Application of composition in preparation of medicine for intervening body weight rebound after weight loss treatment

Abstract

The present invention relates to the field of weight loss, and discloses an application of a composition in preparation of a drug for intervening weight rebound after weight loss treatment, the composition comprises a gastric content and a lipase inhibitor, and the new weight of a subject after weight loss can be effectively maintained by administration of the drug to the subject after weight loss.

Description

Technical Field

[0001] The present invention relates to the field of weight loss, in particular to the use of a composition in preparing a medicament for intervening in weight rebound after weight loss treatment. Background Art

[0002] Obesity has become a global public health crisis, exacerbating the burden of chronic diseases such as type 2 diabetes, cardiovascular disease, and fatty liver disease associated with metabolic dysfunction. Despite advances in treatment options (including lifestyle interventions, medications, and metabolic surgery), long-term weight maintenance remains difficult, with relapse rates exceeding 80% for all treatment modalities.

[0003] The article "Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension" introduces that GLP-1 receptor agonists (GLP-1RAs), represented by semaglutide, have become breakthrough therapies through dual mechanisms: central appetite suppression and delayed gastric emptying mediated by hypothalamic GLP-1 receptor activation, which can achieve an average weight loss of 17.3% over 68 weeks, accompanied by improved blood sugar control, reduced systolic blood pressure (4-6 mmHg), and attenuated cardiovascular risk markers. However, discontinuation of the drug will trigger rapid weight rebound, with 56% of patients returning to baseline weight or higher within 52 weeks of treatment. Clinical data show that two-thirds of the weight loss results are usually lost, and the cardiometabolic benefits also regress to pre-treatment levels - this phenomenon is driven by metabolic adaptation mechanisms such as rebound overeating, accelerated gastric emptying (from a 4-hour delay during treatment to a baseline of 1.5 hours), and suppression of leptin levels and a surge in ghrelin. In addition, the paper "Effects of once-weekly semaglutide vs once-daily canagliflozinon body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomized controlled clinical trial" introduced that semaglutide-induced weight loss includes a disproportionate reduction in lean body mass (accounting for 40% of the total weight loss), exacerbating sarcopenia and increasing the risk of fractures and metabolic rigidity during the rebound phase.

[0004] Existing strategies to prevent rebound eating (such as caloric restriction, behavioral counseling, or intermittent GLP-1RA administration) have limited effectiveness due to poor compliance and failure to address the neurohormonal drivers of rebound eating. Although effective, long-term use of GLP-1 receptor agonists can cause systemic risks (including 2.7% of users experiencing elevated pancreatic enzymes ≥3 times the upper limit of normal and gallbladder disease) and cannot address the underlying pathological mechanisms of weight relapse. Therefore, there is an urgent need to develop an innovative therapy that can effectively improve lean body mass, inhibit metabolic compensatory responses, and have a good safety profile to fill the current gap in the clinical management of rebound eating after discontinuation of GLP-1 receptor agonists.

[0005] Gastric bulking agents (such as cross-linked hydrophilic polymers) and lipase inhibitors (such as orlistat) reduce weight through local physical / biochemical mechanisms. Their safety advantages stem from their local effects on the gastrointestinal tract, rather than metabolic absorption. Gastric bulking agents physically occupy a space, prolonging satiety and achieving sustainable weight management without being absorbed or metabolized. Lipase inhibitors, on the other hand, block the hydrolysis of dietary fat by inhibiting lipase activity, reducing caloric intake without affecting protein digestion and absorption, resulting in a more metabolically protective effect than systemic appetite suppressants.

[0006] Both classes of drugs demonstrate minimal hepatotoxicity and renal instability and no central nervous system penetration, meeting the FDA's long-term safety standards for chronic weight management therapies. Summary of the Invention

[0007] Therefore, it is necessary to provide a composition for use in the preparation of a drug for preventing weight rebound after weight loss treatment, which can effectively maintain the new weight of the subject after weight loss, especially the problem of weight rebound after discontinuation of GLP-1 receptor agonists.

[0008] To achieve the above object, the present invention provides use of a composition in the preparation of a medicament for intervening in weight rebound after weight loss therapy, wherein the composition comprises a gastric content and a lipase inhibitor.

[0009] In some embodiments, the gastric volume-occupying substance is a substance or device that directly occupies the stomach physically or temporarily occupies the effective volume of the stomach after the stomach expands, and the lipase inhibitor is a drug that reduces fat absorption by inhibiting lipase activity.

[0010] In some embodiments, the gastric volume absorption rate does not exceed 20%.

[0011] In some embodiments, the lipase inhibitor is absorbed at a rate of no more than 20%.

[0012] In some embodiments, in an in vitro dissolution test, the cumulative dissolution rate of the lipase inhibitor in the composition within 45 minutes is ≥60%.

[0013] In some embodiments, the gastric contents reach at least 75% of the maximum expanded volume within 30 minutes in an in vitro simulated environment.

[0014] In some embodiments, the gastric contents maintain at least 75% of the maximum expanded volume for at least 1 hour in an in vitro simulated environment.

[0015] In some embodiments, the gastric content comprises a hydrogel.

[0016] In some embodiments, the hydrogel has a medium uptake ratio of at least 20 and an elastic modulus of 100 Pa to 10,000 Pa.

[0017] In some embodiments, the weight ratio of the hydrogel to the lipase inhibitor is greater than 10:1.

[0018] In some embodiments, the weight ratio of the hydrogel to the lipase inhibitor is 20:1-60:1.

[0019] In some embodiments, the weight ratio of the hydrogel to the lipase inhibitor is 25:1-50:1.

[0020] In some embodiments, the composition comprises 30 mg-120 mg of a lipase inhibitor.

[0021] In some embodiments, the medicament is used for subjects who have lost ≥5% of their body weight upon termination of weight loss therapy.

[0022] In some embodiments, the medicament is for initiation of use no more than 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, or 9 months after cessation of weight loss therapy.

[0023] In some embodiments, the drug is administered orally to the subject.

[0024] In some embodiments, the baseline value at the time of terminating the weight loss therapy is used as a reference value, and the drug is used to maintain or reduce the subject's body weight after terminating the weight loss therapy.

[0025] In some embodiments, the drug is used to slow down the rate of weight rebound in the subject after terminating the weight loss therapy, taking the baseline value at the time of terminating the weight loss therapy as the reference value.

[0026] In some embodiments, the baseline value at the time of terminating the weight loss therapy is used as a reference value, and the drug is used to maintain or increase the lean body mass percentage of the subject after terminating the weight loss therapy.

[0027] In some embodiments, the drug is used to slow down the rate of decline of the subject's lean body mass percentage after terminating the weight loss therapy, taking the baseline value at the time of terminating the weight loss therapy as a reference value.

[0028] In some embodiments, the weight loss therapy comprises pharmaceutical weight loss and / or surgical weight loss.

[0029] In some embodiments, the drug achieves weight loss through at least one of the following mechanisms: (1) inhibiting hunger signal transmission, (2) enhancing satiety perception, (3) delaying the emptying rate of gastric contents, (4) inhibiting lipid / carbohydrate absorption, (5) blocking fat cell storage pathways, or (6) promoting lipid catabolism.

[0030] In some embodiments, the drug for weight loss is selected from the following group: GLP-1 receptor agonists, GIP receptor agonists, amylin receptor agonists, GCGR agonists, centrally acting appetite suppressants (such as phentermine), sympathomimetic amines (benzphetamine, phenmethazine), lipase inhibitors, SGLT2 inhibitors (canagliflozin, dapagliflozin), and serotonin-norepinephrine reuptake inhibitors.

[0031] In some embodiments, the pharmaceutical weight loss comprises administering at least one drug that targets the GLP-1 receptor.

[0032] In some embodiments, the GLP-1 receptor agonist is selected from one or more of semaglutide, liraglutide, dulaglutide, beroglutide, tilpotide, or exenatide.

[0033] Another aspect of the present invention discloses the use of a composition in the preparation of a drug for intervening in weight rebound after weight loss therapy. The composition comprises a gastric content and a lipase inhibitor, and the drug is used to slow down the rate of increase in the subject's body fat percentage after terminating the weight loss therapy.

[0034] In some embodiments, the medicament is used to reduce or maintain a subject's body fat percentage after terminating a weight loss therapy.

[0035] Another aspect of the present invention discloses the use of a composition in the preparation of a medicament for intervening in weight rebound after weight loss treatment, wherein the composition comprises gastric contents.

[0036] In some embodiments, the gastric contents reach at least 75% of the maximum expanded volume within 30 minutes in an in vitro simulated environment.

[0037] In some embodiments, the gastric content comprises a hydrogel.

[0038] In some embodiments, the hydrogel has a medium uptake ratio of at least 20 and an elastic modulus of 100 Pa to 10,000 Pa.

[0039] In some embodiments, the composition further comprises a lipase inhibitor.

[0040] In some embodiments, the composition is used for subjects who have lost ≥ 5% of their body weight upon termination of weight loss therapy.

[0041] In some embodiments, the medicament is for initiation of use no more than 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, or 9 months after cessation of weight loss therapy.

[0042] In some embodiments, the drug is administered orally to the subject.

[0043] In some embodiments, the baseline value at the time of terminating the weight loss therapy is used as a reference value, and the drug is used to maintain or reduce the subject's body weight after terminating the weight loss therapy.

[0044] In some embodiments, the baseline value at the time of terminating the weight loss therapy is used as a reference value, and the drug is used to slow down the rate of weight rebound in the subject after terminating the weight loss therapy.

[0045] In some embodiments, the baseline value at the time of terminating the weight loss therapy is used as a reference value, and the drug is used to maintain or increase the lean body mass percentage of the subject after terminating the weight loss therapy.

[0046] In some embodiments, the baseline value at the time of terminating the weight loss therapy is used as a reference value, and the drug is used to slow down the rate of decline of the subject's lean body mass percentage after terminating the weight loss therapy.

[0047] In some embodiments, the weight loss therapy comprises pharmaceutical weight loss and / or surgical weight loss.

[0048] In some embodiments, the drug achieves weight loss through at least one of the following mechanisms: (1) inhibiting hunger signal transmission, (2) enhancing satiety perception, (3) slowing the emptying rate of gastric contents, (4) inhibiting lipid / carbohydrate absorption, (5) blocking fat cell storage pathways, or (6) promoting lipid catabolism.

[0049] In some embodiments, the drug achieves weight loss through at least one of the following mechanisms: (1) inhibiting hunger signal transmission, (2) enhancing satiety perception, (3) slowing the emptying rate of gastric contents, (4) inhibiting lipid / carbohydrate absorption, (5) blocking fat cell storage pathways, or (6) promoting lipid catabolism.

[0050] In some embodiments, the drug for weight loss is selected from the following group: GLP-1 receptor agonists, GIP receptor agonists, amylin receptor agonists, GCGR agonists, centrally acting appetite suppressants (such as phentermine), sympathomimetic amines (benzphetamine, phenmethazine), lipase inhibitors, SGLT2 inhibitors (canagliflozin, dapagliflozin), and serotonin-norepinephrine reuptake inhibitors.

[0051] In some embodiments, the pharmaceutical weight loss comprises administering at least one drug that targets the GLP-1 receptor.

[0052] In some embodiments, the GLP-1 receptor agonist is selected from one or more of semaglutide, liraglutide, dulaglutide, beroglutide, tilpotide, or exenatide.

[0053] Another aspect of the present invention discloses the use of a composition in the preparation of a drug for intervening in weight rebound after weight loss therapy, wherein the composition comprises a gastric content and a lipase inhibitor, and the drug is used for subjects who have undergone at least 2 months of weight loss therapy, and the drug is used to start administration within no more than 6 months after the termination of the weight loss therapy.

[0054] In some embodiments, the weight loss therapy is a drug therapy with a GLP-1 receptor agonist.

[0055] The above technical solution has the following beneficial effects:

[0056] The present composition, through the synergistic effect of a hydrogel and a lipase inhibitor, modulates energy metabolism and nutrient distribution from multiple dimensions, achieving long-term weight maintenance and improving lean body mass after weight loss therapy. Its core mechanism lies in its dual-channel effects of physical gastric volume occupation and targeted fat absorption inhibition.

[0057] The hydrogel rapidly absorbs water and swells in gastric fluid, forming a three-dimensional network structure that occupies the effective volume of the stomach. It activates the gastric wall tension receptors through physical stimulation, inhibits the secretion of ghrelin and delays gastric emptying, thereby enhancing satiety and reducing energy intake.

[0058] At the same time, lipase inhibitors inhibit fat absorption, and the proportion of uninhibited amino acid absorption is relatively increased, thereby improving the bioavailability of essential amino acids and increasing the proportion of lean body mass by promoting muscle protein anabolism.

[0059] Lipase inhibitors specifically bind to serine residues at the active sites of gastric and pancreatic lipases, irreversibly blocking the hydrolysis of dietary fat into absorbable free fatty acids and monotriglycerides, allowing some fat to be excreted through the intestines without being broken down. This specific inhibition strategy reduces caloric intake while preserving the complete absorption of carbohydrates, amino acids, and micronutrients, resulting in a unique nutrient allocation optimization effect. Uninhibited essential amino acids promote ribosome biogenesis by activating key metabolic pathways, resulting in increased net muscle protein synthesis and an increase in lean body mass.

[0060] The synergistic effect of the two further extends through the metabolic regulation network: the hydrogel's delay in gastric emptying prolongs the stimulation of intestinal L cells by unabsorbed fat, promoting increased secretion of glucagon-like peptide-1 (GLP-1) and enhancing central satiety; while the lipase inhibitor reduces rebound hyperlipidemia, interrupting the vicious cycle of lipid metabolism disorders after drug discontinuation. This organic combination of physical intervention in the stomach and molecular targeted inhibition not only effectively offsets the muscle loss caused by traditional weight loss therapies, but also prevents metabolic imbalances through nutrient redistribution mechanisms, providing dual protection for weight rebound control.

[0061] The technical advantages of this composition are fully supported by the material properties in the process of drug intervention in weight rebound after weight loss treatment: the hydrogel exhibits excellent liquid absorption and swelling capacity and suitable mechanical strength in simulated gastric fluid, which not only ensures rapid volume occupancy efficiency but also maintains the stability required to resist gastric peristalsis. Orlistat inhibits fat absorption, and the absorption rate of uninhibited amino acids is relatively increased. Amino acids activate the small G protein Rag by binding to sensor proteins such as Sestrin2 and SAR1B, thereby localizing mTOR to the surface of the lysosomal membrane and ultimately activating mTORC1 to promote muscle protein synthesis. The two complement each other through their temporal and spatial distribution and mechanism of action, forming a full-chain weight management program covering intake inhibition, nutrition optimization, metabolic regulation and lean body protection. BRIEF DESCRIPTION OF THE DRAWINGS

[0062] Figure 1 This is the in vitro gastrointestinal behavior simulation curve of the sample in Example 1.

[0063] Figure 2 This is the dissolution curve of the lipase inhibitor of the sample in Example 2.

[0064] Figure 3 These are the results of the in vitro lipase inhibition experiment of Example 3.

[0065] Specific implementation party

[0066] The invention discloses an application of a composition in preparing a medicine for intervening in weight rebound after weight loss treatment. The composition comprises a gastric content and a lipase inhibitor.

[0067] In the present invention, "intervention of weight rebound" refers to achieving at least one of the following effects: maintaining the subject's weight stably at the level at the end of weight loss treatment or the start of administration of the drug of the present invention; delaying the rate at which the subject's weight returns to the baseline level before weight loss treatment; or continuing to achieve a decrease in weight and / or body fat percentage after cessation of weight loss treatment measures.

[0068] The gastric volume-occupying substance is a substance or device that temporarily occupies the effective volume in the stomach by direct physical occupation or physical occupation after stomach expansion. The lipase inhibitor reduces fat absorption by inhibiting lipase activity. The two act synergistically in the gastrointestinal tract to achieve weight rebound control.

[0069] In the present invention, the form of the gastric contents includes but is not limited to:

[0070] (1) Dietary fiber, high molecular weight polymer or hydrogel particles that absorb water and swell after oral administration;

[0071] (2) Degradable or non-degradable solid / liquid spacer materials.

[0072] The above substances or devices achieve the purpose of reducing energy intake by mechanically limiting gastric capacity, delaying gastric emptying or enhancing satiety.

[0073] The absorption rate of the gastric volume does not exceed 20%.

[0074] In some embodiments, the absorption rate of gastric contents does not exceed 10%.

[0075] The absorption rate of the lipase inhibitor does not exceed 20%.

[0076] In some embodiments, the lipase inhibitor is absorbed no more than 5%.

[0077] In the present invention, the "absorption rate" is defined as bioavailability, that is, the proportion of the drug entering the systemic circulation after oral administration, usually expressed as the percentage of the area under the plasma drug concentration-time curve (AUC) relative to intravenous injection, and the plasma concentration can be detected by LC-MS / MS.

[0078] In an in vitro dissolution test, the cumulative dissolution rate of the lipase inhibitor in the composition within 45 minutes is ≥60%.

[0079] In some embodiments, the cumulative dissolution rate of the lipase inhibitor in the composition within 45 minutes in an in vitro dissolution test is 60%-70%, 70%-80%, 80%-90% or more than 90%.

[0080] The lipase inhibitor in the composition is tested for in vitro dissolution (according to USP <711> Paddle method, dissolution conditions: 900 ml of 0.5% sodium chloride solution containing 3% sodium lauryl sulfate (pH adjusted to 6.0 with phosphoric acid) as the dissolution medium, at a speed of 75 rpm:

[0081] (a) Cumulative dissolution within 20 minutes ≥ 45%.

[0082] (b) Cumulative dissolution within 45 minutes ≥ 75%.

[0083] The stomach content reaches at least 75% of the maximum expansion volume within 30 minutes in an in vitro simulated environment.

[0084] In some embodiments, the gastric contents reach at least 90% of the maximum expanded volume within 30 minutes in an in vitro simulated environment.

[0085] In some embodiments, the gastric contents reach at least 90% or 95% of the maximum expanded volume within 30 minutes in an in vitro simulated environment.

[0086] The gastric contents maintain at least 75% of the maximum expansion volume for at least 1 hour in an in vitro simulated environment.

[0087] The gastric content includes a hydrogel.

[0088] In the present invention, the hydrogel may be a cross-linked hydrophilic polymer.

[0089] The hydrophilic polymer is selected from polysaccharides, polyacrylates, polyacrylamides, ethylene maleic anhydride polymers, polyvinyl alcohol, polyvinyl pyrrolidone, cross-linked polyethylene oxides, starch grafted polyacrylonitrile and any copolymers thereof.

[0090] The hydrophilic polymer is a polysaccharide selected from the following compounds or their derivatives: starch, hydroxyethyl starch, hydroxypropyl starch, carboxymethyl starch, amylose, dextran, chitin, pullulan, gellan gum, xylan, carrageenan, agar, locust bean gum, guar gum, gum arabic, pectin, cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, ethyl hydroxyethyl cellulose, hydroxybutyl methyl cellulose, hydroxyethyl methyl cellulose, oxidized cellulose, carboxymethyl cellulose, galactomannan, alginate, chitosan, cyclodextrin, xanthan gum, hyaluronic acid, heparin, chondroitin sulfate, keratan, dermatan and polysaccharides having glucosamine residues in natural or diacetylated form and any mixtures thereof.

[0091] Cross-linking between hydrophilic polymers can be achieved directly between hydrophilic polymers or by using a cross-linking agent.

[0092] The crosslinking agent may be the hydrophilic polymer itself. When the crosslinking agent of the crosslinked hydrophilic polymer is the hydrophilic polymer itself, the hydrophilic polymer can be considered to be self-crosslinking, that is, all or a portion of the hydrophilic polymer acts as the crosslinking agent. The hydrophilic polymer may include different segments, each of which can act as a crosslinking agent independently.

[0093] In the present invention, hydrogels formed by chemically crosslinking hydrophilic polymers can form a more stable and rigid network. The degree and type of crosslinking agent used can affect the physical properties of the resulting hydrogel, such as water retention, swelling rate, media uptake rate, elastic modulus, mechanical strength, and degradation rate.

[0094] In the present invention, citric acid can be used to cross-link carboxymethyl cellulose to construct a three-dimensional network structure hydrogel. In another embodiment, PEG and citric acid form a spacer cross-linking agent, which is then cross-linked with polysaccharides to form a highly absorbent hydrogel gastric volume.

[0095] The hydrogel reaches at least 75% of the maximum swelling volume within 30 minutes in an in vitro simulated environment.

[0096] The maximum swelling volume (V_max) was defined as the volume of the hydrogel measured after immersion in a diluted simulated gastric fluid (simulated gastric fluid: water ratio of 1:8) for 1 hour.

[0097] The gastric contents maintain at least 75% of the maximum expansion volume for at least 1 hour, 2 hours, 3 hours, or 4 hours in an in vitro simulated environment.

[0098] The elastic modulus of the hydrogel is 100 Pa to 10000 Pa.

[0099] The hydrogel has a rheological property or mechanical strength elastic modulus G' value in the range of about 100 Pa to about 10,000 Pa, about 100 Pa to about 500 Pa, about 100 Pa to about 1,000 Pa, about 100 Pa to about 2,000 Pa, about 100 Pa to about 5,000 Pa, about 500 Pa to about 1,000 Pa, about 500 Pa to about 2,000 Pa, about 500 Pa to about 5,000 Pa, about 500 Pa to about 10,000 Pa, about 1,000 Pa to about 2,000 Pa, about 1,000 Pa to about 5,000 Pa, about 1,000 Pa to about 10,000 Pa, about 2,000 Pa to about 5,000 Pa, about 2,000 Pa to about 10,000 Pa, or about 5,000 Pa to about 10,000 Pa. The specific elastic modulus value contributes to a feeling of fullness after ingestion of the hydrogel.

[0100] The hydrogel may be in powder form, and the powder particle size range may be: about 0.01 mm to about 5 mm, about 0.01 mm to about 0.02 mm, about 0.01 mm to about 0.05 mm, about 0.01 mm to about 0.1 mm, about 0.01 mm to about 0.2 mm, about 0.01 mm to about 0.5 mm, about 0.01 mm to about 1 mm, about 0.01 mm to about 2 mm, about 0.02 mm to about 0.05 mm, about 0.02 mm to about 0.1 mm, about 0.02 mm to about 0.2 mm, about 0.02 mm to about 0.5 mm, About 0.02mm to about 1mm, about 0.02mm to about 2mm, about 0.02mm to about 5mm, about 0.05mm to about 0.1mm, about 0.1mm to about 0.2mm, about 0.1mm to about 0.5mm, about 0.1mm to about 1mm, about 0.1mm to about 2mm, about 0.1mm to about 5mm, about 0.2mm to about 0.5mm, about 0.2mm to about 1mm, about 0.2mm to about 2mm, about 0.2mm to about 5mm, about 1mm to about 2mm, about 1mm to about 5mm, or about 2mm to about 5mm.

[0101] The hydrogel may have a medium uptake ratio (MUR) of at least 20, at least 50, at least 70, at least 90, or at least 100. The hydrogel may have a medium uptake ratio ranging from about 20 to about 200. The medium may be diluted simulated gastric fluid (SGF).

[0102] Lipase inhibitors are substances used to reduce the activity of lipase in the gastrointestinal tract. The pancreas secretes lipase in the presence of fat. Their primary effect is to reduce fat absorption in the gastrointestinal tract. This allows fat to be excreted in the stool rather than being absorbed as a source of calories, thereby managing weight.

[0103] Lipase inhibitors affect the amount of fat absorbed. Furthermore, they are not absorbed into the bloodstream. They bind to lipase in the intestine, preventing the hydrolysis of dietary triglycerides into monotriglycerides and fatty acids. This reduces the absorption of dietary fat. Lipase inhibitors covalently bind to the active serine site on lipase. This covalent bond is strong, meaning the lipase inhibitor is likely to remain attached to the lipase.

[0104] The lipase inhibitor is selected from lipstatin, tetrahydrolipidase (orlistat), FL-386, WAY-121898, BAY-N-3176, valeric acid lactone, esterase inhibitor, erbinolactone A, erbinolactone B, RHC; 80267, cetilistat and any mixture thereof.

[0105] The composition weight ratio of the hydrogel to the lipase inhibitor may be greater than about 10.

[0106] In some embodiments, the weight ratio of the hydrogel to the lipase inhibitor is 20:1-60:1.

[0107] In some embodiments, the weight ratio of the hydrogel to the lipase inhibitor is 25:1-50:1.

[0108] In some embodiments, the composition comprises 30 mg-120 mg of a lipase inhibitor.

[0109] The composition may further include an amylase inhibitor, a glucosidase inhibitor, or any combination thereof.

[0110] Amylase inhibitors and / or glucosidase inhibitors are intestinal enzymes that slow the absorption of carbohydrates by inhibiting enzymes responsible for digestion. Amylases and / or glucosidases can release glucose from larger carbohydrates through hydrolysis. Amylases hydrolyze complex starches into oligosaccharides, while glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides in the small intestine into glucose and other monosaccharides. Inhibiting these enzymes can slow the digestion of complex carbohydrates. Because carbohydrates are not broken down into glucose molecules, less glucose may be absorbed. The short-term effect of using amylase inhibitors and / or glucosidase inhibitors is lowering blood sugar levels, and the long-term effect is lowering glycated hemoglobin (HbA1c) levels.

[0111] The amylase inhibitor and / or the glucosidase inhibitor is selected from acarbose, voglibose, miglitol, emiglitate, canaglibose, pranamicin Q, saboteur and any mixture thereof.

[0112] The composition may further include pharmaceutically acceptable excipients.

[0113] The term "pharmaceutically acceptable excipient" is intended to include, but is not limited to, solvents, dispersion media, coatings, antibacterial agents, antifungal agents, isotonic agents, absorption delay agents, diluents, fillers, thickeners, disintegrants, emulsifiers, lubricants, adhesives, colorants, film formers, preservatives, stabilizers, wetting agents, salts (for varying osmotic pressure or as buffers), plasticizers, antiadhesives, opacifying agents, and the like, and mixtures thereof. The use of such media or formulations for pharmaceutically active substances is well known in the art. Unless any conventional media or formulation is incompatible with the composition, such media or formulations should be considered for use in therapeutic compositions and treatment / prevention methods. Supplementary active compounds may also be added.

[0114] Excipients may be selected from, but are not limited to, agents such as gum tragacanth, gum arabic, corn starch, or gelatin; excipients such as dicalcium phosphate; disintegrants such as corn starch, potato starch, alginic acid, and the like; lubricants such as magnesium stearate; and sweeteners such as sucrose, lactose, or saccharin; or flavorings such as peppermint, oil of wintergreen, or cherry flavoring. When the unit dosage form is a capsule, a liquid carrier may be included in addition to the aforementioned types of materials. Various other materials may be present as coatings or otherwise modify the physical form of the dosage unit. For example, tablets, pills, or capsules may be coated with shellac and / or sugar. Syrups or elixirs may contain similar substances, such as sucrose as a sweetener; methylparaben and propylparaben as preservatives; dyes; and flavorings such as cherry or orange flavor. Of course, any materials used to prepare any unit dosage form should be pharmaceutically pure and substantially non-toxic in the dosages used. Additionally, the analogs can be incorporated into sustained-release preparations and formulations.

[0115] In one embodiment, the excipient may be an excipient for oral administration.

[0116] Pharmaceutically acceptable excipients may be selected from fillers or diluents, disintegrants, colorants, lubricants, binders, thickeners, film formers, wetting agents or emulsifiers and any mixtures thereof.

[0117] The weight ratio of the excipient to the lipase inhibitor ranges from about 0.01 to about 2, about 0.01 to about 0.02, about 0.01 to about 0.05, about 0.01 to about 0.1, about 0.01 to about 0.2, about 0.01 to about 0.5, about 0.01 to about 1, about 0.02 to about 0.05, about 0.02 to about 0.1, about 0.02 to about 0.2, about 0.02 to about 0.5, about 0.02 to about 1 , about 0.02 to about 2, about 0.05 to about 0.1, about 0.05 to about 0.2, about 0.05 to about 0.5, about 0.05 to about 1, about 0.05 to about 2, about 0.1 to about 0.2, about 0.1 to about 0.5, about 0.1 to about 1, about 0.1 to about 2, about 0.2 to about 0.5, about 0.2 to about 1, about 0.2 to about 2, about 0.5 to about 1, about 0.5 to about 2, or about 1 to about 2.

[0118] The weight loss treatment includes drug weight loss and / or surgical weight loss.

[0119] Weight loss medications primarily work by regulating metabolism or suppressing appetite. For example, orlistat, an oral medication, inhibits gastrointestinal lipase activity, reducing dietary fat absorption by 25%. A 60mg dose is required three times daily with or after meals. GLP-1 receptor agonists such as liraglutide (0.6-3.0mg subcutaneously daily) and semaglutide (0.5-2.4mg once weekly) control appetite by delaying gastric emptying and enhancing satiety signals. Telportide, a dual-target agonist, is injected once a week (starting at 2.5mg, maximum 15mg) to accelerate metabolism by simultaneously activating both GLP-1 and GIP receptors.

[0120] Surgical weight loss focuses on structural changes to the digestive system. Laparoscopic sleeve gastrectomy reduces stomach volume by removing approximately 80% of the stomach tissue, reducing ghrelin production. Postoperatively, the patient must gradually adapt to eating smaller, more frequent meals. Gastric bypass reshapes the intestinal pathways, limiting food absorption and promoting metabolic regulation. Long-term vitamin supplementation is required postoperatively. Furthermore, minimally invasive techniques such as left gastric artery embolization (LEACE) reduce ghrelin production by embolizing the left gastric artery. These procedures are suitable for patients who cannot tolerate traditional surgery, leaving only a minimal incision and allowing for rapid recovery.

[0121] The drug achieves weight loss through at least one of the following mechanisms: (1) inhibiting hunger signal transmission, (2) enhancing satiety perception, (3) delaying the emptying rate of gastric contents, (4) inhibiting lipid / carbohydrate absorption, (5) blocking fat cell storage pathways, or (6) promoting lipid catabolism.

[0122] Inhibiting hunger signaling is primarily achieved by regulating hypothalamic neuronal activity. For example, GLP-1 drugs can activate specific neurons in the dorsomedial hypothalamic nucleus (DMH), inhibiting the activity of AgRP / NPY hunger neurons in the arcuate nucleus (ARC), thereby triggering satiety signals in advance. This mechanism can reduce the desire to eat, and clinical trials have shown that it can reduce the frequency of spontaneous eating by approximately 1.8 times per day.

[0123] Enhancing the perception of fullness depends on the linkage between the gastrointestinal tract and the central nervous system. Gastric fullness stimulates the vagus nerve to transmit signals to the nucleus tractus solitarius. At the same time, hormones such as GLP-1 and CCK secreted by the intestines strengthen the fullness signal through chemical receptors. High-fiber foods can enhance this effect by prolonging gastric emptying time.

[0124] Delaying the rate of gastric emptying involves inhibiting the frequency of gastric smooth muscle contractions and gastric acid secretion. For example, GLP-1 drugs can prolong gastric emptying time by 30-50%, continuously activating stretch receptors in the gastric wall to generate mechanical signals of fullness. However, it should be noted that this mechanism may increase the risk of gastroparesis, especially in diabetic patients, where the incidence of abnormal gastric electrical rhythms may be 1.7 times higher.

[0125] Inhibition of lipid absorption is primarily achieved by blocking lipase activity or the cholesterol absorption pathway. For example, orlistat inhibits intestinal lipase from breaking down triglycerides, ezetimibe targets the NPC1L1 protein to prevent cholesterol influx, and dietary fiber promotes lipid excretion through physical adsorption. Inhibition of carbohydrate absorption is primarily achieved by competing with intestinal wall cells and oligosaccharides, reversibly binding to α-glucosidase, and inhibiting enzyme activity, thereby delaying carbohydrate degradation and slowing intestinal glucose absorption.

[0126] The key to blocking the adipocyte storage pathway lies in regulating key factors in fat differentiation. For example, ActRII antibodies inhibit the TGF-β / Smad pathway by downregulating PPARγ and C / EBPα expression, reducing adipocyte differentiation and lipid droplet formation. Laekna Pharmaceuticals' LAE102 has been shown in preclinical studies to reduce white fat accumulation and, in combination with GLP-1, to reduce the risk of muscle loss by 40%.

[0127] Lipid catabolism enhances fatty acid oxidation by activating HSL enzymes and the AMPK pathway. For example, β3 adrenergic receptor agonists stimulate lipolysis, cold exposure or GLP-1 / GCGR dual agonists induce browning of white fat, and increase UCP1 protein expression to improve the efficiency of heat production and energy consumption.

[0128] In the method of the present invention, the drug is used for subjects who have undergone at least 1, 2, 3, or 4 courses of drug weight loss treatment.

[0129] In the method of the present invention, the drug is used for subjects whose weight loss ratio is ≥5% when the weight loss treatment is terminated.

[0130] In the method of the present invention, the drug is used for subjects whose proportion is 5%-10%, 10%-15%, 15%-20%, 10%-25% or more when weight loss treatment is terminated.

[0131] The method of the invention, wherein the drug is used to start use within no more than 1 month, 2 months, 3 months, 4 months, 5 months, 6 months or 9 months after terminating the weight loss treatment.

[0132] In the method of the present invention, the drug is used for at least 1 month, 2 months, 3 months, 4 months, 5 months, 6 months or 12 months after the termination of weight loss treatment.

[0133] The drug is orally administered to a subject. The composition can be prepared into a capsule formulation for convenient oral administration.

[0134] When preparing drug capsules, the hydrogel is composed of dry gel particles that have not absorbed water and a lipase inhibitor.

[0135] When the composition is orally administered, it can be administered with water. It can be administered with about 100 mL to about 700 mL, about 100 mL to about 250 mL, about 100 mL to about 500 mL, about 250 mL to about 500 mL, about 250 mL to about 700 mL, or about 400 mL to about 600 mL of water.

[0136] The baseline value at the time of termination of weight loss therapy is used as a reference value, and the drug is used to maintain or reduce the subject's body weight after termination of weight loss therapy.

[0137] The baseline value at the time of terminating the weight loss treatment is used as a reference value, and the drug is used to slow down the rate of weight rebound of the subject after terminating the weight loss treatment.

[0138] Compared with the blank control group, after the weight loss treatment is terminated, the drug is used to reduce the weight rebound rate of the subject to less than 50%, or even to less than 0%. A negative weight rebound rate indicates that the drug has the function of further reducing weight.

[0139] After terminating the weight loss treatment, the drug causes the subject's weight regain rate to be less than 50% after half a year of administration.

[0140] The weight rebound rate is defined as: the subject's weight before weight loss treatment is A kg, the subject's weight after weight loss treatment is B kg, and the subject's weight after terminating weight loss treatment and using the method of the present invention is C kg.

[0141] Weight rebound rate = (CB) / (BA)×100%.

[0142] The baseline value at the time of termination of weight loss therapy is used as a reference value, and the drug is used to maintain or increase the proportion of lean body mass of the subject after termination of weight loss therapy.

[0143] The baseline value at the time of terminating the weight loss therapy is used as a reference value, and the drug is used to slow down the rate of decline of the subject's lean body mass percentage after terminating the weight loss therapy.

[0144] The baseline value after drug discontinuation is used as a reference value, and the drug is used to reduce or maintain the subject's body fat percentage after terminating weight loss.

[0145] "Lean body mass" is defined as a subject's total body mass minus fat mass and the subject's bone mass. Lean body mass and fat mass can be measured using methods such as bioelectrical impedance analysis (BIA), magnetic resonance imaging (MRI), or dual X-ray absorptiometry (DXA). "Body fat percentage" is defined as a subject's fat mass divided by their total body mass.

[0146] The drug for weight loss treatment is selected from the following group: GLP-1 receptor agonists, GIP receptor agonists, amylin receptor agonists, GCGR agonists, centrally acting appetite suppressants (such as phentermine), sympathomimetic amines (benzphetamine, phendimetrazine), lipase inhibitors, SGLT2 inhibitors (canagliflozin, dapagliflozin), and serotonin-norepinephrine reuptake inhibitors.

[0147] In the present invention, the weight loss method comprises administering at least one drug targeting the GLP-1 receptor.

[0148] In the present invention, the GLP-1 receptor agonist is selected from one or more of semaglutide, liraglutide, dulaglutide, beroglutide, tilpotide or exenatide.

[0149] GLP-1 receptor agonists (such as semaglutide and liraglutide) achieve weight loss by suppressing appetite, delaying gastric emptying, and regulating blood sugar. This approach, combined with appetite suppression and delayed gastric emptying, leads to an imbalance in the ratio of fat to muscle loss. Compared to traditional diet and exercise, approximately 40% of weight loss with GLP-1 drugs is muscle loss, while 60% is fat loss. However, after discontinuation of the drug, weight rebound is characterized by preferential fat accumulation and lagging muscle recovery. Some data suggest that one year after discontinuation, weight rebound averages 14%, with fat regain exceeding half of the lost fat, while muscle recovery accounts for less than 30% of the regained weight. The core mechanisms of this body composition imbalance include a memory effect in adipocytes (retained expansion potential) and hormonal imbalances (a 50%-80% surge in ghrelin and a 5%-8% decrease in basal metabolic rate), which accelerate fat synthesis and hinder muscle regeneration. As a result, this non-proportional rebound may cause the body fat percentage of the subjects to exceed the pre-drug level for a period of time after stopping the drug. For example, 44% of patients who stopped taking semaglutide had a body fat percentage increase of 2.3%-4.7% compared with the baseline, and even developed "sarcopenic obesity."

[0150] The method of the present invention can be applied to intervene in the problem of weight rebound after weight loss with GLP-1 receptor agonists. In particular, after administering the composition of the present invention, the lipase inhibitor inhibits fat absorption, and the absorption ratio of uninhibited amino acids is relatively increased, thereby improving the bioavailability of essential amino acids. Compared with the rebound after drug withdrawal, this improves the synthesis of lean body, reduces the rate of fat rebound, and thus reduces or maintains the body fat percentage after weight loss.

[0151] Another aspect of the present invention discloses the use of a composition in the preparation of a drug for intervening in weight rebound after weight loss treatment, wherein the composition comprises a gastric content and a lipase inhibitor, and the drug is used to slow the rate of increase in the subject's body fat percentage after terminating the weight loss treatment.

[0152] The drug is used to reduce or maintain the body fat percentage of a subject after terminating weight loss therapy.

[0153] The composition comprises the gastric content described above and a lipase inhibitor.

[0154] Another aspect of the present invention provides use of the composition in preparing a medicament for intervening in weight rebound after weight loss therapy, wherein the composition comprises gastric contents.

[0155] The stomach content reaches at least 75% of the maximum expansion volume within 30 minutes in an in vitro simulated environment.

[0156] The gastric content includes a hydrogel.

[0157] The hydrogel product of the present invention may comprise unexpanded xerogel particles or hydrogel after water absorption and swelling equilibrium.

[0158] The hydrogel reaches at least 75% of its maximum expansion volume within 30 minutes in an in vitro simulated environment, has a medium uptake rate of at least 20, and an elastic modulus of 100 Pa to 10,000 Pa after swelling with water absorption.

[0159] The composition comprises a lipase inhibitor.

[0160] The drug is used for subjects whose weight loss ratio is ≥5% when weight loss treatment is terminated.

[0161] The drug is used to be started within no more than 1 month, 2 months, 3 months, 4 months, 5 months, 6 months or 9 months after the termination of weight loss treatment.

[0162] In some embodiments, the drug is administered orally to the subject.

[0163] In some embodiments, the baseline value at the time of terminating the weight loss therapy is used as a reference value, and the drug is used to maintain or reduce the subject's body weight after terminating the weight loss therapy.

[0164] In some embodiments, the drug is used to slow down the rate of weight rebound in the subject after terminating the weight loss therapy, taking the baseline value at the time of terminating the weight loss therapy as the reference value.

[0165] In some embodiments, the baseline value at the time of terminating the weight loss therapy is used as a reference value, and the drug is used to maintain or increase the lean body mass percentage of the subject after terminating the weight loss therapy.

[0166] In some embodiments, the drug is used to slow down the rate of decline of the subject's lean body mass percentage after terminating the weight loss therapy, taking the baseline value at the time of terminating the weight loss therapy as a reference value.

[0167] The weight loss treatment includes drug weight loss and / or surgical weight loss.

[0168] The drug achieves weight loss through at least one of the following mechanisms: (1) inhibiting hunger signal transmission, (2) enhancing satiety perception, (3) delaying the emptying rate of gastric contents, (4) inhibiting lipid / carbohydrate absorption, (5) blocking fat cell storage pathways, or (6) promoting lipid catabolism.

[0169] The drug for weight loss is selected from the following group: GLP-1 receptor agonists, GIP receptor agonists, amylin receptor agonists, GCGR agonists, centrally acting appetite suppressants (such as phentermine), sympathomimetic amines (benzphetamine, phendimetrazine), lipase inhibitors, SGLT2 inhibitors (canagliflozin, dapagliflozin), and serotonin-norepinephrine reuptake inhibitors.

[0170] The drug weight loss comprises administering at least one drug targeting the GLP-1 receptor.

[0171] The GLP-1 receptor agonist is selected from one or more of semaglutide, liraglutide, dulaglutide, beroglutide, tilpotide or exenatide.

[0172] In some embodiments, the composition includes an excipient or carrier, for example, an aqueous carrier. Various aqueous carriers can be used, such as buffered saline. These compositions may contain pharmaceutically acceptable excipients.

[0173] Another aspect of the present invention discloses the use of a composition in the preparation of a drug for intervening in weight rebound after weight loss therapy, wherein the composition comprises a gastric content and a lipase inhibitor, and the drug is used for subjects who have undergone at least 2 months of weight loss therapy, and the drug is used to start administration within no more than 6 months after the termination of the weight loss therapy.

[0174] In some embodiments, the weight loss therapy is medication with a GLP-1 receptor agonist.

[0175] In order to explain the technical content, structural features, achieved objectives and effects of the technical solution in detail, the following is a detailed description in conjunction with specific embodiments and accompanying drawings.

[0176] Sample preparation

[0177] (1) Synthesis of cross-linking agent

[0178] Polyethylene glycol (PEG, 5K) was weighed and mixed with the CA solution, and heated to react to form a spacer crosslinker.

[0179] (2) Preparation of hydrogel particles

[0180] A spacer crosslinker solution with an equivalent citric acid content (equivalent to 20 mg CA) was added to water. CMC (10 g) was then added to the solution and stirred at room temperature. The resulting homogenous solution was poured into a stainless steel tray. The tray was dried in a convection oven at 50°C. After complete drying, the CMC flakes were ground using a cutting mill. The granular material was sieved to a particle size of 0.1 to 1 mm.

[0181] (3) Composition mixing

[0182] Orlistat (API), microcrystalline cellulose and sodium starch glycolate are mixed in a dry mixer to obtain Part A. Polyvinylpyrrolidone and sodium lauryl sulfate are dissolved in purified water and homogenized to obtain Part B. Part B is added to Part A and kneaded using a wet mixer. The resulting paste is granulated and passed through an extruder. The extrudate is then passed through a spheronizer to form micropellets. The wet pellets obtained are dried in a fluidized bed dryer with talc at 40°C and then sieved. The fraction with a particle size of 0.1 to 2 mm is collected as pellets to obtain pellets containing 50% orlistat (API).

[0183] The hydrophilic hydrogel particles and the pills were fully mixed, and different composition samples were obtained according to different mass ratios of the hydrogel and orlistat (API).

[0184] Table 1. Composition sample data

[0185]

[0186] Example 1

[0187] Sample 4 in the GI digestion in vitro model: simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF) medium uptake rate change curve is as follows Figure 1 shown.

[0188] Example 2

[0189] Sample 4 was subjected to a dissolution test.

[0190] Dissolution conditions: Dissolution medium: pH 6.0 + 3.0% SDS, n = 12

[0191] Table 2. Dissolution test of the composition

[0192]

[0193] Example 3

[0194] In vitro lipase inhibition test of sample 4 composition, the experimental conditions are as follows:

[0195] Table 3. In vitro lipase inhibition test conditions of the compositions

[0196]

[0197] Example 4

[0198] SD rats were fed a high-fat diet for 8 consecutive weeks to establish an obesity model. They were then injected with 0.2 mg / kg semaglutide twice weekly. After 6 weeks of treatment, semaglutide injections were discontinued, and the animals were weighed and divided into an experimental group and a control group. The experimental group received 200 mg / kg of Sample 4 of the present invention orally before meals daily for more than 3 weeks; the control group was allowed to eat freely. The animals were then weighed at their final body weight and lean body mass, and the weight rebound rate was calculated. The results are shown in the following table.

[0199] Table 4. Animal weight rebound intervention experiment

[0200]

[0201] In the experiment, dual-energy X-ray absorptiometry (DXA) was used to detect the changes in lean body mass ratio and body fat percentage. In the present invention, body weight is defined as fat weight + lean body mass.

[0202] In the experiment, the samples were administered for 3 weeks, 4 weeks, 5 weeks, and 6 weeks, and the corresponding weight rebound rates were 10.2%, 7.0%, -1.3%, and -2.3%.

[0203] Three weeks after GLP-1 injection, the lean body mass ratio was 62.3%. After the experiment in the experimental group, the lean body mass ratio increased to 64.7%, 65.8%, 67.0% and 68.3%.

[0204] In the control group, due to weight rebound and no specific inhibition of fat absorption, the proportion of lean body mass gradually decreased over time. The data for 3 weeks, 4 weeks, 5 weeks, and 6 weeks were 61.1%, 60.2%, 59.2%, and 58.5%, respectively.

[0205] According to the experimental results, in the SD rat obesity model, the control group did not impose any intervention measures after stopping simeglutide treatment, and the weight rebounded significantly and the proportion of lean body mass decreased (ie, the body fat percentage increased). Six weeks after discontinuation of the drug, the proportion of lean body mass continued to decrease from 62.3% to 58.5%, indicating a significant decrease in the proportion of lean body mass, indicating that the metabolic rebound was mainly due to fat accumulation. In contrast, after the experimental group 1 was intervened with the composition after discontinuation of the drug, it not only suppressed weight rebound, but also significantly increased the proportion of lean body mass. This may be attributed to the fact that orlistat reduces dietary fat absorption by inhibiting lipase activity, and the absorption ratio of uninhibited protein nutrients (such as essential amino acids) is relatively increased, thereby increasing the bioavailability of amino acids, promoting muscle protein anabolism, and ultimately reducing body fat rate and improving lean body mass ratio.

[0206] Example 5

[0207] The difference from Example 4 is that after 6 weeks of continuous treatment with semaglutide, the drug was stopped and a normal diet was followed for 3 weeks before gavage feeding of Sample 4 of the present invention. The results are as follows:

[0208] Table 5. Animal weight rebound intervention experiment

[0209]

[0210] Sample 4 was administered 3 weeks after drug withdrawal. The results showed that the body weight did not rebound further, and the body fat percentage to lean body mass ratio steadily increased to 67.7% after 8 weeks. This indicates that even with delayed intervention, the method of the present invention can still protect the body fat percentage and lean body mass ratio by blocking new fat accumulation and maintaining amino acid metabolic efficiency.

[0211] Example 6

[0212] SD rats were fed a high-fat diet for 8 consecutive weeks to establish an obesity model. They were then injected with 0.2 mg / kg semaglutide twice weekly. After 6 weeks of treatment, semaglutide injections were discontinued, and the animals were weighed and divided into an experimental group and a control group. The experimental group received a sample of the present invention at 200 mg / kg (based on rat body weight) before meals daily for 6 weeks. The animals were then weighed at their final body weight and lean body mass, and the weight rebound rate was calculated. The results are shown in the following table.

[0213] Table 6. Animal weight rebound intervention experiment

[0214]

[0215] The rats in the experimental group of sample 1 began to have oily spots in their stools in the second week, and later developed severe steatorrhea and other side effects of orlistat.

[0216] The experimental control group received orlistat or xerogel orally; the blank control group received a free diet. The animals were then weighed for final body weight and lean body mass, and weight rebound rate was calculated. The results are shown in the following table.

[0217] Table 7. Animal weight rebound control experiment

[0218]

[0219] Rats in the orlistat control group began to have oily spots in their stools during the first week and subsequently developed severe steatorrhea and other side effects of orlistat.

[0220] The above experiments demonstrate that a ratio of gel to orlistat in the stomach of 25-50 significantly inhibits fat absorption and reduces food intake. Furthermore, the gel swells well in the stomach, significantly occupying the stomach volume. This indicates that combinations within this ratio range exhibit excellent weight loss efficacy and safety, making them suitable for further development and application.

[0221] It should be noted that, in this document, relational terms such as first and second, etc., are used solely to distinguish one entity or operation from another, and do not necessarily require or imply any actual relationship or order between these entities or operations. Furthermore, the terms "include," "comprise," or any other variations thereof are intended to encompass non-exclusive inclusion, such that a process, method, article, or terminal device comprising a series of elements includes not only those elements, but also other elements not explicitly listed, or elements inherent to such process, method, article, or terminal device. Without further limitation, elements defined by the phrase "include..." or "comprising..." do not exclude the presence of additional elements in the process, method, article, or terminal device comprising the elements. Furthermore, in this document, "greater than," "less than," "exceeding," etc., are understood to exclude the number itself; "above," "below," "within," etc., are understood to include the number itself.

[0222] Although the above embodiments have been described, those skilled in the art may make additional changes and modifications to these embodiments once they know the basic creative concepts. Therefore, the above descriptions are merely embodiments of the present invention and do not limit the scope of patent protection of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention's description and drawings, or directly or indirectly applied in other related technical fields, are also included in the scope of patent protection of the present invention.

Claims

1. Use of the composition in the preparation of a medicament for preventing weight rebound after weight loss therapy, characterized in that: The composition includes a gastric occupancy material and a lipase inhibitor.

2. The use according to claim 1, characterized in that The stomach content reaches at least 75% of the maximum expansion volume within 30 minutes in an in vitro simulated environment.

3. The use according to claim 1, characterized in that The gastric contents maintain at least 75% of the maximum expansion volume for at least 1 hour in an in vitro simulated environment.

4. The use according to claim 1, wherein The gastric content includes a hydrogel.

5. The use according to claim 4, characterized in that The hydrogel has a medium uptake rate of at least 20 and an elastic modulus of 100 Pa to 10,000 Pa.

6. The use according to claim 4, characterized in that The weight ratio of the hydrogel to the lipase inhibitor is 20:1-60:

1.

7. The use according to claim 6, characterized in that The weight ratio of the hydrogel to the lipase inhibitor is 25:1-50:

1.

8. The use according to claim 1, characterized in that The drug is used for subjects whose weight loss ratio is ≥5% when terminating weight loss treatment.

9. The use according to claim 1, characterized in that The drug is intended to be started within no more than 1 month, 2 months, 3 months, 4 months, 5 months, 6 months or 9 months after termination of weight loss therapy.

10. The use according to claim 1, characterized in that The drug is administered orally to the subject.

11. The use according to claim 1, characterized in that The drug is used to maintain or reduce the body weight of a subject after terminating weight loss therapy.

12. The use according to claim 1, wherein The drug is used to slow down the rate of weight rebound in a subject after terminating weight loss therapy.

13. The use according to claim 1, wherein The drug is used to maintain or increase the lean body mass percentage of a subject after terminating weight loss therapy.

14. The use according to claim 1, wherein The drug is used to slow down the rate of decline of the subject's lean body mass percentage after terminating weight loss therapy.

15. The use according to claim 1, wherein The weight loss treatment includes drug weight loss and / or surgical weight loss.

16. The use according to claim 15, characterized in that The weight loss drug is selected from the group consisting of: GLP-1 receptor agonists, GIP receptor agonists, amylin receptor agonists, GCGR agonists, centrally acting appetite suppressants, sympathomimetic amines, lipase inhibitors, SGLT2 inhibitors, and serotonin-norepinephrine reuptake inhibitors.

17. The use according to claim 15, characterized in that The drug weight loss comprises administering at least one drug targeting the GLP-1 receptor.

18. The use according to claim 16, characterized in that The GLP-1 receptor agonist is selected from one or more of semaglutide, liraglutide, dulaglutide, beroglutide, tilpotide or exenatide.

19. Use of the composition in the preparation of a medicament for preventing weight rebound after weight loss therapy, characterized in that: The composition comprises a gastric content and a lipase inhibitor, and the drug is used to slow down the rate of increase of the subject's body fat percentage after terminating weight loss therapy.

20. The use according to claim 19, characterized in that The drug is used to reduce or maintain the body fat percentage of a subject after terminating weight loss therapy.

21. Use of the composition in the preparation of a medicament for preventing weight rebound after weight loss therapy, characterized in that: The composition includes a gastric occupant and a lipase inhibitor; The drug is for use in subjects who have undergone weight loss therapy for at least 2 months, and the drug is for use starting within no more than 6 months after terminating the weight loss therapy.

22. The use according to claim 21, characterized in that The weight loss therapy is a drug therapy with administration of a GLP-1 receptor agonist.

Images