Selenium-rich composite tablet as well as preparation method and application thereof

Abstract

The invention provides a selenium-rich composite tablet and a preparation method and application thereof, and belongs to the technical field of biological medicine preparations, the tablet takes selenium-rich yeast, L-selenium-methyl selenocysteine, compound protein peptide and soybean protein hydrolysate as main components, and the bioavailability and synergistic effect of selenium are remarkably improved by optimizing the raw material ratio. Wherein the compound protein peptide is modified by combining a step enzymolysis technology with selenylation, so that the activity and the stability of the peptide are enhanced; the soybean protein hydrolysate is subjected to a specific enzymolysis process, the nutritional value and the absorption efficiency of the tablet are further improved, the selenium-rich composite tablet has the remarkable effects of improving the immunity of the human body and resisting oxidation and aging, and the defects that a traditional selenium supplementing preparation is low in absorption rate and poor in stability are overcome.

Description

Technical Field

[0001] This invention belongs to the field of biopharmaceutical preparation technology, specifically relating to a selenium-enriched composite tablet, its preparation method, and its uses. Background Technology

[0002] Selenium is an essential trace element for the human body, possessing important physiological functions such as antioxidation, enhanced immunity, and anti-aging. However, the uneven distribution of selenium in nature and its low absorption and utilization rate in the human body have led to widespread selenium deficiency, especially in selenium-deficient areas. Traditional selenium supplementation methods mainly include inorganic selenium (such as sodium selenite) and organic selenium (such as selenium-enriched yeast), but these forms have significant limitations. While inorganic selenium is less expensive, it has low bioavailability and potentially high toxicity; organic selenium forms such as selenium-enriched yeast have better safety profiles, but their absorption efficiency is still limited by the carrier form and the gastrointestinal environment. Furthermore, the functionality of a single selenium source is limited, making it difficult to meet the body's multiple selenium requirements.

[0003] Therefore, developing a highly efficient, safe, and synergistic compound selenium supplement has become a current research focus.

[0004] In view of this, the present invention is hereby proposed. Summary of the Invention

[0005] The primary objective of this invention is to provide a selenium-enriched composite tablet. By combining two organic selenium sources—selenium-enriched yeast and L-selenomethylselenocysteine—and introducing a stepwise enzymatic hydrolysis technique and selenization modification process, a highly efficient and stable selenium-enriched composite tablet has been developed. This tablet not only enhances the synergistic effect of selenium through optimized raw material ratios but also significantly enhances the absorption and utilization of selenium by utilizing the synergistic effect of composite protein peptides and soybean protein hydrolysate. In particular, the combination of marine collagen peptides and selenized whey protein hydrolysate not only improves the stability of the peptides but also achieves targeted release of selenium through selenization modification.

[0006] The second objective of this invention is to provide a method for preparing the above-mentioned selenium-enriched composite tablets, which employs a wet granulation process to ensure the uniformity of the tablets and the feasibility of industrial production.

[0007] A third objective of this invention is to provide the use of the above-mentioned selenium-enriched compound tablet in the preparation of a drug for improving human immunity, anti-oxidation, or anti-aging.

[0008] In order to achieve the above-mentioned objectives of the present invention, the following technical solution is adopted: A selenium-enriched compound tablet, comprising the following raw materials by weight percentage: Selenium-enriched yeast 40-60%; L-Selenium-methylselenocysteine ​​10-25%; Complex protein peptides 15-30%; Soy protein hydrolysate 5-10%; Additives 5-15%.

[0009] This invention provides a selenium-enriched compound tablet. Its core, through specific raw material combinations and optimized proportions, significantly improves the bioavailability, stability, and functionality of selenium. The tablet's main components are selenium-enriched yeast, L-selenomethylselenocysteine, complex protein peptides, soybean protein hydrolysate, and excipients. Selenium-enriched yeast, as a mature organic selenium source, primarily exists in the form of selenomethionine, exhibiting good safety and stability; however, its absorption efficiency is significantly affected by the intestinal environment when used alone. L-selenomethylselenocysteine, on the other hand, is an active small-molecule organic selenium compound that can directly participate in the human selenium metabolism pathway. The combination of these two ingredients in a specific ratio retains the sustained-release properties of selenium-enriched yeast while compensating for the selenium deficiency in yeast through the rapid absorption of small-molecule selenium, forming a synergistic effect. Furthermore, the compound... Synthetic peptides are obtained by stepwise enzymatic hydrolysis to produce marine collagen peptides. These marine collagen peptides are then mixed with whey protein hydrolysate in a specific ratio (2:1-1:2). After selenization modification of the whey protein hydrolysate, it not only provides abundant amino acids and peptide chains as carriers for selenium, but also enhances the targeting and stability of selenium through selenium-peptide bond binding. The marine collagen peptides are rich in hydrophilic amino acids such as glycine and proline, which can improve the solubility of tablets. The cysteine ​​residues in the whey protein hydrolysate are selenized to form a stable selenocysteine ​​structure, further preventing premature release of selenium in the acidic environment of the stomach. In addition, the addition of soybean protein hydrolysate, through targeted enzymatic hydrolysis by alkaline protease, produces small molecule peptides, which not only enhance the nutritional value of the tablets, but also promote the dispersion and absorption of other active ingredients due to their surface activity.

[0010] More importantly, the formulation of this invention solves three major bottleneck problems of traditional selenium supplements: First, by combining two selenium sources and controlling the ratio of raw materials, a balance between rapid absorption and long-term release of selenium is achieved, avoiding the problems of low bioavailability or excessively rapid metabolism of a single selenium source; second, by utilizing the stepwise enzymatic hydrolysis and selenization modification technology of complex protein peptides, a stable selenium-peptide delivery system is constructed, which significantly improves the retention rate of selenium in the gastrointestinal environment; and third, through the synergistic effect of soybean protein hydrolysate and excipients, the physical properties and biocompatibility of the tablets are optimized.

[0011] Preferably, as a further specific embodiment, the composite protein peptide is a mixture of marine collagen peptides obtained by stepwise enzymatic hydrolysis with pepsin and trypsin and whey protein hydrolysate.

[0012] This invention further defines the complex protein peptide in the selenium-enriched compound tablets, specifying that the complex protein peptide is a mixture of marine collagen peptides obtained through stepwise enzymatic hydrolysis with pepsin and trypsin, and whey protein hydrolysate. This stepwise enzymatic hydrolysis technology, combined with a specific protein source, significantly enhances the functionality of the complex protein peptide and its effectiveness as a selenium carrier, thereby further improving the bioavailability and stability of the entire selenium-enriched compound tablet. In the gradient enzymatic hydrolysis process, pepsin and trypsin are used, each acting on different peptide bond sites. Pepsin preferentially cleaves the carboxyl-terminal peptide bonds of aromatic amino acids under acidic conditions, while trypsin specifically cleaves the carboxyl-terminal peptide bonds of arginine and lysine under neutral to slightly alkaline conditions. By using these two enzymes in stages, marine collagen can be hydrolyzed more thoroughly, generating peptides with a more uniform molecular weight distribution and rich in specific amino acid sequences. These peptides not only have higher solubility and absorption but also provide more active sites for subsequent selenization modification.

[0013] Marine collagen peptides, as collagen derived from marine organisms, are rich in glycine, proline, and hydroxyproline. The special helical structure formed by these amino acids exposes more hydrophobic and hydrophilic regions after enzymatic hydrolysis, thereby enhancing the amphiphilicity of the peptides and making them more likely to bind with selenium compounds and form stable complexes in the gastrointestinal environment. The introduction of whey protein hydrolysate supplements the lack of sulfur-containing amino acids in marine collagen peptides. The thiol groups of these amino acids are ideal sites for selenization modification and can react with selenium sources such as sodium selenite to generate stable selenocysteine ​​structures. By mixing these two protein hydrolysates in a specific ratio, this invention achieves complementary amino acid composition and functional synergy, avoiding the functional limitations of single-source peptides and further enhancing the selenium binding capacity through selenization modification.

[0014] Preferably, as a further specific embodiment, the mass ratio of the marine collagen peptides to whey protein hydrolysate is (2:1) to (1:2).

[0015] This invention further defines the selenium-enriched compound tablets by specifying that the mass ratio of marine collagen peptides to whey protein hydrolysate is 2:1 to 1:2. This specific ratio range creates an ideal balance of amino acid composition, enabling the compound protein peptides to maintain sufficient structural stability while possessing excellent selenium-binding capacity. The marine collagen peptides are rich in special amino acids such as glycine, proline, and hydroxyproline. The unique helical structure formed by these amino acids provides a stable spatial conformation for the complex. The whey protein hydrolysate contributes a large number of sulfur-containing amino acids. The active thiol groups of these amino acids are key sites for selenization reactions. When the ratio of the two is controlled between 2:1 and 1:2, the compound protein peptides will not suffer from insufficient selenium-binding sites due to excessive collagen peptides, nor will the overall stability of the peptide chain be affected by excessive whey protein hydrolysate.

[0016] Preferably, as a further specific embodiment, the whey protein hydrolysate is selenized.

[0017] This invention specifies that the whey protein hydrolysate undergoes selenization modification. By subjecting the whey protein hydrolysate to specific selenization treatment, the performance limitations of traditional selenium supplements are fundamentally changed, solving key issues such as the stability and bioavailability of selenium in the carrier system. The selenization modification of the whey protein hydrolysate is not a simple physical mixing or adsorption, but rather a precisely controlled chemical reaction that covalently binds selenium atoms to specific sites on the peptide chain. This chemical modification allows the selenium element to form a stable organic selenium compound with the protein peptide carrier. Essentially, it utilizes the abundant sulfur-containing amino acids in the whey protein hydrolysate and selenium sources such as sodium selenite to undergo a redox reaction under specific conditions, generating stable selenocysteine ​​and other selenoamino acid structures. This chemical bonding method has significant advantages over physical mixing or simple complexation. On the one hand, selenium atoms are firmly fixed to the peptide chain backbone through covalent bonds, preventing premature release or conversion in the gastrointestinal environment. On the other hand, the three-dimensional structure of the peptide chain provides a protective microenvironment for the selenium element, enabling it to resist degradation by gastric acid and proteases during digestion, ensuring that the selenium element can be targeted and delivered to the intestinal absorption site.

[0018] Preferably, as a further specific embodiment, the soybean protein hydrolysate is a polypeptide mixture obtained by alkaline protease hydrolysis.

[0019] This invention further defines the soybean protein hydrolysate, specifying that it is a polypeptide mixture obtained by alkaline protease hydrolysis. The alkaline protease has unique site specificity in hydrolyzing soybean protein, primarily cleaving the carboxyl-terminal peptide bonds of hydrophobic amino acids. This selective hydrolysis produces small peptide fragments that retain sufficient functional active sites and possess ideal solubility and permeability, providing an ideal molecular basis for its subsequent use as a selenium carrier and nutritional supplement. Compared with conventional neutral or complex proteases, the soybean peptides produced by alkaline protease hydrolysis have a more uniform molecular weight distribution. Peptides within this specific molecular weight range will not lose their carrier function due to excessively small molecular weight, nor will they affect absorption efficiency due to excessively large molecular weight.

[0020] More importantly, the soybean protein hydrolysate obtained by alkaline protease hydrolysis exhibits unique multi-level structural characteristics. At the primary structural level, the C-terminus of the peptides produced by enzymatic hydrolysis is mostly hydrophobic amino acids. This amphiphilic structure allows them to self-assemble into stable micelle structures in aqueous solution, providing an ideal encapsulation environment for hydrophobic active ingredients. At the higher structural level, these peptides form dynamic supramolecular assemblies through intermolecular interactions. This special morphology significantly increases the specific surface area, which is beneficial for the loading and release of active ingredients. More importantly, certain specific peptides in soybean protein hydrolysate can undergo molecular recognition and co-assembly with complex protein peptides to form a more stable hybrid carrier system. When soybean protein hydrolysate is mixed with marine collagen peptides / selenized whey protein hydrolysate in a specific ratio, core-shell structured nanoparticles are spontaneously formed. The more hydrophobic peptides aggregate to form the core, while the hydrophilic peptides are distributed on the surface. This self-assembly structure not only improves the encapsulation efficiency of selenium but also endows the carrier system with pH-responsive release characteristics, remaining stable under gastric acid conditions and orderly releasing active ingredients in the neutral environment of the intestine.

[0021] This invention also provides a method for preparing the above-mentioned selenium-enriched composite tablet, comprising the following steps: Mix the selenium-enriched yeast, L-seleno-methylselenocysteine, complex protein peptides, soybean protein hydrolysate, and excipients evenly. The granules are prepared by wet granulation and then compressed into tablets to obtain the final product.

[0022] Preferably, as a further specific embodiment, the method for preparing the complex protein peptide is as follows: After crushing the cod skin, it was sequentially hydrolyzed with pepsin and trypsin for 4-8 hours to obtain the hydrolysis product. The enzymatic hydrolysate is mixed with whey protein hydrolysate and then selenized to obtain the final product.

[0023] This invention also specifically defines the preparation method of the complex protein peptide, revealing a technical solution of pulverizing cod skin and sequentially hydrolyzing it with pepsin and trypsin for 4-8 hours, then mixing the hydrolysate with whey protein hydrolysate and performing selenization modification. By precisely controlling the hydrolysis conditions and subsequent processing, a complex protein peptide system with unique selenium carrier function is developed. Cod skin, as an important source of marine collagen, is rich in glycine-XY repeating sequences (X is usually proline, and Y is usually hydroxyproline) in its molecular structure. This special triple helix conformation can produce peptides with specific biological activities under moderate enzymatic hydrolysis conditions. Therefore, this invention first uses pepsin for preliminary hydrolysis under acidic conditions to selectively cleave the carboxyl-terminal peptide bonds of aromatic amino acids, thus moderately relaxing the tight collagen helix structure. Subsequently, under neutral to slightly alkaline conditions, trypsin is used to specifically cleave the carboxyl-terminal peptide bonds of arginine and lysine, producing functional peptides with concentrated molecular weight distribution.

[0024] Preferably, as a further specific embodiment, the selenization modification method involves reacting whey protein hydrolysate with sodium selenite followed by dialysis purification.

[0025] This invention further specifies the method of selenization modification, clearly indicating a technical solution of reacting whey protein hydrolysate with sodium selenite followed by dialysis purification. By precisely defining the selenization reaction conditions and purification process, key issues such as stability, safety, and bioavailability in the binding of selenium to protein peptides are solved. The reaction between whey protein hydrolysate and sodium selenite is not a simple mixing and adsorption, but a redox process occurring under specific conditions. The free thiol groups in the whey protein peptide chains act as electron donors, converting the selenium in sodium selenite into selenium. 47 Restore to Se 2- At the same time, a stable selenocysteine ​​structure is formed.

[0026] Preferably, as a further specific embodiment, the binder in the wet granulation is a polyvinylpyrrolidone solution, and the amount used is 3-8% of the total mass of the material.

[0027] The present invention also provides the use of the above-mentioned selenium-enriched compound tablets in the preparation of drugs for improving human immunity, anti-oxidation or anti-aging.

[0028] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) This invention provides a selenium-enriched composite tablet. By combining two organic selenium sources, selenium-enriched yeast and L-seleno-methylselenocysteine, and introducing stepwise enzymatic hydrolysis technology and selenization modification process, a highly efficient and stable selenium-enriched composite tablet is developed. This tablet not only enhances the synergistic effect of selenium by optimizing the raw material ratio, but also significantly enhances the absorption and utilization of selenium by utilizing the dual carrier effect of composite protein peptides and soybean protein hydrolysate. Among them, the combination of marine collagen peptides and selenized whey protein hydrolysate not only improves the stability of the peptides, but also achieves targeted release of selenium through selenization modification.

[0029] (2) The present invention provides a method for preparing a selenium-enriched composite tablet as described above. The preparation method adopts a wet granulation process, which ensures the uniformity of the tablet and the feasibility of industrial production.

[0030] (3) The present invention also provides the use of the above-mentioned selenium-enriched compound tablet in the preparation of drugs for improving human immunity, anti-oxidation or anti-aging. Detailed Implementation

[0031] The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. However, those skilled in the art will understand that the embodiments described below are some embodiments of the present invention, but not all embodiments, and are only used to illustrate the present invention, and should not be regarded as limiting the scope of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0032] To more clearly illustrate the technical solutions in this invention, specific embodiments are described below.

[0033] Example 1: 1. Raw material composition and source Selenium-enriched yeast: 60% (Lesaffre, USA, LY117, selenium content 2000±200μg / g). L-Seleno-methylselenocysteine: 10% (Sigma-Aldrich, purity ≥98%). Complex protein peptides: 15% (marine collagen peptides: whey protein hydrolysate = 2:1); Soybean protein hydrolysate: 5% (Shandong Yuwang Group, alkaline protease hydrolysis); Excipients: 10% (microcrystalline cellulose, magnesium stearate); 2. Preparation of complex protein peptides Marine collagen peptides: Cod skin pretreatment: After cutting cod skin (Norwegian Marine Harvest) into pieces, add 0.1M HCl (pH 2.0) at a ratio of 1:10 (w / v), add pepsin, and hydrolyze by shaking at 35°C for 2 hours; Trypsin hydrolysis: Adjust pH to 7.5, add trypsin (1.5% substrate mass), hydrolyze at 35℃ for 2 hours, inactivate enzyme, centrifuge (8000 rpm, 20 minutes), and freeze dry; Selenized whey protein hydrolysate: Whey protein hydrolysis: Whey protein was hydrolyzed with 2.4 L of Alcalase (4% enzyme concentration, pH 8.5, 50℃) for 4 hours, followed by ultrafiltration (3000 Da cutoff). Selenization modification: The hydrolysate was reacted with sodium selenite for 2 hours, and then purified by dialysis to remove unreacted raw materials; Compound: Marine collagen peptides and selenized whey protein hydrolysate are mixed in a 2:1 ratio; 3. Preparation of soybean protein hydrolysate Enzymatic hydrolysis: Soy protein isolate (5% solution) was hydrolyzed with 2.4L of Alcalase (4% enzyme amount, pH 8.5, 50℃) to DH=18%, and after enzyme inactivation, it was ultrafiltered (3000Da) and spray dried. 4. Wet granulation and tableting Mixing: All raw materials are mixed after passing through an 80-mesh sieve; Granulation: PVP solution (3% of material mass) is used as binder, wet granulation (30 mesh sieve); Tableting: The granules are dried and then compressed into tablets (hardness 80-100N, disintegration time ≤15 minutes).

[0034] Example 2: 1. Raw material composition and source Selenium-enriched yeast: 40% (Lesaffre, USA, LY117, selenium content 2000±200μg / g). L-Selenium-methylselenocysteine: 15% (Sigma-Aldrich, purity ≥98%). Complex protein peptides: 30% (marine collagen peptides: whey protein hydrolysate = 2:1); Soybean protein hydrolysate: 10% (Shandong Yuwang Group, alkaline protease hydrolysis); Excipients: 5% (microcrystalline cellulose, magnesium stearate); 2. Preparation of complex protein peptides Marine collagen peptides: Cod skin pretreatment: After cutting cod skin (Norwegian Marine Harvest) into pieces, add 0.1M HCl (pH 2.0) at a ratio of 1:10 (w / v), add pepsin, and hydrolyze by shaking at 37°C for 4 hours; Trypsin hydrolysis: Adjust pH to 7.5, add trypsin (1.5% substrate mass), hydrolyze at 37°C for 4 hours, inactivate enzyme, centrifuge (8000 rpm, 20 minutes), and freeze dry; Selenized whey protein hydrolysate: Whey protein hydrolysis: Whey protein was hydrolyzed with 2.4 L of Alcalase (4% enzyme concentration, pH 8.5, 50℃) for 4 hours, followed by ultrafiltration (3500 Da cutoff). Selenization modification: The hydrolysate was reacted with sodium selenite for 2 hours and then purified by dialysis; Compound: Marine collagen peptides and selenized whey protein hydrolysate are mixed in a 1:2 ratio; 3. Preparation of soybean protein hydrolysate Enzymatic hydrolysis: Soy protein isolate (5% solution) was hydrolyzed with 2.4L of Alcalase (4% enzyme amount, pH 8.5, 50℃) to DH=18%, and after enzyme inactivation, it was ultrafiltered (3000Da) and spray dried. 4. Wet granulation and tableting Mixing: Mix all ingredients thoroughly; Granulation: PVP solution (8% of material mass) is used as binder, wet granulation (30 mesh sieve); Tableting: The granules are dried and then compressed into tablets (hardness 80-100N, disintegration time ≤15 minutes).

[0035] Example 3: 1. Raw material composition and source Selenium-enriched yeast: 50% (Lesaffre, USA, LY117, selenium content 2000±200μg / g); L-Seleno-methylselenocysteine: 25% (Sigma-Aldrich, purity ≥98%) Complex protein peptides: 15% (marine collagen peptides: whey protein hydrolysate = 2:1); Soybean protein hydrolysate: 5% (Shandong Yuwang Group, alkaline protease hydrolysis); Excipients: 5% (microcrystalline cellulose, magnesium stearate); 2. Preparation of complex protein peptides Marine collagen peptides: Cod skin pretreatment: After cutting cod skin (Norwegian Marine Harvest) into pieces, add 0.1M HCl (pH 2.0) at a ratio of 1:10 (w / v), add pepsin, and hydrolyze by shaking at 37°C for 4 hours; Trypsin hydrolysis: Adjust pH to 7.5, add trypsin (1.5% substrate mass), hydrolyze at 37°C for 4 hours, inactivate enzyme, centrifuge (8000 rpm, 20 minutes), and freeze dry; Selenized whey protein hydrolysate: Whey protein hydrolysis: Whey protein was hydrolyzed with 2.4 L of Alcalase (4% enzyme concentration, pH 8.5, 50℃) for 4 hours, followed by ultrafiltration (3500 Da cutoff). Selenization modification: The hydrolysate was reacted with sodium selenite for 2 hours and then purified by dialysis; Compound: Marine collagen peptides and selenized whey protein hydrolysate are mixed in a 1:2 ratio; 3. Preparation of soybean protein hydrolysate Enzymatic hydrolysis: Soy protein isolate (5% solution) was hydrolyzed with 2.4L of Alcalase (4% enzyme amount, pH 8.5, 50℃) to DH=18%, and after enzyme inactivation, it was ultrafiltered (3000Da) and spray dried. 4. Wet granulation and tableting Mixing: Mix all the ingredients; Granulation: PVP solution (8% of material mass) is used as binder, wet granulation (30 mesh sieve); Tableting: The granules are dried and then compressed into tablets (hardness 80-100N, disintegration time ≤15 minutes).

[0036] Example 4: 1. Raw material composition and source Selenium-enriched yeast: 42.5% (Lesaffre, USA, LY117, selenium content 2000±200μg / g). L-Seleno-methylselenocysteine: 17.5% (Sigma-Aldrich, purity ≥98%). Complex protein peptides: 22.5% (marine collagen peptides: whey protein hydrolysate = 2:1); Soybean protein hydrolysate: 7.5% (Shandong Yuwang Group, alkaline protease hydrolysis); Excipients: 10% (microcrystalline cellulose, magnesium stearate); 2. Preparation of complex protein peptides Marine collagen peptides: Cod skin pretreatment: After cutting cod skin (Norwegian Marine Harvest) into pieces, add 0.1M HCl (pH 2.0) at a ratio of 1:10 (w / v), add pepsin, and hydrolyze by shaking at 37°C for 3 hours; Trypsin hydrolysis: Adjust pH to 7.5, add trypsin (1.5% substrate mass), hydrolyze at 37°C for 3 hours, inactivate enzyme, centrifuge (8000 rpm, 20 minutes), and freeze dry; Selenized whey protein hydrolysate: Whey protein hydrolysis: Whey protein was hydrolyzed with 2.4L of Alcalase (4% enzyme concentration, pH 8.0, 50℃) for 3 hours, followed by ultrafiltration (3500 Da cutoff). Selenization modification: The hydrolysate was reacted with sodium selenite for 2 hours and then purified by dialysis; Compound: Marine collagen peptides and selenized whey protein hydrolysate are mixed in a 1:1 ratio; 3. Preparation of soybean protein hydrolysate Enzymatic hydrolysis: Soy protein isolate (5% solution) was hydrolyzed with 2.4L of Alcalase (4% enzyme amount, pH 8.5, 50℃) to DH=18%, and after enzyme inactivation, it was ultrafiltered (3000Da) and spray dried. 4. Wet granulation and tableting Mixing: Mix all the ingredients; Granulation: PVP solution (5.5% of material mass) is used as a binder, and wet granulation is performed (30-mesh sieve). Tableting: The granules are dried and then compressed into tablets (hardness 80-100N, disintegration time ≤15 minutes).

[0037] Comparative Example 1: The specific preparation steps are the same as in Example 4, except that the mass ratio of marine collagen peptides to whey protein hydrolysate is adjusted to 1:5.

[0038] Comparative Example 2: The specific preparation steps are the same as in Example 4, except that the mass ratio of marine collagen peptides to whey protein hydrolysate is adjusted to 5:1.

[0039] Comparative Example 3: The specific preparation steps are the same as in Example 4, except that the whey protein hydrolysate is not selenized.

[0040] Experiment Example 1: 1. Experimental Objective The superiority of the present invention over the prior art was verified by measuring the selenium bioavailability, antioxidant activity and immunomodulatory capacity of the selenium-enriched composite tablets prepared in Examples 1-4 and Comparative Examples 1-3.

[0041] 2. Experimental Materials and Methods 2.1 Experimental Materials 100 mg of selenium-enriched composite tablets prepared in Examples 1-4 and Comparative Examples 1-3; Simulated gastric juice: 0.1M HCl + pepsin (2mg / mL), pH 1.2; Simulated intestinal fluid: PBS (pH 6.8) + trypsin (10 U / mL), pH 6.8; Caco-2 cells (human colon cancer cell line, used for absorption experiments); DPPH (1,1-diphenyl-2-trinitrophenylhydrazine, used for antioxidant activity assays); RAW264.7 cells (mouse macrophage cell line, used for immunomodulation experiments). 2.2 Experimental Methods 2.2.1 Selenium bioavailability determination In vitro digestion model: After crushing 100mg of tablets, incubate them in simulated gastric fluid for 2 hours (37℃, 100rpm). Take 0.5mL of sample every 30min to stop the reaction, then centrifuge and collect the supernatant. The remaining mixture after gastric digestion was then adjusted to pH and transferred to simulated intestinal fluid for incubation for 4 hours. After centrifugation (10,000 rpm, 15 minutes), the supernatant was collected. The soluble selenium content was determined by combining the gastric and intestinal digestion supernatants (atomic fluorescence spectrometry). Caco-2 cell uptake experiment: The supernatant after in vitro digestion was co-incubated with Caco-2 cells for 2 hours, and the selenium content in the cells was measured. 2.2.2 Antioxidant activity assay (DPPH free radical scavenging rate) The supernatant after in vitro digestion was mixed with DPPH solution (0.1 mM) and reacted for 30 minutes. The absorbance at 517 nm was measured, and the clearance rate was calculated. 2.2.3 Immunomodulatory capacity assay (NO release) After stimulating RAW264.7 cells with LPS, they were incubated with the supernatant after in vitro digestion for 24 hours, and the NO content in the supernatant was measured (Griess reagent method). The final test results are shown in Table 1 below: Table 1 Test Results Group Soluble selenium content (μg / 100mg) Caco-2 cell uptake rate (%) DPPH clearance rate (%) NO release (μM) Example 1 52.3 76.3 83.9 41.2 Example 2 51.8 74.8 81.6 42.8 Example 3 53.6 75.3 85.4 43.6 Example 4 55.7 83.5 87.2 45.9 Comparative Example 1 38.2 59.1 67.8 27.6 Comparative Example 2 39.5 61.4 69.2 29.3 Comparative Example 3 34.9 55.4 62.5 26.8 This experiment demonstrates the superior efficacy of the selenium-enriched composite tablets of the present invention by testing the selenium bioavailability, antioxidant activity, and immunomodulatory capacity of the selenium-enriched composite tablets prepared in Examples 1-4 and Comparative Examples 1-3. Example 4 showed the best performance in all indicators, with a soluble selenium content of 55.7 μg / 100 mg, significantly higher than other groups. This reflects the synergistic effect of the specific ratio of selenium-enriched yeast and L-selenomethylselenocysteine. This ratio design (42.5% selenium-enriched yeast, 17.5% L-selenomethylselenocysteine) not only balances the rapid absorption and long-term release of selenium but also... The dual carrier effect of complex protein peptides and soybean protein hydrolysate further enhances the stability and targeting of selenium. The Caco-2 cell absorption experiment results show that the selenium absorption rate of Example 4 is 83.5%, which is significantly higher than that of Comparative Examples 1-3. This indicates that the optimized formula can effectively overcome the defect of low absorption rate of traditional selenium supplements. This high absorption performance is attributed to the stepwise enzymatic hydrolysis technology and selenization modification process of complex protein peptides. In this process, marine collagen peptides and selenized whey protein hydrolysate are mixed in a 1:1 mass ratio to form a stable selenium-peptide delivery system, thereby achieving precise release and efficient absorption of selenium in the gastrointestinal environment.

[0042] In terms of antioxidant activity, Example 4 showed a DPPH free radical scavenging rate of up to 87.2%, which was significantly better than other groups. This result is closely related to the bioavailability of selenium, because as the core component of glutathione peroxidase, the antioxidant capacity of selenium directly depends on its effective concentration in the body. Example 4 ensured a continuous supply of selenium in the body by optimizing the raw material ratio, thereby significantly improving the antioxidant effect.

[0043] In contrast, Comparative Examples 1 and 2, due to the imbalance of the complex protein peptide ratio (1:5 and 5:1), resulted in a further decrease in DPPH scavenging rates to 67.8% and 69.2%, respectively. This indicates that the specific ratio (1:1) of marine collagen peptides to whey protein hydrolysate is crucial for maintaining the activity and stability of selenium. Comparative Example 3, which was not selenized, had the lowest DPPH scavenging rate, fully demonstrating the key role of selenization modification in enhancing selenium binding capacity and antioxidant function.

[0044] The results of the immunomodulatory capacity assay further support the technical advantages of this invention. The NO release in Example 4 was 45.9 μM, significantly higher than other groups, indicating that it can effectively activate macrophages and enhance the body's immune response. This effect is complementary to the bioavailability and antioxidant activity of selenium, because selenium not only participates in the metabolic regulation of immune cells but also indirectly enhances immune function by reducing oxidative stress. The NO release in Comparative Examples 1-3 was generally low, especially in Comparative Example 3 (26.8 μM), further confirming the decisive influence of selenization modification and the ratio of complex protein peptides on functionality.

[0045] In summary, this experiment comprehensively evaluated the performance of selenium-enriched compound tablets through systematic in vitro and cellular experiments. The data results fully support the technical advantages and inventiveness of this invention. Example 4, as the optimal solution, showed significantly better performance than the comparative examples and existing technologies in terms of soluble selenium content, cell absorption rate, antioxidant activity, and immunomodulatory capacity. This verifies the significant progress made by this invention in formulation design, process optimization, and functional enhancement. This achievement not only provides a scientific basis for the development of selenium supplements but also offers an efficient and safe solution to address selenium deficiency and related health problems, possessing significant theoretical and practical value.

[0046] 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 the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A selenium-enriched compound tablet, characterized in that, The product comprises the following raw materials by weight percentage: Selenium-enriched yeast 40-60%; L-Selenium-methylselenocysteine ​​10-25%; Complex protein peptides 15-30%; Soy protein hydrolysate 5-10%; Additives 5-15%.

2. The selenium-enriched composite tablet according to claim 1, characterized in that, The complex protein peptide is a mixture of marine collagen peptides obtained by stepwise enzymatic hydrolysis with pepsin and trypsin, and whey protein hydrolysate.

3. The selenium-enriched composite tablet according to claim 2, characterized in that, The mass ratio of the marine collagen peptides to whey protein hydrolysate is (2:1) to (1:2).

4. The selenium-enriched composite tablet according to claim 2, characterized in that, The whey protein hydrolysate is selenized.

5. The selenium-enriched composite tablet according to claim 1, characterized in that, The soy protein hydrolysate is a mixture of polypeptides obtained by alkaline protease hydrolysis.

6. A method for preparing a selenium-enriched composite tablet as described in any one of claims 1-5, characterized in that, Includes the following steps: Mix the selenium-enriched yeast, L-seleno-methylselenocysteine, complex protein peptides, soybean protein hydrolysate, and auxiliary materials evenly. The granules are prepared by wet granulation and then compressed into tablets to obtain the final product.

7. The preparation method according to claim 6, characterized in that, The preparation method of the complex protein peptide is as follows: After crushing the cod skin, it was sequentially hydrolyzed with pepsin and trypsin for 4-8 hours to obtain the hydrolysis product. The enzymatic hydrolysate is mixed with whey protein hydrolysate and then selenized to obtain the final product.

8. The preparation method according to claim 7, characterized in that, The selenization modification method involves reacting whey protein hydrolysate with sodium selenite followed by dialysis purification.

9. The preparation method according to claim 6, characterized in that, The binder used in the wet granulation process is a polyvinylpyrrolidone solution, and the amount used is 3-8% of the total mass of the material.

10. Use of a selenium-enriched compound tablet as described in any one of claims 1-5 in the preparation of a medicament for improving human immunity, anti-oxidation, or anti-aging.