A selenium-containing compound vitamin chewable tablet and its preparation method

Abstract

This invention relates to a selenium-containing compound vitamin chewable tablet and its preparation method, comprising the following raw materials in parts by weight: 10-16 parts selenium-enriched yeast, 25-35 parts L-ascorbic acid, 0.5-1 part vitamin K, 10-20 parts sorbitol, 1-3 parts DL-α-tocopherol acetate, 3-8 parts sodium octenyl succinate starch, 1-5 parts acetylated distarch adipate, 0.7-1.2 parts magnesium stearate, 0.3-0.5 parts potassium citrate, 0.04-0.07 parts steviol glycosides, and 5-10 parts modified silica. This invention improves the crispness and palatability of the chewable tablet by adding acetylated distarch adipate and sodium octenyl succinate starch; the addition of modified silica effectively reduces vitamin attenuation and improves the stability of the components.

Description

Technical Field

[0001] This invention belongs to the medical field, specifically relating to a selenium-containing compound vitamin chewable tablet and its preparation method. Background Technology

[0002] Vitamins are a collective term for a series of organic compounds. They are a class of trace organic substances essential for humans and animals to maintain normal physiological functions. Most cannot be produced by the organism itself and must be obtained from food; only a few can be synthesized in the body or produced by intestinal microorganisms. Trace elements are important substances for human growth and development, enhancing physical strength, and maintaining health. They are usually ingested through food. Selenium is an indispensable trace element for human life activities. It is an essential component of various selenium-containing enzymes and proteins in the human body, such as thioreductase, deiodinase, and glutathione peroxidase, participating in various metabolic processes. Selenium deficiency can lead to a decline in the body's immune function.

[0003] However, as a major agricultural country since ancient times, my country's diet has been primarily plant-based, resulting in a relatively monotonous dietary structure and a serious imbalance in the intake of trace elements and vitamins. Currently, there are many pharmaceutical and health food products available to supplement vitamins and trace elements, such as chewable tablets. Multivitamin complex products are the preferred choice for consumers due to their comprehensive vitamin content. However, the taste and stability of current vitamin chewable tablets are still unsatisfactory, therefore further research is needed on selenium-containing multivitamin chewable tablets. Summary of the Invention

[0004] The primary objective of this invention is to provide a selenium-containing compound vitamin chewable tablet.

[0005] The second objective of this invention is to provide a method for preparing selenium-containing compound vitamin chewable tablets.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: This invention provides a selenium-containing compound vitamin chewable tablet, comprising the following raw materials in parts by weight: 10-16 parts selenium-enriched yeast, 25-35 parts L-ascorbic acid, 0.5-1 part vitamin K, 10-20 parts sorbitol, 1-3 parts DL-α-tocopherol acetate, 3-8 parts sodium starch octenyl succinate, 1-5 parts acetylated distarch adipate, 0.7-1.2 parts magnesium stearate, 0.3-0.5 parts potassium citrate, 0.04-0.07 parts steviol glycosides, and 5-10 parts modified silicon dioxide; The preparation process of the modified silica is as follows: (1) Add silicon dioxide to a mixed solution of concentrated sulfuric acid and hydrogen peroxide to react, and then filter, wash and dry to obtain hydroxylated silicon dioxide; (2) After pretreatment of citrus fiber, it is added to an aqueous solution containing TEMPO and sodium bromide, the pH is adjusted and the reaction is carried out. After dialysis and freeze drying, carboxylated citrus fiber is obtained. (3) Hydroxylated silica and carboxylated citrus fiber were added to anhydrous ethanol for reaction, and after filtration, washing and drying, modified silica was obtained.

[0007] Preferably, in step (1), the ratio of silicon dioxide to the mixed solution is 1g:10-20mL; the volume ratio of concentrated sulfuric acid to hydrogen peroxide is (6-9):(1-4); the reaction temperature is 60-80℃, and the reaction time is 1-3h.

[0008] Preferably, in step (2), the ratio of the amount of pretreated citrus fiber, TEMPO, sodium bromide and water is 1g:0.10-0.15g:0.30-0.40g:100mL; the reaction temperature is 30-40℃ and the time is 5-6h; the pH is adjusted to 10-11.

[0009] Preferably, in step (3), the ratio of hydroxylated silica, carboxylated citrus fiber, and anhydrous ethanol is 1:(5-10):10-20; the reaction temperature is 70-80℃, and the reaction time is 2-5h.

[0010] Preferably, in step (2), the specific method for pretreatment of citrus fiber is as follows: after ball milling, citrus fiber powder is homogenized under high pressure, freeze-dried, and ground to obtain pretreated citrus fiber.

[0011] Preferably, the ball milling process has a power of 40-45Hz, a rotation speed of 550-580r / min, and a time of 4-6h; the high-pressure homogenization process has a pressure of 20-40MPa.

[0012] Preferably, the vitamin K is vitamin K2; and the selenium-enriched yeast contains ≥99% organic selenium.

[0013] Organic selenium is easily absorbed by organisms, and the present invention preferably uses selenium-enriched yeast with an organic selenium content (accounting for more than 99% of the total selenium) as raw material.

[0014] This invention provides a method for preparing the selenium-containing compound vitamin chewable tablets, comprising the following steps: weighing each raw material component according to the ratio and setting aside; first mixing the other raw materials except magnesium stearate, wet granulating and drying; then adding magnesium stearate, mixing evenly, and then compressing into tablets to obtain the final product.

[0015] Preferably, the pressure during tablet compression is 8-12 kN.

[0016] Compared with the prior art, the main advantages of the present invention are as follows: This invention provides a selenium-containing multivitamin chewable tablet. By adding acetylated distarch adipate and sodium octenyl succinate starch, the tablet's crispness and palatability are improved. The chewable tablet also contains modified silica, which has good flowability and compressibility. The increased specific surface area of ​​the modified silica enhances its adsorption capacity, providing more adsorption sites for the active ingredients, effectively reducing vitamin attenuation and improving the stability of the components.

[0017] This invention provides a method for preparing selenium-containing compound vitamin chewable tablets. The process is simple and suitable for industrial production and widespread application. Attached Figure Description

[0018] Figure 1 Scanning electron microscope image of the modified silica obtained in Example 1 of this invention.

[0019] Figure 2 Morphological diagram of fibroblasts cultured in the experimental group in Example 1 of this invention.

[0020] Figure 3 Morphological diagram of fibroblasts cultured in the control group in Experiment Example 1 of this invention. Detailed Implementation

[0021] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. It should be noted that, without conflict, the various embodiments or technical features described below can be arbitrarily combined to form new embodiments. Specific conditions not specified in the embodiments shall be performed according to conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, all reagents or instruments used are conventional products obtained through commercial channels.

[0022] Example 1 This embodiment relates to a selenium-containing compound vitamin chewable tablet, comprising the following raw materials in parts by weight: 13 parts of selenium-enriched yeast (organic selenium content ≥99%), 30 parts of L-ascorbic acid, 0.8 parts of vitamin K2, 15 parts of sorbitol, 2 parts of DL-α-tocopherol acetate, 5 parts of sodium starch octenyl succinate, 3 parts of acetylated distarch adipate, 1.0 part of magnesium stearate, 0.4 parts of potassium citrate, 0.05 parts of steviol glycosides, and 8 parts of modified silicon dioxide.

[0023] The preparation process of modified silica in this embodiment is as follows: (1) Add silica (particle size 20-30 nm) to a mixed solution of concentrated sulfuric acid (98% by mass) and hydrogen peroxide (30% by mass), wherein the ratio of silica to the mixed solution is 1 g: 15 mL; the volume ratio of concentrated sulfuric acid to hydrogen peroxide is 8: 3; stir at 70 °C for 2 h, and after filtration, washing and drying, hydroxylated silica is obtained. (2) The citrus fiber was pretreated first. The specific method was as follows: the citrus fiber powder was ball-milled under the conditions of 45 Hz power, 560 r / min rotation speed and 4 h time. Then, it was subjected to high-pressure homogenization under 40 MPa pressure. After freeze drying and grinding, the pretreated citrus fiber (D) was obtained. 50 (Approximately 40 μm).

[0024] After pretreatment of citrus fiber, it was added to an aqueous solution containing TEMPO (tetramethylpiperidine oxide) and sodium bromide, wherein the ratio of pretreated citrus fiber, TEMPO, sodium bromide and water was 1g:0.12g:0.35g:100mL; NaClO was then added to adjust the pH to 10.5, and the reaction was stirred at 35℃ for 6h. After dialysis and freeze-drying, carboxylated citrus fiber was obtained. (3) Hydroxylated silica and carboxylated citrus fibers were added to anhydrous ethanol, wherein the ratio of hydroxylated silica, carboxylated citrus fibers, and anhydrous ethanol was 1:8:15; the mixture was stirred at 75°C for 4 hours, and then filtered, washed, and dried to obtain modified silica. The scanning electron microscope image of the obtained modified silica is shown below. Figure 1 As shown.

[0025] The preparation method of selenium-containing compound vitamin chewable tablets in this embodiment includes the following steps: weigh each raw material component according to the ratio and set aside; first mix the other raw materials except magnesium stearate, wet granulate and then dry; then add magnesium stearate, mix evenly and compress into tablets under 10KN pressure to obtain the tablets.

[0026] Example 2 This embodiment relates to a selenium-containing compound vitamin chewable tablet, comprising the following raw materials in parts by weight: 16 parts of selenium-enriched yeast (organic selenium content ≥99%), 35 parts of L-ascorbic acid, 1 part of vitamin K2, 20 parts of sorbitol, 3 parts of DL-α-tocopherol acetate, 8 parts of sodium starch octenyl succinate, 5 parts of acetylated distarch adipate, 1.2 parts of magnesium stearate, 0.5 parts of potassium citrate, 0.07 parts of steviol glycosides, and 10 parts of modified silicon dioxide.

[0027] The preparation process of modified silica in this embodiment is as follows: (1) Add silica to a mixed solution of concentrated sulfuric acid (98% by mass) and hydrogen peroxide (30% by mass), wherein the ratio of silica to the mixed solution is 1g:20mL; the volume ratio of concentrated sulfuric acid to hydrogen peroxide is 9:4; stir the reaction at 80℃ for 1h, and after filtration, washing and drying, hydroxylated silica is obtained. (2) First, the citrus fiber is pretreated. The specific method is as follows: under the ball milling conditions of 45 Hz power, 580 r / min rotation speed and 5 h time, the citrus fiber powder is ball milled, and then high pressure homogenization is carried out under 30 MPa pressure. After freeze drying and grinding, the pretreated citrus fiber is obtained.

[0028] After pretreatment of citrus fiber, it was added to an aqueous solution containing TEMPO and sodium bromide, wherein the ratio of pretreated citrus fiber, TEMPO, sodium bromide and water was 1g:0.15g:0.40g:100mL; NaClO was then added to adjust the pH to 11, and the mixture was stirred at 40℃ for 5h. After dialysis and freeze-drying, carboxylated citrus fiber was obtained. (3) Add hydroxylated silica and carboxylated citrus fiber to anhydrous ethanol, wherein the ratio of hydroxylated silica, carboxylated citrus fiber and anhydrous ethanol is 1:10:20; stir at 80°C for 2 hours, and after filtration, washing and drying, modified silica is obtained.

[0029] The preparation method of selenium-containing compound vitamin chewable tablets in this embodiment includes the following steps: weigh each raw material component according to the ratio and set aside; first mix the other raw materials except magnesium stearate, wet granulate and then dry; then add magnesium stearate, mix evenly and compress at 12KN pressure to obtain tablets.

[0030] Example 3 This embodiment relates to a selenium-containing compound vitamin chewable tablet, comprising the following raw materials in parts by weight: 10 parts of selenium-enriched yeast (organic selenium content ≥99%), 25 parts of L-ascorbic acid, 0.5 parts of vitamin K2, 10 parts of sorbitol, 1 part of DL-α-tocopherol acetate, 3 parts of sodium starch octenyl succinate, 1 part of acetylated distarch adipate, 0.7 parts of magnesium stearate, 0.3 parts of potassium citrate, 0.04 parts of steviol glycosides, and 5 parts of modified silicon dioxide.

[0031] The preparation process of modified silica in this embodiment is as follows: (1) Add silica to a mixed solution of concentrated sulfuric acid (98% by mass) and hydrogen peroxide (30% by mass), wherein the ratio of silica to the mixed solution is 1g:10mL; the volume ratio of concentrated sulfuric acid to hydrogen peroxide is 6:1; stir the reaction at 60℃ for 3h, and after filtration, washing and drying, hydroxylated silica is obtained. (2) First, the citrus fiber is pretreated. The specific method is as follows: under the ball milling conditions of 40Hz power, 550r / min rotation speed and 6h time, the citrus fiber powder is ball milled, and then high pressure homogenization is carried out under 20Mpa pressure. After freeze drying and grinding, the pretreated citrus fiber is obtained.

[0032] After pretreatment of citrus fiber, it was added to an aqueous solution containing TEMPO and sodium bromide, wherein the ratio of pretreated citrus fiber, TEMPO, sodium bromide and water was 1g:0.10g:0.30g:100mL; NaClO was added to adjust the pH to 10, and the reaction was stirred at 30℃ for 6h. After dialysis and freeze-drying, carboxylated citrus fiber was obtained. (3) Hydroxylated silica and carboxylated citrus fiber were added to anhydrous ethanol, wherein the ratio of hydroxylated silica, carboxylated citrus fiber and anhydrous ethanol was 1:5:10; the mixture was stirred at 70°C for 5 hours, and after filtration, washing and drying, modified silica was obtained.

[0033] The preparation method of selenium-containing compound vitamin chewable tablets in this embodiment includes the following steps: weigh each raw material component according to the ratio and set aside; first mix the other raw materials except magnesium stearate, wet granulate and then dry; then add magnesium stearate, mix evenly, and compress into tablets under 8KN pressure to obtain the product.

[0034] Comparative Example 1 The difference between this comparative example and Example 1 is that acetylated distarch adipate is omitted.

[0035] Comparative Example 2 The difference between this comparative example and Example 1 is that acetylated distarch adipate is replaced with sodium octenyl succinate starch.

[0036] Comparative Example 3 The difference between this comparative example and Example 1 is that the modified silica is replaced with a direct mixture of silica and citrus fiber, and the amount used is the same as in Example 1.

[0037] Comparative Example 4 The difference between this comparative example and Example 1 is that the step of citrus fiber pretreatment is omitted.

[0038] Experimental Example 1: Cytotoxicity Experiment Mouse fibroblasts were collected and cultured in DMEM / F12 medium containing 10% FBS, 100 U / mL penicillin, and 100 μg / mL streptomycin in a 37°C, 5% CO2 cell culture incubator. When the mouse fibroblasts reached 70% confluence, they were digested with 0.25% trypsin, centrifuged at 1600 rpm for 5 min, resuspended, and counted. The cell density was adjusted to 5 × 10⁶ cells / mL.4 Cells were seeded at 100 μL / well in 96-well plates. The original culture medium was aspirated from the 96-well plates, and 100 μL of DMEM / F12 medium containing modified silica (10% FBS, 100 U / mL penicillin, 100 μg / mL streptomycin, and 100 μg / mL modified silica prepared in Example 1) was added. The plates were cultured for 24 h as the experimental group. A control group was also set up; the original culture medium was aspirated from the 96-well plates, and DMEM / F12 medium (containing 10% FBS, 100 U / mL penicillin, and 100 μg / mL streptomycin) was added. The plates were cultured for 24 h. The medium was then replaced with 100 μL of live / dead staining solution (AM:PI: medium = 1:1:1000). After staining for 15 min, the fibroblast status was observed using a fluorescence microscope. Live cells were stained green, as shown in the results below. Figure 2 , Figure 3 As shown (magnification × 100). From Figure 2 , Figure 3 It is evident that the cell morphology of the experimental group and the control group is similar, which is the normal morphology of mouse fibroblasts. This indicates that the modified silica prepared in Example 1 did not damage the morphology of mouse fibroblasts and is safe.

[0039] Example 2: Evaluation of Physicochemical Properties According to the determination methods and standards of Part IV of the 2020 edition of the Pharmacopoeia of the People's Republic of China, the hardness of the selenium-containing compound vitamin chewable tablets obtained in Examples 1-3 and Comparative Examples 1-4 was determined, and the results are shown in Table 1.

[0040] Table 1 As shown in Table 1, the chewable tablets of Examples 1-3 of this invention have a moderate hardness compared to Comparative Examples 1-4, resulting in better palatability, stability, and ease of carrying and storage. Specifically, this invention adds acetylated distarch adipate to the raw material components. Acetylated distarch adipate is a modified starch with good stability and mouthfeel, increasing the hardness of the chewable tablets and preventing them from crumbling during chewing. This invention also adds sodium octenyl succinate starch to the raw material components, improving the mouthfeel of the chewable tablets, making them more delicate and smooth. This invention uses acetylated distarch adipate and sodium octenyl succinate starch in combination to improve the crispness of the chewable tablets, eliminating any gritty feeling and enhancing palatability. Chewable tablets with lower hardness, besides having a poor mouthfeel, are also prone to breakage, deformation, or scattering during packaging, transportation, and storage, failing to maintain their integrity. This exposes the drug components to the air, making them susceptible to the effects of light, humidity, oxygen, etc., accelerating drug degradation and deterioration, leading to drug component loss or contamination risks.

[0041] Experimental Example 3 Stability Evaluation 1. The selenium-containing multivitamin chewable tablets obtained in Examples 1-3 and Comparative Examples 1-4 were placed in a constant temperature and humidity container (saturated sodium chloride aqueous solution) at a temperature of 28°C and a relative humidity of 75%. The weight gain rate (%) of the selenium-containing multivitamin chewable tablets was measured after 7 days. The results are shown in Table 2.

[0042] 2. The L-ascorbic acid content of the selenium-containing compound vitamin chewable tablets obtained in Examples 1-3 and Comparative Examples 1-4 was determined according to the determination methods and standards in Part II of the 2020 edition of the Pharmacopoeia of the People's Republic of China. The degradation rate (%) of L-ascorbic acid after storage for 3 months at a temperature of 37°C and a relative humidity of 75% was calculated. The results are shown in Table 2.

[0043] Table 2 As shown in Table 2, Examples 1-3 of the present invention exhibit superior stability compared to Comparative Examples 1-4. Specifically, the present invention incorporates modified silica in the raw material components, which possesses excellent flowability and compressibility. The increased specific surface area of ​​the modified silica enhances its adsorption capacity, providing more adsorption sites for the active ingredients, effectively reducing vitamin attenuation, and improving the stability of the components.

[0044] 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. The basic principles and main features of the present invention have been described above with specific implementation schemes. Based on the present invention, some modifications or substitutions can be made, but these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of protection claimed by the present invention.

Claims

1. A selenium-containing compound vitamin chewable tablet, characterized in that, The raw materials include the following parts by weight: 10-16 parts selenium-enriched yeast, 25-35 parts L-ascorbic acid, 0.5-1 part vitamin K, 10-20 parts sorbitol, 1-3 parts DL-α-tocopherol acetate, 3-8 parts sodium starch octenyl succinate, 1-5 parts acetylated distarch adipate, 0.7-1.2 parts magnesium stearate, 0.3-0.5 parts potassium citrate, 0.04-0.07 parts steviol glycosides, and 5-10 parts modified silica; The preparation process of the modified silica is as follows: (1) Add silicon dioxide to a mixed solution of concentrated sulfuric acid and hydrogen peroxide to react, and after filtration, washing and drying, hydroxylated silicon dioxide is obtained; (2) After pretreating the citrus fiber, pretreated citrus fiber is obtained; Pretreated citrus fibers were added to an aqueous solution containing TEMPO and sodium bromide, the pH was adjusted and the reaction was carried out. After dialysis and freeze-drying, carboxylated citrus fibers were obtained. (3) Hydroxylated silica and carboxylated citrus fiber were added to anhydrous ethanol for reaction, and after filtration, washing and drying, modified silica was obtained.

2. The selenium-containing compound vitamin chewable tablet as described in claim 1, characterized in that, In step (1), the ratio of silicon dioxide to the mixed solution is 1g:10-20mL; the volume ratio of concentrated sulfuric acid to hydrogen peroxide in the mixed solution is (6-9):(1-4); the reaction temperature is 60-80℃ and the reaction time is 1-3h.

3. The selenium-containing compound vitamin chewable tablet as described in claim 1, characterized in that, In step (2), the ratio of pretreated citrus fiber, TEMPO, sodium bromide, and water is 1g:0.10-0.15g:0.30-0.40g:100mL; the reaction temperature is 30-40℃, the reaction time is 5-6h; and the pH is adjusted to 10-11.

4. The selenium-containing compound vitamin chewable tablet as described in claim 1, characterized in that, In step (3), the ratio of hydroxylated silica, carboxylated citrus fiber, and anhydrous ethanol is 1:(5-10):10-20; the reaction temperature is 70-80℃ and the reaction time is 2-5h.

5. The selenium-containing compound vitamin chewable tablet as described in claim 1, characterized in that, In step (2), the specific method for pretreatment of citrus fiber is as follows: after ball milling, citrus fiber powder is homogenized under high pressure, freeze-dried, and ground to obtain pretreated citrus fiber.

6. The selenium-containing compound vitamin chewable tablet as described in claim 5, characterized in that, The ball milling process has a power of 40-45Hz, a rotation speed of 550-580r / min, and a time of 4-6h; the high-pressure homogenization process has a pressure of 20-40MPa.

7. The selenium-containing compound vitamin chewable tablet as described in claim 1, characterized in that, The vitamin K is vitamin K2; the selenium-enriched yeast contains ≥99% organic selenium.

8. The method for preparing selenium-containing compound vitamin chewable tablets according to any one of claims 1-7, characterized in that, The process includes the following steps: Weigh each raw material component according to the formula and set aside; first mix the other raw materials except magnesium stearate, wet granulate and then dry; then add magnesium stearate, mix evenly and then compress into tablets to obtain the final product.

9. The method for preparing selenium-containing compound vitamin chewable tablets as described in claim 8, characterized in that, The pressure during tablet compression is 8-12 kN.

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