A liposome curcumin composition for conditioning the gastrointestinal tract and uses thereof

Abstract

This invention discloses a liposomal curcumin composition for regulating the gastrointestinal tract and its applications, belonging to the technical fields of food and health food. The composition consists of 60-80nm liposomal curcumin, prebiotics, and cardamom extract. The liposomal curcumin uses food-grade phospholipids to construct a biomimetic bilayer structure with an encapsulation rate ≥80%, ethanol residue ≤0.5‰, a 2-hour release rate <33% in simulated gastric juice, and a 2-hour release rate >80% in simulated intestinal juice at pH 7.4. The cardamom extract is a water or alcohol extract of cardamom, with a content of 10-60mg per serving. This invention achieves targeted sustained release of curcumin into the intestine through precise particle size control, synergistically regulating gut microbiota with prebiotics and enhancing gastrointestinal motility with cardamom extract. It regulates gastrointestinal function from multiple dimensions, including mucosal repair, microbiota balance, and motility improvement. The bioavailability is more than 18 times higher than ordinary curcumin. The product has high safety and good stability and can be prepared in various dosage forms such as oral liquid, solid beverage, soft capsules, or tablets, suitable for daily conditioning in people with gastrointestinal dysfunction.

Description

Technical Field

[0001] This invention belongs to the field of food and health food technology, and specifically relates to a liposomal curcumin composition for regulating the gastrointestinal tract and its application. Background Technology

[0002] In contemporary society, gastrointestinal dysfunction has become a prevalent sub-health condition due to multiple factors, including unbalanced diets, irregular work and rest schedules, continuously increasing mental stress, and exposure to environmental pollutants. Epidemiological statistics show that the incidence of functional dyspepsia in Chinese adults reaches 23.5%, the prevalence of irritable bowel syndrome is 5.7%-11.3%, and gastrointestinal symptoms related to gut microbiota imbalance account for more than 40% in urban populations. The core pathological mechanisms of the above-mentioned symptoms involve three dimensions: First, damage to the intestinal mechanical barrier, manifested by downregulation of tight junction proteins (such as atresia and closure proteins) between intestinal mucosal epithelial cells, abnormally increased intestinal permeability, and bacterial endotoxin translocation leading to chronic low-grade inflammation; Second, imbalance of the intestinal microbiota, with a significant decrease in the abundance of beneficial bacteria (such as Bifidobacterium and Lactobacillus), excessive proliferation of opportunistic pathogens (such as Escherichia coli and Clostridium perfringens), and insufficient secretion of microbial metabolites (such as short-chain fatty acids), further exacerbating intestinal immune disorders; Third, abnormal gastrointestinal motility regulation mechanisms, delayed gastric emptying, and slowed intestinal propulsion, leading to chyme retention, abdominal distension and pain, and changes in defecation rhythm.

[0003] Existing gastrointestinal conditioning products suffer from multiple technical deficiencies, making it difficult to achieve systemic conditioning effects. Traditional single-ingredient products, such as simple probiotic preparations, focus only on gut microbiota regulation and cannot simultaneously repair damaged intestinal mucosa or improve gastrointestinal motility, thus having limited efficacy for patients with intestinal barrier damage. Ordinary curcumin powder preparations have extremely poor water solubility (water solubility <0.01μg / mL) and low chemical stability, and are rapidly degraded by gastric acid after oral administration, resulting in a bioavailability of less than 1%, and cannot target intestinal lesions. Although some curcumin formulations using polysaccharide encapsulation improve water solubility to some extent, the release rate in simulated gastric juice at pH 2.0 is as high as 65% or more after 2 hours, with a large amount of active ingredients being degraded in the stomach. Furthermore, the wide particle size distribution (mostly 100-500nm) makes it difficult to efficiently cross the intestinal mucus layer and intestinal epithelial cell barrier, resulting in low efficiency of targeted intestinal drug release. In addition, existing compound formulas mostly adopt a simple compounding mode of "curcumin + single prebiotic", without synergistic optimization of the physicochemical properties and in vivo metabolic pathways of each component. They cannot achieve the multi-pathway synergistic effect of "mucosal repair - flora regulation - dynamic enhancement", and often have problems such as "slow effect, long treatment course and high recurrence rate" in clinical applications.

[0004] Specifically, the application of liposome encapsulation technology in oral curcumin formulations still faces key bottlenecks in the current technology: First, the particle size control precision is insufficient. Conventional liposome preparation methods (such as thin-film dispersion and reverse evaporation) yield products with particle sizes mostly between 100-200 nm, and there are significant batch-to-batch variations (RSD>15%). Large particles are easily captured by the reticuloendothelial system in the gastrointestinal tract or intercepted by the intestinal mucus layer, failing to effectively reach the intestinal epithelial absorption site. Second, the encapsulation efficiency is low. The encapsulation efficiency of most food-grade liposome curcumin is only 50%-70%. 0% free curcumin is prone to oxidative degradation during storage and gastrointestinal transport, affecting product stability; third, pH-responsive release performance is poor. Existing liposomes have poor structural stability in the gastric fluid environment and are prone to burst release, while the release rate in the intestinal fluid environment is slow, which cannot meet the target demand of "low release in the stomach and rapid release in the intestine"; fourth, there are safety concerns. Some processes use high-concentration organic solvents (such as chloroform and methanol) to improve the encapsulation rate. The residual amount of organic solvents in the finished product often exceeds 1‰, which does not meet the hygiene standards for food and health food.

[0005] The aforementioned problems severely limit the practical application value of curcumin in the field of gastrointestinal conditioning. It is necessary to develop a novel curcumin composition that combines high bioavailability, excellent intestinal targeting, and multi-dimensional synergistic effects. Summary of the Invention

[0006] In view of this, the present invention provides a liposomal curcumin composition for regulating the gastrointestinal tract and its application, in order to solve or alleviate one of the technical problems existing in the prior art, and at least provide a beneficial alternative.

[0007] The technical solution of this invention is implemented as follows: a composition for regulating the gastrointestinal tract, consisting of 60-80nm liposomal curcumin, prebiotics and cardamom extract; The liposomal curcumin is constructed with food-grade phospholipids to form a biomimetic bilayer liposome structure. The particle size is 60-80 nm as detected by dynamic light scattering, the encapsulation efficiency is ≥80% as detected by ultrafiltration centrifugation, and the residual ethanol content in the finished product is ≤0.5‰ as detected by gas chromatography. The liposomal curcumin showed a release rate of less than 33% after 2 hours in simulated gastric juice (containing pepsin, activity 3000-5000 U / g) at pH 2.0 with shaking at 37°C and 100 rpm, but a release rate of more than 80% after 2 hours in simulated intestinal juice (containing pancreatic enzymes, activity 4000-6000 U / g) at pH 7.4 with shaking at 37°C and 100 rpm. The food-grade phospholipids are selected from one or more of soybean lecithin, sunflower lecithin, and egg yolk lecithin. The prebiotics are selected from one or more of fructooligosaccharides, inulin, galactooligosaccharides, and xylooligosaccharides, and the content of prebiotics in each composition is 2-8g; The cardamom extract is prepared by water extraction or reflux extraction with 50%-70% ethanol by volume from the dried fruit of cardamom (Elettaria cardamomum), and the content of cardamom extract in each composition is 10-60 mg.

[0008] Preferably, the liposomal curcumin has a particle size of 65-75 nm, and the particle size distribution index (PDI) is controlled to be ≤0.25 by high-pressure homogenization-dynamic light scattering technology. The pressure of high-pressure homogenization is 800-1200 bar, and the number of cycles is 5-10. Of the food-grade phospholipids, soybean lecithin has a purity of ≥95%, sunflower lecithin has a purity of ≥92%, and egg yolk lecithin has a purity of ≥90%. The mass ratio of phospholipids to curcumin is 8:1-15:1, preferably 10:1-12:1.

[0009] Preferably, the encapsulation efficiency of the liposomal curcumin is 85%-92%, as determined by ultrafiltration centrifugation (molecular weight cutoff 10kDa, rotation speed 12000r / min, centrifugation time 30min). The residual ethanol content in the finished product is 0.1‰-0.4‰, which is determined by headspace gas chromatography (capillary column DB-624, flame ionization detector). The composition of the pH 2.0 simulated gastric juice is as follows: Sodium chloride 2.0 g / L, hydrochloric acid 7.0 mL / L, pepsin 3.2 g / L, pH adjusted to 2.0 ± 0.1 with hydrochloric acid; The pH 7.4 simulated intestinal fluid composition is as follows: potassium dihydrogen phosphate 6.8 g / L, sodium hydroxide 0.2 g / L, pancreatic enzyme 10.0 g / L, and the pH value is adjusted to 7.4 ± 0.1 with sodium hydroxide solution.

[0010] Preferably, the liposomal curcumin has a release rate of 18%-30% in simulated gastric fluid at pH 2.0 and a release rate of 85%-95% in simulated intestinal fluid at pH 7.4 after 2 hours. The method for determining the release rate is as follows: Take an appropriate amount of liposomal curcumin composition, put it into a dialysis bag (molecular weight cutoff 3.5kDa), and place it in simulated gastric fluid at pH 2.0 and simulated intestinal fluid at pH 7.4 respectively. Shake at 37℃ for 100 rpm. Take samples at 0.5h, 1h and 2h respectively. Determine the curcumin content in the release solution by ultraviolet-visible spectrophotometry (detection wavelength 425nm) and calculate the cumulative release rate.

[0011] Preferably, in the prebiotic, the degree of polymerization of fructooligosaccharides is 2-8, the average molecular weight of inulin is 3000-5000 Da, the purity of galactooligosaccharides is ≥90%, and the purity of xylooligosaccharides is ≥95%. Each serving of the composition contains 3-5g of prebiotics, preferably 4g; The prebiotics in the composition are used to promote the targeted proliferation of Bifidobacteria and Lactobacillus in the intestine, promote the production of short-chain fatty acids, and regulate the intestinal pH to 6.0-6.8.

[0012] Preferably, the cardamom extract contains ≥6% volatile oil, and the characteristic components, as determined by gas chromatography-mass spectrometry (GC-MS), are α-terpineol, eucalyptol, and α-pinene, with the total content of the three accounting for 45%-60% of the total volatile oil. The method for preparing the water extract is as follows: take dried cardamom fruit, crush it through a 40-mesh sieve, add 8-12 times the amount of purified water, reflux extract 2-3 times, each time for 1.5-2 hours, combine the extracts, concentrate under reduced pressure to a relative density of 1.10-1.15 (60℃), vacuum dry, and crush through an 80-mesh sieve; The method for preparing the alcohol extract is as follows: Take dried cardamom fruit, pulverize it through a 40-mesh sieve, add 8-12 times the volume of 50%-70% ethanol, reflux extract 2-3 times, 1.5-2 hours each time, combine the extracts, recover the ethanol under reduced pressure, concentrate to a relative density of 1.10-1.15 (60℃), vacuum dry, and pulverize through an 80-mesh sieve.

[0013] Preferably, the composition further includes excipients permitted in the food or health food industry for the preparation of oral liquids, solid beverages, soft capsules or tablets; The excipients of the oral liquid include purified water, sorbitol, and citric acid, with the following weight percentages for each component: Liposome curcumin 0.5%-1.5%, prebiotics 10%-20%, cardamom extract 0.02%-0.12%, sorbitol 3%-8%, citric acid 0.1%-0.3%, balance purified water; The excipients of the solid beverage include maltodextrin and sucralose, and the weight percentage of each component is as follows: Liposome curcumin 1%-3%, prebiotics 30%-50%, cardamom extract 0.05%-0.3%, maltodextrin 40%-60%, sucralose 0.05%-0.15%.

[0014] Preferably, the soft capsule shell is composed of gelatin, glycerin, and purified water in a weight ratio of 1:0.4:1.2, and the weight percentage of each component in the contents is as follows: Liposome curcumin 2%-5%, prebiotics 25%-45%, cardamom extract 0.08%-0.5%, soybean oil 20%-40%, beeswax 1%-3%; The excipients of the tablets include microcrystalline cellulose, sodium carboxymethyl starch, and magnesium stearate, with the following weight percentages for each component: Liposome curcumin 1.5%-4%, prebiotics 20%-40%, cardamom extract 0.06%-0.4%, microcrystalline cellulose 30%-50%, sodium carboxymethyl starch 3%-8%, magnesium stearate 0.5%-1.5%.

[0015] Preferably, the optimal way to take the composition is 30-60 minutes after a meal, once or twice a day, with each dose of curcumin being 50-150 mg. The basis for taking it after meals is to match the human gastrointestinal metabolic rhythm. After meals, the pH value in the stomach rises to 3.0-4.0, which can reduce the initial release rate of liposomes in the stomach, prolong their action time in the intestine, and improve the absorption and utilization rate of the ingredients. Animal studies have shown that the bioavailability of curcumin in the postprandial administration group was 27%-35% higher than that in the fasting administration group.

[0016] Preferably, the gastrointestinal problems targeted by the application include insufficient gastrointestinal motility, indigestion, intestinal sensitivity, recurrent bloating and diarrhea, intestinal flora imbalance, and impaired intestinal barrier. The target population for the food or health food mentioned above includes people with irregular eating habits, people with gastrointestinal dysfunction caused by high mental stress, middle-aged and elderly people with decreased intestinal function, and patients with irritable bowel syndrome. The product forms of the application include ready-to-drink oral liquids, portable solid beverages, soft capsule dietary supplements, and chewable tablets.

[0017] The embodiments of the present invention have the following advantages due to the adoption of the above technical solutions: First, by precisely controlling the liposome particle size to 60-80 nm, this size range is both smaller than the pore size of the intestinal mucus layer (approximately 100-200 nm), allowing for efficient penetration of the mucus barrier to reach the intestinal epithelial surface, and larger than the glomerular filtration threshold (approximately 10 nm), preventing the active ingredient from being rapidly cleared through blood circulation. Combined with pH-responsive release characteristics, the liposomes are structurally stable in the acidic environment of the stomach (2-hour release rate <33%), effectively avoiding gastric degradation. After entering the intestine, the neutral pH of the intestinal fluid induces a phase transition in the phospholipid bilayer structure, rapidly releasing curcumin (2-hour release rate >80%), achieving precise delivery to intestinal lesions. In vitro cell experiments show that the uptake rate of 60-80 nm liposomal curcumin by intestinal epithelial cells (Caco-2 cells) is 12.7 times that of ordinary curcumin suspension and 3.2 times that of 100-200 nm liposomes.

[0018] Secondly, liposomal curcumin targets the intestinal mucosa, repairing the damaged intestinal barrier by upregulating the expression of tight junction proteins (Occludin, Claudin-1), inhibiting the activation of the NF-κB inflammatory signaling pathway, and reducing the levels of pro-inflammatory factors such as TNF-α and IL-6. Prebiotics selectively proliferate beneficial bacteria such as Bifidobacterium and Lactobacillus, promoting the production of short-chain fatty acids (acetic acid, propionic acid, butyric acid), regulating intestinal pH, and inhibiting the growth of harmful bacteria. Active ingredients such as α-terpineol and eucalyptol in cardamom extract promote gastrointestinal smooth muscle contraction by activating 5-HT4 receptors, increasing gastric emptying rate and small intestinal propulsion rate. These three components work synergistically to achieve homeostatic regulation of gastrointestinal function from three dimensions: mucosal repair, flora regulation, and motility enhancement. Animal experiments showed that after 28 days of continuous gavage, the intestinal mucosal damage score of model rats decreased by 62%, the abundance of fecal Bifidobacterium increased by 210%, and the gastric emptying rate increased by 38%, significantly better than the single-component control group.

[0019] Third, food-grade phospholipids are used as raw materials, and the residual ethanol content is strictly controlled to be ≤0.5‰ during the preparation process, which is far below the limit standard (≤10mg / kg) specified in GB 2760. The liposome encapsulation technology encapsulates curcumin in a hydrophobic core, isolating it from the influence of oxygen, light and metal ions. Accelerated stability test (40℃±2℃, RH75%±5%) shows that the curcumin retention rate is still 91.3% after 6 months of storage, which is much higher than the 32.7% of ordinary curcumin powder. All components of the composition are of natural origin. No adverse reactions were observed in the acute toxicity test (oral LD50 in mice>15g / kg BW) and the 30-day feeding test, which meets the long-term safety requirements for food and health food.

[0020] Fourth, the 60-80nm liposome structure significantly improves the solubility and dissolution rate of curcumin. In vivo pharmacokinetic experiments in rats showed that after oral administration of the composition of this invention, the time to peak concentration (Tmax) of curcumin was shortened to 1.5h, the peak concentration (Cmax) reached 4.8μg / mL, and the bioavailability (AUC0-24h) was 18.3 times that of ordinary curcumin suspension and 5.7 times that of polysaccharide-encapsulated curcumin, effectively solving the industry problem of low oral bioavailability of natural curcumin.

[0021] The above overview is for illustrative purposes only and is not intended to be limiting in any way. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features of the invention will become readily apparent from the accompanying drawings and the following detailed description. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0023] Figure 1 This is a flowchart illustrating the preparation process of the liposomal curcumin of the present invention. Figure 2 This diagram illustrates the pH-responsive release mechanism of liposomal curcumin according to the present invention. Figure 3 This is a flowchart illustrating the three-dimensional synergistic mechanism of the composition of the present invention in regulating the gastrointestinal tract. Detailed Implementation

[0024] In the following description, only certain exemplary embodiments are briefly described. As those skilled in the art will recognize, the described embodiments can be modified in various ways without departing from the spirit or scope of the invention. Therefore, the drawings and description are considered to be exemplary in nature and not restrictive.

[0025] The embodiments of the present invention will now be described in detail with reference to the accompanying drawings.

[0026] Example 1: Preparation and performance testing of oral liquid liposomal curcumin composition

[0027] 1. Raw material preparation

[0028] Liposome curcumin: Prepared using soybean lecithin (96% purity) and curcumin as raw materials, with a phospholipid:curcumin ratio of 10:1 (w / w), by high-pressure homogenization: Soybean lecithin was dissolved in food-grade ethanol and stirred in a 45°C water bath until completely dissolved. Curcumin was added, and stirring continued for 30 min to form an organic phase. The organic phase was slowly injected into preheated purified water at 55°C, and stirred to form a proemulsion. Subsequently, it was homogenized eight times under high pressure at 1000 bar to obtain a liposome suspension, which was sterilized by a 0.22 μm filter membrane. The particle size was measured to be 68 nm (PDI = 0.21), the encapsulation efficiency was 88%, and the ethanol residue was 0.28‰.

[0029] Prebiotic: Fructooligosaccharides (degree of polymerization 2-8, purity 95%), added at 4g / serving.

[0030] Cardamom extract: water extract (volatile oil content 6.8%), added at 30mg / serving.

[0031] Excipients: Sorbitol (food grade), Citric acid (food grade), purified water.

[0032] 2. Oral liquid preparation process

[0033] Weigh each component according to the formula in Table 1. Add liposome curcumin, fructooligosaccharides, and sorbitol to purified water and stir at 45°C until completely dissolved. Add cardamom extract and stir evenly. Adjust the pH to 4.2±0.1 with citric acid. After sterilization by filtering through a 0.22μm filter membrane, fill into 10mL brown glass bottles and seal to obtain the oral liquid product (each bottle is one dose).

[0034] Table 1. Oral liquid formulation for Example 1 (dosage per 1000 bottles)

[0035] 3. Performance Testing

[0036] (1) Detection of liposome particle size and encapsulation efficiency

[0037] The liposome particle size was determined using a Malvern laser particle size analyzer (Zetasizer Nano ZS90), and the results are shown in Table 2. Free curcumin was separated by ultrafiltration centrifugation (molecular weight cutoff 10 kDa, centrifugation at 12000 r / min for 30 min), and the encapsulation efficiency was determined by HPLC, and the results are shown in Table 3.

[0038] Table 2. Results of liposome particle size detection in Example 1

[0039] Table 3. Results of liposome encapsulation efficiency test in Example 1

[0040] (2) pH response release performance test

[0041] According to the second method (paddle method) of dissolution determination in General Chapter 0931 of Part IV of the Chinese Pharmacopoeia, oral liquid samples were placed in simulated gastric fluid at pH 2.0 and simulated intestinal fluid at pH 7.4, respectively. The samples were taken at 37℃±0.5℃ and 100rpm, and 5mL samples were taken at 0.5h, 1h and 2h respectively (with an equal amount of medium added at the same time). After filtration through a 0.45μm filter membrane, the curcumin concentration was determined by ultraviolet-visible spectrophotometry (425nm), and the cumulative release rate was calculated. The results are shown in Table 4.

[0042] Table 4 Results of pH-responsive release rate test of oral liquid in Example 1

[0043] (3) Detection of ethanol residue

[0044] The residual ethanol in the finished product was determined by headspace gas chromatography (capillary column DB-624, 30m×0.32mm×1.8μm; flame ionization detector; carrier gas N2, flow rate 1.0mL / min; column temperature 40℃ for 5min, then increased to 200℃ at 10℃ / min; injection port temperature 200℃, detector temperature 250℃). The results are shown in Table 5.

[0045] Table 5. Results of Ethanol Residue Detection in Example 1

[0046] (4) Stability test

[0047] The oral liquid samples were stored in an accelerated stability test chamber (40℃±2℃, RH75%±5%), and samples were taken at 0, 1, 3 and 6 months to detect the curcumin content. The results are shown in Table 6.

[0048] Table 6 Results of Accelerated Stability Test of Oral Liquid in Example 1

[0049] Example 2: Preparation and performance testing of solid beverage-type liposomal curcumin composition

[0050] 1. Raw material preparation

[0051] Liposome curcumin: Using sunflower lecithin (purity 93%) and curcumin as raw materials, the ratio of phospholipid to curcumin is 12:1 (w / w). The preparation process is the same as in Example 1. The particle size was measured to be 72nm (PDI=0.23), the encapsulation efficiency was 86%, and the ethanol residue was 0.32‰.

[0052] Prebiotic: Inulin (average molecular weight 3800 Da, purity 94%), added at 4g / serving.

[0053] Cardamom extract: 50% ethanol extract (volatile oil content 7.2%), added at 25mg / serving.

[0054] Excipients: Maltodextrin (DE value 18-20), sucralose (food grade).

[0055] 2. Solid Beverage Preparation Process

[0056] Weigh each component according to the formula in Table 7. Freeze-dry the liposomal curcumin (-50℃, vacuum degree 10Pa, 48h) to obtain liposomal curcumin freeze-dried powder. Mix inulin, maltodextrin, and sucralose evenly, add the liposomal curcumin freeze-dried powder and cardamom extract, mix for 30min (200rpm) using a three-dimensional motion mixer, pass through an 80-mesh sieve, and package into aluminum foil bags, 5g per bag (1 dose), to obtain the solid beverage product.

[0057] Table 7. Solid Beverage Formulation Table for Example 2 (Dosage per 1000 sachets)

[0058] 3. Performance Testing

[0059] (1) Test of rehydration properties of lyophilized liposome powder

[0060] Liposome curcumin lyophilized powder was taken and added to purified water at a ratio of 1:10 (w / v). The mixture was reconstituted by ultrasonication in a water bath at 40℃. The particle size and encapsulation efficiency of the liposomes after rehydration were detected. The results are shown in Table 8.

[0061] Table 8 Results of rehydration performance testing of liposome lyophilized powder in Example 2

[0062] (2) Bulk density and flowability testing

[0063] According to the particle size and particle size distribution determination method in General Chapter 0982 and the flowability determination method in Part IV of the Chinese Pharmacopoeia, the bulk density, angle of repose and compressibility of the solid beverage were tested. The results are shown in Table 9, indicating that the product has good flowability and filling properties and is suitable for industrial packaging.

[0064] Table 9 Results of Bulk Density and Flowability Testing for Solid Beverages in Example 2

[0065] (3) Testing of mixing performance

[0066] Take one packet (5g) of solid beverage sample, add 200mL of 40℃ warm water, stir for 30s, and observe the dispersibility, solubility and precipitation after reconstitution. The results are shown in Table 10.

[0067] Table 10 Results of Solid Beverage Mixing Performance Test in Example 2

[0068] (4) Detection of gut microbiota regulation potential (in vitro fermentation test)

[0069] An in vitro fermentation model of human fecal microbiota was used to investigate the effect of solid beverages on the proliferation of beneficial bacteria. Fresh feces from healthy volunteers were collected, and a 10% fecal microbiota suspension was prepared. This suspension was inoculated into a fermentation medium containing solid beverage (final concentration 5 g / L) and anaerobic incubated at 37°C for 24 h. The colony counts of Bifidobacterium and Lactobacillus were determined using the plate count method. The results are shown in Table 11.

[0070] Table 11. Effects of in vitro fermentation of solid beverages on gut microbiota in Example 2 (n=3)

[0071] Example 3: Preparation and performance testing of soft capsule-type liposomal curcumin composition

[0072] 1. Raw material preparation

[0073] Liposome curcumin: Using egg yolk lecithin (purity 91%) and curcumin as raw materials, the ratio of phospholipid to curcumin is 11:1 (w / w). The preparation process is the same as in Example 1. The particle size was measured to be 70 nm (PDI=0.22), the encapsulation rate was 90%, and the ethanol residue was 0.22‰.

[0074] Prebiotic: Galacto-oligosaccharides (92% purity), added at 4g / serving.

[0075] Cardamom extract: water extract (volatile oil content 6.5%), added at 35mg / serving.

[0076] Ingredients: Soybean oil (food grade), beeswax (food grade), gelatin, glycerin, purified water.

[0077] 2. Soft Capsule Preparation Process

[0078] (1) Preparation of capsule shell: According to the weight ratio of gelatin: glycerol: purified water = 1: 0.4: 1.2, the gelatin was soaked in water for 2 hours, heated to 60°C to melt, glycerol was added, stirred for 30 minutes, and vacuum degassing was performed to obtain capsule shell solution.

[0079] (2) Preparation of contents: Weigh each component according to the formula in Table 12, add liposome curcumin and galactooligosaccharide to molten soybean oil and beeswax, stir at 45°C until uniform, add cardamom extract, and continue stirring for 20 min to obtain soft capsule contents.

[0080] (3) Pelletizing and drying: The capsule shell liquid and contents are pressed into shape using a soft capsule press (0.5 mL die volume), and dried in an environment of 25℃ and RH30% for 24 hours. The capsules are then wiped, inspected, and packaged to obtain the soft capsule product (each capsule is one dose).

[0081] Table 12 Soft Capsule Formulation Table for Example 3 (Dosage per 1000 capsules)

[0082] 3. Performance Testing

[0083] (1) Soft capsule disintegration time limit test

[0084] According to the disintegration time test method in General Chapter 0921 of Part IV of the Chinese Pharmacopoeia, the disintegration time of the soft capsules in simulated gastric juice was tested using a disintegration instrument. The results are shown in Table 13, which meet the requirements of the Chinese Pharmacopoeia (≤60min).

[0085] Table 13 Results of soft capsule disintegration time test in Example 3

[0086] (2) Detection of liposome stability in contents

[0087] The contents of the soft capsules were diluted 10 times with pH 7.4 phosphate buffer, and the liposome particle size and encapsulation efficiency were measured. The results are shown in Table 14, indicating that the liposome structure was not damaged during the soft capsule preparation process.

[0088] Table 14 Results of liposome stability testing of soft capsule contents in Example 3

[0089] (3) Detection of potential for improving gastrointestinal motility (ex vivo intestinal segment test)

[0090] A jejunal segment (approximately 2 cm in length) from a healthy SD rat was suspended in an organ bath containing Krebs-Henseleit buffer. A mixture of 95% O2 and 5% CO2 gas was introduced and kept at a constant temperature of 37°C. After a preload of 1 g and equilibration for 30 min, the contents of the soft capsule were added (final concentration 1 mg / mL). The amplitude and frequency of intestinal contractions were recorded. The results are shown in Table 15, indicating that the product has the effect of promoting gastrointestinal motility.

[0091] Table 15 Results of contractile activity detection of isolated intestinal segments from soft capsules in Example 3 (n=6)

[0092] (4) Long-term stability test

[0093] The soft capsule samples were stored in a long-term stability test chamber (25℃±2℃, RH60%±10%), and samples were taken at 0, 3, 6 and 12 months to detect the curcumin content and peroxide value. The results are shown in Table 16.

[0094] Table 16 Results of the long-term stability test of soft capsules in Example 3

[0095] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any person skilled in the art can easily conceive of various variations or substitutions within the technical scope disclosed in the present invention, and these should all be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A composition for regulating the gastrointestinal tract, characterized in that, It is composed of 60-80nm liposomal curcumin, prebiotics and cardamom extract; The liposomal curcumin is constructed with food-grade phospholipids to form a biomimetic bilayer liposome structure. The particle size is 60-80 nm as detected by dynamic light scattering, the encapsulation efficiency is ≥80% as detected by ultrafiltration centrifugation, and the residual ethanol content in the finished product is ≤0.5‰ as detected by gas chromatography. The liposomal curcumin showed a release rate of less than 33% after 2 hours in simulated gastric juice (containing pepsin, activity 3000-5000 U / g) at pH 2.0 with shaking at 37°C and 100 rpm, but a release rate of more than 80% after 2 hours in simulated intestinal juice (containing pancreatic enzymes, activity 4000-6000 U / g) at pH 7.4 with shaking at 37°C and 100 rpm. The food-grade phospholipids are selected from one or more of soybean lecithin, sunflower lecithin, and egg yolk lecithin. The prebiotics are selected from one or more of fructooligosaccharides, inulin, galactooligosaccharides, and xylooligosaccharides, and the content of prebiotics in each composition is 2-8g; The cardamom extract is prepared by water extraction or reflux extraction with 50%-70% ethanol by volume from the dried fruit of cardamom (Elettaria cardamomum), and the content of cardamom extract in each composition is 10-60 mg.

2. The composition for regulating the gastrointestinal tract according to claim 1, characterized in that, The liposomal curcumin has a particle size of 65-75 nm, and the particle size distribution index (PDI) is controlled to be ≤0.25 by high-pressure homogenization-dynamic light scattering technology. The high-pressure homogenization pressure is 800-1200 bar, and the number of cycles is 5-10. Of the food-grade phospholipids, soybean lecithin has a purity of ≥95%, sunflower lecithin has a purity of ≥92%, and egg yolk lecithin has a purity of ≥90%. The mass ratio of phospholipids to curcumin is 8:1-15:1, preferably 10:1-12:

1.

3. The composition for regulating the gastrointestinal tract according to claim 1, characterized in that, The encapsulation efficiency of the liposomal curcumin was 85%-92%, which was determined by ultrafiltration centrifugation (molecular weight cutoff 10kDa, rotation speed 12000r / min, centrifugation time 30min). The residual ethanol content in the finished product is 0.1‰-0.4‰, which is determined by headspace gas chromatography (capillary column DB-624, flame ionization detector). The composition of the pH 2.0 simulated gastric juice is as follows: Sodium chloride 2.0 g / L, hydrochloric acid 7.0 mL / L, pepsin 3.2 g / L, pH adjusted to 2.0 ± 0.1 with hydrochloric acid; The pH 7.4 simulated intestinal fluid composition is as follows: potassium dihydrogen phosphate 6.8 g / L, sodium hydroxide 0.2 g / L, pancreatic enzyme 10.0 g / L, and the pH value is adjusted to 7.4 ± 0.1 with sodium hydroxide solution.

4. The gastrointestinal regulating composition according to claim 1, characterized in that, The liposomal curcumin showed a release rate of 18%-30% in simulated gastric fluid at pH 2.0 after 2 hours, and a release rate of 85%-95% in simulated intestinal fluid at pH 7.4 after 2 hours. The method for determining the release rate is as follows: Take an appropriate amount of liposomal curcumin composition, put it into a dialysis bag (molecular weight cutoff 3.5kDa), and place it in simulated gastric fluid at pH 2.0 and simulated intestinal fluid at pH 7.4 respectively. Shake at 37℃ for 100 rpm. Take samples at 0.5h, 1h and 2h respectively. Determine the curcumin content in the release solution by ultraviolet-visible spectrophotometry (detection wavelength 425nm) and calculate the cumulative release rate.

5. The composition for regulating the gastrointestinal tract according to claim 1, characterized in that, The prebiotics contain fructooligosaccharides with a degree of polymerization of 2-8, inulin with an average molecular weight of 3000-5000 Da, galactooligosaccharides with a purity of ≥90%, and xylooligosaccharides with a purity of ≥95%. Each serving of the composition contains 3-5g of prebiotics, preferably 4g; The prebiotics in the composition are used to promote the targeted proliferation of Bifidobacteria and Lactobacillus in the intestine, promote the production of short-chain fatty acids, and regulate the intestinal pH to 6.0-6.

8.

6. The gastrointestinal regulating composition according to claim 1, characterized in that, The cardamom extract contained ≥6% volatile oil, and the characteristic components, as determined by gas chromatography-mass spectrometry (GC-MS), were α-terpineol, eucalyptol, and α-pinene, with the total content of the three accounting for 45%-60% of the total volatile oil. The method for preparing the water extract is as follows: take dried cardamom fruit, crush it through a 40-mesh sieve, add 8-12 times the amount of purified water, reflux extract 2-3 times, each time for 1.5-2 hours, combine the extracts, concentrate under reduced pressure to a relative density of 1.10-1.15 (60℃), vacuum dry, and crush through an 80-mesh sieve; The method for preparing the alcohol extract is as follows: Take dried cardamom fruit, pulverize it through a 40-mesh sieve, add 8-12 times the volume of 50%-70% ethanol, reflux extract 2-3 times, 1.5-2 hours each time, combine the extracts, recover the ethanol under reduced pressure, concentrate to a relative density of 1.10-1.15 (60℃), vacuum dry, and pulverize through an 80-mesh sieve.

7. The gastrointestinal regulating composition according to claim 1, characterized in that, The composition also includes excipients permitted in the food or health food industry for the preparation of oral liquids, solid beverages, soft capsules or tablets; The excipients of the oral liquid include purified water, sorbitol, and citric acid, with the following weight percentages for each component: Liposome curcumin 0.5%-1.5%, prebiotics 10%-20%, cardamom extract 0.02%-0.12%, sorbitol 3%-8%, citric acid 0.1%-0.3%, balance purified water; The excipients of the solid beverage include maltodextrin and sucralose, and the weight percentage of each component is as follows: Liposome curcumin 1%-3%, prebiotics 30%-50%, cardamom extract 0.05%-0.3%, maltodextrin 40%-60%, sucralose 0.05%-0.15%.

8. The gastrointestinal regulating composition according to claim 7, characterized in that, The soft capsule shell is composed of gelatin, glycerin, and purified water in a weight ratio of 1:0.4:1.2, and the weight percentage of each component in the contents is as follows: Liposome curcumin 2%-5%, prebiotics 25%-45%, cardamom extract 0.08%-0.5%, soybean oil 20%-40%, beeswax 1%-3%; The excipients of the tablets include microcrystalline cellulose, sodium carboxymethyl starch, and magnesium stearate, with the following weight percentages for each component: Liposome curcumin 1.5%-4%, prebiotics 20%-40%, cardamom extract 0.06%-0.4%, microcrystalline cellulose 30%-50%, sodium carboxymethyl starch 3%-8%, magnesium stearate 0.5%-1.5%.

9. The gastrointestinal regulating composition according to claim 1, characterized in that, The optimal administration of the composition is 30-60 minutes after a meal, once or twice daily, with each dose of curcumin being 50-150 mg. The basis for taking it after meals is to match the human gastrointestinal metabolic rhythm. After meals, the pH value in the stomach rises to 3.0-4.0, which can reduce the initial release rate of liposomes in the stomach, prolong their action time in the intestine, and improve the absorption and utilization rate of the ingredients. Animal studies have shown that the bioavailability of curcumin in the postprandial administration group was 27%-35% higher than that in the fasting administration group.

10. The application of the gastrointestinal conditioning composition according to any one of claims 1-9 in the preparation of gastrointestinal conditioning foods and health foods, wherein the gastrointestinal function problems targeted by the application include insufficient gastrointestinal motility, indigestion, intestinal sensitivity, recurrent abdominal distension and diarrhea, intestinal flora imbalance and intestinal barrier damage; The target population for the food or health food mentioned above includes people with irregular eating habits, people with gastrointestinal dysfunction caused by high mental stress, middle-aged and elderly people with decreased intestinal function, and patients with irritable bowel syndrome. The product forms of the application include ready-to-drink oral liquids, portable solid beverages, soft capsule dietary supplements, and chewable tablets.

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