Compositions and methods to reduce appetite and / or facilitate 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 hydrophilic polymer selected from polysaccharides, their derivatives and mixtures thereof, a crosslinking compound, a foaming agent, and a foam stabilizing agent, and, in a second compartment, separate from the first compartment, an acid selected from tartaric acid, succinic acid, ascorbic acid, and mixtures thereof. The invention also relates to methods of administering the composition according to the invention to a human or animal subject.

Description

Title of the invention: Compositions and methods for reducing appetite and / or facilitating weight loss. Technical field

[0001] The present invention relates to compositions, uses, and methods intended to reduce and / or modulate appetite and / or promote weight loss in humans and / or animals. Prior art

[0002] 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 are the fifth leading risk factor for death globally and claim at least 2.8 million lives each year (Source: World Health Organization - "Obesity and Overweight" - Fact Sheet No. 311). In particular, multiple associated health problems such as cardiovascular disease, diabetes, sleep apnea, and joint problems pose a significant risk to overweight and obese individuals.

[0003] Although being overweight is primarily a human problem, it can also affect domestic animals, especially dogs and cats.

[0004] In principle, it is possible to remedy this by following a diet, but the natural appetite for food makes it difficult to control the diet.

[0005] In addition to traditional recommendations related to diet and physical activity, medications such as GLP-1 receptor agonists are available to treat obesity and overweight. However, these medications can be expensive and, like all medications, can cause undesirable side effects.

[0006] Based on this observation, the medical sector has developed other methods to combat obesity. Examples include gastric stimulation using implantable electronic devices; surgical procedures such as gastroplasty and vertical sleeve gastrectomy with gastric resection (or "sleeve gastrectomy") or gastric bypass. These alternatives are invasive surgical procedures, often irreversible, and require extensive postoperative monitoring throughout the patient's life. Medical devices consisting of balloons implanted in the stomach to reduce food intake exist with different variations in terms of duration of placement. The size and method of placement vary. Gastric balloons have been shown to reduce total body weight by 6 to 15%, but they tend to be most effective at the beginning of their placement, and their effectiveness may decrease over time. Furthermore, the implantation of these gastric balloons can cause discomfort and other gastrointestinal side effects.

[0007] Therefore, there is a need to provide compositions that can stimulate or promote weight loss and / or treat overweight and obesity, these compositions being usable in a non-invasive manner, free from undesirable side effects and contraindications.

[0008] Today, there is an increasing number of "appetite suppressants" based on natural fibers that swell in the presence of water, such as konjac, apple pectin, guar gum, agar-agar, or locust bean gum. These compounds are ingested by the patient in powder form with a relatively large amount of water (from 0.5 to 1 L) to allow for their solubilization or dispersion, followed by swelling due 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 plan ahead before each meal and results in 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 can occur, forming a bezoar.

[0009] 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.

[0010] US6,271,278 describes superporous hydrogel composites obtained from a A composition comprising an ethylenically unsaturated monomer and a multi-olefin crosslinking agent in the presence of a disintegrating compound to improve the mechanical properties of the structure and a foaming agent, notably sodium bicarbonate. US 6,677,318 describes hydrogel-type foams obtained by ionic and covalent crosslinking of polysaccharide polymers and their ingestion to provide a feeling of satiety. However, the foamy structure of these types of devices is obtained before ingestion by the patient, during the preparation of the device. The use of these devices therefore involves the ingestion by the patient of a relatively large volume of hydrogel foam.

[0011] There is therefore a need to provide compositions enabling a reduction of gastric volume without requiring any steps other than its ingestion and in particular without requiring the prior ingestion of large volumes of water.

[0012] The Applicant has previously developed compositions capable of transforming into a hydrogel foam upon introduction into the stomach. These compositions are described in WO2018 / 234680 and comprise a hydrophilic alginate-based polymer, a compound capable of cross-linking the hydrophilic polymer such as calcium carbonate, a foaming agent selected from carbonate and bicarbonate salts, and a foam stabilizing agent. Contact between the composition and the gastric environment causes the composition to swell. Consequently, the remaining empty gastric volume available for food is reduced, and the patient experiences a feeling of satiety rapidly after ingesting this composition.

[0013] However, in the course of its investigations and work on the subject, the Applicant noted 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 ingested food.

[0014] There is therefore a need to provide compositions that reduce appetite and promote weight loss, capable of expanding in the stomach so as to produce in the patient the sensation of satiety as quickly as possible, and which resist pressure in the stomach and flow through the pylorus, so as to prolong the sensation of satiety.

[0015] WO2007 / 113454 describes a composition to prevent esophageal burns In cases of reflux, this product contains alginate, bicarbonate, carbonate, acid, and a binding agent. Administered orally as a powder, it forms a floating raft in the stomach, above the gastric contents. It does not swell in the stomach to occupy a specific volume. This product is not used to suppress appetite and does not reduce gastric volume. Furthermore, this product is intended to protect the stomach from the acidity of gastric reflux, not to prevent passage into the esophagus or pylorus.

[0016] In continuation of its work, the Applicant has developed new compositions which allow a prolonged and controlled reduction of gastric volume in order to reduce appetite and / or facilitate weight loss and, consequently, improve and / or control body appearance in humans and animals.

[0017] The compositions according to the invention are in kit form, 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 selected from tartaric acid, succinic acid, ascorbic acid and mixtures thereof.

[0018] It was unexpectedly discovered that the use of an acid selected from tartaric acid, succinic acid, ascorbic acid, and mixtures thereof 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 remain in the stomach throughout a meal, thereby prolonging the feeling of satiety and reducing food consumption during the meal.

[0019] Surprisingly, the Applicant discovered that not all organic acids with similar pKa, molar mass and solubility characteristics compatible with digestion were equivalent, and that only certain acids were suitable for this application. Summary of the invention

[0020] The invention relates to a composition in the form of a kit comprising, in a first compartment, a first composition comprising a hydrophilic polymer selected from polysaccharides, their derivatives and mixtures thereof, 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 selected from tartaric acid, succinic acid, ascorbic acid and mixtures thereof, the mass ratio between the acid and the hydrophilic polymer ranging from 1:2 to 30:1.

[0021] Advantageously, the hydrophilic polymer is chosen from among the alginates.

[0022] Advantageously, the crosslinking compound is chosen from divalent cation salts, trivalent cation salts and mixtures thereof.

[0023] 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.

[0024] Preferably, the crosslinking compound is calcium carbonate.

[0025] Advantageously, the foaming agent is chosen from among monovalent cation salts, preferably among carbonates and bicarbonates of monovalent cations.

[0026] Preferably, the foaming agent is chosen from sodium carbonate, sodium bicarbonate, ammonium bicarbonate, potassium bicarbonate and mixtures thereof.

[0027] 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.

[0028] Advantageously, the foam stabilizing agent is chosen from among the structuring agents, surfactant compounds and their mixtures.

[0029] Preferably, the structuring agent is chosen from proteins, preferably from gelatins, albumin, ovalbumin, milk casein, lecithin and their salts.

[0030] According to one embodiment, the acid is tartaric acid.

[0031] Preferably, the mass ratio between the acid and the hydrophilic polymer is 1:1 at 20:1, preferably still from 1:1 to 10:1.

[0032] 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 goes from 1:10 to 20:1, preferably from 1:10 to 10:1.

[0033] The invention also relates to the use of an acid selected from tartaric acid, succinic acid and / or ascorbic acid to improve the compressive strength and / or flow resistance of a hydrogel foam composition obtained from a hydrophilic polymer selected from polysaccharides, their derivatives and mixtures, a crosslinking agent, a foaming agent and a foam stabilizing agent.

[0034] 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 that order or in reverse order. Detailed description

[0035] The expression "consists essentially of" followed by one or more characteristics means that 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, in addition to the components or steps explicitly listed.

[0036] The expression "between X and Y" includes the bounds, 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.

[0037] 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 selected from polysaccharides, their derivatives and 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 selected from tartaric acid, succinic acid, ascorbic acid and mixtures thereof, the mass ratio between the acid and the hydrophilic polymer ranging from 1:2 to 30:1.

[0038] 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 kit form according to the invention, the first and second composition being administered successively and not simultaneously, in that order or in reverse order.

[0039] According to a third aspect, the invention relates to the use of an acid selected from tartaric acid, succinic acid, ascorbic acid and mixtures thereof to improve the compressive and flow resistance of a swollen composition obtained from a composition comprising at least one hydrophilic polymer selected 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.

[0040] The different embodiments, variants, preferences and advantages described above for each of the objects of the invention apply to all the objects of the invention and can be taken separately or in combination. The kit composition: The first composition The hydrophilic polymer

[0041] The composition contained in the first compartment of the kit according to the invention comprises at least one hydrophilic polymer selected from polysaccharides, their derivatives and mixtures thereof.

[0042] For the purposes of this invention, "polymer" means oligomers, prepolymers, homopolymers, and copolymers. "Hydrophilic polymer" means a polymer that is capable of absorbing water or that is soluble in water.

[0043] For the purposes of this invention, "polysaccharides and their derivatives" means polymers composed of several sugar units and / or several units derived from sugars and linked together by glycosidic bonds. The derived units may be sugar units bearing a carboxylic acid and / or amine function and / or an alkyl amide group or an ester function of an alkyl carboxylic acid.

[0044] Polysaccharides and their derivatives have the advantage of being water-soluble polymers, capable of swelling by absorbing water, and therefore suitable for ingestion. by humans and animals via the oral route. Polysaccharides are also low- or non-calorific, meaning they provide few calories to the body during digestion. This is particularly advantageous when using the composition according to the invention to reduce weight gain and obesity, especially in patients with diabetes.

[0045] Examples of polysaccharides and polysaccharide derivatives include alkyl celluloses such as C1-C6 alkyl celluloses, in particular methyl cellulose, ethyl cellulose and ethyl methyl cellulose; substituted alkyl celluloses such as C1-C6 alkyl cellulose hydroxides and C1-C6 C1-C6 alkyl cellulose hydroxides, in particular n-propylcellulose hydroxide, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose and carboxymethylcellulose; substituted dextran phosphates such as dextran sulfate, dextran phosphate and diethylamine dextran; glycosaminoglycans, in particular hyaluronic acid, chondroitin and chondroitin sulfate; and polymers and copolymers comprising uronic acid units.

[0046] Advantageously, the hydrophilic polymer is chosen from K (kappa) carrageenan, l (iota) carrageenan, polysaccharides comprising uronic units and mixtures thereof, preferably from polysaccharides comprising uronic units.

[0047] For the purposes of this invention, "uronic units" are understood to mean polymeric units derived from simple sugars obtained by oxidizing the carbon at the end of the chain to a carboxylic acid group. These uronic units are obtained, for example, from mannuronic acid, guluronic acid, glucuronic acid, iduronic acid, or galacturonic acid. Polymers and copolymers comprising uronic units are obtained by forming glycosidic bonds with other monomers.

[0048] Advantageously, at least 50% by mass, preferably at least 80% by mass, of the sugar units of the hydrophilic polymer are uronic acid units. Preferably, the hydrophilic polymer consists essentially of uronic acid units.

[0049] Advantageously, the hydrophilic polymer has an average weight 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.

[0050] According to one embodiment, the hydrophilic polymer is chosen from polysaccharides consisting essentially of aD-galacturonic units, preferably from pectins.

[0051] 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 among the alginates.

[0052] For the purposes of this invention, "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).

[0053] 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 each other directly.

[0054] According to one embodiment, the hydrophilic polymer is partially crosslinked before its introduction into the composition.

[0055] The hydrophilic polymer can be partially crosslinked by the formation of ionic bonds (partial physical crosslinking), covalent bonds (partial chemical crosslinking), or both ionic and covalent bonds (partial mixed crosslinking). Preferably, the hydrophilic polymer is crosslinked by the formation of ionic bonds (partial physical crosslinking) before being incorporated into the composition.

[0056] 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.

[0057] For the purposes of this invention, "crosslinking index" means the ratio of the number of occupied crosslinking sites on a polymer chain to 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.

[0058] According to another embodiment, the hydrophilic polymer is not crosslinked before its introduction into the composition.

[0059] 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, preferably still 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. The crosslinking compound

[0060] The first composition contained in the first compartment of the kit according to the invention comprises at least one crosslinking compound.

[0061] Advantageously, the crosslinking compound is capable of crosslinking the hydrophilic polymer as described above by the formation of ionic bonds.

[0062] Advantageously, the crosslinking compound capable of crosslinking the hydrophilic polymer by the formation of ionic bonds is introduced into the composition in an inactive form. For the purposes of this invention, "inactive form" means that in aqueous solution at neutral pH, the crosslinking of the hydrophilic polymer by this compound does not occur. Upon exposure to acidity, the crosslinking compound dissociates and releases the chemical species capable of crosslinking the hydrophilic polymer by the formation of ionic bonds.

[0063] Advantageously, the crosslinking compound is chosen from divalent cation salts, trivalent cation salts and mixtures thereof.

[0064] Among the divalent cations suitable for the invention, we can mention calcium (II), manganese (II), silver (II), iron (II), copper (II), magnesium (II), and mixtures thereof.

[0065] Among the trivalent cations suitable for the invention, we can mention aluminium, iron (III) and their mixtures.

[0066] Depending on the nature of the cation used, the composition obtained by crosslinking the hydrophilic polymer can have different physical properties. For example, a hydrogel obtained by crosslinking the hydrophilic polymer with magnesium ions will be relatively more mechanically fragile and have a shorter lifespan, whereas a hydrogel obtained by crosslinking the hydrophilic polymer with calcium ions will be mechanically stable 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.

[0067] According to a preferred embodiment, the crosslinking compound is chosen from divalent cation salts.

[0068] Preferably, according to this embodiment, the divalent cation is calcium.

[0069] Advantageously, the divalent cation salts and / or trivalent cation salts are chosen from among the 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 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, less than or equal to 0.5g / L, preferably less than or equal to 0.1g / L.

[0070] Advantageously, the crosslinking compound is chosen from among the salts likely to decompose in 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 Brønsted.

[0071] According to a preferred embodiment, the acid-base species released by the decomposition of the metal salt in aqueous medium is selected from the hydrogen carbonate or bicarbonate ion (HCO3), the carbonate ion (CO32), and mixtures thereof. By decreasing the pH, particularly to a pH less than or equal to 6, these ions are transformed into carbonic acid (H2CO3), which decomposes into carbon dioxide (CO2).

[0072] According to one embodiment, when the crosslinking compound is chosen from among the divalent cations, it is advantageously chosen from calcium carbonate (CaCO3), manganese carbonate (MnCO3), silver carbonate (AgCO3), iron carbonate (FeCO3), copper carbonate (CuCO3), magnesium carbonate (MgCO3), hydroxyapatite (CaO(PO4)6OH2) and mixtures thereof.

[0073] According to one embodiment, when the crosslinking compound is chosen from trivalent cations, it is advantageously chosen from aluminium salts Al3+ such as for example aluminium carbonate (Al2(CO3)3); ferric salts Fe3+, and mixtures thereof.

[0074] Carbonate salts are advantageous in that they contribute to gas release and therefore to foam formation. They are also advantageous in that they leave no residue in the stomach: the majority of the cations and gas released contribute to foam formation.

[0075] According to an alternative embodiment, the crosslinking compound is a salt of a divalent and / or trivalent cation and a counter-ion chosen from a nutrient such as a vitamin.

[0076] According to a preferred embodiment of the invention, the crosslinking compound is calcium carbonate.

[0077] The crosslinking compound is advantageously introduced into the composition in such an amount that the crosslinked polymer, after passing through an acidic 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%.

[0078] The crosslinking compound is advantageously introduced into the composition in such a quantity that the crosslinked polymer, after passing through an acidic 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%.

[0079] A crosslinking ratio that is too low is not suitable for the present invention because 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 adequately retained by the structure When inflated, the gas escapes and the foamy structure does not form or is too short-lived to affect the feeling of satiety.

[0080] The cross-linking of the hydrophilic polymer by the formation of ionic bonds is advantageous in that the cross-linked structure of the composition is reversible, in particular, under the action of monovalent cations in large excess. For example, the cross-linked 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 digestive mechanisms. The foaming agent

[0081] The first composition of the kit according to the invention includes at least one foaming agent.

[0082] The foaming agent is defined in the invention as a compound capable of producing a gas or of decomposing / dissociating into a gas under the action of an environmental factor (temperature, pH, ...) or a chemical compound.

[0083] The foaming agent is distinct from the crosslinking compound capable of crosslinking the hydrophilic polymer by the formation of ionic bonds.

[0084] The foaming agent is advantageously introduced into the first composition according to the invention in an inactive form. By "inactive form" for the purposes of the invention, it is understood 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.

[0085] 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.

[0086] According to one embodiment, the foaming agent is chosen from monovalent cation salts.

[0087] Preferably, according to this embodiment, the foaming agent is chosen from alkali metal salts.

[0088] Advantageously, the foaming agent is chosen from among the salts likely to decompose in 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 Brønsted.

[0089] By passing through an acidic medium, the acid-base species released by the decomposition of the salt in aqueous medium reacts to form the conjugated Brønsted acid.

[0090] The conjugated Brønsted acid is preferably chosen from compounds that can decompose into gas, more preferably into carbon dioxide CO2.

[0091] According to a preferred embodiment, the acid-base species released by the decomposition of the salt in aqueous medium is chosen from the hydrogen carbonate or bicarbonate ion HCO3, the carbonate ion CO32, and mixtures thereof. The conjugated Brønsted acid is then carbonic acid H2CO3, which decomposes into carbon dioxide CO2.

[0092] 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.

[0093] Preferably, the foaming agent is chosen from sodium carbonate (Na2CO3), sodium bicarbonate (NaHCO3), ammonium bicarbonate (NH4CO3), potassium bicarbonate (KHCO3) and mixtures thereof, preferably still, from monovalent metal cation salts, more advantageously from sodium carbonate, sodium bicarbonate, potassium bicarbonate and mixtures thereof.

[0094] When placed in an aqueous medium at neutral pH, particularly 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 HCO3. Upon contact with an acidic medium, particularly at a pH less than or equal to 5, the bicarbonate ions HCO3 react to form carbonic acid H2CO3, which then decomposes into carbon dioxide CO2.

[0095] According to a preferred embodiment, the foaming agent is sodium bicarbonate and / or potassium bicarbonate.

[0096] According to a preferred embodiment, the foaming agent is a mixture of sodium bicarbonate and potassium bicarbonate.

[0097] Preferably, according to this embodiment, the mass ratio between potassium bicarbonate and sodium bicarbonate is from 1 to 100, preferably from 5 to 50, and even more preferably from 10 to 40.

[0098] The amount of foaming agent introduced into the composition according to the invention is determined relative to the amount of crosslinking compound introduced into the same composition. The amount of foaming agent is determined, in particular, by taking into account the potential contribution of the crosslinking compound to gas release and thus to foam formation.

[0099] Advantageously, the foaming agent is introduced into the composition according to the invention in such an amount 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, of preference still greater than or equal to 0.1, the quantities of cations being expressed in moles.

[0100] Advantageously, the foaming agent is introduced into the composition according to the invention in such a quantity that the ratio between the quantity of divalent and / or trivalent cations, preferably divalent, and the quantity 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 quantities of cations being expressed in moles.

[0101] Advantageously, the crosslinking compound and the foaming agent are introduced into the composition according to the invention in a mass ratio of 1:1 to 1:10, preferably from 1:1 to 1:5.

[0102] Thus, the monovalent cation released by the foaming agent is present in proportions such 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.

[0103] The release of gas in the polymer matrix makes it possible to obtain a large number of connected cells to form an open-cell foam.

[0104] 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 crosslinking rate, the amount and type of foaming agent introduced into the matrix, and the amount and nature of the foam stabilizing agent.

[0105] 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.

[0106] According to a particularly preferred embodiment, the crosslinking compound is calcium carbonate and the foaming agent is sodium bicarbonate.

[0107] According to another particularly preferred embodiment, the crosslinking compound is calcium carbonate and the foaming agent is potassium bicarbonate.

[0108] 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. The foam stabilizing agent

[0109] The composition contained in the first compartment of the kit according to the invention comprises at least one foam stabilizing agent.

[0110] For the purposes of this invention, "foam stabilizing agent" means a compound capable of reducing surface tension at the interface of two different media, and in particular at the interface separating a liquid medium from a gaseous medium.

[0111] Preferably, the foam stabilizing agent is chosen from among structuring agents, surfactant compounds and mixtures thereof.

[0112] Structuring agents

[0113] For the purposes of this invention, "structuring agent" means a chemical compound capable of stabilizing the structure of a foam. Structuring agents are classified into two categories according to their chemical nature: peptides and proteins, and saccharides.

[0114] According to one embodiment, the structuring agent is chosen from peptides and proteins.

[0115] For the purposes of this invention, "peptide or protein" means a chain of several amino acids linked together by peptide bonds. More specifically, the term "peptide" is used when the number of amino acids in the chain is less than 50. The term "protein" is used when the number of amino acids in the chain is greater than or equal to 50.

[0116] Preferably, the structuring agent is chosen from among the proteins.

[0117] Preferably, the protein is chosen from among gelatins, albumin, Ovalbumin, milk casein, lecithin, their salts such as sodium caseinate, and mixtures thereof.

[0118] According to a preferred embodiment of the invention, the foam stabilizing agent is gelatin.

[0119] According to one embodiment, the structuring agent is chosen from among the saccharides. By "saccharides" for the purposes of the invention we mean organic compounds comprising one or more simple sugars.

[0120] Preferably, the foam stabilizing saccharides are chosen from xanthan gum, glucomannan gum, gum arabic, locust bean gum and mixtures thereof.

[0121] Surfactant compounds

[0122] For the purposes of this invention, "surfactant compound" means an amphiphilic compound comprising a hydrophobic portion, in particular a long carbon chain, and a hydrophilic portion. Surfactants are classified into four categories according to the nature of the hydrophilic group: anionic surfactants, cationic surfactants, zwitterionic or amphoteric surfactants, and nonionic surfactants.

[0123] Preferably, the surfactant compound is chosen from amphoteric surfactants and non-ionic surfactants.

[0124] For the purposes of this invention, "zwitterionic or amphoteric surfactant" means a surfactant compound whose hydrophilic portion consists of an acid-base group. In acidic media, the hydrophilic group is positively charged. In basic media, the hydrophilic group is negatively charged.

[0125] Among the zwitterionic or amphoteric surfactants suitable for the invention, mention may be made of betaines, imidazoline derivatives, phospholipids and their mixtures. For the purposes of this invention, "phospholipid" means a lipid containing at least one phosphoric acid function. Phospholipids include, in particular, phosphate acids and phosphoglycerides.

[0126] For the purposes of this invention, "non-ionic surfactant" means a compound surfactant in which the hydrophilic part is not charged.

[0127] Examples of non-ionic surfactants include: polymers and copolymers of ethylene glycol and propylene glycol, esters of fatty acids and (poly)ethylene oxide, ethers of fatty alcohols and (poly)ethylene oxide, ethers of (poly)oxyethylenated polyols, esters of fatty acids and polyols, in particular esters of fatty acids and sugars, possibly (poly)oxyethylenated, fatty acid glycerides, oxyethylenated glycerol ethers, glycerol and fatty alcohol ethers, fatty acids.

[0128] For the purposes of this invention, "fatty acid" means a carboxylic acid type compound comprising a linear hydrocarbon chain of 10 to 30 carbon atoms.

[0129] For the purposes of this invention, "ethoxylated" means a chemical compound that has undergone an ethoxylation step by reaction with ethylene oxide.

[0130] According to one embodiment, the non-ionic surfactant is selected 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.

[0131] For example, the non-ionic surfactant may be selected from ethoxylated sorbitans, ethoxylated isosorbides, ethoxylated fatty acid and sorbitan esters, ethoxylated fatty acid and isosorbide esters, fatty acid and sorbitan esters, fatty acid and isosorbide esters, and mixtures thereof.

[0132] Among fatty acid and sorbitan esters, we can mention in particular the commercial products SPAN®, for example SPAN®20, SPAN®40 or SPAN®80 marketed by Croda Inc.

[0133] Among the esters of fatty acids and ethoxylated sorbitans, we can mention in particular the commercial products Tween®, for example Tween®20, Tween®60 or Tween®80 marketed by Croda Inc.

[0134] According to one embodiment, the non-ionic surfactant compound is chosen from fatty acids, preferably linoleic acid.

[0135] According to one embodiment, the foam stabilizing agent is a mixture of different stabilizing agents and / or different surfactant compounds.

[0136] 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, preferably still from 0.1% to 1% by mass of foam stabilizing agent, the percentages are expressed as mass of dry matter relative to the total mass of the composition contained in the first compartment of the kit. Other additives

[0137] 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.

[0138] The presence of a second hydro-swelling polymer in the compositions according to the invention is advantageous in that it allows for the production of foams of greater volume, thus increasing the swelling rate of the composition.

[0139] Advantageously, the hydro-swelling polymer that is not crosslinkable by the formation of ionic bonds is chosen from starch, agar-agar, carrageenan X (lambda), non-crosslinkable celluloses and mixtures thereof.

[0140] Advantageously, the composition according to the invention has a (second) hydro-swelling polymer content ranging from 0% to 50%, preferably from 1% to 30%, preferably still 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.

[0141] The composition according to the invention may further include, but is not limited to, at least one additive selected from colorings, flavorings, sweeteners, preservatives, flavor enhancers, vitamins, anti-caking agents, antioxidants, and dietary fibers.

[0142] Examples of preservatives include potassium sorbate, methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate and sodium benzoate.

[0143] Examples of sweeteners include sucralose, aspartame, acesulfame K and mixtures thereof.

[0144] Among the flavors, we can mention natural flavors, such as limonene or citral, obtained by extraction from citrus peels such as orange and lemon, and artificial or synthetic flavors, such as vanillin or 3-methoxy-4-hydroxybenzaldehyde, ethyl vanillin or 3-ethyl-4-hydroxybenzaldehyde.

[0145] Examples of flavour enhancers include sodium glutamate, guanylates, inosinates, ribonucleotides, glycine, zinc acetate, trisodium pyrophosphate, phyllosilicates and glucomannans.

[0146] For a composition intended for human ingestion, the flavor enhancer may be selected from sodium glutamate, guanylates, inosinates, ribonucleotides, glycine, and zinc acetate. For a composition intended for ingestion by an animal, and in particular by a mammal, the flavor enhancer Can be chosen from trisodium pyrophosphate, phyllosilicates or glucomannans. Other examples include recycled vegetable or animal oils, waste from the food processing and restaurant industries, poultry liver hydrolysates or fish fermentation products.

[0147] According to one embodiment, the first composition according to the invention further comprises an appetite-enhancing product in the form of a mixture of at least one flavoring and at least one flavor enhancer.

[0148] Advantageously, the composition according to the invention comprises from 0.01% to 40%, preferably from 0.05% to 20%, and even more preferably from 0.1% to 10%, at least one additive selected from colorings, flavorings, sweeteners, preservatives, flavor enhancers, vitamins, anti-caking agents, antioxidants, and dietary fibers and mixtures thereof, the percentages being expressed as a mass of dry matter relative to the total mass of the composition contained in the first compartment of the kit.

[0149] According to one embodiment, the first composition consists essentially of, preferably consists of, a hydrophilic polymer selected from polysaccharides, their derivatives and mixtures, a crosslinking compound, a foaming agent and a foam stabilizing agent.

[0150] According to one embodiment, the first composition consists essentially of, preferably consists of, a hydrophilic polymer selected from polysaccharides, their derivatives and mixtures thereof, a crosslinking compound, a foaming agent and a foam stabilizer, and an additive selected from colorings, flavorings, sweeteners, preservatives, flavor enhancers, vitamins, anti-caking agents, antioxidants, dietary fibers and mixtures thereof.

[0151] Process for preparing the first composition

[0152] The composition contained in the first compartment of the kit according to the invention can be prepared according to the process described in WO2018 / 234680.

[0153] In particular, the composition can be prepared by introducing into an aqueous medium, preferably water, the hydrophilic polymer, the crosslinking compound, the foaming agent, the foam stabilizing agent and possibly other additives.

[0154] The aqueous medium preferably has a neutral pH, in particular a pH between 6.5 and 7.5.

[0155] The order in which the compounds defined above are introduced into the aqueous medium is arbitrary and generally has no effect 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.

[0156] By way of example, the process for preparing the first composition comprises the following steps: - the solubilization or dispersion of the hydrophilic polymer in water, - the 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, - the addition of the foam stabilizing agent, - possibly, the addition of other additives.

[0157] According to another variant, the process for preparing the first composition comprises: - the solubilization or dispersion of the foam stabilizing agent in water, - 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.

[0158] 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.

[0159] According to a first embodiment, the composition is obtained directly following the process described above. In this case, the composition is obtained in the form of an aqueous dispersion.

[0160] According to a second embodiment, the process may further include an additional drying step so as to eliminate all or part of the water present in the composition.

[0161] For example, the drying step of the composition can be carried out by the injection of pulsed hot air, by treatment with supercritical carbon dioxide (CO2), by freeze-drying, or by spray drying, 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 solvent exchange step during which the water in the composition is replaced by a more volatile solvent such as an alcohol.

[0162] The process 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.

[0163] By completely drying the composition, the process allows the preparation of a water-free composition that can be in the form of a xerogel, a cryogel, or an aerogel, depending on the drying method used. More specifically, 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 a cryogel. form of an aerogel. When the composition is completely dried by freeze-drying, the composition is obtained in the form of a cryogel.

[0164] By partial drying, the process according to the invention makes it possible to obtain compositions having various consistencies: in solid or liquid, viscous or fluid forms, and in particular in the form of syrups.

[0165] The first composition of the kit according to the invention can also be presented in a soft form of the type of gummy confectionery, better known in the trade as "gummies", or of the type of jellies better known in the trade as "toppers", in particular for animals.

[0166] In particular, by total or partial drying, the process according to the invention allows the preparation of compositions in the form of powders.

[0167] 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.

[0168] The particle size distribution of the powders can be measured using a LASER Mastersizer 3000 particle size analyzer marketed by the company Malvern according to the protocol described in WO2018 / 234680.

[0169] 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 made up 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

[0170] The second compartment of the kit according to the invention comprises a composition comprising at least one acid selected from tartaric acid, succinic acid, ascorbic acid and mixtures thereof.

[0171] According to a preferred embodiment of the invention, the acid is tartaric acid.

[0172] According to one embodiment, the acid is ascorbic acid.

[0173] According to one embodiment, the acid is succinic acid.

[0174] According to one embodiment, the second composition consists essentially of an acid chosen from tartaric acid, succinic acid, ascorbic acid and mixtures thereof.

[0175] The mass ratio between the acid and the hydrophilic polymer ranges from 1:2 to 30:1.

[0176] Advantageously, the mass ratio between the acid and the hydrophilic polymer goes from 1:1 to 20:1, preferably from 1:1 to 10:1.

[0177] 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 goes from 1:10 to 20:1, preferably from 1:10 to 10:1, preferably again from 1:10 to 5:1.

[0178] The second composition may also include a mixture of acid 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.

[0179] The second composition may include other additives as described above for the first composition of the kit, which may be identical or different from those present in that first composition.

[0180] 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 in the form of a capsule.

[0181] 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.

[0182] Advantageously, according to this embodiment, the aqueous solution has a pH between 1 and 5, preferably between 1.5 and 4, more preferably between 1.5 and 2.5.

[0183] Advantageously, the number of H+ ions in the second composition is between 10 and 60 meq, preferably between 20 and 50 meq.

[0184] The kit according to the invention may also include, in a third compartment, at least one food portion. In particular, the kit according to the invention may include a food portion adapted to the subject's diet.

[0185] The kit according to the invention may also include, in another compartment, at least one oral administration device such as, for example, a feeding syringe, a graduated container, a measuring spoon, or a scale. Methods according to the invention:

[0186] The kit-form composition 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 comes into contact with the acidic gastric environment in the subject's stomach, and also by the effect of the second composition, thus reducing the gastric volume available for food ingestion. The second composition allows for a longer residence time of the hydrogel foam in the stomach, thereby contributing to a longer duration of this appetite-suppressant effect.

[0187] The invention also relates to therapeutic 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 that order or in reverse order.

[0188] 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 the form of a kit according to the invention, the first and second compositions being administered successively and not simultaneously, in that order or in reverse order.

[0189] 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.

[0190] Indeed, the method according to the invention provides the subject with a feeling of satiety reached 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.

[0191] 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.

[0192] Advantageously, the method makes it possible to maintain a stable and / or balanced body weight and to avoid regaining weight after weight loss.

[0193] According to one embodiment, the method described above is intended to aesthetically improve the physical appearance of a human or animal subject. For the purposes of this invention, "aesthetically improve the physical appearance of a human or animal subject" means to decrease and / or reduce 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 a body condition score (BCS) between 4 / 9 and 5 / 9 in an animal subject.

[0194] In particular, the method according to the invention comprises the oral administration to a human or animal subject of an effective dose: (1) of a first composition comprising a hydrophilic polymer selected from polysaccharides, their derivatives and mixtures, a crosslinking agent, a foaming agent and a foam stabilizing agent, and (2) of a second composition comprising at least one acid selected 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 that order or in reverse order.

[0195] According to one embodiment, the first composition is ingested by the subject before the second composition. According to this embodiment, the first composition may swell upon contact with gastric acid. Maximum swelling is achieved following ingestion of the second composition containing acid.

[0196] According to a particularly preferred embodiment of the invention, the second composition is ingested by the subject before the first composition.

[0197] Advantageously, the sequential administration of the two compositions according to the invention is carried out by respecting a well-defined time interval, in particular of at most 15 minutes, preferably of at most 10 minutes, preferably still of at most 5 minutes.

[0198] According to a preferred embodiment, one of the compositions is administered immediately after the administration of the other composition.

[0199] Advantageously, the method according to the invention is implemented before the subject ingests a meal. Preferably, the method according to the invention is implemented at most 30 minutes before the subject ingests a meal, preferably at most 25 minutes, preferably even at most 15 minutes, advantageously at most 10 minutes before the subject ingests a meal.

[0200] Advantageously, the kit-form composition according to the invention is administered to the subject at 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 health status, and metabolic rate.

[0201] According to one embodiment, the subject has the composition in kit form according to the invention in the form of a pre-dosed composition corresponding exactly to his needs.

[0202] 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 taking device (spoon or other dosing instrument).

[0203] 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 three times a day.

[0204] Advantageously, the method according to the invention is implemented in such a way that the maximum amount 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, preferably even less than or equal to 10 g per day.

[0205] Advantageously, the method according to the invention is implemented in such a way that the maximum amount 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, preferably even less than or equal to 2 g per day.

[0206] 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.

[0207] According to one embodiment, the method described above includes a step of ingestion of a meal or a portion of food by the subject, after administration of the composition in kit form according to the invention.

[0208] According to one embodiment of the invention, the method described above includes at least one other step prior to administering the composition in kit form according to the invention.

[0209] In particular, the method according to the invention may include a preliminary step of measuring the initial weight of the subject for reference and monitoring purposes throughout the treatment.

[0210] This step can be followed by a step to assess the subject's overweight. Overweight assessment in a human subject is generally carried out by calculating the body mass index (BMI), which is an indicator based on the relationship between weight and height. BMI is calculated by dividing the subject's weight in kilograms by the square of their height in meters. A subject is considered overweight if the BMI is between 25 and 30 kg / m². The subject is considered obese if the BMI is greater than 30 kg / m². Overweight assessment in an animal subject is generally carried out 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 companion animals. The BCS ranges from 1 to 9, with 1 corresponding to the leanest condition and 9 to the most obese. Generally, a NEC score above 5 / 9 is considered to indicate that the animal is overweight. Scores of 7, 8, and 9 / 9 are assigned to obese animals.

[0211] The method according to the invention may also include a step of assessing the subject's needs, taking into account factors such as their age, general health, medical history, nutritional needs, level of physical activity, and any other relevant parameters. This assessment makes it possible to determine the most appropriate weight loss program for the subject and to personalize the dosage and frequency of administration of the composition according to the invention.

[0212] After administering the compositions to the subject, in accordance with the predetermined dosage and frequency, the method according to the invention may include a step of measuring the subject's final weight to evaluate the overall effectiveness of the weight loss program.

[0213] For example, according to one embodiment, the non-therapeutic method described above comprises at least the following steps: - measurement of the subject's initial weight, - assessment of overweight, in particular by calculating the body mass index, - determination of weight loss goals, - Determination of the dosage and / or frequency of administration of the composition according to the invention, - possibly, evaluation of the quantity of food to be ingested after each administration of the composition according to the invention, - ingestion by the subject of the first and second compositions sequentially, either in that order or in reverse order, - ingestion by the subject of a meal or a portion of food after each administration of the composition according to the invention, - possibly, determination of the subject's intermediate weight during the program at certain time points, - where appropriate, adaptation of the weight loss program, - measurement of the subject's final weight.

[0214] 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 the form of a kit according to the invention, the first and second compositions being administered successively and not simultaneously, in that order or in reverse order.

[0215] According to one embodiment, the therapeutic method described above makes it possible to prevent and / or stop and / or delay, and / or reduce pathologies related to overweight and obesity and their symptoms, in particular it makes it possible to prevent and / or stop and / or delay, and / or reduce cardiovascular diseases, diabetes, sleep apnea and / or joint problems and their symptoms.

[0216] 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 glucose levels.

[0217] 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.

[0218] Advantageously, the therapeutic method includes at least one of the preliminary steps described above for the non-therapeutic method.

[0219] Advantageously, the preliminary steps of assessing the patient's needs and determining his initial and final weight are carried out by a qualified health professional, such as a physician, nutritionist or dietitian.

[0220] 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 examinations to evaluate the subject's metabolic status and general health.

[0221] 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: - measurement of the subject's initial weight, and possibly their cholesterol and / or triglyceride and / or blood glucose levels. - assessing the subject's needs by determining the dosage and duration of treatment, - possibly, assessing the quantity of food 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 sequentially over a specified period, - possibly, measuring the subject's weight at intermediate stages of treatment, - possibly, adjusting the dosage and duration of treatment, - measuring the subject's final weight. - evaluation of the effectiveness of the treatment. Mode of action

[0222] 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 this invention, "acidic medium" means a medium having a pH less than or equal to 5, preferably from 0.1 to 5, more preferably from 0.25 to 5, and advantageously from 0.4 to 4.

[0223] 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 the crosslinking of the hydrophilic polymer, these two phenomena occurring simultaneously. The swelling of the composition according to the invention does not require any gas injection. If necessary, the crosslinking compound also contributes to gas release and foam formation.

[0224] The swelling of the first composition in an acidic environment 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.

[0225] Simultaneous administration of the first and second compositions would lead to the instantaneous swelling of the first composition before reaching the subject's stomach, for example at the level of the oral cavity or esophagus, which would make it difficult to ingest the composition.

[0226] Advantageously, the inflated composition has an inflation rate greater than or equal to 700%, preferably greater than or equal to 800%, preferably even greater than or equal to 1000%, and even more preferably greater than or equal to 1200%. Advantageously, the inflated composition has an inflation rate less than or equal to 3000%, preferably less than or equal to 2000%.

[0227] 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 initial composition before ingestion to the volume of the initial composition before ingestion. The swelling rate is determined according to the equation

[0228] with: G: swelling rate (in %), Vt: volume determined at time t (in mL) and Vi: initial volume of the first composition (in mL).

[0229] 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 still at most in 15 minutes, advantageously at most in 10 minutes.

[0230] The volume of the inflated 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 inflated composition in the stomach of an adult human subject is advantageously at least 200 ml, preferably at least 300 ml.

[0231] The composition according to the invention advantageously allows the production of a closed-cell foam. For the purposes of this invention, "closed-cell foam" means a foam having a closed-cell structure, or an open-cell structure but with a closed outer shell.

[0232] A closed foam is advantageous in that the gas responsible for its formation remains trapped within the structure. In particular, in 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 into 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 within the structure. A test for determining whether a foam is closed or open is described in application WO2018 / 234680.

[0233] Thanks to the presence of a foam stabilizing agent, the composition according to the invention, in its inflated form, is mechanically stable over a period of several hours corresponding to the time interval between two consecutive meals. A foam is considered mechanically stable if its inflation rate does not decrease after 10 minutes of inflation, preferably after 15 minutes of inflation.

[0234] Effect of acid on resistance to pressure and flow

[0235] According to one aspect, the invention relates to the use of an acid selected from tartaric acid, succinic acid, ascorbic acid and mixtures thereof to improve the pressure and flow resistance of a swollen composition obtained from a composition comprising at least one hydrophilic polymer selected from polysaccharides, a crosslinking compound, a foaming agent and a foam stabilizing agent.

[0236] The Applicant has discovered in an astonishing way that an acid chosen from tartaric acid, succinic acid and / or ascorbic acid not only allows the composition to swell into a foam, but also keeps the composition swollen in the subject's stomach, 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.

[0237] Indeed, the kit-form composition according to the invention is advantageously intended to be ingested before a meal by a human or animal subject. Following ingestion, the ingested food portion exerts pressure on the swollen composition in the stomach, which can lead to the rapid flow of the composition through the pylorus. Furthermore, if the foam is not sufficiently resistant, it may begin 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, an adult human subject can generally ingest a standard meal weighing up to approximately 500 g. The maximum stomach capacity of an adult human subject for holding a liquid with a density of 1.07 g / ml is approximately 1.3 liters.On the other hand, stomach contractions due to gastrointestinal peristalsis tend to propel the swollen contents further along the digestive tract. Furthermore, particularly in overweight or obese individuals, the pressure exerted on the stomach is greater.

[0238] The use of an acid selected from tartaric acid, succinic acid, and / or ascorbic acid improves the resistance of the inflated composition to pressure, particularly that exerted by the stomach walls and / or by food ingested by the subject. Consequently, the volume of the inflated composition can be maintained. throughout the intake of a meal and during its ingestion, promoting a prolonged feeling of satiety.

[0239] 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. Examples

[0240] The invention is illustrated by the following examples, which are given by way of non-limiting example. In the examples, parts and percentages are expressed by weight unless otherwise indicated.

[0241] I- Preparation of the first composition according to the invention:

[0242] Components: • Sodium alginate (CAS No. 9005-38-3) marketed under the reference Algogel® 3001, available from Algaia, • Calcium carbonate (CAS No. 471-34-1) marketed under the reference AH MIKhart 1® available from La Provençale, • Sodium bicarbonate (CAS No. 144-55-8) marketed under the reference Bicar®Food, available from Solvay, • Potassium bicarbonate (CAS No. 298-14-6) marketed by Evonik, • Fish gelatin available from Lapi Gelatin, • 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) of the brand Nutrinova® available from Celanese, sucralose (CAS No. 56038-13-2) available from Niutang, acesulfam potassium (CAS No. 55589-62-3) of the brand Sunett® (Pharma Grade Type A) available from Celanese, apple flavor IH-773-391-3 available from Givaudan. Protocol:

[0243] Sodium alginate is dissolved in deionized water using a motor and a four-bladed propeller stirrer 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 with stirring until a homogeneous dispersion is obtained. Fish gelatin is then added to the dispersion. If the composition includes additives, these are dissolved in the deionized water before the sodium alginate is added. The prepared compositions are shown in the table below. [Tables 1] Water (g) Sodium alginate (g) CaCO3 (g) NaHCO 3 (g) khco3 (g) Gelatin (g) Additives Sodium benzoate (g) Potassium sorbate (g) Su) (g) A 432.93 13.32 16.67 1.67 31.68 3.74 B 387.77 12 15 1.5 28.51 3.37 0.48 0.48 0.0 C 432.93 13.32 16.67 1.67 31.68 3.74 D 432.93 13.32 16.67 1.67 31.68 3.74 E 432.93 13.32 16.67 1.67 31.68 3.74 3.74

[0244] II- Preparation of the second composition according to the invention

[0245] In a beaker, 150 g of deionized water and 44 mEqH+ of acid are added. The The mixture is manually homogenized until the acid dissolves. The acids tested are: tartaric acid (available at Louis François), succinic acid (available at Laboratorium discounter) and ascorbic acid (available at Laboratorium discounter), malic acid (available at Laboratorium discounter), lactic acid (available at Laboratorium discounter) and hydrochloric acid 23% mass (available at Onyx Bricolage).

[0246] III - Flow characterization protocol:

[0247] The Applicant has developed an original test for comparing 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 to simulate the pressure exerted on the composition (after swelling) by the stomach walls and / or ingested food. The diameter of the orifice is of the same order of magnitude as that of the natural orifices of the stomach (centimeters). The chosen time frame (25 minutes) is typical of the average duration of meal ingestion and gastric emptying of liquids. III-1-Materials:

[0248] • A Pyrex glass beaker (dimensions: Height = 125 mm external diameter) = 90 mm) of 600 mL graduated every 25 mL and pierced with a central 20 mm hole at the bottom of the beaker, • A PLA piston perfectly fitted to the internal diameter of the beaker (approximately 83 mm) allowing for the application of variable weights, • A silicone stopper. III-2-Protocol:

[0249] The swelling is carried out in the beaker, which has a previously plugged opening. No increase in volume is observed after 20 minutes.

[0250] First, the residual water after inflation is removed by carefully pulling out the stopper. The volume of foam thus obtained is noted as VL. The stopper is then replaced to prevent the foam from escaping.

[0251] To measure the natural flow of foam through the orifice, the stopper is removed and the volume of foam remaining in the beaker once the flow has stopped is measured and noted V2.

[0252] To measure the flow under the effect of a 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 applied weight is noted as PL. The volume of foam remaining in the beaker once the flow has stopped is measured and noted as V3.

[0253] If the flow is complete, the procedure is stopped. It should be noted that the curved shape of the beaker's base prevents the piston from sliding perfectly to the bottom. Therefore, a volume of 50 mL corresponds to a complete flow of the foam.

[0254] If the flow is not total, the operation is repeated to obtain the following values: P2 and V4.

[0255] IV - Swelling characterization protocol: Preparation of the acid pool:

[0256] In a 600 mL beaker, heat 50 g of deionized water to 37°C and add 5 mEq H+ of 23% wt. HCl 23% (0.8 g). Activate magnetic stirring. This step simulates the actual conditions of the gastric environment before the ingestion of a meal.

[0257] Preparation of foams and measurement of swelling:

[0258] 30 mL of the first composition are taken at room temperature (between 24 and 25 °C) using a syringe (= V0). The contents of the syringe are poured onto the acid pool in the water bath (= t0), stirring the mixture, and the timer is started. After 30 seconds, the 150 mL of the acid solution (second composition) are carefully added. The hydrogel composition transforms into a foam.

[0259] Swelling is measured every 5 minutes for 25 minutes (Vt = volume measured at time t). Alternate periods of agitation and no agitation 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 s and 1 min depending on the measurement conditions.

[0260] 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: [Math] G = lOQx(.Vt-VÏ) / Vi

[0261] with Vt: volume measured at time t in ml and V0: initial volume before inflation in ml. The inflation measurements are repeated 3 times in order to determine an average inflation rate.

[0262] III- Results:

[0263] The quantities of the various ingredients of the compositions in the kit, the hydrogel composition having a volume of 30 mL (calculated with a density of 1.06 g / ml), are shown in Table 2 below. Compositions A, B, D, F, and G are according to the invention Sodium alginate (g) CaCO 3 (g) NaHCO 3 (g) KHCO 3 (g) Gelatin (g) Additives Sodium benzoate (g) Potassium sorbate (g) Surcralose (g) AceSulf K (g) A (inv) 0.85 1.06 0.10 2.01 0.23 B (in v) 0.84 1.06 0.10 2.01 0.23 0.03 0.03 0.003 0.002 C 0.85 1.06 0.10 2.01 0.23 D (inv) 0.85 1.06 0.10 2.01 0.23 E 0.85 1.06 0.10 2.01 0.23 F (inv) 0.85 1.06 0.10 2.01 0.23 G 0.85 1.06 0.10 2.01 0.23 (inv) H 0.85 1.06 0.10 2.01 0.23

[0264] The swelling and flow results are reported in the table below.

[0265] The results show that tartaric acid, succinic acid and ascorbic acid exhibit excellent swelling properties, with a foam volume that resists 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 at similar, or even significantly lower, applied pressures.

[0266] The composition comprising hydrochloric acid has a low swelling rate and flows completely when a weight of 313 g is applied (composition H). [Tables 3] Composition V0 (ml) Volume (ml) Gonflement 5 min 10 min 15 min 20 min 25 min 5 min 10 A ( invention ) 30 483 483 468 458 451 1511 15: B ( invention ) 30 525 533 530 523 513 1650 16' C ( comparative ) 30 441 436 428 420 420 1372 13^ D ( invention ) 30 416 408 388 375 365 1288 12( E ( comparative ) 30 351 346 335 328 323 1072 io; F ( invention ) 30 420 411 396 391 388 1300 12' G ( invention ) 30 461 458 445 438 438 1438 14i H ( comparative ) 30 238 235 226 216 211 694 68f [Tableaux4] Composition A |b C |d Ie F ( invention ) ( invention ) ( comparative ) ( invention ) ( comparative ) ( inventit ) VI (ml) 445 513 420 365 323 388 V2 (ml) 323 503 405 362 310 380 PI (g) 260 147 230 457 210 450 V3 (ml) 193 200 50 50 50 50 P2 (g) 368 332 V4 (ml) 50 50

Claims

Demands

1. A composition in the form of a kit comprising, in a first compartment, a first composition comprising a) a hydrophilic polymer selected from alginates, b) a crosslinking compound selected from calcium carbonate, manganese carbonate, silver carbonate, iron carbonate, copper carbonate, magnesium carbonate, hydroxyapatite, aluminum carbonate, ferric salts, and mixtures thereof, c) a foaming agent selected from sodium carbonate, sodium bicarbonate, ammonium bicarbonate, potassium bicarbonate, and mixtures thereof, and d) a foam stabilizing agent selected from gelatins, surfactants, and mixtures thereof, and in a second compartment, separate from the first compartment, a second composition comprising at least one acid selected from tartaric acid, succinic acid, ascorbic acid, and mixtures thereof,the mass ratio between the acid and the hydrophilic polymer ranging from 1:2 to 30:

1.

2. Composition according to claim 1, wherein the crosslinking compound is calcium carbonate.

3. Composition according to claim 1 or 2, wherein 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.

4. Composition according to any one of claims 1 to 3, wherein the acid is tartaric acid.

5. Composition according to any one of claims 1 to 4, wherein the mass ratio of the acid to the hydrophilic polymer ranges from 1:1 to 20:1, preferably further from 1:1 to 10:

1.

6. Composition according to any one of claims 1 to 5, wherein 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 is from 1:10 to 20:1, preferably from 1:10 to 10:1.