A guarana extract-EGCG synergistic fat-burning slimming composition

Abstract

The present invention discloses a guarana extract – EGCG synergistic fat-burning composition, belonging to the technical field of functional foods and weight management. The composition comprises guarana extract, epigallocatechin gallate, and konjac glucomannan. By controlling the component ratio and key parameters, a dynamic gel network formed by konjac glucomannan provides in-situ protection of active ingredients and enables programmed release in the gastrointestinal tract, while constructing a multi-level appetite-suppression system with temporal continuity.The invention overcomes problems in the prior art, including poor stability, low bioavailability, and fragmented appetite regulation, and achieves synergistic effects in fat burning and intake control. It is suitable for preparing oral solid formulations, with high safety, good stability, and suitability for large-scale industrial production and commercialization.

Description

[0001] DESCRIPTION

[0002] A guarana extract-EGCG synergistic fat-burning slimming composition

[0003] TECHNICAL FIELD

[0004] The present invention relates to the technical field of functional foods and weight management, and in particular to a guarana extract-EGCG synergistic fat-burning slimming composition.

[0005] BACKGROUND ART

[0006] Obesity is a chronic metabolic disease caused by long-term energy intake exceeding energy expenditure, and its incidence continues to rise worldwide, having become an important factor threatening public health. Obesity not only affects body shape and appearance, but is also a major risk factor for various chronic diseases such as type 2 diabetes, cardiovascular diseases, hypertension, and certain cancers. At present, interventions against obesity mainly include dietary control, exercise therapy, drug therapy, and auxiliary intervention by functional foods. Among these, slimming compositions based on natural plant extracts have become a research and development hotspot because of their relatively high safety and consumer acceptance. An ideal slimming product should be capable of effectively promoting lipolysis and energy expenditure while achieving stable appetite regulation, thereby realizing sustained weight reduction without causing obvious side effects.

[0007] Various slimming compositions containing guarana extract and green-tea extract have already been disclosed in the prior art. For example, European patent application EP2347660A1 discloses a composition for promoting the control of total cholesterol and low-density lipoprotein cholesterol in an individual, and / or reducing body weight, and / or promoting thermogenesis, which comprises green-tea extract (containing at least 50% epigallocatechin gallate), guarana extract, yerba mate extract, and conjugated linoleic acid. This composition mainly enhances energy metabolism through the superposition of multiple thermogenic ingredients. In another example, DESCRIPTION

[0008] Chinese patent CN102048884B relates to a slimming composition containing guarana extract, but its components further include L-carnitine and the like, with emphasis on promoting the oxidative decomposition of fatty acids. In addition, existing studies have revealed that konjac glucomannan, as a soluble dietary fiber, has good water-absorption and swelling properties and can provide a physical sense of satiety. There are even literature reports describing konjac glucomannan as a skeletal material for gastric floating sustained-release tablets, so as to realize drug sustained release and gastric retention. However, none of the above prior-art solutions solves the following technical problems: although EGCG has the potential to promote fat oxidation and inhibit a-glucosidase activity, its chemical properties are extremely unstable, and after oral administration it is readily degraded in gastric acid and in the upper small-intestinal environment, resulting in extremely low actual bioavailability and making it difficult for EGCG to fully exert its blood-glucose-stabilizing and metabolic-regulating effects in vivo. Meanwhile, the appetite-suppression mechanisms in existing compositions are mostly limited to single physical filling or single neural excitation, lacking coherent temporal continuity from physical satiety to metabolic satiety, which leads to short-lived satiety and easy interference by blood-glucose fluctuations, making it difficult to achieve stable appetite control throughout the entire time course.

[0009] Accordingly, there remains an urgent technical gap in the art as to how, without relying on complex encapsulation processes or additional excipients, to simultaneously solve the two interrelated technical problems of poor EGCG stability and fragmented appetite-suppression mechanisms, and to construct a slimming composition capable of integrating efficient delivery of EGCG with time-sequenced regulation of appetite.

[0010] SUMMARY OF THE INVENTION

[0011] The object of the present invention is to overcome the deficiencies of the DESCRIPTION prior art by providing a guarana extract-EGCG synergistic fat-burning slimming composition. Through a specific ratio in parts by weight and limitation of key parameters, the composition uses a dynamic gel network formed by konjac glucomannan to realize gastric protection and programmed release of EGCG, while constructing a multi-level appetite-suppression system involving physical satiety, blood-glucose stabilization, and gut-brain- axis regulation, thereby achieving deep synergy between fat-burning and food-intake-control functions on the basis of significantly improved EGCG stability.

[0012] In order to solve the above technical problems, the present invention provides the following technical solution. In one aspect, the present invention provides a guarana extract-EGCG synergistic fat-burning slimming composition, wherein the composition comprises guarana extract, epigallocatechin gallate, and konjac glucomannan: the konjac glucomannan has a molecular weight greater than 500,000 Da and a purity of not less than 90%; the weight ratio of guarana extract, epigallocatechin gallate, and konjac glucomannan is 10-30:5-20:20-50; the konjac glucomannan forms, upon contact with water, a gel network encapsulating epigallocatechin gallate.

[0013] By combining guarana extract, epigallocatechin gallate, and konjac glucomannan having a molecular weight greater than 500,000 Da and a purity of not less than 90% at a weight ratio of 10-30:5-20:20-50, the konjac glucomannan can form, upon contact with water, a gel network encapsulating epigallocatechin gallate, thereby realizing in-situ physical protection of epigallocatechin gallate without the need for additional encapsulation materials.

[0014] Further, after absorbing water and swelling in gastric fluid, the gel network formed by the konjac glucomannan embeds epigallocatechin gallate DESCRIPTION within the gel network, and the gel network blocks direct contact between gastric acid and the epigallocatechin gallate.

[0015] By embedding epigallocatechin gallate within the gel network formed by konjac glucomannan after water absorption and swelling in gastric fluid, direct contact between gastric acid and epigallocatechin gallate can be blocked by the gel network, thereby significantly reducing the degradation loss of epigallocatechin gallate in the gastric environment.

[0016] Further, the konjac glucomannan gel network encapsulating epigallocatechin gallate enters the small intestine under gastric peristalsis, and the gel network erodes in the small intestine and continuously releases the encapsulated epigallocatechin gallate.

[0017] By allowing the konjac glucomannan gel network encapsulating epigallocatechin gallate to enter the small intestine under gastric peristalsis and erode therein, sustained and stable release of the encapsulated epigallocatechin gallate can be achieved, thereby prolonging the action time of epigallocatechin gallate in the small intestine.

[0018] Further, the konjac glucomannan is fermented by intestinal flora in the colon, while releasing the remaining epigallocatechin gallate that has not been released in the small intestine.

[0019] Through fermentation of konjac glucomannan by intestinal flora in the colon while simultaneously releasing the remaining epigallocatechin gallate not released in the small intestine, epigallocatechin gallate can exert local antioxidant and anti-inflammatory effects in the colon, and can synergistically improve the intestinal microecology together with short-chain fatty acids produced by fermentation of konjac glucomannan.

[0020] Further, the caffeine content in the guarana extract is 8%-l 5% by weight.

[0021] By controlling the caffeine content in the guarana extract within a range of 8%-15% by weight, stable thermogenic stimulation can be provided while avoiding discomfort reactions such as nervous tension caused by excessively DESCRIPTION high caffeine content.

[0022] Further, the purity of the epigallocatechin gallate is greater than 90% by weight.

[0023] By controlling the purity of the epigallocatechin gallate to greater than 90% by weight, stable supply of the effective ingredient in a unit mass of the composition can be ensured, thereby guaranteeing full exertion of its metabolic-regulating function.

[0024] Further, the weight ratio of the guarana extract to the epigallocatechin gallate is from 2:1 to 1:2.

[0025] By controlling the weight ratio of the guarana extract to the epigallocatechin gallate within the range of 2:1 to 1:2, the basal-metabolism-enhancing effect of guarana extract can be matched with the fat-oxidation-promoting effect of epigallocatechin gallate, thereby realizing synergistic enhancement of energy expenditure and fat mobilization.

[0026] Further, the retention rate of epigallocatechin gallate after 2 h in a simulated gastric fluid environment is greater than 80%.

[0027] By ensuring that the retention rate of epigallocatechin gallate after 2 h in a simulated gastric fluid environment is greater than 80%, the actual protective effect of the konjac glucomannan gel network on epigallocatechin gallate can be quantitatively characterized, thereby ensuring stability and consistency of batch-to-batch product quality.

[0028] Further, the composition is prepared as an oral solid preparation in the form of tablets, capsules, or granules.

[0029] By preparing the composition as an oral solid preparation in the form of tablets, capsules, or granules, konjac glucomannan can be ensured to remain in an unswollen state before reaching the stomach, thereby avoiding premature water absorption during storage or oral administration that could affect normal formation of the gel network.

[0030] Further, the viscosity of the konjac glucomannan, measured as a 1% DESCRIPTION aqueous solution at 20 °C, is greater than 20,000 mPa s.

[0031] By controlling the viscosity of the konjac glucomannan to greater than 20,000 mPa s as measured in a 1% aqueous solution at 20 °C, formation of a sufficiently dense and stable gel-network structure in gastric fluid can be ensured, thereby providing the necessary physical strength for encapsulating and protecting epigallocatechin gallate.

[0032] Compared with the prior art, the guarana extract-EGCG synergistic fat-burning slimming composition of the present invention has the following beneficial effects:

[0033] I. By compounding guarana extract, epigallocatechin gallate, and konjac glucomannan satisfying the key-parameter limitations at a specific weight ratio, the present invention can utilize the three-dimensional gel network formed by konjac glucomannan upon contact with water to realize in-situ physical encapsulation of epigallocatechin gallate without the need for additional encapsulation materials or complex encapsulation processes, thereby blocking degradation of the active ingredient by gastric acid, realizing programmed and stable release of the active ingredient throughout the gastrointestinal tract, and constructing an appetite-regulation system with coherent continuity from physical satiety to metabolic satiety. In this way, in-vivo bioavailability of the active ingredient is significantly improved, stable appetite control throughout the whole time course is achieved, and the technical defects existing in the prior art are overcome.

[0034] II. Through precise regulation of the ratio between guarana extract and epigallocatechin gallate, the present invention allows the two ingredients to form a synergistic effect during regulation of fat metabolism in the body, thereby simultaneously realizing elevation of basal metabolic level and promotion of the process of fat oxidation and decomposition. At the same time, by virtue of the characteristic that konjac glucomannan is fermented by flora in the colon, the intestinal microecological environment can be improved. DESCRIPTION

[0035] Thus, while ensuring slimming efficacy, the composition also takes into account stable regulation of glucose and lipid metabolism, reduces possible discomfort reactions caused by the active ingredients, and greatly improves product safety and long-term compliance.

[0036] Other advantages, objectives, and features of the present invention will be set forth in part in the following description, and in part will become apparent to those skilled in the art upon examination and study of the following, or may be learned from the practice of the present invention.

[0037] BRIEF DESCRIPTION OF THE DRAWINGS

[0038] In order to describe the technical solutions in the embodiments of the present invention or in the prior art more clearly, the drawings required for describing the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below merely illustrate certain embodiments of the present invention, and those of ordinary skill in the art may also obtain other drawings according to these drawings without creative effort.

[0039] Figure 1 is a process flow chart for preparation of the hard-capsule formulation in Embodiment 1 of the present invention;

[0040] Figure 2 is a process flow chart for preparation of the oral -tablet formulation in Embodiment 2 of the present invention;

[0041] Figure 3 is a process flow chart for preparation of the oral-granule formulation in Embodiment 3 of the present invention.

[0042] DETAILED DESCRIPTION

[0043] In order to further explain the technical means and effects adopted by the present invention to achieve the intended object of the invention, the specific embodiments, structures, features, and effects according to the present invention are described in detail below in conjunction with the drawings and preferred embodiments.

[0044] Embodiment 1 DESCRIPTION

[0045] This embodiment provides a guarana extract-EGCG synergistic fat-burning slimming composition, specifically in the form of a hard-capsule preparation. The core components of the composition are prepared according to an intermediate ratio range, and the preparation is completed by a conventional solid-preparation process, thereby fully realizing the whole-process effect of the composition in forming a gel network in the stomach to protect EGCG, sustained release in the small intestine, and secondary release by colonic fermentation, while also verifying the synergistic fat-burning effect of guarana extract and EGCG, thus fully demonstrating the practicability and technical effects of the technical solution.

[0046] The raw materials and reagents used in this embodiment are specifically as follows: guarana extract, wherein the caffeine content is 12% by weight; epigallocatechin gallate, having a purity of 95% by weight; konjac glucomannan, having a molecular weight of 800,000 Da, a purity of 92% by weight, and a viscosity of 28,000 mPa s for a 1% aqueous solution at 20 °C; pharmaceutical excipients comprising microcrystalline cellulose and magnesium stearate, both being pharmaceutical-grade specifications for oral solid preparations.

[0047] The core components of the composition in this embodiment are present in the following parts by weight: 20 parts of guarana extract, 10 parts of epigallocatechin gallate, and 35 parts of konjac glucomannan, wherein the weight ratio of guarana extract to epigallocatechin gallate is 2:1.

[0048] The complete formula of the hard-capsule preparation in this embodiment, in parts by weight, is as follows: 20 parts of guarana extract, 10 parts of epigallocatechin gallate, 35 parts of konjac glucomannan, 34 parts of microcrystalline cellulose, and 1 part of magnesium stearate, for a total of 100 parts. DESCRIPTION

[0049] As shown in Figure 1, the specific preparation process of the hard-capsule preparation in this embodiment comprises the following steps:

[0050] Step 1, raw-material pretreatment. Guarana extract, epigallocatechin gallate, konjac glucomannan, and microcrystalline cellulose are separately crushed in a universal pulverizer. After pulverization, they are passed through a standard 80-mesh sieve, and the undersize material is collected for later use. Magnesium stearate is passed through a standard 100-mesh sieve, and the undersize material is collected for later use. During pretreatment, the environmental relative humidity is controlled at not more than 45%, and the environmental temperature is controlled between 18 °C and 26 °C, so as to avoid premature water absorption and moisture uptake by the raw materials.

[0051] Step 2, final blending. All pretreated materials are accurately weighed according to the formula parts by weight. First, guarana extract, epigallocatechin gallate, konjac glucomannan, and microcrystalline cellulose are charged into a three-dimensional motion mixer, and the mixer is set at a speed of 15 r / min for 30 min to complete premixing of the main materials. After premixing is completed, the weighed magnesium stearate is added into the three-dimensional motion mixer, and the mixer is set at 10 r / min for 5 min to complete the final blending operation, thereby obtaining the final blend.

[0052] Step 3, content-uniformity test. The final blend is sampled and tested according to the content-uniformity test method in the General Chapters, Part IV, of the 2025 edition of the Pharmacopoeia. The test indexes are the content uniformity of epigallocatechin gallate and caffeine. The test result meets the limit requirement of A+2.2S < 15.0, and therefore the uniformity of the final blend is determined to be qualified.

[0053] Step 4, capsule filling. The qualified final blend is charged into a fully automatic hard-capsule filling machine. No. 0 gelatin hollow capsules are selected, and the fill weight is set at 0.5 g per capsule. During filling, sampling is conducted once every 15 min to test fill-weight variation, which is DESCRIPTION controlled within ±7.5%. After filling is completed, semi-finished capsules are collected, and defective products such as dented capsules, cracked capsules, and poorly locked capsules are rejected.

[0054] Step 5, finished-product testing and packaging. The filled semi-finished capsules are subjected to full-item testing according to the requirements for hard capsules in the General Chapters, Part IV, of the 2025 edition of the Pharmacopoeia. The test items include appearance, fill-weight variation, disintegration time limit, microbial limits, and assay. After all test items meet the standard requirements, sealed packaging is carried out using medical high-density polyethylene bottles, with 60 capsules per bottle, and the packaged products are then warehoused for storage.

[0055] The slimming hard-capsule composition prepared in this embodiment is subjected to the following performance and efficacy verifications. All verification experiments are carried out with three parallel groups, and the experimental results are expressed as the average values of the parallel groups.

[0056] I. Determination of EGCG retention rate in an in vitro simulated gastric fluid environment.

[0057] In this experiment, the paddle method (Method II) in the dissolution and release test method of the General Chapters, Part IV, of the 2025 edition of the Pharmacopoeia is adopted. Simulated gastric fluid is prepared according to pharmacopoeial standards, with a pH of 1.2. The experimental temperature is controlled at 37 °C ± 0.5 °C, and the paddle speed is set at 50 r / min.

[0058] The experimental procedure is as follows. Six hard capsules prepared in this embodiment are placed into six dissolution cups, respectively, and 900 mL of simulated gastric fluid is added into each dissolution cup. The instrument is started and timing begins. Samples are taken at 0.5 h, 1 h, and 2 h, respectively, with each sample volume being 5 mL. After each sampling, blank simulated gastric fluid of the same temperature and same volume is io DESCRIPTION replenished immediately. The obtained samples are analyzed by high-performance liquid chromatography to determine the content of epigallocatechin gallate, and the cumulative release amount of EGCG at each time point is calculated, thereby further calculating the EGCG retention rate after 2 h in the simulated gastric fluid environment.

[0059] The experimental results show that, in the simulated gastric fluid environment, the cumulative release amount of EGCG from the composition of this embodiment is 7.2% at 0.5 h, 11.5% at 1 h, and 13.8% at 2 h, corresponding to an EGCG retention rate of 86.2% after 2 h. During the experiment, it can be observed that after the capsule contents come into contact with simulated gastric fluid, the konjac glucomannan rapidly hydrates and swells to form a visibly discernible viscoelastic three-dimensional gel network, in which EGCG and guarana extract are encapsulated, thereby directly verifying the action mechanism whereby the composition forms a gel network in situ in the gastric environment to realize physical protection of EGCG.

[0060] IE Determination of in vitro release behavior throughout the whole gastrointestinal tract.

[0061] This experiment continues the system used in the above simulated gastric fluid experiment. After being kept in the simulated gastric fluid environment for 2 h, the dissolution system is replaced with simulated intestinal fluid, which is prepared according to pharmacopoeial standards and has a pH of 6.8. The experimental temperature and speed remain unchanged, thereby simulating the physiological process in which the composition enters the small intestine from the stomach. In the simulated intestinal fluid environment, samples are taken at 0.5 h, 1 h, 2 h, 4 h, and 6 h to determine the cumulative release amount of EGCG.

[0062] After being kept in the simulated intestinal fluid environment for 6 h, the dissolution system is replaced with simulated colonic fluid. The simulated n DESCRIPTION colonic fluid is prepared according to physiological conditions and contains an intestinal-flora suspension prepared from healthy human fecal filtrate, has a pH of 7.4, and is cultured under anaerobic conditions. The experimental temperature is maintained at 37 °C ± 0.5 °C. Samples are taken at 2 h, 4 h, 8 h, and 12 h to determine the cumulative release amount of EGCG.

[0063] The experimental results show that the cumulative release amount of EGCG from the composition of this embodiment reaches 68.5% after 6 h in the simulated intestinal fluid environment, exhibiting a sustained and stable release characteristic without dose dumping, thereby verifying that the gel network gradually erodes in the small-intestinal environment and realizes programmed sustained release of EGCG. In the simulated colonic fluid environment, the cumulative release amount of EGCG reaches 97.2% at 12 h, thereby verifying the mechanism whereby konjac glucomannan is fermented by intestinal flora in the colon to release the remaining EGCG and fully realizing the spatiotemporally programmed release of EGCG throughout the whole gastrointestinal tract.

[0064] III. Verification of in vivo efficacy in animals.

[0065] SPF-grade male C57BL / 6J mice having a body weight of 18 g to 22 g are used in this experiment. An obese-mouse model is established by feeding a high-fat diet for 8 weeks. After successful modeling, the mice are randomly divided into four groups, namely a model control group, a component control group, a konjac-only group, and the experimental group of this embodiment, with 12 mice in each group.

[0066] The administration regimen for each group is specifically as follows. The model control group is given physiological saline by gavage in an equivalent volume. The component control group is given a physical mixture of guarana extract and EGCG in an amount equivalent to that of the experimental group by gavage. The konjac-only group is given konjac glucomannan in an amount equivalent to that of the experimental group by gavage. The experimental DESCRIPTION group of this embodiment is given the composition contents prepared in this embodiment by gavage. The dosage is 200 mg / kg body weight per day for all groups, and gavage is performed once daily at a fixed time for 8 consecutive weeks. During the experiment, all mice are allowed free access to food and water and are maintained under a 12 h light / 12 h dark environment. Mouse body weight and food intake are recorded weekly. At the end of the experiment, body-fat percentage, serum GLP-1 level, and fecal short-chain fatty-acid content are determined.

[0067] The experimental results show that, after 8 consecutive weeks of administration, the body weight of mice in the experimental group of this embodiment is reduced by 21.3% compared with the model control group, the body-fat percentage is reduced by 32.7% compared with the model control group, and the average daily food intake is reduced by 28.4% compared with the model control group, all being significantly superior to those of the component control group and the konjac-only group. The serum GLP-1 level of mice in the experimental group of this embodiment is increased by 126.5% compared with the model control group, and the butyrate content in feces is increased by 89.2% compared with the model control group, thereby verifying that the composition realizes long-acting appetite suppression through regulation of the gut-brain axis while also realizing the synergistic fat-burning effect of guarana extract and EGCG.

[0068] Through the detailed preparation process, this embodiment clarifies the industrial implementation path of the composition. Through multi-dimensional performance-verification experiments, the whole-gastrointestinal-tract action mechanism of the composition is fully reproduced, thereby verifying the core technical effects of gastric protection of EGCG, programmed release, and synergistic fat burning.

[0069] Embodiment 2

[0070] This embodiment provides a guarana extract-EGCG synergistic DESCRIPTION fat-burning slimming composition, specifically in the form of an oral-tablet preparation. Preparation is completed by a conventional tablet-manufacturing process, thereby further verifying the gel-network-forming ability, EGCG-protective effect, and slimming efficacy of the composition in tablet form, and expanding the industrial application scenarios of the composition.

[0071] The raw materials and reagents used in this embodiment are specifically as follows: guarana extract, wherein the caffeine content is 10% by weight; epigallocatechin gallate, having a purity of 93% by weight; konjac glucomannan, having a molecular weight of 600,000 Da, a purity of 91% by weight, and a viscosity of 22,000 mPa s for a 1% aqueous solution at 20 °C; pharmaceutical excipients comprising microcrystalline cellulose, crospovidone, and magnesium stearate, all being pharmaceutical-grade specifications for oral solid preparations.

[0072] The core components of the composition in this embodiment are present in the following parts by weight: 12 parts of guarana extract, 8 parts of epigallocatechin gallate, and 25 parts of konjac glucomannan, wherein the weight ratio of guarana extract to epigallocatechin gallate is 3:2.

[0073] The complete formula of the tablet preparation in this embodiment, in parts by weight, is as follows: 12 parts of guarana extract, 8 parts of epigallocatechin gallate, 25 parts of konjac glucomannan, 52 parts of microcrystalline cellulose, 2 parts of crospovidone, and 1 part of magnesium stearate, for a total of 100 parts.

[0074] As shown in Figure 2, the specific preparation process of the oral-tablet preparation in this embodiment comprises the following steps:

[0075] Step 1, raw-material pretreatment. Guarana extract, epigallocatechin gallate, konjac glucomannan, microcrystalline cellulose, and crospovidone are separately crushed in a universal pulverizer. After pulverization, they are DESCRIPTION passed through a standard 80-mesh sieve, and the undersize material is collected for later use. Magnesium stearate is passed through a standard 100-mesh sieve, and the undersize material is collected for later use. During pretreatment, the environmental relative humidity is controlled at not more than 45%, and the environmental temperature is controlled between 18 °C and 26 °C, so as to avoid premature water absorption and moisture uptake by the raw materials.

[0076] Step 2, granulation. All pretreated materials are accurately weighed according to the formula parts by weight. Guarana extract, epigallocatechin gallate, konjac glucomannan, microcrystalline cellulose, and crospovidone are first charged into a high-speed mixing granulator, the agitator speed is set at 150 r / min, the chopper speed is set at 3000 r / min, and the premixing time is 5 min, thereby completing premixing of the main materials. After premixing is completed, the liquid-spraying system is started, purified water is sprayed into the granulator as a wetting agent, and, after spraying is completed, stirring and granulation are continued for 3 min to obtain wet granules.

[0077] Step 3, drying and sizing. The prepared wet granules are charged into a fluidized-bed dryer, the inlet-air temperature is set at 60 °C, the material temperature is controlled below 45 °C, and the drying time is 20 min. After drying is completed, the moisture content of the granules is measured and controlled within 3.0%-5.0%. The dried granules are then charged into an oscillating granulator and sized through a standard 24-mesh sieve, and unqualified granules with agglomeration or excessive fine powder are removed, thereby obtaining qualified dry granules.

[0078] Step 4, final blending. The qualified dry granules after sizing are charged into a three-dimensional motion mixer, and the weighed magnesium stearate is added at the same time. The mixer is set at 12 r / min for 8 min to complete the final blending operation, thereby obtaining the final mixed granules.

[0079] Step 5, content-uniformity test. The final mixed granules are sampled DESCRIPTION and tested according to the content-uniformity test method in the General Chapters, Part IV, of the 2025 edition of the Pharmacopoeia. The test indexes are the content uniformity of epigallocatechin gallate and caffeine. The test result meets the limit requirement of A+2.2S < 15.0, and therefore the uniformity of the final mixed granules is determined to be qualified.

[0080] Step 6, tableting. The qualified final mixed granules are charged into a rotary tablet press. Shallow concave punches having a punch diameter of 10 mm are used, and the tableting pressure is set at 40 kN to 60 kN to compress uncoated tablets having a tablet weight of 0.6 g / tablet. During tableting, sampling is conducted once every 20 min to test tablet hardness and weight variation, with tablet hardness controlled at 6 kg to 8 kg and weight variation controlled within ±5.0%. After tableting is completed, semi-finished uncoated tablets are collected, and defective products such as cracked tablets, loose tablets, and pitted tablets are rejected.

[0081] Step 7, finished-product testing and packaging. The pressed semi-finished uncoated tablets are subjected to full-item testing according to the requirements for tablets in the General Chapters, Part IV, of the 2025 edition of the Pharmacopoeia. The test items include appearance, weight variation, disintegration time limit, hardness, friability, microbial limits, and assay. After all test items meet the standard requirements, packaging is carried out by an aluminum-plastic blister packaging machine, with 12 tablets per plate. After packaging, external sealing is performed using laminated-film pouches, and the products are then warehoused for storage.

[0082] The slimming tablet composition prepared in this embodiment is subjected to the following performance and efficacy verifications. All verification experiments are carried out with three parallel groups, and the experimental results are expressed as the average values of the parallel groups.

[0083] I. Determination of EGCG retention rate in an in vitro simulated gastric DESCRIPTION fluid environment.

[0084] The experimental method is consistent with that of Embodiment 1. The paddle method (Method II) in the dissolution and release test method of the General Chapters, Part IV, of the 2025 edition of the Pharmacopoeia is used. The simulated gastric fluid has a pH of 1.2, the temperature is 37 °C ± 0.5 °C, and the rotation speed is 50 r / min. Sampling is conducted at 0.5 h, 1 h, and 2 h to determine the cumulative release amount of EGCG, and the EGCG retention rate after 2 h is calculated.

[0085] The experimental results show that, in the simulated gastric fluid environment, the cumulative release amount of EGCG from the composition of this embodiment is 8.7% at 0.5 h, 13.2% at 1 h, and 16.1% at 2 h, corresponding to an EGCG retention rate of 83.9% after 2 h. During the experiment, it can be observed that after the tablets disintegrate, the konjac glucomannan rapidly comes into contact with the simulated gastric fluid and hydrates and swells to form a dense three-dimensional gel network, thereby encapsulating EGCG within the network and verifying that, even in tablet form, the composition can still realize the core effects of in-situ gel-network formation and physical protection of EGCG.

[0086] IE Determination of in vitro release behavior throughout the whole gastrointestinal tract.

[0087] The experimental method is consistent with that of Embodiment 1. Full-process incubation is successively carried out in simulated gastric fluid for 2 h, simulated intestinal fluid for 6 h, and simulated colonic fluid for 12 h, and the cumulative release amount of EGCG at different time points is determined.

[0088] The experimental results show that the cumulative release amount of EGCG from the composition of this embodiment reaches 65.8% after 6 h in the simulated intestinal fluid environment, exhibiting a sustained and stable release characteristic, and reaches 96.7% after 12 h in the simulated colonic DESCRIPTION fluid environment, thereby verifying that, even in tablet form, the composition can still realize programmed release of EGCG throughout the whole gastrointestinal tract and fully realize the whole-process effect of gastric protection, sustained release in the small intestine, and fermentation-triggered release in the colon.

[0089] III. Verification of satiety in a human tasting trial.

[0090] Twenty healthy overweight volunteers are recruited for this experiment. The volunteers are aged 20 to 45 years and have a body mass index of 24 kg / m2to 28 kg / m2. They are randomly divided into two groups, namely an experimental group and a placebo group, with 10 volunteers in each group. Volunteers in the experimental group take the composition tablets prepared in this embodiment, 2 tablets each time, while volunteers in the placebo group take blank tablets without active ingredients, 2 tablets each time. After an overnight fast of 12 h, the volunteers take the samples while drinking 200 mL of warm water. A visual analog scoring method is used to determine hunger scores at 0.5 h, 1 h, 2 h, 4 h, and 6 h after administration. The scoring range is 0 to 10, wherein 0 means completely no hunger and 10 means extreme hunger.

[0091] The experimental results show that, within 6 h after administration, the hunger scores of the volunteers in the experimental group remain below 3 points throughout the whole period and are significantly lower than those of the placebo group, thereby verifying that the composition realizes whole-time-course appetite suppression through physical satiety, metabolic satiety, and gut-brain- axis regulation, without an obvious rebound in hunger.

[0092] Through the detailed granulation and tableting process, this embodiment clarifies the industrial implementation path of the tablet dosage form. Through in vitro release experiments and human tasting trials, the core technical effects of the composition under different dosage forms and ratios are verified.

[0093] Embodiment 3

[0094] This embodiment provides a guarana extract-EGCG synergistic DESCRIPTION fat-burning slimming composition, specifically in the form of an oral-granule preparation. Granules are prepared by a wet-granulation process, thereby verifying, under conditions of high active-ingredient content, the gel-network-forming ability, EGCG-protective effect, and synergistic fat-burning efficacy of the composition, and further improving the application scenarios of the technical solution.

[0095] The raw materials and reagents used in this embodiment are specifically as follows: guarana extract, wherein the caffeine content is 14% by weight; epigallocatechin gallate, having a purity of 98% by weight; konjac glucomannan, having a molecular weight of 1,200,000 Da, a purity of 95% by weight, and a viscosity of 35,000 mPa s for a 1% aqueous solution at 20 °C; pharmaceutical excipients comprising maltodextrin, steviol glycosides, and citric acid, all being pharmaceutical-grade or food-grade specifications for oral solid preparations.

[0096] The core components of the composition in this embodiment are present in the following parts by weight: 28 parts of guarana extract, 18 parts of epigallocatechin gallate, and 45 parts of konjac glucomannan, wherein the weight ratio of guarana extract to epigallocatechin gallate is 14:9.

[0097] The complete formula of the granule preparation in this embodiment, in parts by weight, is as follows: 28 parts of guarana extract, 18 parts of epigallocatechin gallate, 45 parts of konjac glucomannan, 8 parts of maltodextrin, 0.8 part of steviol glycosides, and 0.2 part of citric acid, for a total of 100 parts.

[0098] As shown in Figure 3, the specific preparation process of the oral-granule preparation in this embodiment comprises the following steps:

[0099] Step 1, raw-material pretreatment. Guarana extract, epigallocatechin gallate, konjac glucomannan, maltodextrin, steviol glycosides, and citric acid DESCRIPTION are separately crushed in a universal pulverizer. After pulverization, they are passed through a standard 80-mesh sieve, and the undersize material is collected for later use. During pretreatment, the environmental relative humidity is controlled at not more than 45%, and the environmental temperature is controlled between 18 °C and 26 °C, so as to avoid premature water absorption and moisture uptake by the raw materials.

[0100] Step 2, granulation. All pretreated materials are accurately weighed according to the formula parts by weight and are all charged into a high-speed mixing granulator. The agitator speed is set at 120 r / min, the chopper speed is set at 2500 r / min, and the premixing time is 8 min, thereby completing premixing of all materials. After premixing is completed, the liquid-spraying system is started, a 70% ethanol aqueous solution by volume fraction is sprayed into the granulator as a wetting agent, and, after spraying is completed, stirring and granulation are continued for 2 min to obtain wet granules.

[0101] Step 3, drying and sizing. The prepared wet granules are charged into a fluidized-bed dryer, the inlet- air temperature is set at 55 °C, the material temperature is controlled below 40 °C, and the drying time is 25 min. After drying is completed, the moisture content of the granules is measured and controlled within 2.0%-4.0%. The dried granules are then charged into an oscillating granulator, first sized through a standard 14-mesh sieve to remove excessively large agglomerated granules, then screened through a standard 60-mesh sieve to remove excessively fine powders, thereby obtaining qualified dry granules between 14 mesh and 60 mesh.

[0102] Step 4, content-uniformity test. The qualified dry granules after sizing are sampled and tested according to the content-uniformity test method in the General Chapters, Part IV, of the 2025 edition of the Pharmacopoeia. The test indexes are the content uniformity of epigallocatechin gallate and caffeine. The test result meets the limit requirement of A+2.2S < 15.0, and therefore the DESCRIPTION granule uniformity is determined to be qualified.

[0103] Step 5, finished-product testing and packaging. The qualified dry granules are subjected to full-item testing according to the requirements for granules in the General Chapters, Part IV, of the 2025 edition of the Pharmacopoeia. The test items include appearance, particle size, loss on drying, dissolvability, microbial limits, and assay. After all test items meet the standard requirements, unit-dose packaging is carried out using medical laminated pouches, with 2 g per pouch, and the packaged products are then warehoused for storage.

[0104] The slimming granule composition prepared in this embodiment is subjected to the following performance and efficacy verifications. All verification experiments are carried out with three parallel groups, and the experimental results are expressed as the average values of the parallel groups.

[0105] I. Determination of EGCG retention rate in an in vitro simulated gastric fluid environment.

[0106] The experimental method is consistent with that of Embodiment 1. The paddle method (Method II) in the dissolution and release test method of the General Chapters, Part IV, of the 2025 edition of the Pharmacopoeia is used. The simulated gastric fluid has a pH of 1.2, the temperature is 37 °C ± 0.5 °C, and the rotation speed is 50 r / min. Sampling is conducted at 0.5 h, 1 h, and 2 h to determine the cumulative release amount of EGCG, and the EGCG retention rate after 2 h is calculated.

[0107] The experimental results show that, in the simulated gastric fluid environment, the cumulative release amount of EGCG from the composition of this embodiment is 5.8% at 0.5 h, 9.6% at 1 h, and 11.3% at 2 h, corresponding to an EGCG retention rate of 88.7% after 2 h. During the experiment, it can be observed that after the granules dissolve, the konjac glucomannan rapidly hydrates and swells to form a denser three-dimensional DESCRIPTION gel network than those in Embodiments 1 and 2, thereby providing a more significant encapsulation effect for EGCG and verifying the enhanced protective effect of high-molecular- weight and high-viscosity konjac glucomannan on EGCG.

[0108] II. Determination of in vitro release behavior throughout the whole gastrointestinal tract.

[0109] The experimental method is consistent with that of Embodiment 1. Full-process incubation is successively carried out in simulated gastric fluid for 2 h, simulated intestinal fluid for 6 h, and simulated colonic fluid for 12 h, and the cumulative release amount of EGCG at different time points is determined.

[0110] The experimental results show that the cumulative release amount of EGCG from the composition of this embodiment reaches 71.2% after 6 h in the simulated intestinal fluid environment, exhibiting a more stable and sustained release characteristic without any dose dumping. The cumulative release amount of EGCG reaches 98.1% after 12 h in the simulated colonic fluid environment, thereby verifying that, under the conditions of a high ratio of active ingredients and high-molecular-weight konjac glucomannan, the composition can still fully realize programmed release of EGCG throughout the whole gastrointestinal tract while ensuring sufficient release of the active ingredients.

[0111] III. Verification of in vivo fat-burning efficacy in animals.

[0112] SPF-grade male SD rats having a body weight of 180 g to 220 g are used in this experiment. An obese-rat model is established by feeding a high-fat diet for 12 weeks. After successful modeling, the rats are randomly divided into two groups, namely a model control group and the experimental group of this embodiment, with 10 rats in each group.

[0113] The administration regimen for each group is specifically as follows. The model control group is given physiological saline by gavage in an equivalent DESCRIPTION volume, and the experimental group of this embodiment is given the granules of the composition prepared in this embodiment by gavage. The dosage is 300 mg / kg body weight per day, gavage is performed once daily at a fixed time for 12 consecutive weeks. During the experiment, all rats are allowed free access to food and water and are maintained under a 12 h light / 12 h dark environment. Rat body weight and body length are recorded weekly. At the end of the experiment, body-fat percentage, fasting blood glucose, serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol are determined.

[0114] The experimental results show that, after 12 consecutive weeks of administration, the body weight of rats in the experimental group of this embodiment is reduced by 24.6% compared with the model control group, Lee's index is reduced by 16.8% compared with the model control group, body-fat percentage is reduced by 37.2% compared with the model control group, and fasting blood glucose is reduced by 18.3% compared with the model control group. Serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol are all significantly lower than those of the model control group, thereby verifying that, under the condition of a high ratio of active ingredients, the composition has a synergistic fat-burning effect and also has an auxiliary effect in improving disturbances of glucose and lipid metabolism.

[0115] Through the detailed wet-granulation process, this embodiment clarifies the industrial implementation path of the granule dosage form. Through in vitro release experiments and in vivo animal experiments, the core technical effects of the composition under high-ratio conditions are verified, thereby further proving the stability and universality of the technical solution.

[0116] Comparative Example

[0117] This comparative example is the control experimental group of Embodiment 1. The component species and parts by weight of the DESCRIPTION composition are exactly the same as those of Embodiment 1, and only the key parameters of the konjac glucomannan are adjusted, while the remaining preparation process and experimental methods are all the same as those of Embodiment 1. This comparative example is used to comparatively verify the influence of the key parameters of konjac glucomannan on the core technical effects of the composition, thereby highlighting the superiority of the technical solution of the present invention.

[0118] Among the raw materials and reagents used in this comparative example, the specifications of guarana extract, epigallocatechin gallate, and pharmaceutical excipients are exactly the same as those of Embodiment 1, and only the parameters of the konjac glucomannan are adjusted as follows: molecular weight 300,000 Da, purity 85% by weight, and viscosity of 8,000 mPa s for a 1% aqueous solution at 20 °C.

[0119] The core components of the composition in this comparative example are exactly the same as those of Embodiment 1 in parts by weight, namely: 20 parts of guarana extract, 10 parts of epigallocatechin gallate, and 35 parts of konjac glucomannan. The complete formula of the hard-capsule preparation is exactly the same as that of Embodiment 1.

[0120] The preparation steps, parameters, and environmental-control requirements of this comparative example are exactly the same as those of Embodiment 1, thereby producing hard capsules of the same specification.

[0121] The performance- and efficacy-verification experimental methods, detection indexes, and parallel-group settings of this comparative example are exactly the same as those of Embodiment 1, and the experimental results are compared with those of Embodiment 1.

[0122] I. Determination of EGCG retention rate in an in vitro simulated gastric fluid environment.

[0123] The experimental results show that, in the simulated gastric fluid environment, the cumulative release amount of EGCG from the composition DESCRIPTION of this comparative example is 32.6% at 0.5 h, 51.8% at 1 h, and 68.3% at 2 h, corresponding to an EGCG retention rate of 31.7% after 2 h, which is significantly lower than the experimental result of Embodiment 1. During the experiment, it can be observed that the konjac glucomannan used in this comparative example, after coming into contact with the simulated gastric fluid, can only form a loose flocculent structure and cannot form a dense and stable three-dimensional gel network, such that effective encapsulation and protection of EGCG cannot be realized. This directly verifies that the key parameters of konjac glucomannan are necessary conditions for realizing gastric protection of EGCG.

[0124] IE Determination of in vitro release behavior throughout the whole gastrointestinal tract.

[0125] The experimental results show that the cumulative release amount of EGCG from the composition of this comparative example reaches 92.5% after 2 h in the simulated intestinal fluid environment, showing an obvious dose-dumping phenomenon and making it impossible to achieve a sustained and stable release effect. In the simulated colonic fluid environment, no obvious secondary-release phenomenon is observed, and the final cumulative release amount at 12 h is 94.1%, which is significantly different from the programmed-release characteristics of Embodiment 1. This verifies that konjac glucomannan not meeting the parameter requirements cannot realize the spatiotemporally programmed release of EGCG throughout the whole gastrointestinal tract, and cannot realize the effects of stable glucose control in the small intestine and gut-brain- axis regulation in the colon.

[0126] III. Verification of in vivo efficacy in animals.

[0127] The experimental method and grouping are consistent with those of Embodiment 1. The experimental results show that, after 8 consecutive weeks of administration, the body weight of mice in the comparative-example group is reduced by only 8.7% compared with the model control group, the body-fat DESCRIPTION percentage is reduced by only 12.4% compared with the model control group, and the average daily food intake is reduced by only 9.6% compared with the model control group. There is no significant difference in serum GLP-1 level or fecal butyrate content as compared with the model control group. The slimming efficacy and appetite-suppression effect are far lower than those of the experimental group of Embodiment 1, and the expected core technical effects of synergistic fat burning and whole-time-course appetite suppression cannot be realized.

[0128] By adjusting the key parameters of konjac glucomannan while keeping all other conditions the same as those of Embodiment 1, this comparative example ultimately shows that the composition cannot form a stable gel network, cannot realize gastric protection and programmed release of EGCG, and cannot realize the expected slimming and appetite-suppression effects. This directly proves that the key parameters of konjac glucomannan are necessary technical features for realizing the core technical effects of the present invention, and highlights the superiority of the technical solution of the present invention.

[0129] In order to visually show the differences in core parameters and key performance indexes among the three embodiments and the one comparative example, the core data are summarized in the following table. DESCRIPTION

[0130] It can be clearly seen from the above table that all three embodiments realize an EGCG retention rate of more than 80% in simulated gastric fluid and possess complete programmed-release characteristics and the expected slimming efficacy. By contrast, the comparative example loses the core technical effects of the present invention merely by adjusting the key parameters of konjac glucomannan, which directly proves that the technical DESCRIPTION features in the technical solution are necessary conditions for achieving the object of the present invention.

[0131] The foregoing descriptions are only preferred embodiments of the present invention and are not intended to limit the present invention in any form. Although the present invention has been disclosed above with reference to preferred embodiments, the present invention is not limited thereto. Any person skilled in the art, without departing from the scope of the technical solution of the present invention, may make some changes or modifications to the disclosed technical contents to form equivalent embodiments with equivalent changes. However, any simple modification, equivalent change, or modification made to the above embodiments according to the technical essence of the present invention without departing from the contents of the technical solution of the present invention shall still fall within the scope of the technical solution of the present invention.

Claims

CLAIMS1. A guarana extract-EGCG synergistic fat-burning slimming composition, characterized in that the composition comprises guarana extract, epigallocatechin gallate, and konjac glucomannan: the konjac glucomannan has a molecular weight greater than 500,000 Da and a purity of not less than 90%; the weight ratio of guarana extract, epigallocatechin gallate, and konjac glucomannan is 10-30:5-20:20-50; the konjac glucomannan forms, upon contact with water, a gel network encapsulating epigallocatechin gallate.

2. The guarana extract-EGCG synergistic fat-burning slimming composition according to claim 1, characterized in that, after absorbing water and swelling in gastric fluid, the gel network formed by the konjac glucomannan embeds the epigallocatechin gallate within the gel network, and the gel network blocks direct contact between gastric acid and the epigallocatechin gallate.

3. The guarana extract-EGCG synergistic fat-burning slimming composition according to claim 1, characterized in that the konjac glucomannan gel network encapsulating epigallocatechin gallate enters the small intestine under gastric peristalsis, and the gel network erodes in the small intestine and continuously releases the encapsulated epigallocatechin gallate.

4. The guarana extract-EGCG synergistic fat-burning slimming composition according to claim 1, characterized in that the konjac glucomannan is fermented by intestinal flora in the colon, while releasing the remaining epigallocatechin gallate that has not been released in the small intestine.

5. The guarana extract-EGCG synergistic fat-burning slimming composition according to claim 1, characterized in that the caffeine content in the guarana extract is 8%-l 5% by weight.

6. The guarana extract-EGCG synergistic fat-burning slimming composition according to claim 1, characterized in that the purity of theCLAIMS epigallocatechin gallate is greater than 90% by weight.

7. The guarana extract-EGCG synergistic fat-burning slimming composition according to claim 1, characterized in that the weight ratio of the guarana extract to the epigallocatechin gallate is from 2:1 to 1:2.

8. The guarana extract-EGCG synergistic fat-burning slimming composition according to claim 1, characterized in that the retention rate of epigallocatechin gallate after 2 h in a simulated gastric fluid environment is greater than 80%.

9. The guarana extract-EGCG synergistic fat-burning slimming composition according to claim 1, characterized in that the composition is prepared as an oral solid preparation in the form of tablets, capsules, or granules.

10. The guarana extract-EGCG synergistic fat-burning slimming composition according to claim 1, characterized in that the viscosity of the konjac glucomannan, measured as a 1% aqueous solution at 20 °C, is greater than 20,000 mPa s.

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