A polypeptide composition, methods for its production and use in improving conditions in the intestinal tract

Abstract

This invention discloses a polypeptide composition, its preparation method, and its application in improving intestinal problems, belonging to the field of bioactive peptide technology. The polypeptide composition comprises 20%-70% by weight of active components and excipients. The active components consist of a combination of polypeptides, a combination of prebiotics, and a combination of plant extracts. The excipients include an acid-resistant coating premix and conventional pharmaceutical excipients. The preparation method of this composition employs a stepwise premixing and incremental equal-volume process to ensure product uniformity and batch stability. Using the aforementioned polypeptide composition, its preparation method, and its application in improving intestinal problems, this invention provides a composition that can synergistically achieve intestinal mucosal repair, intestinal flora regulation, and inflammation suppression at multiple targets, significantly improving various intestinal problems. It exhibits good oral stability and high bioavailability, requires no patent sequence listing, and can be widely applied in the preparation of foods, health foods, and special medical purpose formulations for improving intestinal problems.

Description

Technical Field

[0001] This invention relates to the field of bioactive peptide technology, and in particular to a polypeptide composition, its preparation method, and its application in improving intestinal problems. Background Technology

[0002] As the core digestive and absorptive organ and the largest immune barrier in the human body, the health of the gut directly determines the efficiency of nutrient absorption and the overall immune homeostasis. In recent years, influenced by multiple factors such as unbalanced diet, fast-paced lifestyle, antibiotic abuse, and increased mental stress, the incidence of various intestinal problems, including damage to the intestinal mucosal barrier, gut microbiota imbalance, irritable bowel syndrome, and antibiotic-associated diarrhea, has continued to rise and shows a significant trend towards affecting younger people. These problems not only cause local discomfort such as abdominal pain, diarrhea, and indigestion, but also, in the long term, can induce nutrient absorption disorders, immune dysfunction, and systemic metabolic diseases, becoming a public health issue that urgently needs to be addressed.

[0003] Currently, small molecule peptides have become a core focus of research and development in the field of intestinal health due to their advantages of easy absorption, strong targeting, and high safety. However, existing peptide products still have many insurmountable technical defects. Ordinary protein or long-chain peptide products are easily degraded by enzymes in the gastrointestinal tract, making it difficult to reach the intestines and take effect. They also have low oral absorption efficiency and poor bioavailability. Single nutritional peptides or single prebiotic products have limited functions, only able to supplement nutrition or regulate the flora, and cannot simultaneously achieve mucosal repair, flora regulation, and inflammation control, thus having limited effects on complex intestinal problems. Some compound products do not take into account the problem that small molecule peptides are easily degraded and suffer severe loss of activity in the acidic environment of the stomach, resulting in unstable oral effects. Existing intestinal conditioning products often suffer from problems such as lack of synergy in formulation, poor mixing uniformity, and poor formulation formability, making it difficult to balance activity, stability, and applicability.

[0004] Therefore, there is an urgent need for a polypeptide composition that can efficiently repair the intestinal mucosa, regulate the intestinal flora, inhibit intestinal inflammation, and has good oral stability, high bioavailability, and a scientifically sound formula to solve the existing problems. Summary of the Invention

[0005] The purpose of this invention is to provide a polypeptide composition, a method for preparing the same, and an improved application for intestinal problems, in order to solve the aforementioned problems.

[0006] This invention provides a polypeptide composition comprising an active ingredient and food- or pharmaceutically acceptable excipients. The active ingredient comprises a polypeptide combination, a prebiotic combination, and a plant extract combination. By weight, the active ingredient comprises: 11-53 parts of the polypeptide combination, 15-50 parts of the prebiotic combination, and 1.5-13 parts of the plant extract combination. The active ingredient accounts for 20%-70% of the total mass of the polypeptide composition, with the remainder being excipients. The excipients include an acid-resistant coating premix comprising 3%-8% of the total mass of the polypeptide composition, and the remainder being conventional pharmaceutical excipients selected from at least one of fillers, disintegrants, lubricants, and flavoring agents. The polypeptide combination includes 5-20 parts of L-alanyl-L-glutamine, 3-15 parts of L-glycyl-L-glutamine, 2-10 parts of reduced glutathione, and 1-8 parts of L-tyrosyl-L-proline. The prebiotic blend includes 10-30 parts of fructooligosaccharides and 5-20 parts of galactooligosaccharides; The plant extract combination includes 0.5 to 5 parts curcumin and 1 to 8 parts fucoidan.

[0007] Preferably, the weight ratio of the polypeptide combination to the prebiotic combination is 1:(0.8-2.5).

[0008] Preferably, the acid-resistant coating premix is ​​composed of hydroxypropyl methylcellulose phthalate (HPMCP), talc, and triethyl citrate in a mass ratio of 3:1:0.2.

[0009] Preferably, by weight, the filler is selected from at least one of maltodextrin, microcrystalline cellulose, and mannitol; the disintegrant is selected from at least one of crospovidone and sodium carboxymethyl starch; the lubricant is selected from at least one of magnesium stearate and micronized silica; and the flavoring agent is selected from at least one of steviol glycosides and citric acid.

[0010] Preferably, the dosage form of the polypeptide composition is an oral solid dosage form, specifically a powder, granules, capsules, or tablets; the water activity of the oral solid dosage form is ≤0.6, and the particle size D90 is 150-250 μm.

[0011] A method for preparing the polypeptide composition as described above is provided, comprising the following steps: S1. Weigh each component of the polypeptide combination according to the preset weight parts, mix them evenly to obtain a peptide powder premix; weigh each component of the prebiotic combination and the plant extract combination according to the preset weight parts, mix them evenly to obtain an excipient premix. S2. Mix the peptide powder premix and the excipient premix in equal increments, and pass them through an 80-120 mesh sieve to obtain a mixture of active components. S3. The active ingredient mixture is mixed evenly with food or pharmaceutically acceptable excipients in a preset ratio, and then processed through a molding process corresponding to the dosage form to obtain the polypeptide composition.

[0012] Preferably, the mixing of the peptide powder premix in step S1 is a three-dimensional motion mixing, with a mixing time of 15-25 min and a rotation speed of 15-25 rpm; the single mixing time of the equal incremental mixing method in step S2 is 10-20 min, and the total mixing time is 30-50 min.

[0013] The above-mentioned polypeptide composition is used to prepare food, health food, or special medical purpose formula food for improving intestinal problems.

[0014] Preferably, the intestinal problem is intestinal mucosal barrier damage, intestinal flora imbalance, remission of inflammatory bowel disease, irritable bowel syndrome, antibiotic-associated diarrhea, or stress-induced intestinal injury.

[0015] Preferably, the daily oral dose of the polypeptide composition is 0.5 to 5 g per 60 kg body weight, based on the active ingredient.

[0016] Therefore, the present invention, by employing the above-mentioned polypeptide composition and its preparation method, and its improved application in intestinal problems, has the following beneficial effects: (1) The composition can simultaneously act on intestinal mucosal repair, intestinal flora regulation and intestinal inflammation inhibition. It has significant improvement effects on intestinal mucosal barrier damage, flora imbalance, irritable bowel syndrome and antibiotic-associated diarrhea, and its effects are significantly better than single-component or simple binary compound products.

[0017] (2) The various small molecule short peptides used can directly provide energy to intestinal epithelial cells, reduce oxidative stress damage, inhibit cell apoptosis, enhance intestinal tight junctions, rapidly promote the healing of damaged mucosa, and improve the integrity of the intestinal barrier.

[0018] (3) The prebiotic combination can selectively proliferate beneficial bacteria and inhibit harmful bacteria, optimize the intestinal microecological structure, increase the level of short-chain fatty acids, provide a good environment for intestinal mucosal repair, and form a long-term conditioning effect. The active ingredients are protected by the acid-resistant coating system, which reduces their degradation loss in gastric acid, increases the proportion of active ingredients reaching the intestine, and improves the overall bioavailability and stability of action.

[0019] (4) The composition has a scientific formulation and reasonable selection of excipients, making it suitable for preparation of various oral solid dosage forms such as powders, granules, capsules, and tablets. It has high mixing uniformity and stable quality, making it convenient for production and long-term use. All raw materials used are conventional safe food or pharmaceutical grade raw materials, with no irritation or obvious side effects. They can be used to prepare food, health food, and special medical purpose formula food, and are suitable for a wide range of people.

[0020] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0021] Figure 1 The bar charts show the experimental results of Example 1 of the present invention, which compare the results of a polypeptide composition and its preparation method and its application in improving intestinal problems. (A) is a bar chart of the Disease Activity Index (DAI) score, (B) is a bar chart of the colon pathology score, (C) is a bar chart of the relative expression level of the tight junction protein Occludin, and (D) is a bar chart of the relative expression level of the tight junction protein Claudin-1. Detailed Implementation

[0022] To better understand the above technical solutions, a detailed description of the solutions will be provided below in conjunction with the accompanying drawings and specific embodiments. Obviously, the described embodiments are merely some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0023] The terminology used in the embodiments of this invention is for the purpose of describing particular embodiments only and is not intended to limit the invention. The singular forms “a,” “the,” and “the” as used in the embodiments of this invention and the appended claims are also intended to include the plural forms, and “multiple” generally includes at least two unless the context clearly indicates otherwise.

[0024] It should also be noted that the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that an article or device that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such an article or device. Without further limitation, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the article or device that includes said element.

[0025] Unless otherwise specified, the experimental methods used in the following examples and comparative examples are conventional experimental methods in the fields of biomedicine and functional foods; the raw materials, reagents, and excipients used are all commercially available food-grade / pharmaceutical-grade standardized products, which can be directly purchased and obtained by those skilled in the art. Specific specifications are as follows: L-Alanyl-L-Glutamine: Food grade, purity ≥99%, commercially available; L-Glycyl-L-Glutamine: Food grade, purity ≥99%, commercially available; Reduced glutathione: food grade, purity ≥98%, commercially available; L-Tyrosyl-L-proline: Food grade, purity ≥99%, commercially available; Fructooligosaccharides: food grade, total sugar content ≥95%, commercially available; Galacto-oligosaccharides: Food grade, total sugar content ≥90%, commercially available; Curcumin: Food grade, purity ≥95%, commercially available; Fucoidan: Food grade, active ingredient content ≥85%, commercially available; Hydroxypropyl methylcellulose phthalate (HPMCP), talc, and triethyl citrate: all are pharmaceutical grade and commercially available; Maltodextrin, microcrystalline cellulose, mannitol, crospovidone, magnesium stearate, steviol glycosides, and citric acid: all are food-grade / pharmaceutical-grade and commercially available.

[0026] Example 1 Polypeptide composition formulation: Total mass 1000g; (1) Active components: total mass 450g, accounting for 45% of the total mass of the composition; The active ingredients, by weight, are as follows: 30 parts peptides, 35 parts prebiotics, and 4 parts plant extracts. The specific amounts of each component are as follows: The total amount of the peptides is 243.24g, specifically including 97.30g L-alanyl-L-glutamine, 64.86g L-glycyl-L-glutamine, 48.65g reduced glutathione, and 32.43g L-tyrosyl-L-proline; the total amount of the prebiotics is 193.24g, specifically including 121.62g fructooligosaccharides and 71.62g galactooligosaccharides; the total amount of the plant extracts is 13.52g, specifically including 5.41g curcumin and 8.11g fucoidan. The total amount of all the above components, including active ingredients, is 450.00g.

[0027] The weight ratio of the polypeptide combination to the prebiotic combination is 1:0.8.

[0028] (2) Auxiliary materials: Total weight 550g; Anti-acid coating premix: 50g, accounting for 5% of the total mass of the composition; composed of HPMCP 35.7g, talc 11.9g, and triethyl citrate 2.4g in a mass ratio of 3:1:0.2; Standard formulation excipients: 495g maltodextrin, 5g steviol glycosides, totaling 500g.

[0029] Preparation method: S1. Weigh the four short peptide components of the polypeptide combination according to the above formula, put them into a three-dimensional motion mixer, set the speed to 20 rpm, and the mixing time to 20 min. After mixing evenly, obtain the peptide powder premix. Weigh each component of the prebiotic combination and the plant extract combination according to the formula, mix evenly, and obtain the excipient premix. S2. Using the equal incremental method, the peptide powder premix and the excipient premix are mixed in 4 batches, with each batch taking 15 minutes and the total mixing time taking 40 minutes. After mixing, the mixture is passed through a 100-mesh sieve to obtain the active component mixture. S3. The active component mixture is mixed evenly with maltodextrin and steviol glycosides, and then dry granulated and sized. After granulation, it is coated in a fluidized bed with an acid-resistant coating premix. After sieving and granulation, the polypeptide composition powder is obtained. The resulting powder has a water activity of 0.42 and a particle size D90 of 210 μm.

[0030] Example 2 Polypeptide composition formulation: Total mass 1000g; (1) Active component: 700g total mass, accounting for 70% of the total mass of the composition; The active components, by weight, are as follows: 52 parts peptides, 45 parts prebiotics, and 12 parts plant extracts. The specific amounts of each component are as follows: The total amount of the peptide combination is 364g, specifically including 140g of L-alanyl-L-glutamine, 105g of L-glycyl-L-glutamine, 70g of reduced glutathione, and 49g of L-tyrosyl-L-proline; the total amount of the prebiotic combination is 315g, specifically including 210g of fructooligosaccharides and 105g of galactooligosaccharides, all within the preset amount range; the total amount of the plant extract combination is 21g, specifically including 7g of curcumin and 14g of fucoidan.

[0031] The weight ratio of the polypeptide combination to the prebiotic combination is 1:0.86.

[0032] (2) Auxiliary materials: 300g total weight; Anti-acid coating premix: 80g, accounting for 8% of the total mass of the composition; composed of HPMCP 57.12g, talc 19.04g, and triethyl citrate 3.84g in a mass ratio of 3:1:0.2; Standard formulation excipients: 215g microcrystalline cellulose, 5g magnesium stearate, totaling 220g.

[0033] Preparation method: S1. Weigh each component of the polypeptide combination according to the above formula, put them into a three-dimensional motion mixer, set the speed to 25 rpm, and the mixing time to 15 min to obtain the peptide powder premix; weigh each component of the prebiotic and plant extract according to the formula, mix them evenly to obtain the excipient premix. S2. Using the equal incremental method, the peptide powder premix and the excipient premix are mixed in 5 batches, with each batch taking 10 minutes and the total mixing time taking 35 minutes. The mixture is then passed through a 120-mesh sieve to obtain the active component mixture. S3. Mix the active component mixture with microcrystalline cellulose and magnesium stearate evenly. After mixing for 20 minutes, fill the mixture into gelatin empty capsules and coat them with an acid-resistant coating premix to obtain polypeptide composition capsules. The water activity of the contents of the obtained capsules is 0.38 and the particle size D90 is 180 μm.

[0034] Example 3 Polypeptide composition formulation: Total mass 1000g; (1) Active component: 200g total mass, accounting for 20% of the total mass of the composition; The active components, by weight, are as follows: 12 parts peptide combination, 16 parts prebiotic combination, and 2 parts plant extract combination. The specific amounts of each component are as follows: The total amount of the peptide combination is 85.72g, specifically including 35.72g of L-alanyl-L-glutamine, 21.43g of L-glycyl-L-glutamine, 14.29g of reduced glutathione, and 14.28g of L-tyrosyl-L-proline; the total amount of the prebiotic combination is 114.28g, specifically including 71.43g of fructooligosaccharides and 42.85g of galactooligosaccharides, all within the preset amount range; the total amount of the plant extract combination is 14.29g, specifically including 4.29g of curcumin and 10.00g of fucoidan.

[0035] The weight ratio of the polypeptide combination to the prebiotic combination is 1:1.33.

[0036] (2) Auxiliary materials: Total weight 800g; Anti-acid coating premix: 30g, accounting for 3% of the total mass of the composition; composed of HPMCP2 1.42g, talc 7.14g, and triethyl citrate 1.44g in a mass ratio of 3:1:0.2; Standard formulation excipients: mannitol 690g, crospovidone 75g, magnesium stearate 4g, citric acid 1g, total 770g.

[0037] Preparation method: S1. Weigh each component of the peptide combination according to the above formula, put them into a three-dimensional motion mixer, set the speed to 15 rpm, and the mixing time to 25 min to obtain peptide powder premix; weigh each component of prebiotic and plant extract according to the formula, mix them evenly to obtain excipient premix. S2. Using the equal incremental method, the peptide powder premix and the excipient premix are mixed in 3 batches, with each batch taking 20 minutes and the total mixing time taking 50 minutes. The mixture is then passed through an 80-mesh sieve to obtain the active component mixture. S3. Mix the active component mixture with mannitol, crospovidone, and citric acid evenly. After wet granulation, drying, and sizing, add magnesium stearate and mix for 10 min. Compress to obtain unmixed tablets. Coat with an acid-resistant coating premix to obtain polypeptide composition tablets. The resulting tablets have a water activity of 0.55 and a particle size D90 of 240 μm.

[0038] Comparative Example 1 Polypeptide composition formulation: Total mass 1000g; (1) Active component: 450g total mass, accounting for 45% of the total mass of the composition; The active ingredients, by weight, are as follows: 30 parts of a single polypeptide, 35 parts of a prebiotic combination, and 4 parts of a plant extract combination. The specific amounts of each component are as follows: the single polypeptide is L-alanyl-L-glutamine, with a total amount of 243.24g; the total amount of the prebiotic combination is 193.24g, specifically including 121.62g of fructooligosaccharides and 71.62g of galactooligosaccharides; the total amount of the plant extract combination is 13.52g, specifically including 5.41g of curcumin and 8.11g of fucoidan. The total amount of the above components is 450.00g of active ingredients.

[0039] (2) Auxiliary materials: Total weight 550g; Completely consistent with Example 1, namely, 50g of acid-resistant coating premix, 495g of conventional formulation excipients maltodextrin and 5g of steviol glycosides.

[0040] Preparation method: Completely consistent with Example 1.

[0041] Comparative Example 2 Polypeptide composition formulation: Total mass 1000g; (1) Active component: 450g total mass, accounting for 45% of the total mass of the composition; The active components, by weight, consist of: 30 parts of a polypeptide combination, 35 parts of a prebiotic combination, and 4 parts of a plant extract combination. The specific amounts of each component are as follows: The total amount of the polypeptide combination is 243.24g, specifically including 113.52g of L-alanyl-L-glutamine, 75.68g of L-glycyl-L-glutamine, and 54.04g of reduced glutathione. The L-tyrosyl-L-proline component is excluded, and the total amount of polypeptides is consistent with that in Example 1. The components and amounts of the prebiotic combination and the plant extract combination are completely consistent with those in Example 1. The total amount of all the above components, including the active components, is 450.00g.

[0042] (2) Auxiliary materials: Total weight 550g; Completely consistent with Example 1.

[0043] Preparation method: Completely consistent with Example 1.

[0044] Comparative Example 3 Polypeptide composition formulation: Total mass 1000g; (1) Active component: 450g total mass, accounting for 45% of the total mass of the composition; The active components are categorized by weight as follows: 30 parts of peptide combination and 35 parts of prebiotic combination, excluding the plant extract combination. The specific dosage of each component is as follows: The components and dosage of peptide combination and prebiotic combination are completely consistent with those in Example 1. The total dosage of the above components is 436.48g of active components. Any shortfall is made up to 450g with maltodextrin to maintain the total proportion of active components.

[0045] (2) Auxiliary materials: Total weight 550g; Completely consistent with Example 1.

[0046] Preparation method: Completely identical to Example 1, except that the mixing step of the plant extract components is omitted.

[0047] Comparative Example 4 Polypeptide composition formulation: Total mass 1000g; (1) Active component: 450g total mass, accounting for 45% of the total mass of the composition; The components and dosages are completely consistent with those in Example 1.

[0048] (2) Auxiliary materials: Total weight 550g; The acid-resistant coating premix was removed, and the original 50g of the acid-resistant coating premix was made up with maltodextrin. The remaining conventional formulation excipients were completely consistent with those in Example 1, namely 545g of maltodextrin and 5g of steviol glycosides, for a total of 550g.

[0049] Preparation method: It is completely consistent with Example 1, except that the coating process is removed.

[0050] Experimental Example 1 Experimental verification of the effect of peptide composition on improving intestinal damage: The classic dextran sulfate sodium (DSS)-induced mouse ulcerative colitis model was used to verify the effect of the above-mentioned peptide composition on improving intestinal problems. At the same time, the differences in the effects of different formulations were compared to verify the synergistic effect of the components.

[0051] Experimental materials and group assignments: Experimental animals: SPF-grade male C57BL / 6 mice, weighing 20±2g, a total of 70 mice, were randomly divided into 7 groups of 10 mice each: blank control group, model control group, Example 1 group, comparative example 1 group, comparative example 2 group, comparative example 3 group, and comparative example 4 group.

[0052] Modeling method: Except for the blank control group, mice in the other groups were allowed to drink 3% DSS aqueous solution for 7 consecutive days to establish an acute ulcerative colitis model, simulating common intestinal problems such as intestinal mucosal barrier damage, intestinal inflammation, and dysbiosis.

[0053] Administration method: After successful modeling, mice in each group were administered the drug by gavage for 14 consecutive days; the blank control group and the model control group were administered an equal volume of physiological saline by gavage; the dosage of the drugs in Example 1, Comparative Example 1, Comparative Example 2, Comparative Example 3 and Comparative Example 4 was 2g / 60kg body weight based on the active component, and the corresponding polypeptide compositions prepared in Example 1, Comparative Example 1, Comparative Example 2, Comparative Example 3 and Comparative Example 4 were administered.

[0054] Detection indicators and experimental results, such as Figure 1 As shown: (1) Disease Activity Index (DAI) score: Changes in mouse body weight, fecal characteristics, and blood in stool were recorded. The DAI score was calculated, with a higher score indicating more severe intestinal damage. The results are shown in Table 1 below.

[0055] Table 1. DAI scores of mice in each group on day 14 (mean ± standard deviation, n=10)

[0056] ** indicates that the difference is extremely significant compared with the model control group (P < 0.01); ## indicates that the difference is significant compared with all comparative groups (P < 0.05).

[0057] (2) Colonic histopathology and intestinal mucosal barrier related indicators: After the experiment, mouse colon tissue was taken, stained with hematoxylin and eosin (HE), and pathologically scored. The relative expression levels of the intestinal tight junction proteins Occludin and Claudin-1 were detected by Western blot. The higher the protein expression level, the better the intestinal mucosal barrier repair effect. The results are shown in Table 2 below.

[0058] Table 2. Colonic pathological scores and tight junction protein expression results in each group of mice (mean ± standard deviation, n=10)

[0059] ** indicates that the difference is extremely significant compared with the model control group (P < 0.01); ## indicates that the difference is significant compared with all comparative groups (P < 0.05).

[0060] (3) Results of intestinal inflammatory factors and flora detection: Inflammatory factor detection: The levels of pro-inflammatory factors such as TNF-α, IL-6, and IL-1β in the colon tissue of mice in Example 1 group decreased by more than 85% compared with the model control group, and were significantly lower than all comparative groups (P<0.05), indicating the best anti-inflammatory effect; Intestinal flora detection: In Example 1, the abundance of beneficial bacteria such as Bifidobacterium and Lactobacillus in the feces of mice was increased by 4.2 times compared with the model control group, while the abundance of harmful bacteria such as Escherichia coli decreased by 78%. The flora regulation effect was significantly better than all comparative groups.

[0061] Experimental conclusions: The above-mentioned polypeptide composition can significantly improve DSS-induced intestinal damage in mice, reduce DAI scores and pathological scores, repair the intestinal mucosal barrier, inhibit intestinal inflammation, regulate intestinal flora balance, and has a clear improvement effect on a variety of intestinal problems. The overall effect of the Example 1 group is significantly better than all comparative groups. The combination of four specific short peptides, the ternary synergistic system, and the acid-resistant coating design have a synergistic effect and have a significant advantage over single-component and simple compounding schemes.

[0062] Therefore, this invention utilizes the aforementioned polypeptide composition and its preparation method, along with its improved application in addressing intestinal problems. The composition simultaneously acts on intestinal mucosal repair, intestinal flora regulation, and intestinal inflammation suppression, significantly improving intestinal mucosal barrier damage, flora imbalance, irritable bowel syndrome, and antibiotic-associated diarrhea, with effects significantly superior to single-component or simple binary compound products. The various small-molecule short peptides used can directly provide energy to intestinal epithelial cells, reduce oxidative stress damage, inhibit cell apoptosis, enhance intestinal tight junctions, rapidly promote the healing of damaged mucosa, and improve intestinal barrier integrity. The prebiotic combination selectively proliferates beneficial bacteria and inhibits harmful bacteria, optimizing the intestinal microecological structure, increasing short-chain fatty acid levels, providing a favorable environment for intestinal mucosal repair, and forming a long-lasting conditioning effect. An acid-resistant coating system protects the active ingredients, reducing their degradation loss in gastric acid, increasing the proportion of active ingredients reaching the intestines, and improving overall bioavailability and stability.

[0063] The composition is scientifically formulated with appropriate excipients, making it suitable for producing various oral solid dosage forms such as powders, granules, capsules, and tablets. It exhibits high mixing uniformity and stable quality, facilitating production and long-term use. All raw materials used are conventionally safe, food-grade or pharmaceutical-grade ingredients, with no irritation or significant side effects. It can be used to prepare food, health food, and special medical purpose formula foods, and is suitable for a wide range of people.

[0064] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A polypeptide composition comprising an active ingredient and excipients, characterized in that, The active components include a polypeptide combination, a prebiotic combination, and a plant extract combination; by weight, the active components include: 11-53 parts of the polypeptide combination, 15-50 parts of the prebiotic combination, and 1.5-13 parts of the plant extract combination; the active components account for 20%-70% of the total mass of the polypeptide composition, with the remainder being excipients; the excipients include an acid-resistant coating premix accounting for 3%-8% of the total mass of the polypeptide composition, and the remainder being conventional pharmaceutical excipients, wherein the conventional pharmaceutical excipients are selected from at least one of fillers, disintegrants, lubricants, and flavoring agents; The polypeptide combination includes 5-20 parts of L-alanyl-L-glutamine, 3-15 parts of L-glycyl-L-glutamine, 2-10 parts of reduced glutathione, and 1-8 parts of L-tyrosyl-L-proline. The prebiotic combination includes 10-30 parts of fructooligosaccharides and 5-20 parts of galactooligosaccharides; The plant extract combination includes 0.5 to 5 parts curcumin and 1 to 8 parts fucoidan.

2. The polypeptide composition according to claim 1, characterized in that, The weight ratio of the polypeptide combination to the prebiotic combination is 1:(0.8-2.5).

3. The polypeptide composition according to claim 1, characterized in that, The acid-resistant coating premix is ​​composed of hydroxypropyl methylcellulose phthalate, talc, and triethyl citrate in a mass ratio of 3:1:0.

2.

4. The polypeptide composition according to claim 1, characterized in that, By weight, the filler is selected from at least one of maltodextrin, microcrystalline cellulose, and mannitol; the disintegrant is selected from at least one of crospovidone and sodium carboxymethyl starch; the lubricant is selected from at least one of magnesium stearate and micronized silica; and the flavoring agent is selected from at least one of steviol glycosides and citric acid.

5. The polypeptide composition according to claim 1, characterized in that, The dosage form of the polypeptide composition is an oral solid dosage form, specifically a powder, granules, capsules, or tablets; the water activity of the oral solid dosage form is ≤0.6, and the particle size D90 is 150-250 μm.

6. A method for preparing a polypeptide composition according to any one of claims 1-5, characterized in that, Includes the following steps: S1. Weigh each component of the polypeptide combination according to the preset weight parts, mix them evenly to obtain a peptide powder premix; weigh each component of the prebiotic combination and the plant extract combination according to the preset weight parts, mix them evenly to obtain an excipient premix. S2. Mix the peptide powder premix and the excipient premix in equal increments, and pass them through an 80-120 mesh sieve to obtain a mixture of active components. S3. The active ingredient mixture is mixed evenly with food or pharmaceutically acceptable excipients in a preset ratio, and then processed through a molding process corresponding to the dosage form to obtain the polypeptide composition.

7. The method for preparing the polypeptide composition according to claim 6, characterized in that, The mixing of the peptide powder premix in step S1 is a three-dimensional motion mixing, with a mixing time of 15-25 min and a rotation speed of 15-25 rpm; the mixing time of a single mixing in step S2 using the equal incremental mixing method is 10-20 min, and the total mixing time is 30-50 min.

8. The use of the polypeptide composition according to any one of claims 1-5 in the preparation of food, health food or special medical purpose formulation for improving intestinal problems.

9. The application according to claim 8, characterized in that, The intestinal problems mentioned include damage to the intestinal mucosal barrier, intestinal flora imbalance, remission of inflammatory bowel disease, irritable bowel syndrome, antibiotic-associated diarrhea, or stress-induced intestinal damage.

10. The application according to claim 8, characterized in that, The daily oral dose of the polypeptide composition is 0.5–5 g per 60 kg body weight, based on the active ingredient.

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