Choline-containing composition of various vitamins and minerals as well as preparation method and application thereof

Abstract

To provide a composition of various vitamins and minerals having solved problems such as moisture absorption and browning.SOLUTION: The present application relates to a choline-containing composition of various vitamins and minerals as well as a preparation method and application thereof. According to the method, the hygroscopicity of choline bitartrate is improved, the cracking and swelling phenomena of the prepared tablets are obviously improved, and a colored coating containing synthetic pigments does not need to be used for covering potential browning of the tablets. After transparent coating is conducted, after three-month accelerated stability investigation is conducted under the conditions of 37°C and 75% of relative humidity, the nutrient content is stable, and the appearance is perfect.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] This application is based on and claims priority to CN Application No. 202210826070.7, filed July 14, 2022. The disclosure of this CN application is incorporated herein in its entirety.

[0002] Technical Field The present application relates to the technical field of pharmaceuticals or health foods, in particular to a composition, in particular a choline-containing composition of multiple vitamins and minerals, its preparation method and its use. [Background technology]

[0003] Vitamins are a type of organic trace substance necessary for the human body to maintain normal physiological functions, including vitamin A, vitamin C, and B vitamins. Minerals are a general term for various inorganic substances that make up human tissues and maintain normal physiological functions, including macro elements such as calcium and magnesium, and trace elements such as iron, zinc, and selenium. Vitamins and minerals play an important role in the growth, metabolism, and development of the human body, but most of them cannot be synthesized by the human body and must be obtained from food. Nutritional supplements containing multiple vitamins and minerals in tablet form can also be used when nutrients from food are insufficient.

[0004] However, the system of multiple vitamin and mineral tablets is complicated, and after moisture absorption, the ingredients react with each other and are prone to browning, especially when vitamin choline is added. Choline is an organic base and a major component of lecithin and sphingomyelin, which can ensure the development of the brain and nervous system and promote fat metabolism in the liver. Among the multiple vitamin and mineral tablets on the market, there are only a handful of products that contain choline. Choline bitartrate and choline chloride, the two common choline sources, are white crystalline powders that are prone to moisture absorption and have large amounts added, making them difficult to use in the manufacturing process. Currently, the appearance of multiple vitamin and mineral tablets on the market is often modified by color coating, but although the color coating can hide the brown color of the tablet after moisture absorption, it cannot hide the damage of the coating after the tablet swells due to moisture absorption. Summary of the Invention [Problem to be solved by the invention]

[0005] Contents of the invention In order to solve the problems existing in the prior art, the present application discloses a tablet containing multiple vitamins and minerals. The tablet has a beautiful appearance and only requires a transparent coating. The nutrient content is stable even after accelerated stability testing for one month under conditions of 37°C and 75% relative humidity. The present application further discloses a process for producing the tablet, which effectively solves the problems of swelling, splitting and browning of tablets containing multiple vitamins and minerals. [Means for solving the problem]

[0006] Specifically, in one embodiment, the present application provides a composition comprising vitamins, choline and minerals, the composition comprising the following ingredients: Ingredient 1: Choline Bitartrate; Ingredient 2: The following nutrients: Minerals including calcium, magnesium, iron, zinc, and selenium; Ingredient 3: The following nutrients: Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin B1, Vitamin B6, Niacin, Biotin, Pantothenic Acid, Vitamin B2, Vitamin B 12 , and vitamins, including folic acid; Ingredient 4: Ascorbyl palmitate.

[0007] In some embodiments, the choline bitartrate is present in the form of a separate dosage unit, for example in the form of a microcapsule. In some embodiments, in addition to the choline bitartrate, the microcapsule further comprises a filler and an encapsulant. In some embodiments, the filler is selected from the group consisting of cornstarch, microcrystalline cellulose, and dextrin (e.g., maltodextrin). In some embodiments, the encapsulant is selected from the group consisting of ethyl cellulose, cellulose acetate, and hydroxypropyl cellulose.

[0008] In some embodiments, the minerals are present in the form of separate dosage units, such as in the form of mineral granules. In some embodiments, in addition to the nutrients, the mineral granules further comprise a binder. In some embodiments, the binder is selected from the group consisting of hydroxypropylmethylcellulose, methylcellulose, sodium carboxymethylcellulose, povidone, copovidone, and gelatin.

[0009] In some embodiments, component 3 does not include vitamin C.

[0010] In some embodiments, the components included in component 3 are divided into two groups:

[0011] Group 1: Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin B1, Vitamin B6, Niacin, Biotin, and Pantothenic Acid; Group 2: Vitamin B2, Vitamin B 12 , and folic acid; The first group further comprises a filler, and the first group further comprises a lubricant.

[0012] In some embodiments, the filler is selected from the group consisting of starch, microcrystalline cellulose, dextrin, and maltodextrin.

[0013] In some embodiments, the first group further comprises one or more selected from the group consisting of microcrystalline cellulose, maltodextrin, copovidone, starch, and croscarmellose sodium. In some embodiments, the lubricant is selected from the group consisting of silicon dioxide, magnesium stearate, talcum powder, and micronized silica gel. In some embodiments, the first and second groups are mixed separately and then combined.

[0014] In some embodiments, the content of each nutrient in the composition, by weight %, is as follows: 0.16-0.80 parts vitamin A, 0.002-0.015 parts vitamin D, 5-150 parts vitamin E, 0.015-0.10 parts vitamin K, 0.5-20 parts vitamin B1, 0.5-20 parts vitamin B2, 0.5-10 parts vitamin B6, 0.0005-0.01 parts vitamin B 12 , 3-15 parts niacin, 0.08-0.50 parts folic acid, 0.01-0.10 parts biotin, 1-20 parts pantothenic acid, 30-500 parts vitamin C, 100-1000 parts choline, 200-1000 parts calcium, 65-350 parts magnesium, 5-20 parts iron, 3-15 parts zinc, and 10-100 parts selenium. The source that provides Vitamin C is ascorbyl palmitate; The source of choline is choline bitartrate.

[0015] In some embodiments, the composition is a tablet or capsule.

[0016] In some embodiments, based on a 2000 tablet / capsule basis, the composition comprises the following nutrients: 80-400mg of vitamin A, 1-7.5mg of vitamin D, 2.5-75g of vitamin E, 7.5-50mg of vitamin K, 0.25-10g of vitamin B1, 0.25-10g of vitamin B2, 0.25-5g of vitamin B6, 0.25-5mg of vitamin B 12 , 1.5 to 7.5 g niacin, 40 to 250 mg folic acid, 5 to 50 mg biotin, 0.5 to 10 g pantothenic acid, 15 to 250 g vitamin C, 50 to 500 g choline, 100 to 500 g calcium, 32.5 to 175 g magnesium, 2.5 to 10 g iron, 1.5 to 7.5 g zinc, and 5 to 50 g selenium.

[0017] In another aspect, the present application provides a method for preparing a composition according to any one of claims 1 to 6, comprising the steps of: (1) Preparing choline bitartrate microcapsules; (2) Preparation of mineral granules: mixing raw materials supplying calcium, magnesium, iron, and zinc, and granulating them to obtain mineral granules; (3) Preparation of Vitamin Premix: Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin B1, Vitamin B6, niacin, biotin, and pantothenic acid are uniformly mixed to obtain Vitamin Premix 1; Vitamin B2, Vitamin B 12 、 folic acid are mixed uniformly to obtain vitamin premix 2; Vitamin premix 1 and Vitamin premix 2 are mixed uniformly to obtain vitamin premix; (4) Formulation: choline bitartrate microcapsules, mineral granules, vitamin premix and ascorbyl palmitate are mixed to obtain a blended material, which is then formulated to obtain a required dosage form; Optionally, the method further comprises the step of coating the dosage form obtained in step (4).

[0018] In some embodiments, the source providing selenium is mixed with the sources providing calcium, magnesium, iron and zinc in step (2) or mixed with the components of Vitamin Premix 1 in step (3).

[0019] The amount of each nutrient added in the present invention is within the appropriate range required by the human body, and the raw materials that supply each nutrient are known to those skilled in the art, and those skilled in the art can select them based on general technical knowledge. More specifically, the raw materials that supply calcium can include calcium carbonate, calcium acetate, calcium chloride, calcium citrate, calcium gluconate, calcium lactate, calcium hydrogen phosphate, calcium dihydrogen phosphate, tricalcium phosphate (calcium phosphate), calcium sulfate, L-calcium lactate, calcium glycerophosphate, calcium citrate malate, etc. The raw materials that supply magnesium can include magnesium carbonate, magnesium sulfate, magnesium oxide, magnesium chloride, magnesium L-threonate, magnesium gluconate, etc. The raw materials that supply iron can include ferrous gluconate, ferrous fumarate, ferrous sulfate, ferrous lactate, ferrous succinate, ferric pyrophosphate, ferric citrate, sodium ferrous citrate, etc. Examples of raw materials that supply zinc include zinc sulfate, zinc citrate, zinc citrate (trihydrate), zinc gluconate, zinc oxide, zinc lactate, zinc acetate, and zinc chloride. Examples of raw materials that supply selenium include sodium selenite, selenium-enriched yeast, L-selenium-methylselenocysteine, selenocarrageenan, selenoprotein, and sodium selenate. Examples of raw materials that supply vitamin A include retinyl acetate, retinyl palmitate, and β-carotene. Examples of raw materials that supply vitamin B1 include thiamine hydrochloride and thiamine nitrate. Examples of raw materials that supply vitamin B2 include riboflavin and riboflavin-5'-sodium phosphate. Examples of raw materials that supply vitamin B6 include pyridoxine hydrochloride. Vitamin B 12Examples of raw materials that supply niacin include nicotinic acid and nicotinamide. Examples of raw materials that supply pantothenic acid include D-calcium pantothenate and D-sodium pantothenate. Examples of raw materials that supply vitamin E include D-α-tocopherol, D-α-tocopherol acetate, D-α-tocopherol succinate, dl-α-tocopherol acetate, dl-α-tocopherol succinate, and vitamin E calcium. Examples of raw materials that supply vitamin K include vitamin K1 and vitamin K2. Examples of raw materials that supply vitamin D include vitamin D2 and vitamin D3. Examples of raw materials that supply biotin include D-biotin.

[0020] In some embodiments, the choline bitartrate microcapsules are prepared by the following steps: a) Mix choline bitartrate and bulking agent uniformly; b) Mixing the capsule material uniformly to obtain a coating solution; c) The products obtained in steps a) and b) are mixed uniformly and dried to obtain choline bitartrate microcapsules.

[0021] In some embodiments, drying is performed in a spray dryer and a fluidized bed, respectively.

[0022] In some embodiments, a sieving operation is further included after drying.

[0023] In some embodiments, the filler and encapsulant are as defined above.

[0024] In some embodiments, in step (2), a binder is added to the mixed raw materials and granulated (e.g., boiling granulation).

[0025] In some embodiments, the binding agent is as defined in any one of the preceding items.

[0026] In some embodiments, the preparation of vitamin premix 1 also includes the step of adding a bulking agent to the vitamins.

[0027] In some embodiments, the step of adding a lubricant to the vitamins during preparation of vitamin premix 2 is also included.

[0028] In some embodiments, the fillers and lubricants are as defined in any one of the preceding paragraphs.

[0029] In some embodiments, in step (4), the mixed material further comprises one or more of a filler, a binder, and a disintegrant.

[0030] In some embodiments, the filler is selected from the group consisting of starch, microcrystalline cellulose, and dextrin (eg, maltodextrin).

[0031] In some embodiments, the binder is selected from the group consisting of hydroxypropyl methylcellulose, methylcellulose, sodium carboxymethylcellulose, povidone, copovidone, and gelatin.

[0032] In some embodiments, the disintegrant is croscarmellose sodium.

[0033] In another aspect, the present application provides the use of a composition according to any one of the items of the first aspect in the manufacture of a dietary supplement. Effect of the Invention

[0034] Beneficial Effects of the Invention The present application provides a choline-containing composition of multiple vitamins and minerals, as well as its preparation method and use, which can achieve at least one of the following technical effects: 1. The hygroscopicity of choline bitartrate is improved; 2. The composition slows or prevents complexation reactions of vitamin C while preserving the antioxidant capacity of vitamin C; 3. The tablets prepared by the method of the present invention can adopt a transparent coating, so that their appearance is beautiful, and the problems of browning, tablet breakage and swelling are significantly improved. [Brief description of the drawings]

[0035] The accompanying drawings described herein are used to provide a further understanding of the present invention and constitute a part of this application. The schematic examples of the present invention and the description thereof are used to explain the present invention and are not to be construed as an inappropriate limitation of the present invention. In the accompanying drawings: [Figure 1] FIG. 1 shows the changes observed for the tablets prepared in Examples 1 to 4 under conditions of 37° C. and 75% RH for one day. [Diagram 2] FIG. 2 shows the changes observed when the tablets prepared in Comparative Examples 1 to 4 were kept at 37° C. and 75% RH for one day. [Diagram 3] FIG. 3 shows the weight increase observed for the tablets prepared in Examples 1 to 4 and Comparative Examples 1 to 4 under conditions of 37° C. and 75% RH for one day. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0036] A concrete model for implementing the invention Hereinafter, the embodiments of the present invention will be described in detail with examples. However, it will be understood by those skilled in the art that the following examples are used only to illustrate the present invention and should not be considered as limiting the scope of the present invention. If there are no specific conditions in the examples, they are carried out according to conventional conditions or conditions suggested by the manufacturer. Furthermore, among the reagents or instruments used, those without manufacturer's instructions are all conventional products available on the market. EXAMPLES

[0037] Example 1 Formulation 1 (1700g, 2000 tablets): Calcium 240g, Magnesium 70g, Iron 7g, Zinc 8g, Selenium 26mg, Vitamin A 340mg, Vitamin D 8mg, Vitamin E 10g, Vitamin K 45mg, Vitamin B13g, Vitamin B23g, Vitamin B63g, Vitamin B 12 3mg, Niacin 10g, Folic Acid 300mg, Biotin 42mg, Pantothenic Acid 6g, Vitamin C 50g, Choline Bitartrate 110g.

[0038] The preparation process was as follows: (1) Preparation of choline bitartrate microcapsules 1) 1kg of choline bitartrate was crushed and sieved, then 50g of cornstarch was added and mixed well for later use; 2) 50g of ethyl cellulose and 3g of silicon dioxide were weighed out in proportion and dissolved in a high-speed homogenizer to obtain a coating solution for later use; 3) The mixture of choline bitartrate and corn starch from step 1) was mixed with the coating solution from step 2) and homogenized with a high speed homogenizer; 4) The mixture of step 3) was spray-dried in a spray dryer, and then transferred to a fluidized bed for drying to obtain choline bitartrate microcapsules; 5) The choline bitartrate microcapsules were sieved and stored in a dry environment.

[0039] (2) Preparation of mineral granules Calcium carbonate, ferrous fumarate, zinc gluconate, and magnesium carbonate were taken according to the prescribed amounts and added to a fluidized bed, and boiling granulation was carried out using 3% hydroxypropylmethylcellulose solution as a binder. After granulation, the resulting mineral granules were sieved for later use.

[0040] (3) Preparation of vitamin premix Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin B1, Vitamin B6, Niacin, Biotin, Pantothenic Acid, and Selenium-enriched Yeast were taken according to the prescribed amounts and mixed uniformly with the same amount of microcrystalline cellulose. 12 , folic acid, and silicon dioxide were taken according to the prescribed amounts and mixed uniformly with the above vitamin mixture to obtain a vitamin premix.

[0041] (4) Blending and tableting One or more of mineral granules, vitamin premix, choline bitartrate microcapsules, ascorbyl palmitate (for vitamin C supplementation), microcrystalline cellulose, maltodextrin, copovidone, starch, croscarmellose sodium, and magnesium stearate were taken according to the prescribed amounts, mixed together, and then subjected to tableting;

[0042] (5) Coating An appropriate amount of transparent coating agent was taken and dissolved in an appropriate amount of water so that the mass fraction of the coating agent became 10%. After preheating the coating pan, uncoated tablets were placed in the coating pan, and the coating liquid was sprayed onto the tablet surfaces to form a film while controlling the conditions of inlet air temperature 70±10°C, tablet bed temperature 50±5°C, outlet air temperature 55±10°C, and spray pressure 0.4MPa, to obtain coated tablets.

[0043] Example 2 Formulation 2 (1700g, 2000 tablets) Calcium 240g, Magnesium 70g, Iron 7g, Zinc 12.5g, Selenium 80mg, Vitamin A 358mg, Vitamin D 10mg, Vitamin E 25g, Vitamin K 80mg, Vitamin B13.5g, Vitamin B23.5g, Vitamin B63.5g, Vitamin B 12 5mg, niacin 12g, folic acid 300mg, biotin 50mg, pantothenic acid 5g, vitamin C 50g, choline bitartrate 120g. The preparation process was the same as in Example 1.

[0044] Example 3 Formulation 3 (1700g, 2000 tablets) Calcium 300g, Magnesium 70g, Iron 16g, Zinc 8g, Selenium 26mg, Vitamin A 340mg, Vitamin D 8mg, Vitamin E 10g, Vitamin K 45mg, Vitamin B13g, Vitamin B23g, Vitamin B63g, Vitamin B 12 3mg, niacin 10g, folic acid 300mg, biotin 42mg, pantothenic acid 6g, vitamin C 50g, choline bitartrate 120g. The preparation process was the same as in Example 1.

[0045] Example 4 Formulation 4 (1700g, 2000 tablets) Calcium 300g, Magnesium 70g, Iron 10g, Zinc 2.8g, Selenium 26mg, Vitamin A 160mg, Vitamin D 8mg, Vitamin E 12g, Vitamin K 20mg, Vitamin B1 1.6g, Vitamin B2 3.5g, Vitamin B6 1.6g, Vitamin B 12 1.6mg, niacin 3.2g, folic acid 400mg, biotin 26mg, pantothenic acid 1.26g, vitamin C 50g, choline bitartrate 120g. The preparation process was the same as in Example 1.

[0046] Comparative Example 1 Comparative formulation 1 (1700g, 2000 tablets) Calcium 240g, Magnesium 70g, Iron 7g, Zinc 8g, Selenium 26mg, Vitamin A 340mg, Vitamin D 8mg, Vitamin E 10g, Vitamin K 45mg, Vitamin B13g, Vitamin B23g, Vitamin B63g, Vitamin B 12 3mg, Niacin 10g, Folic Acid 300mg, Biotin 42mg, Pantothenic Acid 6g, Vitamin C 50g, Choline Bitartrate 110g.

[0047] (1) Preparation of mineral granules Calcium carbonate, ferrous fumarate, zinc gluconate, magnesium carbonate, and selenium-enriched yeast were taken according to the prescribed amounts and added to a fluidized bed dryer, and boiling granulation was carried out using 3% hydroxypropylmethylcellulose solution as a binder. After granulation, the resulting mineral granules were sieved for later use.

[0048] (2) Preparation of vitamin premix Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin B1, Vitamin B6, Niacin, Biotin, and Pantothenic Acid were taken according to the prescribed amounts and mixed uniformly with the same amount of microcrystalline cellulose. Vitamin B2, Vitamin B 12 The folic acid was taken according to the prescribed amount, mixed uniformly with silicon dioxide, and then mixed uniformly with the above vitamin mixture to obtain a vitamin premix.

[0049] (3) Blending and tableting Mineral granules, vitamin premix, commercial choline bitartrate, commercial ascorbic acid, microcrystalline cellulose, and magnesium stearate were taken according to the prescribed amounts, blended together, and then compressed into tablets;

[0050] (4) Coating An appropriate amount of transparent coating agent was taken and dissolved in an appropriate amount of water so that the mass fraction of the coating agent became 10%. After preheating the coating pan, uncoated tablets were placed in the coating pan, and the coating liquid was sprayed onto the tablet surfaces to form a film while controlling the conditions of inlet air temperature 70±10°C, tablet bed temperature 50±5°C, outlet air temperature 55±10°C, and spray pressure 0.4MPa, to obtain coated tablets.

[0051] Comparative Example 2 Comparative formulation 2 (1700g, 2000 tablets) Calcium 240g, Magnesium 70g, Iron 7g, Zinc 8g, Selenium 26mg, Vitamin A 340mg, Vitamin D 8mg, Vitamin E 10g, Vitamin K 45mg, Vitamin B13g, Vitamin B23g, Vitamin B63g, Vitamin B 123mg, Niacin 10g, Folic Acid 300mg, Biotin 42mg, Pantothenic Acid 6g, Vitamin C 50g, Choline Bitartrate 110g.

[0052] (1) Preparation of mineral particles Calcium carbonate, ferrous fumarate, zinc gluconate, magnesium carbonate, and selenium-enriched yeast were taken according to the prescribed amounts and added to a fluidized bed dryer, and boiling granulation was carried out using 3% hydroxypropylmethylcellulose solution as a binder. After granulation, the resulting mineral granules were sieved for later use.

[0053] (2) Preparation of vitamin premix Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin B1, Vitamin B6, Niacin, Biotin, and Pantothenic Acid were taken according to the prescribed amounts and mixed uniformly with the same amount of microcrystalline cellulose. Vitamin B2, Vitamin B 12 The folic acid was taken according to the prescribed amount, mixed uniformly with silicon dioxide, and then mixed with the above vitamin mixture to obtain a vitamin premix.

[0054] (3) Blending and tableting Mineral granules, vitamin premix, commercially available choline bitartrate, ascorbyl palmitate, microcrystalline cellulose, and magnesium stearate were taken according to the prescribed amounts, blended together, and then compressed into tablets;

[0055] (4) Coating An appropriate amount of transparent coating agent was taken and dissolved in an appropriate amount of water so that the mass fraction of the coating agent became 10%. After preheating the coating pan, uncoated tablets were placed in the coating pan, and the coating liquid was sprayed onto the tablet surfaces to form a film while controlling the conditions of inlet air temperature 70±10°C, tablet bed temperature 50±5°C, outlet air temperature 55±10°C, and spray pressure 0.4MPa, to obtain coated tablets.

[0056] Comparative Example 3 Comparative formulation 3 (1700g, 2000 tablets) Calcium 240g, Magnesium 70g, Iron 7g, Zinc 8g, Selenium 26mg, Vitamin A 340mg, Vitamin D 8mg, Vitamin E 10g, Vitamin K 45mg, Vitamin B13g, Vitamin B23g, Vitamin B63g, Vitamin B 12 3mg, Niacin 10g, Folic Acid 300mg, Biotin 42mg, Pantothenic Acid 6g, Vitamin C 50g, Choline Bitartrate 110g.

[0057] (1) Preparation of choline bitartrate microcapsules 1) 1kg of choline bitartrate was crushed and sieved, then 50g of cornstarch was added and mixed well for later use; 2) 50g of ethyl cellulose and 3g of silicon dioxide were weighed out and dissolved in a high-speed homogenizer to obtain a coating solution for later use; 3) The mixture of choline bitartrate and corn starch from step 1) was mixed with the coating solution from step 2) and homogenized with a high speed homogenizer; 4) The mixture of step 3) was spray-dried in a spray dryer, and then transferred to a fluidized bed for drying to obtain choline bitartrate microcapsules; 5) The choline bitartrate microcapsules were sieved and stored in a dry environment.

[0058] (2) Preparation of mineral granules Calcium carbonate, ferrous fumarate, zinc gluconate, magnesium carbonate, and selenium-enriched yeast were taken according to the prescribed amounts and added to a fluidized bed dryer, and boiling granulation was carried out using 3% hydroxypropylmethylcellulose solution as a binder. After granulation, the resulting mineral granules were sieved for later use.

[0059] (3) Preparation of vitamin premix Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin B1, Vitamin B6, Niacin, Biotin, and Pantothenic Acid were taken according to the prescribed amounts and mixed uniformly with the same amount of microcrystalline cellulose. Vitamin B2, Vitamin B 12, folic acid, and silicon dioxide were taken according to the prescribed amounts and mixed uniformly, and then mixed uniformly with the above vitamin mixture to obtain a vitamin premix.

[0060] (4) Blending and tableting Mineral granules, vitamin premix, choline bitartrate microcapsules, commercial ascorbic acid, microcrystalline cellulose, and magnesium stearate were taken according to the prescribed amounts, blended together, and then compressed into tablets;

[0061] (5) Coating An appropriate amount of transparent coating agent was taken and dissolved in an appropriate amount of water so that the mass fraction of the coating agent became 10%. After preheating the coating pan, uncoated tablets were placed in the coating pan, and the coating liquid was sprayed onto the tablet surfaces to form a film while controlling the conditions of inlet air temperature 70±10°C, tablet bed temperature 50±5°C, outlet air temperature 55±10°C, and spray pressure 0.4MPa, to obtain coated tablets.

[0062] Comparative Example 4 Comparative formulation 4 (1700g, 2000 tablets) Calcium 240g, Magnesium 70g, Iron 7g, Zinc 8g, Selenium 26mg, Vitamin A 340mg, Vitamin D 8mg, Vitamin E 10g, Vitamin K 45mg, Vitamin B13g, Vitamin B23g, Vitamin B63g, Vitamin B 12 3mg, Niacin 10g, Folic Acid 300mg, Biotin 42mg, Pantothenic Acid 6g, Vitamin C 50g, Choline Bitartrate 110g.

[0063] (1) Preparation of choline bitartrate microcapsules 1) 1kg of choline bitartrate was crushed and sieved, then 50g of cornstarch was added and mixed well for later use; 2) 50g of ethyl cellulose and 3g of silicon dioxide were weighed out and dissolved in a high-speed homogenizer to obtain a coating solution for later use; 3) The mixture of choline bitartrate and corn starch from step 1) was mixed with the coating solution from step 2) and homogenized with a high speed homogenizer; 4) The mixture of step 3) was spray-dried in a spray dryer, and then transferred to a fluidized bed for drying to obtain choline bitartrate microcapsules; 5) The choline bitartrate microcapsules were sieved and stored in a dry environment.

[0064] (2) Preparation of mineral granules Calcium carbonate, ferrous fumarate, zinc gluconate, magnesium carbonate, and selenium-enriched yeast were taken according to the prescribed amounts and added to a fluidized bed dryer, and boiling granulation was carried out using 3% hydroxypropylmethylcellulose solution as a binder. After granulation, the resulting mineral granules were sieved for later use.

[0065] (3) Preparation of vitamin premix Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin B1, Vitamin B6, Niacin, Biotin, Pantothenic Acid, Vitamin B2, Vitamin B 12 , and folic acid were taken according to the prescribed amounts and mixed in a three-dimensional mixer for later use.

[0066] (4) Blending and tableting Mineral granules, vitamin premix, choline bitartrate microcapsules, ascorbyl palmitate, microcrystalline cellulose, magnesium stearate were taken according to the prescribed amounts, blended together and then compressed into tablets;

[0067] (5) Coating An appropriate amount of transparent coating agent was taken and dissolved in an appropriate amount of water so that the mass fraction of the coating agent became 10%. After preheating the coating pan, uncoated tablets were placed in the coating pan, and the coating liquid was sprayed onto the tablet surfaces to form a film while controlling the conditions of inlet air temperature 70±10°C, tablet bed temperature 50±5°C, outlet air temperature 55±10°C, and spray pressure 0.4MPa, to obtain coated tablets.

[0068] Test Example 1 According to the process requirements of the above examples, the raw materials and preparation process for preparing tablets of multiple vitamins and minerals were selected, and the changes in the tablets were observed under conditions of 37°C and 75% RH for one day, and the changes in the appearance of the tablets are shown in Figure 1.

[0069] According to the process requirements of the above comparative example, the raw materials and preparation process for preparing multiple vitamin and mineral tablets were selected, and the changes in the tablets were observed for one day under conditions of 37°C and 75% RH, and the changes in the appearance of the tablets are shown in Figure 2.

[0070] According to the process requirements of the above comparative example, the raw materials and preparation process for preparing multiple vitamin and mineral tablets were selected, and the changes in the tablets were observed for one day under conditions of 37°C and 75% RH, and the weight increase of the tablets is shown in Figure 3.

[0071] For the above examples, the tablets were compressed and coated according to the designed amount of nutrients for 2 months, then placed in HDPE bottles, 4g of desiccant was added, sealed and capped, and the stability of the tablet ingredients was examined in a constant temperature acceleration box at 37℃ and 75%RH. After 3 months, the nutrient content in the accelerated test samples was detected, and the results are shown in the table below.

[0072] [Table 1]

[0073] Experimental Results In each example, the tablets were prepared according to the process described in the present invention and were coated with a colorless transparent coating. The color of the tablets was light yellow and uniform. Under high temperature and humidity conditions, the color of the tablets was relatively stable. In each comparative example, due to the incompatibility of some materials, immature process, and high hygroscopicity, the tablets showed problems such as browning and spots during high temperature and humidity accelerated process.

[0074] In addition, except for Comparative Examples 1 and 2, the weight gain rate was small in all other Examples and Comparative Examples, and the tablets of the present invention had a low moisture absorption rate and good stability. In addition, the nutrient content in the Example samples after 3 months of accelerated stability testing was measured, and the tablets of the present invention had good stability.

[0075] Test Example 2: Effect of Choline Bitartrate Processing on Hygroscopicity of Tablets Choline is an important nutrient for the human body, but its common compound form, choline bitartrate, has strong hygroscopicity and is easy to attract moisture in tablets, which will have a certain impact on the stability of other materials. In this example, the effects of different choline bitartrate processing processes on the hygroscopicity of tablets are studied.

[0076] 1. Preparation of polyethylene glycol-coated choline: take an appropriate amount of polyethylene glycol, dissolve it in water to obtain a coating solution for later use, add choline bitartrate into the fluidized bed, and spray the coating solution to obtain polyethylene glycol-coated choline. The content of choline bitartrate was 90%.

[0077] 2. Fatty acid mono- and diglyceride embedding process: take an appropriate amount of choline bitartrate, put it into the stirring granulator, turn on the machine, take an appropriate amount of fatty acid mono- and diglyceride, melt it, mix fatty acid mono- and diglyceride and choline bitartrate under stirring, granulate and trim. The content of choline bitartrate is 70%.

[0078] 3. Blending and granulation process of microcrystalline cellulose: Microcrystalline cellulose was mixed with choline bitartrate, put into fluidized bed, and granulated with hydroxypropyl methylcellulose as binder. The content of choline bitartrate was 70%.

[0079] 4. Polyethylene glycol freeze-drying process: Polyethylene glycol was dissolved in water, and choline bitartrate was dissolved therein, stirred to completely dissolve, freeze-dried in a freeze-dryer, and granulated. The content of choline bitartrate was 90%.

[0080] 5. Silicon dioxide embedding process: Take an appropriate amount of silicon dioxide and mix it evenly with choline bitartrate in a three-dimensional mixer. The content of choline bitartrate was 95%.

[0081] 6. Ethyl cellulose microencapsulation process (the process of the present application): take an appropriate amount of choline bitartrate and pass it through an 80 mesh sieve; take an appropriate amount of corn starch, silicon dioxide, and ethyl cellulose and mix them uniformly, then mix and dissolve them well using a high-speed homogenizer, and dry them using a spray dryer to obtain a sample with a choline bitartrate content of 95%.

[0082] 7. Polyvinyl alcohol microencapsulation process: take an appropriate amount of choline bitartrate and pass it through an 80 mesh sieve; take an appropriate amount of corn starch, silicon dioxide, and polyvinyl alcohol and mix well, then mix and dissolve well in a high-speed homogenizer, and dry with a spray dryer to obtain a sample with a choline bitartrate content of 95%.

[0083] 8. β-cyclodextrin spray drying process: take an appropriate amount of choline bitartrate and pass it through an 80 mesh sieve; take an appropriate amount of corn starch, silicon dioxide and β-cyclodextrin, mix and dissolve well in a high-speed homogenizer, and dry it in a spray dryer to obtain a sample with a choline bitartrate content of 95%.

[0084] The prepared sample was added to a mixed raw material of tablets of multiple vitamins and minerals according to the actual amount of choline, and subjected to tableting while controlling the weight and hardness of the tablets, the specific operation being the same as in Example 1. The hygroscopicity of the tablets was examined under the conditions of 37°C and 75% RH.

[0085] [Table 2]

[0086] In the control group, no choline was used. The experimental results show that the tablets prepared according to the present invention have better moisture-proof performance, which has significant advantages compared with other preparation methods.

[0087] Although specific models for carrying out the present invention have been described in detail, those skilled in the art will appreciate that, in accordance with all teachings disclosed herein, various modifications and substitutions can be made to those details, and all such modifications are within the scope of the present invention, the full scope of which is given by the appended claims and their equivalents.

Claims

1. A choline-containing composition of multiple vitamins and minerals, including the following ingredients: Component 1: Choline bitartrate; Ingredient 2: The following nutrients: minerals including calcium, magnesium, iron, zinc, and selenium; Ingredient 3: The following nutrients: Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin B １ Vitamin B ６ Niacin, biotin, pantothenic acid, vitamin B ２ Vitamin B １２ , and vitamins including folic acid; Ingredient 4: Ascorbyl palmitate.

2. Choline bitartrate exists in the form of a separate formulation unit, for example, in the form of microcapsules; Preferably, in addition to choline bitartrate, the microcapsules further comprise a filler and a capsule material; Preferably, the filler is selected from the group consisting of corn starch, microcrystalline cellulose, dextrin, and maltodextrin; Preferably, the capsule material is selected from the group consisting of ethylcellulose, cellulose acetate, and hydroxypropylcellulose, as described in claim 1.

3. Minerals exist in the form of separate formulation units, for example, in the form of mineral granules; Preferably, in addition to nutrients, the mineral granules further contain a binder; Preferably, the binder is selected from the group consisting of hydroxypropyl methylcellulose, methylcellulose, sodium carboxymethylcellulose, povidone, copovidone, and gelatin, as described in claim 1.

4. Component 3 does not contain vitamin C; Preferably, the components contained in component 3 can be divided into the following two groups: Group 1: Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin B １ Vitamin B ６ niacin, biotin, and pantothenic acid; Group 2: Vitamin B ２ Vitamin B １２ , and folic acid, The first group further comprises a filler; preferably, the filler is selected from the group consisting of starch, microcrystalline cellulose, dextrin, and maltodextrin; The second group further includes a lubricant; preferably, the lubricant is selected from the group consisting of silicon dioxide, magnesium stearate, talcum powder, and finely powdered silica gel; Preferably, the composition according to claim 1, wherein the first group and the second group are mixed separately and then combined.

5. The content of each nutrient in the composition, per part by weight, 0.16 to 0.80 parts of vitamin A, 0.002 to 0.015 parts of vitamin D, 5 to 150 parts of vitamin E, 0.015 to 0.10 parts of vitamin K, 0.5 to 20 parts of vitamin B １ , 0.5 to 20 parts of vitamin B ２ , 0.5 to 10 parts of vitamin B ６ , 0.0005 to 0.01 parts of vitamin B １２ , 3 to 15 parts of niacin, 0.08 to 0.50 parts of folic acid, 0.01 to 0.10 parts of biotin, 1 to 20 parts of pantothenic acid, 30 to 500 parts of vitamin C, 100 to 1000 parts of choline, 200 to 1000 parts of calcium, 65 to 350 parts of magnesium, 5 to 20 parts of iron, 3 to 15 parts of zinc, 0.010 to 0.1 parts of selenium The raw material that provides vitamin C is ascorbyl palmitate; The composition according to claim 1, wherein the raw material supplying choline is choline bitartrate.

6. It is a tablet or capsule; Preferably, based on a calculation of 1,000 tablets or 1,000 capsules, the composition according to claim 1 contains the following nutrients: 80-400 mg of vitamin A, 1-7.5 mg of vitamin D, 2.5-75 g of vitamin E, 7.5-50 mg of vitamin K, and 0.25-10 g of vitamin B １ 0.25 to 10 g of vitamin B ２ 0.25 to 5 g of Vitamin B ６ 0.25-5 mg of Vitamin B １２ 1.5-7.5g niacin, 40-250mg folic acid, 5-50mg biotin, 0.5-10g pantothenic acid, 15-250g vitamin C, 50-500g choline, 100-500g calcium, 32.5-175g magnesium, 2.5-10g iron, 1.5-7.5g zinc, and 5-50mg selenium.

7. A method for preparing the composition according to any one of claims 1 to 6, comprising the following steps: (1) Prepare choline bitartrate microcapsules; (2) Preparation of mineral granules: Raw materials supplying calcium, magnesium, iron, and zinc are mixed and granulated to obtain mineral granules; (3) Preparation of vitamin premix: Vitamin A, Vitamin D, Vitamin E, Vitamin K, Vitamin B １ Vitamin B ６ Mix niacin, biotin, and pantothenic acid to obtain vitamin premix 1; vitamin B ２ Vitamin B １２ , and folic acid are mixed to obtain vitamin premix 2; vitamin premix 1 and vitamin premix 2 are mixed to obtain vitamin premix; preferably, the raw material that supplies selenium in step (2) is mixed with the raw materials that supply calcium, magnesium, iron and zinc, or is mixed with the components of vitamin premix 1 in step (3); (4) Formulation: Mix choline bitartrate microcapsules, mineral granules, vitamin premix and ascorbyl palmitate to obtain a mixed material, which is then formulated to obtain the required dosage form; The method optionally further includes a step of coating the dosage form obtained in step (4).

8. The preparation method according to claim 7, wherein choline bitartrate microcapsules are prepared by the following steps: a) Mix choline bitartrate with the filler; b) Mix the capsule materials to obtain a coating solution; c) The products obtained in steps a) and b) are mixed and dried to obtain choline bitartrate microcapsules; Preferably, drying is carried out using a spray dryer and a fluidized bed, respectively; Preferably, a sieving process is further included after drying; Preferably, the filler is selected from the group consisting of corn starch, microcrystalline cellulose, dextrin, and maltodextrin, and the capsule material is selected from the group consisting of ethylcellulose, cellulose acetate, and hydroxypropylcellulose.

9. In step (2), a binder is added to the mixed raw materials and granulation is carried out; Preferably, the binder is selected from the group consisting of hydroxypropyl methylcellulose, methylcellulose, sodium carboxymethylcellulose, povidone, copovidone, and gelatin, in the preparation method according to claim 7.

10. The preparation of vitamin premix 1 further includes the step of adding fillers to the vitamins; Preferably, the preparation of vitamin premix 2 further includes the step of adding a lubricant to the vitamins; Preferably, the filler is selected from the group consisting of starch, microcrystalline cellulose, dextrin, and maltodextrin, and the lubricant is selected from the group consisting of silicon dioxide, magnesium stearate, talcum powder, and micronized silica gel, according to claim 7.

11. In step (4), the mixed material further comprises one or more selected from the group consisting of fillers, binders, and disintegrants; Preferably, the filler is selected from the group consisting of starch, microcrystalline cellulose, and dextrin (e.g., maltodextrin); Preferably, the binder is selected from the group consisting of hydroxypropyl methylcellulose, methylcellulose, sodium carboxymethylcellulose, povidone, copovidone, and gelatin; Preferably, the disintegrant is croscarmellose sodium, according to claim 7.

12. Use of the composition according to any one of claims 1 to 6 in the manufacture of a nutritional supplement.

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