Nutrition intervention composition with functions of regulating liver metabolism, promoting liver repair and resisting liver fibrosis

Abstract

The invention discloses a nutrition intervention composition with functions of regulating liver metabolism, promoting liver repair and resisting hepatic fibrosis. The nutrition intervention composition comprises purple perilla micro-capsule powder, a protein component, a liver peptide component, glutathione-rich yeast, a silybum marianum component, corn oligopeptide powder, oat powder and a fermentation product of germinated brown rice powder. According to the nutrition intervention composition disclosed by the invention, the microencapsulated perilla frutescens extract is organically integrated with antioxidant, regeneration-promoting and metabolism-regulating components such as a protein component, a liver peptide component, glutathione-rich yeast, a silybum marianum component and corn oligopeptide, so that the stability and bioavailability of fat-soluble active components are improved; the functions of exogenous anti-oxidation, endogenous anti-oxidation supplement, hepatocyte repair and intestinal-hepatic axis regulation are synergistically enhanced, so that the synergistic and lasting liver protection, repair and anti-fibrosis effects are realized.

Description

Technical Field

[0001] This invention relates to the field of functional food technology. Specifically, this invention provides a nutritional intervention composition that has the functions of regulating liver metabolism, promoting liver repair, and resisting liver fibrosis. Background Technology

[0002] The liver is the body's metabolic and detoxification center, participating in the synthesis, metabolism, and storage of proteins, lipids, carbohydrates, vitamins, and minerals, and undertaking the metabolism and elimination of exogenous harmful substances. Chronic liver disease can lead to persistent inflammation, metabolic disorders, and fibrosis, eventually progressing to cirrhosis, liver failure, and even liver cancer. Simultaneously, liver disease patients often suffer from malnutrition, and nutritional deficiencies, in turn, exacerbate liver function damage, affecting treatment effectiveness and prognosis. Therefore, providing systematic nutritional support and targeted repair tailored to the metabolic characteristics of the liver has become an important direction in clinical and functional food research and development.

[0003] Existing products for liver health and nutritional intervention in liver disease are mostly based on single active ingredients or conventional formulas, lacking an integrated design that combines "metabolism regulation, repair promotion, and fibrosis inhibition." In addition, many fat-soluble hepatoprotective active ingredients have low bioavailability and poor stability, making it difficult to ensure effective exposure in the liver with conventional dosage forms. Furthermore, existing formulas rarely take into account the synergistic effects of gut-liver axis repair, nutritional energy supply, and hepatocyte regeneration factors, resulting in limited clinical or animal effects and making it difficult to effectively intervene in the process of liver fibrosis.

[0004] Therefore, there is an urgent need for a nutritional intervention composition that can systematically regulate liver metabolism, promote hepatocyte repair, and has anti-liver fibrosis function to solve the above-mentioned technical problems. Summary of the Invention

[0005] Therefore, the first objective of this invention is to provide a nutritional intervention composition that has the functions of regulating liver metabolism, promoting liver repair and anti-liver fibrosis, aiming to solve the problems of existing liver protection / nutritional preparations having single components, poor stability and low bioavailability, making it difficult to simultaneously regulate liver metabolism, provide antioxidant repair and promote hepatocyte regeneration. The second objective of this invention is to provide a method for preparing a nutritional intervention composition that has the functions of regulating liver metabolism, promoting liver repair and resisting liver fibrosis, in order to solve the problems of large loss of active ingredients, unstable ingredient content, poor stability and oral bioavailability of finished products, and difficulty in large-scale production in existing preparation processes. The third objective of this invention is to provide the use of a nutritional intervention composition that has the functions of regulating liver metabolism, promoting liver repair and resisting liver fibrosis, in order to solve the problem of the lack of systematic dietary nutrition support products for people with abnormal liver function, and the inability to simultaneously achieve basic nutritional supplementation, metabolic regulation and liver repair support in food or nutritional preparations.

[0006] To achieve the first objective of this invention, this invention provides a nutritional intervention composition that has the functions of regulating liver metabolism, promoting liver repair and resisting liver fibrosis. The nutritional intervention composition includes perilla microcapsule powder, protein components, liver peptide components, glutathione-enriched yeast, milk thistle components, corn oligopeptide powder, oat flour and fermented products of germinated brown rice flour.

[0007] In any of the above technical solutions, the nutritional intervention composition further includes: amino acids, including at least one or a combination of branched-chain amino acids and taurine; and / or vitamins, including at least one or a combination of vitamin A, vitamin C, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, folic acid, pantothenic acid, and biotin; and / or minerals, including at least one or a combination of magnesium, calcium, zinc, and selenium.

[0008] In any of the above technical solutions, the components and their corresponding masses are: 1-15g of perilla microcapsule powder; 1.5-20g of protein component; 0.04-12g of liver peptide component; glutathione-enriched yeast and 0.01-1g of milk thistle component; 0.20-2.0g of corn oligopeptide powder; and 1-10g of fermented germinated brown rice flour.

[0009] In any of the above technical solutions, the nutritional intervention composition further includes: 1-6g of amino acids; 207-854μg of vitamins; and 212-1164mg of minerals.

[0010] In any of the above technical solutions, the protein component includes 0.5-10g of concentrated whey protein and 1-10g of soy protein isolate; the liver peptide component includes 0.01-3g of sheep liver peptide, 0.01-3g of bovine liver peptide, 0.01-3g of deer liver peptide, and 0.01-3g of albumin peptide; glutathione-enriched yeast; amino acids including 1-6g of branched-chain amino acids and 0.05-0.09g of taurine; and vitamins including 120-375μg of vitamin A, 15-100mg of vitamin C, and 1.5g of other components. -10μg Vitamin D, 2.1-20mg Vitamin E, 0.2-4mg Vitamin B1, 0.2-2mg Vitamin B2, 0.2-2mg Vitamin B6, 0.4-4μg Vitamin B12, 2.1-20mg Niacin, 60-260μg Folic Acid, 0.8-7μg Pantothenic Acid, 4.5-50μg Biotin; Minerals include 53-300mg Magnesium, 150-800mg Calcium, 1.7-12mg Zinc, 7.5-52μg Selenium.

[0011] To achieve the second objective of this invention, this invention also provides a method for preparing a nutritional intervention composition with functions of regulating liver metabolism, promoting liver repair, and resisting liver fibrosis. The preparation method includes the following steps: S100, pulverizing germinated brown rice flour to obtain pulverized raw material; S200, mixing the pulverized raw material with water to form a fermentation raw material, inoculating the fermentation raw material with compound bacteria, and anaerobic fermenting at 35-38℃ for 24-26 hours and sterilizing to obtain an intermediate product; S300, filtering, concentrating under reduced pressure, and spray drying the intermediate product to obtain a fermentation product of germinated brown rice flour; S400, mixing the fermentation product of germinated brown rice flour, perilla microcapsule powder, and other components evenly to obtain the nutritional intervention composition.

[0012] In any of the above technical solutions, in step S200, the compound bacteria include Lactobacillus bulgaricus, Bifidobacterium lactis, and Bifidobacterium bifidum; wherein, the inoculum amount of Lactobacillus bulgaricus in the fermentation raw materials is 10. 8 -10 9 CFU / mL, the inoculum size of Bifidobacterium lactis in the fermentation feed was 10. 7 -10 8 CFU / mL, the inoculum size of Bifidobacterium bifidum in the fermentation feed was 10. 9 -10 10 CFU / mL.

[0013] In any of the above technical solutions, in step S400, the perilla microcapsule powder is prepared by the following steps: S411, pulverizing perilla leaves and mixing them with water to obtain a raw material liquid; S412, adding cellulase to the raw material liquid to carry out an enzymatic hydrolysis reaction to obtain an enzymatic hydrolysis product; S413, sequentially inoculating the enzymatic hydrolysis product with Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium animalis for multi-stage anaerobic fermentation, sterilizing after each stage of fermentation to obtain a fermentation product; S414, filtering, concentrating under reduced pressure, and spray drying the fermentation product to obtain a perilla extract; S415, mixing the perilla extract with wall material and emulsifier, emulsifying, homogenizing, and drying to obtain perilla microcapsule powder.

[0014] In any of the above technical solutions, in step S415, the wall material is composed of gum arabic: octenyl succinate starch ester: microcrystalline cellulose in a mass ratio of 1:(1.2-1.5):(0.4-0.7); the emulsifier is composed of Tween 80: sodium caseinate: monoglyceride stearate in a mass ratio of 1:(1.2-1.4):(0.5-0.7); the mass ratio of perilla extract to wall material is 1:(1.3-1.6); and the mixing temperature is 60-70℃.

[0015] To achieve the third objective of this invention, this invention also provides a use of a nutritional intervention composition for preparing foods, health foods, or pharmaceuticals for the prevention and / or adjuvant treatment of liver injury and liver fibrosis.

[0016] The technical effects that can be achieved by adopting the technical solution of the present invention are as follows: (1) This formula organically integrates antioxidant, regeneration and metabolism-regulating components such as perilla microcapsule powder, liver peptide components and protein components, glutathione-rich yeast, milk thistle components and corn oligopeptides. It can simultaneously inhibit oxidative stress and inflammation, promote hepatocyte repair and inhibit hepatic stellate cell activation, thereby producing synergistic and lasting liver protection and anti-fibrotic effects on the three pathways of regulating metabolism, promoting repair and inhibiting fibrosis.

[0017] (2) Enzymatic hydrolysis and graded fermentation are used to enrich functional small molecules, and then fat-soluble active ingredients are encapsulated by microencapsulation, which significantly improves the tolerance to light, heat and gastric acid, masks taste and improves intestinal release, thereby improving oral bioavailability and batch-to-batch consistency, which is conducive to industrial scale-up and quality control.

[0018] (3) The formula takes into account short peptides, energy supply, fermentation products and active ingredients. It not only directly provides hepatocytes with repair raw materials and metabolic cofactors, but also indirectly reduces the burden on the liver by improving the intestinal microecology and reducing the entry of endotoxins into the portal vein circulation, thereby enhancing long-term efficacy and tolerability. Detailed Implementation

[0019] To better understand the above-mentioned objectives, features, and advantages of the present invention, the present invention will be further described in detail below with reference to specific embodiments. It should be noted that, unless otherwise specified, the embodiments and features described in these embodiments can be combined with each other.

[0020] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and therefore the scope of protection of the invention is not limited to the specific embodiments disclosed below.

[0021] To make the above-mentioned objectives, features and advantages of this aspect more apparent and understandable, specific embodiments of this aspect are described in detail below.

[0022] Malnutrition is common among liver disease patients, especially those with chronic or severe liver disease. Increasing evidence suggests that prescribing specific supplements or nutritional products with proven hepatoprotective effects can prevent or slow the progression of liver disease. Existing products for liver health and nutritional intervention in liver disease are mostly single-active or conventional formulations, lacking an integrated design encompassing "metabolism regulation, repair promotion, and fibrosis inhibition." Furthermore, many fat-soluble hepatoprotective active ingredients suffer from low bioavailability and poor stability, making it difficult to ensure effective exposure in the liver with conventional formulations. Moreover, existing formulations rarely simultaneously address the synergistic effects of gut-hepatic axis repair, nutritional energy supply, and hepatocyte regeneration factors, resulting in limited clinical or animal efficacy and hindering effective intervention in the progression of liver fibrosis.

[0023] In view of this, this embodiment provides a nutritional intervention composition with functions of regulating liver metabolism, promoting liver repair and anti-liver fibrosis. The nutritional intervention composition includes perilla microcapsule powder, protein components, liver peptide components, glutathione-enriched yeast, milk thistle components, corn oligopeptide powder, oat flour and fermented products of germinated brown rice flour.

[0024] Preferably, the nutritional intervention composition of this embodiment provides systematic nutritional and functional support to the liver through a multi-target, multi-pathway synergistic effect of "antioxidant / anti-inflammatory, cell membrane and mitochondrial protection, promotion of hepatocyte repair and regeneration, inhibition of fibrosis, and maintenance of metabolic balance." In other words, perilla microcapsule powder provides plant-based active substances as the main antioxidants, liver peptide components directly provide short peptide signals or nutritional bases to promote hepatocyte repair, milk thistle components and glutathione-enriched yeast amplify the protective effect by protecting cell membranes, enhancing the antioxidant enzyme system, and supplementing glutathione precursors; the remaining proteins, branched-chain amino acids, vitamins, and minerals are responsible for the building blocks and cofactors of metabolic enzymes required for repair, thereby forming a complementary and enhanced liver protection network.

[0025] Furthermore, the polyphenols and flavonoids abundant in perilla, the glutathione precursor provided by yeast extract, and trace elements such as selenium work together to significantly enhance the body's antioxidant capacity. The specific mechanisms include: directly scavenging free radicals and reducing lipid peroxidation; increasing the activity of endogenous antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and promoting glutathione (GSH) synthesis. By reducing oxidative stress, cell membrane lipid peroxidation and mitochondrial damage are inhibited, thereby reducing hepatocyte necrosis and apoptosis, which is a fundamental step in protecting liver function.

[0026] Preferably, the active ingredients of perilla, along with micronutrients and glutathione-enriched yeast in the composition, can synergistically inhibit pro-inflammatory signaling pathways, such as the expression of NF-κB and downstream cytokines like TNF-α and IL-6, thereby reducing chronic inflammatory responses. Reducing inflammation can directly protect hepatocytes and also decrease inflammation-driven fibrosis. Simultaneously, components such as phospholipids and albumin peptides can improve immune homeostasis and phagocytic cell function, helping to more efficiently clear damage products and repair the environment.

[0027] Preferably, hepatic peptide components, albumin peptides, and sufficient high-quality proteins and branched-chain amino acids (BCAAs) provide hepatocytes with direct amino acid raw materials and signal stimulation. BCAAs can promote protein synthesis by activating signals such as mTOR, supporting hepatocytes in synthesizing albumin and repairing structural proteins required for protein synthesis; certain hepatic peptides may also stimulate growth factor expression or promote cell cycle progression, increasing the regenerative capacity of hepatocytes. Overall, these components act as both building blocks and repair signals, accelerating the functional recovery of damaged liver tissue through a dual effect.

[0028] Preferably, a key step in liver fibrosis is the activation of hepatic stellate cells (HSCs) by Kupffer cells or other pro-inflammatory environments, prompting them to secrete excessive collagen and extracellular matrix (ECM). This approach aims to reduce oxidative stress and inflammatory stimulation, thereby decreasing pro-fibrotic signals at their source. Furthermore, studies have shown that milk thistle and perilla components can inhibit TGF-β1 signaling or downregulate α-SMA / collagen gene expression, thus weakening HSC activation. Thirdly, it improves hepatocyte health and function, reducing persistent necrosis / inflammatory triggers, thereby overall reducing the driving force of fibrosis progression. The synergistic effect of multiple components in the composition is more likely to produce a stronger anti-fibrotic effect than a single component.

[0029] Furthermore, milk thistle seed oil is produced in solid form, specifically powdered or encapsulated milk thistle seed oil. These forms convert the fat-soluble active ingredients from milk thistle seeds into a convenient and easily digestible solid raw material. Through multiple mechanisms, including antioxidant, anti-inflammatory, membrane protection, and bile flow promotion, it provides protection, support, and repair for hepatocytes, and improves the liver's metabolic environment. The solid form enhances formulation compatibility, stability, and controllability, facilitating the production of powders, instant powders, or capsules. Powder forms are easy to mix with other powder components, promoting uniform formulation, quality control, and mass production. Microencapsulation improves the stability of antioxidant components, masks taste, and enhances intestinal release.

[0030] Preferably, medium-chain triglycerides (MCTs), carbohydrate carriers, and specific vitamins and minerals provide the liver with rapidly available energy and metabolic cofactors. MCTs are easily oxidized by hepatocytes and do not easily accumulate in the liver, thus reducing the burden of fatty liver in cases of energy deficiency or abnormal lipid metabolism. B vitamins, magnesium, zinc, and other substances act as enzyme cofactors, supporting the normal metabolism of carbohydrates, lipids, and proteins, helping to restore metabolic homeostasis and reduce the toxic effects of metabolites on the liver.

[0031] Preferably, the composition formulation includes fermentation products and intestinal prebiotics and probiotic substrates such as xylooligosaccharides and glutathione-enriched yeast. These components reduce the entry of endotoxins from the intestine into the portal circulation and decrease inflammatory stimulation of the liver by regulating the composition of the intestinal flora. In addition, the fermentation products generate short-chain fatty acids and other metabolites during the preparation process. These substances have anti-inflammatory effects, promote epithelial barrier function, and regulate metabolism, thereby indirectly protecting the liver through the gut-hepatic axis.

[0032] Preferably, the active ingredients in plants such as perilla are often sensitive to light, heat, and acidity / alkali. Microencapsulation technology can improve the chemical stability of these active ingredients, reduce gastric acid degradation, improve dissolution and oral bioavailability, and enable controlled release or intestinal release. Microencapsulation also improves flavor and powder flowability, facilitating the formulation into powders, instant powders, or capsules, thus improving patient compliance and the reproducibility of industrial production.

[0033] Preferably, the protein components are a blend of whey protein concentrate and soy protein isolate. Whey protein concentrate is one of the best sources of branched-chain amino acids, which helps increase muscle protein, reduce muscle soreness after exercise, reduce fat synthesis and hunger, and help the body improve immunity. Soy protein isolate, as a high-quality plant protein, can promote bone health, lower blood lipids, and the amino acids of whey protein concentrate work synergistically to meet the metabolic needs of the liver at different stages.

[0034] Preferably, the liver peptide components are derived from liver extracts of various animals such as sheep, cattle, and deer. Sika deer are a Class I protected animal in China, and the deer liver peptides used in this product come from artificially bred sika deer. Bovine liver peptides and sheep liver peptides are made from fresh livers of cattle and sheep raised on the Xilin Gol Grassland in Inner Mongolia, processed through quick-freezing, enzymatic hydrolysis, bioactive peptide membrane separation and concentration, and purification. Liver peptides from different sources contain characteristic small molecule active peptides, and their combined use can provide a more comprehensive effect of promoting hepatocyte regeneration, repairing and improving the vitality of chemically damaged hepatocytes, and resisting lipid peroxidation. Albumin peptides can restore or enhance the liver's ability to synthesize proteins, repair damaged hepatocytes, promote hepatocyte regeneration, and improve or restore liver function.

[0035] Preferably, the milk thistle component is used in solid form, specifically as microencapsulated milk thistle seed oil. This treatment effectively masks the taste, improves its stability to the external environment, and enhances oral bioavailability through enteric release.

[0036] Preferably, the amino acids include branched-chain amino acids and taurine. Branched-chain amino acids can improve energy metabolism disorders, reduce the burden on the liver, promote albumin synthesis, help reduce edema and ascites in patients, inhibit liver fibrosis, improve liver function, and reduce treatment-related complications; taurine can regulate liver lipid metabolism, stabilize cell membrane permeability, act as an antioxidant, inhibit alcoholic liver damage, resist liver fibrosis, and reduce the degree of hepatic steatosis.

[0037] Furthermore, the branched-chain amino acids are preferably fast-dissolving branched-chain amino acid microcapsule powders, which contain L-leucine, L-isoleucine and L-valine.

[0038] Preferably, the vitamins include vitamin A, vitamin C, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, folic acid, pantothenic acid, and biotin. Vitamin A can prevent and inhibit the proliferation of cancer cells in the liver, protecting the liver; vitamin C has antioxidant properties; vitamin D assists in anti-liver fibrosis; vitamin E has antioxidant and anti-inflammatory effects; vitamin B1 is an important coenzyme for human energy metabolism; vitamin B2, as a coenzyme of glutathione reductase, improves the body's antioxidant defense system; vitamin B6 is a coenzyme for the metabolism of amino acids, glycogen, and fats in the body; vitamin B12 is a coenzyme for the synthesis of proteins and nucleic acids; niacin, as a coenzyme, participates in regulating energy, amino acid, and glucose metabolism; and participates in the conversion of proteins and other substances; folic acid, as a one-carbon unit coenzyme, participates in the synthesis of proteins and nucleic acids; pantothenic acid is a coenzyme for the metabolism of the three major energy substances in the body; biotin regulates gluconeogenesis of branched-chain amino acids, and the synthesis and decomposition of fats; magnesium is an activator of many enzymes in the human body, regulating energy metabolism.

[0039] Preferred minerals include magnesium, calcium, zinc, and selenium. Calcium maintains healthy bones and teeth, supports nerve and muscle activity, and regulates enzyme activity; zinc is a component of many enzymes in the human body, regulating enzyme activity, regulating energy metabolism, and promoting bile secretion in the liver; selenium has antioxidant properties, can bind with heavy metals in the body to exert detoxification and elimination effects, can help slow the progression of liver fibrosis, and can be used in combination therapy for viral hepatitis.

[0040] Furthermore, the nutritional intervention composition comprises the following components: 1-15g perilla microcapsule powder, 0.5-10g concentrated whey protein, 1-6g branched-chain amino acids, 1-10g soy protein isolate, 0.05-1g glutathione-enriched yeast, 0.5-5g phospholipids, 0.01-1g milk thistle seed oil, 0.1-3g medium-chain triglyceride microcapsule powder, 0.01-3g sheep liver peptide, 0.01-3g bovine liver peptide, 0.01-3g deer liver peptide, 0.01-3g albumin peptide, 0.20-2.0g corn oligopeptide powder, 0.05-0.09g taurine, 120-375μg vitamin A, 15- 100mg Vitamin C, 1.5-10μg Vitamin D, 2.1-20mg Vitamin E, 0.2-4mg Vitamin B1, 0.2-2mg Vitamin B2, 0.2-2mg Vitamin B6, 0.4-4μg Vitamin B12, 2.1-20mg Niacin, 60-260μg Folic Acid, 0.8-7μg Pantothenic Acid, 4.5-50μg Biotin, 53-300mg Magnesium, 150-800mg Calcium, 1.7-12mg Zinc, 7.5-52μg Selenium, 0.07-0.10g Xylooligosaccharides, 0.5-5g Oat Flour, 0.5-5g Sprouted Brown Rice Flour.

[0041] Furthermore, glutathione-enriched yeast (containing glutathione) is used to enhance antioxidant enzyme activity to repair abnormal liver function, inhibit lipid droplet deposition in hepatocytes, improve hepatocyte inflammatory infiltration and alcoholic liver damage, and significantly reduce serum transaminase levels; phospholipids participate in cell membrane composition, which helps hepatocyte repair, and lowering cholesterol can effectively prevent the formation of fatty liver and alleviate hepatocyte necrosis, and can improve protein synthesis in the liver; medium-chain triglyceride microcapsule powder is easily absorbed and can provide rapid energy to help burn fat; corn oligopeptide powder reduces liver damage through antioxidation, regulation of alcohol metabolism-related enzymes, and regulation of fatty acid metabolism; xylooligosaccharides can promote the proliferation of beneficial bacteria, improve intestinal flora balance, and reduce the formation of toxic metabolites, thus reducing the burden on the liver to decompose toxins; oat flour and sprouted brown rice flour provide energy sources, and sprouted brown rice flour is rich in γ-aminobutyric acid, which can indirectly pave the way for the core ingredients such as perilla, milk thistle, and liver peptides to play their role by regulating central stress response and intestinal function, thus forming a more three-dimensional and comprehensive liver health support system.

[0042] In addition, this nutritional intervention composition also contains functional excipients to improve the processing characteristics, stability, and palatability of the product. For example, flavoring agents such as xylitol and steviol glycosides are used to mask the unpleasant taste of the active ingredients and provide sugar-free or low-sugar sweetness, making the product suitable for liver disease patients with diabetes and other conditions requiring blood sugar control; stabilizers such as guar gum are used to maintain powder uniformity and suspension stability after reconstitution, ensuring accurate dosage and a smooth taste. Preferably, 3-13g of perilla microcapsule powder is extracted from fresh, tender perilla leaves harvested manually at the initial flowering stage. The powder is processed through crushing, extraction, filtration, and encapsulation, preserving its beneficial components to a relatively high extent. Microencapsulation of the perilla extract stably preserves polyphenols and volatile oils, improves the acid resistance and oral bioavailability of active ingredients, and masks the taste for easier formulation. Functionally, it helps reduce oxidative stress and inflammatory responses, and by improving lipid metabolism and the gut-liver axis microecology, it plays an auxiliary role in maintaining liver metabolic balance and supporting liver repair.

[0043] This embodiment also provides a method for preparing a nutritional intervention composition with functions of regulating liver metabolism, promoting liver repair, and resisting liver fibrosis. The preparation method includes the following steps: S100. Mix oat flour and sprouted brown rice flour and grind them to obtain the ground raw material; S200: Mix the crushed raw material with water to form a fermentation raw material, inoculate the fermentation raw material with compound bacteria, and anaerobic ferment at 35-38℃ for 24-26 hours and then sterilize to obtain an intermediate product; S300: Filter the intermediate product, concentrate it under reduced pressure and spray dry it to obtain the fermented product of germinated brown rice flour; S400: Mix the fermentation product of sprouted brown rice flour, perilla microcapsule powder and other components evenly to obtain a nutritional intervention composition.

[0044] Preferably, in step S100, the germinated brown rice flour is pulverized. Pulverization and uniform mixing physically disrupt the cell walls and endosperm structure of the grains, significantly increasing the specific surface area and porosity of the raw material. This increases the surface area for subsequent contact with water, enzymes, and microorganisms. Mixing ensures a uniform distribution of nutrients throughout the raw material, thereby affecting the substrate accessibility and rate of subsequent enzymatic hydrolysis and microbial metabolism. Appropriate particle size can also alter swelling properties, hygroscopicity, and rheological characteristics, which are beneficial for the uniformity of the fermentation system and heat / mass transfer. This leads to a faster release rate of soluble sugars, short peptides, and fermentable substrates that are more readily utilized by microorganisms, shortens the fermentation start-up period, and increases product yield. Furthermore, the recovery rate of soluble active ingredients is higher during aqueous phase extraction or subsequent concentration.

[0045] In step S200, the pulverized raw materials are mixed with water to form fermentation raw materials, inoculated with compound bacteria, and anaerobic fermented at 35-38℃ for 24-26 hours, followed by sterilization to obtain an intermediate product. Fermentation can increase the content of available short peptides, free amino acids, soluble polysaccharides, and small molecules, enhance nutrition and bioactivity, reduce anti-nutritional factors, and improve taste. Under suitable temperature and anaerobic conditions, the inoculated compound bacteria utilize the soluble sugars, oligosaccharides, and proteins released from the powder for metabolism, producing metabolites beneficial to functionality. The enzyme system of microorganisms decomposes complex macromolecules, increasing the solubility and bioavailability of active ingredients. Sterilization after fermentation can terminate metabolism and ensure product safety, while retaining microbial metabolites and the improved matrix structure.

[0046] Furthermore, in step S200, the complex microorganisms include *Lactobacillus bulgaricus*, *Bifidobacterium lactis*, and *Bifidobacterium bifidum*. *Lactobacillus bulgaricus* primarily produces acid, rapidly lowering the system pH, inhibiting other microorganisms, and contains enzymes such as proteases / β-glucosidases, promoting partial hydrolysis of large protein / polysaccharide molecules, releasing soluble peptides and sugars, and improving flavor and fermentation kinetic stability. *Bifidobacterium lactis* efficiently produces acetic acid / lactic acid and other metabolites, enhancing its antibacterial spectrum, helping to stabilize the ecosystem, facilitating the production of short-chain fatty acids and beneficial small molecules generated during fermentation, promoting the favorable direction of gut-liver axis signaling, and possessing specific enzymatic hydrolysis capabilities for certain oligosaccharides / cellulose, further increasing fermentable substrates and functional products. *Bifidobacterium bifidum* is typically used at higher inoculum levels to fill the gaps in degrading specific complex carbohydrates or producing more targeted metabolites, enhancing the yield of short-chain fatty acids and free amino acids, promoting the accumulation of more small peptides and GSH precursors, and improving the overall stability of the fermentation system and the yield of target products.

[0047] Furthermore, the inoculum size of Lactobacillus bulgaricus in the fermentation feed was 10. 8 -10 9 CFU / mL, the inoculum size of Bifidobacterium lactis in the fermentation feed was 10. 7 -10 8 CFU / mL, the inoculum size of Bifidobacterium bifidum in the fermentation feed was 10. 9 -10 10 CFU / mL; high inoculation ratios of the above three components can rapidly initiate and maintain efficient anaerobic fermentation, promoting the biodegradation of starch, fiber, and protein in the substrate, producing a large amount of organic acids, short-chain fatty acids, soluble short peptides and free amino acids, as well as glutathione precursors, thereby improving nutrient availability, enhancing antioxidant precursor reserves, improving flavor, and inhibiting the growth of spoilage / pathogenic bacteria; at the same time, fermentation can degrade anti-nutritional factors and optimize gut-liver axis-related metabolic signals, providing intermediate products rich in functional small molecules for subsequent vacuum concentration and spray drying.

[0048] Preferably, in step S300, the intermediate product is filtered, concentrated under reduced pressure, and spray-dried to obtain the fermentation product of germinated brown rice flour. Filtration is used to separate the solid and liquid phases. Reduced pressure concentration removes water at low temperature to increase the concentration of solids and protect the heat-sensitive active substances. Spray drying atomizes the concentrated liquid and rapidly dries it into powder. With the help of a carrier or wall material, heat / oxygen-sensitive components can be encapsulated and stabilized to obtain a stable fermentation product powder of germinated brown rice flour.

[0049] Preferably, in step S400, the fermentation product of germinated brown rice flour, perilla microcapsule powder, and other components are mixed evenly and processed into the desired dosage form to obtain a nutritional intervention composition. The various functional powders are then evenly mixed according to the formula and finally formulated. By controlling the mixing uniformity, particle size, and coating / microencapsulation process, the release location and rate of each component can be controlled, achieving stable dosage and synergistic bioavailability.

[0050] Furthermore, in step S400, the perilla microcapsule powder is prepared by the following steps: S411. Crush the perilla leaves and mix them with water to obtain the raw material liquid; S412. Add cellulase to the raw material solution to carry out enzymatic hydrolysis to obtain the enzymatic hydrolysis product; S413. Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium animalis are inoculated into the enzymatic hydrolysis product in sequence to carry out multi-stage anaerobic fermentation. After each stage of fermentation, the product is sterilized to obtain the fermentation product. S414. The fermentation product was filtered, concentrated under reduced pressure, and spray-dried to obtain perilla extract; S415. Perilla extract is mixed with wall material and emulsifier, emulsified, homogenized and dried to obtain perilla microcapsule powder.

[0051] Preferably, in step S411, the perilla leaves are pulverized and mixed with water to obtain a raw material liquid. Pulverization mechanically disrupts the cell walls / intercellular matrix and breaks the cell membranes, releasing intracellular polyphenols, flavonoids, volatile oils, sugars, and proteins from the solid matrix into the aqueous phase. Water acts as a solvent, promoting the dissolution of soluble components and forming a uniform suspension / emulsion raw material liquid. Pulverization increases the specific surface area and reduces the particle size, thereby improving the initial extraction efficiency and substrate accessibility for subsequent enzymatic hydrolysis / fermentation; it reduces diffusion limitations and shortens the initiation period for enzymatic hydrolysis and fermentation; it yields a homogeneous process material, facilitating metering, stirring, and heat / mass transfer, which is beneficial for scale-up production and ensuring batch-to-batch consistency. Simultaneously, it provides a more readily available matrix for subsequent cellulase activity and microbial metabolism, improving the final product yield and activity retention.

[0052] Preferably, in step S412, cellulase is added to the raw material solution to carry out an enzymatic hydrolysis reaction to obtain the enzymatic hydrolysis product. Cellulase catalyzes the hydrolysis of β-1,4-glucan bonds in plant cell walls, degrading cellulose and hemicellulose into soluble cellulosic oligosaccharides and glucose. Simultaneously, it disrupts the cell wall structure, further releasing intercalated or bound polyphenols, flavonoids, and volatile substances. Enzymatic hydrolysis also reduces system viscosity, improves flowability, and generates fermentable sugars and oligosaccharides that can be utilized by fermenting bacteria. A raw material solution concentration of 100-120 U / mL, a temperature of 35-38℃, and a time of 5-7 hours provide mild conditions to ensure enzyme activity and selective degradation.

[0053] Preferably, in step S413, *Lactobacillus acidophilus*, *Lactobacillus casei*, and *Bifidobacterium animalis* are sequentially inoculated for multi-stage anaerobic fermentation. Each stage of fermentation is sterilized to obtain fermentation products. The inoculated probiotics further hydrolyze macromolecules and catalyze the biotransformation of plant secondary metabolites through their exo / endozymes. Simultaneously, the microbial metabolism produces beneficial metabolites such as lactic acid, acetic acid, short-chain fatty acids, small peptides, and GSH precursors, while lowering the pH to inhibit contaminating bacteria. The staged inoculation and multi-stage fermentation utilize the specific enzyme systems of different microbial species to sequentially complete different transformations, while each stage of sterilization terminates the corresponding metabolic stage, fixes metabolites, and prevents over-fermentation or byproduct accumulation, thereby achieving a controllable product profile.

[0054] Preferably, in step S414, the fermentation product is filtered, concentrated under reduced pressure, and spray-dried to obtain perilla extract. The solid and liquid phases are separated by filtration to remove insoluble residues. Reduced pressure concentration evaporates water at a lower temperature to enrich soluble active ingredients and reduce thermal degradation. Spray drying atomizes the concentrate into microdroplets and rapidly dries it into powder particles. If a film-forming carrier / protectant is added, stable dry powder particles are formed during the drying process. The entire process transforms the liquid extract into a powder form that is easy to store and process.

[0055] Preferably, in step S415, the perilla extract is mixed with a wall material and an emulsifier, emulsified, homogenized, and dried to obtain perilla microcapsule powder. The extract containing both fat-soluble and water-soluble active ingredients is mixed with a selected wall material and emulsifier, and emulsified and homogenized at 60-70°C to form a fine and stable oil / water dispersion. High-shear homogenization significantly reduces droplet / particle size, followed by drying to solidify the wall material and embed the internal active ingredients, thereby forming microcapsules or coated particles. Microencapsulation significantly improves the chemical stability, antioxidant capacity, and gastric acid resistance of fat-soluble components, masks bitterness / astringency, and improves storage stability; controlled release enhances oral bioavailability and reduces gastric degradation or local side effects; it improves powder flowability and compatibility, facilitating the formulation of powders, instant powders, or capsules; microcapsules also reduce the loss of active ingredients during processing and standardize the content of each batch, contributing to quality consistency and label accuracy.

[0056] Furthermore, the wall material is composed of gum arabic: octenyl succinate starch ester: microcrystalline cellulose in a mass ratio of 1:(1.2-1.5):(0.4-0.7), and the emulsifier is composed of Tween 80: sodium caseinate: glyceryl monostearate in a mass ratio of 1:(1.2-1.4):(0.5-0.7); the mass ratio of perilla extract to wall material is 1:(1.3-1.6). These parameters ensure sufficient hydrophobic / hydrophilic wall material and co-emulsifier to form a continuous and dense coating for effective... It protects fat-soluble polyphenols and volatile oils, improves antioxidant stability, gastric acid tolerance, and oral bioavailability, and improves powder flowability, anti-caking, and mechanical strength through trace amounts of microcrystalline cellulose, facilitating spray drying and subsequent formulation processing; the appropriate emulsifier ratio is conducive to the formation of fine and stable oil / water emulsion droplets to improve the loading rate, and minimizes the degradation of heat-sensitive active ingredients; at the same time, these range parameters have process robustness, which is conducive to scale-up production, ensuring batch-to-batch consistency, and achieving a balance between cost and performance.

[0057] In summary, steps S100-S400 constitute a closed-loop process from physical pretreatment of raw materials, biotransformation, concentration / stabilization, and precise formulation. Physical crushing improves the accessibility of raw materials, fermentation bioengineers and enriches functional small molecules, vacuum concentration and spray drying stabilize these metabolites and convert them into easily compatible powders, and finally, intelligent formulation and formulation achieve the target release spectrum and synergistic effects, ensuring that the product has both nutritional support and functional benefits.

[0058] Example 1 This embodiment provides a nutritional intervention composition with functions of regulating liver metabolism, promoting liver repair, and resisting liver fibrosis, and its dosage form is a powder; the nutritional intervention composition includes the following components: 10g Perilla microcapsule powder, 5g concentrated whey protein, 3g instant branched-chain amino acid microcapsule powder, 5g soy protein isolate, 0.08g glutathione-enriched yeast, 2g phospholipids, 0.5g milk thistle seed oil, 2g medium-chain triglyceride microcapsule powder, 2g sheep liver peptide, 2g bovine liver peptide, 2g deer liver peptide, 2g albumin peptide, 1g corn oligopeptide powder, 0.07g taurine, 250μg vitamin A, 65mg vitamin C, 5μg vitamin D, 10mg vitamin E, 2. 5mg Vitamin B1, 1.5mg Vitamin B2, 1.5mg Vitamin B6, 2μg Vitamin B12, 13.5mg Niacin, 126μg Folic Acid, 4μg Pantothenic Acid, 32μg Biotin, 260mg Magnesium Carbonate, 460mg Calcium Carbonate, 8mg Zinc Citrate, 20μg Sodium Selenite, 0.08g Xylooligosaccharides, 3g Oat Flour, 3g Germinated Brown Rice Flour (containing GABA), 0.1g Stevioside, 1g Guar Gum, 3g Xylitol; The nutritional intervention composition is prepared using the following steps: S100. Grind the sprouted brown rice flour to obtain the ground raw material; S200: Mix the pulverized raw materials with water to form fermentation raw materials, and inoculate the fermentation raw materials with an inoculum amount of 5.5*10. 8 CFU / mL Lactobacillus bulgaricus, inoculation amount was 5.5*10 7 CFU / mL Bifidobacterium lactis, inoculation amount was 5.5*10 9 A complex of CFU / mL Bifidobacterium bifidum was anaerobic fermented at 36℃ for 25 h and then sterilized to obtain an intermediate product. S300: The intermediate product is filtered, concentrated under reduced pressure, and spray-dried to obtain the fermented product of germinated brown rice flour; S400: Mix the fermentation product of sprouted brown rice flour, perilla microcapsule powder and other components evenly, and use an automatic powder packaging machine to package it into 8g / packet to obtain the nutritional intervention composition powder. In step S400, the perilla microcapsule powder is prepared by the following steps: S411. Crush the perilla leaves (wild red perilla variety from Changbai Mountain) and mix them with water to obtain the raw material liquid; S412. Add cellulase to the raw material solution at a concentration of 110 U / mL. Perform enzymatic hydrolysis at 36°C for 6 hours to inactivate the enzyme and obtain the enzymatic hydrolysis product. S413. Add Lactobacillus acidophilus to the enzymatic hydrolysis product and carry out anaerobic fermentation at 36℃ for 11 hours. Sterilize the product, add Lactobacillus casei and carry out anaerobic fermentation at 36℃ for 7 hours. Sterilize the product, and finally add Bifidobacterium animalis and carry out anaerobic fermentation at 36℃ for 14 hours. Sterilize the product after fermentation to obtain the fermentation product. S414. The fermentation product is filtered, concentrated under reduced pressure and spray-dried to obtain the nutritional intervention composition. S415. Mix wall material and water at a volume ratio of 1:13, heat to 65°C, stir evenly, then add emulsifier and perilla extract, stir and emulsify, and shear at high speed to obtain primary emulsion. The emulsion is then homogenized under high pressure, concentrated, and spray-dried to obtain perilla microcapsule powder. The wall material is composed of gum arabic, octenyl succinate starch ester, and microcrystalline cellulose in a mass ratio of 1:1.4:0.6; the emulsifier is composed of Tween 80, sodium caseinate, and monoglyceride stearate in a mass ratio of 1:1.3:0.6; and the perilla extract is in a mass ratio of 1:1.5 to the wall material.

[0059] Example 2 This embodiment provides a nutritional intervention composition with functions of regulating liver metabolism, promoting liver repair, and resisting liver fibrosis, and its dosage form is an instant powder; the nutritional intervention composition includes the following components: 1g Perilla microcapsule powder, 0.5g concentrated whey protein, 1g instant branched-chain amino acid microcapsule powder, 1g soy protein isolate, 0.05g glutathione-enriched yeast, 0.5g phospholipids, 0.01g milk thistle seed oil, 0.1g medium-chain triglyceride microcapsule powder, 0.01g sheep liver peptide, 0.01g bovine liver peptide, 0.01g deer liver peptide, 0.01g albumin peptide, 0.20g corn oligopeptide powder, 0.05g taurine, 120μg vitamin A, 15mg vitamin C, 1.5μg vitamin D, 2.1mg vitamin C. Vitamin E, 0.2mg Vitamin B1, 0.2mg Vitamin B2, 0.2mg Vitamin B6, 0.4μg Vitamin B12, 2.1mg Niacin, 60μg Folic Acid, 0.8μg Pantothenic Acid, 4.5μg Biotin, 53mg Magnesium Carbonate, 150mg Calcium Carbonate, 1.7mg Zinc Citrate, 7.5μg Sodium Selenite, 0.07g Xylooligosaccharides, 0.5g Oat Flour, 0.5g Germinated Brown Rice Flour (containing GABA), 0.05g Steviosides, 0.5g Guar Gum, 1g Xylitol; The nutritional intervention composition is prepared using the following steps: S100. Grind the sprouted brown rice flour to obtain the ground raw material; S200: Mix the pulverized raw materials with water to form fermentation raw materials, and inoculate the fermentation raw materials with an inoculum amount of 10. 8 CFU / mL Lactobacillus bulgaricus, inoculation amount 10 7 CFU / mL Bifidobacterium lactis, inoculation amount was 10 9 A complex of CFU / mL Bifidobacterium bifidum was anaerobic fermented at 35℃ for 26 h and then sterilized to obtain an intermediate product. S300: The intermediate product is filtered, concentrated under reduced pressure, and spray-dried to obtain the fermented product of germinated brown rice flour; S400: Mix the fermentation product of sprouted brown rice flour, perilla microcapsule powder and other components evenly, and use an automatic powder packaging machine to package it into 8g / packet to obtain the nutritional intervention composition instant powder. In step S400, the perilla microcapsule powder is prepared by the following steps: S411. Crush the perilla leaves and mix them with water to obtain the raw material liquid; S412. Add cellulase to the raw material solution at a concentration of 100 U / mL. Perform enzymatic hydrolysis at 35°C for 7 hours to inactivate the enzyme and obtain the enzymatic hydrolysis product. S413. Add Lactobacillus acidophilus to the enzymatic hydrolysis product and carry out anaerobic fermentation at 35℃ for 12 hours. Sterilize the product, add Lactobacillus casei and carry out anaerobic fermentation at 35℃ for 8 hours. Sterilize the product, and finally add Bifidobacterium animalis and carry out anaerobic fermentation at 35℃ for 15 hours. Sterilize the product after fermentation to obtain the fermentation product. S414. The fermentation product was filtered, concentrated under reduced pressure, and spray-dried to obtain perilla extract; S415. Mix wall material and water at a volume ratio of 1:10, heat to 60°C, stir evenly, then add emulsifier and perilla extract, stir and emulsify, and shear at high speed to obtain primary emulsion. The emulsion is then homogenized under high pressure, concentrated, and spray-dried to obtain perilla microcapsule powder. The wall material is composed of gum arabic, octenyl succinate starch ester, and microcrystalline cellulose in a mass ratio of 1:1.2:0.4; the emulsifier is composed of Tween 80, sodium caseinate, and monoglyceride stearate in a mass ratio of 1:1.2:0.5; and the perilla extract is in a mass ratio of 1:1.3 to the wall material.

[0060] Example 3 This embodiment provides a nutritional intervention composition with functions of regulating liver metabolism, promoting liver repair, and resisting liver fibrosis, and its dosage form is a powder; the nutritional intervention composition includes the following components: 15g Perilla microcapsule powder, 10g whey protein concentrate, 6g instant branched-chain amino acid microcapsule powder, 10g soy protein isolate, 1g glutathione-enriched yeast, 5g phospholipids, 1g milk thistle seed oil, 3g medium-chain triglyceride microcapsule powder, 3g sheep liver peptide, 3g bovine liver peptide, 3g deer liver peptide, 3g albumin peptide, 2.0g corn oligopeptide powder, 0.09g taurine, 375μg vitamin A, 100mg vitamin C, 10μg vitamin D, 20mg vitamin C. E, 4mg Vitamin B1, 2mg Vitamin B2, 2mg Vitamin B6, 4μg Vitamin B12, 20mg Niacin, 260μg Folic Acid, 7μg Pantothenic Acid, 50μg Biotin, 300mg Magnesium Carbonate, 800mg Calcium Carbonate, 12mg Zinc Citrate, 52μg Sodium Selenite, 0.10g Xylooligosaccharides, 5g Oat Flour, 5g Germinated Brown Rice Flour (containing γ-aminobutyric acid), 0.2g Steviosides, 2g Guar Gum, 5g Xylitol; The nutritional intervention composition is prepared using the following steps: S100. Grind the sprouted brown rice flour to obtain the ground raw material; S200: Mix the pulverized raw materials with water to form fermentation raw materials, and inoculate the fermentation raw materials with an inoculum amount of 10. 9 CFU / mL Lactobacillus bulgaricus, inoculation amount 10 8CFU / mL Bifidobacterium lactis, inoculation amount was 10 10 A complex of CFU / mL Bifidobacterium bifidum was anaerobic fermented at 38℃ for 24 h and then sterilized to obtain an intermediate product. S300: The intermediate product is filtered, concentrated under reduced pressure, and spray-dried to obtain the fermented product of germinated brown rice flour; S400: Mix the fermentation product of sprouted brown rice flour, perilla microcapsule powder and other components evenly, and use an automatic powder packaging machine to package it into 8g / packet to obtain the nutritional intervention composition powder. In step S400, the perilla microcapsule powder is prepared by the following steps: S411. Crush the perilla leaves and mix them with water to obtain the raw material liquid; S412. Add cellulase to the raw material solution at a concentration of 120 U / mL. Perform enzymatic hydrolysis at 38°C for 5 hours to inactivate the enzyme and obtain the enzymatic hydrolysis product. S413. Add Lactobacillus acidophilus to the enzymatic hydrolysis product and carry out anaerobic fermentation at 38℃ for 10 hours. Sterilize the product, add Lactobacillus casei and carry out anaerobic fermentation at 38℃ for 6 hours. Sterilize the product, and finally add Bifidobacterium animalis and carry out anaerobic fermentation at 38℃ for 13 hours. Sterilize the product after fermentation to obtain the fermentation product. S414. The fermentation product was filtered, concentrated under reduced pressure, and spray-dried to obtain perilla extract; S415. Mix wall material and water at a volume ratio of 1:15, heat to 70°C, stir evenly, then add emulsifier and perilla extract, stir and emulsify, and shear at high speed to obtain primary emulsion. The emulsion is then homogenized under high pressure, concentrated, and spray-dried to obtain perilla microcapsule powder. The wall material is composed of gum arabic, octenyl succinate starch ester, and microcrystalline cellulose in a mass ratio of 1:1.5:0.7; the emulsifier is composed of Tween 80, sodium caseinate, and monoglyceride stearate in a mass ratio of 1:1.4:0.7; and the perilla extract is in a mass ratio of 1:1.6 to the wall material.

[0061] Example 4 This embodiment provides a nutritional intervention composition with functions of regulating liver metabolism, promoting liver repair, and resisting liver fibrosis, and its dosage form is a powder; the nutritional intervention composition includes the following components: 8g Perilla microcapsule powder, 8g concentrated whey protein, 4g instant branched-chain amino acid microcapsule powder, 4g soy protein isolate, 0.06g glutathione-enriched yeast, 3g phospholipids, 0.65g milk thistle seed oil, 1.5g medium-chain triglyceride microcapsule powder, 1.5g sheep liver peptide, 1.5g bovine liver peptide, 1.5g deer liver peptide, 1.5g albumin peptide, 1.8g corn oligopeptide powder, 0.06g taurine, 350μg vitamin A, 85mg vitamin C, 8μg vitamin D, 15mg vitamin E 2mg Vitamin B1, 1.1mg Vitamin B2, 1.1mg Vitamin B6, 3μg Vitamin B12, 15mg Niacin, 150μg Folic Acid, 3.5μg Pantothenic Acid, 25μg Biotin, 180mg Magnesium Carbonate, 350mg Calcium Carbonate, 6.5mg Zinc Citrate, 30μg Sodium Selenite, 0.09g Xylooligosaccharides, 3.5g Oat Flour, 2.5g Germinated Brown Rice Flour (containing GABA), 0.15g Steviosides, 1.5g Guar Gum, 2g Xylitol; The nutritional intervention composition is prepared using the following steps: S100. Grind the sprouted brown rice flour to obtain the ground raw material; S200: Mix the pulverized raw materials with water to form fermentation raw materials, and inoculate the fermentation raw materials with an inoculum amount of 6*10. 8 CFU / mL Lactobacillus bulgaricus, inoculation amount was 6*10 7 CFU / mL Bifidobacterium lactis, inoculation amount was 6*10 9 A complex of CFU / mL Bifidobacterium bifidum was anaerobic fermented at 37°C for 25 h and then sterilized to obtain an intermediate product. S300: The intermediate product is filtered, concentrated under reduced pressure, and spray-dried to obtain the fermented product of germinated brown rice flour; S400: Mix the fermentation product of sprouted brown rice flour, perilla microcapsule powder and other components evenly, and use an automatic powder packaging machine to package it into 8g / packet, which is the nutritional intervention composition powder. In step S400, the perilla microcapsule powder is prepared by the following steps: S411. Crush the perilla leaves and mix them with water to obtain the raw material liquid; S412. Add cellulase to the raw material solution at a concentration of 110 U / mL. Perform enzymatic hydrolysis at 37°C for 6 hours to inactivate the enzyme and obtain the enzymatic hydrolysis product. S413. Add Lactobacillus acidophilus to the enzymatic hydrolysis product and carry out anaerobic fermentation at 37℃ for 11 hours. Sterilize the product, add Lactobacillus casei and carry out anaerobic fermentation at 37℃ for 7 hours. Sterilize the product, and finally add Bifidobacterium animalis and carry out anaerobic fermentation at 37℃ for 14 hours. Sterilize the product after fermentation to obtain the fermentation product. S414. The fermentation product was filtered, concentrated under reduced pressure, and spray-dried to obtain perilla extract; S415. Mix wall material and water at a volume ratio of 1:14, heat to 68°C, stir evenly, then add emulsifier and perilla extract, stir and emulsify, and shear at high speed to obtain primary emulsion. The emulsion is then homogenized under high pressure, concentrated, and spray-dried to obtain perilla microcapsule powder. The wall material is composed of gum arabic, octenyl succinate starch ester, and microcrystalline cellulose in a mass ratio of 1:1.3:0.5; the emulsifier is composed of Tween 80, sodium caseinate, and monoglyceride stearate in a mass ratio of 1:1.3:0.6; and the perilla extract is in a mass ratio of 1:1.4 to the wall material.

[0062] Comparative Example 1 This comparative example provides a nutritional intervention composition. The composition and preparation method are the same as those shown in Example 1, except that ordinary perilla extract is used, that is, 10g of ordinary perilla extract (unmicroencapsulated) is used, and step S415 is omitted.

[0063] Comparative Example 2 This comparative example provides a nutritional intervention composition. The composition and preparation method are the same as those in Example 1, except that unfermented sprouted brown rice flour is used, i.e., the preparation method does not include step S100-300.

[0064] Comparative Example 3 This comparative example provides a nutritional intervention composition. The composition and preparation method are the same as those in Example 1, except that in step S200, only Lactobacillus bulgaricus is used for fermentation, while other conditions remain unchanged.

[0065] Comparative Example 4 This comparative example provides a nutritional intervention composition. The composition and preparation method are the same as those shown in Example 1, except that it does not contain liver peptide components, i.e., it does not contain sheep liver peptide, bovine liver peptide, deer liver peptide and albumin peptide.

[0066] Comparative Example 5 This comparative example provides a nutritional intervention composition. The composition and preparation method are the same as those shown in Example 1, except that it does not contain water thistle seed oil, i.e., water thistle components.

[0067] Comparative Example 6 This comparative example provides a nutritional intervention composition. The composition and preparation method are the same as those in Example 1, except that the ratio of gum arabic: octenyl succinate starch ester: microcrystalline cellulose is 1:0.8:0.6.

[0068] Comparative Example 7 This comparative example provides a nutritional intervention composition, the composition and preparation method of which are the same as those shown in Example 1, except that the ratio of gum arabic: octenyl succinate starch ester: microcrystalline cellulose is 1:1.4:1.2.

[0069] Comparative Example 8 This comparative example provides a nutritional intervention composition. The composition and preparation method are the same as those in Example 1, except that the wall material is composed only of gum arabic and octenyl succinate starch ester, with the ratio of gum arabic to octenyl succinate starch ester being 1:1.4.

[0070] Comparative Example 9 This comparative example provides a nutritional intervention composition. The composition and preparation method are the same as those in Example 1, except that the mass ratio of perilla extract to wall material is changed to 1:0.8.

[0071] Test method: GABA content determination: To verify the content of γ-aminobutyric acid (GABA) derived from germinated brown rice flour in the product, the products obtained in Examples 1-4 were tested according to "T / CGTA 03-2024 Determination of γ-aminobutyric acid in germinated brown rice by high performance liquid chromatography-tandem mass spectrometry".

[0072] Test results: The GABA content in the products of Examples 1-4 was determined to be 986 μg / bag, 354 μg / bag, 1520 μg / bag, and 735 μg / bag, respectively.

[0073] Animal experiments verified: Experimental animals and grouping: 120 healthy male SD rats were randomly divided into 12 groups of 10 rats each.

[0074] Blank control group: fed with normal feed and administered physiological saline by gavage.

[0075] Model control group: The liver fibrosis model was induced by intraperitoneal injection of carbon tetrachloride olive oil solution and oral administration of physiological saline.

[0076] Positive control group: During the modeling process, the contents of a commercially available brand of silymarin capsules were administered via gavage.

[0077] Examples 1-4 and Comparative Examples 1-5: During modeling, the nutritional intervention composition solutions prepared in Examples 1, 2, 3, 4 and Comparative Examples 1, 2, 3, 4, 5 were administered by gavage.

[0078] Experiment duration: 8 weeks of continuous intervention.

[0079] Testing indicators: Serum biochemical indicators: At the end of the experiment, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were measured to evaluate the degree of hepatocellular damage; Indicators of oxidative stress in liver tissue: A portion of liver tissue homogenate was taken, and the activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected to evaluate antioxidant capacity. Liver fibrosis markers: Serum hyaluronic acid (HA) and type III procollagen (PCⅢ) levels were detected using enzyme-linked immunosorbent assay (ELISA). Test results: Table 1 Note: Compared with the blank control group, **P<0.01; compared with the model control group, ##P<0.01; compared with the positive control group, △P<0.05, △△P<0.01; compared with the Example 1 group, ▲P<0.05, ▲▲P<0.01.

[0080] Table 2 Note: Compared with the blank control group, **P<0.01; compared with the model control group, ##P<0.01; compared with the positive control group, △P<0.05, △△P<0.01; compared with the Example 1 group, ▲P<0.05, ▲▲P<0.01.

[0081] The perilla microcapsule powders obtained in Example 1 and Comparative Examples 6-9 were subjected to the following performance tests: Encapsulation rate determination: The content of rosmarinic acid, the main active ingredient in perilla microcapsule powder, was determined by high performance liquid chromatography, and the encapsulation rate was calculated.

[0082] In vitro release assay: Using a dissolution tester, the sample was incubated in artificial gastric fluid (pH 1.2) for 2 hours, and then transferred to artificial intestinal fluid (pH 6.8) for further assay. The cumulative release was calculated.

[0083] Accelerated stability test: The samples were placed at 40℃±2℃ and 75%RH±5%RH and samples were taken at the end of 0, 1, 2, 3 and 6 months to detect the rosmarinic acid retention rate.

[0084] Table 3 Results analysis: As shown in Table 1, compared with the blank control group, the ALT, AST, HA, and PCⅢ levels in the model control group were significantly increased, indicating that the liver fibrosis model was successfully established. The above indicators in each treatment group were significantly lower than those in the model control group. Notably, all indicators in Example 1 and Example 4 groups were significantly better than those in the positive control group, with Example 1 showing the most significant effect. This indicates that the nutritional intervention composition provided by this invention, especially under optimized process parameters, is significantly more effective than the single-component silymarin in reducing transaminase levels and combating liver fibrosis.

[0085] As shown in Table 2, the model control group exhibited significantly decreased SOD activity and significantly increased MDA content, indicating severe liver oxidative stress damage. All treatment groups effectively increased SOD activity and decreased MDA content. Among them, groups 1 and 4 showed significantly better results than the positive control group in increasing SOD activity and decreasing MDA content, demonstrating that the composition of the present invention has stronger comprehensive antioxidant capacity, and that the processes in Examples 1 and 4 exhibited the best effects.

[0086] Data from Comparative Example 1 shows that the unmicroencapsulated perilla extract was significantly less effective than that of Example 1, directly demonstrating the indispensable role of microencapsulation in improving the bioavailability and stability of active ingredients. Comparative Examples 2 and 3 were both significantly less effective than Example 1, proving that the multi-stage fermentation process using a specific complex of bacteria on germinated brown rice flour can significantly enhance the bioactivity of the product. Comparative Examples 4 and 5 showed the most significant decrease in effectiveness, strongly demonstrating that the hepatic peptide and milk thistle components, along with perilla microencapsulated powder and other components, produced a synergistic effect in this composition, rather than a simple additive effect.

[0087] As shown in Table 3, the wall material formulation of the present invention can significantly improve the encapsulation rate, gastrointestinal stability and targeted release performance of the active ingredients of Perilla frutescens. As can be seen from Example 1 and Comparative Examples 6-9, the encapsulation rate of the active ingredients in Example 1 is greater than 95%, which is much higher than that in the comparative examples. Moreover, Example 1 can provide the best gastrointestinal targeted release characteristics, with less than 10% release in the stomach and more than 90% release in the intestine, which significantly improves oral bioavailability. In addition, the retention rate is greater than 88% in the 6-month accelerated test, ensuring shelf-life quality.

[0088] The above test data fully demonstrate that the present invention, through its formulation and preparation method, has achieved unexpected technical effects in improving liver function, resisting liver fibrosis, and providing antioxidant protection. The provided nutritional intervention composition can significantly improve liver function indicators in rats with carbon tetrachloride-induced liver fibrosis, effectively combat liver oxidative stress, and significantly inhibit the progression of liver fibrosis. Its comprehensive liver-protective and anti-fibrotic effects are significantly superior to commercially available single-component silymarin products.

[0089] In the description of this specification, the terms "one embodiment," "some embodiments," "specific embodiment," etc., refer to a specific feature, structure, material, or characteristic described in connection with that embodiment or example, which is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0090] While the present invention has been disclosed above, it is not limited thereto. Any person skilled in the art can make various modifications and alterations without departing from the spirit and scope of the invention; therefore, the scope of protection of the present invention should be determined by the scope defined in the claims.

Claims

1. A nutritional intervention composition having the functions of regulating liver metabolism, promoting liver repair, and resisting liver fibrosis, characterized in that, The nutritional intervention composition includes perilla microcapsule powder, protein components, liver peptide components, glutathione-enriched yeast, milk thistle components, corn oligopeptide powder, oat flour, and fermented products of sprouted brown rice flour.

2. The nutritional intervention composition according to claim 1, characterized in that, The nutritional intervention composition further includes: Amino acids, including at least one or a combination of branched-chain amino acids and taurine; and / or vitamins, including at least one or a combination of vitamin A, vitamin C, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, folic acid, pantothenic acid, and biotin; and / or minerals, including at least one or a combination of magnesium, calcium, zinc, and selenium.

3. The nutritional intervention composition according to claim 1, characterized in that, The components and their corresponding masses are as follows: 1-15g of the aforementioned perilla microcapsule powder; 1.5-20g of the protein component; 0.04-12g of the aforementioned liver peptide component; 0.01-1g of the milk thistle component; 0.20-2.0g of the corn oligopeptide powder; 1-10g of the fermentation product of the germinated brown rice flour.

4. The nutritional intervention composition according to claim 3, characterized in that, The nutritional intervention composition further includes: 1-6g of amino acids; 207-854 μg of vitamins; 212-1164mg of minerals.

5. The nutritional intervention composition according to claim 4, characterized in that, The protein components include 0.5-10g of whey protein concentrate and 1-10g of soy protein isolate; The liver peptide components include 0.01-3g sheep liver peptide, 0.01-3g bovine liver peptide, 0.01-3g deer liver peptide, and 0.01-3g albumin peptide; The amino acids include 1-6g of branched-chain amino acids and 0.05-0.09g of taurine; The vitamins include 120-375 μg vitamin A, 15-100 mg vitamin C, 1.5-10 μg vitamin D, 2.1-20 mg vitamin E, 0.2-4 mg vitamin B1, 0.2-2 mg vitamin B2, 0.2-2 mg vitamin B6, 0.4-4 μg vitamin B12, 2.1-20 mg niacin, 60-260 μg folic acid, 0.8-7 μg pantothenic acid, and 4.5-50 μg biotin. The minerals include 53-300 mg magnesium, 150-800 mg calcium, 1.7-12 mg zinc, and 7.5-52 μg selenium.

6. A method for preparing a nutritional intervention composition having the functions of regulating liver metabolism, promoting liver repair, and resisting liver fibrosis, characterized in that, The preparation method is used to prepare the nutritional intervention composition according to any one of claims 1-3, and the preparation method includes the following steps: S100. Grind the sprouted brown rice flour to obtain the ground raw material; S200: Mix the pulverized raw material with water to form a fermentation raw material, inoculate the fermentation raw material with compound bacteria, and anaerobic ferment at 35-38℃ for 24-26 hours and then sterilize to obtain an intermediate product; S300: The intermediate product is filtered, concentrated under reduced pressure, and spray-dried to obtain the fermented product of germinated brown rice flour; S400: The fermentation product of the germinated brown rice flour, the perilla microcapsule powder and the remaining components are mixed evenly to obtain a nutritional intervention composition.

7. The preparation method according to claim 6, characterized in that, In step S200, the compound bacteria include Lactobacillus bulgaricus, Bifidobacterium lactis, and Bifidobacterium bifidum; The inoculum size of *Lactobacillus bulgaricus* in the fermentation feedstock is 10. 8 -10 9 CFU / mL, the inoculum amount of Bifidobacterium lactis in the fermentation feed is 10. 7 -10 8 CFU / mL, the inoculum amount of Bifidobacterium bifidum in the fermentation raw material is 10 CFU / mL. 9 -10 10 CFU / mL.

8. The preparation method according to claim 6, characterized in that, In step S400, the perilla microcapsule powder is prepared by the following steps: S411. Crush the perilla leaves and mix them with water to obtain the raw material liquid; S412. Add cellulase to the raw material solution to carry out enzymatic hydrolysis to obtain the enzymatic hydrolysis product; S413. Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium animalis are sequentially inoculated into the enzymatic hydrolysis product for multi-stage anaerobic fermentation. After each stage of fermentation, the product is sterilized to obtain the fermentation product. S414. The fermentation product is filtered, concentrated under reduced pressure and spray-dried to obtain perilla extract; S415. The perilla extract is mixed with wall material and emulsifier, emulsified, homogenized and dried to obtain the perilla microcapsule powder.

9. The preparation method according to claim 8, characterized in that, In step S415, The wall material is composed of gum arabic: octenyl succinate starch ester: microcrystalline cellulose in a mass ratio of 1:(1.2-1.5):(0.4-0.7); The emulsifier is composed of Tween 80: sodium caseinate: glyceryl monostearate in a mass ratio of 1:(1.2-1.4):(0.5-0.7). The mass ratio of the perilla extract to the wall material is 1:(1.3-1.6). The mixing temperature is 60-70℃.

10. Use of a nutritional intervention composition according to any one of claims 1-5, characterized in that, The nutritional intervention composition is used to prepare foods, health foods, or medicines for the prevention and / or adjuvant treatment of liver damage and liver fibrosis.

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