Method for preparing food-suppressing capsules containing multi-element nutritional microspheres and the resulting products

Abstract

To provide a preparation method for a diet-reducing capsule that can be quickly decomposed and accomplish improvement in healthy weight loss, nutrition supplement, intestinal adjustment, and probiotic planting ratio, and a diet-reducing capsule produced according to the preparation method.SOLUTION: The disclosure relates to a technological field in food biology and discloses a preparation method for a food intake inhibiting capsule including a multi-element nutrient microsphere and a product obtained. The food intake inhibiting capsule is composed of a porous capsule shell, a multi-element nutrient microsphere 8, and its matrix gel 9. The porous capsule shell is formed using laser perforation technology and accelerates decomposition of the capsule utilizing hydrodynamics. The multi-element nutrient microsphere is a micro container which is formed by using probiotics as a core material and using a freeze-dried protective agent, a natural polymer material embedded with vitamin, mineral and prebiotics, and an enteric coating material as wall materials.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present invention relates to a method for preparing anti-feedant capsules containing multi-element nutritional microspheres and the resulting anti-feedant capsules, which belong to the field of food biotechnology. [Background technology]

[0002] Daily supplementation of vitamins, minerals and probiotics is crucial, as they play different and important roles in the process of human metabolism, growth, development and health maintenance. And because some vitamins and probiotics lose their activity in the environment of gastric acid and bile salts due to their special properties, according to Chinese regulations, dietary supplement products need to reach the amount required by the human body during their storage period before they can play a role in health care, so vitamins and probiotics need to be protected.

[0003] In addition, as the standard of living of the people has improved, some people have unbalanced and unreasonable eating habits, and obesity has become an increasingly serious problem, resulting in a succession of serious health hazards for human diseases such as hypertension, type II diabetes, cardiovascular disease, cerebrovascular disease, and even some types of cancer. Therefore, weight management is an important means of preventing and delaying the occurrence and onset of these diseases.

[0004] Currently, many programs have been developed for weight management, usually involving lifestyle, pharmacological and surgical interventions. However, lifestyle interventions are easy to discontinue, and pharmacological and surgical interventions have significant side effects and are contrary to the principles of health. Basically, weight loss occurs when consumption is greater than intake, but increasing consumption requires a lot of exercise, which is difficult for people who are stressed or lack exercise. Therefore, it is particularly important to devise a way to lose weight healthily, with the goal of reducing intake and controlling food intake.

[0005] Regarding the problem of dietary control for weight loss, several measures have been taken. Patent CN113975335B uses green coffee bean extract, rosehip extract, saffron extract, and L-carnitine as raw materials to prepare a composition that controls appetite and induces satiety, and can achieve weight loss by inducing increased secretion of glucagon-like peptide-1 (GLP-1), which regulates the feeding center of the brain-gut axis and then affects the satiety center. However, this method has the risk that the increase in GLP-1 can cause side effects such as palpitations in obese people, or that the organs that secrete GLP-1 are overburdened and accelerated aging. Patent CN102905762B provides a gel mass of methylcellulose, which can give a feeling of satiety, but it lacks vitamins and minerals that meet the daily nutritional needs of the human body, and long-term deficiencies can cause physiological dysfunction, making it not worth the cost. At the same time, it is worth paying attention that obese patients may have different intestinal flora from normal, which may also be the cause of obesity, and weight loss is a long-term process, and without the hints of "vitamins", "minerals", "health", etc., obese people may only care about their weight and neglect their health, which will not lead to the formation of good eating habits. Therefore, the present invention aims to develop an appetite suppressant capsule that simultaneously supplements various nutrients. Summary of the Invention

[0006] The object of the present invention is to provide a method for preparing an food intake suppressing capsule (i.e., an intake reducing capsule) which disintegrates quickly and can achieve healthy weight loss, nutritional supplementation, intestinal regulation and improved probiotic inoculation rate, and a food intake suppressing capsule produced according to the method.

[0007] The specific technical solutions of the present invention are as follows:

[0008] 1. A method for preparing an anti-feedant capsule containing multi-element nutritional microspheres, the method comprising: Step (1) of adding sodium carboxymethylcellulose to an aqueous solution containing a polybasic carboxylic acid, stirring uniformly, drying in an oven, and then crosslinking at high temperature, crushing, sieving, washing and filtering with distilled water to prepare hydrogel wet particles; (2) inoculating the probiotics into a sterile medium with a fixed inoculation amount, repeatedly activating the probiotics under the same culture conditions for five generations, collecting the bacterial sludge by low-temperature centrifugation, washing the bacterial sludge with sterile saline, then uniformly mixing with an aqueous solution of a freeze-drying protection agent to obtain a bacterial suspension, then adding an aqueous solution of a natural polymer material to the bacterial suspension and mixing uniformly again, then hardening the resulting mixture, washing and filtering it to obtain the hardened probiotics, which are then stored at low temperature for preparation; (3) uniformly mixing the vitamin, mineral and prebiotic powders and passing them through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder; and then uniformly mixing the vitamin-mineral-prebiotic complex powder with the aqueous solution of natural polymer material to obtain a vitamin-mineral-prebiotic-natural polymer material mixed liquid; (4) uniformly mixing the hardened probiotic, vitamin-mineral-prebiotic-natural polymer material mixture to obtain a nutritional mixture, and then mixing the nutritional mixture with an aqueous solution of enteric coating material, followed by washing and filtering to obtain probiotic-prebiotic-vitamin-mineral wet microspheres; (5) homogeneously mixing the probiotic-prebiotic-vitamin-mineral wet microspheres and the hydrogel wet particles, followed by freeze-drying after preliminary cooling treatment, and then crushing and sieving to obtain capsule contents; and (6) fixing and laser drilling the capsule shell to obtain a porous capsule shell, and then bonding the porous capsule shell with the capsule contents to prepare an food-suppressing capsule containing the multi-element nutritional microspheres.

[0009] Furthermore, in step (1), the sodium carboxymethylcellulose and the polybasic carboxylic acid are crosslinked to form a three-dimensional network structure, and the viscosity of the sodium carboxymethylcellulose is 7,000 to 15,000.

[0010] Furthermore, in step (1), the polybasic carboxylic acid is any one selected from the group consisting of citric acid, aconitic acid, oxalic acid, tartaric acid, malic acid, acetic acid, malonic acid, succinic acid, adipic acid, azelaic acid, terephthalic acid, trimellitic acid, trimesic acid, ethylenediaminetetraacetic acid, and 2-methylglutaric acid, and is preferably citric acid.

[0011] Furthermore, in step (1), the viscosity of the sodium carboxymethylcellulose is 7,000 to 15,000, the mass ratio of the sodium carboxymethylcellulose to the polybasic carboxylic acid is 310 to 350:1, and the mass ratio of the sodium carboxymethylcellulose to water is 1:10 to 22.

[0012] Furthermore, in step (1), the stirring is performed as follows: first, the mixture is stirred at a rotation speed of 50-70 rpm for 80-100 min, and then at a rotation speed of 20-40 rpm for 14-20 h; and the oven drying is performed as follows: the oven temperature is adjusted to 40-60°C, the mixture is dried for 20-28 h, and the gel is turned over and then dried for 28-36 h.

[0013] Furthermore, in step (1), high-temperature crosslinking refers to treating the dried gel at high temperature, the high-temperature crosslinking temperature is 110 to 130°C, and the time is 3.6 to 4.4 hours.

[0014] Furthermore, in step (1), crushing and sieving are performed as follows: the crosslinked product is crushed by a crusher and then sieved through 18 mesh and 26 mesh sieves, and distilled water washing is performed as follows: the solid hydrogel particles are washed with distilled water 2 to 6 times, each time for 2 to 4 h, and the mass ratio of solid hydrogel particles to distilled water is 1:100 to 200 for each washing.

[0015] Further, in step (2), the probiotic is selected from the group consisting of Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus fermentum, Lactobacillus salivarius, Lactobacillus helveticus, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus crispatus, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus acidophilus, Lactobacillus acidophilus), Lactobacillus casei subsp.casei, Lactobacillus paracasei, Lactobacillus reuteri, Bifidobacterium lactis, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium adolescentis, Bifidobacterium animalis, and Streptococcus thermophilus. The mixed strain is selected from the group consisting of Bifidobacterium longum and Lactobacillus acidophilus.

[0016] Furthermore, in step (2), the natural polymer material is any one or more selected from the group consisting of sodium alginate, chitosan, modified starch, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxypropylcellulose, gellan gum, κ-carrageenan, gum arabic, pectin, carrageenan, gellan gum, xanthan gum, maltodextrin, β-cyclodextrin, gelatin, soybean isolated protein, and whey protein, and is preferably sodium alginate, chitosan, and gellan gum, and the weight ratio thereof is sodium alginate:chitosan:gellan gum=40:3:5.

[0017] Furthermore, in step (2), the freeze-drying protection agent is any one or more selected from the group consisting of soluble starch, hydroxyethyl starch, resistant dextrin, fructose, glucose, lactose, sucrose, ribose, rhamnose, galactose, fucose, mannose, arabinose, xylan, skim milk powder, glycerol, lactitol, sorbitol, mannitol, xylitol, erythritol, maltitol, sodium glutamate, antifreeze peptides, silk peptides, fish collagen peptides, collagen, and polyvinylpyrrolidone, and is preferably soluble starch, skim milk powder, glycerol, and xylan, and the weight ratio thereof is soluble starch:skim milk powder:glycerol:xylan=5:6:1:10.

[0018] Furthermore, in step (2), the inoculation amount of the probiotics is 1.5 to 4.5% of the mass of the sterilized medium, and the sterilized medium is an MRS liquid medium.

[0019] Furthermore, in step (2), the method for activating probiotics can be operated according to the method disclosed in the prior art, and the low-temperature centrifugation method involves centrifuging the sterilized medium inoculated with probiotics at 3-5°C, the centrifugation rotation speed is 3500-5500 rpm, and the centrifugation time is 10-20 min.

[0020] Furthermore, in step (2), the bacterial sludge is washed with sterile saline, the washing times are 1 to 3 times, and the mass concentration of the sterile saline is 0.85% to 0.95%.

[0021] Furthermore, in step (2), the mass fraction of the lyoprotectant in the aqueous solution of the lyoprotectant is 6% to 20%.

[0022] Furthermore, in step (2), the bacterial sludge and an aqueous solution of a freeze-drying protection agent are mixed in a volume ratio of 1:3 to 5, and then stirred at a stirring speed of 200 to 400 rpm for 10 to 20 minutes.

[0023] Furthermore, in step (2), the concentration of probiotics in the bacterial suspension is 10 9 CFU / mL.

[0024] Furthermore, in step (2), the mass concentration of the aqueous solution of the natural polymer material is 0.5% to 1.5%, and the volume ratio of the bacterial suspension to the aqueous solution of the natural polymer material is 1:0.5 to 1.5.

[0025] Furthermore, in step (2), 0.1 mol / L of CaCl 2 It is cured with a solution and the curing time is 20 to 40 minutes.

[0026] Furthermore, in step (2), the low-temperature storage temperature is 3 to 5°C.

[0027] Furthermore, in step (3), the vitamins are vitamin A, vitamin D 3 , Vitamin E, Vitamin K 2 , Vitamin B 1 , Vitamin B 2 , Vitamin B 6 , Vitamin B 12 , Vitamin B 13 , Vitamin B 15, vitamin C, biotin, niacinamide, folic acid, inositol, and pantothenic acid, the mineral is at least one selected from the group consisting of calcium, magnesium, manganese, iron, zinc, cobalt, molybdenum, chromium, copper, selenium, iodine, phosphorus, potassium, sodium, sulfur, and chlorine, preferably calcium, magnesium, manganese, iron, zinc, selenium, and copper, the prebiotic is oligofructose, The sugar can be any one selected from the group consisting of lactose, oligoxylose, oligogalactose, oligoisomaltose, soybean oligosaccharides, oligomannose, lactofructose, raffinose, fructose, oligochitosan, resistant starch, wheat dextrin, inulin, polydextrose, arginose, Aspergillus niger oligosaccharides, Spirulina, Ascophyllum nodosum, Chlorella vulgaris, and microalgae, and preferably oligofructose.

[0028] In a specific embodiment of the present invention, in step (3), the vitamins are vitamin A, vitamin D 3 , Vitamin E, Vitamin K 2 , Vitamin B 1 , Vitamin B 2 , Vitamin B 6 , Vitamin B 12 , niacinamide, folic acid, vitamin C, pantothenic acid, and the minerals include calcium carbonate, magnesium gluconate, manganese sulfate, ferrous lactate, zinc gluconate, sodium selenite, and copper sulfate. The contents of these vitamins and minerals in the vitamin-mineral-prebiotic-natural polymer material mixture are as follows: vitamin A 95-128 μg / g, vitamin D 3 1-6μg / g, Vitamin E 1-6mg / g, Vitamin K 2 6-10μg / g, Vitamin B 1 0.1-0.6mg / g, Vitamin B 2 0.1-0.6mg / g, Vitamin B 6 0.1-0.6mg / g, Vitamin B 120.1-0.7 μg / g, niacinamide 1-7 mg / g, folic acid 40-80 μg / g, vitamin C 10-40 mg / g, pantothenic acid 0.5-2.5 mg / g, calcium carbonate 93-133 mg / g, magnesium gluconate 27-51 mg / g, manganese sulfate 0.58-0.98 mg / g, ferrous lactate 1-5 mg / g, zinc gluconate 0.1-2.5 mg / g, sodium selenite 10-17 μg / g, and copper sulfate 0.01-0.30 mg / g.

[0029] Furthermore, in step (3), the content of prebiotics in the vitamin-mineral-prebiotic-natural polymer material mixture is 0.3 to 1.0 g / 100 mL.

[0030] Furthermore, in step (3), the natural polymer material is any one or more selected from the group consisting of sodium alginate, chitosan, modified starch, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxypropylcellulose, gellan gum, κ-carrageenan, gum arabic, pectin, carrageenan, gellan gum, xanthan gum, maltodextrin, β-cyclodextrin, gelatin, soybean isolated protein, and whey protein, and is preferably sodium alginate, chitosan, and gellan gum, and the weight ratio thereof is sodium alginate:chitosan:gellan gum=40:3:5.

[0031] Furthermore, in step (3), the vitamin-mineral-prebiotic complex powder and the aqueous solution of the natural polymer material are mixed in a mass ratio of 1-2:11.

[0032] Furthermore, in step (3), the mass concentration of the aqueous solution of the natural polymer material is 2% to 4%.

[0033] Furthermore, in step (3), the vitamin-mineral-prebiotic complex powder and the aqueous solution of the natural polymer material are mixed at a rotation speed of 150 to 350 rpm for 10 to 30 minutes.

[0034] Furthermore, in step (4), the enteric coating material is any one or more selected from the group consisting of cordyceps, fucoidan, diclofenac, acrylic resin I, acrylic resin II, acrylic resin III, cellulose acetate benzoate, cellulose acetate succinate, cellulose hydroxypropyl methylcellulose succinate, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, 1,2,4-benzenetricarboxylic acid cellulose acetate, 1,2,4-benzenetricarboxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, and polyvinyl alcohol acetate benzenedicarboxylate, and is preferably hydroxypropyl methylcellulose phthalate.

[0035] Furthermore, in step (4), the mixing time of the hardened probiotics and vitamin-mineral-prebiotic-natural polymer material mixture is 10-30 min, and the mixing rotation speed is 100-300 rpm; the mixing time of the nutrient mixture and the aqueous solution of enteric coating material is 10-30 min, and the mixing rotation speed is 100-300 rpm.

[0036] Furthermore, in step (4), the mass concentration of the aqueous solution of the enteric coating material is 4% to 12%.

[0037] Furthermore, in step (4), the washing is performed with sterile distilled water 2 to 4 times.

[0038] Further, in step (4), the hardened probiotics and the vitamin-mineral-prebiotic-natural polymer material mixture are mixed in a mass ratio of 1:2-4.

[0039] In step (4), the nutrient mixture and the aqueous solution of enteric coating material are mixed together, and the mass ratio is 1:4-6.

[0040] Furthermore, in step (5), the mixing mass ratio of the probiotic-prebiotic-vitamin-mineral wet microspheres and the hydrogel wet particles is 1:13-17.

[0041] Furthermore, in step (5), the mixing time of the probiotic-prebiotic-vitamin-mineral wet microspheres and the hydrogel wet particles is 10-20 min, and the mixing rotation speed is 30-60 rpm.

[0042] Furthermore, in step (5), the pre-cooling treatment is carried out as follows: treatment at −80° C. for 1 to 4 hours, and the freeze-drying conditions are a temperature of −55° C., a vacuum degree of 25 Pa, and a time of 24 to 48 hours.

[0043] Furthermore, in step (6), when drilling holes with a laser, the laser light source used is a cold light source, the diameter of the holes is 0.5-1.5 mm, and the number of the holes is 1-4.

[0044] Furthermore, in step (6), the material of the capsule shell is any one of gelatin, pullulan polysaccharide, and glutinous rice starch, preferably gelatin.The model of the capsule shell is any one of 000#, 00#, 0#, 1#, 2#, 3#, 4#, and their extended models, preferably 00# or their extended models.

[0045] Furthermore, in step (6), the capsule shell is perforated at a specific position, which may be either end of the capsule shell, the capsule shell waist, the capsule shell sidewall, or a combination of these positions. Preferably, the perforation positions are any one of "symmetrical positions at the waist center", "symmetrical positions at the centers of both ends", "equidistant symmetrical positions between both ends and the waist", and "diagonally symmetrical positions, equidistant from the apex and the center line". Here, the "symmetrical positions at the waist center" refers to perforation at the center of the capsule shell waist, and the perforated holes are distributed symmetrically around the capsule central axis (as shown in Figures 8 and 9). The "symmetrical positions at the centers of both ends" refers to perforation at the centers of both ends of the capsule shell, and the perforated holes are on the central axis of the capsule shell (as shown in Figure 10). The "equidistant symmetrical positions between both ends and the waist" refers to perforation at the symmetrical positions at the waist center and the symmetrical positions at both ends (as shown in Figure 11). Diagonal symmetry - the perforation position is equidistant from the apex and the center line means that the perforations are made on the side wall of the capsule shell, the holes are on the center line of the location surface, and the connecting line between the two holes is a diagonal line (shown in Figure 12).

[0046] Furthermore, in step (6), when the porous capsule shells and the capsule contents are combined, the mass of the capsule contents accommodated in each porous capsule shell is 0.60 to 0.75 g.

[0047] Furthermore, each of the components used in the present invention is commercially available and its structure and composition are known to those skilled in the art.

[0048] The food-suppressing capsules prepared according to the method of the present invention are comprised of a porous capsule shell and capsule contents, which are multi-element nutrient-containing microspheres (as shown in FIG. 1) and matrix gel-hydrogel particles containing multi-element nutrient microspheres (as shown in FIG. 2). The hydrogel particles have a three-dimensional three-dimensional mesh structure composed of polybasic carboxylic acid cross-linked sodium carboxymethylcellulose, the hydrogel particles are bionic cellulose high water-absorbent gel, absorb water and swell in the stomach to increase satiety, reduce food intake, and at the same time support the microspheres and promote gastrointestinal release; the microspheres containing multi-element nutrients are microcontainers composed of probiotics as the core material and protective layers as the wall material, the protective layers are three layers, the three protective layers are respectively a freeze-dried protective agent layer, a natural polymer material layer embedded with vitamins, minerals and prebiotics, and an enteric coating material layer from the inside to the outside, which improves the probiotics incorporation rate and nutrient utilization rate; the porous capsule shell is formed by perforating the capsule shell using laser technology, and the shell uses hydrodynamics to accelerate the disintegration of the capsule. The capsule can achieve the multi-purpose of green weight loss, nutritional supplementation and intestinal regulation, and improve the compliance of the user.

[0049] The present invention has the following beneficial effects. (1) The present invention organically integrates four issues, namely, weight control, intestinal flora adjustment, trace organic matter supplementation and trace element supplementation, to develop this food intake suppression capsule, which can simultaneously perform multiple health care functions, ensure the effectiveness of time, not only contribute to the recovery of the body, but also help people acquire good lifestyle habits. In addition, the present invention does not add other harmful substances or chemical components with strong oxidizing effects, so the prepared food intake suppression capsule is safe and healthy. (2) The hydrogel particles of the present invention can absorb water, dissolve and swell, occupy a certain volume in the stomach, create a feeling of fullness, reduce food intake, and achieve the purpose of weight loss. After absorbing water, dissolving and swelling, the hydrogel particles of the present invention have the same mechanical properties as ordinary vegetables, and are finally excreted from the body together with food residue to form feces. In addition, the present invention can adjust the dosage (within the dosage range) according to the individual's condition (e.g., appetite), and achieve weight loss tailored to the individual. At the same time, the ingested vitamins and minerals can prevent certain diseases, especially malnutrition caused by reduced food intake, and probiotics can contribute to intestinal regulation and help restore the normal physiological function of the bacterial flora. (3) The microspheres containing multi-element nutrients of the present invention have the following advantages: A. The addition of enteric coating material makes the microspheres enteric and can effectively resist damage from gastric acid and bile salts; the addition of freeze-drying protectant reduces the appearance of micro-ice crystals on the microspheres during the freeze-drying process, reducing the possibility of micro-ice crystals damaging the probiotic flora; the addition of prebiotics not only provides nutrition for the intestinal implantation of probiotics, but also allows the human body to directly absorb it, improving nutrition; B. The natural polymer material encapsulates prebiotics, vitamins and minerals, reducing the direct contact between them and probiotics, and avoiding problems such as efficacy reduction caused by the mutual reaction of prebiotics, vitamins, minerals and probiotics; C. The microspheres prepared by the method of the present invention have a viable cell count of 10 8 CFU / g, probiotic embedding rate can reach more than 80%, vitamin embedding rate more than 80%, mineral embedding rate more than 70%, prebiotic embedding rate more than 75%. Such microspheres can not only effectively improve the acid resistance, salt resistance and long-term storage stability of probiotics, but also greatly improve the low survival rate of probiotics after freeze-drying. (4) The present invention involves the mixing of hydrogel wet particles and multi-element nutritional wet microspheres (i.e. probiotic-prebiotic-vitamin-mineral wet microspheres) followed by freeze-drying, such a process allows the microspheres to adhere to the surface of the hydrogel particles or be interposed between the hydrogel particles, providing a transient and stable microenvironment for the existence of the microspheres, and preparing for the subsequent release of the microspheres, contributing to improving the availability and in vivo absorption and metabolism of prebiotics, probiotics, vitamins and minerals. (5) In the present invention, laser perforation technology is introduced to perforate a specific position of the capsule shell with a hole diameter that does not allow the capsule contents to come out. This change in the appearance of the capsule shell does not have a negative effect on safety and efficacy, and can promote the dissolution of gastric juice in the capsule shell, further promote the release of the capsule contents, and finally make the feeling of fullness come more timely, effectively improving the enthusiasm and compliance of users, creating a sense of trust, increasing self-confidence, and more conducive to their own good lifestyle habits. (6) The method for preparing the food intake suppressing capsule of the present invention is simple, economical, and suitable for industrial production. [Brief description of the drawings]

[0050] [Figure 1] A morphology diagram of multi-element nutritional microspheres, where 1 is an enteric coating material layer, 2 is a natural polymer material layer, 3 is a lyoprotectant layer, 4 is a probiotic core, 5 is vitamins, 6 is minerals, and 7 is prebiotics. [Diagram 2] FIG. 1 is a morphology diagram of matrix gel particles containing multi-element nutrient microspheres, where 8 is the multi-element nutrient containing microsphere and 9 is the matrix gel particle. [Diagram 3] FIG. 13 is a graph showing test results of the swelling ratio and elastic modulus of sample gels. [Figure 4] FIG. 1 shows the results of the effect of different concentrations of enteric coating material on probiotic viability. [Diagram 5] FIG. 1 shows the results of the effect of different residence times of microspheres in artificial intestinal fluid on probiotic viability. [Figure 6] FIG. 1 shows the test results of capsule disintegration time. [Figure 7] FIG. 2 shows the weight change in obese adult rats after taking a capsule of the present invention. [Figure 8] This is a schematic diagram showing the positions of two holes at symmetrical positions in the center of the waist, where A is the front and B is the side. [Figure 9] This is a schematic diagram showing the positions of the holes (4 holes) symmetrically positioned in the center of the waist, where A is the front and B is the side. [Figure 10] This is a schematic diagram showing the hole positions (2 holes) at symmetrical positions in the center of both ends, where A is the front surface and B is the top surface. [Figure 11] This is a schematic diagram of the hole positions (4 holes) at equidistant symmetrical positions on both ends and the waist, where A is the front and B is the side. [Figure 12] This is a schematic diagram showing the positions of two holes (diagonally symmetrical) equidistant from the apex and center line. A is the front view and B is the side view.

[0051] In Figures 8 to 12 above, a circle shown by a solid line indicates a case where the hole is on the front side of the capsule shell, a circle shown by a dashed line indicates a case where the hole is on the back side of the capsule shell, and an ellipse shown by a solid line indicates a case where the hole is on the side of the capsule shell. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0052] The present invention will be described in more detail below with reference to specific examples, comparative examples and the accompanying drawings.

[0053] In the following examples and comparative examples, unless otherwise specified, the concentrations are all in mass %.

[0054] In the following Examples and Comparative Examples, unless otherwise specified, all sterilization procedures for sterilized aqueous solutions, MRS medium, etc. are carried out by moist heat sterilization at a sterilization temperature of 121° C. for a sterilization time of 20 minutes.

[0055] In each of the following Examples and Comparative Examples, unless otherwise specified, in step (2), the probiotics are a mixed bacterial flora consisting of Bifidobacterium longum and Lactobacillus acidophilus, the freeze-drying protective agent is soluble starch, skim milk powder, glycerol and xylan (the weight ratio of which is soluble starch:skim milk powder:glycerol:xylan=5:6:1:10), and the concentration of the probiotics in the bacterial suspension is 10 9 CFU / mL, in steps (2) and (3), the natural polymer materials are sodium alginate, chitosan and gellan gum (the weight ratio of sodium alginate:chitosan:gellan gum=40:3:5), in step (3), the prebiotic is oligofructose, in step (4), the enteric coating material is cellulose hydroxypropyl methylcellulose phthalate, and in step (6), the capsule shell material is gelatin, all of which are type 00#, and the mass of the capsule contents contained in the food-suppressing capsules is 0.75 g / capsule.

[0056] Example 1 In step (1), sodium carboxymethylcellulose (viscosity 11000) is added to an aqueous solution containing citric acid (the mass ratio of sodium carboxymethylcellulose to citric acid is 330:1, and the mass ratio of sodium carboxymethylcellulose to distilled water is 1:16), first stirred at 60 rpm for 90 min, then stirred at 30 rpm for 16 h to obtain a gel, which is dried in a 45°C oven for 24 h, turned over and continued to dry for 32 h, then high-temperature cross-linked at 120°C for 4 h, crushed and sieved to obtain solid hydrogel particles, which are washed with distilled water 4 times, each time for 3 h (the mass ratio of solid hydrogel particles to distilled water is 1:150 during each washing), and filtered to prepare hydrogel wet particles; In step (2), the probiotics were inoculated into sterile MRS liquid medium with an inoculum amount of 3%, and repeatedly activated for five generations under the same culture conditions (36.5°C, 24h), and the bacterial sludge was collected by low-temperature centrifugation (4°C, 4500rpm, 15min), and the bacterial sludge was washed twice with 0.9% sterile saline, and then the bacterial sludge was uniformly mixed with an aqueous solution of a 13% freeze-drying protection agent in a volume ratio of 1:4 to obtain a bacterial suspension, and then the bacterial suspension was uniformly mixed with an aqueous solution of a 1% natural polymer material in a volume ratio of 1:1, and then the resulting mixture was diluted with 0.1mol / L CaCl 2 The hardened probiotics were then cured in the solution for 30 minutes, washed and filtered to obtain the hardened probiotics, which were then stored at a low temperature of 4°C for preparation. In step (3), the vitamin, mineral and prebiotic powders are uniformly mixed and passed through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder. The vitamin-mineral-prebiotic complex powder is then uniformly mixed with a 3% aqueous solution of natural polymeric materials in a mass ratio of 1.5:11 (250 rpm, 20 min) to obtain a vitamin-mineral-prebiotic-natural polymeric material mixture, in which the vitamin, mineral and prebiotic contents are: vitamin A 111 μg / g, vitamin D 3 4μg / g, Vitamin E 4mg / g, Vitamin K 2 8μg / g, Vitamin B 1 0.4mg / g, Vitamin B 2 0.4mg / g, Vitamin B 6 0.4mg / g, Vitamin B 12 0.4 μg / g, niacinamide 4 mg / g, folic acid 60 μg / g, vitamin C 25 mg / g, pantothenic acid 1.5 mg / g, calcium carbonate 113 mg / g, magnesium gluconate 39 mg / g, manganese sulfate 0.78 mg / g, ferrous lactate 3 mg / g, zinc gluconate 1.5 mg / g, sodium selenite 14 μg / g, and copper sulfate 0.16 mg / g, for a prebiotic content of 0.65 g / 100 mL. In step (4), the hardened probiotics, vitamin-mineral-prebiotics-natural polymer material mixture is mixed uniformly in a mass ratio of 1:3 (200 rpm, 20 min) to obtain a nutritional mixture, which is then mixed uniformly with an aqueous solution of enteric coating material with a concentration of 8% in a mass ratio of 1:5, washed and filtered three times to obtain probiotic-prebiotic-vitamin-mineral wet microspheres; In step (5), the probiotic-prebiotic-vitamin-mineral wet microspheres and hydrogel wet particles are mixed uniformly in a mass ratio of 1:15 (45 rpm, 15 min), then pre-cooled at −80°C for 2.5 h, and freeze-dried at −55°C, vacuum of 25 Pa for 36 h after pre-cooling, and then crushed and sieved to obtain capsule contents; In step (6), the capsule shell is fixed and two holes are drilled by laser at symmetrical positions in the center of its waist (as shown in FIG. 8), with a hole diameter of 1 mm, to obtain a porous capsule shell, which is then combined with the capsule contents to prepare an anti-feeding capsule containing multi-element nutritional microspheres.

[0057] Example 2 In step (1), sodium carboxymethylcellulose (viscosity 15000) is added to an aqueous solution containing citric acid (the mass ratio of sodium carboxymethylcellulose to citric acid is 350:1, and the mass ratio of sodium carboxymethylcellulose to distilled water is 1:10), first stirred at 70 rpm for 100 min, then stirred at 40 rpm for 20 h to obtain a gel, which is dried in an oven at 60°C for 28 h, then turned over and continued to dry for 36 h, and then high-temperature cross-linked at 125°C for 4.4 h, crushed and sieved to obtain solid hydrogel particles, which are washed with distilled water 6 times, each time for 4 h (the mass ratio of solid hydrogel particles to distilled water is 1:200 during each washing), and filtered to prepare hydrogel wet particles; In step (2), the probiotics were inoculated into sterile MRS liquid medium at an inoculum amount of 4.5%, and repeatedly activated for five generations under the same culture conditions (38°C, 27h), and the bacterial sludge was collected by low-temperature centrifugation (5°C, 5500rpm, 20min), and the bacterial sludge was washed three times with 0.95% sterile saline, and then the bacterial sludge was uniformly mixed with an aqueous solution of a 20% concentration of a freeze-drying protectant in a volume ratio of 1:5 to obtain a bacterial suspension, and then the bacterial suspension was uniformly mixed with an aqueous solution of a 1.5% concentration of a natural polymer material in a volume ratio of 1:1.5, and then the resulting mixture was diluted with 0.1mol / L CaCl 2 The hardened probiotics were then cured in the solution for 40 minutes, washed and filtered to obtain the hardened probiotics, which were then stored at a low temperature of 5°C for preparation. In step (3), the vitamin, mineral and prebiotic powders are uniformly mixed and passed through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder. The vitamin-mineral-prebiotic complex powder is then uniformly mixed with a 4% aqueous solution of natural polymeric materials in a mass ratio of 2:11 (350 rpm, 30 min) to obtain a vitamin-mineral-prebiotic-natural polymeric material mixture, in which the vitamin, mineral and prebiotic contents are: vitamin A 128 μg / g, vitamin D 3 6μg / g, Vitamin E 6mg / g, Vitamin K 2 10μg / g, Vitamin B 1 0.6mg / g, Vitamin B 2 0.6mg / g, Vitamin B 6 0.6mg / g, Vitamin B 12 0.7 μg / g, niacinamide 7 mg / g, folic acid 80 μg / g, vitamin C 40 mg / g, pantothenic acid 2.5 mg / g, calcium carbonate 133 mg / g, magnesium gluconate 51 mg / g, manganese sulfate 0.98 mg / g, ferrous lactate 5 mg / g, zinc gluconate 2.5 mg / g, sodium selenite 17 μg / g, and copper sulfate 0.3 mg / g, with a prebiotic content of 1.0 g / 100 mL. In step (4), the hardened probiotics, vitamin-mineral-prebiotics-natural polymer material mixture is mixed uniformly in a mass ratio of 1:4 (300 rpm, 30 min) to obtain a nutritional mixture, which is then mixed uniformly with an aqueous solution of enteric coating material with a concentration of 8% in a mass ratio of 1:6, washed and filtered four times to obtain probiotic-prebiotic-vitamin-mineral wet microspheres; In step (5), the probiotic-prebiotic-vitamin-mineral wet microspheres and hydrogel wet particles are mixed uniformly in a mass ratio of 1:17 (60 rpm, 20 min), then pre-cooled at −80°C for 4 h, and freeze-dried at −55°C, vacuum of 25 Pa for 48 h after pre-cooling, and then crushed and sieved to obtain capsule contents; In step (6), the capsule shell is fixed, and two holes are drilled by laser at symmetrical positions in the center of its waist, with a hole diameter of 1 mm, to obtain a porous capsule shell, and then the porous capsule shell is combined with the capsule contents to prepare an anti-feeding capsule containing multi-element nutritional microspheres.

[0058] Example 3 In step (1), sodium carboxymethylcellulose (viscosity 7000) is added to an aqueous solution containing citric acid (the mass ratio of sodium carboxymethylcellulose to citric acid is 310:1, and the mass ratio of sodium carboxymethylcellulose to distilled water is 1:22), and the mixture is first stirred at 50 rpm for 80 min, and then stirred at 20 rpm for 14 h to obtain a gel, which is dried in an oven at 40°C for 20 h, and then dried for 28 h after turning over, and then crosslinked at high temperature at 110°C for 3.6 h, crushed and sieved to obtain solid hydrogel particles, which are washed with distilled water twice, each time for 2 h, and filtered (the mass ratio of solid hydrogel particles to distilled water is 1:100 during each washing), to prepare hydrogel wet particles; In step (2), the probiotics were inoculated into sterile MRS liquid medium at an inoculation amount of 1.5%, and repeatedly activated for five generations under the same culture conditions (35°C, 21h), and the bacterial sludge was collected by low-temperature centrifugation (3°C, 3500rpm, 10min), and the bacterial sludge was washed once with 0.85% sterile saline, and then the bacterial sludge was uniformly mixed with an aqueous solution of a 6% freeze-drying protection agent at a volume ratio of 1:3 to obtain a bacterial suspension, and then the bacterial suspension was uniformly mixed with an aqueous solution of a 0.5% natural polymer material at a volume ratio of 1:0.5, and then the resulting mixture was diluted with 0.1mol / L CaCl 2 The hardened probiotics were then cured in the solution for 20 minutes, washed and filtered to obtain the hardened probiotics, which were then stored at a low temperature of 3°C for preparation. In step (3), the vitamins, minerals and prebiotics are mixed uniformly and passed through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder. The vitamin-mineral-prebiotic complex powder is then mixed uniformly with a 3% aqueous solution of natural polymeric materials in a mass ratio of 1:11 (150 rpm, 10 min) to obtain a vitamin-mineral-prebiotic-natural polymeric material mixture, in which the vitamin, mineral and prebiotic contents are: vitamin A 95 μg / g, vitamin D 3 1μg / g, Vitamin E lmg / g, Vitamin K 2 6μg / g, Vitamin B 1 0.1mg / g, Vitamin B 2 0.1mg / g, Vitamin B 6 0.1mg / g, Vitamin B 12 0.1 μg / g, niacinamide 1 mg / g, folic acid 40 μg / g, vitamin C 10 mg / g, pantothenic acid 0.5 mg / g, calcium carbonate 93 mg / g, magnesium gluconate 27 mg / g, manganese sulfate 0.58 mg / g, ferrous lactate 1 mg / g, zinc gluconate 0.1 mg / g, sodium selenite 10 μg / g, and copper sulfate 0.01 mg / g, with a prebiotic content of 0.3 g / 100 mL. In step (4), the hardened probiotics, vitamin-mineral-prebiotics-natural polymer material mixture is mixed uniformly in a mass ratio of 1:2 (100 rpm, 10 min) to obtain a nutritional mixture, which is then mixed uniformly with an aqueous solution of enteric coating material with a concentration of 8% in a mass ratio of 1:4, washed twice and filtered to obtain probiotic-prebiotic-vitamin-mineral wet microspheres; In step (5), the probiotic-prebiotic-vitamin-mineral wet microspheres and hydrogel wet particles are mixed uniformly in a mass ratio of 1:13 (30 rpm, 10 min), then pre-cooled at −80°C for 1 h, and freeze-dried at −55°C, vacuum of 25 Pa for 24 h after pre-cooling, and then crushed and sieved to obtain capsule contents; In step (6), the capsule shell is fixed and two holes are drilled by laser at the central symmetrical positions on both ends of the whole capsule shell, with the hole diameter of 1 mm, to obtain a porous capsule shell, and then the porous capsule shell is combined with the capsule contents to prepare an anti-feeding capsule containing multi-element nutritional microspheres.

[0059] Example 4 In step (1), sodium carboxymethylcellulose (viscosity 11000) is added to an aqueous solution containing citric acid (the mass ratio of sodium carboxymethylcellulose to citric acid is 350:1, and the mass ratio of sodium carboxymethylcellulose to distilled water is 1:10), first stirred at 60 rpm for 90 min, then stirred at 40 rpm for 20 h to obtain a gel, which is dried in a 40°C oven for 20 h, then kept dried for 28 h after turning over, then high-temperature crosslinked at 120°C for 4 h, crushed and sieved to obtain solid hydrogel particles, which are washed with distilled water 6 times, each time for 4 h (the mass ratio of solid hydrogel particles to distilled water is 1:200 during each washing), and filtered to prepare hydrogel wet particles; In step (2), the probiotics were inoculated into sterile MRS liquid medium at an inoculum amount of 1.5%, and repeatedly activated for five generations under the same culture conditions (36.5°C, 24h), and the bacterial sludge was collected by low-temperature centrifugation (5°C, 5500rpm, 20min), and the bacterial sludge was washed once with 0.85% sterile saline, and then the bacterial sludge was uniformly mixed with an aqueous solution of a 13% concentration of a freeze-drying protectant in a volume ratio of 1:3 to obtain a bacterial suspension, and then the bacterial suspension was uniformly mixed with an aqueous solution of a 1% concentration of a natural polymer material in a volume ratio of 1:0.5, and then the resulting mixture was diluted with 0.1mol / L CaCl 2 The hardened probiotics were then cured in the solution for 30 minutes, washed and filtered to obtain the hardened probiotics, which were then stored at a low temperature of 4°C for preparation. In step (3), the vitamin, mineral and prebiotic powders are uniformly mixed and passed through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder. The vitamin-mineral-prebiotic complex powder is then uniformly mixed with a 2% aqueous solution of natural polymeric materials in a mass ratio of 1:11 (250 rpm, 20 min) to obtain a vitamin-mineral-prebiotic-natural polymeric material mixture, in which the vitamin, mineral and prebiotic contents are: vitamin A 111 μg / g, vitamin D 3 4μg / g, Vitamin E 4mg / g, Vitamin K 2 8μg / g, Vitamin B 1 0.4mg / g, Vitamin B 2 0.4mg / g, Vitamin B 6 0.4mg / g, Vitamin B 12 0.4 μg / g, niacinamide 4 mg / g, folic acid 60 μg / g, vitamin C 25 mg / g, pantothenic acid 1.5 mg / g, calcium carbonate 113 mg / g, magnesium gluconate 39 mg / g, manganese sulfate 0.78 mg / g, ferrous lactate 3 mg / g, zinc gluconate 1.5 mg / g, sodium selenite 14 μg / g, and copper sulfate 0.16 mg / g, for a prebiotic content of 0.65 g / 100 mL. In step (4), the hardened probiotics, vitamin-mineral-prebiotics-natural polymer material mixture is mixed uniformly in a mass ratio of 1:2 (350 rpm, 30 min) to obtain a nutritional mixture, which is then mixed uniformly with an aqueous solution of enteric coating material with a concentration of 8% in a mass ratio of 1:6, washed and filtered three times to obtain probiotic-prebiotic-vitamin-mineral wet microspheres; In step (5), the probiotic-prebiotic-vitamin-mineral wet microspheres and hydrogel wet particles are mixed uniformly in a mass ratio of 1:15 (45 rpm, 15 min), then pre-cooled at −80°C for 2.5 h, and freeze-dried at −55°C, vacuum of 25 Pa for 36 h after pre-cooling, and then crushed and sieved to obtain capsule contents; In step (6), the capsule shell is fixed and four holes are drilled by laser at equidistant symmetrical positions on both ends and waist of the capsule shell (as shown in FIG. 11 ), with a hole diameter of 1 mm, to obtain a porous capsule shell, which is then combined with the capsule contents to prepare an anti-feeding capsule containing multi-element nutritional microspheres.

[0060] Example 5 In step (1), sodium carboxymethylcellulose (viscosity 15000) is added to an aqueous solution containing citric acid (the mass ratio of sodium carboxymethylcellulose to citric acid is 310:1, and the mass ratio of sodium carboxymethylcellulose to distilled water is 1:16), first stirred at 70 rpm for 100 min, then stirred at 20 rpm for 14 h to obtain a gel, which is dried in an oven at 45°C for 24 h, then turned over and continued to dry for 32 h, and then high-temperature crosslinked at 130°C for 4.4 h, crushed and sieved to obtain solid hydrogel particles, which are washed with distilled water twice, each time for 2 h (the mass ratio of solid hydrogel particles to distilled water is 1:100 during each washing), and filtered to prepare hydrogel wet particles; In step (2), the probiotics were inoculated into sterile MRS liquid medium at an inoculum amount of 3% and repeatedly activated for five generations under the same culture conditions (38°C, 27h), the bacterial sludge was collected by low-temperature centrifugation (5°C, 5500rpm, 25min), the bacterial sludge was washed twice with 0.9% sterile saline, and then the bacterial sludge was uniformly mixed with an aqueous solution of a 20% concentration of a freeze-drying protectant in a volume ratio of 1:3 to obtain a bacterial suspension, and then the bacterial suspension was uniformly mixed with an aqueous solution of a 1.5% concentration of a natural polymer material in a volume ratio of 1:1, and then the resulting mixture was diluted with 0.1mol / L CaCl 2 The hardened probiotics were then cured in the solution for 40 minutes, washed and filtered to obtain the hardened probiotics, which were then stored at a low temperature of 5°C for preparation. In step (3), the vitamin, mineral and prebiotic powders are uniformly mixed and passed through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder. The vitamin-mineral-prebiotic complex powder is then uniformly mixed with a 4% aqueous solution of natural polymeric materials in a mass ratio of 1:11 (150 rpm, 30 min) to obtain a vitamin-mineral-prebiotic-natural polymeric material mixture, in which the vitamin, mineral and prebiotic contents are: vitamin A 111 μg / g, vitamin D 3 4μg / g, Vitamin E 4mg / g, Vitamin K 2 8μg / g, Vitamin B 1 0.4mg / g, Vitamin B 2 0.4mg / g, Vitamin B 6 0.4mg / g, Vitamin B 12 0.4 μg / g, niacinamide 4 mg / g, folic acid 60 μg / g, vitamin C 25 mg / g, pantothenic acid 1.5 mg / g, calcium carbonate 113 mg / g, magnesium gluconate 39 mg / g, manganese sulfate 0.78 mg / g, ferrous lactate 3 mg / g, zinc gluconate 1.5 mg / g, sodium selenite 14 μg / g, and copper sulfate 0.16 mg / g, and the prebiotic content is 0.65 g / 100 mL; In step (4), the hardened probiotics, vitamin-mineral-prebiotic-natural polymer material mixture is mixed uniformly in a mass ratio of 1:3 (200 rpm, 20 min) to obtain a nutritional mixture, which is then mixed uniformly with an aqueous solution of enteric coating material with a concentration of 8% in a mass ratio of 1:6, washed and filtered three times to obtain probiotic-prebiotic-vitamin-mineral wet microspheres; In step (5), the probiotic-prebiotic-vitamin-mineral wet microspheres and hydrogel wet particles are mixed uniformly in a mass ratio of 1:17 (60 rpm, 20 min), then pre-cooled at −80°C for 4 h, and freeze-dried at −55°C, vacuum of 25 Pa for 48 h after pre-cooling, and then crushed and sieved to obtain capsule contents; In step (6), the capsule shell is fixed, and two holes are drilled by laser at the same position on the diagonal symmetry of the entire capsule, one at the apex and the other at the same distance from the center line (as shown in FIG. 12), with a hole diameter of 1 mm, to obtain a porous capsule shell, which is then combined with the capsule contents to prepare an anti-feeding capsule containing multi-element nutritional microspheres.

[0061] Example 6 In step (1), sodium carboxymethylcellulose (viscosity 7000) is added to an aqueous solution containing citric acid (the mass ratio of sodium carboxymethylcellulose to citric acid is 330:1, and the mass ratio of sodium carboxymethylcellulose to distilled water is 1:22), first stirred at 50 rpm for 80 min, then stirred at 30 rpm for 16 h to obtain a gel, which is dried in an oven at 60°C for 28 h, then turned over and continued to dry for 36 h, and then high-temperature crosslinked at 110°C for 3.6 h, crushed and sieved to obtain solid hydrogel particles, which are washed with distilled water 4 times, each time for 3 h (the mass ratio of solid hydrogel particles to distilled water is 1:150 during each washing), and filtered to prepare hydrogel wet particles; In step (2), the probiotics were inoculated into sterile MRS liquid medium at an inoculum amount of 4.5% and repeatedly activated for five generations under the same culture conditions (35°C, 21h), the bacterial sludge was collected by low-temperature centrifugation (4°C, 4500rpm, 15min), the bacterial sludge was washed three times with 0.95% sterile saline, and then the bacterial sludge was uniformly mixed with an aqueous solution of a 6% freeze-drying protection agent at a volume ratio of 1:5 to obtain a bacterial suspension, and then the bacterial suspension was uniformly mixed with an aqueous solution of a 1% natural polymer material at a volume ratio of 1:1, and then the resulting mixture was diluted with 0.1mol / L CaCl 2 The hardened probiotics were then cured in the solution for 20 minutes, washed and filtered to obtain the hardened probiotics, which were then stored at a low temperature of 3°C for preparation. In step (3), the vitamin, mineral and prebiotic powders are uniformly mixed and passed through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder. The vitamin-mineral-prebiotic complex powder is then uniformly mixed with a 4% aqueous solution of natural polymeric materials in a mass ratio of 2:11 (350 rpm, 30 min) to obtain a vitamin-mineral-prebiotic-natural polymeric material mixture, in which the vitamin, mineral and prebiotic contents are: vitamin A 128 μg / g, vitamin D 3 6μg / g, Vitamin E 6mg / g, Vitamin K 2 10μg / g, Vitamin B 1 0.6mg / g, Vitamin B 2 0.6mg / g, Vitamin B 6 0.6mg / g, Vitamin B 12 0.7 μg / g, niacinamide 7 mg / g, folic acid 80 μg / g, vitamin C 40 mg / g, pantothenic acid 2.5 mg / g, calcium carbonate 133 mg / g, magnesium gluconate 51 mg / g, manganese sulfate 0.98 mg / g, ferrous lactate 5 mg / g, zinc gluconate 2.5 mg / g, sodium selenite 17 μg / g, and copper sulfate 0.3 mg / g, with a prebiotic content of 1.0 g / 100 mL. In step (4), the hardened probiotics, vitamin-mineral-prebiotic-natural polymer material mixture is mixed uniformly in a mass ratio of 1:4 (300 rpm, 30 min) to obtain a nutritional mixture, which is then mixed uniformly with an aqueous solution of enteric coating material with a concentration of 8% in a mass ratio of 1:4, washed and filtered four times to obtain probiotic-prebiotic-vitamin-mineral wet microspheres; In step (5), the probiotic-prebiotic-vitamin-mineral wet microspheres and hydrogel wet particles are mixed uniformly in a mass ratio of 1:13 (30 rpm, 10 min), then pre-cooled at −80°C for 1 h, and freeze-dried at −55°C, vacuum of 25 Pa for 18 h after pre-cooling, and then crushed and sieved to obtain capsule contents; In step (6), the capsule shell is fixed, and two holes are drilled by laser at symmetrical positions in the center of its waist, with a hole diameter of 1 mm, to obtain a porous capsule shell, and then the porous capsule shell is combined with the capsule contents to prepare an anti-feeding capsule containing multi-element nutritional microspheres.

[0062] Example 7 In step (1), sodium carboxymethylcellulose (viscosity 11000) is added to an aqueous solution containing citric acid (the mass ratio of sodium carboxymethylcellulose to citric acid is 310:1, and the mass ratio of sodium carboxymethylcellulose to distilled water is 1:22), first stirred at 60 rpm for 90 min, then stirred at 20 rpm for 14 h to obtain a gel, which is dried in an oven at 60°C for 28 h, then turned over and continued to dry for 36 h, and then high-temperature cross-linked at 120°C for 4 h, crushed and sieved to obtain solid hydrogel particles, which are washed with distilled water twice, each time for 2 h (the mass ratio of solid hydrogel particles to distilled water is 1:100 during each washing), and filtered to prepare hydrogel wet particles; In step (2), the probiotics were inoculated into sterile MRS liquid medium at an inoculum amount of 4.5%, and repeatedly activated for five generations under the same culture conditions (36.5°C, 24h), and the bacterial sludge was collected by low-temperature centrifugation (3°C, 3500rpm, 10min), and the bacterial sludge was washed twice with 0.95% sterile saline, and then the bacterial sludge was uniformly mixed with an aqueous solution of a 6% freeze-drying protection agent at a volume ratio of 1:5 to obtain a bacterial suspension, and then the bacterial suspension was uniformly mixed with an aqueous solution of a 1.5% natural polymer material at a volume ratio of 1:1.5, and then the resulting mixture was diluted with 0.1mol / L CaCl 2 The hardened probiotics were then cured in the solution for 30 minutes, washed and filtered to obtain the hardened probiotics, which were then stored at a low temperature of 4°C for preparation. In step (3), the vitamin, mineral and prebiotic powders are uniformly mixed and passed through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder. The vitamin-mineral-prebiotic complex powder is then uniformly mixed with a 4% aqueous solution of natural polymeric materials in a mass ratio of 1:11 (350 rpm, 30 min) to obtain a vitamin-mineral-prebiotic-natural polymeric material mixture, in which the vitamin, mineral and prebiotic contents are: vitamin A 128 μg / g, vitamin D 3 6μg / g, Vitamin E 6mg / g, Vitamin K 2 10μg / g, Vitamin B 1 0.6mg / g, Vitamin B 2 0.6mg / g, Vitamin B 6 0.6mg / g, Vitamin B 12 0.7 μg / g, niacinamide 7 mg / g, folic acid 80 μg / g, vitamin C 40 mg / g, pantothenic acid 2.5 mg / g, calcium carbonate 133 mg / g, magnesium gluconate 51 mg / g, manganese sulfate 0.98 mg / g, ferrous lactate 5 mg / g, zinc gluconate 2.5 mg / g, sodium selenite 17 μg / g, and copper sulfate 0.3 mg / g, with a prebiotic content of 1.0 g / 100 mL. In step (4), the hardened probiotics, vitamin-mineral-prebiotics-natural polymer material mixture is mixed uniformly in a mass ratio of 1:4 (300 rpm, 30 min) to obtain a nutritional mixture, which is then mixed uniformly with an aqueous solution of enteric coating material with a concentration of 8% in a mass ratio of 1:5, washed twice and filtered to obtain probiotic-prebiotic-vitamin-mineral wet microspheres; In step (5), the probiotic-prebiotic-vitamin-mineral wet microspheres and hydrogel wet particles are mixed uniformly in a mass ratio of 1:13 (45 rpm, 15 min), then pre-cooled at −80°C for 2.5 h, and freeze-dried at −55°C, vacuum of 25 Pa for 36 h after pre-cooling, and then crushed and sieved to obtain capsule contents; In step (6), the capsule shell is fixed, and two holes are drilled by laser at equidistant symmetrical positions in the center of its waist, with a hole diameter of 0.5 mm, to obtain a porous capsule shell, and then the porous capsule shell is combined with the capsule contents to prepare an anti-feeding capsule containing multi-element nutritional microspheres.

[0063] Example 8 In step (1), sodium carboxymethylcellulose (viscosity 15000) is added to an aqueous solution containing citric acid (the mass ratio of sodium carboxymethylcellulose to citric acid is 330:1, and the mass ratio of sodium carboxymethylcellulose to distilled water is 1:16), first stirred at 50 rpm for 80 min, then stirred at 30 rpm for 16 h to obtain a gel, which is dried in an oven at 45°C for 28 h, then turned over and continued to dry for 36 h, and then high-temperature cross-linked at 120°C for 4 h, crushed and sieved to obtain solid hydrogel particles, which are washed with distilled water 4 times, each time for 3 h (the mass ratio of solid hydrogel particles to distilled water is 1:200 during each washing), and filtered to prepare hydrogel wet particles; In step (2), the probiotics were inoculated into sterile MRS liquid medium at an inoculation amount of 3%, and repeatedly activated for five generations under the same culture conditions (38°C, 21h), and the bacterial sludge was collected by low-temperature centrifugation (4°C, 3500rpm, 20min), and the bacterial sludge was washed three times with 0.9% sterile saline, and then uniformly mixed with an aqueous solution of a freeze-drying protectant to obtain a bacterial suspension. Then the bacterial suspension was uniformly mixed with an aqueous solution of a natural polymer material with a concentration of 1% in a volume ratio of 1:1.5, and the resulting mixture was then uniformly mixed with 0.1mol / L CaCl 2 The hardened probiotics were then cured in the solution for 30 minutes, washed and filtered to obtain the hardened probiotics, which were then stored at a low temperature of 4°C for preparation. In step (3), the vitamin, mineral and prebiotic powders are mixed uniformly and passed through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder. The vitamin-mineral-prebiotic complex powder is then mixed uniformly with a 2% aqueous solution of natural polymeric materials in a mass ratio of 2:11 (150 rpm, 30 min) to obtain a vitamin-mineral-prebiotic-natural polymeric material mixture, in which the vitamin, mineral and prebiotic contents are: vitamin A 95 μg / g, vitamin D 3 1μg / g, Vitamin E lmg / g, Vitamin K 2 6μg / g, Vitamin B 1 0.1mg / g, Vitamin B 2 0.1mg / g, Vitamin B 6 0.1mg / g, Vitamin B 12 0.1 μg / g, niacinamide 1 mg / g, folic acid 40 μg / g, vitamin C 10 mg / g, pantothenic acid 0.5 mg / g, calcium carbonate 93 mg / g, magnesium gluconate 27 mg / g, manganese sulfate 0.58 mg / g, ferrous lactate 1 mg / g, zinc gluconate 0.1 mg / g, sodium selenite 10 μg / g, and copper sulfate 0.01 mg / g, with a prebiotic content of 0.3 g / 100 mL. In step (4), the hardened probiotics, vitamin-mineral-prebiotics-natural polymer material mixture is mixed uniformly in a mass ratio of 1:3 (100 rpm, 30 min) to obtain a nutritional mixture, which is then mixed uniformly with an aqueous solution of enteric coating material with a concentration of 8% in a mass ratio of 1:6, washed and filtered three times to obtain probiotic-prebiotic-vitamin-mineral wet microspheres; In step (5), the probiotic-prebiotic-vitamin-mineral wet microspheres and hydrogel wet particles are mixed uniformly in a mass ratio of 1:13 (45 rpm, 10 min), then pre-cooled at −80°C for 1 h, and freeze-dried at −55°C, vacuum of 25 Pa for 48 h after pre-cooling, and then crushed and sieved to obtain capsule contents; In step (6), the capsule shell is fixed and two holes are drilled by laser at symmetrical positions in the center of its waist to obtain a porous capsule shell with a hole diameter of 0.75 mm. Then, the porous capsule shell is combined with the capsule contents to prepare an anti-feeding capsule containing multi-element nutritional microspheres.

[0064] Example 9 In step (1), sodium carboxymethylcellulose (viscosity 7000) is added to an aqueous solution containing citric acid (the mass ratio of sodium carboxymethylcellulose to citric acid is 350:1, and the mass ratio of sodium carboxymethylcellulose to distilled water is 1:22), first stirred at 60 rpm for 90 min, then stirred at 30 rpm for 16 h to obtain a gel, which is dried in an oven at 45°C for 28 h, then turned over and continued to dry for 36 h, then high-temperature cross-linked at 110°C for 4 h, crushed and sieved to obtain solid hydrogel particles, which are washed with distilled water 4 times, each time for 2 h (the mass ratio of solid hydrogel particles to distilled water is 1:200 during each washing), and filtered to prepare hydrogel wet particles; In step (2), the probiotics were inoculated into sterile MRS liquid medium at an inoculation amount of 1.5% and repeatedly activated for five generations under the same culture conditions (37°C, 21h), the bacterial sludge was collected by low-temperature centrifugation (5°C, 5500rpm, 15min), the bacterial sludge was washed three times with 0.85% sterile saline, and then the bacterial sludge was uniformly mixed with an aqueous solution of a 13% concentration of a freeze-drying protectant in a volume ratio of 1:5 to obtain a bacterial suspension, and then the bacterial suspension was uniformly mixed with an aqueous solution of a 1.5% concentration of a natural polymer material in a volume ratio of 1:0.5, and then the resulting mixture was diluted with 0.1mol / L CaCl 2 The hardened probiotics were then cured in the solution for 30 minutes, washed and filtered to obtain the hardened probiotics, which were then stored at a low temperature of 3°C for preparation. In step (3), the vitamin, mineral and prebiotic powders are mixed uniformly and passed through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder. The vitamin-mineral-prebiotic complex powder is then mixed uniformly with a 4% aqueous solution of natural polymeric materials in a mass ratio of 1.5:11 (350 rpm, 10 min) to obtain a vitamin-mineral-prebiotic-natural polymeric material mixture, in which the vitamin, mineral and prebiotic contents are: vitamin A 95 μg / g, vitamin D 3 1μg / g, Vitamin E lmg / g, Vitamin K 2 6μg / g, Vitamin B 1 0.1mg / g, Vitamin B 2 0.1mg / g, Vitamin B 6 0.1mg / g, Vitamin B 12 0.1 μg / g, niacinamide 1 mg / g, folic acid 40 μg / g, vitamin C 10 mg / g, pantothenic acid 0.5 mg / g, calcium carbonate 93 mg / g, magnesium gluconate 27 mg / g, manganese sulfate 0.58 mg / g, ferrous lactate 1 mg / g, zinc gluconate 0.1 mg / g, sodium selenite 10 μg / g, and copper sulfate 0.01 mg / g, with a prebiotic content of 0.3 g / 100 mL. In step (4), the hardened probiotics, vitamin-mineral-prebiotics-natural polymer material mixture is mixed uniformly in a mass ratio of 1:4 (300 rpm, 10 min) to obtain a nutritional mixture, which is then mixed uniformly with an aqueous solution of enteric coating material with a concentration of 8% in a mass ratio of 1:6, washed three times and filtered to obtain probiotic-prebiotic-vitamin-mineral wet microspheres; In step (5), the probiotic-prebiotic-vitamin-mineral wet microspheres and hydrogel wet particles are mixed uniformly in a volume ratio of 1:17 (60 rpm, 10 min), then pre-cooled at −80°C for 2.5 h, and freeze-dried at −55°C, vacuum of 25 Pa for 48 h after pre-cooling, and then crushed and sieved to obtain capsule contents; In step (6), the capsule shell is fixed, and two holes are drilled by laser at symmetrical positions in the center of its waist, with a hole diameter of 1 mm, to obtain a porous capsule shell, and then the porous capsule shell is combined with the capsule contents to prepare an anti-feeding capsule containing multi-element nutritional microspheres.

[0065] Comparative Example 1 In step (1), sodium carboxymethylcellulose (viscosity 11000) is added to an aqueous solution containing citric acid (the mass ratio of sodium carboxymethylcellulose to citric acid is 330:1, and the mass ratio of sodium carboxymethylcellulose to distilled water is 1:16), first stirred at 60 rpm for 90 min, then stirred at 30 rpm for 16 h to obtain a gel, which is dried in a 45°C oven for 24 h, turned over and continued to dry for 32 h, then high-temperature cross-linked at 120°C for 4 h, crushed and sieved to obtain solid hydrogel particles, which are washed with distilled water 4 times, each time for 3 h (the mass ratio of solid hydrogel particles to distilled water is 1:150 during each washing), and filtered to prepare hydrogel wet particles; In step (2), the probiotics were inoculated into sterile MRS liquid medium at an inoculum amount of 3% and repeatedly activated for five generations under the same culture conditions (37°C, 24h), the bacterial sludge was collected by low-temperature centrifugation (4°C, 4500rpm, 15min), the bacterial sludge was washed twice with 0.9% sterile saline, and then the bacterial sludge was uniformly mixed with an aqueous solution of lyophilization protection agent with a concentration of 13% in a volume ratio of 1:4 to obtain a bacterial suspension, and then the bacterial suspension was diluted with 0.1mol / L CaCl 2 The hardened probiotics were then cured in the solution for 30 minutes, washed and filtered to obtain the hardened probiotics, which were then stored at a low temperature of 4°C for preparation. In step (3), the vitamin, mineral and prebiotic powders are mixed uniformly and passed through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder. The vitamin-mineral-prebiotic complex powder is then mixed uniformly with a 3% aqueous solution of natural polymeric materials in a mass ratio of 1.5:11 (150 rpm, 20 min) to obtain a vitamin-mineral-prebiotic-natural polymeric material mixture, in which the vitamin, mineral and prebiotic contents are: vitamin A 111 μg / g, vitamin D 3 4μg / g, Vitamin E 4mg / g, Vitamin K 2 8μg / g, Vitamin B 1 0.4mg / g, Vitamin B 2 0.4mg / g, Vitamin B 6 0.4mg / g, Vitamin B 12 0.4 μg / g, niacinamide 4 mg / g, folic acid 60 μg / g, vitamin C 25 mg / g, pantothenic acid 1.5 mg / g, calcium carbonate 113 mg / g, magnesium gluconate 39 mg / g, manganese sulfate 0.78 mg / g, ferrous lactate 3 mg / g, zinc gluconate 1.5 mg / g, sodium selenite 14 μg / g, and copper sulfate 0.16 mg / g, for a prebiotic content of 0.65 g / 100 mL. In step (4), the hardened probiotics, vitamin-mineral-prebiotics-natural polymer material mixture is uniformly mixed (200 rpm, 20 min) in a mass ratio of 1:3 to obtain a nutrient mixture; In step (5), the nutrient mixture and the hydrogel wet particles are mixed uniformly in a mass ratio of 1:15 (45 rpm, 15 min), then pre-cooled at −80°C for 2.5 h, and freeze-dried at −55°C, vacuum of 25 Pa for 36 h after pre-cooling, and then crushed and sieved to obtain the capsule contents; In step (6), the capsule shell is fixed, and four holes are drilled by laser in the center of its waist, with the hole diameter being 1 mm, to obtain a porous capsule shell, and then the porous capsule shell is combined with the capsule contents to prepare an anti-feeding capsule containing multi-element nutritional microspheres.

[0066] Comparative Example 2 In step (1), sodium carboxymethylcellulose (viscosity 11000) is added to an aqueous solution containing citric acid (the mass ratio of sodium carboxymethylcellulose to citric acid is 330:1, and the mass ratio of sodium carboxymethylcellulose to distilled water is 1:16), and the mixture is stirred at 60 rpm for 90 min, and then stirred at 30 rpm for 16 h to obtain a gel. The gel is dried in an oven at 45°C for 24 h, and then dried for 32 h after turning over, and then crosslinked at high temperature at 120°C for 4 h, crushed and sieved to obtain solid hydrogel particles. The solid hydrogel particles are washed with distilled water 4 times, and filtered for 3 h each time (the mass ratio of solid hydrogel particles to distilled water is 1:150 each time to prepare hydrogel wet particles; In step (2), the probiotics were inoculated into sterile MRS liquid medium at an inoculum amount of 3% and repeatedly activated for five generations under the same culture conditions (37°C, 24h), the bacterial sludge was collected by low-temperature centrifugation (4°C, 4500rpm, 15min), the bacterial sludge was washed twice with 0.9% sterile saline, and then the bacterial sludge was uniformly mixed with an aqueous solution of lyophilization protection agent with a concentration of 13% in a volume ratio of 1:4 to obtain a bacterial suspension, and then the bacterial suspension was diluted with 0.1mol / L CaCl 2 The hardened probiotics were then cured in the solution for 30 minutes, washed and filtered to obtain the hardened probiotics, which were then stored at a low temperature of 4°C for preparation. In step (3), the vitamin, mineral and prebiotic powders are uniformly mixed and passed through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder (the vitamins are vitamin A, vitamin D, vitamin E, vitamin E, vitamin D ... 3 , Vitamin E, Vitamin K 2 , Vitamin B 1 , Vitamin B 2 , Vitamin B 6 , Vitamin B 12 , niacinamide, folic acid, vitamin C, pantothenic acid, and the minerals are calcium carbonate, magnesium gluconate, manganese sulfate, ferrous lactate, zinc gluconate, sodium selenite, and copper sulfate, and the contents of vitamins, minerals, and prebiotics in the final food-suppressing capsule containing the multi-element nutritional microspheres are the same as those in Example 1), In step (4), the vitamin-mineral-prebiotic complex powder, the bacterial suspension and the hydrogel wet particles are mixed uniformly in a mass ratio of 0.5:0.5:15 (45 rpm, 15 min), then pre-cooled at −80°C for 2.5 h, and freeze-dried at −55°C, vacuum of 25 Pa for 36 h after pre-cooling, and then crushed and sieved to obtain the capsule contents; In step (5), the capsule shell is fixed, and two holes are drilled by laser in the center of its waist, with a hole diameter of 1 mm, to obtain a porous capsule shell, and then the porous capsule shell is combined with the capsule contents to prepare an anti-feeding capsule containing multi-element nutritional microspheres.

[0067] Comparative Example 3 In step (1), sodium carboxymethylcellulose (viscosity 3000) is added to an aqueous solution containing citric acid (the mass ratio of sodium carboxymethylcellulose to citric acid is 380:1, and the mass ratio of sodium carboxymethylcellulose to distilled water is 1:32), first stirred at 100 rpm for 150 min, then stirred at 60 rpm for 30 h to obtain a gel, which is dried in an oven at 75 ° C for 30 h, then kept dried for 40 h after turning over, then high-temperature cross-linked at 130 ° C for 6 h, crushed and sieved to obtain solid hydrogel particles, which are washed with distilled water 8 times, each time for 4 h (the mass ratio of solid hydrogel particles to distilled water is 1:150 during each washing), and filtered to prepare hydrogel wet particles; In step (2), the probiotics were inoculated into sterile MRS liquid medium at an inoculum amount of 7% and repeatedly activated for five generations under the same culture conditions (39°C, 29h), the bacterial sludge was collected by low-temperature centrifugation (6°C, 6600rpm, 30min), the bacterial sludge was washed four times with 0.95% sterile saline, and then the bacterial sludge was uniformly mixed with an aqueous solution of 25% freeze-drying protection agent at a volume ratio of 1:2 to obtain a bacterial suspension, and then the bacterial suspension was diluted with 0.1mol / L CaCl 2 The hardened probiotics were then cured in the solution for 50 minutes, washed and filtered to obtain the hardened probiotics, which were then stored at a low temperature of 6°C for preparation. In step (3), the vitamin, mineral and prebiotic powders are mixed uniformly and passed through a 70 mesh sieve to obtain a vitamin-mineral-prebiotic complex powder. The vitamin-mineral-prebiotic complex powder is then mixed uniformly with a 6% aqueous solution of natural polymeric material in a mass ratio of 3:11 (200 rpm, 30 min) to obtain a vitamin-mineral-prebiotic-natural polymeric material mixture, in which the vitamin, mineral and prebiotic contents are: vitamin A 111 μg / g, vitamin D 3 4μg / g, Vitamin E 4mg / g, Vitamin K 2 8μg / g, Vitamin B 1 0.4mg / g, Vitamin B 2 0.4mg / g, Vitamin B 6 0.4mg / g, Vitamin B12 0.4 μg / g, niacinamide 4 mg / g, folic acid 60 μg / g, vitamin C 25 mg / g, pantothenic acid 1.5 mg / g, calcium carbonate 113 mg / g, magnesium gluconate 39 mg / g, manganese sulfate 0.78 mg / g, ferrous lactate 3 mg / g, zinc gluconate 1.5 mg / g, sodium selenite 14 μg / g, and copper sulfate 0.16 mg / g, for a prebiotic content of 0.65 g / 100 mL. In step (4), the hardened probiotics, vitamin-mineral-prebiotics-natural polymer material mixture is mixed uniformly in a mass ratio of 1:6 (400 rpm, 40 min) to obtain a nutritional mixture, which is then mixed uniformly with an aqueous solution of enteric coating material with a concentration of 2% in a mass ratio of 1:8, washed and filtered five times to obtain probiotic-prebiotic-vitamin-mineral wet microspheres; In step (5), the probiotic-prebiotic-vitamin-mineral wet microspheres and hydrogel wet particles are mixed uniformly in a mass ratio of 1:20 (60 rpm, 40 min), then pre-cooled at −80°C for 5 h, and freeze-dried at −55°C, vacuum of 25 Pa for 60 h after pre-cooling, and then crushed and sieved to obtain capsule contents; In step (6), the capsule shell is fixed, and four holes are drilled by laser in the center of its waist, with the hole diameter being 1 mm, to obtain a porous capsule shell, and then the porous capsule shell is combined with the capsule contents to prepare an anti-feeding capsule containing multi-element nutritional microspheres.

[0068] The performance of food intake inhibiting capsules containing the multi-element nutritional microspheres of the present invention is measured.

[0069] (1) Acid stability test of probiotics in microspheres Each sample was left in the simulated gastric fluid for 2 h, then the microspheres were separated, washed, and stored at 4°C. 1 g of microspheres was added to 9 mL of phosphate buffer, then placed on a shaking table at 37°C and shaken at 230 rpm for 30 min. Samples were then taken and the total viable bacterial count was calculated.

[0070] The plate counting method was used to measure the total viable count of probiotics, and the specific operation was as follows: In a sterile operation cabinet, the activated strains were mixed uniformly, and then diluted with sterile water in 10-fold increments under sterile operation conditions to obtain three suitable dilution gradients, which were then uniformly inoculated onto MRS agar solid medium and cultured upside down in a 37°C incubator for 24 hours. The plates with 30 to 300 colonies were counted, and the total number of colonies was calculated using the formula: total number of colonies (CFU / g) = average number of colonies of the same dilution gradient × dilution factor × 5. The test results are shown in Table 1.

[0071] (2) Measurement of embedding rate Each sample was placed in the simulated gastric fluid for 2 hours, after which the microspheres were separated, washed and stored at 4°C. 1 g microspheres were added to 9 mL phosphate buffer, shaken on a shaking table at 37°C, 230 rpm for 30 min, sampled, and the viable cell count was calculated, and the vitamin, mineral and prebiotic contents were measured. The embedding rate was calculated according to the following formula: Embedding rate / %=(H 2 / H 0 ) x 100

[0072] In the formula: H 0 is the initial amount of live bacteria (CFU / g), vitamins, minerals or prebiotics added, and H 2 is the number of viable bacteria (CFU / g), vitamins, minerals or prebiotics content embedded in the microspheres.

[0073] The test results are shown in Table 2.

[0074] (3) Time stability studies of vitamins, minerals, probiotics and prebiotics The samples were placed at room temperature and pressure (indoors), and the vitamin, mineral, probiotic and prebiotic contents in the samples were measured every two weeks for 10 weeks. The fat-soluble vitamin content was measured according to BJS 201717 Determination of 9 kinds of fat-soluble vitamins in health foods, the water-soluble vitamin content was measured according to BJS 201716 Determination of 9 kinds of water-soluble vitamins in health foods, the mineral content was measured according to BJS 201718 Determination of 9 kinds of mineral elements in health foods, the probiotic content was measured according to the same method as in Test (1), and the oligofructose (prebiotic) detection method was measured according to GB / T 23528.2-2021 Quality requirements for oligosaccharides Part 2: Oligofructose. The test results are shown in Tables 3, 4, 5 and 6.

[0075] (4) Gel swelling ratio (MUR) measurement research A constant mass of sample (M 0 ) were weighed and placed in 100 mL of diluted artificial gastric juice (volume ratio of artificial gastric juice to sterile distilled water was 1:8, pH 2.10) at 37°C, and the mixture was gently stirred at a rotation speed of 45 rpm for 0.5 h while timing was performed (to prevent air bubbles from forming). After timing, the excess diluted artificial gastric juice was immediately removed with a stainless steel filter, the surface moisture was wiped off with absorbent paper, and the weight of the specimen was measured and counted (M 1 ), and the MUR was calculated using the following formula: Three samples were repeated in parallel, and the results were averaged. Formula:MUR=(M 1 -M 0 ) / M 0 The test results are shown in Figure 3.

[0076] (5) Elasticity measurement research The elastic modulus of the sample was evaluated by dynamic mechanical analysis (DMA). Immediately after the swelling ratio measurement, the sample was placed between the parallel plates (configured with cross shadow lines, diameter 40 mm) of a rotational rheometer, and then the elastic modulus was measured. The gap between the plates was 4 mm, and the value of the elastic modulus at a frequency of 10 rad / s was taken as the elastic modulus of the sample particles. Three samples were repeated in parallel, and the results were averaged. The test results are shown in Figure 3.

[0077] (6) Study on the effect of different concentrations of enteric coating materials on the viability of probiotics in microspheres The samples used in this test are prepared according to the method of Example 1, except that the concentration of the enteric coating material is changed according to FIG. 4, and other conditions are the same as those of Example 1.

[0078] The samples (different concentrations of enteric coating materials) were placed in sterile water for 2 h, then the microspheres were separated, washed and prepared for storage at 4°C. 1 g of microspheres was added to 9 mL of phosphate buffer, then placed on a shaking table at 37°C and shaken at 230 rpm for 30 min, sampled and the total viable bacteria count was calculated.

[0079] The method for measuring the total viable cell count of probiotics was the same as in Test (1). The test results are shown in Figure 4.

[0080] (7) Study on the effect of the residence time of microspheres in the intestine on the viability of probiotics in the microspheres The sample used in this test is the sample prepared in Example 1.

[0081] The samples were placed in sterile water for 2 hours, then the microspheres were separated, washed, and stored at 4°C. 1g of microspheres was added to each of nine containers containing 9mL of artificial intestinal fluid. The containers were then placed on a shaking table at 37°C and shaken at 230 rpm for different times (0min, 15min, 30min, 45min, 60min, 75min, 90min, 105min, 120min), samples were taken, and the total viable bacterial count was calculated.

[0082] The method for measuring the total viable cell count of probiotics was the same as in Test (1). The test results are shown in Figure 5.

[0083] (8) Measurement study of the effect of different laser drilling methods on capsule disintegration time The samples used in this test were prepared according to the method of Example 1, except that the method of laser drilling the capsule shell was different, and the other conditions were the same as those of Example 1.

[0084] The study design for the effect of different laser drilling methods on capsule disintegration time is shown in Table 7 below:

[0085] [Table 7]

[0086] Capsule disintegration time measurement method: Tested according to the 2020 edition of the Pharmacopoeia of the People's Republic of China, Part 4 General Provisions 0921 Disintegration Time Test Method. Test samples of 6 capsules were taken, and the disintegration time measuring device was inspected, and then the test was performed with a baffle, the temperature was set to 37°C, and the time until the capsule was completely dissolved in the artificial gastric juice was recorded. The capsule should be completely disintegrated within 30 minutes. If one capsule did not completely disintegrate, another 6 capsules should be taken for retest. If one capsule did not completely disintegrate again, it was recorded as failing. Three capsule samples were repeated in parallel, and the average value of the results was taken. The test results are shown in Figure 6.

[0087] (9) Study on the weight loss effect of the capsule prepared in this invention Example 1 was selected as the test sample. Five male and five female obese rats of the same age and sexual maturity were used, with the males weighing 500-520g and the females weighing 400-420g. The obese rats were given one capsule 30 minutes before meals at regular intervals every day, and given normal food 30 minutes later. The experiment was continued for 63 days, and the weights of the obese rats were measured and recorded at 20:00 every 7 days. The test results are shown in Figure 7.

[0088] The performance test results for Examples 1 to 9 and Comparative Examples 1 to 3 are as follows.

[0089] [Table 1]

[0090] [Table 2]

[0091] [Table 3]

[0092] [Table 4]

[0093] [Table 5]

[0094] [Table 6]

[0095] As can be seen from Table 1, in comparison with Comparative Examples 1 to 3, the viable cell counts of Examples 1 to 9 were all 10 8As can be seen from Table 2, the embedding rates of probiotics and vitamins in Examples 1 to 9 are all above 80%, the embedding rates of minerals are all above 70%, and the embedding rates of prebiotics are all above 75%, which indicates that the embedding rates of nutrients in the microspheres are good. As can be seen from Tables 3, 4, 5 and 6, the storage resistance of probiotics, vitamins, minerals and prebiotics are all good. As can be seen from FIG. 3, compared with Comparative Example 3, the swelling rate and elasticity modulus of Examples 1 to 9 are good. As can be seen from FIG. 4, in the microsphere preparation process, the embedding rates of probiotics The survival number increases with the increase of the concentration of enteric coating material, and then tends to decrease. When the concentration of enteric coating material is 8%, the survival number of probiotics reaches the maximum value. As can be seen from FIG. 5, the microspheres are basically completely released after staying in the artificial intestinal fluid for 30 minutes, and exist stably in the artificial intestinal fluid. As can be seen from FIG. 6, different laser drilling methods have a great effect on the capsule disintegration time, where the optimal case is to drill two holes symmetrically at the center of the waist of the capsule shell with a hole diameter of 1 mm, which can greatly increase the disintegration speed. As can be seen from FIG. 7, the body weight of adult male and female rats taking the capsule of the present invention changed significantly, and the weight loss rate after 2 months was 14.11% and 10.73%, respectively.

[0096] Although the contents of the present invention have been described in detail in the above preferred embodiments, it should be understood that the above description does not limit the present invention. Various modifications and replacements of the present invention will be obvious to those skilled in the art upon reading the above contents. Therefore, the protection scope of the present invention should be limited by the appended claims.

Claims

1. Step (1) of adding sodium carboxymethyl cellulose to an aqueous solution containing a polybasic carboxylic acid, stirring uniformly to obtain a gel, drying the gel in an oven, then subjecting it to high-temperature cross-linking to obtain a cross-linked product, crushing the cross-linked product and sieving it to obtain solid hydrogel particles, washing the solid hydrogel particles with distilled water and filtering to prepare hydrogel wet particles; Step (2) of inoculating probiotics into a sterilized medium, repeatedly culturing for 5 generations under the same culture conditions, collecting bacterial sludge by low-temperature centrifugation, washing the bacterial sludge with sterilized physiological saline, uniformly mixing the washed bacterial sludge with an aqueous solution of a cryoprotectant to obtain a bacterial suspension, then adding an aqueous solution of a natural polymer material to the bacterial suspension and mixing uniformly again, then curing the obtained mixture, washing and filtering after curing to obtain cured probiotics, and storing them at a low temperature for preparation; Step (3) of uniformly mixing vitamin, mineral and prebiotic powders, passing through a 70-mesh sieve to obtain a vitamin-mineral-prebiotic composite powder, and then uniformly mixing the vitamin-mineral-prebiotic composite powder with an aqueous solution of a natural polymer material to obtain a vitamin-mineral-prebiotic-natural polymer material mixture; Step (4) of uniformly mixing the cured probiotics with the vitamin-mineral-prebiotic-natural polymer material mixture to obtain a nutrient mixture, then mixing the nutrient mixture with an aqueous solution of an enteric coating material to form microspheres, washing and filtering the obtained microspheres to obtain probiotic-prebiotic-vitamin-mineral wet microspheres; Step (5) of uniformly mixing the probiotic-prebiotic-vitamin-mineral wet microspheres and the hydrogel wet particles, freeze-drying after preliminary cooling treatment, then crushing and sieving to obtain capsule contents; Step (6) of perforating a capsule shell with a laser to obtain a porous capsule shell, and then combining the porous capsule shell and the capsule contents to prepare an appetite-suppressing capsule containing multi-element nutrient microspheres, including: In step (1), the viscosity of sodium carboxymethyl cellulose is 7000 to 15000 mPa·s, the mass ratio of sodium carboxymethyl cellulose to polybasic carboxylic acid is 310 to 350:1, the mass ratio of sodium carboxymethyl cellulose to water is 1:10 to 22, and the stirring is carried out as follows: First, stir at a rotational speed of 50 to 70 rpm for 80 to 100 min, then stir at a rotational speed of 20 to 40 rpm for 14 to 20 h. The oven drying temperature is 40 to 60 °C. First, dry for 20 to 28 h, then turn the gel over and continue drying for 28 to 36 h. The high-temperature cross-linking temperature is 110 to 130 °C, and the time is 3.6 to 4.4 h. Crushing and sieving are carried out as follows: Crush the cross-linked product with a crusher, and then sieve it with 18-mesh and 26-mesh sieves. Distilled water washing is carried out as follows: Wash the solid hydrogel particles with distilled water 2 to 6 times, 2 to 4 h each time. The mass ratio of the solid hydrogel particles to distilled water during each washing is 1:100 to 200. In step (6), the laser light source of the laser is a cold light source, the pore diameter of the perforation is 0.5 to 1.5 mm, the number of perforations is 1 to 4, and when binding the porous capsule shell and the capsule content, the mass of the capsule content contained in each porous capsule shell is 0.60 to 0.75 g. A method for preparing an appetite-suppressing capsule containing multi-element nutrient microspheres, characterized in that.

2. In step (1), the polybasic carboxylic acid is any one selected from the group consisting of citric acid, aconitic acid, oxalic acid, tartaric acid, malic acid, malonic acid, succinic acid, adipic acid, azelaic acid, terephthalic acid, trimellitic acid, trimesic acid, ethylenediaminetetraacetic acid, and 2-methylglutaric acid. In step (2), the probiotics are two or more mixed strains selected from the group consisting of Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus fermentum, Lactobacillus salivarius, Lactobacillus helveticus, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus crispatus, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus acidophilus, Lactobacillus casei subsp. casei, Lactobacillus paracasei, Lactobacillus reuteri, Bifidobacterium lactis, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium adolescentis, Bifidobacterium animalis, and Streptococcus thermophilus, In step (3), the vitamin is at least one selected from the group consisting of vitamin A, vitamin D ３ , vitamin E, vitamin K ２ , vitamin B １ , vitamin B ２ , vitamin B ６ , vitamin B １２ , vitamin B １３ , vitamin B １５ , vitamin C, biotin, niacinamide, folic acid, inositol, and pantothenic acid, and the mineral is at least one selected from the group consisting of calcium, magnesium, manganese, iron, zinc, cobalt, molybdenum, chromium, copper, selenium, iodine, phosphorus, potassium, sodium, sulfur, and chlorine, and the prebiotics is any one selected from the group consisting of oligofructose, oligoxylose, oligogalactose, oligoisomaltose, soy oligosaccharide, oligomannose, lactofructose, raffinose, fructose, oligochitosan, resistant starch, wheat dextrin, inulin, polydextrose, argynose, Aspergillus niger oligosaccharide, spirulina, Ascophyllum nodosum, Chlorella vulgaris, and microalgae In steps (2) and (3), the natural polymer material is any one or more selected from the group consisting of sodium alginate, chitosan, modified starch, carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, gellan gum, κ-carrageenan, gum arabic, pectin, carrageenan, gellan gum, xanthan gum, maltodextrin, β-cyclodextrin, gelatin, soy protein isolate, and whey protein, In step (2), the lyoprotectant is any one or more selected from the group consisting of soluble starch, hydroxyethyl starch, resistant dextrin, fructose, glucose, lactose, sucrose, ribose, rhamnose, galactose, fucose, mannose, arabinose, xylan, non-fat dry milk, glycerol, lactitol, sorbitol, mannitol, xylitol, erythritol, maltitol, sodium glutamate, antifreeze peptide, silk peptide, fish collagen peptide, collagen, and polyvinylpyrrolidone, In step (4), the enteric coating material is any one or more selected from the group consisting of Cordyceps sinensis, fucoidan, diclofenac, acrylic resin I, acrylic resin II, acrylic resin III, cellulose acetate benzoate, cellulose acetate succinate, cellulose hydroxypropyl methylcellulose succinate, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, cellulose acetate 1,2,4-benzenetricarboxylate, 1,2,4-benzenetricarboxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, and polyvinyl alcohol acetate benzenedicarboxylate. The preparation method according to claim 1 is characterized in that.

3. In step (2), the inoculum amount of the probiotics is 1.5 to 4.5%, the sterilized medium is MRS liquid medium, the low-temperature centrifugation method is centrifugation at 3 to 5 °C, the centrifugation rotation speed is 3500 to 5500 rpm, the centrifugation time is 10 to 20 min, the number of washing times with the sterilized physiological saline is 1 to 3 times, the salt concentration of the sterilized physiological saline is 0.85% to 0.95% by mass, in the aqueous solution of the lyoprotectant, the mass fraction of the lyoprotectant is 6% to 20%, the bacterial sludge and the aqueous solution of the lyoprotectant are mixed at a volume ratio of 1:3 to 5, and then stirred at a stirring speed of 200 to 400 rpm for 10 to 20 min. The concentration of the probiotics in the bacterial suspension is 10 ９ CFU / mL, and it is cured with a 0.1 mol / L CaCl ２ solution, the curing time is 20 to 40 min, and the low-temperature storage temperature is 3 to 5 °C. The preparation method according to claim 1 or 2, characterized in that.

4. In step (3), the mass ratio of the total mass of vitamins, minerals, and prebiotics to the mass of the aqueous solution of the natural polymer material is 1-2:

11. The composite powder of vitamins-minerals-prebiotics and the aqueous solution of the natural polymer material are mixed at a rotation speed of 150-350 rpm for 10-30 min. In the vitamins-minerals-prebiotics-natural polymer material mixture, the vitamins include vitamin A 95-128 μg / g, vitamin D ３ 1-6 μg / g, vitamin E 1-6 mg / g, vitamin K ２ 6-10 μg / g, vitamin B １ 0.1-0.6 mg / g, vitamin B ２ 0.1-0.6 mg / g, vitamin B ６ 0.1-0.6 mg / g, vitamin B １２ 0.1-0.7 μg / g, niacinamide 1-7 mg / g, folic acid 40-80 μg / g, vitamin C 10-40 mg / g, pantothenic acid 0.5-2.5 mg / g. The minerals include calcium carbonate 93-133 mg / g, magnesium gluconate 27-51 mg / g, manganese sulfate 0.58-0.98 mg / g, ferrous lactate 1-5 mg / g, zinc gluconate 0.1-2.5 mg / g, sodium selenite 10-17 μg / g, copper sulfate 0.01-0.30 mg / g. The prebiotic content is 0.3-1.0 g / 100 mL. The preparation method according to claim 1 or 2, characterized in that.

5. In step (4), the mixing time of the cured probiotics and the vitamin - mineral - prebiotic - natural polymer material mixture, and the mixing time of the nutrient mixture and the aqueous solution of the enteric coating material are each 10 to 30 min, the mixing rotation speed is 100 to 300 rpm, the mass concentration of the aqueous solution of the enteric coating material is 4% to 12%, and the washing is performed 2 to 4 times with sterile distilled water. The preparation method according to claim 1 or 2, characterized in that.

6. In step (5), the mixing time of the probiotic - prebiotic - vitamin - mineral wet microspheres and the hydrogel wet particles is 10 to 20 min, the mixing rotation speed is 30 to 60 rpm, the preliminary cooling treatment is performed at -80 °C for 1 to 4 h, and the freeze - drying is performed under the conditions of a temperature of -55 °C, a vacuum degree of 25 Pa, and a time of 24 to 48 h. The preparation method according to claim 1 or 2, characterized in that.

7. In step (6), the material of the capsule shell is any one of gelatin, pullulan polysaccharides, and glutinous rice starch, the model of the capsule shell is any one of Japanese Pharmacopoeia capsules No. 000, 00, 0, 1, 2, 3, 4, and their extended models, and the perforation position of the capsule shell is any one of the central - symmetric position at the waist, the central - symmetric position at both ends, the equidistant - symmetric position between both ends and the waist, and the oblique - symmetric / equidistant position from the vertex and the center line. The preparation method according to claim 1, characterized in that.

8. An appetite - suppressing capsule containing multi - element nutrient microspheres, manufactured according to the preparation method of an appetite - suppressing capsule containing multi - element nutrient microspheres according to claim 1 or 2.

9. An appetite suppressant capsule containing the multi-element nutrient microspheres according to claim 8, wherein the appetite suppressant capsule comprises a porous capsule shell and a capsule content, the capsule content being microspheres containing multi-element nutrients and hydrogel particles, the hydrogel particles having a three-dimensional network structure composed of polybasic carboxylic acid-crosslinked sodium carboxymethylcellulose, the microspheres containing multi-element nutrients being microcapsules composed of probiotics as a core material and a protective layer as a wall material, the protective layer being, from the inside to the outside, a lyoprotectant layer, a natural polymer material layer embedded with vitamins, minerals and prebiotics, and an enteric coating material layer, and the porous capsule shell being formed by perforating the capsule shell using laser technology. An appetite suppressant capsule characterized by the above.

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