior when the owner leaves,

[0151] - Destruction,

[0152] - Urine / defecation,

[0153] - Excessive welcome,

[0154] - Barking / whining.

[0155] The study was conducted in two phases:

[0156] Phase 1 (at D0): evaluation of the frequency of appearance of separation-related disorders in the animal with its owner over 24 hours according to the following criteria:

[0157] - Not assigned (N),

[0158] - From time to time (D),

[0159] - Often (S),

[0160] - All the time (T).

[0161] Phase 2 (at D15 and D30): measurement of the improvement of the animal's disorders over 24 hours by the owner according to whether he observes:

[0162] - No improvement (-),

[0163] - An average improvement (+),

[0164] - A good improvement (++),

[0165] - An excellent improvement (+++). The results obtained in phase 1 are presented in table 7 below:

[0166] [Table 7] Table 7 Percentage of individuals by behavior observed at t = JO for 24H.

[0167] The results obtained in phase 2 are presented in tables 8 and 9 below:

[0168] [Table 8]

[0169] Table 8: Percentage of individuals by behavior observed at t = D15 for 24 hours.

[0170] [Table 9]

[0171] Table 9: Percentage of individuals by behavior observed at t = D30 for 24 hours.

[0172] For an average of 80% of dogs, an improvement in the disorders was observed.

[0173] In addition, an increase in this improvement is observed at D30 compared to D15. For example, for the destruction disorder, there is a 92% improvement at D30 compared to 83% at D30. For the urine / defecation disorder, an evolution at D30 of 81% improvement in the disorders is observed compared to 72% for D15.

[0174] Thus, the combination of alpha-s1-casein hydrolyzate / fish protein hydrolyzate shows an improvement in the problems related to the separation of the animal from its owner at D15 and D30. We also note an increase in the improvement of the problems as the duration of treatment increases. No negative effects on behavior were observed.

[0175] REFERENCES

[0176] 1. Lanoir D, Canini F, Messaoudi M, Lefranc-Millot C, Demagny B et al. Long term effects of a bovine milk alpha-S1 casein hydrolyzate on healthy low and high stress responders. 2002, Stress, Vol 5 (suppl.), page 124

[0177] 2. Landsberg G.M, Hunthausen W.L, et Ackerman L.J. Behavior problems of the dog and cat. 2013, Third edition. Edinburgh: Saunders / Elsevier. ISBN 978-0-7020- 4335-2. SF433

[0178] 3. Landsberg G.M, Melese P, Sherman B.L, Neilson J.C, Zimmerman A et Clarke T.P. Effectiveness of fluoxetine chewable tablets in the treatment of canine separation anxiety. 2008 January, Journal of Veterinary Behavior, Vol. 3, n° 1 , pages 12-19.

[0179] 4. Sherman B.L Separation anxiety in dogs. 2008 January, Compendium on Continuing Education for the Practising Veterinarian -North American Edition, 30 (1 ), pages 27-42.

[0180] 5. Radosta L et Fagen A. Separation-Related Disorders and the Differences Between Dogs and Cats. 2017, Today’s Veterinary Practice, Vol 7, n° 3, pages 53-58

Claims

CLAIMS

1. Composition comprising: - an alpha-s1-casein hydrolyzate, - a fish protein hydrolyzate, the peptide distribution of the fish protein hydrolyzate being: • at least 2% by mass, relative to the total mass of peptides in the hydrolyzate, of peptides with a molecular weight strictly greater than 10 kDa, • from 25 to 80% by mass, relative to the total mass of peptides in the hydrolyzate, of peptides with a molecular weight strictly greater than 1.5 kDa and less than or equal to 10 kDa, • from 15 to 70% by mass, relative to the total mass of peptides in the hydrolyzate, of peptides with a molecular weight strictly less than 1.5 kDa.

2. A composition according to claim 1, wherein the fish protein hydrolysate is obtained from cod (Gadus morhua), pollock (Pollachius virens), haddock (Melanogrammus aeglefinus) and / or plaice (Pleuronectes platessa).

3. Composition according to claim 1 or 2, in which the mass ratio of alpha-s1-casein hydrolyzate / fish protein hydrolyzate is in a range from 3 / 1 to 2 / 1, preferably equal to 2.5 / 1.

4. Composition according to any one of the preceding claims, in which the concentration of alpha-s1-casein hydrolyzate is in a range from 1% to 70%, preferably from 1 to 60%, more preferably from 10% to 50% or even from 15 to 50%, relative to the total mass of the composition.

5. A composition according to any preceding claim, wherein the alpha-s1-casein hydrolysate is a tryptic alpha-s1-casein hydrolysate.

6. Composition according to any one of the preceding claims, in which the concentration of fish protein hydrolyzate is in a range from 5% to 20% by mass relative to the total mass of the composition, preferably from 10% to 15%.

7. Composition according to any one of the preceding claims, further comprising an excipient, preferably chosen from texturizing agents, bulking agents, oils, chelating agents, colorants, preservatives, antioxidants, flavorings, and mixtures thereof.

8. A composition according to any preceding claim, wherein the bulking agent is selected from lactose, maltodextrin, pregelatinized starch, flours, cellulose fiber, microcrystalline cellulose, sorbitol, mannitol, sodium lactate, waxes and maltitol and mixtures thereof.

9. A composition according to any preceding claim, wherein the concentration of filler is in the range of 10% to 80% by mass relative to the total mass of the composition.

10. A composition according to any one of the preceding claims, wherein the texturizing agent is selected from glycerin, xylitol, sorbitol, polyethylene glycol, propylene glycol, polypropylene glycol, cetyl alcohol, glycerol monostearate, acetylated glycerides, diacetyl monoglyceride, acetic esters of monoglycerides and diglycerides, sorbitan esters, glycerol monooleate, linolein, magnesium stearate and mixtures thereof.

11. A composition according to any preceding claim, wherein the concentration of texturizing agent is in the range from 1% to 10% by mass relative to the total mass of the composition.

12. A food supplement comprising a composition according to any one of the preceding claims, in liquid or solid form, preferably a treat, snack, bite, powder, tablet or capsule containing powder or granules.

13. Composition or food supplement according to any one of the preceding claims for its use in the management and / or prevention of anxiety disorders in animals, preferably domestic animals, preferably dogs or cats.

14. Use of a composition or food supplement according to any one of the preceding claims for preventing or alleviating anxiety disorders in animals, preferably domestic animals, preferably chosen from dogs and cats, linked to separation from their owner.

15. Use of a combination of alpha-s1-casein hydrolyzate and fish protein hydrolyzate as defined in claim 1 in a food supplement for animals, preferably domestic animals, preferably dogs or cats.

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