Compositions and methods for reducing appetite and / or facilitating weight loss

Abstract

The present invention relates to a composition for reducing appetite and / or promoting weight loss, the composition comprising, in a first compartment, a first composition comprising a hydrophilic polymer selected from among polysaccharides, derivatives thereof, and mixtures thereof, a crosslinking compound, a foaming agent, and a foam-stabilising agent and, in a second compartment, separated from the first compartment, an acid selected from among tartaric acid, succinic acid, ascorbic acid and mixtures thereof. The invention also relates to methods for administering the composition according to the invention to a human or animal subject.

Description

[0001] COMPOSITIONS AND METHODS FOR REDUCING APPETITE AND / OR FACILITATING WEIGHT LOSS

[0002] TECHNICAL FIELD

[0003] The present invention relates to compositions, uses, and methods for reducing and / or modulating appetite and / or promoting weight loss in humans and / or animals.

[0004] STATE OF THE PRIOR ART

[0005] Obesity and overweight are conditions that affect more than 1.9 billion people aged 18 and over worldwide (World Health Organization global estimates). By 2030, the number of overweight people is expected to reach 3.3 billion. Overweight and obesity represent the fifth leading risk factor for death worldwide and claim at least 2.8 million lives each year (Source: World Health Organization - "Obesity and Overweight" - Fact Sheet No. 311). It is more particularly the multiple related problems such as cardiovascular diseases, diabetes, sleep apnea and joint problems that represent a risk for overweight or obese people.

[0006] Although being overweight is primarily a human problem, it can also affect pets, especially dogs and cats.

[0007] In principle, this can be remedied by dieting, but the natural appetite for food makes it difficult to control the diet.

[0008] In addition to traditional diet and exercise recommendations, medications such as GLP1 receptor agonists are available to treat obesity and overweight. However, these medications can be expensive and, like any medication, can cause unwanted side effects.

[0009] Based on this observation, the medical sector has developed other methods to combat obesity. Examples include gastric simulation using implantable electronic devices; surgical procedures such as gastroplasty and vertical calibrated gastroplasty with gastric resection (or "sleeve gastrectomy") or gastric bypass (or "Bypass"). These alternatives are invasive surgical procedures that are often irreversible and require extensive post-operative monitoring throughout the patient's life. Medical devices consisting of balloons implanted in the stomach to reduce feeding capacity exist with different variations in terms of implantation time, size and method of implantation.Gastric balloons have been shown to help reduce weight by 6 to 15 percent, but they tend to be most effective early in their implantation, and their effectiveness may decrease over time. Additionally, gastric balloon implantation may cause discomfort and other gastrointestinal side effects.

[0010] Therefore, there is a need to provide compositions which can stimulate or promote weight loss and / or treat overweight and obesity, these compositions being usable in a non-invasive manner, devoid of undesirable side effects and contraindications.

[0011] Today, there are more and more "appetite suppressants" based on natural fibers that swell in the presence of water, such as Konjac, apple pectin, guar gum, Agar-Agar, or carob gum. These compounds are ingested by the patient in the form of a powder and with a relatively large quantity of water (from 0.5 to 1 L) in order to allow their solubilization or dispersion followed by their swelling linked to the hydration of the polymer chains that compose them. The solubilization or dispersion and swelling time of the polymer chains is long and can reach almost 1 hour, which requires the patient to organize before each meal and a loss of effectiveness given the kinetics of gastric emptying. The main problem with these devices lies in the fact that the volume occupied by the device in the patient's stomach remains insufficient to generate a significant feeling of satiety.In exceptional situations, intestinal obstructions may occur, forming a bezoar.

[0012] More recently, the use of super-absorbent hydrogels and hydrogel foams with swelling properties has been developed to facilitate the reduction of gastric volume in the treatment of obesity and overweight. US6,271,278 describes super-porous hydrogel composites obtained from a composition comprising an ethylenically unsaturated monomer and a multi-olefin crosslinking agent in the presence of a disintegrating compound used to improve the mechanical properties of the structure and a foaming agent, in particular sodium bicarbonate. US6,677,318 describes hydrogel-type foams obtained by ionic and covalent crosslinking of polysaccharide polymers and their ingestion in order to provide a feeling of satiety. However, the foam structure of these types of devices is obtained before ingestion by the patient, during the preparation of said device.The use of these devices therefore involves the ingestion by the patient of a relatively large volume of hydrogel foam.

[0013] There is therefore a need to provide compositions allowing a reduction in gastric volume without requiring any steps other than its ingestion and in particular without requiring the prior ingestion of large volumes of water.

[0014] The Applicant has previously developed compositions capable of transforming into a hydrogel foam following their introduction into the stomach. These compositions are described in WO2018 / 234680 and comprise an alginate-based hydrophilic polymer, a compound capable of crosslinking the hydrophilic polymer such as calcium carbonate, a foaming agent chosen from carbonate salts and bicarbonate salts and a foam stabilizing agent. Contacting the composition with the gastric environment causes the composition to swell. Thus, the remaining empty gastric volume, available for food, is reduced and the patient experiences a feeling of satiety quickly after absorption of this composition.

[0015] However, in the course of its investigations and work on the subject, the Applicant noticed that after ingestion and swelling, these hydrogel foams could be easily expelled from the stomach through the pylorus, either under the effect of natural gastrointestinal peristalsis or under the effect of pressure exerted by the ingested food.

[0016] There is therefore a need to provide appetite-reducing and weight-loss promoting compositions which are capable of expanding in the stomach so as to produce in the patient the fastest possible feeling of satiety, and which resist pressure in the stomach and flow through the pylorus, so as to perpetuate the feeling of satiety.

[0017] WO2007 / 113454 describes a composition for preventing esophageal burns in the event of reflux, comprising an alginate, a bicarbonate, a carbonate, an acid and a clumping agent. The composition, administered orally in powder form, forms a raft in the stomach floating above the gastric contents. The composition does not swell in the stomach to occupy a certain volume. The composition is not used to moderate appetite and does not allow a reduction of gastric volume. Furthermore, this composition is intended to protect the stomach from the acidity of gastric reflux and not to prevent passage into the esophagus or the pylorus.

[0018] In continuation of its work, the Applicant has developed new compositions which allow a prolonged and controlled reduction of gastric volume with the aim of reducing appetite and / or facilitating weight loss and, consequently, improving and / or controlling bodily appearance in humans and animals.

[0019] The compositions according to the invention are in the form of a kit comprising two compositions packaged and administered separately. The compositions according to the invention comprise in a first compartment a first composition comprising a hydrophilic polymer, a crosslinking compound, a foaming agent and a foam stabilizing agent, as described in WO2018 / 234680, and in a second compartment, separate from the first compartment, a second composition comprising at least one acid chosen from tartaric acid, succinic acid, ascorbic acid and mixtures thereof.

[0020] It was unexpectedly discovered that the use of an acid selected from tartaric acid, succinic acid, ascorbic acid and their mixtures makes it possible to obtain hydrogel foams with good swelling properties and a foam volume resistant to passage (elimination) through the pylorus, even when this foam is subjected to high pressures. This advantage allows the hydrogel foam to be retained in the stomach throughout the intake of a meal, thus prolonging the feeling of satiety and reducing food consumption during the meal.

[0021] Surprisingly, the Applicant discovered that not all organic acids which have similar characteristics of pKa, molar mass and solubility compatible with digestion were equivalent and that only certain acids could be suitable for this application.

[0022] SUMMARY OF THE INVENTION

[0023] The invention relates to a composition in the form of a kit comprising, in a first compartment, a first composition comprising a hydrophilic polymer chosen from polysaccharides, their derivatives and their mixtures, a crosslinking compound, a foaming agent and a foam stabilizing agent, and in a second compartment, separate from the first compartment, a second composition comprising at least one acid chosen from tartaric acid, succinic acid, ascorbic acid and their mixtures, the mass ratio between the acid and the hydrophilic polymer ranging from 1:2 to 30:1.

[0024] Advantageously, the hydrophilic polymer is chosen from alginates. Advantageously, the crosslinking compound is chosen from divalent cation salts, trivalent cation salts and their mixtures.

[0025] Preferably, the crosslinking compound is chosen from calcium carbonate, manganese carbonate, silver carbonate, iron carbonate, copper carbonate, magnesium carbonate, hydroxyapatite, aluminum carbonate, ferric salts, and mixtures thereof.

[0026] Preferably, the crosslinking compound is calcium carbonate.

[0027] Advantageously, the foaming agent is chosen from salts of monovalent cations, preferably from carbonates and bicarbonates of monovalent cations.

[0028] Preferably, the foaming agent is selected from sodium carbonate, sodium bicarbonate, ammonium bicarbonate, potassium bicarbonate and mixtures thereof.

[0029] Advantageously, in the first composition, the ratio between the quantity of divalent and / or trivalent cations and the quantity of monovalent cations is greater than or equal to 0.01, preferably greater than or equal to 0.05, the quantities of cations being expressed in moles.

[0030] Advantageously, the foam stabilizing agent is chosen from structuring agents, surfactant compounds and their mixtures.

[0031] Preferably, the structuring agent is chosen from proteins, preferably from gelatins, albumin, ovalbumin, milk casein, lecithin and their salts.

[0032] According to one embodiment, the acid is tartaric acid.

[0033] Preferably, the mass ratio between the acid and the hydrophilic polymer ranges from 1:1 to 20:1, more preferably from 1:1 to 10:1.

[0034] Advantageously, the ratio between, on the one hand, the mass of the acid, and on the other hand, the sum of the masses of the crosslinking compound and the foaming agent ranges from 1:10 to 20:1, preferably from 1:10 to 10:1.

[0035] The invention also relates to the use of an acid chosen from tartaric acid, succinic acid and / or ascorbic acid for improving the compressive strength and / or flow resistance of a composition in the form of a hydrogel foam obtained from a hydrophilic polymer chosen from polysaccharides, their derivatives and their mixtures, a crosslinking agent, a foaming agent and a foam stabilizing agent.

[0036] The invention also relates to a non-therapeutic method for controlling and / or modulating and / or reducing and / or moderating and / or regulating appetite in a human or animal subject, the method comprising at least the oral administration to the subject of a composition as described above and in detail below, the first and second compositions being administered successively and not simultaneously, in this order or in the reverse order.

[0037] The invention also relates to a therapeutic method for preventing and / or treating and / or controlling and / or modulating and / or moderating and / or reducing and / or regulating overweight and / or obesity in a human or animal subject, the method comprising the oral administration to a human or animal subject of a composition according to the invention, the first and second compositions being administered successively and not simultaneously, in this order or in the reverse order. Advantageously, the maximum swelling of the composition in the stomach of the patient is reached at most in 30 minutes, preferably at most in 25 minutes, more preferably in 10 minutes.

[0038] Advantageously, the composition remains swollen in the patient's stomach for at least 20 minutes, preferably at least 30 minutes, more preferably at least 40 minutes and more preferably at least 60 minutes and more preferably at least 90 minutes.

[0039] Advantageously, the composition retains 90%, preferably 70%, more preferably 50% of its swollen volume in the patient's stomach for at least 15 minutes, preferably at least 20 minutes, more preferably at least 30 minutes and more preferably for at least 40 minutes.

[0040] DETAILED DESCRIPTION

[0041] The expression "consists essentially of" followed by one or more characteristics means that, in addition to the components or steps explicitly listed, components or steps which do not significantly modify the properties and characteristics of the invention may be included in the process or material of the invention.

[0042] The expression "between X and Y" includes the limits, unless explicitly stated otherwise. This expression therefore means that the interval in question includes the values ​​X, Y and all values ​​from X to Y.

[0043] According to a first aspect, the invention relates to a composition in the form of a kit comprising, in a first compartment, a first composition comprising at least one hydrophilic polymer chosen from polysaccharides, their derivatives and their mixtures, a crosslinking compound, a foaming agent and a foam stabilizing agent, and in a second compartment, separate from the first compartment, a second composition comprising at least one acid chosen from tartaric acid, succinic acid, ascorbic acid and their mixtures, the mass ratio between the acid and the hydrophilic polymer ranging from 1:2 to 30:1.

[0044] According to a second aspect, the invention relates to therapeutic and non-therapeutic methods, as described in detail below, these methods comprising at least one step of oral administration, to a human or animal subject, of a composition in the form of a kit according to the invention, the first and second compositions being administered successively and not simultaneously, in this order or in the reverse order.

[0045] According to a third aspect, the invention relates to the use of an acid chosen from tartaric acid, succinic acid, ascorbic acid and mixtures thereof to improve the resistance to compression and flow of a swollen composition obtained from a composition comprising at least one hydrophilic polymer chosen from polysaccharides, a crosslinking compound, a foaming agent and a foam stabilizing agent, i.e. the first composition of the kit according to the invention.

[0046] The various embodiments, variations, preferences and advantages described above for each of the objects of the invention apply to all of the objects of the invention and may be taken separately or in combination.

[0047] The composition in kit form:

[0048] The first composition

[0049] • The hydrophilic polymer

[0050] The composition contained in the first compartment of the kit according to the invention comprises at least one hydrophilic polymer chosen from polysaccharides, their derivatives and their mixtures.

[0051] For the purposes of the invention, the term "polymer" means oligomers, prepolymers, homopolymers and copolymers. The term "hydrophilic polymer" means a polymer that is capable of absorbing water or that is soluble in water.

[0052] For the purposes of the invention, the term "polysaccharides and their derivatives" means polymers consisting of several monosaccharide units and / or several units derived from monosaccharides and linked together by osidic bonds. The derived units may be monosaccharide units carrying a carboxylic acid and / or amine function and / or an alkyl amide group or an ester function of an alkyl carboxylic acid. Polysaccharides and their derivatives have the advantage of being water-soluble polymers, capable of swelling by absorption of water, suitable for oral ingestion by humans and animals. Polysaccharides are also low or non-calorie, that is to say they provide few calories to the body during their digestion. This is particularly advantageous in the context of the use of the composition according to the invention for reducing weight gain and obesity, particularly in patients suffering from diabetes.

[0053] As polysaccharides and polysaccharide derivatives, mention may be made of alkyl celluloses such as C1-C6 alkyl celluloses and in particular methyl cellulose, ethyl cellulose and ethylmethyl cellulose; substituted alkyl celluloses such as C1-C6 alkyl cellulose hydroxides and C1-C6 C1-C6 alkyl cellulose hydroxides and in particular n-propylcellulose hydroxide, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose and carboxymethylcellulose; substituted dextrans such as dextran sulfate, dextran phosphate and diethylamine dextran; glycosaminoglycans and in particular hyaluronic acid, chondroitin and chondroitin sulfate; and polymers and copolymers comprising uronic acid units.

[0054] Advantageously, the hydrophilic polymer is chosen from K (kappa) carrageenan, i (iota) carrageenan, polysaccharides comprising uronic units and mixtures thereof, preferably from polysaccharides comprising uronic units.

[0055] For the purposes of the invention, the term "uronic units" means polymeric units derived from simple oses obtained by oxidation of the carbon located at the end of the chain into a carboxylic acid function. Said uronic units are, for example, obtained from mannuronic acid, guluronic acid, glucuronic acid, iduronic acid or galacturonic acid. Polymers and copolymers comprising uronic units are obtained by forming osidic bonds with other monomers.

[0056] Advantageously, at least 50% by mass, preferably at least 80% by mass of the monosaccharide units of the hydrophilic polymer are uronic units. Preferably, the hydrophilic polymer consists essentially of uronic units.

[0057] Advantageously, the hydrophilic polymer has a weight-average molar mass ranging from 400,000 g / mol to 3,000,000 g / mol, preferably from 500,000 g / mol to 2,000,000 g / mol, and even more preferably from 500,000 g / mol to 1,000,000 g / mol.

[0058] According to one embodiment, the hydrophilic polymer is chosen from polysaccharides consisting essentially of aD-galacturonic units, preferably from pectins.

[0059] According to a preferred embodiment, the hydrophilic polymer is chosen from polymers comprising mannuronic units and guluronic units. Advantageously, according to this embodiment, the hydrophilic polymer is chosen from alginates.

[0060] For the purposes of the invention, the term "alginates" means statistical or block polymers of formula (I) essentially consisting of mannuronic units (derived from mannuronic acid) and guluronic units (derived from guluronic acid).

[0061] Advantageously, at least 15% by mass, preferably at least 25% by mass and more preferably at least 50% by mass of the alginate consists of chain segments on which two guluronic units follow one another directly.

[0062] According to one embodiment, the hydrophilic polymer is partially crosslinked before its introduction into the composition.

[0063] The hydrophilic polymer may be partially crosslinked by the formation of ionic bonds (partial physical crosslinking), covalent bonds (partial chemical crosslinking) or ionic and covalent bonds (partial mixed crosslinking). Preferably, the hydrophilic polymer is crosslinked by the formation of ionic bonds (partial physical crosslinking) before its introduction into the composition.

[0064] According to this same embodiment, the hydrophilic polymer has a crosslinking index of less than or equal to 50%, preferably less than or equal to 30%, even more preferably less than or equal to 10%, before its introduction into the composition.

[0065] For the purposes of the invention, the term "crosslinking index" means the ratio between the number of occupied crosslinking sites in a polymer chain and the number of possible crosslinking sites on the same polymer. The crosslinking index is calculated taking into account the nature and quantity of the monomers and crosslinking agents used.

[0066] According to another embodiment, the hydrophilic polymer is not crosslinked before its introduction into the composition.

[0067] Advantageously, the composition contained in the first compartment of the kit according to the invention comprises from 0.05% to 60% by mass, preferably from 0.5% to 40% by mass, more preferably from 1% to 20% by mass of hydrophilic polymer, the percentages being expressed in mass of dry matter relative to the total mass of the composition contained in the first compartment of the kit.

[0068] • The crosslinking compound

[0069] The first composition contained in the first compartment of the kit according to the invention comprises at least one crosslinking compound.

[0070] Advantageously, the crosslinking compound is capable of crosslinking the hydrophilic polymer as described above by the formation of ionic bonds.

[0071] Advantageously, the crosslinking compound capable of crosslinking the hydrophilic polymer by the formation of ionic bonds is introduced into the composition in a non-active form. By "non-active form" is meant, within the meaning of the invention, that in aqueous solution and at neutral pH, the crosslinking of the hydrophilic polymer by this compound does not occur. By passing into an acidic medium, the crosslinking compound dissociates and releases the chemical species capable of crosslinking the hydrophilic polymer by the formation of ionic bonds. Advantageously, the crosslinking compound is chosen from divalent cation salts, trivalent cation salts and mixtures thereof.

[0072] Among the divalent cations suitable for the invention, mention may be made of calcium (II), manganese (II), silver (II), iron (II), copper (II), magnesium (II), and mixtures thereof.

[0073] Among the trivalent cations suitable for the invention, mention may be made of aluminum, iron (III) and their mixtures.

[0074] Depending on the nature of the cation used, the composition obtained by crosslinking the hydrophilic polymer may have different physical properties. For example, a hydrogel obtained by crosslinking the hydrophilic polymer with magnesium ions will be relatively more mechanically fragile and will have a more limited lifespan, while a hydrogel obtained by crosslinking the hydrophilic polymer with calcium ions will be mechanically stable and over long periods. The choice of cation therefore makes it possible to modulate the lifespan of the crosslinked gel in the stomach of the subject to whom the composition according to the invention is administered.

[0075] According to a preferred embodiment, the crosslinking compound is chosen from divalent cation salts.

[0076] Preferably, according to this embodiment, the divalent cation is calcium.

[0077] Advantageously, the divalent cation salts and / or the trivalent cation salts are chosen from salts insoluble in water at room temperature and at neutral pH, in particular at a pH between 6.5 and 7.5. Preferably, the divalent cation salts and / or the trivalent cation salts have a solubility in water at neutral pH, in particular at a pH ranging from 6.5 to 7.5, determined at 20°C, of ​​less than or equal to 0.5 g / L, preferably less than or equal to 0.1 g / L.

[0078] Advantageously, the crosslinking compound is chosen from salts capable of decomposing in an aqueous medium on the one hand into divalent and / or trivalent cations and on the other hand into an acid-base species, in the sense of Brônsted.

[0079] According to a preferred embodiment, the acid-base species released by the decomposition of the metal salt in an aqueous medium is chosen from the hydrogen carbonate or bicarbonate ion HCO3; the carbonate ion COs 2' and their mixtures. By reducing the pH, particularly at a pH less than or equal to 6, these ions are transformed into carbonic acid H2CO3 which decomposes into carbon dioxide CO2.

[0080] According to one embodiment, when the crosslinking compound is chosen from divalent cations, it is advantageously chosen from calcium carbonate (CaCOs), manganese carbonate (MnCOs), silver carbonate (AgCOs), iron carbonate (FeCOs), copper carbonate (CuCOs), magnesium carbonate (MgCOs), hydroxyapatite (Caio(P04)eOH2) and mixtures thereof.

[0081] According to one embodiment, when the crosslinking compound is chosen from trivalent cations, it is advantageously chosen from aluminum salts Al 3+ such as for example aluminum carbonate (A^COsh)! ferric salts Fe 3+ ' and their mixtures.

[0082] Carbonate salts are advantageous in that they contribute to gas release and thus to foam formation. They are also advantageous in that they do not leave any residue in the stomach: the majority of the released cations and gas contribute to foam formation.

[0083] According to an alternative embodiment, the crosslinking compound is a salt of a divalent and / or trivalent cation and of a counterion chosen from a nutrient substance such as for example a vitamin.

[0084] According to a preferred embodiment of the invention, the crosslinking compound is calcium carbonate.

[0085] The crosslinking compound is advantageously introduced into the composition in an amount such that the crosslinked polymer, after passing through an acid medium, in particular at a pH less than or equal to 5, has a crosslinking rate less than or equal to 100%, preferably less than or equal to 95%, and even more preferably less than or equal to 90%.

[0086] The crosslinking compound is advantageously introduced into the composition in an amount such that the crosslinked polymer, after passing into an acid medium, in particular at a pH less than or equal to 5, has a crosslinking rate greater than or equal to 5%, preferably greater than or equal to 10%, even more preferably greater than or equal to 15%, and advantageously greater than or equal to 20%. Too low a crosslinking rate is not suitable for the present invention in that it would not allow the formation of a sufficiently mechanically stable foam. Indeed, if the hydrophilic polymer is not sufficiently crosslinked, the gas produced by the decomposition of the foaming agent cannot be sufficiently retained by the swollen structure, the gas escapes and the foamy structure does not form or is too ephemeral in nature to act on the feeling of satiety.

[0087] Crosslinking the hydrophilic polymer by the formation of ionic bonds is advantageous in that the crosslinked structure of the composition is reversible, in particular, under the action of monovalent cations in large excess. For example, the crosslinked structure can be disintegrated by the ingestion of monovalent metal salts such as sodium chloride NaCl. Consequently, the composition according to the invention is easily digestible and eliminated by the body via conventional digestion mechanisms.

[0088] • The foaming agent

[0089] The first composition of the kit according to the invention comprises at least one foaming agent.

[0090] The foaming agent is defined in the invention as a compound capable of producing a gas or of decomposing / dissociating into gas under the action of an environmental factor (temperature, pH, etc.) or a chemical compound.

[0091] The foaming agent is distinct from the crosslinking compound capable of crosslinking the hydrophilic polymer by the formation of ionic bonds.

[0092] The foaming agent is advantageously introduced into the first composition according to the invention in a non-active form. By "non-active form" is meant, within the meaning of the invention, that in aqueous solution at neutral pH and in particular at a pH ranging from 6.5 to 7.5 and at room temperature, the foaming agent does not decompose.

[0093] Advantageously, the decomposition into gas of the foaming agent is initiated by contact with an acidic medium, preferably at a pH less than or equal to 5. Placed in an acidic medium, the foaming agent decomposes into gas, preferably into carbon dioxide CO2. According to one embodiment, the foaming agent is chosen from monovalent cation salts.

[0094] Preferably, according to this embodiment, the foaming agent is chosen from alkali metal salts.

[0095] Advantageously, the foaming agent is chosen from salts capable of decomposing in an aqueous medium and at neutral pH, in particular at a pH ranging from 6.5 to 7.5, on the one hand into monovalent cations and on the other hand into an acid-base species, in the sense of Brônsted.

[0096] Upon passage through an acid medium, the acid-base species released by the decomposition of the salt in an aqueous medium reacts to form the conjugated Brônsted acid.

[0097] The conjugated Brônsted acid is preferably chosen from compounds capable of decomposing into gas, more preferably into carbon dioxide CO2.

[0098] According to a preferred embodiment, the acid-base species released by the decomposition of the salt in an aqueous medium is chosen from the hydrogen carbonate or bicarbonate ion HCO3; the carbonate ion COs 2' and their mixtures. The conjugated Brônsted acid is then carbonic acid H2CO3 which decomposes into carbon dioxide CO2.

[0099] According to a preferred embodiment, the foaming agent is chosen from carbonates and bicarbonates of monovalent cations, alone or in mixtures, preferably from carbonates and bicarbonates of alkali metal cations.

[0100] Preferably, the foaming agent is selected from sodium carbonate (Na2CO3), sodium bicarbonate (NaHCOs), ammonium bicarbonate (NH4CO3), potassium bicarbonate (KHCO3) and mixtures thereof, more preferably from salts of monovalent metal cations, more advantageously from sodium carbonate, sodium bicarbonate, potassium bicarbonate and mixtures thereof.

[0101] Placed in an aqueous medium and at neutral pH, in particular at a pH ranging from 6.5 to 7.5, the salts mentioned above decompose into monovalent cations (Na+ , NH4 + OR K + ) and bicarbonate ions HCOs'. In contact with an acidic medium, particularly at a pH less than or equal to 5, bicarbonate ions HCOs' react to form carbonic acid H2CO3 which then decomposes into carbon dioxide CO2.

[0102] According to a preferred embodiment, the foaming agent is sodium bicarbonate and / or potassium bicarbonate.

[0103] According to a preferred embodiment, the foaming agent is a mixture of sodium bicarbonate and potassium bicarbonate.

[0104] Preferably, according to this embodiment, the mass ratio between potassium bicarbonate and sodium bicarbonate ranges from 1 to 100, preferably from 5 to 50, more preferably from 10 to 40.

[0105] The quantity of foaming agent introduced into the composition according to the invention is determined relative to the quantity of crosslinking compound introduced into the same composition. The quantity of foaming agent is in particular determined by taking into account the possible contribution of the crosslinking compound to the release of gas and therefore to the formation of foam.

[0106] Advantageously, the foaming agent is introduced into the composition according to the invention in an amount such that the ratio between the amount of divalent and / or trivalent cations, preferably divalent, and the amount of monovalent cations in the composition is greater than or equal to 0.01, preferably greater than or equal to 0.05, more preferably greater than or equal to 0.1, the amounts of cations being expressed in moles.

[0107] Advantageously, the foaming agent is introduced into the composition according to the invention in an amount such that the ratio between the amount of divalent and / or trivalent cations, preferably divalent, and the amount of monovalent cations in the composition is less than or equal to 10, preferably less than or equal to 5, preferably less than or equal to 2, the amounts of cations being expressed in moles.

[0108] Advantageously, the crosslinking compound and the foaming agent are introduced into the composition according to the invention in a mass ratio ranging from 1:1 to 1:10, preferably ranging from 1:1 to 1:5.

[0109] Thus, the monovalent cation released by the foaming agent is present in such proportions that it does not compete with the divalent and / or trivalent cations responsible for the crosslinking of the hydrophilic polymer to the point of significantly degrading the crosslinking of the hydrophilic polymer. The release of gas into the polymer matrix makes it possible to obtain a large number of connected cells to form an open-cell foam.

[0110] The amount of gas trapped in the matrix depends on the viscosity of the medium before crosslinking, the amount of crosslinking agent and therefore the rate of crosslinking, the amount and type of foaming agent introduced into the matrix, the amount and nature of the foam stabilizing agent.

[0111] In the context of this invention, the release of gas and the crosslinking of the hydrophilic polymer are carried out simultaneously so as to trap the gas formed inside the polymer matrix and allow the formation of a foam.

[0112] According to a particularly preferred embodiment, the crosslinking compound is calcium carbonate and the foaming agent is sodium bicarbonate.

[0113] According to another particularly preferred embodiment, the crosslinking compound is calcium carbonate and the foaming agent is potassium bicarbonate.

[0114] According to another particularly preferred embodiment, the crosslinking compound is calcium carbonate and the foaming agent is a mixture of sodium bicarbonate and potassium bicarbonate.

[0115] • The foam stabilizing agent

[0116] The composition contained in the first compartment of the kit according to the invention comprises at least one foam stabilizing agent.

[0117] For the purposes of the invention, the term "foam stabilizing agent" means a compound capable of reducing the surface tension at the interface of two different media and in particular at the interface separating a liquid medium from a gaseous medium.

[0118] Preferably, the foam stabilizing agent is chosen from structuring agents, surfactant compounds and mixtures thereof.

[0119] Structuring agents

[0120] For the purposes of the invention, the term "structuring agent" means a chemical compound capable of stabilizing the structure of a foam. Structuring agents are classified into two categories based on their chemical nature: peptides and proteins, and saccharides.

[0121] According to one embodiment, the structuring agent is chosen from peptides and proteins.

[0122] For the purposes of the invention, the term "peptide or protein" means a chain of several amino acids linked together by peptide bonds. More particularly, we speak of a "peptide" when the number of amino acids present in the chain is less than 50. We speak of a protein when the number of amino acids present in the chain is greater than or equal to 50.

[0123] Preferably, the structuring agent is chosen from proteins.

[0124] More preferably, the protein is chosen from gelatins, albumin, ovalbumin, milk casein, lecithin, their salts such as for example sodium caseinate, and their mixtures.

[0125] According to a preferred embodiment of the invention, the foam stabilizing agent is gelatin.

[0126] According to one embodiment, the structuring agent is chosen from saccharides. For the purposes of the invention, the term “saccharides” means organic compounds comprising one or more simple oses.

[0127] Preferably, the foam stabilizing saccharides are chosen from xanthan gum, glucomannan gum, gum arabic, locust bean gum and mixtures thereof.

[0128] Surfactant compounds

[0129] For the purposes of the invention, the term "surfactant compound" means an amphiphilic compound comprising a hydrophobic part, in particular a long carbon chain, and a hydrophilic part. Surfactants are classified into 4 categories depending on the nature of the hydrophilic group: anionic surfactants, cationic surfactants, zwitterionic or amphoteric surfactants, and non-ionic surfactants.

[0130] Preferably, the surfactant compound is chosen from amphoteric surfactants and non-ionic surfactants.

[0131] For the purposes of the invention, the term "zwitterionic or amphoteric surfactant" means a surfactant compound whose hydrophilic part consists of an acid-base group. In an acidic medium, the hydrophilic group is positively charged. In a basic medium, the hydrophilic group is negatively charged.

[0132] Among the zwitterionic or amphoteric surfactant compounds suitable for the invention, mention may be made of betaines, imidazoline derivatives, phospholipids and mixtures thereof. For the purposes of the invention, the term "phospholipid" means a lipid containing at least one phosphoric acid function. Phospholipids include in particular phosphatic acids and phosphoglycerides.

[0133] For the purposes of the invention, the term "non-ionic surfactant" means a surfactant compound in which the hydrophilic part is not charged.

[0134] Among the non-ionic surfactant compounds, we can cite for example: polymers and copolymers of ethylene glycol and propylene glycol, esters of fatty acid and of ethylene (poly)oxide, ethers of fatty alcohols and of ethylene (poly)oxide, ethers of (poly)oxyethylenated polyols, esters of fatty acid and polyols in particular esters of fatty acid and sugars, optionally (poly)oxyethylenated, fatty acid glycerides, oxyethylenated glycerol ethers, ethers of glycerol and fatty alcohols, fatty acids.

[0135] For the purposes of the invention, the term “fatty acid” means a carboxylic acid type compound comprising a linear hydrocarbon chain ranging from 10 to 30 carbon atoms.

[0136] For the purposes of the invention, the term "ethoxylated" means a chemical compound which has undergone an ethoxylation step by reaction with ethylene oxide.

[0137] According to one embodiment, the non-ionic surfactant is chosen from polyethylene oxide hydrocarbons, preferably from polyoxyethylene glycol ethers and esters, fatty acid and polyol esters, ethoxylated fatty acid and polyol esters and mixtures thereof.

[0138] For example, the non-ionic surfactant may be selected from ethoxylated sorbitans, ethoxylated isosorbides, ethoxylated sorbitan fatty acid esters, ethoxylated isosorbide fatty acid esters, sorbitan fatty acid esters, isosorbide fatty acid esters, and mixtures thereof. Among the sorbitan fatty acid esters, mention may be made in particular of the commercial SPAN® products, for example SPAN®20, SPAN®40 or SPAN®80 marketed by Croda Inc.

[0139] Among the ethoxylated sorbitan fatty acid esters, we can notably cite the commercial Tween® products, for example Tween®20, Tween®60 or Tween®80 marketed by Croda Inc.

[0140] According to one embodiment, the non-ionic surfactant compound is chosen from fatty acids, preferably linoleic acid.

[0141] According to one embodiment, the foam stabilizing agent is a mixture of different stabilizing agents and / or different surfactant compounds.

[0142] Advantageously, the composition contained in the first compartment of the kit according to the invention comprises from 0.01% to 5% by mass, preferably from 0.05% to 2% by mass, more preferably from 0.1% to 1% by mass of foam stabilizing agent, the percentages being expressed in mass of dry matter relative to the total mass of the composition contained in the first compartment of the kit.

[0143] • Other additives

[0144] The first composition contained in the first compartment of the kit according to the invention may comprise a second hydro-swelling polymer. This second hydro-swelling polymer differs from the hydrophilic polymer described above in that it is not crosslinkable by the formation of ionic bonds.

[0145] The presence of a second hydro-swelling polymer in the compositions according to the invention is advantageous in that it makes it possible to obtain foams of greater volume, thus increasing the swelling rate of the composition.

[0146] Advantageously, the hydro-swelling polymer which cannot be crosslinked by the formation of ionic bonds is chosen from starch, agar-agar, carrageenan X (lambda), non-crosslinkable celluloses and their mixtures.

[0147] Advantageously, the composition according to the invention has a content of (second) hydro-swelling polymer ranging from 0% to 50%, preferably from 1% to 30%, more preferably from 5% to 20%, the percentages being expressed in mass of dry matter relative to the total mass of the composition contained in the first compartment of the kit.

[0148] The composition according to the invention may further comprise, and in a non-exhaustive manner, at least one additive chosen from colorants, flavors, sweeteners, preservatives, flavor enhancers, vitamins, anti-caking agents, antioxidants, and dietary fibers.

[0149] Examples of preservatives include potassium sorbate, methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, and sodium benzoate.

[0150] Examples of sweeteners include succralose, aspartame, acesulfame K and their mixtures.

[0151] Flavorings include natural flavors, such as limonene or citral, obtained by extraction from citrus peel such as orange and lemon, and artificial or synthetic flavors, such as vanillin or 3-methoxy-4-hydroxybenzaldehyde, ethylvanillin or 3-ethyl-4-hydroxybenzaldehyde.

[0152] Flavor enhancers include sodium glutamate, guanylates, inosinates, ribonucleotides, glycine, zinc acetate, trisodium pyrophosphate, phyllosilicates, and glucomannans.

[0153] For a composition intended to be ingested by humans, the flavor enhancer may be chosen from sodium glutamate, guanylates, inosinates, ribonucleotides, glycine and zinc acetate. For a composition intended to be ingested by an animal, and in particular by a mammal, the flavor enhancer may be chosen from trisodium pyrophosphate, phyllosilicates or glucomannans. Mention may also be made of recycled vegetable or animal oils, waste from the food industry and restaurants, hydrolyzates of poultry livers or even products of fish fermentation.

[0154] According to one embodiment, the first composition according to the invention further comprises a palatability product in the form of a mixture of at least one flavoring and at least one flavor enhancer.

[0155] Advantageously, the composition according to the invention comprises from 0.01% to 40%, preferably from 0.05% to 20%, more preferably from 0.1% to 10% of at least one additive chosen from colorants, flavors, sweeteners, preservatives, flavor enhancers, vitamins, anti-caking agents, antioxidants, and dietary fibers and mixtures thereof, the percentages being expressed in mass of dry matter relative to the total mass of the composition contained in the first compartment of the kit.

[0156] According to one embodiment, the first composition consists essentially of, preferably consists of, a hydrophilic polymer chosen from polysaccharides, their derivatives and their mixtures, a crosslinking compound, a foaming agent and a foam stabilizing agent.

[0157] According to one embodiment, the first composition consists essentially of, preferably consists of, a hydrophilic polymer chosen from polysaccharides, their derivatives and their mixtures, a crosslinking compound, a foaming agent and a foam stabilizing agent, and an additive chosen from colorants, flavors, sweeteners, preservatives, flavor enhancers, vitamins, anti-caking agents, antioxidants, dietary fibers and their mixtures.

[0158] Process for preparing the first composition

[0159] The composition contained in the first compartment of the kit according to the invention can be prepared according to the method described in WO2018 / 234680.

[0160] In particular, the composition may be prepared by introducing into an aqueous medium, preferably into water, the hydrophilic polymer, the crosslinking compound, the foaming agent, the foam stabilizing agent and optionally the other additives.

[0161] The aqueous medium preferably has a neutral pH, in particular a pH between 6.5 and 7.5.

[0162] The order of introduction of the compounds defined above into the aqueous medium is arbitrary and generally has no impact on the properties of the final composition. The compounds defined above can thus be introduced into the aqueous medium simultaneously or by successive additions in any order.

[0163] For example, the method for preparing the first composition comprises the following steps:

[0164] - solubilization or dispersion of the hydrophilic polymer in water, - addition of the foaming agent and the crosslinking compound capable of crosslinking the hydrophilic polymer by the formation of ionic bonds until a homogeneous dispersion is obtained,

[0165] - the addition of the foam stabilizing agent,

[0166] - possibly the addition of other additives.

[0167] According to another variant, the process for preparing the first composition comprises:

[0168] - solubilization or dispersion of the foam stabilizing agent in water,

[0169] - the introduction of the hydrophilic polymer, the foaming agent, and the crosslinking compound capable of crosslinking the hydrophilic polymer by the formation of ionic bonds.

[0170] This variant is particularly suitable when the foam stabilizing agent is in the form of a solid, for example gelatin, and therefore requires a prior dissolution and / or dispersion step.

[0171] According to a first embodiment, the composition is obtained directly at the end of the process described above. In this case, the composition is obtained in the form of an aqueous dispersion.

[0172] According to a second embodiment, the method may further comprise an additional drying step so as to eliminate all or part of the water present in the composition.

[0173] For example, the step of drying the composition can be carried out by injecting hot pulsed air, by treatment with supercritical carbon dioxide CO2, by freeze-drying or by atomization, preferably by treatment with supercritical carbon dioxide CO2. When the drying of the composition is carried out by treatment with supercritical carbon dioxide CO2, this requires a preliminary step of solvent exchange during which the water in the composition is replaced by a more volatile solvent of the alcohol type.

[0174] The method according to the invention therefore makes it possible to obtain compositions with a controlled water content, depending on the duration and intensity of the drying applied. By completely drying the composition, the method allows the preparation of a water-free composition which can be in the form of a xerogel, a cryogel or an aerogel depending on the drying method used. More particularly, when the composition is completely dried by the injection of pulsed hot air, the composition is obtained in the form of a xerogel. When the composition is completely dried by treatment with supercritical carbon dioxide CO2, the composition is obtained in the form of an aerogel. When the composition is completely dried by lyophilization, the composition is obtained in the form of a cryogel.

[0175] By partial drying, the process according to the invention allows the production of compositions having varied consistencies: in solid or liquid, viscous or fluid forms, and in particular in the form of syrups.

[0176] The first composition of the kit according to the invention can also be presented in a soft form of the gelled confectionery type, better known in the trade as "gummies", or of the jellies type better known in the trade as "toppers", in particular for animals.

[0177] In particular, by total or partial drying, the process according to the invention allows the preparation of compositions in the form of powders.

[0178] Advantageously, the powders obtained by drying the first composition have a particle size less than or equal to 2 mm, preferably less than or equal to 1 mm, even more preferably less than or equal to 0.8 mm.

[0179] The particle size of the powders can be measured using a LASER Mastersizer 3000 particle size analyzer marketed by Malvern according to the protocol described in WO2018 / 234680.

[0180] The first composition of the kit according to the invention may be in the form of a capsule with a core / shell structure comprising a core consisting of the first composition and at least one coating layer covering all or part of the surface of the core. The core of the capsule may be in the form of a powder or in the form of a viscous liquid or a gel. The second composition

[0181] The second compartment of the kit according to the invention comprises a composition comprising at least one acid chosen from tartaric acid, succinic acid, ascorbic acid and mixtures thereof.

[0182] According to a preferred embodiment of the invention, the acid is tartaric acid.

[0183] According to one embodiment, the acid is ascorbic acid.

[0184] According to one embodiment, the acid is succinic acid.

[0185] According to one embodiment, the second composition consists essentially of an acid chosen from tartaric acid, succinic acid, ascorbic acid and mixtures thereof.

[0186] The mass ratio of acid to hydrophilic polymer ranges from 1:2 to 30:1.

[0187] Advantageously, the mass ratio between the acid and the hydrophilic polymer ranges from 1:1 to 20:1, preferably from 1:1 to 10:1.

[0188] Advantageously, the ratio between, on the one hand, the mass of the acid, and on the other hand, the sum of the masses of the crosslinking compound and the foaming agent ranges from 1:10 to 20:1, preferably from 1:10 to 10:1, more preferably from 1:10 to 5:1.

[0189] The second composition may also comprise an acid mixture comprising at least one acid selected from tartaric acid, succinic acid, ascorbic acid and mixtures thereof and at least one other acid selected from lactic acid, fumaric acid, citric acid, malic acid and mixtures thereof.

[0190] The second composition may include other additives as described above for the first composition of the kit, which may be the same as or different from those present in this first composition.

[0191] According to one embodiment, the second composition is in solid form, in particular in the form of powder, coated or uncoated tablets, coated or uncoated granules or even in capsule form. According to another embodiment, the second composition is in liquid form. According to this embodiment, the second composition, in particular the acid, is advantageously in the form of an aqueous solution. Preferably, the second composition is in capsule form.

[0192] Advantageously, according to this embodiment, the aqueous solution has a pH of between 1 and 5, preferably between 1.5 and 4, more preferably between 1.5 and 2.5.

[0193] Advantageously, the number of H+ ions in the second composition is between 10 and 60 meq, preferably between 20 and 50 meq.

[0194] The kit according to the invention may also comprise, in a third compartment, at least one food portion. In particular, the kit according to the invention may comprise a food portion adapted to the subject's diet.

[0195] The kit according to the invention may also comprise, in another compartment, at least one oral administration device such as, for example, a feeding syringe, a graduated container, a measuring spoon or even a scale.

[0196] Methods according to the invention:

[0197] The composition in kit form described above is intended to be ingested by a human or animal subject, and in particular by mammals, in order to produce an “appetite suppressant” effect, linked to a feeling of satiety. This feeling of satiety is obtained by the swelling of the first composition when it is brought into contact with the acidic gastric environment in the stomach of the subject, and also under the effect of the second composition, thus causing a reduction in the gastric volume available for the ingestion of food. The second composition allowing an extension of the stay of the hydrogel foam in the stomach, it contributes to a longer duration of this appetite suppressant effect.

[0198] The invention also relates to therapeutic methods and non-therapeutic methods comprising the oral administration to a human or animal subject of a composition in kit form according to the invention, the first and second compositions being administered successively and not simultaneously, in this order or in the reverse order.

[0199] According to a first aspect, the invention relates to a non-therapeutic method for controlling and / or modulating and / or moderating and / or reducing and / or regulating appetite in a human or animal subject, the method comprising administering to the subject, orally, a composition in kit form according to the invention, the first and second compositions being administered successively and not simultaneously, in this order or in the reverse order.

[0200] According to one embodiment, the method described below is intended to control and / or modulate and / or moderate and / or reduce and / or regulate the sensation of hunger and / or delay the onset of the sensation of hunger.

[0201] Indeed, the method according to the invention provides the subject with a feeling of satiety achieved more quickly and / or which lasts longer than if he had not ingested the composition and / or if he had reduced the volume of food ingested at each meal.

[0202] According to one embodiment, the method described above is intended to stimulate and / or promote and / or induce weight loss in a human or animal subject. According to another embodiment, the method described above is intended to control and / or modulate and / or moderate and / or reduce and / or regulate weight gain in a human or animal subject.

[0203] Advantageously, the method allows you to maintain a stable and / or balanced body weight and to avoid regaining weight after weight loss.

[0204] According to one embodiment, the method described above is intended to aesthetically improve the bodily appearance of the human or animal subject. By "aesthetically improving the bodily appearance of the human or animal subject" is meant, within the meaning of the invention, decreasing and / or reducing the body mass index. Advantageously, the objective of this method is to achieve a body mass index (BMI) value between 18 and 25 kg / m2 in a human subject and to achieve a body condition score (BCS) between 4 / 9 and 5 / 9 in an animal subject.

[0205] In particular, the method according to the invention comprises the oral administration to a human or animal subject of an effective dose:

[0206] (1) a first composition comprising a hydrophilic polymer chosen from polysaccharides, their derivatives and their mixtures, a crosslinking agent, a foaming agent and a foam stabilizing agent, and

[0207] (2) a second composition comprising at least one acid chosen from tartaric acid, succinic acid, ascorbic acid and mixtures thereof, the mask ratio between the acid and the hydrophilic polymer being between 1:2 and 30:1, the first and second compositions being administered successively and not simultaneously, in this order or in the reverse order.

[0208] According to one embodiment, the first composition is ingested by the subject before the second composition. According to this embodiment, the first composition can swell upon contact with gastric acid. Maximum swelling is achieved following ingestion of the second composition comprising the acid.

[0209] According to another embodiment, the second composition is ingested by the subject before the first composition.

[0210] Preferably, the first composition and / or the second composition is ingested simultaneously with an amount of water, preferably less than 200 mL, more preferably less than 150 mL, and more preferably less than 100 mL.

[0211] Advantageously, the sequential administration of the two compositions according to the invention is carried out while respecting a well-defined time interval, in particular of at most 15 minutes, preferably of at most 10 minutes, more preferably of at most 5 minutes.

[0212] According to a preferred embodiment, one of the compositions is administered immediately after administration of the other composition.

[0213] Advantageously, the method according to the invention is implemented before the ingestion of a meal by the subject. Preferably, the method according to the invention is implemented at most 30 minutes before the ingestion of a meal by the subject, preferably at most 25 minutes, more preferably at most 15 minutes, advantageously at most 10 minutes before the ingestion of a meal by the subject.

[0214] Advantageously, the composition in kit form according to the invention is administered to the subject according to a predetermined dosage and frequency. Advantageously, the doses and frequencies of administration are adapted to the specific needs and characteristics of the subject, taking into account factors such as age, weight, height, general state of health and metabolic rate.

[0215] According to one embodiment, the subject has the composition in the form of a kit according to the invention in the form of a pre-dosed composition corresponding exactly to his needs. According to another embodiment, the patient has a volume of composition according to the invention and takes the dose of the first and second compositions corresponding to his needs, by means of a suitable sampling device (spoon or other dosing instrument).

[0216] Advantageously, the method according to the invention is implemented at least once a day, preferably at least twice a day. Advantageously, the method according to the invention is implemented at most 3 times a day.

[0217] Advantageously, the method according to the invention is implemented in such a way that the maximum quantity of acid of the second composition, in particular tartaric acid, ingested by the subject, is less than or equal to 20 g per day, preferably less than or equal to 16 g per day, more preferably less than or equal to 10 g per day.

[0218] Advantageously, the method according to the invention is implemented in such a way that the maximum quantity of succinic acid and / or ascorbic acid ingested by the subject is less than or equal to 9 g per day, preferably less than or equal to 5 g per day, more preferably less than or equal to 2 g per day.

[0219] Advantageously, the subject's weight is regularly assessed over time. If necessary, adjustments to the dosages and frequencies of the composition according to the invention can be made to maximize the effectiveness of weight control and / or loss and / or moderation.

[0220] According to one embodiment, the method described above comprises a step of ingestion of a meal or a food portion by the subject, after administration of the composition in the form of a kit according to the invention.

[0221] According to one embodiment of the invention, the method described above comprises at least one other step prior to the administration of the composition in kit form according to the invention.

[0222] In particular, the method according to the invention may comprise a preliminary step of measuring the initial weight of the subject for reference and monitoring purposes throughout the treatment.

[0223] This step can be followed by a step of assessing the subject's overweight. The assessment of overweight in a human subject is generally done by calculating the body mass index (BMI), which is an indicator based on the relationship between weight and height. The BMI is calculated by dividing the subject's weight in kilograms by the square of their height in meters. A subject is overweight if the BMI is between 25 and 30 kg / m2. The subject is obese if the BMI is greater than 30 kg / m2. The assessment of overweight in an animal subject is generally done by calculating a body condition score (BCS), which is an indicator based on the relationship between weight and morphological criteria according to the animal's breed, particularly pets. The BCS ranges from 1 to 9, with 1 corresponding to the leanest state and 9 to the most obese. Generally, a NEC above 5 / 9 is considered to be an overweight animal. Scores of 7, 8 and 9 / 9 are given to obese animals.

[0224] The method according to the invention may also comprise a step of assessing the subject's needs, taking into account factors such as his age, general health, medical history, nutritional needs, level of physical activity and any other relevant parameter. This assessment makes it possible to determine the most appropriate weight loss program for the subject and to personalize the dosage and frequencies of administration of the composition according to the invention.

[0225] After administering the compositions to the subject, in accordance with the predetermined dosage and frequency, the method according to the invention may comprise a step of measuring the final weight of the subject to evaluate the overall effectiveness of the weight loss program.

[0226] For example, according to one embodiment, the non-therapeutic method described above comprises at least the following steps:

[0227] - measurement of the subject's initial weight,

[0228] - assessment of overweight, in particular by calculating the body mass index,

[0229] - determination of weight loss goals,

[0230] - determination of the dosage and / or frequency of administration of the composition according to the invention,

[0231] - optionally, evaluation of the quantity of meals to be ingested after each administration of the composition according to the invention, - ingestion by the subject of the first composition and the second composition in a sequential manner, in this order or in the reverse order,

[0232] - ingestion by the subject of a meal or a portion of food after each administration of the composition according to the invention,

[0233] - possibly, determination of the subject's intermediate weight during the program at certain time intervals,

[0234] - if necessary, adaptation of the weight loss program,

[0235] - measurement of the subject's final weight.

[0236] According to another aspect, the invention relates to a composition in kit form as defined above for its use as a medicament.

[0237] According to another aspect, the invention relates to a composition in kit form as defined above for its use in the prevention and / or treatment of overweight, obesity, diabetes, high blood pressure, cardiovascular diseases, fatty liver, sleep apnea and / or joint problems.

[0238] According to another aspect, the invention relates to a therapeutic method for preventing and / or treating and / or controlling and / or modulating and / or moderating and / or reducing and / or regulating overweight and / or obesity in a human or animal subject, the method comprising the oral administration to a human or animal subject of a composition in kit form according to the invention, the first and second compositions being administered successively and not simultaneously, in this order or in the reverse order.

[0239] According to one embodiment, the therapeutic method described above makes it possible to prevent and / or prevent and / or delay, and / or reduce pathologies linked to overweight and obesity and their symptoms. In particular, it also makes it possible to prevent and / or prevent and / or delay, and / or reduce cardiovascular diseases, diabetes, fatty liver disease, sleep apnea and / or joint problems and their symptoms.

[0240] According to one embodiment, the therapeutic method described above contributes to the improvement of lipid metabolism, in particular to rebalancing metabolic parameters such as cholesterol and triglyceride levels and blood sugar levels. All preferences, embodiments and examples described for the non-therapeutic method above are also applicable to the therapeutic method for preventing and / or treating overweight and / or obesity.

[0241] Advantageously, the therapeutic method comprises at least one of the preliminary steps described above for the non-therapeutic method.

[0242] Advantageously, the preliminary steps of assessing the patient's needs and determining their initial and final weight are carried out by a qualified health professional, such as a doctor, nutritionist or dietitian.

[0243] For obesity, it may be essential to consider the subject's medical history, such as diabetes, high blood pressure, heart disease, etc. This assessment may also be supplemented by other tests to assess the subject's metabolic status and general health.

[0244] For example, according to one embodiment, the method for preventing and / or treating overweight and / or obesity, according to the invention, comprises the following steps:

[0245] - measurement of the subject's initial weight, and possibly their cholesterol and / or triglyceride and / or blood sugar levels,

[0246] - assessment of the subject's needs by determining the dosage and duration of treatment,

[0247] - possibly, evaluation of the quantity of meals to be ingested after each administration of the composition according to the invention,

[0248] - ingestion by the subject of the first composition and the second composition in a sequential manner over a specified period,

[0249] - possibly, measurement of the subject's weight at intermediate stages of treatment,

[0250] - possibly, adaptation of the dosage and duration of treatment,

[0251] - measurement of the subject's final weight,

[0252] - evaluation of the effectiveness of the treatment.

[0253] Mode of action

[0254] Contact of the first composition with an acidic medium, in particular the second composition, leads to its swelling and the formation of a foam. For the purposes of the invention, the term “acidic medium” means a medium having a pH less than or equal to 5, preferably ranging from 0.1 to 5, more preferably ranging from 0.25 to 5, and advantageously ranging from 0.4 to 4.

[0255] The swelling of the first composition in an acidic medium is made possible by two phenomena: foaming resulting from the decomposition of the foaming agent into gas and crosslinking of the hydrophilic polymer, these two phenomena occurring simultaneously. The swelling of the composition according to the invention does not require any injection of gas. Where appropriate, the crosslinking compound also contributes to the release of gas and the formation of foam.

[0256] The swelling of the first composition in an acidic medium occurs in the subject's stomach through the successive administration (in two stages) of the two compositions. Thus, after being ingested, the composition according to the invention swells in the stomach.

[0257] Simultaneous administration of the first and second compositions would lead to instant swelling of the first composition before reaching the subject's stomach, for example in the oral cavity or esophagus, which would make it difficult to swallow the composition.

[0258] Advantageously, in the presence of acid as defined above, the first composition has a swelling rate greater than or equal to 700%, preferably greater than or equal to 800%, more preferably greater than or equal to 1000%, even more preferably greater than or equal to 1200%. Advantageously, the swollen composition has a swelling rate less than or equal to 3000%, preferably less than or equal to 2000%.

[0259] The swelling rate is defined as the ratio of the difference between the volume of the expanded composition after foaming and the volume of the first composition before ingestion to the volume of the first composition before ingestion. The swelling rate is determined according to the equation

[0260] G = 100x(Vt - Vï) / Vi with: G: swelling rate (in %), Vt: volume determined at time t (in mL) and Vi: initial volume of the first composition (in mL). Advantageously, the maximum swelling of the composition according to the invention is reached at most in 30 minutes, preferably at most in 25 minutes, more preferably at most in 15 minutes, advantageously at most in 10 minutes.

[0261] The volume of the swollen composition is controlled by the choice of the administered dose of the composition in kit form according to the invention. It depends on the nature of the subject, human or animal, its age and the volume of its stomach. For example, the volume of the swollen composition in the stomach of an adult human subject is advantageously at least 200 ml, preferably at least 300 ml.

[0262] Advantageously, the composition remains swollen in the patient's stomach for at least 20 minutes, preferably at least 30 minutes, more preferably at least 40 minutes and more preferably at least 60 minutes.

[0263] Preferably, the composition retains 90%, preferably 70%, more preferably 50% of its swollen volume in the patient's stomach for at least 15 minutes, preferably at least 20 minutes, more preferably at least 30 minutes and more preferably for at least 40 minutes.

[0264] Advantageously, after ingestion, the composition according to the invention is eliminated naturally through the pylorus after a time of at least 40 minutes, preferably at least 60 minutes, more preferably at least 90 minutes and more preferably at least 180 minutes.

[0265] The composition according to the invention advantageously makes it possible to obtain a closed foam. For the purposes of the invention, the term "closed foam" means a foam having a closed-cell structure, or an open-cell structure but with a closed outer shell.

[0266] A closed foam is advantageous in that the gas responsible for its formation remains trapped inside the structure. In particular, in the context of the compositions according to the invention, the gas released during the foaming of the composition remains trapped within the polymer matrix, thus preventing the release of gas inside the stomach. The hydrophilic polymer present in the composition according to the invention then constitutes a continuous phase within the foam structure and forms a three-dimensional network. In the case where a non-crosslinkable hydroswelling polymer is present in the composition, this polymer forms a dispersed phase within the foam structure. The foam stabilizing agent is located at the interface between the hydrophilic polymer and the gas bubbles trapped in the structure. A test for determining the closed or open nature of a foam is described in application WO2018 / 234680.

[0267] Thanks to the presence of a foam stabilizing agent, the composition according to the invention in its swollen form is mechanically stable over a period of a few hours corresponding to the time interval between the intake of two consecutive meals. A foam is considered to be mechanically stable if its swelling rate does not decrease after 10 minutes of swelling, preferably after 15 minutes of swelling.

[0268] Effect of acid on pressure and flow resistance

[0269] According to one aspect, the invention relates to the use of an acid chosen from tartaric acid, succinic acid, ascorbic acid and mixtures thereof for improving the pressure and flow resistance of a swollen composition obtained from a composition comprising at least one hydrophilic polymer chosen from polysaccharides, a crosslinking compound, a foaming agent and a foam stabilizing agent.

[0270] The Applicant has surprisingly discovered that an acid chosen from tartaric acid, succinic acid and / or ascorbic acid not only allows the composition to swell in the form of foam, but also to keep the composition swollen in the stomach of the subject, at least for the duration of a meal, and for a prolonged period compared to the administration of a first composition without separate administration of an acid.

[0271] Indeed, the composition in kit form according to the invention is advantageously intended to be ingested before a meal is taken by a human or animal subject. Following the taking of a meal, the ingested food portion exerts pressure on the swollen composition in the stomach, which can cause the composition to flow rapidly through the pylorus. Furthermore, if the foam is not strong enough, it is possible that it begins to pass through the pylorus before the food reaches the patient's stomach, or even before the foam has had time to reach its maximum swelling. The feeling of satiety then does not last long. In the absence of the composition according to the invention, in general, an adult human subject can ingest a standard meal having a weight of up to approximately 500 g. The maximum capacity of the stomach of the adult human subject to accommodate a liquid having a density of 1.07 g / ml is approximately 1.3 liters.On the other hand, contractions in the stomach due to the phenomenon of gastrointestinal peristalsis tend to propel the swollen composition towards the rest of the digestive tract. In addition, especially in overweight or obese subjects, the pressure exerted on the stomach is greater.

[0272] The use of an acid selected from tartaric acid, succinic acid and / or ascorbic acid makes it possible to improve the resistance of the swollen composition to pressure, in particular that exerted by the walls of the stomach and / or by the food ingested by the subject. Consequently, the volume of the swollen composition can be maintained throughout the intake of a meal and during its ingestion, promoting a prolonged satiety effect.

[0273] The use of an acid chosen from tartaric acid, succinic acid and / or ascorbic acid also makes it possible to improve the resistance of the swollen composition to flow, in particular through the pylorus.

[0274] EXAMPLES

[0275] The invention is illustrated by the following examples given without limitation. In the examples, parts and percentages are expressed by weight unless otherwise indicated.

[0276] I- Preparation of the first composition according to the invention:

[0277] Components:

[0278] • Sodium alginate (CAS No. 9005-38-3) marketed under the reference Algogel® 3001 available from Algaia,

[0279] • Calcium carbonate (CAS No. 471-34-1) marketed under the reference AH MIKhart 1® available from La Provençale,

[0280] • Sodium bicarbonate (CAS No. 144-55-8) marketed under the reference Bicar®Food available from Solvay,

[0281] • Potassium bicarbonate (CAS No. 298-14-6) marketed by Evonik, • Fish gelatin available from Lapi Gelatine,

[0282] • Additives: sodium benzoate (CAS No. 532-32-1) marketed under the reference Purox®S grains available from Emerald, potassium sorbate (CAS No. 24634-61-5) from the Nutrinova® brand available from Celanese, sucralose (CAS No. 56038-13-2) available from Niutang, acesulfam potassium (CAS No. 55589-62-3) from the Sunett® brand (Pharma Type A grade) available from Celanese, apple flavor IH -773-391-3 available from Givaudan.

[0283] Protocol:

[0284] Sodium alginate is dissolved in deionized water under the agitation of a motor and a 4-blade propeller stirring rod until a homogeneous solution is obtained (without aggregates of undissolved sodium alginate). Calcium carbonate, sodium bicarbonate and potassium bicarbonate are dispersed in the sodium alginate solution under agitation until a homogeneous dispersion is obtained. Fish gelatin is then added to the dispersion. In the case where the composition includes additives, these are dissolved in deionized water before the sodium alginate is added. The prepared compositions are reported in the table below.

[0285]

[0286] II- Preparation of the second composition according to the invention

[0287] In a beaker, 150 g of deionized water and 44 mEqH+ of acid are added. The mixture is homogenized manually until the acid dissolves. The acids tested are: tartaric acid (available from Louis François), succinic acid (available from Laboratorium discounter) and ascorbic acid (available from Laboratorium discounter), malic acid (available from Laboratorium discounter), lactic acid (available from Laboratorium discounter) and hydrochloric acid 23% by mass (available from Onyx Bricolage).

[0288] III- Flow characterization protocol:

[0289] The Applicant has developed an original test for comparing the different formulations based on the flow of the formulation through an orifice located at the base of a beaker-type container. This flow can be accelerated by pressure in order to simulate the pressure exerted on the composition (after swelling) by the walls of the stomach and / or ingested food. The diameter of the orifice is of the same order as that of the natural orifices of the stomach (centimeter). The times chosen (25 minutes) are typical of the average duration of ingestion of a meal and gastric emptying on liquids.

[0290] 1-1 -Material:

[0291] • A Pyrex glass beaker (dimensions: Height = 125 mm external diameter = 90 mm) of 600 mL graduated every 25 mL and pierced with a central orifice of 20 mm at the bottom of the beaker,

[0292] • A PLA piston perfectly adjusted to the internal diameter of the beaker (approximately 83 mm) allowing variable weights to be applied,

[0293] • A silicone stopper. lll-2-Protocol:

[0294] The swelling is carried out in the beaker pierced with a previously plugged hole. No increase in volume is observed beyond 20 minutes. First, the residual water after swelling is eliminated by gently removing the stopper. The volume of foam thus obtained is noted V1. The stopper is then replaced to prevent the foam from flowing out.

[0295] To measure the natural flow of foam through the orifice, the stopper is removed and the remaining volume of foam in the beaker after the flow has stopped is measured and noted as V2.

[0296] To measure flow under weight, the piston is placed on the foam. The weight on the piston is gradually increased until the flow of foam through the orifice restarts. The weight applied is denoted P1. The remaining volume of foam in the beaker after the flow has stopped is measured and denoted V3.

[0297] If the flow is complete, the manipulation is stopped. It should be noted that the curved shape of the bottom of the beaker prevents the piston from sliding perfectly to the bottom. Therefore, a volume of 50 mL corresponds to a total flow of foam.

[0298] If the flow is not total, the operation is repeated to obtain the following values: P2 and V4.

[0299] IV- Swelling characterization protocol:

[0300] Preparation of the acid puddle:

[0301] In a 600 mL beaker, heat 50 g of deionized water in a water bath to 37°C, to which 5 mEq H+ of 23% HCl by mass (0.8 g) are added. Set up magnetic stirring. This step simulates the real conditions of the gastric environment before the ingestion of a meal.

[0302] Preparation of foams and measurement of swelling:

[0303] 30 mL of the first composition is taken at room temperature (between 24 and 25 °C) using a syringe (= V0). The contents of the syringe are poured onto the acid pool which is in the water bath = tO while stirring the medium and the stopwatch is started. After 30 seconds, the 150 mL of the acid solution (second composition) are gently added. The hydrogel composition transforms into foam.

[0304] Swelling is measured every 5 minutes for 25 minutes (Vt = volume measured at time t). Alternate between periods of stirring and no stirring approximately every 2 minutes 30 seconds (depending on the amount of hydrogel that has reacted). The volume of the composition is recorded at regular intervals using a stopwatch, between 10 seconds and 1 minute depending on the measurement conditions.

[0305] The swelling of the composition is monitored until the volume stabilizes and reaches a plateau. The volume corresponding to this plateau is considered to be the volume corresponding to the maximum swelling Vmax of the composition. The swelling rate of the composition is determined according to the following equation

[0306] G = 100x(Vt — Vi) / Vi with Vt: volume measured at time t in ml and V0: initial volume before swelling in ml. The swelling measurements are repeated 3 times in order to determine an average swelling rate.

[0307] Ill- Results:

[0308] The quantities of the different ingredients of the compositions in the kit, the hydrogel composition being of a volume of 30 mL (calculated with a density of 1.06 g / mL) are shown in the following Table 2. Compositions A, B, D, F and G are according to the invention.

[0309]

[0310] The swelling and flow results are reported in Table 3 and Table 4 respectively.

[0311] The results show that tartaric acid, succinic acid and ascorbic acid exhibit efficient blowing properties, with a foam volume resistant to passage through the orifice even at high pressures: 628 g and 479 g with tartaric acid (compositions A and B), 457 g with succinic acid (composition D) and 450 g and 325 g with ascorbic acid (compositions F and G). For an equivalent number of meq H+, the other acids tested produce foams that flow completely for similar or even significantly lower applied pressures.

[0312] The composition comprising hydrochloric acid has a low swelling rate and flows completely by applying a weight equal to 313 g (composition H).

[0313]

[0314] Table 4: Flow results of the compositions studied in vitro

Claims

CLAIMS 1. Composition in the form of a kit comprising, in a first compartment, a first composition comprising a hydrophilic polymer chosen from polysaccharides, their derivatives and their mixtures, a crosslinking compound, a foaming agent and a foam stabilizing agent, and in a second compartment, separate from the first compartment, a second composition comprising at least one acid chosen from tartaric acid, succinic acid, ascorbic acid and their mixtures, the mass ratio between the acid and the hydrophilic polymer ranging from 1:2 to 30:

1.

2. Composition according to claim 1, in which the hydrophilic polymer is chosen from alginates.

3. Composition according to claim 1 or claim 2, in which the crosslinking compound is chosen from divalent cation salts, trivalent cation salts and mixtures thereof.

4. Composition according to claim 3, in which the crosslinking compound is chosen from calcium carbonate, manganese carbonate, silver carbonate, iron carbonate, copper carbonate, magnesium carbonate, hydroxyapatite, aluminum carbonate, ferric salts, and mixtures thereof.

5. Composition according to claim 4, in which the crosslinking compound is calcium carbonate.

6. Composition according to any one of claims 1 to 5, in which the foaming agent is chosen from salts of monovalent cations, preferably from carbonates and bicarbonates of monovalent cations.

7. Composition according to claim 6, in which the foaming agent is chosen from sodium carbonate, sodium bicarbonate, ammonium bicarbonate, potassium bicarbonate and mixtures thereof.

8. Composition according to any one of claims 3 to 7, in which in the first composition, the ratio between the quantity of divalent and / or trivalent cations and the quantity of monovalent cations is greater than or equal to 0.01, preferably greater than or equal to 0.05, the quantities of cations being expressed in moles.

9. Composition according to any one of claims 1 to 8, in which the foam stabilizing agent is chosen from structuring agents, surfactant compounds and mixtures thereof.

10. Composition according to claim 9, in which the structuring agent is chosen from proteins, preferably from gelatins, albumin, ovalbumin, milk casein, lecithin and their salts.

11. Composition according to any one of claims 1 to 10, in which the acid is tartaric acid.

12. Composition according to any one of claims 1 to 11, in which the mass ratio between the acid and the hydrophilic polymer ranges from 1:1 to 20:1, more preferably from 1:1 to 10:

1.

13. Composition according to any one of claims 1 to 12, in which the ratio between, on the one hand, the mass of the acid, and on the other hand, the sum of the masses of the crosslinking compound and the foaming agent ranges from 1:10 to 20:1, preferably from 1:10 to 10:

1.

14. A non-therapeutic method for controlling and / or modulating and / or reducing and / or moderating and / or regulating appetite in a human or animal subject, the method comprising at least the oral administration to the subject of a composition according to any one of claims 1 to 13, the first and second compositions being administered successively and not simultaneously, in this order or in the reverse order.

15. A therapeutic method for preventing and / or treating and / or controlling and / or modulating and / or moderating and / or reducing and / or regulating overweight and / or obesity in a human or animal subject, the method comprising administering orally to a human or animal subject a composition according to any one of claims 1 to 13, the first and second compositions being administered successively and not simultaneously, in that order or in reverse order.

16. A method according to claim 14 or claim 15, wherein maximum swelling of the composition is achieved in the patient's stomach in at most 30 minutes, preferably in at most 25 minutes, more preferably in 10 minutes.

17. A method according to any one of claims 14 to 16, wherein the composition remains swollen in the stomach of the patient for at least 20 minutes, preferably at least 30 minutes, more preferably at least 40 minutes and more preferably at least 60 minutes and more preferably at least 90 minutes.

18. A method according to any one of claims 14 to 17, wherein the composition retains 90%, preferably 70%, more preferably 50% of its swollen volume in the patient's stomach for at least 15 minutes, preferably at least 20 minutes, more preferably at least 30 minutes and more preferably for at least 40 minutes.

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