ORALLY ADMINISTERED HYDROGEL COMPOSITION, KIT AND USE

Description

FIELD OF INVENTION

[0001] The present invention relates to an orally assimilable hydrogel composition, a kit comprising such a composition, and the use of such a composition for the treatment of overweight or obese individuals, or for the delivery of pharmaceutical or nutritional actives into the stomach of an individual, in a time-delayed manner. EARLIER ART

[0002] The prevalence of obesity, defined as a Body Mass Index (BMI) > 30 kg / m², has doubled in 34 years. The World Health Organization (WHO) estimates that in 2016, 1.9 billion adults (over 18 years of age) and 41 million children (over 5 years of age) were overweight or obese. These figures have been steadily increasing ever since. It is estimated that by 2030, a record 3.3 billion overweight or obese adults will be reached. Obesity has a significant societal and economic impact. It is generally associated with serious and even fatal complications. It is estimated that every minute in the world, more than 5.3 people die from the direct consequences of obesity or being overweight.

[0003] Depending on their BMI, three types of treatment are offered to patients: drug treatment, surgical treatment and treatment by placement of a gastric balloon.

[0004] Treatment by placement of a gastric balloon is generally intended for patients with moderate to severe obesity with a BMI greater than 30 and less than 40 kg / m2.

[0005] These gastric balloons are inflatable medical devices, usually made of silicone, that can be filled with either a gas, a liquid, or both. The procedure for placing a balloon is simple: it is inserted deflated, endoscopically, into the patient's stomach. It is then inflated using a catheter. The placement and inflation procedure can take up to 20 minutes. After inflation, the catheter is removed.

[0006] At the end of the treatment period, which lasts 3 to 6 months depending on the balloons, the balloon is removed, once again, endoscopically.

[0007] However, treating patients with gastric balloons according to prior art presents several drawbacks. In particular, endoscopic procedures for placing and removing gastric balloons are invasive and hazardous. Some serious complications related to the long-term presence of gastric balloons in the stomach have been reported. These include alterations of the gastric mucosa, with the formation of ulcers and / or gastric perforations, compression of underlying organs causing sometimes acute pancreatitis, or intestinal obstructions in cases of balloon migration. WO2007 / 039294 discloses compositions for use in inducing satiety sensitivity, reducing appetite, treating overweight and obesity, and also for the release of pharmaceutical and nutraceutical products using gelling compositions.Reconstituted dry powder in water containing sodium alginate, sodium carbonate, calcium carbonate, glucono-delta lactone, fructose, and sodium bicarbonate is available. WO2018 / 100340 describes a hydrogel containing water, alginate, glucono-delta lactone, and microparticles containing inorganic calcium and recombinant gelatin. WO 2008 / 157318 describes a gelling composition containing a gelling agent (alginate), 0.2–0.9 mM of a divalent cation, 20–90% calcium, and 2 mM of glucuronic acid entities present in the alginate. SUMMARY OF THE INVENTION

[0008] In view of the above, one problem that the invention proposes to solve is in particular to provide means of treating overweight or obese individuals, which avoid the use of inflatable gastric balloons, which require placement in the stomach or removal by endoscopic means.

[0009] The solution of the invention to this problem primarily aims at providing an orally assimilable hydrogel composition comprising: an alginate polymer forming a gel in aqueous solution, in the presence of a cation; a cation for polymerizing the alginate polymer in aqueous solution; an aqueous solution, in sufficient quantity; a dissolving agent for said alginate polymer in the aqueous solution; a gelling retardant; and a flotation agent for forming CO2 bubbles in the hydrogel composition, the hydrogel formed by means of said hydrogel composition being dissolved by means of a final orally assimilable dissolving agent, as described in claim 1.

[0010] Advantageously: - the composition further comprises an agent for strengthening the mechanical structure of the hydrogel; - the composition further comprises a radiopaque agent; - the alginate polymer is a sodium alginate polymer, and in that the cation is calcium; - the dissolving agent for the alginate polymer in aqueous solution is sucrose; - the gelation retardant is Na₂HPO₄; - the agent for strengthening the mechanical structure of the hydrogel is selected from sorbitol, spermine, chitosan, agarose, sodium dodecyl sulfate, phosphatidylcholine, microcrystalline cellulose; - the radiopaque agent is selected from compounds containing barium, for example BaSO₄, and compounds containing iodine; - the final dissolving agent is chosen from among the citrates, calcium chelators, for example sodium citrate, citric acid or EDTA;- the flotation agent is CaCO3, glucono-δ-lactone or a microorganism; the composition includes 0.5 to 5% sodium alginate with a viscosity between 20-200 mPa.s, 1 to 3% CaSO4, 0.10 to 0.20% Na2HPO4, 8 to 15% sucrose, 2 to 8% CaCO3 or 0.1 to 2% yeast, 0.5% to 8% BaSO4, and 0.5 to 8% chitosan with a viscosity between 10 and 50 mPa.s or 0.5 to 8% cellulose, the percentages being mass percentages given in g / 100 ml.

[0011] The solution of the invention has as its second object the use of a composition as defined above, for the treatment of overweight individuals, who have a Body Mass Index greater than or equal to 25 kg / m².

[0012] Advantageously: - the use is for the treatment of obese individuals, who have a Body Mass Index greater than or equal to 30 kg / m2.

[0013] The third object of the solution of the invention is the use of a composition as defined above, for the delivery of pharmaceutical or nutritional active ingredients into the stomach of an individual, in a time-delayed manner.

[0014] The solution of the invention has as its fourth object comprising a composition as defined above, and a dissolving agent assimilable by oral route. BRIEF DESCRIPTION OF THE FIGURES

[0015] The invention will be better understood upon reading the following non-limiting description, drawn up with reference to the accompanying drawings, in which: there figure 1 illustrates, schematically, the different steps for placing a hydrogel according to the invention in a patient's stomach, as well as its dissolution; the figure 2consists of four photographs: photographs A and C showing a hydrogel composition and a hydrogel formed from said composition, without a reinforcing agent; photographs B and D showing a hydrogel composition and a hydrogel formed from said composition, with a reinforcing agent. figure 3 illustrates the results obtained, in terms of setting time, of hydrogel compositions according to the invention, depending on the reinforcing agents it comprises; the figure 4A illustrates the different steps implemented to determine the resistance of hydrogels to pH transitions after the ingestion of a food bolus; the figure 4B presents the results obtained on the in vitro stability of hydrogels according to the invention, comprising or not a strengthening agent, after ingestion of a food bolus; figure 5Aillustrates the results obtained, in terms of weight loss, of hydrogels according to the invention, with different reinforcing agents; the figure 5B illustrates the results obtained, in terms of volume loss, of hydrogels according to the invention, with different reinforcing agents; the figure 6 shows the results obtained, in terms of weight loss, of hydrogels, within the framework of an in vitro experiment aimed at simulating artificial digestion in the presence of natural calcium chelators; the figure 7A illustrates a first method for generating CO2 bubbles in the hydrogel according to the invention, using the so-called calcium carbonate system; the figure 7B illustrates a second method for generating CO2 bubbles in the hydrogel according to the invention, using the so-called NaHCO3 + Glucono-δ-lactone system; the figure 7Cillustrates a third way to generate CO2 bubbles in the hydrogel according to the invention, using the so-called yeast / sucrose system; the figure 8A is a photograph illustrating the flotation of a hydrogel according to the invention, in a simulating acidic solution, in vitro, the acidic solution of a human stomach; and the figure 8B is an endoscopic view of two balloons of a hydrogel according to the invention, floating in the stomach of a mini-pig. DETAILED DESCRIPTION OF THE INVENTION

[0016] The invention relates to a hydrogel composition.

[0017] This composition is assimilated orally by an individual or human patient in the form of a drinkable syrup. This individual is, for example, an adult. However, it can also be adolescents or even children aged at least 5 years old.

[0018] The composition according to the invention comprises an alginate polymer. This alginate polymer forms a gel in aqueous solution in the presence of a cation. Advantageously, the alginate polymer is a sodium alginate polymer, the polymerization of which is initiated by calcium. The calcium source is, for example, CaSO₄.

[0019] The aqueous solution is, for example, water. It is present in the solution in sufficient quantity for the hydrogel to form.

[0020] The composition according to the invention further comprises an agent for dissolving the alginate polymer in the aqueous solution.

[0021] The composition according to the invention also includes a gelling retardant. Preferably, the gelling retardant is Na₂HPO₄.

[0022] The composition according to the invention further comprises a flotation agent. The flotation agent is responsible for the formation of gas bubbles within the hydrogel composition. Advantageously, the flotation agent is CaCO3, glucono-δ-lactone, or a microorganism. The hydrogel according to the invention floats in an acidic solution simulating in vitro The acidic solution of a human stomach is illustrated in figure 8A It is further illustrated in the endoscopic view shown at the figure 8B .

[0023] The composition according to the invention advantageously comprises a reinforcing agent. This reinforcing agent strengthens the mechanical structure of the hydrogel. The reinforcing agent is preferably of the polymeric type, forming macromolecules that are incorporated into the hydrogel to increase its mechanical strength. Preferably, the reinforcing agent for the mechanical structure of the hydrogel is selected from sorbitol, spermine, chitosan, agarose, sodium dodecyl sulfate, phosphatidylcholine, and microcrystalline cellulose.

[0024] The composition according to the invention also advantageously comprises a radiopaque agent. Preferably, the radiopaque agent is chosen from compounds containing barium and compounds containing iodine. More preferably, the radiopaque agent is BaSO4.

[0025] In other words, the composition according to the invention comprises 0.5 to 5% sodium alginate with a viscosity between 20-200 mPa.s and / or 1 to 3% CaSO4 and / or 0.10 to 0.20% Na2HPO4 and / or 8 to 15% sucrose and / or 2 to 8% CaCO3 or 0.1 to 2% yeast and / or 0.5% to 8% BaSO4 and / or 0.5 to 8% chitosan with a viscosity between 10 and 50 mPa.s or 0.5 to 8% cellulose, the percentages being mass percentages given in g / 100 ml.

[0026] According to the invention, the hydrogel formed using the hydrogel composition is dissolved with an orally absorbable dissolving agent. This dissolving agent is referred to as the final dissolving agent. It is advantageously chosen from among citrates and calcium chelators, for example, phytic acid, oxalic acid, sodium citrate, citric acid, or EDTA. The hydrogel dissolves advantageously completely and does not give rise to aggregates as degradation products.

[0027] For the implementation of the invention, a kit is provided, for example, to a patient or to healthcare personnel.

[0028] This kit includes a first container and a second container.

[0029] The first container comprises the following compounds in powder form: the alginate polymer, the cation-forming compound for the polymerization of the alginate polymer, the dissolving agent for the alginate polymer, the gelling retardant, the flotation agent, and, advantageously, the strengthening agent, and the radio-opaque agent.

[0030] The second container contains the hydrogel dissolving agent, also in powder form.

[0031] The contents of the first container are dissolved in the aqueous solution to form the hydrogel composition.

[0032] As shown in step A of the figure 1This hydrogel composition is ingested by the patient, after dissolution, like a syrup. In practice, the retarding agent delays the polymerization of the alginate polymer. Therefore, the composition is, at this stage of implementation of the invention, oral.

[0033] The composition absorbed orally is then brought into the patient's stomach via the esophagus.

[0034] The polymerization-retarding agent has a temporary effect. As shown in the figure 1 In step B, after the hydrogel composition enters the stomach, for example, 2 to 3 minutes later, the composition undergoes gelation in the stomach. In practice, the calcium provided by the CaSO4 enables this gelation.

[0035] The stomach has an acidic pH, which varies over time. This acidity is due to the presence of hydrochloric acid in the stomach. Gelation is accompanied by a reaction of the buoyancy agent. In one example, the buoyancy agent reacts with the hydrochloric acid present in the stomach to form gas bubbles, namely CO2, in the gelling composition. The gas bubbles formed are trapped in the developing gel. This gel is therefore an aerogel. It can be described as a hybrid hydrogel / aerogel. In another example, the buoyancy agent is formed by microorganisms contained in the hydrogel composition. These microorganisms are, for example, yeasts, which are trapped in the gel and produce CO2 bubbles after consuming the sucrose also present in the gel. They carry out glycolysis of glucose into pyruvate with release of CO2, or glycolysis of glucose into ethanol, in the presence of O2.

[0036] The gel thus formed, which is shown to the figure 1 Step C, is essentially in the form of a roughly spherical or ovoid balloon. The gel floats in the stomach where it occupies a space that depends on the amount of the composition admitted into the stomach.

[0037] For digestion, the stomach contracts and then relaxes. The strengthening agent reinforces the structure of the gel according to the invention. Its presence prolongs the residence time of the hydrogel inside the stomach. It allows the hydrogel to mechanically resist the contraction forces exerted by the stomach's muscular layers.

[0038] Alginate gels are resistant in acidic environments and are not degraded by human α-amylase, unlike chitosan and starch gels. The gel according to the invention, which is established in the stomach, is stable. Its stability is maintained for several weeks or months.

[0039] As shown in the figure 1 In step D, advantageously, the hydrogel composition according to the invention is taken sequentially over a period of 3 weeks. Each week, the patient swallows a predetermined volume of the composition, which will form a 200 to 250 ml balloon. In total, three 200 to 250 ml balloons will be present in the patient's stomach. Sequential administration allows the patient to become accustomed to feeling a mass in the stomach and limits certain adverse events such as nausea, vomiting, and abdominal pain.

[0040] It is possible to verify the placement and proper holding of the hydrogel according to the invention in the patient's stomach, in particular thanks to the presence of the radio-opaque agent, by simply taking an X-ray of the abdominal area of ​​the patient's body where the stomach is located.

[0041] For the removal of the hydrogel, as shown in the figure 1, step E, the dissolving agent contained in the second container of the kit according to the invention is used.

[0042] This dissolving agent is, for example, dissolved in an aqueous solution. It is then ingested by the patient. The solution containing this agent is then carried to the stomach via the duodenum. Once in contact with the hydrogel of the invention, it dissolves it, and the hydrogel is expelled from the patient's stomach during gastric emptying. This last step is denoted F in the figure 1 .

[0043] According to the invention, the hydrogel composition is thus suitable for use in the treatment of overweight individuals with a Body Mass Index greater than or equal to 25 kg / m2. Advantageously, it is used for the treatment of obese individuals with a Body Mass Index greater than or equal to 30 kg / m2.

[0044] According to the invention, the hydrogel composition can be used for the delayed delivery of pharmaceutical or nutritional active ingredients to an individual's stomach. The active ingredients are advantageously contained within the hydrogel composition, then trapped therein, and their release into the stomach is delayed.

[0045] Ultimately, the invention relates to an innovative Class III intragastric device capable of reducing both the safety issues associated with gastric balloons and their costs. It was preferentially developed for adults with a BMI between 30 and 40 kg / m², but could eventually be offered to adolescents or children. The gel composition according to the invention is unique and composed of biocompatible agents. No toxic agents are used. The composition is administered orally in the form of a syrup. It forms a spherical or ovoid structure, aerated by the presence of bubbles, and radiopaque when in contact with gastric juices, particularly at pH levels between 2 and 3. This structure is stable for more than four months in the simulated intragastric environment. It retains 80% of its weight / volume at the end of treatment.It can be completely dissolved, without forming aggregates after a few hours via the second solution, also aqueous, administered orally and also composed of a food additive. EXAMPLE 1: PREPARATION OF HYDROGEL

[0046] The hydrogel composition according to the following invention has been prepared, in which the percentages are given by weight relative to the volume w / v: Na-Alginate 2% CaSO4 1,75% Na2HPO4 0,16% sucrose 12% CaCO3 1% Water 83,09%

[0047] For the preparation of this hydrogel, all the ingredients were mixed in powder form in a beaker and then water was added to obtain a volume of hydrogel of 250 mL corresponding to a balloon assimilated in one dose by a patient. EXAMPLE 2: ANOTHER EXAMPLE OF HYDROGEAL COMPOSITION

[0048] The hydrogel composition according to the following invention has been prepared, in which the percentages are given by weight relative to the volume w / v: Na-Alginate 2% CaSO4 1,75% Na2HPO4 0,14% Sucrose (D+) 12% CaCO3 5% Chitosan 0,5 - 1% Cellulose 0,5 - 1% BaSO 4 5% Water qs EXAMPLE 2: HYDROGELFILLER

[0049] It should be noted that the scientific literature is sparse regarding the compressive forces encountered inside the lumen of the human stomach. According to one document, these forces do not exceed 13 kPa. According to a second document, during digestion, these forces vary between 5 kPa and 67 kPa. According to a third document, they average 96 ± 12 Pa for a fed human stomach. The mechanical properties of the hydrogel according to the invention were evaluated by static compression tests using a Lloyd™ LRX PLUS material compression strength measuring machine. Prior to testing, the parameters of this machine were optimized based on the properties of the gels, and in particular, the gel dimensions, force range, strain rate, and maximum deformation. A preload of 0.5 N and a compression rate of 10 mm / min were selected.

[0050] The hydrogel from example 1 was tested. Before breaking, this gel, which does not contain a reinforcing agent, is able to withstand an average stress of 1342 ± 50 Pa corresponding to an average deformation of 26 ± 9% of its length.

[0051] The photos of the figure 2 Photograph C on the left shows a gel obtained according to the hydrogel composition of the invention according to Example 1, without a strengthening agent (chitosan), and photograph D on the right shows a gel having the same composition, but containing chitosan as a strengthening agent. As can be seen in these photographs, the strengthening agent allows the final gel to maintain its desired shape after 25 minutes.

[0052] The strengthening agents listed in the table below were introduced into the gel in Example 1 at concentrations ranging from 0.1 to 20% w / v. A summary of the gels produced and their stress / strain data can be found in the table below. [Table 1] Reinforcement agent Concentration (% w / v) Maximum pressure before rupture (Pa) Maximum tension before breakage (%) Gel formation? Sorbitol 12 892 18 Yes - 2 phases Sperm 0,1 No 1 1409 24 Yes Chitosan (High viscosity) 0,1 No 1 4361 28 Yes Chitosan (Low viscosity) 0,1 No 1 1673 23 Yes 5 9499 32 Yes 10 6322 29 Yes Agarose 1 1678 25 Yes 5 8287 35 Yes 10 7549 32 Yes Cellulose 10 12273 41 Yes Barium sulfate 5 3886 26 Yes 20 6182 24 Yes 80 5961 27 Yes Calcium carbonate 20 4362 28 Yes Sodium Dodecyl Sulfate (SDS) 0,1 1348 26 Yes 1 2773 23 Yes Phosphatidylcholine 0,1 658 14 Yes 10 833 21 Yes 10 1314 22 Yes Chitosan LV - Barium sulfate 5 - 5 9126 26 Yes EXAMPLE 3: GELDING TIME OF HYDROGELS CONTAINING A STRENGTHENING AGENT

[0053] In this example, gelation times were determined for alginate gel compositions comprising a strengthening agent, capable of withstanding a maximum stress of at least 4000 Pa. This gelation time should not be less than 5 minutes so that the patient has time to drink the composition according to the invention and for it to be absorbed into the stomach. These compositions are those of Example 2, which include chitosan HV (0.1 and 1% w / v) and LV (0.1, 1, 5 and 10% w / v), agarose (1, 5 and 10% w / v), cellulose (10% w / v), barium sulfate (1, 5, 10 and 20% w / v), calcium carbonate (20% w / v) and chitosan LV - barium sulfate (both at 5% w / v). Initially, the setting time of these reinforced gels was determined. To this end, once mixed, the powders are added to distilled water and then the solution is stirred with a spatula for a few seconds.The aqueous dispersion is stirred at room temperature on a rocker plate set at 10 rpm. Every minute, the container is tilted 90° to check whether the solution is still flowing. Measurements are stopped after 25 minutes. This time limit was chosen taking into account that half the gastric emptying time after water ingestion is 13 ± 1 min.

[0054] The results are shown at the figure 3As shown in this figure, chitosan, particularly LV chitosan, is of greatest interest because it has little impact on setting time and provides good mechanical strength. Calcium carbonate also has little impact on gelation kinetics but offers less mechanical reinforcement. Conversely, cellulose and barium sulfate induce high resistance to stress / deformation but trigger rapid gelation. Barium sulfate is also of interest for its contrast-enhancing properties in fluoroscopy and computed tomography. Finally, a composite based on LV chitosan and barium sulfate has good mechanical properties but still forms a gel too quickly. However, because it combines the mechanical properties of chitosan and the contrast-enhancing properties of barium sulfate, this composite could be a good compromise. EXAMPLE 4: STABILITY OF IN VITRO HYDROGELS AND IMPACT OF THE REINFORCING AGENT

[0055] Hydrogels according to the invention were placed for 4 months in simulated gastric juice oscillating from an extremely acidic pH, at pH = 2.4 for 3 hours or 16 hours, to a nearly neutral pH of 6.4 for 3 hours, as schematically illustrated in the figure 4A Two transitions per day (3:00am -> 3:00am -> 3:00am -> 4:00pm) were carried out for 4 consecutive months.

[0056] To the figure 4BFigure 1 illustrates the results obtained in terms of percentage weight loss over time. Hydrogel 1 is a hydrogel containing the alginate polymer polymerized by the cation in aqueous solution in the presence of a strengthening agent. Hydrogel 2 is the hydrogel from Example 2, including a strengthening agent. Hydrogel 3 is formed from a polymerized alginate, without a strengthening agent, containing a radiopaque agent, namely BaSO4. Hydrogel 4 is formed from a polymerized alginate, without a strengthening agent and without a radiopaque agent.

[0057] As can be seen in the curves shown in the figure 4B , only hydrogels 1 and 2 containing a strengthening agent show a resistance over time that is almost constant during the 4 months of the experiment.

[0058] In the absence of such an agent, the stability of the hydrogel is not guaranteed over time. EXAMPLE 5: STABILITY OF HYDROGELS ACCORDING TO pH

[0059] The physicochemical stability of hydrogels according to the invention in simulated gastric fluid (pH 2.5 and 6.4) was evaluated by measuring their weight and volume weekly for a period of six weeks. Four gel compositions were compared in this study: the basic composition of Example 1, as well as compositions containing 10% w / v chitosan LV, 10% w / v agarose, and 10% w / v BaSO4.

[0060] As shown to Figures 5A And 5BThe composition of Example 1 (10% w / v) shows a rapid but variable decrease in weight and a slower decrease in volume. This temporal evolution corresponds to the buoyancy of these gels. The composition containing chitosan LV (10% w / v) is of interest, and we observe that the weight and volume increase slowly over time. However, the hydrogel thus formed is not capable of floating. The hydrogel containing agarose (10% w / v) is somewhat stable for four weeks before a degradation in weight and volume is observed. This gel is not capable of floating, just like the previous gel. The hydrogel containing barium sulfate (10% w / v) exhibits a slow and constant decrease in its weight and volume and, like the other gels, is not capable of floating. EXAMPLE 6: EX-VIVO STABILITY AND IMPACT OF THE REINFORCING AGENT: IN VITRO ARTIFICIAL DIGESTION

[0061] The hydrogel composition according to Example 2 was subjected to stability tests using artificial digestion tests. in vitro. A quantity of hydrogel corresponding to a volume of 50 mL was placed for 14 consecutive days at 37°C with stirring in a digestion buffer, at pH = 3, with or without foods containing high levels of calcium chelators, namely lentils, which contain phytic acid, spinach, which contains oxalic acid, or orange juice, which contains citric acid. As shown in the figure 6 The hydrogel according to the invention exhibits perfect resistance to the extreme conditions associated with digestion (acidic pH and natural calcium chelators provided by food), the control being carried out when said hydrogel does not contain calcium chelators. EXAMPLE 7: HYDROGEAL BLOTTABILITY

[0062] The foaming and swelling capacities of the hydrogels according to the invention are related to the content and reactivity of the buoyancy agents. Calcium carbonate has been used successfully to produce CO₂ and aerogels. By adopting the basic composition of Example 1, an acidic medium proved sufficient to trigger the dissolution of calcium carbonate and the flotation of the gels. Alternatively, the calcium carbonate system can be replaced by either a gluconolactone-sodium bicarbonate system or a yeast-sucrose system. All three systems are presented in figures 7A, 7B and 7C .

[0063] There figure 7A is a photograph showing the gel obtained according to the composition of Example 1, in an acidic solution containing HCl. As shown in this figure, the gel floats, in vitro, in this acidic solution. The figure 5B is an endoscopic view of two balloons of the same gel. in vivoin the stomach of a mini-pig, 1 week after ingestion of the hydrogel composition. Similarly, the hydrogel, or rather the hydrogel-aerogel hybrid, floats in the stomach of this mini-pig.

[0064] The calcium carbonate system is simple to implement and safe. It has been studied with hydrogels containing chitosan as a strengthening agent. All the gels tested proved to be mechanically stable. However, at pH 2.5, after one day, none of them floated, although some bubbles were observed on their surface. In contrast, immediately after incubation in an acidified medium at pH 1.2, all the tested samples floated rapidly. After seven days, no change was observed.

[0065] The gluconolactone-sodium bicarbonate system illustrated in the figure 7BThis system is based on the hydrolysis of lactone to produce gluconic acid, which in turn reacts with sodium bicarbonate to produce CO2. It was tested with chitosan-reinforced alginate gels. The results show that the chitosan-reinforced gels are not significantly weakened by the foaming system and some even float on the first day of incubation at pH 2.5. The presence of chitosan improves the elastic properties of the gels and prevents weakening and destruction induced by gas expansion. The swelling of the gels is inversely proportional to the chitosan concentration.

[0066] The yeast-sucrose system (Saccharomyces cerevisiae / sucrose) is commonly used in baking to ensure the expansion of bread dough before it solidifies during baking. In this bio-fermentation process, CO₂ is produced by the consumption of sucrose followed by aerobic or anaerobic glycolysis. This system was tested with chitosan-reinforced alginate gels. For all compositions, the gels were mechanically stable, likely due to the cross-linking action of the chitosan. From the first day, some of the tested compositions, containing 0.6% and 0.9% (w / v) of dry yeast, were able to generate sufficient gas to form an aerogel. After three days of incubation, hydrogels containing 0.3% (w / v) of dry yeast were also able to float.

Claims

1. Hydrogel composition for oral administration comprising: an alginate polymer that forms a gel in an aqueous solution, in the presence of a cation; a cation for polymerisation of the alginate polymer in an aqueous solution; an aqueous solution, in a sufficient quantity; an agent for dissolving the said alginate polymer in the aqueous solution; a gelation retardig agent; a floatation agent for forming bubbles of CO2 in the hydrogel composition; and an agent for strengthening the mechanical structure of the hydrogel, the hydrogel formed by means of the said hydrogel composition being dissolved by means of an orally administered final dissolving agent.

2. Composition according to Claim 1, characterised in that the strengthening agent is of the polymeric type, forming macromolecules incorporated into the hydrogel.

3. Composition according to one of Claims 1 or 2, characterised in that it further includes a radiopaque agent.

4. Composition according to one of Claims 1, 2 or 3, characterised in that the alginate polymer is a sodium alginate polymer, and in that the cation is calcium.

5. Composition according to one of the preceding Claims, characterised in that the agent for dissolving the alginate polymer in the aqueous solution is sucrose.

6. Composition according to one of the preceding Claims, characterised in that the gelation retarding agent is Na2HPO4.

7. Composition according to one of the preceding Claims, characterised in that the agent for strengthening the mechanical structure of the hydrogel is selected from sorbitol, spermine, chitosan, agarose, sodium dodecyl sulfate, phosphatidylcholine, microcrystalline cellulose.

8. Composition according to one of the preceding Claims, characterised in that the radiopaque agent is selected from compounds including barium, for example BaSO4, and compounds including iodine.

9. Composition according to one of the preceding Claims, characterised in that the final dissolving agent is selected from citrates, calcium chelators, for example sodium citrate, citric acid or EDTA.

10. Composition according to one of the preceding Claims, characterised in that the floatation agent is CaCO3, glucono-δ-lactone or a microorganism.

11. Composition according to one of the preceding Claims, characterised in that it comprises 0.5 to 5% sodium alginate with a viscosity of between 20-200 mPa.s, 1 to 3% CaSO4, 0.10 to 0.20% Na2HPO4, 8 to 15% sucrose, 2 to 8% CaCO3 or 0.1 to 2% yeast, 0.5% to 8% BaSO4, and 0.5 to 8% chitosan with a viscosity of between 10 and 50 mPa.s or 0.5 to 8% cellulose, the percentages being weight percentages given in g / 100 ml.

12. Use of a composition according to one of the preceding Claims for the treatment of overweight individuals with a Body Mass Index greater than or equal to 25 kg / m2.

13. Use according to Claim 12 for the treatment of obese individuals with a Body Mass Index greater than or equal to 30 kg / m2.

14. Use of a composition according to one of Claims 1 to 11 for delivering pharmaceutical or nutritional ingredients into the stomach of an individual.

15. A kit comprising a composition according to one of Claims 1 to 11 and an orally administered dissolving agent.