Gastric space-occupying hydrogel tablet as well as preparation method and application thereof

Abstract

The invention discloses a stomach space-occupying hydrogel tablet as well as a preparation method and application thereof. The preparation method comprises the following steps: carrying out cross-linking reaction on a hydrophilic polysaccharide compound and / or a derivative thereof and a water-soluble polymer to prepare hydrogel; crushing to obtain gel base material particles; and mixing the gel base material particles with an adhesive, sodium alginate, calcium chloride and ethanol, granulating, and tabletting. The gastric space-occupying hydrogel tablet provided by the invention takes a hydrophilic polysaccharide compound and / or a derivative thereof and a water-soluble polymer as cores, a three-dimensional network structure gel is formed through a cross-linking reaction, the three-dimensional network structure gel and other functional combinations are mixed, crushed and tableted to prepare the tablet, a core functional system of the gastric space-occupying hydrogel tablet is composed of a hydrophilic cross-linked gel base material and an adhesive, and the core functional system of the gastric space-occupying hydrogel tablet is composed of the hydrophilic cross-linked gel base material and the adhesive. The components can be singly selected or compounded for use according to performance requirements, so that collaborative optimization of mechanical strength, space occupying effect and biocompatibility is realized.

Description

Technical Field

[0001] This invention belongs to the field of functional food technology, and in particular relates to a gastric space-occupying hydrogel tablet, its preparation method and application. Background Technology

[0002] Obesity and overweight have become a global public health problem. Gastric displacement technology is one method for treating obesity. It induces a feeling of fullness by physically filling the stomach and is a safe and effective non-drug weight management approach. However, existing products have many technical bottlenecks that make it difficult to meet the needs of clinical applications. 1. Endoscopic implantable gastric balloon: As a traditional invasive product, it requires professional hospital equipment and endoscopic operation to complete the implantation and removal, and needs to be replaced regularly within 6 months. Patients experience obvious foreign body sensation in the stomach after implantation, and are prone to adverse reactions such as abdominal pain and vomiting during the adaptation period. Long-term placement also faces safety risks such as intestinal obstruction caused by balloon rupture, gastric ulcers caused by gastric wall friction, and even gastric perforation. Clinical tolerance is poor.

[0003] 2. Oral expansion products (such as GVR100 and similar preparations): These products use dietary fiber microspheres as the core. Although they do not require invasive operation, their expansion stability in the gastric acid environment is insufficient. They need to be taken with a lot of water to achieve the expected space-occupying effect, which is inconvenient for patients. In addition, the residence time in the stomach is short (usually 4-6 hours), and they need to be taken 2-3 times a day, resulting in poor compliance.

[0004] 3. Expandable capsules from abroad (such as Epitomee capsules): These products form a triangular three-dimensional structure in the stomach after oral administration to occupy space. However, their manufacturing process is complex and relies on precision folding and pH-responsive material technology. There is a foreign technology monopoly, which leads to high product prices. At the same time, the formation and disintegration process of the three-dimensional rigid structure is not controllable enough, and there is still a potential risk of gastrointestinal obstruction.

[0005] 4. Synthetic polymer-based research products: Some studies use synthetic polymer materials such as polyacrylic acid and polyacrylamide to construct gastric spacer systems. However, these materials pose risks of residual acrylic acid and acrylamide monomers and initiator residues. Long-term intake may cause gastrointestinal irritation and potential toxic side effects, and their biosafety is difficult to guarantee.

[0006] In summary, the core challenges of existing gastric spacer technologies lie in: insufficient material safety, high process complexity or technological monopoly, poor ease of use, and significant risks such as gastrointestinal obstruction and residual toxicity. Therefore, developing a gastric spacer product that is safe in raw materials, has controllable processes, no technological barriers, is easy to use, and exhibits excellent biocompatibility has become an urgent need in the weight management field. Summary of the Invention

[0007] To address the aforementioned technical problems, this invention provides a gastric space-occupying hydrogel tablet, its preparation method, and its application. This invention uses food-grade materials as the core, and safely modifies them to prepare the gastric space-occupying hydrogel tablet.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows: On one hand, the present invention provides a method for preparing a gastric space-occupying hydrogel tablet, comprising the following steps: (1) A hydrogel is prepared by crosslinking a hydrophilic polysaccharide compound and / or its derivatives and a water-soluble polymer; the hydrogel substrate particles are obtained by pulverizing. (2) The gel substrate particles are mixed with adhesive, sodium alginate, calcium chloride and ethanol and granulated; (3) The granules prepared in step (2) are compressed into tablets to obtain the gastric spacer hydrogel tablets; In step (1), the hydrophilic polysaccharide compound and its derivatives are konjac gum and / or cellulose derivatives; the water-soluble polymer is sodium polyacrylate.

[0009] In the technical solution of the present invention, hydrophilic polysaccharide compounds such as konjac gum have high swelling properties and can achieve cross-linking polymerization under photoinitiation. The hydrogel prepared by it has strong cross-linking stability, and can ultimately achieve high occupancy effect and large-scale production of gastric space-occupying hydrogel tablets.

[0010] In the technical solution of the present invention, cellulose derivatives are widely available and have low raw material costs. They can be cross-linked by thermal cross-linking / acid-base catalytic cross-linking, which can reduce costs and control the preparation of hydrogels without the need for special equipment.

[0011] In the technical solution of the present invention, the sodium polyacrylate is co-crosslinked with hydrophilic polysaccharide compounds and / or their derivatives, which can enhance the mechanical strength of the hydrogel, resist gastric motility damage, and improve the stability of the tablet.

[0012] Preferably, the cellulose derivative is selected from one or more of sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, and hydroxyethyl cellulose. In the technical solution of the present invention, in step (1), when preparing hydrogels using a variety of different hydrophilic polysaccharide compounds and / or their derivatives, there are no particular restrictions on the ratio of the various hydrophilic polysaccharide compounds and / or their derivatives.

[0013] In a preferred embodiment, the preparation process of the hydrogel in step (1) is as follows: i. The hydrophilic polysaccharide compound and / or its derivatives are konjac gum: Acrylated konjac gum was prepared; an aqueous mixture containing acrylated konjac gum and sodium polyacrylate was prepared; a photoinitiator was added to perform ultraviolet crosslinking; Preferably, the preparation method of the acrylated konjac gum is as follows: S1. Konjac gum is washed with anhydrous ethanol reflux 1-3 times, sieved, and then dissolved in water to prepare konjac gum solution; Preferably, the time for each anhydrous ethanol reflux washing is 1 to 3 hours; Preferably, the sieving is performed through an 80-100 mesh sieve; Preferably, the konjac gum solution contains 1% to 2% konjac gum by mass.

[0014] S2. After adding triethylamine and acryloyl chloride, react at a constant temperature of 30~50℃ for 4~5 hours; then dry under vacuum at 40~60℃ for 6~8 hours to obtain acrylated konjac gum. Preferably, the triethylamine is added at 25-30°C; Preferably, the molar ratio of hydroxyl groups to triethylamine in the konjac gum is 1:1 to 1.2; the molar ratio of hydroxyl groups to acryloyl chloride in the konjac gum is 1:1.1 to 1.3. Preferably, after adding triethylamine, stir for 8-10 minutes and then slowly add acryloyl chloride dropwise.

[0015] In some specific embodiments, step S2 further includes washing with anhydrous ethanol, filtration, and washing until the pH of the filtrate is neutral before vacuum drying.

[0016] In the technical solution of the present invention, the acrylated konjac gum prepared by the above steps was found to have a double bond grafting rate of 25% to 40% by nuclear magnetic resonance hydrogen spectroscopy.

[0017] Preferably, the mass ratio of the acryloyl konjac gum to sodium polyacrylate is (3~5):(2~4). Preferably, the total mass concentration in the aqueous mixture is 8% to 12%.

[0018] In some specific embodiments, the photoinitiator is Irgacure 2959; the ultraviolet crosslinking uses a 365 nm UV LED lamp with a power of 80~120W and an irradiation distance of 15~20 cm; the ultraviolet crosslinking temperature is 25~35℃; and the ultraviolet crosslinking time is 10~30 minutes. Preferably, the mass of the photoinitiator is 0.1% to 0.5% of the total mass of the water mixture.

[0019] ii. The hydrophilic polysaccharide compound and / or its derivatives are cellulose derivatives: Prepare an aqueous mixture of cellulose derivatives and citric acid or malic acid, and react at 60~120℃ for 2~4 hours; Preferably, the mass ratio of the cellulose derivative to citric acid or malic acid is (5-10):(1-2). Preferably, the total mass fraction of the water mixture is 10% to 15%.

[0020] In a preferred embodiment, in step (1), the pulverization is carried out using a high-speed pulverizer; the high-speed pulverizer operates at a speed of 10,000 to 15,000 rpm; in the technical solution of the present invention, particles with a particle size of 0.05 to 0.1 cm can be obtained through the above pulverization. Preferably, the pulverization process further includes vacuum drying and sieving; Preferably, the vacuum drying is performed at 40~60℃ until the moisture content is ≤10%; Preferably, the vacuum degree of the vacuum drying is -0.08 to -0.09 MPa; Preferably, the sieving is performed through a 10-20 mesh sieve; in the technical solution of the present invention, sieving can remove agglomerates.

[0021] In a preferred embodiment, in step (2), the adhesive is selected from one or more of polyvinyl acetate adhesives, cellulose derivative adhesives, and starch adhesives, preferably polyvinyl acetate adhesives or a mixture of polyvinyl acetate adhesives and other types of adhesives; In some specific embodiments, when the adhesive is a polyvinyl acetate adhesive used in combination with other types of adhesives, the weight percentage of the polyvinyl acetate adhesive in all adhesives is ≥0.5%.

[0022] In some specific embodiments, the povidone adhesives include PVP K17, PVP K30, PVP K90, etc.; the molecular weight of the povidone adhesives is 10,000~130,000 Da; the povidone adhesives have strong adhesive power and can rapidly swell and disintegrate upon contact with gastric acid, thus improving the stability and disintegration rate of gastric space-occupying hydrogel tablets.

[0023] In some specific embodiments, the cellulose derivative adhesive may include hydroxypropyl methylcellulose (HPMC E5, HPMC E15, etc.) and hydroxypropyl cellulose (HPC L, HPC M, etc.); in some embodiments, the cellulose derivative adhesive is added in the form of an aqueous solution, the concentration of which may be 2% and the viscosity may be 5~15 mPa·s; the cellulose derivative adhesive has moderate adhesive strength, which can improve the storage stability and low hygroscopicity of the gastric spacer hydrogel tablet.

[0024] In some specific embodiments, the starch-based adhesive may include pregelatinized starch, dextrin, sodium carboxymethyl starch (CMS-Na), etc.; the degree of gelatinization of the pregelatinized starch is ≥90%; the degree of crosslinking of the sodium carboxymethyl starch is ≤10%; the starch-based adhesive has mild bonding force and can assist in disintegration.

[0025] Preferably, the degree of crosslinking of the polyvinyl acetate adhesive is 15% to 25%.

[0026] Preferably, the sodium alginate is high-viscosity sodium alginate with a viscosity of 200~300 mPa·s; and the content of guluronic acid in the sodium alginate is ≥60%.

[0027] Preferably, the mass ratio of the gel substrate particles to the adhesive, sodium alginate, and calcium chloride is (50-70):(5-10):(8-15):(2-5).

[0028] Preferably, an anti-adhesion agent is added during the mixing and granulation process; the anti-adhesion agent is magnesium stearate; the mass ratio of the gel substrate particles to the anti-adhesion agent is (30-50):(1-2).

[0029] Preferably, the mass of the ethanol is 10-15% of the total mass of the solid components in the remaining components.

[0030] In a preferred embodiment, in step (2), the rotation speed of the mixing and granulation is 30~50 rpm; the mixing and granulation time is 10~15 minutes.

[0031] In the technical solution of the present invention, compressible particles with a particle size of 0.8~1.2 mm are prepared by mixing and granulation, and the moisture content of the particles is determined and controlled to be 3%~6% by Karl Fischer method.

[0032] In a preferred embodiment, in step (3), the pressure of the tablet is 5~10 MPa.

[0033] In some specific embodiments, the tablets obtained by compression have a diameter of 8-12 mm, a tablet weight of 0.5-1.0 g, a hardness of 3-6 kgf, and a disintegration time of <30 minutes in artificial gastric juice.

[0034] In another aspect, the present invention provides a gastric spacer hydrogel tablet prepared by the above preparation method.

[0035] In the technical solution of this invention, the gastric space-occupying hydrogel tablets, through in vitro verification experiments using a transparent human stomach model, show that: under simulated human gastric environment (37℃, pH 1.2 artificial gastric fluid), they begin to disintegrate and form hydrogel clusters within 0.5 h; the hydrogel clusters are morphologically stable after 1 h; they maintain a good space-occupying state for 3-9 h; particles begin to be slowly released after 12 h; and smooth discharge from the pylorus is achieved after 16 h. Compared with traditional hydrogel tablets, they have advantages such as uniform particle size, strong resistance to gastric motility, long duration of space-occupying effect, and good storage stability. Furthermore, they can be adapted to different clinical needs through flexible compounding of substrate and binder, and can be widely used in fields such as long-acting intragastric space-occupying, targeted drug delivery, and assisted feeding control.

[0036] In another aspect, the present invention provides the application of the above-described preparation method or the above-described gastric space-occupying hydrogel tablet in the preparation of obesity control or weight management products.

[0037] The above technical solution has the following advantages or beneficial effects: 1. The gastric space-occupying hydrogel tablets provided by this invention overcome the risks of invasive operation dependence, material safety hazards, process monopoly, poor convenience of administration and gastrointestinal obstruction of existing gastric space-occupying products. The gastric space-occupying hydrogel tablets prepared with safe and non-toxic raw materials, controllable process, convenient use, stable space-occupying and no risk of blockage have good application prospects.

[0038] 2. The gastric space-occupying hydrogel tablet provided by the present invention uses hydrophilic polysaccharide compounds and / or their derivatives and water-soluble polymers as the core, which are cross-linked to form a three-dimensional network structure gel. After being mixed with other functional combinations, the gel is pulverized and compressed to obtain tablets. Its core functional system consists of "hydrophilic cross-linked gel substrate + binder". Acid-responsive excipient PVP-P can also be used as a binder. Each component can be selected individually or used in combination according to performance requirements, thereby achieving synergistic optimization of mechanical strength, space-occupying effect and biocompatibility.

[0039] The present invention has the following advantages over the prior art: 1. The raw materials of this invention have high safety: all components are food-grade materials, and the monomer residue is eliminated after purification treatment after acrylyl modification. The photoinitiated polymerization process is safe and controllable, with no potential toxic side effects, and has excellent biocompatibility and gastrointestinal tolerance. 2. The process of this invention is controllable and non-monopolistic: the preparation process is compatible with existing tableting equipment, the technical path is clear, no precision special equipment is required, breaking the foreign technology monopoly and reducing production costs; 3. This invention is convenient to use: it can be taken orally once a day without the need for large amounts of water or professional hospital procedures, resulting in high patient compliance; 4. Balance between safety and effectiveness: The characteristics of low expansion rate in the esophagus, rapid expansion and occupancy in the stomach, and controllable degradation and excretion in gastric acid completely avoid the risks of esophageal obstruction and pyloric obstruction, while achieving long-term stable occupancy, making it a promising candidate for weight management applications. Attached Figure Description

[0040] Figure 1 This is a schematic diagram illustrating the preparation and application process of the gastric space-occupying hydrogel tablet in this embodiment of the invention.

[0041] Figure 2 The test chart of the gastric space-occupying hydrogel tablet in Example 1 of the present invention shows the trend of change in water and artificial gastric fluid at different time periods.

[0042] Figure 3 This is a test graph showing the changing trend of the gastric spacer hydrogel tablet in artificial gastric fluid in Embodiment 1 of the present invention.

[0043] Figure 4 This is a test graph showing the changing trend of the gastric space-occupying hydrogel tablet in a simulated gastric environment at different time periods in Embodiment 1 of the present invention.

[0044] Figure 5 This is a test chart showing the changing trend of the gastric spacer hydrogel tablet in water and artificial gastric fluid at different time periods in Embodiment 2 of the present invention.

[0045] Figure 6 This is a test graph showing the changing trend of the gastric spacer hydrogel tablet in artificial gastric fluid in Embodiment 2 of the present invention. Detailed Implementation

[0046] The following embodiments are merely some, not all, of the embodiments of the present invention. Therefore, the detailed descriptions of the embodiments provided below are not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0047] In this invention, unless otherwise specified, all equipment and raw materials are commercially available or commonly used in the industry. The methods described in the following embodiments are conventional methods in the art, unless otherwise specified.

[0048] Example 1 This embodiment uses acrylated konjac gum as the main component to prepare a gastric space-occupying hydrogel tablet. Its preparation and application process are as follows: Figure 1 As shown, the specific preparation process is as follows: 1. Preparation of Acrylated Konjac Gum: Food-grade konjac gum was washed twice under reflux with anhydrous ethanol (1 hour each time), sieved through an 80-mesh sieve, and dissolved in deionized water at a 1% (w / w) concentration. Triethylamine (an acid-binding agent, with a molar ratio of hydroxyl groups in konjac gum to triethylamine of 1:1.05) was added at 30°C, and the mixture was stirred for 10 minutes. Acryloyl chloride (with a molar ratio of hydroxyl groups in konjac gum to acryloyl chloride of 1:1.1) was slowly added dropwise, and the mixture was reacted at 30°C for 4 hours. The reaction solution was then precipitated with three times its volume of anhydrous ethanol, filtered, and washed with anhydrous ethanol until the pH of the filtrate reached 7. The filtrate was then vacuum-dried at 40°C for 8 hours to obtain acrylated konjac gum. The acrylated konjac gum prepared in this example had a double bond grafting rate of 40% as determined by 1H NMR spectroscopy.

[0049] 2. Preparation of hydrogels: Acrylated konjac gum and sodium polyacrylate were mixed at a mass ratio of 3:4 and dissolved in deionized water to prepare a mixture with a total mass concentration of 12%. Irgacure 2959 (photoinitiator) was added at 0.5% of the total mass of the mixture. The mixture was then crosslinked and formed at 35°C for 25 minutes under irradiation with a 120W 365 nm UV LED lamp (irradiation distance of 15 cm).

[0050] 3. Preparation of gel substrate particles: The hydrogel was pulverized into uniform particles with a particle size of 0.05 cm using a high-speed pulverizer at 15,000 rpm, and then vacuum dried at 40°C to a moisture content of 2% (vacuum degree -0.08 MPa). The particles were then passed through a 20-mesh sieve to remove lumps, thus obtaining the gel substrate particles.

[0051] 4. Mixed granulation: Pretreatment: Pass food-grade calcium chloride with a purity of ≥99% through an 80-mesh sieve; evenly disperse 10 parts by weight of PVP K17 (crosslinking degree of 25%) with 13.1 parts by weight of water; 50 parts by weight of gel matrix particles were mixed with the above-mentioned PVP K17 dispersion, 2 parts by weight of magnesium stearate (anti-adhesion agent), 15 parts by weight of sodium alginate (high viscosity sodium alginate with a viscosity of 260 mPa·s and a guluronic acid content of 60%), and 2 parts by weight of calcium chloride. Then anhydrous ethanol (10% of the total solid mass) was added and stirred in a three-dimensional motion mixer (30 rpm) for 10 minutes to prepare compressible particles with a particle size of 1.2 mm. Approximately 1000 particles with an average weight of 1.6 mg were prepared, and the water content was controlled at 4% (determined by Karl Fischer method).

[0052] 5. Tableting: Compressible granules are placed in a tablet press (with a die diameter of 12 mm) and compressed into tablets at a pressure of 7 MPa, with a tablet weight of 0.5~1.0 g and a hardness of 3~6 kgf.

[0053] The gastric spacer hydrogel tablets prepared in this embodiment have an expansion rate of less than 1.5 times in pure water after 0.5 hours, thus posing no risk of esophageal obstruction; in artificial gastric fluid at pH 1.2, the swelling rate is 5 times after 2 hours, and the spacer remains stable for 8 hours; after degradation, the particle size is less than 5 mm, allowing it to pass smoothly through the pylorus.

[0054] This embodiment investigated the changing trends of gastric space-occupying hydrogel tablets in water at 37°C and in an artificial gastric fluid environment, specifically as follows: Figure 2 As shown in the images (in each small image, the left side is the aqueous solution and the right side is the artificial gastric fluid): the gastric space-occupying hydrogel tablets can rapidly disintegrate and expand in artificial gastric fluid within a short period of time. Compared with the simple aqueous solution, the tablets show a better space-occupying effect in artificial gastric fluid.

[0055] This embodiment investigated the changing trend of gastric space-occupying hydrogel tablets in simulated gastric fluid at 37°C. Figure 3 As shown in the figure, the prepared gastric space-occupying hydrogel tablets were placed in simulated gastric fluid. It can be seen that the tablets exhibited disintegration and swelling after 5 minutes; with the extension of time, the hydrogel clumps stabilized after 30 minutes; and after 14 hours, the gastric space-occupying hydrogel particles in the tablets had been decomposed, with a particle size of less than 5 mm. Therefore, the gastric space-occupying hydrogel tablets provided by this invention can smoothly pass through the pylorus and be excreted from the body after ingestion.

[0056] Figure 4 The diagram shows a stomach model, which allows for a direct observation of the changes in the state of the gastric space-occupying hydrogel tablet as it enters the stomach, simulating the entire process from ingestion to excretion. As can be seen from the diagram, the gastric space-occupying hydrogel tablet begins to disintegrate and form hydrogel clusters within 5 minutes; at 30 minutes, the hydrogel clusters are stable and maintain a good space-occupying state; and at 14 hours, it begins to slowly release particles. Therefore, the gastric space-occupying hydrogel tablet prepared in this invention can pass through the pylorus and be smoothly excreted.

[0057] Further verification shows that when the gastric space-occupying hydrogel tablets prepared in this embodiment are used as products for obesity control or weight management, they are taken once a day, one tablet each time, without the need for drinking a large amount of water, 50-100mL of warm water is sufficient.

[0058] Example 2 This embodiment uses cellulose derivative sites as the main component to prepare gastric space-occupying hydrogel tablets, and the preparation and application process is as follows: Figure 1 As shown, the specific preparation process is as follows: 1. Preparation of hydrogels Sodium carboxymethyl cellulose and citric acid were mixed at a mass ratio of 5:2 and dissolved in deionized water to prepare a mixture with a total mass concentration of 15%. The mixture was reacted at 120°C for 4 hours. After cooling, precipitation, washing and drying, a cross-linked gel was obtained. 2. Preparation of gel substrate particles: The hydrogel was pulverized into uniform particles with a particle size of 0.05 cm using a high-speed pulverizer at 15,000 rpm, and then vacuum dried at 40°C to a moisture content of 2% (vacuum degree -0.08 MPa). The particles were then passed through a 20-mesh sieve to remove lumps, thus obtaining the gel substrate particles.

[0059] 3. Mixing and granulation: Pretreatment: Pass food-grade calcium chloride with a purity of ≥99% through an 80-mesh sieve; evenly disperse 10 parts by weight of PVP K17 (crosslinking degree of 25%) with 13.1 parts by weight of water; 50 parts by weight of gel matrix particles were mixed with the above-mentioned PVP K17 dispersion, 2 parts by weight of magnesium stearate (anti-adhesion agent), 15 parts by weight of sodium alginate (high viscosity sodium alginate with a viscosity of 260 mPa·s and a guluronic acid content of 60%), and 2 parts by weight of calcium chloride. Then anhydrous ethanol (10% of the total solid mass) was added and stirred in a three-dimensional motion mixer (30 rpm) for 10 minutes to prepare compressible particles with a particle size of 0.8-1.2 mm. Approximately 1000 particles with an average weight of 1.6 mg were prepared, and the water content was controlled at 4% (determined by Karl Fischer method).

[0060] 5. Tableting: Compressible granules are placed in a tablet press (with a die diameter of 12 mm) and compressed into tablets at a pressure of 7 MPa, with a tablet weight of 0.5~1.0 g and a hardness of 3~6 kgf.

[0061] This embodiment investigated the changing trends of gastric space-occupying hydrogel tablets in water at 37°C and in an artificial gastric fluid environment, specifically as follows: Figure 5 As shown in the images (in each small image, the left side is the aqueous solution and the right side is the artificial gastric fluid): the gastric space-occupying hydrogel tablets can rapidly disintegrate and expand in artificial gastric fluid within a short period of time. Compared with the simple aqueous solution, the tablets show a better space-occupying effect in artificial gastric fluid.

[0062] This embodiment investigated the changing trend of gastric space-occupying hydrogel tablets in simulated gastric fluid at 37°C. Figure 6As shown in the figure, the prepared gastric space-occupying hydrogel tablets were placed in simulated gastric fluid. It can be seen that the tablets exhibited disintegration and swelling after 5 minutes; with the extension of time, the hydrogel clumps stabilized after 30 minutes; and after 14 hours, the gastric space-occupying hydrogel particles in the tablets had been decomposed, with a particle size of less than 5 mm. Therefore, the gastric space-occupying hydrogel tablets provided by this invention can smoothly pass through the pylorus and be excreted from the body after ingestion.

[0063] Further verification shows that when the gastric space-occupying hydrogel tablets prepared in this embodiment are used as products for obesity control or weight management, they are taken once a day, one tablet each time, without the need for drinking a large amount of water, 50-100 mL of warm water is sufficient.

[0064] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing a hydrogel tablet for gastric space-occupying lesions, characterized in that, Includes the following steps: (1) A hydrogel is prepared by crosslinking a hydrophilic polysaccharide compound and / or its derivatives and a water-soluble polymer; the hydrogel substrate particles are obtained by pulverizing. (2) The gel substrate particles are mixed with adhesive, sodium alginate, calcium chloride and ethanol and granulated; (3) The granules prepared in step (2) are compressed into tablets to obtain the gastric spacer hydrogel tablets; In step (1), the hydrophilic polysaccharide compound and its derivatives are konjac gum and / or cellulose derivatives; the water-soluble polymer is sodium polyacrylate; Preferably, the cellulose derivative is selected from one or more of sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, and hydroxyethyl cellulose.

2. The preparation method according to claim 1, characterized in that, In step (1), the hydrophilic polysaccharide compound and / or its derivatives are konjac gum, and the preparation process of the hydrogel is as follows: Acrylated konjac gum was prepared; an aqueous mixture containing acrylated konjac gum and sodium polyacrylate was prepared; a photoinitiator was added to perform ultraviolet crosslinking; Preferably, the mass ratio of the acryloyl konjac gum to sodium polyacrylate is (3~5):(2~4). Preferably, the total mass concentration in the aqueous mixture is 8% to 12%; Preferably, the photoinitiator is Irgacure 2959; the ultraviolet crosslinking uses a 365 nm UV LED lamp with a power of 80~120W and an irradiation distance of 15~20 cm; the ultraviolet crosslinking temperature is 25~35℃; and the ultraviolet crosslinking time is 10~30 minutes. Preferably, the mass of the photoinitiator is 0.1% to 0.5% of the total mass of the water mixture.

3. The preparation method according to claim 2, characterized in that, The preparation method of the acrylated konjac gum includes the following steps: S1. Konjac gum is washed with anhydrous ethanol reflux 1-3 times, sieved, and then dissolved in water to prepare konjac gum solution; S2. After adding triethylamine and acryloyl chloride, react at a constant temperature of 30~50℃ for 4~5 hours; then dry under vacuum at 40~60℃ for 6~8 hours to obtain acrylated konjac gum. Preferably, in step S1, the time for each anhydrous ethanol reflux washing is 1 to 3 hours; Preferably, in step S1, the sieving is performed through an 80-100 mesh sieve; Preferably, in step S1, the konjac gum solution contains 1% to 2% konjac gum by mass. Preferably, in step S2, the triethylamine is added at 25-30°C; Preferably, in step S2, the molar ratio of hydroxyl groups to triethylamine in the konjac gum is 1:1 to 1.2; the molar ratio of hydroxyl groups to acryloyl chloride in the konjac gum is 1:1.1 to 1.

3. Preferably, in step S2, after adding triethylamine, the mixture is stirred for 8-10 minutes and then acryloyl chloride is slowly added dropwise; Preferably, step S2 further includes washing with anhydrous ethanol, filtration, and washing until the pH of the filtrate is neutral before vacuum drying.

4. The preparation method according to claim 1, characterized in that, The hydrophilic polysaccharide compound and / or its derivatives are cellulose derivatives, and the preparation process of the hydrogel is as follows: Prepare an aqueous mixture of cellulose derivatives and citric acid or malic acid, and react at 60~120℃ for 2~4 hours; Preferably, the mass ratio of the cellulose derivative to citric acid or malic acid is (5-10):(1-2). Preferably, the total mass fraction of the water mixture is 10% to 15%.

5. The preparation method according to claim 1, characterized in that, In step (1), the pulverization is carried out using a high-speed pulverizer; the high-speed pulverizer operates at a speed of 10,000 to 15,000 rpm; Preferably, the pulverization process further includes vacuum drying and sieving; Preferably, the vacuum drying is performed at 40~60℃ until the moisture content is ≤10%; Preferably, the vacuum degree of the vacuum drying is -0.08 to -0.09 MPa; Preferably, the sieving is performed through a 10-20 mesh sieve.

6. The preparation method according to claim 1, characterized in that, In step (2), the adhesive is selected from one or more of polyvinyl acetate adhesives, cellulose derivative adhesives, and starch adhesives, preferably polyvinyl acetate adhesives or a mixture of polyvinyl acetate adhesives and other types of adhesives; Preferably, when the adhesive is a polyvinyl acetate adhesive used in combination with other types of adhesives, the weight percentage of the polyvinyl acetate adhesive in all adhesives is ≥0.5%; Preferably, the polyvinyl acetate adhesive is selected from at least one of PVP K17, PVP K30, and PVP K90; the molecular weight of the polyvinyl acetate adhesive is 10,000 to 130,000 Da. Preferably, the degree of crosslinking of the polyvinyl acetate adhesive is 15% to 25%; Preferably, the cellulose derivative adhesive is selected from at least one of hydroxypropyl methylcellulose and hydroxypropyl cellulose; Preferably, the starch-based binder is selected from at least one of pregelatinized starch, dextrin, and sodium carboxymethyl starch; the degree of gelatinization of the pregelatinized starch is ≥90%. Preferably, the sodium alginate is high-viscosity sodium alginate with a viscosity of 200~300 mPa·s; and the content of guluronic acid in the sodium alginate is ≥60%.

7. The preparation method according to claim 1, characterized in that, The mass ratio of the gel substrate particles to the adhesive, sodium alginate, and calcium chloride is (50-70):(5-10):(8-15):(2-5). Preferably, an anti-adhesion agent is added during the mixing and granulation process; the anti-adhesion agent is magnesium stearate; the mass ratio of the gel substrate particles to the anti-adhesion agent is (30-50):(1-2). Preferably, the mass of the ethanol is 10-15% of the total mass of the solid components in the remaining components.

8. The preparation method according to claim 1, characterized in that, In step (2), the rotation speed of the mixing and granulation is 30~50 rpm; the mixing and granulation time is 10~15 minutes; Preferably, in step (3), the pressure of the tablet is 5~10 MPa.

9. The gastric space-occupying hydrogel tablet prepared by any one of the preparation methods according to claims 1-8.

10. The application of the preparation method according to any one of claims 1-8 or the gastric spacer hydrogel tablet according to claim 9 in the preparation of obesity control or weight management products.

Images