Composition for regulating intestinal microenvironment and relaxing bowel and preparation method thereof

By using specific compositions, including artichoke-rohan fruit-heat seed compound extraction peptides and Bacillus coagulis-Lactobacillus reuteri calcium alginate microspheres, the existing intestinal moistening and laxative products have poor stability, high safety risks and challenges in preservation of active ingredients, and the effect of moistening and laxative intestinal moistening and laxative intestinal moistening and enhancing intestinal immunity is achieved.

CN119745066APending Publication Date: 2025-04-04SHANDONG JINSHI PHARM DEV CO LTD

Patent Information

Application Number
CN202510002672.4
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-01-02
Publication Date
2025-04-04

AI Technical Summary

Technical Problem

The existing intestinal moistening and laxative products have poor stability, high safety risks, and great challenges in preserving active ingredients, making it difficult to effectively regulate the intestinal microenvironment in the long term.

Method used

A composition using a specific number of artichoke-rohan fruit-heat seed composite extracting peptides, Bacillus coli-Lactobacillus reuteri calcium alginate microspheres, Escherichia coli, Salmonella bacterium, licorice extract, Cassia extract, Cistanche extract, Dendrobium officinale extract and other components is used to regulate the intestinal microenvironment through multiple angles, improve the bacterial structure, inhibit harmful bacteria, promote the growth of beneficial bacteria, lubricate the intestine tract, reduce inflammation, and enhance intestinal immunity.

Benefits of technology

It has achieved the effect of moistening the intestines and enhancing intestinal immunity, which is safe, stable and efficient, and can effectively regulate the intestinal microenvironment for a long time.

✦ Generated by Eureka AI based on patent content.

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Patent Text Reader

Abstract

The invention relates to a composition for regulating intestinal microenvironment and relaxing bowel and a preparation method thereof, and belongs to the technical field of biology. The composition comprises the following components in specific parts: artichoke-siraitia grosvenorii-fructus cannabis composite extract peptide, bacillus coagulans-lactobacillus reuteri calcium alginate microspheres, escherichia coli bacteriocin, salmonella bacteriocin, a liquorice extract, a semen cassiae extract, a herba cistanche extract, a dendrobium officinale extract and the like. Wherein the artichoke-siraitia grosvenorii-fructus cannabis compound extract peptide, bacillus coagulans-lactobacillus reuteri calcium alginate microspheres, the liquorice extract, the semen cassiae extract, the herba cistanche extract and the dendrobium officinale extract are obtained by a special preparation method. Through cooperation of the components, the intestinal microenvironment can be adjusted from multiple angles, and the comprehensive effects of improving the intestinal flora structure, inhibiting harmful bacteria, promoting the growth of beneficial bacteria, lubricating the intestinal tract, relieving intestinal inflammation, enhancing the intestinal mucosal barrier function, improving the intestinal immunity and the like are achieved.
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Description

Technical Field

[0001] The invention belongs to the field of biotechnology, and particularly relates to a composition for regulating intestinal microenvironment and moistening the intestine for defecation and a preparation method thereof. Background Art

[0002] In modern society, with the accelerated pace of life, changes in eating habits and increased mental stress, intestinal problems are increasingly becoming one of the important factors that trouble people's health. Among them, constipation, as a common symptom of intestinal dysfunction, brings physical discomfort and psychological burden to many patients.

[0003] The intestinal microenvironment is a complex and delicate ecosystem, inhabited by trillions of microorganisms, including bacteria, fungi, viruses, etc. These microorganisms interact with each other and are interdependent with the host, playing a vital role in maintaining the normal physiological function of the intestine. For example, beneficial bacteria can ferment undigested carbohydrates to produce short-chain fatty acids, which can not only provide energy for intestinal epithelial cells, but also regulate the pH of the intestine, inhibit the growth and reproduction of harmful bacteria, enhance the intestinal barrier function, and prevent harmful substances from entering the human blood circulation. At the same time, the intestinal microbiota is also involved in the metabolism of bile acids, the synthesis of vitamins, and the development and regulation of the immune system.

[0004] However, an unhealthy lifestyle often disrupts the balance of the intestinal microenvironment. A long-term high-fat, low-fiber diet will reduce the food source of beneficial bacteria, leading to a decrease in the number of beneficial bacteria; while excessive intake of processed foods, abuse of antibiotics, and lack of exercise will promote the growth of harmful bacteria and cause an imbalance in the intestinal microenvironment. Once the intestinal microenvironment is unbalanced, the intestinal peristalsis, digestion and absorption, and immune functions will be affected, leading to intestinal problems such as constipation. Constipation not only causes uncomfortable symptoms such as abdominal distension, abdominal pain, and loss of appetite, but may also cause excessive absorption of toxins in the intestines, increasing the liver's detoxification burden. Long-term accumulation may even cause serious complications such as intestinal inflammation, polyps, hemorrhoids, and cardiovascular and cerebrovascular diseases.

[0005] Based on the close connection between the intestinal microenvironment and constipation, regulating the intestinal microenvironment to achieve the purpose of lubricating the intestine and promoting bowel movements has become a research hotspot in the health field. In recent years, researchers have developed a series of laxative products designed to regulate the intestinal microenvironment by conducting in-depth studies on the composition, function and interaction mechanism of the intestinal microbiota with the host. The mechanism of action of these products mainly includes the following aspects: First, supplementing beneficial bacteria, such as bifidobacteria and Lactobacillus acidophilus, etc., to improve the balance of intestinal microecology by directly increasing the number of beneficial bacteria; second, providing prebiotics, that is, food for beneficial bacteria, such as oligofructose and inulin, which can promote the growth and reproduction of the original beneficial bacteria in the intestine; third, using natural plant extracts, such as aloe vera, senna leaves, dietary fiber, etc., these ingredients can stimulate intestinal peristalsis, increase stool volume, soften stool, and thus promote defecation. At the same time, some plant extracts also have certain antibacterial and anti-inflammatory effects, which help to inhibit the growth of harmful bacteria and indirectly regulate the intestinal microenvironment.

[0006] Although the existing laxative products on the market have certain effects, they still generally have the following problems:

[0007] (1) First, the stability of the product effect is poor. On the one hand, the human intestinal microenvironment is complex and varies from person to person. The types and numbers of intestinal flora in different individuals vary greatly, and the same product may have different effects on different people. For example, some people can effectively improve constipation after taking probiotic supplements, but for others, the effect may not be obvious because of the special structure of the original flora in their intestines or the presence of certain factors that inhibit the colonization of probiotics. On the other hand, external environmental factors can also interfere with the effect of the product. Sudden changes in dietary structure, taking antibiotics when sick, etc. may affect the product's regulatory effect on the intestinal microenvironment, making it difficult to maintain a stable and sustained effect of moisturizing the intestines and relieving constipation.

[0008] (2) Secondly, there are potential safety risks. In order to achieve a quick laxative effect, some products add some highly irritating ingredients. For example, some plant laxatives containing anthraquinone compounds may cause damage to intestinal nerves and muscles, weaken intestinal peristalsis, and cause dependence if used for a long time. They may even cause colon melanosis and increase the risk of intestinal cancer.

[0009] (3) Furthermore, the preservation of active ingredients in the product is a challenge. Probiotic products need to ensure the activity of probiotics in order to work. However, probiotics have strict requirements on the environment and are easily inactivated during processing, transportation and storage. For example, changes in temperature and humidity or prolonged contact with oxygen may cause a large number of probiotics to die, thus affecting the actual efficacy of the product.

[0010] Therefore, it is necessary to continuously develop and improve technology to prepare more stable, efficient, safe and easy-to-store laxative products to provide better protection for improving intestinal health and alleviating constipation problems. Summary of the invention

[0011] In order to improve the adaptability, stability and efficiency of laxative products, and solve the problems of safety and storage stability, the present invention provides a composition for regulating intestinal microenvironment and laxative, and a preparation method thereof, wherein the composition comprises a specific number of artichoke-monogrophobia-hemp seed composite extract peptides, Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres, Escherichia coli bacteriocins, Salmonella bacteriocins, licorice extract, cassia seed extract, Cistanche extract, Dendrobium candidum extract and other ingredients. The combination of these ingredients can regulate the intestinal microenvironment from multiple angles, including improving the structure of intestinal flora, inhibiting harmful bacteria, promoting the growth of beneficial bacteria, lubricating the intestine, reducing intestinal inflammation, enhancing the barrier function of the intestinal mucosa and improving intestinal immunity, so as to achieve the effects of laxative and intestinal immunity enhancement, and is safe, stable and efficient. Its specific technical scheme is as follows:

[0012] A composition for regulating intestinal microenvironment and moistening the intestine for defecation, the composition comprises the following raw materials in parts by mass: 10 to 15 parts of artichoke-monogrophoside-hemp seed composite extract peptide, 6 to 10 parts of Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres, 0.005 to 0.015 parts of Escherichia coli bacteriocin, 0.005 to 0.015 parts of Salmonella bacteriocin, 3 to 5 parts of liquorice extract, 1 to 3 parts of cassia seed extract, 5 to 8 parts of Cistanche deserticola extract, 0.3-0.8 parts of Dendrobium officinale extract, 1-3 parts of almonds, 3-6 parts of mulberry leaves, 1-3 parts of Codonopsis pilosula, 1-3 parts of black sesame, 5-8 parts of Sophora japonica seeds, 2-5 parts of Astragalus, 5-10 parts of malt, 0.01-0.03 parts of glutamine, 0.1-0.3 parts of sodium butyrate, 12-18 parts of resistant starch, 0.0001-0.0003 parts of zinc gluconate, 20-30 parts of stachyose and 18-22 parts of flaxseed gum.

[0013] In the above-mentioned composition, the preparation method of the artichoke-monogrophobia-hemp seed composite extraction peptide comprises the following steps: according to the mass ratio of artichoke:monogrophobia:hemp seed=(10-15):(5-10):(3-5), artichoke, monk fruit and hemp seed are mixed and crushed to obtain a mixture, 8 to 12 times the mass of distilled water of the mixture is added, the pH value is adjusted to 8.0-9.0 with sodium hydroxide, the mixture is stirred and extracted at 40°C to 50°C and 200r / min to 300r / min for 1h to 2h, the mixture is centrifuged at 8000r / min to 10000r / min for 20min to 30min, the supernatant is collected, the pH value is adjusted to 6.0-7.0 with hydrochloric acid, 0.05% to 0.1% of the mass of serrapeptase is added to the supernatant, the mixture is enzymolyzed at 45°C to 50°C for 60min to 90min, and the enzyme is inactivated by heating; after cooling to room temperature, The method comprises the following steps: adjusting the pH value to 7.0-8.0, adding 0.05%-0.1% aminopeptidase by weight of the supernatant, performing enzymolysis at 45-55°C for 50-80 minutes, and heating to inactivate the enzyme; after the temperature is lowered to room temperature, adding 0.05%-0.1% ficin by weight of the supernatant, adjusting the pH value to 6.0-7.0, performing enzymolysis at 60-65°C for 60-90 minutes, and heating to inactivate the enzyme; after the temperature is lowered to room temperature, adjusting the pH value to 7.0-7.5, adding 0.002%-0.005% aspartate aminotransferase by weight of the supernatant and 0.005%-0.008% pyridoxal phosphate by weight of the supernatant, performing enzymolysis at 37-40°C for 60-90 minutes, and heating to inactivate the enzyme; after the temperature is lowered to room temperature, filtering with a 5 kDa ultrafiltration membrane, collecting the filtrate below 5 kDa, and freeze-drying to obtain the artichoke-monk fruit-hemp seed composite extracted peptide.

[0014] In the above composition, the preparation method of the Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres comprises the following steps: according to the mass ratio of Bacillus coagulans:Lactobacillus reuteri:sterile physiological saline = (0.3-0.5): (0.3-0.5): (35-55), Bacillus coagulans with a bacterial activity of 1.5 billion CFU / g-2.5 billion CFU / g and Lactobacillus reuteri with a bacterial activity of 1.5 billion CFU / g-2.5 billion CFU / g are added to sterile physiological saline, mixed and dispersed evenly, to obtain a bacterial solution; according to the mass ratio of sodium alginate: The method comprises the following steps: dissolving sodium alginate in sterile water at a mass ratio of sterile water = 1: (50-100) to obtain a sodium alginate solution; adding the bacterial solution dropwise to the sodium alginate solution at a volume ratio of bacterial solution: sodium alginate solution = 1: (1.5-3) while stirring the sodium alginate solution at 15 r / min-30 r / min, controlling the dropping speed to 20 drops / min-30 drops / min, and stirring at 30 r / min-60 r / min for 20 min-30 min after the dropping is completed to ensure uniform coagulation of Bacillus coagulans. dispersed in a sodium alginate solution to form a mixed solution; according to the volume ratio of the mixed solution: the calcium chloride aqueous solution = 1: (3-5), under the stirring state of the calcium chloride aqueous solution at 10r / min-20r / min, the mixed solution is added dropwise at a rate of 1 drop / s-2 drops / s to a calcium chloride aqueous solution at a temperature of 4°C-8°C and a mass concentration of 2%-4%, and the dropping height is controlled at 10cm-15cm. After the dropping is completed, the mixture is stirred at 10r / min-20r / min for 30min-60min to obtain a reaction solution; the reaction The method comprises the following steps: forming calcium alginate microspheres encapsulating Bacillus coagulans and Lactobacillus reuteri in the reaction solution, namely, Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres; filtering the reaction solution through a 650-800 mesh sterile sieve to allow the Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres to adhere to the sieve; then washing the Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres with a sterile physiological saline of 1 to 2 times the volume of the reaction solution to remove residual impurities on the surface; finally, collecting the Bacillus coagulans calcium alginate microspheres and storing them in a cold storage at 4° C. to 5° C.

[0015] In the above composition, the preparation method of the Cassia seed extract comprises the following steps: taking Cassia seed medicinal material, crushing it, using petroleum ether 8 to 10 times the mass of the Cassia seed medicinal material to reflux extract at 40°C to 50°C for 2 to 3 times, each time for 1.5 hours to 2 hours, filtering to remove the petroleum ether extract, evaporating the solvent from the medicinal residue, and removing fat-soluble impurities (including anthraquinone compounds); adding 6 to 8 times the mass of the medicinal residue and 70% to 80% volume concentration of ethanol aqueous solution to the medicinal residue, reflux extracting at 60°C to 70°C for 2 to 3 times, and evaporating the solvent from the medicinal residue to remove fat-soluble impurities (including anthraquinone compounds); adding 6 to 8 times the mass of the medicinal residue and 70% to 80% volume concentration of ethanol aqueous solution to the medicinal residue, and reflux extracting at 60°C to 70°C for 2 to 3 times. The method comprises the steps of: performing the step of: removing the ethanol-water extract by 1 to 3 times, each time for 1 hour to 1.5 hours, combining the extracts of the ethanol-water solution, concentrating under reduced pressure until there is no ethanol, and obtaining a concentrated solution; adding water 2 to 3 times the volume of the concentrated solution to suspend the concentrated solution, adsorbing the sample through an AB-8 macroporous adsorption resin column, and then eluting with water for 3 to 4 column volumes to remove sugar impurities; eluting with an ethanol-water solution with a volume concentration of 40% to 50% for 3 to 4 column volumes, collecting the eluate of the ethanol-water solution, concentrating under reduced pressure, and drying to obtain a Cassia seed extract.

[0016] In the above-mentioned composition, the preparation method of the licorice extract comprises the following steps: crushing the licorice material into coarse powder, adding water 8 to 10 times the mass of the coarse powder, decocting at 100°C for 90 to 120 minutes, filtering to obtain filtrate A and medicinal residues; adding water 6 to 8 times the mass of the medicinal residues to the medicinal residues, decocting at 100°C for 90 to 120 minutes, filtering to obtain filtrate B, combining filtrate A and filtrate B to obtain a medicinal solution; adding ethanol 1 to 2 times the volume of the medicinal solution to the medicinal solution, standing for 12 to 24 hours (precipitating impurities), filtering, and collecting the filtrate; decompressing and concentrating the filtrate to be free of ethanol, applying the sample to a 001×7 type strong acid cation exchange resin column for adsorption, and then eluting with 0.5 mol / L to 0.8 mol / L ammonia water for 3 to 4 column volumes, collecting the eluate of ammonia water, decompressing and concentrating, and drying to obtain the licorice extract.

[0017] In the above composition, the preparation method of the Cistanche deserticola extract comprises the following steps: taking Cistanche deserticola medicinal material, using ethanol aqueous solution with a volume concentration of 30% to 40% of 4 times to 6 times the mass of Cistanche deserticola medicinal material, cold soaking at 4°C to 10°C for 24h to 36h, filtering, and obtaining filtrate C and medicinal residues; concentrating the filtrate C under reduced pressure until there is no ethanol to obtain a water liquid, extracting it with n-butanol for 3 to 4 times, each time with n-butanol The amount of 1 / 3 to 1 / 2 of the volume of the water liquid, combining the n-butanol extracts, concentrating the extracts under reduced pressure, and drying to obtain extract C; adding medicinal residues to the The residue is decocted with water 8 to 10 times the mass at 100° C. for 90 to 120 minutes, filtered to obtain a filtrate D, concentrated to 50% to 60% by volume, adsorbed on an AB-8 macroporous adsorption resin column, then eluted with water for 2 to 3 column volumes to remove impurities, then eluted with 50% to 60% by volume ethanol aqueous solution for 3 to 4 column volumes, the eluate of the ethanol aqueous solution is collected, the extract C is added to the eluate of the ethanol aqueous solution, mixed evenly, concentrated under reduced pressure, and dried to obtain a Cistanche deserticola extract.

[0018] In the above-mentioned composition, the preparation method of the Dendrobium officinale extract comprises the following steps: cutting the fresh stems of the Dendrobium officinale into segments, adding a 0.5wt% to 1wt% citric acid aqueous solution with a mass of 3 to 5 times the mass of the fresh stems, ultrasonically extracting at 40°C to 50°C and 20kHz to 40kHz for 30min to 45min, filtering to obtain a filtrate E and a medicinal residue; adding a 0.3wt% to 0.8wt% oxalic acid aqueous solution with a mass of 2 to 4 times the mass of the medicinal residues to the medicinal residues, ultrasonically extracting at 40°C to 50°C and 20kHz to 40kHz for 20min to 30min, filtering to obtain a filtrate F, combining the filtrate E and the filtrate F, concentrating under reduced pressure to 30% to 40% of the volume, passing the sample through a Sephadex G-25 polysaccharide gel column, and then eluting with water for 3 to 4 column volumes, collecting the water eluate, concentrating under reduced pressure, and drying to obtain the Dendrobium officinale extract.

[0019] In the above composition, the almond is almond dry powder passing through a 80-120 mesh sieve, the mulberry leaf is mulberry leaf dry powder passing through a 80-120 mesh sieve, the codonopsis is codonopsis dry powder passing through a 80-120 mesh sieve, the black sesame is black sesame dry powder passing through a 80-120 mesh sieve, the sophora japonica seed is sophora japonica seed dry powder passing through a 80-120 mesh sieve, the astragalus is astragalus dry powder passing through a 80-120 mesh sieve, and the malt is malt dry powder passing through a 80-120 mesh sieve; the particle size of the resistant starch is passing through a 80-120 mesh sieve; and the particle size of the flaxseed gum is passing through a 80-120 mesh sieve.

[0020] The preparation method of the above-mentioned composition for regulating intestinal microenvironment and moistening the intestine and promoting bowel movements comprises the following steps:

[0021] S1: According to the mass proportions, artichoke-monogrophobia-hemp seed composite extract peptide, Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres, Escherichia coli bacteriocin, Salmonella bacteriocin, licorice extract, cassia seed extract, Cistanche extract and Dendrobium candidum extract were stirred and mixed at 30 r / min to 50 r / min for 10 min to 15 min to obtain mixture I;

[0022] S2: According to the mass proportions, the crushed and sieved almonds, mulberry leaves, codonopsis pilosula, black sesame, sophora japonica seeds, astragalus and malt were stirred and mixed at 60 r / min to 100 r / min for 15 min to 20 min to obtain a mixture II;

[0023] S3: dissolving glutamine, sodium butyrate and zinc gluconate in 0.5 to 1 part of warm water at 40°C to 60°C according to their mass proportions to obtain a solution; stirring and mixing the solution, resistant starch, stachyose and flaxseed gum at 50 rpm to 80 rpm for 10 to 15 minutes, and drying to obtain a mixture III;

[0024] S4: Mixture I, mixture II and mixture III are stirred and mixed at 30 r / min to 50 r / min for 20 min to 30 min to obtain a composite material.

[0025] The composition is mixed with pharmaceutically acceptable auxiliary materials to prepare enteric-coated tablets or enteric-coated capsules.

[0026] The present invention provides a composition for regulating intestinal microenvironment and moistening the intestine for defecation and a preparation method thereof, and the beneficial effects are as follows:

[0027] 1. The composition of the present invention comprises specific portions of artichoke-monogrophodium-hemp seed composite extract peptide, Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres, Escherichia coli bacteriocin, Salmonella bacteriocin, licorice extract, cassia seed extract, Cistanche extract, Dendrobium candidum extract, almond, mulberry leaf, Codonopsis pilosula, black sesame, Sophora japonica seed, Astragalus, malt, glutamine, sodium butyrate, resistant starch, zinc gluconate, stachyose and flaxseed gum. The combination of these ingredients can regulate the intestinal microenvironment from multiple angles, including improving the structure of intestinal flora, inhibiting harmful bacteria, promoting the growth of beneficial bacteria, lubricating the intestine, alleviating intestinal inflammation, enhancing the barrier function of the intestinal mucosa and improving intestinal immunity, so as to achieve the effects of moisturizing the intestine and enhancing intestinal immunity.

[0028] 2. Artichoke-Lo Han Guo-Hemp Seed Composite Extraction Peptide Artichoke, Lo Han Guo and Hemp Seed in a specific proportion are used to extract proteins and water-soluble substances, and serrapeptidase, aminopeptidase, ficin and aspartate aminotransferase are used for graded enzymatic hydrolysis to obtain extracted peptides and water-soluble substances below 5kDa. Nutrients in artichokes such as polyphenolic compounds, flavonoids, etc., mogrosides in Lo Han Guo, and unsaturated fatty acids in hemp seeds work together in composite extraction peptides. Polyphenols in artichokes can resist oxidation and reduce oxidative stress damage in the intestine. Mogrosides have a certain sweetness and can moisturize the intestinal mucosa. Unsaturated fatty acids in hemp seeds can lubricate the intestine. After enzymatic hydrolysis by serrapeptidase, aminopeptidase, ficin, aspartate aminotransferase, etc., the resulting composite extraction peptide has a smaller molecular weight and is more easily absorbed by the human intestine. After entering the intestine, these specific oligopeptides can directly participate in the physiological regulation of the intestine. As signal molecules, they stimulate intestinal cells to secrete some substances that are beneficial to intestinal peristalsis, such as neurotransmitters, thereby promoting intestinal peristalsis and achieving the effect of moistening the intestine and relieving constipation; the components in the composite extracted peptides can provide nutrition for beneficial bacteria in the intestine; some peptide substances can be used by beneficial bacteria such as bifidobacteria to promote their growth and reproduction, thereby improving the structure of intestinal flora. The increase of beneficial bacteria can competitively inhibit the growth of harmful bacteria, reduce the damage of toxins produced by harmful bacteria to the intestinal mucosa, and help maintain the stability of the intestinal microenvironment. The composite extracted peptide enhances intestinal immunity in a variety of ways: on the one hand, it promotes the repair and growth of intestinal mucosal cells and enhances the integrity of the intestinal mucosal barrier. Peptides participate in the synthesis of proteins in intestinal mucosal cells as raw materials, making mucosal cells healthier. On the other hand, it regulates intestinal immune cells, stimulates the activity of immune cells such as lymphocytes in the intestine, improves the immune defense ability of the intestine, and reduces the occurrence of intestinal infections.

[0029] 3. Bacillus coagulans and Lactobacillus reuteri are intestinal probiotics. Bacillus coagulans can metabolize in the intestine to produce lactic acid, acidifying the intestinal environment. This acidic environment is conducive to inhibiting the growth of harmful bacteria (such as Escherichia coli, Salmonella, etc.). At the same time, lactic acid can stimulate intestinal peristalsis, promote defecation, and play a role in lubricating the intestines and relieving constipation. Lactobacillus reuteri can form a biological barrier on the surface of the intestinal mucosa, prevent the adhesion and invasion of harmful bacteria, and maintain the integrity of the intestinal mucosa. Calcium alginate microspheres serve as carriers to provide protection for Bacillus coagulans and Lactobacillus reuteri. When passing through the acidic environment of the stomach, the microspheres can reduce the damage of gastric acid to probiotics, allowing more probiotics to reach the intestine alive and take effect. This protective effect ensures the effective colonization of probiotics in the intestine and helps to regulate the intestinal microenvironment in a long-term and stable manner.

[0030] When Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres enter the intestine, the probiotics therein can competitively utilize the nutrients and living space in the intestine, inhibiting the growth of harmful bacteria. At the same time, probiotics can produce some metabolites that are beneficial to the intestine during their growth and reproduction, such as short-chain fatty acids. Short-chain fatty acids can provide energy for intestinal cells, promote the growth and repair of intestinal cells, and can regulate the immune function of the intestine and enhance intestinal immunity. These probiotics can activate the intestinal immune system, stimulate the activity of immune cells in the intestine (such as macrophages, lymphocytes, etc.); induce immune cells to produce some immunoregulatory factors, and enhance the immune defense capabilities of the intestine.

[0031] Fourth, in the preparation method of the Cassia seed extract of the present invention, fat-soluble impurities, sugar impurities, anthraquinone compounds, etc. are removed through a specific extraction process, and the components in the Cassia seed that are beneficial to intestinal regulation are retained, and anthraquinone compounds are prevented from excessively stimulating the intestinal nerves, which can protect sensitive intestines and improve intestinal health more gently and safely. After the Cassia seed extract enters the intestine, the active ingredients it contains can affect the growth and metabolism of the intestinal flora, create more suitable conditions for the growth of beneficial bacteria, promote the proliferation of beneficial bacteria such as bifidobacteria, inhibit the excessive growth of harmful bacteria, make the intestinal flora structure more reasonable, and then create a good intestinal microecological environment. On the one hand, the Cassia seed extract helps to maintain the stability of the intestinal microenvironment, reduce the damage of harmful bacteria and their toxins to the intestinal mucosa, protect the integrity of the intestinal mucosal barrier, and make the physical defense function of the intestine better; on the other hand, it can regulate the activity of immune cells in the intestine, stimulate the enhancement of the function of intestinal-related lymphocytes, and prompt immune cells to secrete more immunomodulatory factors, thereby improving the overall immune defense ability of the intestine.

[0032] Fifth, the present invention adopts a specific method to prepare liquorice extract, Cistanche extract and Dendrobium candidum extract. The extract is obtained through a series of extraction processes, and a large amount of impurities are removed compared to dry powder. The liquorice extract is enriched with effective ingredients such as glycyrrhizic acid in liquorice through the steps of decoction, alcohol precipitation, ion exchange resin adsorption and elution. The Cistanche extract is subjected to processes such as cold soaking, extraction, and macroporous adsorption resin treatment to obtain more active ingredients. The Dendrobium candidum extract is subjected to operations such as ultrasonic extraction and gel column chromatography, and the purity of the effective ingredients is also higher. In this way, when regulating the intestinal microenvironment and improving intestinal immunity, high-purity and high-concentration effective ingredients can play a role more accurately and efficiently.

[0033] The extraction process releases active ingredients from plant tissues. The Dendrobium officinale extract is extracted with citric acid and oxalic acid solutions with the assistance of ultrasound, which can better dissolve active ingredients such as polysaccharides and dendrobine. The preparation of licorice extract makes glycyrrhizic acid and other ingredients easier for the human body to absorb and utilize. The Cistanche extract is extracted by a combination of cold soaking and hot extraction to fully release active ingredients such as phenylethanol glycosides. The active ingredients in these extracts exist in a form that is easier to be absorbed by the intestines. Compared with dry powder, the extracts can enter intestinal cells faster to exert a regulatory effect, effectively promoting the repair of intestinal mucosal cells and regulating the balance of intestinal flora.

[0034] When the three extracts are used together, their active ingredients produce a synergistic effect. The anti-inflammatory components of the licorice extract can reduce intestinal inflammation and create a good intestinal microenvironment for the effects of the Cistanche extract and the Dendrobium candidum extract. The nutrients in the Cistanche extract can nourish intestinal cells and work together with the polysaccharides and other components in the Dendrobium candidum extract to enhance the barrier function of the intestinal mucosa and improve intestinal immunity. At the same time, they can jointly regulate intestinal peristalsis and intestinal flora, promote the growth of beneficial bacteria, and inhibit the reproduction of harmful bacteria, thereby more effectively achieving the effects of moisturizing the intestines and regulating the intestinal microecology. This synergistic effect is difficult to achieve with simple dry powder mixing.

[0035] 6. Almonds, mulberry leaves, codonopsis, black sesame, sophora japonica, astragalus, malt, these ingredients are rich in nutrients such as protein, dietary fiber, vitamins and minerals, which provide sufficient nutrition for intestinal cells and maintain normal physiological functions of the intestines. The dietary fiber can increase the volume of feces, absorb water, make feces soft, and stimulate intestinal peristalsis, promote defecation, and improve constipation symptoms. These ingredients have a certain effect of regulating qi and blood, which can improve the circulation of qi and blood in the intestines and promote the transportation and transformation function of the intestines, thereby achieving the effect of moisturizing the intestines and relieving constipation.

[0036] 7. Glutamine is one of the main energy sources for intestinal cells, which can provide nutritional support for intestinal cells and promote the growth and repair of intestinal cells; resistant starch and flaxseed gum can be fermented and utilized by beneficial bacteria in the intestine, providing carbon sources for beneficial bacteria and promoting their growth and reproduction. Sodium butyrate can promote the growth and differentiation of intestinal mucosal cells, enhance intestinal barrier function, and reduce the absorption of harmful substances; stachyose has the effect of promoting the proliferation of beneficial bacteria such as bifidobacteria, which helps to improve the intestinal microecological environment; zinc gluconate can participate in the repair of intestinal mucosa and the regulation of immune function, and enhance the resistance of the intestine. DETAILED DESCRIPTION

[0037] The present invention is further described below in conjunction with specific implementation cases, but the present invention is not limited to these embodiments.

[0038] Example 1

[0039] A composition for regulating intestinal microenvironment and moistening the intestines and promoting bowel movements, the composition comprising the following raw materials in parts by mass: 12 parts of artichoke-monogrophoside-hemp seed composite extracted peptide, 8 parts of bacillus coagulans-lactobacillus reuteri calcium alginate microspheres, 0.01 parts of Escherichia coli bacteriocin, 0.01 parts of Salmonella bacteriocin, 4 parts of licorice extract, 2 parts of cassia seed extract, 6 parts of cistanche extract, 0.5 parts of dendrobium candidum extract, 2 parts of almonds, 5 parts of mulberry leaves, 2 parts of codonopsis pilosula, 2 parts of black sesame, 6 parts of sophora japonica seeds, 3 parts of astragalus, 8 parts of malt, 0.02 parts of glutamine, 0.2 parts of sodium butyrate, 15 parts of resistant starch, 0.0002 parts of zinc gluconate, 25 parts of stachyose and 20 parts of flaxseed gum.

[0040] In the above-mentioned composition, the preparation method of the composite peptide extraction of artichoke-monogrophoside-hemp seed comprises the following steps: mixing artichoke, monk fruit and hemp seed according to the mass ratio of artichoke:monogrophoside:hemp seed=13:8:4, crushing to obtain a mixture, adding distilled water 10 times the mass of the mixture, adjusting the pH to 8.5 with sodium hydroxide, stirring and extracting at 45°C and 250r / min for 1.5h, centrifuging at 9000r / min for 25min, collecting the supernatant, adjusting the pH to 6.5 with hydrochloric acid, adding 0.08% of the mass of serrapeptase in the supernatant, enzymolysis at 47°C for 80min, heating to 85°C to inactivate the enzyme for 15min; after cooling to room temperature, adjusting the pH to 7.5, adding the supernatant The method comprises the following steps: adding 0.08% aminopeptidase by weight of the supernatant, performing enzymolysis at 50° C. for 60 min, heating to 85° C. for inactivating the enzyme for 15 min; after cooling to room temperature, adding 0.08% ficin by weight of the supernatant, adjusting the pH to 6.5, performing enzymolysis at 62° C. for 80 min, heating to 85° C. for inactivating the enzyme for 15 min; after cooling to room temperature, adjusting the pH to 7.3, adding 0.003% aspartate aminotransferase by weight of the supernatant and 0.006% pyridoxal phosphate by weight of the supernatant, performing enzymolysis at 38° C. for 70 min, heating to 85° C. for inactivating the enzyme for 15 min; after cooling to room temperature, filtering with a 5 kDa ultrafiltration membrane, collecting the filtrate below 5 kDa, and freeze-drying to obtain the artichoke-siraitia grosvenori-hemp seed composite extracted peptide.

[0041] In the above-mentioned composition, the preparation method of Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres comprises the following steps: according to the mass ratio of Bacillus coagulans: Lactobacillus reuteri: sterile saline = 0.45:0.35:40, Bacillus coagulans with a bacterial activity of 2 billion CFU / g and Lactobacillus reuteri with a bacterial activity of 2 billion CFU / g are added to sterile saline, mixed and dispersed evenly to obtain a bacterial solution; according to the mass ratio of sodium alginate: sterile water = 1:80, sodium alginate is dissolved in sterile water to obtain a sodium alginate solution; according to the volume ratio of bacterial solution: sodium alginate solution = 1:2.2, under the stirring state of the sodium alginate solution at 20r / min, the bacterial solution is added dropwise to the sodium alginate solution, the dripping speed is controlled to 25 drops / min, and after the dropwise addition is completed, it is stirred at 50r / min for 25min to ensure that Bacillus coagulans is evenly dispersed in the sodium alginate solution to form a microsphere. a mixture; according to the volume ratio of the mixture: the calcium chloride aqueous solution = 1:4, under the stirring state of the calcium chloride aqueous solution at 15r / min, the mixed solution is added dropwise at 2 drops / s to the calcium chloride aqueous solution with a temperature of 6°C and a mass concentration of 3%, the dropping height is controlled at 12cm, after the dropwise addition is completed, the mixture is reacted for 40min under stirring at 15r / min to obtain a reaction solution; calcium alginate microspheres encapsulating bacillus coagulans and lactobacillus reuteri, i.e., bacillus coagulans-lactobacillus reuteri calcium alginate microspheres, are formed in the reaction solution; the reaction solution is filtered through a 650-mesh sterile sieve to make the bacillus coagulans-lactobacillus reuteri calcium alginate microspheres adhere to the sieve, and then the bacillus coagulans-lactobacillus reuteri calcium alginate microspheres are rinsed with sterile physiological saline with a volume of 1.5 times that of the reaction solution to remove residual impurities on the surface, and finally the bacillus coagulans calcium alginate microspheres are collected and stored in a refrigerator at 4°C.

[0042] In the above-mentioned composition, the preparation method of cassia seed extract comprises the following steps: taking cassia seed medicinal material, crushing it, refluxing extraction with petroleum ether 9 times the mass of cassia seed medicinal material at 45°C for 2 times, each time for 2 hours, filtering, removing the petroleum ether extract, evaporating the solvent from the residue, and removing fat-soluble impurities (including anthraquinone compounds); adding 75% volume concentration of ethanol aqueous solution 7 times the mass of the residue to the residue, refluxing extraction at 65°C for 2 times, each time for 1.5 hours, combining the extract of ethanol aqueous solution, and concentrating under reduced pressure until there is no ethanol to obtain a concentrated solution; adding 2.5 times the volume of water of the concentrated solution to the concentrated solution, suspending it, loading it and adsorbing it through an AB-8 type macroporous adsorption resin column, and then eluting it with water for 3 column volumes to remove sugar impurities; and then eluting it with 45% volume concentration of ethanol aqueous solution for 4 column volumes, collecting the eluate of ethanol aqueous solution, concentrating it under reduced pressure, and drying to obtain cassia seed extract.

[0043] In the above-mentioned composition, the preparation method of the licorice extract comprises the following steps: grinding the licorice material into coarse powder, adding water of 9 times the mass of the coarse powder, boiling at 100°C for 110 minutes, filtering to obtain filtrate A and medicinal residues; adding water of 7 times the mass of the medicinal residues to the medicinal residues, boiling at 100°C for 100 minutes, filtering to obtain filtrate B, combining filtrate A and filtrate B to obtain a medicinal solution; adding ethanol of 1.5 times the volume of the medicinal solution to the medicinal solution, standing for 20 hours (to precipitate impurities), filtering, and collecting the filtrate; decompressing and concentrating the filtrate to be free of ethanol, applying the sample to a 001×7 type strongly acidic cation exchange resin column for adsorption, and then eluting with 0.6 mol / L ammonia water for 4 column volumes, collecting the eluate of the ammonia water, decompressing and concentrating, and drying to obtain the licorice extract.

[0044] In the above-mentioned composition, the preparation method of the Cistanche deserticola extract comprises the following steps: taking Cistanche deserticola medicinal material, using 35% volume concentration of ethanol aqueous solution with a mass of 5 times that of the Cistanche deserticola medicinal material, cold soaking at 6°C for 30 hours, filtering, and obtaining filtrate C and medicinal residues; filtrate C is concentrated under reduced pressure until there is no ethanol to obtain a water liquid, and extracted with n-butanol for 3 times, each time the amount of n-butanol used is 1 / 3 of the volume of the water liquid, the n-butanol extract is combined, the extract is concentrated under reduced pressure, and dried to obtain extract C; water with a mass of 9 times that of the medicinal residue is added to the medicinal residue, decocted at 100°C for 100 minutes, filtered, and filtrate D is concentrated to 54% of the volume, the sample is adsorbed on an AB-8 type macroporous adsorption resin column, and then eluted with water for 2 column volumes to remove impurities, and then eluted with 56% volume concentration of ethanol aqueous solution for 3 column volumes, the eluate of the ethanol aqueous solution is collected, the extract C is added to the eluate of the ethanol aqueous solution, mixed evenly, concentrated under reduced pressure, and dried to obtain the Cistanche deserticola extract.

[0045] In the above-mentioned composition, the preparation method of the Dendrobium officinale extract comprises the following steps: cutting the fresh stems of the Dendrobium officinale into segments, adding a 0.8wt% citric acid aqueous solution with a mass of 4 times that of the fresh stems, ultrasonically extracting at 45°C and 30kHz for 40min, filtering to obtain a filtrate E and a medicinal residue; adding a 0.5wt% oxalic acid aqueous solution with a mass of 3 times that of the medicinal residue to the medicinal residue, ultrasonically extracting at 45°C and 30kHz for 25min, filtering to obtain a filtrate F, combining the filtrate E and the filtrate F, concentrating under reduced pressure to 35% of the volume, passing the sample through a Sephadex G-25 polysaccharide gel column, and then eluting with water for 4 column volumes, collecting the water eluate, concentrating under reduced pressure, and drying to obtain the Dendrobium officinale extract.

[0046] In the above composition, almonds are almond dry powder passing through a 100-mesh sieve, mulberry leaves are mulberry leaf dry powder passing through a 100-mesh sieve, Codonopsis pilosula is Codonopsis pilosula dry powder passing through a 100-mesh sieve, black sesame is black sesame dry powder passing through a 100-mesh sieve, Sophora japonica seed is Sophora japonica seed dry powder passing through a 100-mesh sieve, astragalus is astragalus dry powder passing through a 100-mesh sieve, and malt is malt dry powder passing through a 100-mesh sieve; the particle size of resistant starch is passing through a 100-mesh sieve; and the particle size of flaxseed gum is passing through a 100-mesh sieve.

[0047] The preparation method of the above-mentioned composition for regulating intestinal microenvironment and moistening the intestine and promoting bowel movements comprises the following steps:

[0048] S1: Artichoke-monogrophobia-hemp seed composite extract peptide, Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres, Escherichia coli bacteriocin, Salmonella bacteriocin, licorice extract, Cassia seed extract, Cistanche extract and Dendrobium candidum extract were stirred and mixed at 40 r / min for 12 min to obtain mixture I;

[0049] S2: crushing and sieving almonds, mulberry leaves, codonopsis pilosula, black sesame, sophora japonica seeds, astragalus and malt according to their weight proportions, and stirring and mixing at 80 r / min for 18 min to obtain mixture II;

[0050] S3: Dissolve glutamine, sodium butyrate and zinc gluconate in 0.8 parts of 50° C. warm water according to their mass fractions to obtain a solution; stir and mix the solution, resistant starch, stachyose and flaxseed gum at 60 r / min for 12 min, and dry to obtain a mixture III;

[0051] S4: Mixture I, mixture II and mixture III were stirred and mixed at 40 r / min for 25 min to obtain a composition.

[0052] The composition is mixed with pharmaceutically acceptable auxiliary materials to prepare enteric-coated tablets or enteric-coated capsules.

[0053] Example 2

[0054] A composition for regulating intestinal microenvironment and moistening the intestine and promoting bowel movements, the composition comprising the following raw materials in parts by mass: 10 parts of artichoke-monohanguo-hemp seed composite extracted peptide, 6 parts of bacillus coagulans-lactobacillus reuteri calcium alginate microspheres, 0.005 parts of Escherichia coli bacteriocin, 0.005 parts of Salmonella bacteriocin, 3 parts of liquorice extract, 1 part of cassia seed extract, 5 parts of cistanche extract, 0.3 parts of dendrobium candidum extract, 1 part of almond, 3 parts of mulberry leaf, 1 part of codonopsis pilosula, 1 part of black sesame, 5 parts of sophora japonica seed, 2 parts of astragalus, 5 parts of malt, 0.01 part of glutamine, 0.1 part of sodium butyrate, 12 parts of resistant starch, 0.0001 part of zinc gluconate, 20 parts of stachyose and 18 parts of flaxseed gum.

[0055] In the above-mentioned composition, the preparation method of the composite peptide extraction of artichoke-monogrophoside-hemp seed comprises the following steps: mixing artichoke, monk fruit and hemp seed according to the mass ratio of artichoke:monogrophoside:hemp seed=10:5:3, crushing to obtain a mixture, adding 8 times the mass of distilled water of the mixture, adjusting the pH to 8.0 with sodium hydroxide, stirring and extracting at 40°C and 200r / min for 1h, centrifuging at 8000r / min for 20min, collecting the supernatant, adjusting the pH to 6.0 with hydrochloric acid, adding 0.05% of the mass of serrapeptase in the supernatant, enzymolysis at 45°C for 60min, heating to 85°C to inactivate the enzyme for 15min; after cooling to room temperature, adjusting the pH to 7.0, adding the supernatant 0.05% aminopeptidase by weight is enzymatically hydrolyzed at 45°C for 50 minutes, and the temperature is increased to 85°C for 15 minutes to inactivate the enzyme; after the temperature is reduced to room temperature, 0.05% ficin by weight of the supernatant is added, the pH is adjusted to 6.0, the temperature is reduced to 60°C for 60 minutes, and the temperature is increased to 85°C for inactivation of the enzyme for 15 minutes; after the temperature is reduced to room temperature, the pH is adjusted to 7.0, 0.002% aspartate aminotransferase by weight of the supernatant and 0.005% pyridoxal phosphate by weight of the supernatant are added, the temperature is reduced to 37°C for 60 minutes, and the temperature is increased to 85°C for inactivation of the enzyme for 15 minutes; after the temperature is reduced to room temperature, 5kDa ultrafiltration membrane is used for filtering, filtrate below 5kDa is collected, and freeze-dried to obtain artichoke-siraitia grosvenori-hemp seed composite extracted peptide.

[0056] In the above-mentioned composition, the preparation method of Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres comprises the following steps: according to the mass ratio of Bacillus coagulans: Lactobacillus reuteri: sterile saline = 0.3:0.3:35, Bacillus coagulans with a bacterial activity of 1.5 billion CFU / g and Lactobacillus reuteri with a bacterial activity of 1.5 billion CFU / g are added to sterile saline, mixed and dispersed evenly to obtain a bacterial solution; according to the mass ratio of sodium alginate: sterile water = 1:50, sodium alginate is dissolved in sterile water to obtain a sodium alginate solution; according to the volume ratio of bacterial solution: sodium alginate solution = 1:1.5, under the stirring state of the sodium alginate solution at 15r / min, the bacterial solution is added dropwise to the sodium alginate solution, the dripping speed is controlled to 20 drops / min, and after the dropwise addition is completed, it is stirred at 30r / min for 20min to ensure that Bacillus coagulans is evenly dispersed in the sodium alginate solution to form a microsphere. a mixture; according to the volume ratio of the mixture: the calcium chloride aqueous solution = 1:3, under the stirring state of the calcium chloride aqueous solution at 10r / min, the mixed solution is added dropwise at 1 drop / s to the calcium chloride aqueous solution with a temperature of 4°C and a mass concentration of 2%, the dropping height is controlled at 10cm, after the dropwise addition is completed, the mixture is reacted for 30min under stirring at 10r / min to obtain a reaction solution; calcium alginate microspheres encapsulating bacillus coagulans and lactobacillus reuteri, i.e., bacillus coagulans-lactobacillus reuteri calcium alginate microspheres, are formed in the reaction solution; the reaction solution is filtered through a 650-mesh sterile sieve to make the bacillus coagulans-lactobacillus reuteri calcium alginate microspheres adhere to the sieve, and then the bacillus coagulans-lactobacillus reuteri calcium alginate microspheres are rinsed with sterile physiological saline with a volume of 1 times the reaction solution to remove residual impurities on the surface, and finally the bacillus coagulans calcium alginate microspheres are collected and stored in a refrigerator at 4°C.

[0057] In the above-mentioned composition, the preparation method of cassia seed extract comprises the following steps: taking cassia seed medicinal material, crushing it, refluxing extraction with petroleum ether 10 times the mass of cassia seed medicinal material at 50°C for 3 times, each time for 2 hours, filtering, removing the petroleum ether extract, evaporating the solvent from the residue, and removing fat-soluble impurities (including anthraquinone compounds); adding 80% volume concentration of ethanol aqueous solution 8 times the mass of the residue to the residue, refluxing extraction at 70°C for 3 times, each time for 1.5 hours, combining the extract of ethanol aqueous solution, and concentrating under reduced pressure until there is no ethanol to obtain a concentrated solution; adding 3 times the volume of water of the concentrated solution to the concentrated solution, suspending it, loading it and adsorbing it through an AB-8 type macroporous adsorption resin column, and then eluting it with water for 4 column volumes to remove sugar impurities; and then eluting it with 50% volume concentration of ethanol aqueous solution for 4 column volumes, collecting the eluate of ethanol aqueous solution, concentrating it under reduced pressure, and drying it to obtain cassia seed extract.

[0058] In the above-mentioned composition, the preparation method of the licorice extract comprises the following steps: grinding the licorice material into coarse powder, adding water 10 times the mass of the coarse powder, decocting at 100°C for 120 minutes, filtering to obtain filtrate A and medicinal residues; adding water 8 times the mass of the medicinal residues to the medicinal residues, decocting at 100°C for 120 minutes, filtering to obtain filtrate B, combining filtrate A and filtrate B to obtain a medicinal solution; adding ethanol 2 times the volume of the medicinal solution to the medicinal solution, standing for 24 hours (to precipitate impurities), filtering, and collecting the filtrate; decompressing and concentrating the filtrate until there is no ethanol, applying the sample to a 001×7 type strong acid cation exchange resin column for adsorption, and then eluting with 0.8 mol / L ammonia water for 4 column volumes, collecting the eluate of the ammonia water, decompressing and concentrating, and drying to obtain the licorice extract.

[0059] In the above-mentioned composition, the preparation method of the Cistanche deserticola extract comprises the following steps: taking Cistanche deserticola medicinal material, using an ethanol aqueous solution with a volume concentration of 40% and a mass of 6 times that of the Cistanche deserticola medicinal material, cold soaking at 10°C for 36 hours, filtering, and obtaining a filtrate C and a medicinal residue; the filtrate C is concentrated under reduced pressure until there is no ethanol, obtaining a water liquid, extracting with n-butanol for 4 times, each time using n-butanol in an amount of 1 / 2 of the volume of the water liquid, combining the n-butanol extract, concentrating the extract under reduced pressure, and drying to obtain an extract C; adding water with a mass of 10 times that of the medicinal residue to the medicinal residue, boiling at 100°C for 120 minutes, filtering, and obtaining a filtrate D, the filtrate D is concentrated to 60% of the volume, the sample is adsorbed on an AB-8 type macroporous adsorption resin column, and then eluted with water for 3 column volumes to remove impurities, and then eluted with an ethanol aqueous solution with a volume concentration of 60% for 4 column volumes, collecting the eluate of the ethanol aqueous solution, adding the extract C to the eluate of the ethanol aqueous solution, mixing evenly, concentrating under reduced pressure, and drying to obtain the Cistanche deserticola extract.

[0060] In the above-mentioned composition, the preparation method of the Dendrobium officinale extract comprises the following steps: cutting the fresh stems of the Dendrobium officinale into segments, adding a 1wt% citric acid aqueous solution with a mass of 5 times the mass of the fresh stems, ultrasonically extracting at 50°C and 40kHz for 45min, filtering to obtain a filtrate E and a medicinal residue; adding a 0.8wt% oxalic acid aqueous solution with a mass of 4 times the mass of the medicinal residues to the medicinal residues, ultrasonically extracting at 50°C and 40kHz for 30min, filtering to obtain a filtrate F, combining the filtrate E and the filtrate F, concentrating under reduced pressure to 40% of the volume, passing the sample through a Sephadex G-25 polysaccharide gel column, and then eluting with water for 4 column volumes, collecting the water eluate, concentrating under reduced pressure, and drying to obtain the Dendrobium officinale extract.

[0061] In the above composition, almonds are almond dry powder passed through a 120-mesh sieve, mulberry leaves are mulberry leaf dry powder passed through a 120-mesh sieve, Codonopsis pilosula is Codonopsis pilosula dry powder passed through a 120-mesh sieve, black sesame is black sesame dry powder passed through a 120-mesh sieve, Sophora japonica seed is Sophora japonica seed dry powder passed through a 120-mesh sieve, Astragalus membranaceus is Astragalus membranaceus dry powder passed through a 120-mesh sieve, and malt is malt dry powder passed through a 120-mesh sieve; the particle size of the resistant starch is passed through a 120-mesh sieve; and the particle size of the flaxseed gum is passed through a 120-mesh sieve.

[0062] The preparation method of the above-mentioned composition for regulating intestinal microenvironment and moistening the intestine and promoting bowel movements comprises the following steps:

[0063] S1: According to the mass proportions, artichoke-monogrophobia-hemp seed composite extract peptide, Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres, Escherichia coli bacteriocin, Salmonella bacteriocin, licorice extract, cassia seed extract, Cistanche deserticola extract and Dendrobium officinale extract were stirred and mixed at 30 r / min for 10 min to obtain mixture I;

[0064] S2: crush and sieve almonds, mulberry leaves, codonopsis pilosula, black sesame, sophora japonica seeds, astragalus and malt according to their weight proportions, and stir and mix them at 60 r / min for 15 min to obtain mixture II;

[0065] S3: Dissolve glutamine, sodium butyrate and zinc gluconate in 0.5 parts of 40° C. warm water according to their mass fractions to obtain a solution; stir and mix the solution, resistant starch, stachyose and flaxseed gum at 50 r / min for 10 min, and dry to obtain a mixture III;

[0066] S4: Mixture I, mixture II and mixture III were stirred and mixed at 30 r / min for 20 min to obtain a composition.

[0067] The composition is mixed with pharmaceutically acceptable auxiliary materials to prepare enteric-coated tablets or enteric-coated capsules.

[0068] Example 3

[0069] A composition for regulating intestinal microenvironment and moistening the intestine and promoting bowel movements, the composition comprising the following raw materials in parts by mass: 15 parts of artichoke-monohanguo-hemp seed composite extracted peptide, 10 parts of bacillus coagulans-lactobacillus reuteri calcium alginate microspheres, 0.015 parts of Escherichia coli bacteriocin, 0.015 parts of Salmonella bacteriocin, 5 parts of liquorice extract, 3 parts of cassia seed extract, 8 parts of cistanche extract, 0.8 parts of dendrobium candidum extract, 3 parts of almond, 6 parts of mulberry leaf, 3 parts of codonopsis pilosula, 3 parts of black sesame, 8 parts of sophora japonica seed, 5 parts of astragalus, 10 parts of malt, 0.03 parts of glutamine, 0.3 parts of sodium butyrate, 18 parts of resistant starch, 0.0003 parts of zinc gluconate, 30 parts of stachyose and 22 parts of flaxseed gum.

[0070] In the above-mentioned composition, the preparation method of the composite peptide extraction of artichoke-monogrophoside-hemp seed comprises the following steps: according to the mass ratio of artichoke:monogrophoside:hemp seed=15:10:5, artichoke, monk fruit and hemp seed are mixed and crushed to obtain a mixture, 12 times the mass of distilled water of the mixture is added, the pH value is adjusted to 9.0 with sodium hydroxide, the mixture is stirred and extracted at 50°C and 300r / min for 2h, the mixture is centrifuged at 10000r / min for 30min, the supernatant is collected, the pH value is adjusted to 7.0 with hydrochloric acid, 0.1% of the mass of serrapeptase is added to the supernatant, the mixture is enzymolyzed at 50°C for 90min, the temperature is raised to 85°C for enzyme inactivation for 15min; after cooling to room temperature, the pH value is adjusted to 8.0, the above The method comprises the following steps: adding 0.1% aminopeptidase by weight of the supernatant, performing enzymolysis at 55°C for 80 minutes, heating the supernatant to 85°C for 15 minutes, adding 0.1% ficin by weight of the supernatant after the supernatant is cooled to room temperature, adjusting the pH value to 7.0, performing enzymolysis at 65°C for 90 minutes, heating the supernatant to 85°C for 15 minutes, adjusting the pH value to 7.5, adding 0.005% aspartate aminotransferase by weight of the supernatant and 0.008% pyridoxal phosphate by weight of the supernatant, performing enzymolysis at 40°C for 90 minutes, heating the supernatant to 85°C for 15 minutes, and filtering the supernatant with a 5 kDa ultrafiltration membrane after the supernatant is cooled to room temperature, collecting the filtrate below 5 kDa, and freeze-drying the supernatant to obtain the artichoke-siraitia grosvenori-hemp seed composite extracted peptide.

[0071] In the above composition, the preparation method of Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres comprises the following steps: according to the mass ratio of Bacillus coagulans: Lactobacillus reuteri: sterile saline = 0.5:0.5:55, Bacillus coagulans with a bacterial activity of 2.5 billion CFU / g and Lactobacillus reuteri with a bacterial activity of 2.5 billion CFU / g are added to sterile saline, mixed and dispersed evenly to obtain a bacterial solution; according to the mass ratio of sodium alginate: sterile water = 1:100, sodium alginate is dissolved in sterile water to obtain a sodium alginate solution; according to the volume ratio of bacterial solution: sodium alginate solution = 1:3, under the stirring state of the sodium alginate solution at 30r / min, the bacterial solution is added dropwise to the sodium alginate solution, the dripping speed is controlled to 30 drops / min, and after the dropwise addition is completed, it is stirred at 60r / min for 30min to ensure that the Bacillus coagulans is evenly dispersed in the sodium alginate solution to form a microsphere. a mixture; according to the volume ratio of the mixture: the calcium chloride aqueous solution=1:5, under the stirring state of the calcium chloride aqueous solution at 20r / min, the mixed solution is added dropwise to the calcium chloride aqueous solution with a temperature of 8°C and a mass concentration of 4% at 2 drops / s, the dropping height is controlled at 15cm, after the dropwise addition is completed, the mixture is reacted for 60min under stirring at 20r / min to obtain a reaction solution; calcium alginate microspheres encapsulating bacillus coagulans and lactobacillus reuteri, i.e., bacillus coagulans-lactobacillus reuteri calcium alginate microspheres, are formed in the reaction solution; the reaction solution is filtered through an 800-mesh sterile sieve to make the bacillus coagulans-lactobacillus reuteri calcium alginate microspheres adhere to the sieve, and then the bacillus coagulans-lactobacillus reuteri calcium alginate microspheres are rinsed with sterile physiological saline with a volume of 2 times the reaction solution to remove residual impurities on the surface, and finally the bacillus coagulans calcium alginate microspheres are collected and stored in a refrigerator at 5°C.

[0072] In the above-mentioned composition, the preparation method of cassia seed extract comprises the following steps: taking cassia seed medicinal material, crushing it, refluxing extraction with petroleum ether 8 times the mass of cassia seed medicinal material at 40°C for 2 times, each time for 1.5 hours, filtering, removing the petroleum ether extract, evaporating the solvent from the medicinal residue, and removing fat-soluble impurities (including anthraquinone compounds); adding 6 times the mass of the medicinal residue and 70% volume concentration of ethanol aqueous solution to the medicinal residue, refluxing extraction at 60°C for 2 times, each time for 1 hour, combining the extract of ethanol aqueous solution, and concentrating under reduced pressure until there is no ethanol to obtain a concentrated solution; adding 2 times the volume of water of the concentrated solution to the concentrated solution, suspending it, loading it and adsorbing it through an AB-8 type macroporous adsorption resin column, and then eluting it with water for 3 column volumes to remove sugar impurities; and then eluting it with 40% volume concentration of ethanol aqueous solution for 3 column volumes, collecting the eluate of ethanol aqueous solution, concentrating it under reduced pressure, and drying it to obtain cassia seed extract.

[0073] In the above-mentioned composition, the preparation method of the licorice extract comprises the following steps: crushing the licorice material into coarse powder, adding water 8 times the mass of the coarse powder, decocting at 100°C for 90 minutes, filtering to obtain filtrate A and medicinal residues; adding water 6 times the mass of the medicinal residues to the medicinal residues, decocting at 100°C for 90 minutes, filtering to obtain filtrate B, combining filtrate A and filtrate B to obtain a medicinal solution; adding ethanol 1 times the volume of the medicinal solution to the medicinal solution, standing for 12 hours (precipitating impurities), filtering, and collecting the filtrate; decompressing and concentrating the filtrate until there is no ethanol, applying the sample to a 001×7 type strong acid cation exchange resin column for adsorption, and then eluting with 0.5 mol / L ammonia water for 3 column volumes, collecting the eluate of the ammonia water, decompressing and concentrating, and drying to obtain the licorice extract.

[0074] In the above-mentioned composition, the preparation method of the Cistanche deserticola extract comprises the following steps: taking Cistanche deserticola medicinal material, using 4 times the mass of Cistanche deserticola medicinal material and 30% volume concentration of ethanol aqueous solution, cold soaking at 4°C for 24 hours, filtering, and obtaining filtrate C and medicinal residues; filtrate C is concentrated under reduced pressure until there is no ethanol to obtain a water liquid, and extracted with n-butanol for 3 times, each time the amount of n-butanol used is 1 / 3 of the volume of the water liquid, and the n-butanol extract is combined, and the extract is concentrated under reduced pressure and dried to obtain extract C; water with 8 times the mass of the medicinal residue is added to the medicinal residue, decocted at 100°C for 90 minutes, filtered, and filtrate D is concentrated to 50% of the volume, the sample is adsorbed on an AB-8 type macroporous adsorption resin column, and then eluted with water for 2 column volumes to remove impurities, and then eluted with 50% volume concentration of ethanol aqueous solution for 3 column volumes, the eluate of the ethanol aqueous solution is collected, and the extract C is added to the eluate of the ethanol aqueous solution, mixed evenly, concentrated under reduced pressure, and dried to obtain the Cistanche deserticola extract.

[0075] In the above-mentioned composition, the preparation method of the Dendrobium officinale extract comprises the following steps: cutting the fresh stems of the Dendrobium officinale into segments, adding a 0.5wt% citric acid aqueous solution with a mass of 3 times the mass of the fresh stems, ultrasonically extracting at 40°C and 20kHz for 30min, filtering to obtain a filtrate E and a medicinal residue; adding a 0.3wt% oxalic acid aqueous solution with a mass of 2 times the mass of the medicinal residues to the medicinal residues, ultrasonically extracting at 40°C and 20kHz for 20min, filtering to obtain a filtrate F, combining the filtrate E and the filtrate F, concentrating under reduced pressure to 30% of the volume, passing the sample through a Sephadex G-25 polysaccharide gel column, and then eluting with water for 3 column volumes, collecting the water eluate, concentrating under reduced pressure, and drying to obtain the Dendrobium officinale extract.

[0076] In the above composition, almonds are almond dry powder passing through an 80-mesh sieve, mulberry leaves are mulberry leaf dry powder passing through an 80-mesh sieve, Codonopsis pilosula is Codonopsis pilosula dry powder passing through an 80-mesh sieve, black sesame is black sesame dry powder passing through an 80-mesh sieve, Sophora japonica seed is Sophora japonica seed dry powder passing through an 80-mesh sieve, Astragalus membranaceus is Astragalus membranaceus dry powder passing through an 80-mesh sieve, and malt is malt dry powder passing through an 80-mesh sieve; the particle size of resistant starch is passing through an 80-mesh sieve; and the particle size of flaxseed gum is passing through an 80-mesh sieve.

[0077] The preparation method of the above-mentioned composition for regulating intestinal microenvironment and moistening the intestine and promoting bowel movements comprises the following steps:

[0078] S1: According to the mass proportions, artichoke-monogrophobia-hemp seed composite extract peptide, Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres, Escherichia coli bacteriocin, Salmonella bacteriocin, licorice extract, cassia seed extract, Cistanche extract and Dendrobium candidum extract were stirred and mixed at 50 r / min for 15 min to obtain mixture I;

[0079] S2: crush and sieve almonds, mulberry leaves, codonopsis pilosula, black sesame, sophora japonica seeds, astragalus and malt according to their weight proportions, and stir and mix them at 100 r / min for 20 min to obtain mixture II;

[0080] S3: Dissolve glutamine, sodium butyrate and zinc gluconate in 1 part of 60°C warm water according to their mass fractions to obtain a solution; stir and mix the solution, resistant starch, stachyose and flaxseed gum at 80 r / min for 15 min, and dry to obtain a mixture III;

[0081] S4: Mixture I, mixture II and mixture III were stirred and mixed at 50 r / min for 30 min to obtain a composition.

[0082] The composition is mixed with pharmaceutically acceptable auxiliary materials to prepare enteric-coated tablets or enteric-coated capsules.

[0083] In the preparation methods of the artichoke-monk fruit-hemp seed composite extraction peptides of the above embodiments, the artichoke is a fresh artichoke bud, the monk fruit is monk fruit flesh, and the hemp seed is shelled hemp seed; the enzyme activity of serrapeptidase is 200,000 U / g, the enzyme activity of aminopeptidase is 100,000 U / g, the enzyme activity of ficin is 100,000 U / g, and the enzyme activity of aspartate aminotransferase is 200,000 U / g.

[0084] In the above embodiments: resistant starch comes from Qingdao Qingshan Bioengineering Co., Ltd., resistant starch RS3; stachyose comes from Beijing Biolab Technology Co., Ltd.; flaxseed gum comes from Shandong Fuwangjia Biotechnology Co., Ltd.

[0085] In the above embodiments: the preparation method of Escherichia coli bacteriocin comprises the following steps:

[0086] N1: E. coli was inoculated into 50 mL LB liquid medium (10 g / L tryptone, 5 g / L yeast extract, 10 g / L sodium chloride, pH 7.0), and cultured in a shaker at 37°C and 200 r / min for 16 h to activate the strain;

[0087] N2: Transfer the activated strain to 500 mL of fresh LB liquid medium at a volume inoculation rate of 3%, and continue culturing at 37°C and 200 r / min for 36 h until the bacterial growth enters the early stable stage, and obtain the bacterial liquid;

[0088] N3: Centrifuge the cultured bacterial solution at 4°C, 8000r / min for 20min, and collect the supernatant; add ammonium sulfate to the supernatant to dissolve it until the saturation reaches 80%, and let it stand at 4°C for 12h to precipitate the bacteriocin; then centrifuge at 4°C, 10000r / min for 20min, and collect the precipitate; dissolve the precipitate with pH7.0, 20mM phosphate buffer with a mass 4 times that of the precipitate to obtain a crude bacteriocin extract.

[0089] N4: Load the crude bacteriocin extract onto a SP Sepharose Fast Flow cation exchange column that has been pre-equilibrated with pH 7.0, 20 mM phosphate buffer, and control the loading flow rate at 2 mL / min; elute with 3 times the volume of the crude bacteriocin extract in 20 mM phosphate buffer (pH 7.0) containing 1 M NaCl to obtain an eluate, which is spray-dried to obtain Escherichia coli bacteriocin.

[0090] In the above embodiments: the preparation method of Salmonella bacteriocin comprises the following steps:

[0091] M1: Take Salmonella and streak it on LB agar plate (tryptone 10g / L, yeast extract 5g / L, sodium chloride 10g / L, agar 15g / L, pH 7.2), and culture it in a 37℃ incubator for 24h;

[0092] M2: Pick a single colony after activation and inoculate it into 50 mL LB liquid medium (tryptone 10 g / L, yeast extract 5 g / L, sodium chloride 10 g / L, pH 7.2), shake and culture at 37°C and 150 r / min for 12 h to obtain seed solution;

[0093] M3: The seed liquid was transferred to 500 mL of optimized fermentation medium (the optimized fermentation medium was LB liquid medium with 0.5 wt% glucose and 0.2 wt% magnesium sulfate added) at a volume inoculation rate of 3%, and cultured at 37°C and 200 r / min for 48 h to allow a large amount of bacteriocin to be synthesized and secreted into the culture medium to obtain a bacterial liquid.

[0094] M4: Centrifuge the bacterial solution at 4°C, 8000r / min for 20min, collect the supernatant, add ammonium sulfate to the supernatant to dissolve it until the saturation reaches 80%, and let it stand at 4°C for 12h to precipitate the bacteriocin; then centrifuge at 4°C, 10000r / min for 20min, collect the precipitate; dissolve the precipitate with pH7.0, 20mM phosphate buffer with a mass 4 times that of the precipitate to obtain a crude bacteriocin extract.

[0095] M5: Load the crude bacteriocin extract onto a Sephadex G-75 gel filtration column that has been pre-equilibrated with a pH 7.0, 20 mM phosphate buffer, and control the loading flow rate at 2 mL / min; elute with 2 times the volume of the crude bacteriocin extract in a 20 mM phosphate buffer (pH 7.0) containing 1 M NaCl to obtain an eluate, which is spray-dried to obtain the Salmonella bacteriocin.

[0096] Comparative Example 1

[0097] In the composition, no artichoke-monk fruit-hemp seed composite extract peptide is added, and the content of artichoke-monk fruit-hemp seed composite extract peptide is replaced by corn starch; other parameters and methods are the same as in Example 1.

[0098] Comparative Example 2

[0099] In the preparation method of the composite extracted peptide of artichoke-monk fruit-hemp seed, aminopeptidase and ficin are not used for enzymatic hydrolysis; other parameters and methods are the same as those in Example 1.

[0100] Comparative Example 3

[0101] In the preparation method of the composite extracted peptide of artichoke-monohanguo-hemp seed, no ficin and aspartate aminotransferase are used for enzymatic hydrolysis, and no pyridoxal phosphate is added; other parameters and methods are the same as in Example 1.

[0102] Comparative Example 4

[0103] In the composition, Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres are not added, and the content of Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres is replaced by corn starch; other parameters and methods are the same as in Example 1.

[0104] Comparative Example 5

[0105] In the composition, Escherichia coli bacteriocin and Salmonella bacteriocin are not added, and the contents of Escherichia coli bacteriocin and Salmonella bacteriocin are replaced by corn starch; other parameters and methods are the same as in Example 1.

[0106] Comparative Example 6

[0107] In the composition, the Cassia seed extract is replaced by Cassia seed dry powder; other parameters and methods are the same as in Example 1.

[0108] Comparative Example 7

[0109] In the composition, the liquorice extract is replaced by liquorice dry powder, the Cistanche extract is replaced by Cistanche dry powder, and the Dendrobium officinale extract is replaced by Dendrobium officinale dry powder; other parameters and methods are the same as in Example 1.

[0110] The safety and efficacy tests were performed on the compositions of the above-mentioned embodiments and comparative examples.

[0111] 1. Safety Testing

[0112] 100 healthy adult Kunming mice, half male and half female, were randomly divided into 10 groups (10 mice in each group), and each group was given 0.5 g of the composition of each embodiment and each comparative example by gavage, and observed for 14 consecutive days, and the appearance, behavioral activities, diet, feces and other general conditions of the mice were recorded. No poisoning or death occurred in any group, and the product was safe and non-toxic.

[0113] 2. Detection of the ratio of beneficial bacteria to harmful bacteria in feces and immunoglobulin content

[0114] The compositions of the examples and comparative examples were respectively loaded into No. 5 enteric-coated capsules, wherein the capsules contained 0.10 mL of the composition and the remainder was corn starch, to obtain capsules. Corn starch was loaded into No. 5 enteric-coated capsules to obtain blank capsules.

[0115] 110 healthy adult SD rats were selected, half male and half female (weight 180-220g), and after adaptive feeding for 4 weeks, they were randomly divided into 11 groups (10 in each group), of which 1 group was a blank control group (give blank capsules), and the remaining groups were given capsules of each embodiment and comparative example respectively. Oral administration once a day, continuous administration for 1 week, before and after administration, about 0.2g of fresh feces of rats were collected respectively, placed in a sterile container, and the number of common beneficial bacteria (bifidobacteria, lactobacilli) and harmful bacteria (Escherichia coli, Salmonella) in feces was detected by real-time fluorescence quantitative PCR, and the ratio of the number of beneficial bacteria and harmful bacteria was calculated, the ratio of beneficial bacteria to harmful bacteria = the number of beneficial bacteria (the total number of lactic acid bacteria and bifidobacteria) / the number of harmful bacteria (the total number of Escherichia coli and Salmonella), that is, the multiple of beneficial bacteria relative to harmful bacteria, referred to as the multiple of beneficial bacteria; the content of immunoglobulin A (IgA) in feces was detected by enzyme-linked immunosorbent assay (ELISA). The test results are shown in Table 1 below.

[0116] Table 1 Proportion of beneficial bacteria and harmful bacteria and immunoglobulin content in rat feces (average value)

[0117]

[0118] Among them, during the drug administration experiment, one rat in the comparative example 6 group had soft stools 3 times, one rat had soft stools 2 times, and two rats had soft stools once.

[0119] 3. Tests on bowel movement, bowel movement time and bowel movement volume

[0120] The compositions of the examples and comparative examples were respectively loaded into No. 5 enteric-coated capsules, wherein the capsules contained 0.10 mL of the composition and the remainder was corn starch, to obtain capsules. Corn starch was loaded into No. 5 enteric-coated capsules to obtain blank capsules.

[0121] (1) Small Intestinal Propulsion Test: 110 healthy adult Kunming mice were selected, half male and half female. After 4 weeks of adaptive training, they were randomly divided into 11 groups (10 mice in each group), of which 1 group was a blank control group and was given 1 blank capsule; the remaining groups were given 1 capsule of each embodiment and comparative example respectively, and the administration was continued for 4 days. On the 4th day, 2 hours after administration, each mouse was orally administered 0.2 ml of a physiological saline suspension containing 5% activated carbon. After 20 minutes, 5 mice in each group were killed, the small intestine was removed, the total length of the small intestine and the length of activated carbon propulsion were measured, and the small intestine propulsion rate (activated carbon propulsion length / total small intestine length × 100%) was calculated; the other 5 mice were closely observed for the time when the mice first discharged black stool, and the total weight of the stool within 24 hours was recorded. The test results are shown in Table 2 below.

[0122] Table 2 Results of the bowel-moistening and laxative, defecation time and defecation volume test (average values)

[0123] Sample Small intestinal propulsion rate (%) Defecation time (h) 24h stool volume (g) Blank control group 43.7 14 2.6 Example 1 65.8 10 3.5 Example 2 68.3 9 3.4 Example 3 67.0 10 3.7 Comparative Example 1 54.1 12 2.9 Comparative Example 2 59.6 11 3.1 Comparative Example 3 58.3 11 3.0 Comparative Example 4 56.7 12 2.8 Comparative Example 5 58.9 13 3.2 Comparative Example 6 62.8 12 3.2 Comparative Example 7 55.4 13 2.9

[0124] 4. Human Trial Evaluation

[0125] The compositions of the examples and comparative examples were respectively loaded into No. 1 enteric-coated capsules, wherein the capsules contained 0.25 mL of the composition and the remainder was corn starch, to obtain capsules. Corn starch was loaded into No. 1 enteric-coated capsules to obtain blank capsules.

[0126] 60 patients with constipation symptoms were selected and divided into 10 groups, with 6 people in each group (half male and half female), and each group took the capsules of Examples 1 to 3 and Comparative Examples 1 to 7 respectively, and took 1 capsule each morning and evening every day for 4 weeks, and recorded the defecation of the subjects, including the number of defecation and stool characteristics (using the Bristol stool characteristics scoring scale, 1 to 2 usually indicates constipation, 3 to 4 usually indicates normal, and 5 to 6 usually indicates soft stool), and at the same time, observed whether there were any adverse reactions. The results are shown in Table 3 below.

[0127] Table 3 Evaluation of human trial effects (average value)

[0128]

[0129]

[0130] It can be seen from the above experimental results that the laxative composition prepared by Examples 1 to 3 has safe ingredients and is non-toxic. It can significantly increase the number of beneficial bacteria in the intestine and the content of immunoglobulin A (IgA), regulate the intestinal microenvironment, and stimulate intestinal peristalsis, increase stool volume, soften stool, and improve the symptoms of constipation patients with difficult defecation, and has an obvious laxative effect. It can be seen from the results of Comparative Example 1 that the composite extracted peptide of artichoke-monogrophobia-hemp seed, as a peptide substance, provides nutrition for beneficial bacteria, promotes the growth and reproduction of beneficial bacteria, indirectly inhibits the growth of harmful bacteria, optimizes the structure of intestinal flora, and thus improves the intestinal microenvironment; promotes the repair and renewal of intestinal cells, and helps to maintain the integrity of the intestinal mucosa; stimulates the secretion of digestive juice, thereby enhancing gastrointestinal peristalsis, helps digestion and absorption of food, and reduces the residence time of food in the intestine; and can also provide specific nutrition and improve intestinal immunity. It can be seen from the results of Comparative Examples 2 and 3 that in the preparation method of artichoke-monogrophoside-hemp seed composite extraction peptide, aminopeptidase and ficin are not used for enzymolysis; or ficin and aspartate aminotransferase are not used for enzymolysis, the composition of the product obtained by extraction changes, and the effect changes; from the result of Comparative Example 4, it can be seen that Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres can directly supplement beneficial bacteria, directly increase the number of beneficial bacteria in the intestine after entering the intestine, compete with harmful bacteria for living space and nutrients, inhibit the growth and reproduction of harmful bacteria, and regulate the balance of intestinal flora; can ferment to produce beneficial substances such as short-chain fatty acids, promote intestinal peristalsis, enhance intestinal digestion and absorption function, and at the same time stimulate the activity of intestinal immune cells and improve intestinal immunity. As shown in the results of comparative example 5, Escherichia coli bacteriocin and Salmonella bacteriocin have antibacterial activity, can specifically inhibit the growth and reproduction of harmful bacteria such as Escherichia coli and Salmonella, reduce the number of harmful bacteria in the intestine, reduce its damage and inflammatory response to the intestinal mucosa, maintain the balance of intestinal microecology, and then enhance intestinal immunity. As shown in the results of comparative example 6, Cassia seed extract is replaced by Cassia seed dry powder, and the anthraquinone compounds and other ingredients in Cassia seed are not removed in Cassia seed dry powder, resulting in stimulation of intestinal nerves, for intestinal sensitive people, it will increase the risk of soft stool and diarrhea, and the intestinal improvement effect is poor. And the Cassia seed extract removing ingredients such as quinone compounds has a better intestinal function regulation effect, reduces damage to the intestine, protects the integrity of the intestinal mucosa, is gentle and non-irritating, and is conducive to the stability of intestinal function improvement. From the results of Comparative Example 7, it can be seen that the licorice extract is replaced by licorice powder, the Cistanche extract is replaced by Cistanche powder, and the Dendrobium officinale extract is replaced by Dendrobium officinale powder; the active ingredients have low purity, low content, and low utilization rate, resulting in poor intestinal improvement effects. The licorice extract, Cistanche extract, and Dendrobium officinale extract extracted by a special method have a more efficient intestinal function improvement effect.

Claims

1. A composition for regulating intestinal microenvironment and moistening the intestines to promote bowel movements, characterized in that: The composition comprises the following raw materials in parts by weight: 10 to 15 parts of artichoke-monogrophobia-hemp seed composite extract peptide, 6 to 10 parts of Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres, 0.005 to 0.015 parts of Escherichia coli bacteriocin, 0.005 to 0.015 parts of Salmonella bacteriocin, 3 to 5 parts of licorice extract, 1 to 3 parts of cassia seed extract, 5 to 8 parts of Cistanche deserticola extract, 0. 3 to 0.8 parts, 1 to 3 parts of almonds, 3 to 6 parts of mulberry leaves, 1 to 3 parts of Codonopsis pilosula, 1 to 3 parts of black sesame, 5 to 8 parts of Sophora japonica seeds, 2 to 5 parts of Astragalus, 5 to 10 parts of malt, 0.01 to 0.03 parts of glutamine, 0.1 to 0.3 parts of sodium butyrate, 12 to 18 parts of resistant starch, 0.0001 to 0.0003 parts of zinc gluconate, 20 to 30 parts of stachyose and 18 to 22 parts of flaxseed gum.

2. A composition for regulating intestinal microenvironment and moistening the intestines and promoting bowel movements according to claim 1, characterized in that: The preparation method of the composite peptide extraction of artichoke, monk fruit and hemp seed comprises the following steps: mixing artichoke, monk fruit and hemp seed according to the mass ratio of artichoke: monk fruit: hemp seed=(10-15):(5-10):(3-5), crushing to obtain a mixture, adding distilled water 8 to 12 times the mass of the mixture, adjusting the pH value to 8.0 to 9.0 with sodium hydroxide, stirring and extracting at 40° C. to 50° C. and 200 r / min to 300 r / min for 1 h to 2 h, centrifuging at 8000 r / min to 10000 r / min for 20 min to 30 min, collecting the supernatant, adjusting the pH value to 6.0 to 7.0 with hydrochloric acid, adding 0.05% to 0.1% of the mass of serrapeptase in the supernatant, and performing enzymolysis at 45° C. to 50° C. for 60 min to 90 mi n, heating to inactivate enzyme; after cooling to room temperature, adjusting pH to 7.0-8.0, adding 0.05%-0.1% aminopeptidase by weight of the supernatant, enzymolysis at 45°C-55°C for 50min-80min, heating to inactivate enzyme; after cooling to room temperature, adding 0.05%-0.1% fig protease by weight of the supernatant, adjusting pH to 6.0-7.0, enzymolysis at 60°C-65°C for 60min-90min, heating to inactivate enzyme; cooling After reaching room temperature, adjusting the pH to 7.0-7.5, adding 0.002%-0.005% by weight of aspartate aminotransferase and 0.005%-0.008% by weight of pyridoxal phosphate to the supernatant, performing enzymolysis at 37-40° C. for 60-90 minutes, and heating to inactivate the enzyme; after cooling to room temperature, filtering with a 5 kDa ultrafiltration membrane, collecting the filtrate below 5 kDa, and freeze-drying to obtain artichoke-monk fruit-hemp seed composite extracted peptide.

3. A composition for regulating intestinal microenvironment and moistening the intestines and promoting bowel movements according to claim 1, characterized in that: The preparation method of the Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres comprises the following steps: adding Bacillus coagulans with a bacterial activity of 1.5 billion CFU / g to 2.5 billion CFU / g and Lactobacillus reuteri with a bacterial activity of 1.5 billion CFU / g to 2.5 billion CFU / g into sterile physiological saline according to a mass ratio of Bacillus coagulans:Lactobacillus reuteri:sterile physiological saline=(0.3-0.5):(0.3-0.5):(35-55), mixing and dispersing them uniformly to obtain a bacterial solution; mixing and dispersing the Bacillus coagulans-Lactobacillus reuteri with a mass ratio of sodium alginate:sterile water=1 :(50-100) mass ratio, sodium alginate is dissolved in sterile water to obtain a sodium alginate solution; according to the volume ratio of bacterial liquid: sodium alginate solution = 1:(1.5-3), under the stirring state of the sodium alginate solution at 15r / min-30r / min, the bacterial liquid is added dropwise to the sodium alginate solution, and the dropping speed is controlled to be 20 drops / min-30 drops / min. After the dropwise addition is completed, stirring is carried out at 30r / min-60r / min for 20min-30min to ensure that the Bacillus coagulans is evenly dispersed in a sodium alginate solution, forming a mixed solution; according to the volume ratio of the mixed solution: the calcium chloride aqueous solution = 1: (3-5), under the stirring state of the calcium chloride aqueous solution at 10r / min-20r / min, the mixed solution is added dropwise at a rate of 1 drop / s-2 drops / s to a calcium chloride aqueous solution having a temperature of 4°C-8°C and a mass concentration of 2%-4%, and the dropping height is controlled at 10cm-15cm. After the dropping is completed, the mixture is stirred at 10r / min-20r / min for 30min-60min to obtain a reaction solution; the reaction solution The method comprises the following steps: forming calcium alginate microspheres encapsulating Bacillus coagulans and Lactobacillus reuteri, namely, Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres; filtering the reaction solution through a 650-800 mesh sterile sieve to allow the Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres to adhere to the sieve; then washing the Bacillus coagulans-Lactobacillus reuteri calcium alginate microspheres with a sterile physiological saline of 1 to 2 times the volume of the reaction solution to remove residual impurities on the surface; finally, collecting the Bacillus coagulans calcium alginate microspheres and storing them in a cold storage at 4° C. to 5° C.

4. A composition for regulating intestinal microenvironment and moistening the intestines and promoting bowel movements according to claim 1, characterized in that: The preparation method of the cassia seed extract comprises the following steps: taking cassia seed medicinal material, crushing it, using petroleum ether 8 times to 10 times the mass of the cassia seed medicinal material to reflux extract 2 to 3 times at 40°C to 50°C, each time for 1.5 hours to 2 hours, filtering to remove the petroleum ether extract, evaporating the solvent from the medicinal residues, and removing fat-soluble impurities; adding 6 times to 8 times the mass of the medicinal residues and 70% to 80% volume concentration of ethanol aqueous solution to the medicinal residues, reflux extracting at 60°C to 70°C for 2 to 3 times, each time for 1 hour to 1.5 hours, combining the extracts of the ethanol aqueous solution, and concentrating under reduced pressure until there is no ethanol to obtain a concentrated solution; adding 2 times to 3 times the volume of water of the concentrated solution to the concentrated solution for suspension, applying the sample to an AB-8 type macroporous adsorption resin column for adsorption, and then eluting with water for 3 to 4 column volumes to remove sugar impurities; and then eluting with 40% to 50% volume concentration of ethanol aqueous solution for 3 to 4 column volumes, collecting the eluate of the ethanol aqueous solution, concentrating under reduced pressure, and drying to obtain the cassia seed extract.

5. The composition for regulating intestinal microenvironment and moistening the intestines and promoting bowel movements according to claim 1, characterized in that: The preparation method of the licorice extract comprises the following steps: grinding the licorice material into coarse powder, adding water of 8 to 10 times the mass of the coarse powder, decocting at 100°C for 90 to 120 minutes, filtering to obtain filtrate A and medicinal residues; adding water of 6 to 8 times the mass of the medicinal residues to the medicinal residues, decocting at 100°C for 90 to 120 minutes, filtering to obtain filtrate B, combining filtrate A and filtrate B to obtain a medicinal solution; adding ethanol of 1 to 2 times the volume of the medicinal solution to the medicinal solution, standing for 12 to 24 hours, filtering, and collecting the filtrate; decompressing and concentrating the filtrate until there is no ethanol, applying the sample to a 001×7 type strong acid cation exchange resin column for adsorption, and then eluting with 0.5 mol / L to 0.8 mol / L ammonia water for 3 to 4 column volumes, collecting the eluate of the ammonia water, decompressing and concentrating, and drying to obtain the licorice extract.

6. The composition for regulating intestinal microenvironment and moistening the intestines and promoting bowel movements according to claim 1, characterized in that: The preparation method of the Cistanche deserticola extract comprises the following steps: taking Cistanche deserticola medicinal material, cold soaking it at 4°C to 10°C for 24h to 36h with an ethanol aqueous solution with a volume concentration of 30% to 40% that of the Cistanche deserticola medicinal material, filtering to obtain a filtrate C and a medicinal residue; concentrating the filtrate C under reduced pressure until there is no ethanol to obtain a water liquid, extracting it 3 to 4 times with n-butanol, each time with n-butanol being 1 / 3 to 1 / 2 of the volume of the water liquid, combining the n-butanol extracts, concentrating the extracts under reduced pressure, and drying to obtain an extract C; adding 8 to 6 times the volume of the medicinal residue to the medicinal residue; 10 times the mass of water, boiled at 100°C for 90min-120min, filtered to obtain filtrate D, concentrated filtrate D to 50%-60% of volume, adsorbed on AB-8 macroporous adsorption resin column, then eluted with water for 2-3 column volumes to remove impurities, then eluted with 50%-60% volume concentration of ethanol aqueous solution for 3-4 column volumes, collected the eluate of ethanol aqueous solution, added extract C to the eluate of ethanol aqueous solution, mixed evenly, concentrated under reduced pressure, and dried to obtain Cistanche deserticola extract.

7. The composition for regulating intestinal microenvironment and moistening the intestines and promoting bowel movements according to claim 1, characterized in that: The preparation method of the Dendrobium officinale extract comprises the following steps: cutting the fresh stems of the Dendrobium officinale into segments, adding a 0.5wt%-1wt% citric acid aqueous solution with a mass of 3 to 5 times the mass of the fresh stems, ultrasonically extracting at 40°C to 50°C and 20kHz to 40kHz for 30min to 45min, filtering to obtain a filtrate E and a medicinal residue; adding a 0.3wt%-0.8wt% oxalic acid aqueous solution with a mass of 2 to 4 times the mass of the medicinal residues to the medicinal residues, ultrasonically extracting at 40°C to 50°C and 20kHz to 40kHz for 20min to 30min, filtering to obtain a filtrate F, combining the filtrate E and the filtrate F, concentrating under reduced pressure to 30% to 40% of the volume, passing the sample through a Sephadex G-25 polysaccharide gel column, and then eluting with water for 3 to 4 column volumes, collecting the water eluate, concentrating under reduced pressure, and drying to obtain iron.

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