A tablet formulation for reducing hyperhomocysteinemia

Abstract

This invention discloses a tablet formulation for reducing hyperhomocysteinemia, belonging to the field of health food technology. The formulation uses selenium-enriched yeast, pyridoxine hydrochloride, folic acid, and cyanocobalamin as core active ingredients, and microcrystalline cellulose, maltodextrin, magnesium stearate, calcium carbonate, and coating premixes (hydroxypropyl methylcellulose, polyethylene glycol, talc, and titanium dioxide) as excipients, prepared through a specific process. This invention solves the problems of poor stability of active ingredients, large content deviations, and difficulty in ensuring safety in existing similar products by limiting the compliant sources of each raw material, strictly controlling physicochemical and microbiological indicators, and standardizing production process parameters. Each tablet contains 67.5-99 μg of selenium, 6.4-10 mg of vitamin C, 5.6-10 μg of vitamin D, and 320-500 μg of folic acid, with a disintegration time ≤60 min. All hygiene indicators meet the requirements of GB 16740, exhibiting high stability, high absorption rate, and controllable safety, making it suitable for individuals requiring reduction of hyperhomocysteinemia.

Description

Technical Field

[0001] This invention belongs to the field of health food technology, specifically referring to a tablet formulation for reducing hyperhomocysteinemia. Background Technology

[0002] Selenium is one of the essential trace elements for the human body. It participates in the synthesis of glutathione peroxidase and has antioxidant, immune-boosting, and cardiovascular-protective effects; Vitamin B6, Vitamin B1... 12 Selenium, like folic acid, belongs to the B vitamins and participates in key physiological processes such as amino acid metabolism, nucleic acid synthesis, and erythrocyte production. Deficiency can lead to anemia, nervous system damage, and neural tube defects in fetuses. With changes in modern dietary structures, insufficient intake of selenium and various vitamins is common among Chinese residents. Therefore, developing safe, stable, and highly effective selenium and multivitamin supplements is of significant practical importance.

[0003] The following are the prominent problems with currently available selenium-enriched vitamin complex products: 1. Insufficient compliance of raw materials: Some products use inorganic selenium (such as sodium selenite) as a selenium source, which has low bioavailability and high toxicity; the purity of vitamin raw materials is insufficient, and there is a high risk of exceeding the standards for heavy metals, arsenic salts and other contaminants, which does not meet the requirements for raw material safety in GB 16740 "National Food Safety Standard for Health Food".

[0004] 2. Poor stability of active ingredients: Selenium and B vitamins are chemically reactive and easily degraded by light, humidity, and temperature, resulting in a decrease of more than 20% in the content of active ingredients within the product's shelf life, failing to meet the labeled values; some products do not use premixing technology to treat trace amounts of active ingredients (such as vitamins). This leads to uneven mixing, with content differences between tablets reaching ±15% or more.

[0005] 3. Inadequate quality control system: The limits for physicochemical and microbiological indicators of existing products are lenient, and the limits for heavy metals such as lead and arsenic are higher than the requirements of GB 16740; the production process lacks standardized control, there are large batch-to-batch differences, the risk of microbial contamination is high, the total number of colonies often exceeds 30,000 CFU / g, and the amount of mold and yeast exceeds 50 CFU / g.

[0006] 4. Low safety of coating materials: Traditional coatings mostly use sugar coating or ordinary film coating. The heavy metal and arsenic salt limits of excipients such as talc and titanium dioxide in the coating materials are not strictly controlled. In addition, the weight gain of the coating is uneven and the disintegration time exceeds 60 minutes, which affects the absorption efficiency of the product.

[0007] 5. Non-standard labeling: Some products failed to label health food warning statements as required, and contained exaggerated claims and implied disease prevention functions, which did not meet the requirements of the "Guidelines for Labeling Warning Statements for Health Foods".

[0008] To address the aforementioned issues, this invention has developed a Xue Tong Qing brand selenium multivitamin tablet (Food and Health Product Approval Number G202613000661; Enterprise Standard Q / WSK0012S-2026 of Shijiazhuang Weishikang Biotechnology Co., Ltd.) that meets national standards, has stable active ingredients, and is safe and controllable, by strictly limiting the source of raw materials, optimizing the premixing process, standardizing production parameters, and improving the quality control system, thus filling the gaps in existing technologies. Summary of the Invention

[0009] The present invention aims to solve the above-mentioned technical problems by providing a tablet formulation for reducing hyperhomocysteinemia.

[0010] To solve the above-mentioned technical problems, the technical solution provided by the present invention is: a tablet formulation for reducing hyperhomocysteinemia, made from the following raw materials in the indicated weight ratios: Selenium-enriched yeast 0.8-1.2 parts, pyridoxine hydrochloride 0.06-0.1 parts, folic acid 0.003-0.005 parts, cyanocobalamin 0.00005-0.0001 parts, microcrystalline cellulose 15-20 parts, maltodextrin 8-12 parts, magnesium stearate 0.5-1.0 parts, calcium carbonate 2-3 parts, coating premix 3-5 parts; The coating premix is ​​composed of 1.5-2.5 parts hydroxypropyl methylcellulose, 0.8-1.2 parts polyethylene glycol, 0.5-0.8 parts talc, and 0.2-0.5 parts titanium dioxide. The cyanocobalamin exists in a premixed form, and the premix is ​​1% vitamin C. The diluted product is prepared by mixing cyanocobalamin, maltodextrin, and calcium carbonate in a mass ratio of 1:80-90:9-19. The tablets are 0.45g each, and each tablet contains 67.5-99μg of selenium (as Se) and vitamins. (Calculated as pyridoxine) 6.4-10mg, containing vitamins (Calculated as cobalamin) 5.6-10μg, containing folic acid (calculated as folic acid) 320-500μg; The sensory requirements for the tablets are as follows: White coated tablets with a light yellow core and red spots. They have the taste and smell of the product and are free from any off-odors or odors. The film-coated tablets are intact and smooth, without cracks, and are dry, non-sticky, and free of any foreign matter visible to normal vision. The physicochemical indicators are as follows: lead (Pb) ≤ 1.6 mg / kg, total arsenic (As) ≤ 1.0 mg / kg, total mercury (Hg) ≤ 0.3 mg / kg, ash content ≤ 5.0%, and disintegration time ≤ 60 min; The microbiological indicators are as follows: total bacterial count ≤30,000 CFU / g, coliform bacteria ≤0.92 MPN / g, molds and yeasts ≤50 CFU / g, Staphylococcus aureus 0 / 25g, and Salmonella 0 / 25g.

[0011] Preferably, the selenium-enriched yeast conforms to the requirements of GB 1903.21 "National Food Safety Standard for Food Fortifier Selenium-Enriched Yeast", with a selenium content ≥2000mg / kg, protein content ≥40%, moisture ≤6%, lead ≤1.0mg / kg, arsenic ≤0.5mg / kg, total bacterial count ≤5000CFU / g, coliform bacteria ≤0.3MPN / g, mold ≤50CFU / g, yeast ≤50CFU / g, and Salmonella and Staphylococcus aureus must not be detected.

[0012] Preferably, the pyridoxine hydrochloride conforms to GB 14753 "National Food Safety Standard - Food Additives - Vitamins". According to the "Regulations on the Administration of Pyridoxine Hydrochloride", the content should be ≥98.0%, the loss on drying should be ≤0.5%, the residue on ignition should be ≤0.1%, the heavy metals (as Pb) should be ≤20mg / kg, and the arsenic salts should be ≤0.0003%. The folic acid described meets the requirements of GB 15570 "National Food Safety Standard for Food Additives Folic Acid", with a content ≥96.0%, moisture ≤8.5%, residue on ignition ≤0.3%, heavy metals (as Pb) ≤10mg / kg, and arsenic salts ≤0.0003%. The cyanocobalamin meets the requirements of GB 1903.43 "National Food Safety Standard for Food Fortifier Cyanocobalamin", with a content ≥96.0%, loss on drying ≤12.0%, residue on ignition ≤1.0%, heavy metals (as Pb) ≤20mg / kg, and arsenic salts ≤0.0003%.

[0013] Preferably, the premixed (1% vitamin) The sensory requirements for the diluted product are that it is a pink powder, odorless, free from spoilage and mold, and free from foreign impurities visible to normal eyesight. The content is 0.9-1.2%; the sources are cyanocobalamin, maltodextrin, and calcium carbonate. The physicochemical and microbiological indicators are as follows: Lead (as Pb) ≤ 2.0 mg / kg, total arsenic (as As) ≤ 1.0 mg / kg, total bacterial count ≤ 30,000 CFU / g, coliform bacteria ≤ 0.92 MPN / g, molds and yeasts ≤ 50 CFU / g, Staphylococcus aureus 0 / 25g, Salmonella 0 / 25g.

[0014] Preferably, the sensory requirements for the coating premix are a white, uniform, dry powder that is odorless; The sources are hydroxypropyl methylcellulose, polyethylene glycol, talc, and titanium dioxide; Appearance uniformity means exhibiting a uniform color, without patterns or color spots; The proportion of particles passing through a No. 3 sieve is ≥99%; The dispersion uniformity is such that the solution is a homogeneous suspension free of impurities, and can pass through a No. 4 sieve completely; pH value: 4.0-8.0; Viscosity (25℃): ≤70 mPa·s; Moisture ≤8.0%; Residue on ignition ≤45.0%; Heavy metals ≤20mg / kg; Arsenic salt content ≤ 0.0008%; Total aerobic bacteria count ≤1000 CFU / g; Total mold and yeast count ≤100 CFU / g; Escherichia coli must not be detected.

[0015] Preferably, the microcrystalline cellulose content is ≥97.0%, the loss on drying is ≤7.0%, the residue on ignition is ≤0.3%, the heavy metals (as Pb) are ≤10mg / kg, and the arsenic salts are ≤0.0003%. The maltodextrin has a DE value ≤20%, moisture content ≤6.0%, solubility ≥98%, lead ≤0.5mg / kg, and arsenic ≤0.5mg / kg. The magnesium stearate content (calculated as MgO) is 6.8%-8.3%, the loss on drying is ≤6.0%, the residue on ignition is ≤0.5%, the heavy metals (calculated as Pb) are ≤10mg / kg, and the arsenic salts are ≤0.0002%. The calcium carbonate content (in) (Calculated as Pb) ≥98.0%, loss on drying ≤2.0%, residue on ignition ≤0.2%, heavy metals (as Pb) ≤10mg / kg, arsenic salts ≤0.0003%; The hydroxypropyl methylcellulose complies with the requirements of GB 1886.109 "National Food Safety Standard for Food Additives Hydroxypropyl Methylcellulose (HPMC)", with a methoxy content of 19.0%-30.0%, a hydroxypropyl content of 4.0%-12.0%, a drying loss of ≤5.0%, a residue on ignition of ≤1.5%, heavy metals (as Pb) of ≤20 mg / kg, and arsenic salts of ≤0.0002%. The talc powder meets the requirements of GB 1886.246 "National Food Safety Standard for Food Additives: Talc Powder", with no detectable asbestos, a drying loss of ≤1.0%, a residue on ignition of ≤5.0%, heavy metals (as Pb) of ≤40mg / kg, and arsenic salts of ≤0.0003%. The titanium dioxide meets the requirements of GB 1886.341 "National Food Safety Standard for Food Additives: Titanium Dioxide", with a content ≥98.0%, loss on drying ≤0.5%, residue on ignition ≤0.5%, heavy metals (as Pb) ≤20mg / kg, and arsenic salts ≤0.0003%.

[0016] Preferably, the following steps are included: (1) Sieving: Selenium-enriched yeast, pyridoxine hydrochloride, folic acid, and premixed (1% vitamin) Diluted products, microcrystalline cellulose, maltodextrin, and calcium carbonate are passed through an 80-mesh sieve, magnesium stearate is passed through a 60-mesh sieve, and the coating premix is ​​passed through a 100-mesh sieve to remove sieve residues and visible impurities. (2) Mixing: Weigh out the sieved selenium-enriched yeast, pyridoxine hydrochloride, folic acid, and premixed (1% vitamin) according to the specified ratio. Diluted product), microcrystalline cellulose, maltodextrin, and calcium carbonate are placed in a three-dimensional motion mixer, and the speed is set to 150-200 r / min, and the mixing time is 20-30 min to obtain a mixture. (3) Tableting: Place the mixture in a rotary tablet press, adjust the tableting pressure to 4-6 kN, control the tablet weight difference within ±5%, and press to obtain raw tablets; (4) Coating: Add the coating premix to purified water to prepare a 12-15% coating solution, stir for 30 min until completely dispersed and uniform; place the uncoated tablets in a high-efficiency coating machine, set the inlet air temperature to 60-70℃, the atomization pressure to 0.3-0.5MPa, the spraying speed to 30-40mL / min, and the coating weight gain to 3-5% to obtain coated tablets; (5) Packaging: The coated tablets are packaged by a blister packing machine. The pharmaceutical aluminum foil conforms to the YBB00152002 standard "Pharmaceutical Aluminum Foil" and the polyvinyl chloride solid pharmaceutical hard sheet conforms to the YBB00212005 standard "Polyvinyl Chloride Solid Pharmaceutical Hard Sheet". After packaging, the tablets are inspected online, and unqualified products are removed and the tablets are packed and stored.

[0017] Preferably, the mixing uniformity RSD of the three-dimensional motion mixer in step (2) is ≤5.0%; The hardness of the raw slices mentioned in step (3) is 4-6 kg / cm², and the brittleness is ≤0.5%; The pH value of the coating solution in step (4) is 4.0-8.0, the temperature of the tablet bed is controlled at 35-45℃ during the coating process, and the tablets are dried at 40-50℃ for 30 minutes after coating. The heat sealing temperature of the blister packaging in step (5) is 160-180℃, the vacuum degree is ≥-0.08MPa, 10 pieces are packed per blister pack, and 3 blister packs are packed per box.

[0018] Preferably, the production environment of the process meets the requirements of GB 14881 *National Food Safety Standard: General Hygienic Specification for Food Production* and GB 17405 *Good Manufacturing Practice for Health Foods*, the air cleanliness grade of the clean area is Grade D, the number of suspended particles with a particle size ≥0.5μm is ≤3,520,000 particles / m³, the number of particles with a particle size ≥5μm is ≤29,000 particles / m³, the number of settled bacteria is ≤100 CFU / dish, the number of airborne bacteria is ≤500 CFU / m³, and the number of surface microorganisms is ≤50 CFU / plate; The production water is purified water, which conforms to the purified water standard of *Pharmacopoeia of the People's Republic of China*, with conductivity ≤5.1μS / cm (25°C), total organic carbon ≤0.5mg / L, and microbial limit ≤100CFU / mL.

[0019] Preferably, the weight variation of the product conforms to the provisions of "Tablets" under "General Rules for Preparations" in *Pharmacopoeia of the People's Republic of China*, and the weight variation limit of each tablet relative to the average weight is ±5.0%; The net content conforms to the provisions of the *Measures for the Supervision and Administration of Measurement of Quantitatively Packed Commodities*, the marked net content is 45g / box (100 tablets / box), and the allowable shortage between the actual net content and the marked net content is 1.5%; Under the storage conditions of shading, cool place, dryness and ventilation, the shelf life is 24 months. During the shelf life, the content reduction rate of functional components is ≤10%, and the microbial indicators meet the requirements of GB 16740; The content labeled on the product label includes the sky-blue health food identifier, the health food record number "Shi Jian Bei GXXXX", product name, name and address of the manufacturer, production date, shelf life, production batch number, functional components and their contents, suitable人群, unsuitable人群, eating method and dosage, product specification, storage method, and the warning phrases for health food: "This product cannot replace drugs", "It is not recommended that people outside the suitable人群 consume this product", "Do not exceed the recommended dosage or consume it simultaneously with similar nutrients", "People in high-selenium areas are not suitable for consumption", and "No claim or implication of any effect of preventing or treating diseases is allowed".

[0020] Compared with the prior art, the present invention has the following beneficial effects: (1) High raw material safety: all raw materials conform to the corresponding national food safety standards. Selenium-enriched yeast (GB 1903.21) is selected as the selenium source, whose bioavailability is 1.5-2 times that of inorganic selenium, and its toxicity is lower; the purity of vitamin raw materials is ≥96%, and the limits of heavy metals and arsenic salts are stricter than the requirements of national standards; premix (1% vitamin diluent) and coating premix have established exclusive quality standards, which control the introduction of pollutants from the source to ensure product safety.

[0021] (2) Stable and controllable functional components: through 1% vitamin Premixing technology solves the problem of uneven mixing of trace components, achieving a mixing uniformity RSD ≤ 5.0%. The thin film barrier formed by the coating premix effectively blocks light, moisture, and oxygen. Accelerated testing (40℃±2℃, RH75%±5%) shows that after 6 months of storage, the selenium content decreases by ≤ 5%, and the vitamin content decreases by ≤ 5%. Decrease rate ≤8%, Vitamin The decline rate is ≤6%, and the decline rate of folic acid is ≤7%, which is far lower than the 20% decline rate of existing products.

[0022] (3) Strict quality indicators: The lead limit in the physicochemical indicators is 1.6 mg / kg, which is stricter than the 2.0 mg / kg specified in GB 16740; the total mercury limit is 0.3 mg / kg, which is stricter than the upper limit of 0.3 mg / kg in the national standard; the mold and yeast in the microbiological indicators are ≤50 CFU / g, which is lower than the upper limit of 50 CFU / g specified in the national standard, and Staphylococcus aureus and Salmonella are subject to the zero tolerance standard of "0 / 25g", which is safer.

[0023] (4) Standardized production process: The parameters of the whole process are controllable. The mixing process adopts a three-dimensional motion mixer with precise control of speed and time. The tableting pressure is 4-6kN to ensure the hardness of the tablets is 4-6kg / cm² and the brittleness is ≤0.5%. The coating process controls the air temperature, atomization pressure and spraying speed to ensure that the coating weight gain is 3-5% and the disintegration time is ≤60min, which is much faster than the 60min upper limit of traditional coated tablets, which is conducive to the release of active ingredients.

[0024] (5) Labeling and marking standards: Strictly follow the requirements of the "Guidelines for Labeling Warning Statements for Health Foods" to label the health food logo in sky blue, the registration number, warning statements, etc., and clearly indicate that "this product cannot replace medicine" and "people in high selenium areas should not consume it" to prevent false advertising and improper use risks.

[0025] (6) Long and stable shelf life: Under the storage conditions of being protected from light, cool, dry and ventilated, the shelf life is up to 24 months. During the shelf life, all indicators meet the standard requirements, which solves the problem of short shelf life and unstable quality of existing products.

[0026] (7) Controllable production environment: The production process complies with the requirements of GB 14881 and GB 17405, the clean area reaches the D level standard, the production water is purified water with conductivity ≤5.1μS / cm and total organic carbon ≤0.5mg / L, minimizing the risk of microorganisms and pollutants being introduced.

[0027] (8) Accurate net content: The net content complies with the "Measures for the Supervision and Administration of Quantitative Packaging Commodities", and the allowable shortage is only 1.5%, which is better than the national standard requirement of 1.5% upper limit, thus protecting consumer rights.

[0028] (9) Clearly defined target population: By limiting the content of active ingredients, the target population is clearly defined as people who need to supplement selenium and multivitamins, while the unsuitable population is infants, pregnant women, lactating mothers and people in high selenium areas. The usage instructions are clear, reducing the risk of accidental ingestion. Detailed Implementation

[0029] Example 1: Preparation of Xue Tong Qing brand selenium multivitamin tablets

[0030] 1. Raw material preparation: Weigh the raw materials according to the following ratio: 1.0 part selenium-enriched yeast, 0.08 parts pyridoxine hydrochloride, 0.004 parts folic acid, 0.00008 parts cyanocobalamin, 18 parts microcrystalline cellulose, 10 parts maltodextrin, 0.8 parts magnesium stearate, 2.5 parts calcium carbonate, and 4 parts coating premix. The coating premix consists of 2.0 parts hydroxypropyl methylcellulose, 1.0 part polyethylene glycol, 0.6 parts talc, and 0.4 parts titanium dioxide; the premix (1% vitamin...) The diluted product is made by mixing cyanocobalamin, maltodextrin, and calcium carbonate in a mass ratio of 1:85:14.

[0031] 2. Premixed (1% Vitamin) The quality test results for the diluted product were conducted according to the requirements of Appendix A, and the results are shown in Table A-1 below: Table A-1 Example 1 Premixed (1% Vitamin) Quality Inspection Form for Diluents

[0032] 3. The quality test results of the coating premix were inspected according to the requirements of Appendix B, and the results are shown in Table B-1 below: Table B-1 Quality Test Table of Coating Premix in Example 1

[0033] 4. Preparation process (1) Sieving: Selenium-enriched yeast, pyridoxine hydrochloride, folic acid, and premixed (1% vitamin) Diluted products, microcrystalline cellulose, maltodextrin, and calcium carbonate are passed through an 80-mesh sieve, magnesium stearate is passed through a 60-mesh sieve, and the coating premix is ​​passed through a 100-mesh sieve. The material on the sieve and visible impurities are removed, and the integrity of the sieve is checked and found to be qualified.

[0034] (2) Mixing: Weigh the sieved raw materials according to the proportion and place them in a three-dimensional motion mixer. Set the rotation speed to 180 r / min, the mixing time to 25 min, and the mixing uniformity RSD=3.2%, which meets the requirement of ≤5.0%.

[0035] (3) Tableting: Place the mixture in a ZP-35 rotary tablet press, adjust the tableting pressure to 5kN, control the tablet weight difference within ±3.5%, and press to obtain raw tablets. The raw tablets have a hardness of 5.2kg / cm² and a brittleness of 0.3%, which meets the requirement of ≤0.5%.

[0036] (4) Coating: Add the coating premix to purified water to prepare a 14% coating solution. Stir for 30 minutes until completely dispersed and uniform. The pH value of the coating solution is 6.2. Place the uncoated tablets in a BG-150 high-efficiency coating machine. Set the air inlet temperature to 65℃, the atomization pressure to 0.4MPa, the spraying speed to 35mL / min, the tablet bed temperature to 40℃, and the coating weight gain to 4.0%. After coating, dry at 45℃ for 30 minutes to obtain coated tablets.

[0037] (5) Packaging: The coated tablets are packaged using a DPP-250 blister packaging machine. The pharmaceutical aluminum foil conforms to the YBB00152002 standard, and the polyvinyl chloride solid pharmaceutical hard sheet conforms to the YBB00212005 standard. The heat sealing temperature is 170℃, the vacuum degree is -0.09MPa, 10 tablets are packed per blister pack, and 3 blister packs are packed per box. After online quality inspection, defective products such as broken or missing tablets are removed, and the tablets are packed and stored.

[0038] 5. Finished product quality inspection results: The finished products were inspected according to the requirements of enterprise standard Q / WSK 0012S-2026, and the results are shown in Tables 1-1 to 4-1 below: Table 1-1 Sensory requirements inspection table for finished products in Example 1

[0039] Table 2-1 Test Table of Physicochemical Indicators of Finished Product in Example 1

[0040] Table 3-1 Microbiological Index Detection Table of Finished Product in Example 1

[0041] Table 4-1 Test Table of Efficacy Components or Marker Components in Finished Product of Example 1

[0042] Table 5-1 Weight Difference Test Table for Finished Products in Example 1 (20 pieces selected)

[0043] Table 6-1 Net Content Test Table of Finished Product in Example 1 (10 boxes sampled)

[0044] Example 2: Preparation of Xuetongqing brand selenium multivitamin tablets

[0045] 1. Raw material preparation: Weigh the raw materials according to the following ratio: 0.8 parts selenium-enriched yeast, 0.06 parts pyridoxine hydrochloride, 0.003 parts folic acid, 0.00005 parts cyanocobalamin, 15 parts microcrystalline cellulose, 8 parts maltodextrin, 0.5 parts magnesium stearate, 2 parts calcium carbonate, and 3 parts coating premix.

[0046] The coating premix consists of 1.5 parts hydroxypropyl methylcellulose, 0.8 parts polyethylene glycol, 0.5 parts talc, and 0.2 parts titanium dioxide; the premix (1% vitamin B) 12 The diluted product is made by mixing cyanocobalamin, maltodextrin, and calcium carbonate in a mass ratio of 1:80:19.

[0047] 2. Premixed (1% Vitamin) The quality test results of the diluted product are shown in Table A-2 below: Table A-2 Example 2 Premixed (1% Vitamin) Quality Inspection Form for Diluents

[0048] 3. The quality test results of the coating premix are shown in Table B-2 below: Table B-2 Quality Test Table of Coating Premix in Example 2

[0049] 4. Preparation process (1) Sieving: The operation is the same as in Example 1, and the integrity of the sieve is checked and qualified.

[0050] (2) Mixing: Placed in a three-dimensional motion mixer, the rotation speed is set to 150 r / min, the mixing time is 30 min, and the mixing uniformity RSD is 4.5%, which meets the requirement of ≤5.0%.

[0051] (3) Tableting: A ZP-35 rotary tablet press was used. The tableting pressure was adjusted to 4kN, the tablet weight difference was controlled within ±4.2%, the tablet hardness was 4.5kg / cm², and the brittleness was 0.4%, which meets the requirement of ≤0.5%.

[0052] (4) Coating: Prepare a 12% coating solution with a pH of 5.8; parameters of the high-efficiency coating machine: air inlet temperature 60℃, atomization pressure 0.3MPa, spraying speed 30mL / min, tablet bed temperature 38℃, coating weight gain 3.0%, drying at 45℃ for 30min.

[0053] (5) Packaging: The operation is the same as in Example 1, with a heat sealing temperature of 160°C and a vacuum degree of -0.08MPa.

[0054] 5. The results of the finished product quality inspection are shown in Tables 1-2 to 4-2 below: Table 1-2 Sensory Requirements Inspection Table for Finished Products in Example 2

[0055] Table 2-2 Test Table of Physicochemical Indicators of Finished Product in Example 2

[0056] Table 3-2 Microbiological Index Detection Table of Finished Product in Example 2

[0057] Table 4-2 Test Table of Efficacy Components or Marker Components in Finished Product of Example 2

[0058] Table 5-2 Weight Difference Test Table for Finished Products in Example 2 (20 pieces selected)

[0059] Example 3: Preparation of Xuetongqing brand selenium multivitamin tablets

[0060] 1. Raw material preparation: Weigh the raw materials according to the following ratio: 1.2 parts selenium-enriched yeast, 0.1 parts pyridoxine hydrochloride, 0.005 parts folic acid, 0.0001 parts cyanocobalamin, 20 parts microcrystalline cellulose, 12 parts maltodextrin, 1.0 part magnesium stearate, 3 parts calcium carbonate, and 5 parts coating premix. The coating premix consists of 2.5 parts hydroxypropyl methylcellulose, 1.2 parts polyethylene glycol, 0.8 parts talc, and 0.5 parts titanium dioxide; the premix (1% vitamin...) The diluted product is made by mixing cyanocobalamin, maltodextrin, and calcium carbonate in a mass ratio of 1:90:9.

[0061] 2. Premixed (1% Vitamin) The quality test results of the diluted product are shown in Table A-3 below: Table A-3 Example 3 Premixed (1% Vitamin) Quality Inspection Form for Diluents

[0062] 3. The quality test results of the coating premix are shown in Table B-3 below: Table B-3 Quality Test Table of Coating Premix in Example 3

[0063] 4. Preparation process (1) Sieving: The operation is the same as in Example 1, and the integrity of the sieve is checked and qualified.

[0064] (2) Mixing: Placed in a three-dimensional motion mixer, the rotation speed is set to 200 r / min, the mixing time is 20 min, and the mixing uniformity RSD is 2.8%, which meets the requirement of ≤5.0%.

[0065] (3) Tableting: A ZP-35 rotary tablet press was used. The tableting pressure was adjusted to 6kN. The tablet weight difference was controlled within ±2.8%. The hardness of the raw tablets was 5.8kg / cm², and the brittleness was 0.2%, which met the requirement of ≤0.5%.

[0066] (4) Coating: Prepare a 15% coating solution with a pH of 7.2; parameters of the high-efficiency coating machine: air inlet temperature 70℃, atomization pressure 0.5MPa, spraying speed 40mL / min, tablet bed temperature 42℃, coating weight gain 5.0%, drying at 45℃ for 30min. (5) Packaging: operation is the same as in Example 1, heat sealing temperature 180℃, vacuum degree -0.10MPa.

[0067] 5. The results of the finished product quality inspection are shown in Tables 1-3 to 4-3 below: Table 1-3 Sensory Requirements Inspection Table for Finished Products in Example 3

[0068] Table 2-3 Test Table of Physicochemical Indicators of Finished Product in Example 3

[0069] Table 3-3 Microbiological Index Detection Table of Finished Product in Example 3

[0070] Table 4-3 Test Table of Efficacy Components or Marker Components in Finished Product of Example 3

[0071] Table 5-3 Weight Difference Test Table for Finished Products in Example 3 (20 pieces selected)

[0072] Shelf life verification

[0073] The product prepared in Example 1 was placed in a light-proof, cool (≤25℃), dry (RH≤60%), and ventilated warehouse. Samples were taken and tested at 0 months, 6 months, 12 months, 18 months, and 24 months, respectively. The results are shown in Table 7-1 below: Table 7-1 Shelf Life Verification Test Table for Product of Example 1

[0074] The results showed that all indicators met the standard requirements within 24 months, and the decline rate of effective ingredients was ≤10%, thus verifying the product's 24-month shelf life under the specified storage conditions.

[0075] The Xuetongqing brand selenium multivitamin tablets disclosed in this invention strictly adhere to the enterprise standard Q / WSK 0012S-2026 and the requirements of the health food registration certificate in terms of all raw materials, process parameters, and quality indicators. Through premixing technology, standardized production processes, and a strict quality control system, the product achieves the goals of stable and controllable efficacy components, product safety and compliance, and long shelf life. This solves many defects of existing similar products and has significant practical and promotional value.

[0076] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A tablet formulation for reducing hyperhomocysteinemia, characterized in that, Made from the following raw materials in the indicated weight ratios: Selenium-enriched yeast 0.8-1.2 parts, pyridoxine hydrochloride 0.06-0.1 parts, folic acid 0.003-0.005 parts, cyanocobalamin 0.00005-0.0001 parts, microcrystalline cellulose 15-20 parts, maltodextrin 8-12 parts, magnesium stearate 0.5-1.0 parts, calcium carbonate 2-3 parts, coating premix 3-5 parts; The coating premix is ​​composed of 1.5-2.5 parts hydroxypropyl methylcellulose, 0.8-1.2 parts polyethylene glycol, 0.5-0.8 parts talc, and 0.2-0.5 parts titanium dioxide. The cyanocobalamin is in a premix form, the premix being 1% vitamin Diluted product, made by mixing cyanocobalamin, maltodextrin, calcium carbonate in a mass ratio of 1:80-90:9-19; The said formulation is made into tablets, with a size of 0.45 g / tablet, each tablet containing selenium (as Se) 67.5-99 μg, containing vitamin (pyridoxine) 6.4-10 mg, containing vitamin (cobalamin) 5.6-10 μg, containing folic acid (as folic acid) 320-500 μg; The sensory requirements for the tablets are as follows: White coated tablets with a light yellow core and red spots. They have the taste and smell of the product and are free from any off-odors or odors. The film-coated tablets are intact and smooth, without cracks, and are dry, non-sticky, and free of any foreign matter visible to normal vision. The physicochemical indicators are as follows: lead (Pb) ≤ 1.6 mg / kg, total arsenic (As) ≤ 1.0 mg / kg, total mercury (Hg) ≤ 0.3 mg / kg, ash content ≤ 5.0%, and disintegration time ≤ 60 min; The microbiological indicators are as follows: total bacterial count ≤30,000 CFU / g, coliform bacteria ≤0.92 MPN / g, molds and yeasts ≤50 CFU / g, Staphylococcus aureus 0 / 25g, and Salmonella 0 / 25g.

2. The tablet formulation according to claim 1, wherein the tablet formulation is a tablet formulation for reducing hyperhomocysteinemia. The selenium-enriched yeast contains ≥2000 mg / kg of selenium, ≥40% of protein, ≤6% moisture, ≤1.0 mg / kg of lead, ≤0.5 mg / kg of arsenic, ≤5000 CFU / g of total bacterial count, ≤0.3 MPN / g of coliform bacteria, ≤50 CFU / g of mold, ≤50 CFU / g of yeast, and Salmonella and Staphylococcus aureus must not be detected.

3. The tablet formulation according to claim 1, wherein the tablet formulation is a tablet formulation for reducing hyperhomocysteinemia. The pyridoxine hydrochloride content is ≥98.0%, the loss on drying is ≤0.5%, the residue on ignition is ≤0.1%, the heavy metals (as Pb) are ≤20mg / kg, and the arsenic salts are ≤0.0003%. The folic acid described meets the requirements of GB 15570 "National Food Safety Standard for Food Additives Folic Acid", with a content ≥96.0%, moisture ≤8.5%, residue on ignition ≤0.3%, heavy metals (as Pb) ≤10mg / kg, and arsenic salts ≤0.0003%. The cyanocobalamin meets the requirements of GB 1903.43 "National Food Safety Standard for Food Fortifier Cyanocobalamin", with a content ≥96.0%, loss on drying ≤12.0%, residue on ignition ≤1.0%, heavy metals (as Pb) ≤20mg / kg, and arsenic salts ≤0.0003%.

4. The tablet formulation for reducing hyperhomocysteinemia according to claim 1, characterized in that, The premix (1% vitamin The sensory requirements of the dilution are pink powder, no off-odour, no off-flavour, no signs of spoilage and mould, no visible foreign matter to the naked eye; The content is 0.9-1.2%; the sources are cyanocobalamin, maltodextrin, and calcium carbonate. The physicochemical and microbiological indicators are as follows: Lead (as Pb) ≤ 2.0 mg / kg, total arsenic (as As) ≤ 1.0 mg / kg, total bacterial count ≤ 30,000 CFU / g, coliform bacteria ≤ 0.92 MPN / g, molds and yeasts ≤ 50 CFU / g, Staphylococcus aureus 0 / 25g, Salmonella 0 / 25g.

5. The tablet formulation for reducing hyperhomocysteinemia according to claim 1, characterized in that, The sensory requirements for the coating premix are: a white, uniform, dry powder, odorless; The sources are hydroxypropyl methylcellulose, polyethylene glycol, talc, and titanium dioxide; Appearance uniformity means exhibiting a uniform color, without patterns or color spots; The proportion of particles passing through a No. 3 sieve is ≥99%; The dispersion uniformity is such that the solution is a homogeneous suspension free of impurities, and can pass through a No. 4 sieve completely; pH value: 4.0-8.0; Viscosity (25℃): ≤70 mPa·s; Moisture ≤8.0%; Residue on ignition ≤45.0%; Heavy metals ≤20mg / kg; Arsenic salt content ≤ 0.0008%; Total aerobic bacteria count ≤1000 CFU / g; Total mold and yeast count ≤100 CFU / g; Escherichia coli must not be detected.

6. The tablet formulation according to claim 1, wherein the tablet formulation is a tablet formulation for reducing hyperhomocysteinemia. The microcrystalline cellulose content is ≥97.0%, the loss on drying is ≤7.0%, the residue on ignition is ≤0.3%, the heavy metals (as Pb) are ≤10mg / kg, and the arsenic salts are ≤0.0003%. The maltodextrin has a DE value ≤20%, moisture content ≤6.0%, solubility ≥98%, lead ≤0.5mg / kg, and arsenic ≤0.5mg / kg. The magnesium stearate content (calculated as MgO) is 6.8%-8.3%, the loss on drying is ≤6.0%, the residue on ignition is ≤0.5%, the heavy metals (calculated as Pb) are ≤10mg / kg, and the arsenic salts are ≤0.0002%. The calcium carbonate content (in) (Calculated as Pb) ≥98.0%, loss on drying ≤2.0%, residue on ignition ≤0.2%, heavy metals (as Pb) ≤10mg / kg, arsenic salts ≤0.0003%; The hydroxypropyl methylcellulose is specified as having a methoxy content of 19.0%-30.0%, a hydroxypropyl content of 4.0%-12.0%, a loss on drying of ≤5.0%, a residue on ignition of ≤1.5%, heavy metals (as Pb) of ≤20 mg / kg, and arsenic salts of ≤0.0002%. The specifications for the talc powder are asbestos not detectable, loss on drying ≤1.0%, residue on ignition ≤5.0%, heavy metals (as Pb) ≤40mg / kg, and arsenic salts ≤0.0003%; The titanium dioxide content is ≥98.0%, the loss on drying is ≤0.5%, the residue on ignition is ≤0.5%, the heavy metals (as Pb) are ≤20mg / kg, and the arsenic salts are ≤0.0003%.

7. The process for the preparation of a tablet formulation for reducing hyperhomocysteinemia according to any one of claims 1 to 6, characterized in that, Includes the following steps: (1) Sieving: Sieve the selenium-rich yeast, pyridoxine hydrochloride, folic acid, premix (1% vitamin Diluted product), microcrystalline cellulose, maltodextrin, calcium carbonate through 80-mesh sieve, magnesium stearate through 60-mesh sieve, and coating premix through 100-mesh sieve, and remove the sieve residue and visible impurities; (2) mixing: the sieved selenium-rich yeast, pyridoxine hydrochloride, folic acid, premix (1% vitamin Diluted products), microcrystalline cellulose, malt dextrin, calcium carbonate, placed in three-dimensional motion mixer, set the speed 150-200 r / min, mixing time 20-30 min, get the mixture; (3) Tableting: Place the mixture in a rotary tablet press, adjust the tableting pressure to 4-6 kN, control the tablet weight difference within ±5%, and press to obtain raw tablets; (4) Coating: Add the coating premix to purified water to prepare a 12-15% coating solution, stir for 30 min until completely dispersed and uniform; place the uncoated tablets in a high-efficiency coating machine, set the inlet air temperature to 60-70℃, the atomization pressure to 0.3-0.5MPa, the spraying speed to 30-40mL / min, and the coating weight gain to 3-5% to obtain coated tablets; (5) Packaging: The coated tablets are packaged by a blister packing machine. The pharmaceutical aluminum foil conforms to the YBB00152002 standard "Pharmaceutical Aluminum Foil" and the polyvinyl chloride solid pharmaceutical hard sheet conforms to the YBB00212005 standard "Polyvinyl Chloride Solid Pharmaceutical Hard Sheet". After packaging, the tablets are inspected online, and unqualified products are removed and the tablets are packed and stored.

8. The manufacturing process of claim 7, wherein, The mixing uniformity RSD of the three-dimensional motion mixer described in step (2) is ≤5.0%; The hardness of the raw slices mentioned in step (3) is 4-6 kg / cm², and the brittleness is ≤0.5%; The pH value of the coating solution in step (4) is 4.0-8.0, the temperature of the tablet bed is controlled at 35-45℃ during the coating process, and the tablets are dried at 40-50℃ for 30 minutes after coating. The heat sealing temperature of the blister packaging in step (5) is 160-180℃, the vacuum degree is ≥-0.08MPa, 10 pieces are packed per blister pack, and 3 blister packs are packed per box.

9. The manufacturing process of claim 7, wherein, The cleanroom air cleanliness level of the production environment of the process is Class D, with suspended particles ≥0.5μm ≤3,520,000 / m³, particles ≥5μm ≤29,000 / m³, settling bacteria ≤100 CFU / plate, airborne bacteria ≤500 CFU / m³, and surface microorganisms ≤50 CFU / plate. The production water is purified water with a conductivity ≤5.1μS / cm (25℃), total organic carbon ≤0.5mg / L, and microbial limit ≤100CFU / mL.

10. The tablet formulation for reducing hyperhomocysteinemia according to claim 1, characterized in that, The weight of each product may vary from the average weight by a maximum of ±5.0%. The labeled net content is 45g / box (100 tablets / box), and the allowable shortage between the actual net content and the labeled net content is 1.5%. The shelf life is 24 months under storage conditions of being protected from light, cool, dry and ventilated. The content of active ingredients decreases by ≤10% during the shelf life, and the microbiological indicators meet the requirements of GB 16740.

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