Weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix and preparation method thereof

Abstract

The present invention discloses a weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix and a preparation method thereof, and relates to the technical field of nutritional supplements. The mineral matrix comprises a composite calcium source, a dual magnesium source, a zinc glycinate chelate, an organic acid buffer system and a ternary aqueous dispersion stabilization system. During preparation, a composite calcium source mixture, a magnesium-zinc source mixture and a weakly acidic aqueous dispersion stabilization matrix are respectively obtained, and then mixed to obtain the mineral matrix, which may be further prepared into an oral liquid, tablets, hard capsules, granules or a solid beverage. The present invention reduces the precipitation rate of mineral elements in a weakly acidic aqueous system, improves the dissolution rates of calcium, magnesium and zinc under low-acid conditions, and improves mouthfeel and multi-dosage-form processing adaptability.

Description

[0001] DESCRIPTION

[0002] Weakly Acidic Uniformly Dispersible Oral Calcium-Magnesium-Zinc Mineral Matrix and Preparation Method Thereof

[0003] Technical Field

[0004] The present invention relates to the technical field of nutritional supplements, and particularly relates to a weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix and a preparation method thereof.

[0005] Background Art

[0006] Calcium, magnesium and zinc are important mineral elements required by the human body, and are commonly used in nutritional supplement products such as oral liquids, tablets, hard capsules, granules and solid beverages. Existing calcium-magnesium-zinc supplement products generally use calcium carbonate, calcium citrate, calcium lactate, magnesium oxide, magnesium citrate, zinc gluconate and the like as mineral sources. However, when multiple mineral elements coexist, they are readily affected by system pH, ionic strength and local concentration, and problems such as insufficient dissolution, flocculation, sedimentation or bottom hard precipitation may occur in a weakly acidic aqueous system, thereby affecting product appearance stability and uniformity of mineral element intake;

[0007] Meanwhile, some calcium salts, magnesium salts and zinc salts have insufficient dissolution under low-acid conditions. Particularly in a low-acid simulated gastric fluid environment, ordinary inorganic salts or some organic salts are difficult to make compatible with both a relatively high mineral content and good dissolution performance. If dissolution is improved merely by increasing acidity, the product may have excessively strong sourness and irritating mouthfeel, which is not conducive to long-term administration. In addition, zinc salts and some magnesium salts have obvious metallic taste, astringency or bitterness, and relying only on sweeteners, flavoring agents and other excipients for masking cannot fundamentally improve mouthfeel and system stability;

[0008] For solid dosage forms, calcium-magnesium-zinc composite mineral powders also have problems such as poor flowability, moisture absorption and caking, uneven capsule filling, insufficient tablet formability and obvious precipitation after reconstitution. Existing solutions mostly focus on single mineral source replacement, single suspension stabilization or single mouthfeel modification, and lack an overall design for a calcium, magnesium and zinc composite system in terms of weakly acidicDESCRIPTION

[0009] dispersion, low-acid dissolution, mouthfeel improvement and multi-dosage-form processing adaptability;

[0010] Therefore, the present invention provides a weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix and a preparation method thereof.

[0011] Summary of the Invention

[0012] To solve the above technical problems, a weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix and a preparation method thereof are provided, and the technical solution solves the above problems of a calcium-magnesium-zinc composite system being prone to precipitation under weakly acidic conditions, insufficient dissolution, poor mouthfeel and poor multi-dosage-form processing adaptability.

[0013] To achieve the above objects, the technical solution adopted by the present invention is as follows:

[0014] A weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix and a preparation method thereof, comprising:

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] By synergistically combining a composite calcium source, a dual magnesium source, a zinc glycinate chelate, an organic acid buffer system and a ternary aqueous dispersion stabilization system, the present invention constructs a calcium-magnesium-zinc composite mineral matrix suitable for a weakly acidic oral system. The present invention solves the problems of existing calcium-magnesium-zinc composite products being prone to flocculation, sedimentation or hard precipitation in a weakly acidic aqueous system, and improves the dispersion uniformity of mineral elements. Meanwhile, the invention improves insufficient dissolution of calcium, magnesium and zinc under low-acid simulated gastric fluid conditions, and reduces metallic astringency and rough mouthfeel caused by ordinary mineral salts. In addition, the obtained mineral matrix can be adapted to multiple dosage forms such as uniformly dispersible oral liquids, tablets, hard capsules, granules or solid beverages, thereby improving product processingDESCRIPTION

[0017] adaptability and storage stability.

[0018] Brief Description of the Drawings

[0019] FIG. l is a flow chart of the preparation method of the present invention.

[0020] Detailed Description of the Embodiments

[0021] The following description is provided to disclose the present invention so that those skilled in the art can practice the present invention. The preferred embodiments in the following description are merely examples, and other obvious variations may occur to those skilled in the art.

[0022] As shown in FIG. 1, in the present invention, calcium citrate malate, calcium lactate gluconate and calcium glycinate chelate are first sieved respectively and then mixed to obtain a composite calcium source mixture; magnesium glycinate chelate, magnesium malate and zinc glycinate chelate are then sieved respectively and mixed to obtain a magnesium-zinc source mixture; meanwhile, citric acid, malic acid, sodium citrate, inulin, gum arabic and hydroxypropyl methylcellulose are mixed to obtain a weakly acidic aqueous dispersion stabilization matrix; finally, the composite calcium source mixture, the magnesium-zinc source mixture and the weakly acidic aqueous dispersion stabilization matrix are mixed to obtain a weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix. The obtained mineral matrix can be further used for preparing a uniformly dispersible oral liquid, tablets, hard capsules, granules or a solid beverage.

[0023] Unless otherwise specified, the amounts of the following components are all calculated on a dry basis. The weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix refers to a calcium-magnesium-zinc mineral composite matrix that can form a relatively uniform dispersion state in a weakly acidic aqueous system and can be used in oral supplement products such as oral liquids, tablets, hard capsules, granules or solid beverages.

[0024] The weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix of the present invention consists of a composite calcium source, a dual magnesium source, a zinc glycinate chelate, an organic acid buffer system and a ternary aqueous dispersion stabilization system. The composite calcium sourceDESCRIPTION

[0025] consists of calcium citrate malate, calcium lactate gluconate and calcium glycinate chelate; the dual magnesium source consists of magnesium glycinate chelate and magnesium malate; the organic acid buffer system consists of citric acid, malic acid and sodium citrate; and the ternary aqueous dispersion stabilization system consists of inulin, gum arabic and hydroxypropyl methylcellulose.

[0026] In the present invention, calcium citrate malate is used to provide the main calcium source and is conducive to improving dissolution performance in a weakly acidic system; calcium lactate gluconate serves as a highly water-soluble auxiliary calcium source and is conducive to improving the dispersibility of the calcium source in a weakly acidic aqueous system; and calcium glycinate chelate serves as an amino acid chelated calcium source and is conducive to improving mouthfeel and dissolution performance under low-acid conditions. Compared with a single calcium source, combined use of the three calcium sources more readily balances water dispersibility, mouthfeel and solid dosage form processing adaptability.

[0027] Magnesium glycinate chelate and magnesium malate together constitute the dual magnesium source. The magnesium glycinate chelate is conducive to reducing the rough feeling and astringency caused by ordinary magnesium salts, and magnesium malate is conducive to improving dispersion and dissolution performance of the magnesium source in a weakly acidic system. After the two are combined, deficiencies of a single magnesium source in water dispersibility, low-acid dissolution rate or powder processing performance can be avoided.

[0028] Zinc glycinate chelate is used as the zinc source. Ordinary zinc salts readily produce an obvious metallic astringent aftertaste in oral liquids or reconstitution systems, whereas zinc glycinate chelate can reduce the aftertaste astringency caused by the zinc source while providing elemental zinc.

[0029] Citric acid, malic acid and sodium citrate constitute the organic acid buffer system. This system is used to maintain the product environment within a weakly acidic range, and is particularly suitable for oral liquids or reconstitution systems having a pH of 3.6-4.6. Through cooperation among citric acid, malic acid andDESCRIPTION

[0030] sodium citrate, local acid-base fluctuation can be reduced, and the risk of precipitation of the calcium, magnesium and zinc composite system in a weakly acidic aqueous system can be lowered.

[0031] Inulin, gum arabic and hydroxypropyl methylcellulose constitute the ternary aqueous dispersion stabilization system. Inulin, as a soluble dietary fiber, is conducive to improving mouthfeel and powder dispersibility; gum arabic is conducive to improving dispersion stability of microparticles in an aqueous system; and hydroxypropyl methylcellulose is conducive to improving suspension stability of the system. The combined use of the three can reduce mineral particle sedimentation, caking or hard precipitation.

[0032] In one embodiment, based on the total dry-basis mass of the mineral matrix, the composite calcium source is present in a mass percentage of 55.0-65.0%, the dual magnesium source is present in a mass percentage of 24.0-31.0%, the zinc glycinate chelate is present in a mass percentage of 1.0-2.0%, the organic acid buffer system is present in a mass percentage of 4.5-6.5%, and the ternary aqueous dispersion stabilization system is present in a mass percentage of 7.0-10.5%. After the above components are compounded, a calcium-magnesium-zinc mineral matrix suitable for a weakly acidic uniformly dispersible oral system can be formed.

[0033] In a preferred embodiment, the mass ratio of calcium citrate malate, calcium lactate gluconate and calcium glycinate chelate is 1:0.51-0.70:0.13-0.20. By controlling this ratio, the composite calcium source can achieve a balance among calcium content, weakly acidic dispersibility and mouthfeel.

[0034] In a preferred embodiment, the mass ratio of magnesium glycinate chelate to magnesium malate is 1.35-1.80:1. By controlling this ratio, the problems of powder moisture absorption and cost caused by merely increasing magnesium glycinate chelate can be avoided, and the insufficient low-acid dissolution and mouthfeel performance caused by merely using magnesium malate can also be avoided.

[0035] In a preferred embodiment, the mass ratio of citric acid, malic acid and sodium citrate is 1:1.20-1.80:0.50-0.85. By controlling this ratio, the system can beDESCRIPTION

[0036] maintained in a weakly acidic buffered environment, thereby reducing local precipitation of calcium-magnesium-zinc composite minerals in an aqueous system.

[0037] In a preferred embodiment, the mass ratio of inulin, gum arabic and hydroxypropyl methylcellulose is 1:0.45-0.75:0.12-0.24. By controlling this ratio, the dispersion stability of mineral particles in the aqueous system can be improved without significantly increasing the viscous mouthfeel of the oral liquid, and powder flowability and anti-caking properties of solid dosage forms can also be improved.

[0038] In one embodiment, the mineral matrix comprises the following components in parts by weight:

[0039] calcium citrate malate 650-760 parts;

[0040] calcium lactate gluconate 390-510 parts;

[0041] calcium glycinate chelate 100-140 parts;

[0042] magnesium glycinate chelate 320-400 parts;

[0043] magnesium malate 200-260 parts;

[0044] zinc glycinate chelate 25-35 parts;

[0045] citric acid 30-45 parts;

[0046] malic acid 45-65 parts;

[0047] sodium citrate 18-32 parts;

[0048] inulin 85-115 parts;

[0049] gum arabic 45-75 parts;

[0050] hydroxypropyl methylcellulose 12-24 parts.

[0051] In one embodiment, the elemental calcium content in calcium citrate malate is 20.0-26.0%, the elemental calcium content in calcium lactate gluconate is 12.0-14.5%, and the elemental calcium content in calcium glycinate chelate is 13.0-20.0%; the elemental magnesium content in magnesium glycinate chelate is 10.0-16.0%, the elemental magnesium content in magnesium malate is 10.0-16.0%, and the elemental zinc content in zinc glycinate chelate is 18.0-22.0%. By controlling the above element content ranges, the elemental calcium, elemental magnesium and elemental zinc provided at the recommended daily dosage can fall within expected ranges.DESCRIPTION

[0052] In one embodiment, based on a recommended daily dosage, the recommended daily dosage of the mineral matrix is 2.0-2.4 g, and provides 180-260 mg of elemental calcium, 70-110 mg of elemental magnesium and 4-8 mg of elemental zinc.

[0053] Embodiment 1: Weakly Acidic Uniformly Dispersible Oral Calcium-Magnesium-Zinc Mineral Matrix

[0054] This embodiment provides a weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix. Based on each recommended daily dosage, the mineral matrix comprises the following components:

[0055] calcium citrate malate 700 mg;

[0056] calcium lactate gluconate 450 mg;

[0057] calcium glycinate chelate 120 mg;

[0058] magnesium glycinate chelate 360 mg;

[0059] magnesium malate 230 mg;

[0060] zinc glycinate chelate 30 mg;

[0061] citric acid 35 mg;

[0062] malic acid 55 mg;

[0063] sodium citrate 25 mg;

[0064] inulin 100 mg;

[0065] gum arabic 60 mg;

[0066] hydroxypropyl methyl cellulose 18 mg.

[0067] The total mass of the above mineral matrix in each recommended daily dosage is 2183 mg.

[0068] Wherein the elemental calcium content in calcium citrate malate is 24.0%, the elemental calcium content in calcium lactate gluconate is 13.0%, and the elemental calcium content in calcium glycinate chelate is 18.0%; the elemental magnesium content in magnesium glycinate chelate is 14.0%, the elemental magnesium content in magnesium malate is 12.0%; and the elemental zinc content in zinc glycinate chelate is 20.0%.

[0069] Calculated according to the above contents, each recommended daily dosage ofDESCRIPTION

[0070] this embodiment can provide about 248.1 mg of elemental calcium, about 78.0 mg of elemental magnesium and about 6.0 mg of elemental zinc.

[0071] The preparation method of this embodiment is as follows:

[0072] 51, taking calcium citrate malate, calcium lactate gluconate and calcium glycinate chelate, respectively passing same through a 60-mesh sieve, and then mixing for 15 minutes to obtain a composite calcium source mixture;

[0073] 52, taking magnesium glycinate chelate, magnesium malate and zinc glycinate chelate, respectively passing same through a 60-mesh sieve, and then mixing for 12 minutes to obtain a magnesium-zinc source mixture;

[0074] 53, taking citric acid, malic acid, sodium citrate, inulin, gum arabic and hydroxypropyl methyl cellulose, and mixing same for 10 minutes to obtain a weakly acidic aqueous dispersion stabilization matrix;

[0075] 54, mixing the composite calcium source mixture, the magnesium-zinc source mixture and the weakly acidic aqueous dispersion stabilization matrix for 20 minutes to obtain the weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix.

[0076] The above preparation method adopts group premixing followed by final mixing. Premixing the composite calcium source is conducive to uniform distribution of the three calcium sources in the powder; premixing the magnesium source and the zinc source is conducive to reducing local enrichment of the trace zinc source; and premixing the organic acid buffer system and the ternary aqueous dispersion stabilization system is conducive to subsequently rapidly forming a weakly acidic dispersion environment in an aqueous system. Finally, the three types of premixes are subjected to final mixing, thereby improving the overall uniformity of the mineral matrix.

[0077] Embodiment 2: No. 00 Hard Capsule

[0078] Using the mineral matrix obtained in Embodiment 1 as the main raw material, a No. 00 hard capsule is prepared. Each recommended daily dosage comprises the following components:DESCRIPTION

[0079] mineral matrix 2183 mg;

[0080] microcrystalline cellulose 120 mg;

[0081] silicon dioxide 18 mg;

[0082] magnesium stearate 12 mg.

[0083] The preparation method is as follows:

[0084] The mineral matrix and microcrystalline cellulose are mixed for 15 minutes, silicon dioxide is added and mixing is continued for 8 minutes, and then magnesium stearate is added and mixed for 3 minutes to obtain a capsule filling mixture. The obtained capsule filling mixture is filled into No. 00 hard capsules to prepare a hard capsule with a daily dosage of 4 capsules.

[0085] Wherein the microcrystalline cellulose is used to improve the volume and filling performance of the capsule contents, the silicon dioxide is used to improve powder flowability, and the magnesium stearate is used to improve lubricity during the filling process.

[0086] Embodiment 3: Tablet

[0087] Using the mineral matrix obtained in Embodiment 1 as the main raw material, a tablet is prepared. Each recommended daily dosage comprises the following components:

[0088] mineral matrix 2183 mg;

[0089] microcrystalline cellulose 180 mg;

[0090] maltodextrin 120 mg;

[0091] croscarmellose sodium 45 mg;

[0092] silicon dioxide 18 mg;

[0093] magnesium stearate 15 mg.

[0094] The preparation method is as follows:

[0095] The mineral matrix, microcrystalline cellulose and maltodextrin are mixed, an appropriate amount of purified water is added to prepare a soft mass, the soft mass is passed through a 20-mesh sieve for granulation, and dried at 50-60°C until the loss on drying is not higher than 5.0%. After sizing, croscarmellose sodium, silicon dioxideDESCRIPTION

[0096] and magnesium stearate are added, and after uniform mixing, tableting is carried out to prepare tablets with a daily dosage of 2 tablets, each tablet having a mass of 1.25-1.30 g.

[0097] Wherein the microcrystalline cellulose and maltodextrin are used to improve tablet formability, the croscarmellose sodium is used to improve disintegration performance, the silicon dioxide is used to improve flowability, and the magnesium stearate is used to improve tableting lubricity.

[0098] Embodiment 4: Uniformly Dispersible Oral Liquid

[0099] Based on the components described in Embodiment 1, a uniformly dispersible oral liquid is prepared. Each recommended daily dosage is prepared into a 30 mL oral liquid, comprising the following components:

[0100] calcium citrate malate 700 mg;

[0101] calcium lactate gluconate 450 mg;

[0102] calcium glycinate chelate 120 mg;

[0103] magnesium glycinate chelate 360 mg;

[0104] magnesium malate 230 mg;

[0105] zinc glycinate chelate 30 mg;

[0106] citric acid 35 mg;

[0107] malic acid 55 mg;

[0108] sodium citrate 25 mg;

[0109] inulin 100 mg;

[0110] gum arabic 60 mg;

[0111] hydroxypropyl methyl cellulose 18 mg;

[0112] appropriate amount of sweetener;

[0113] appropriate amount of edible flavor;

[0114] appropriate amount of purified water.

[0115] The preparation method is as follows:

[0116] About 70% of the prescribed amount of purified water is added into a liquid preparation tank and heated to 40-50°C; inulin, gum arabic and hydroxypropylDESCRIPTION

[0117] methylcellulose are added and stirred until fully swollen and dispersed; citric acid, malic acid and sodium citrate are added, and stirring is continued so that the system forms a weakly acidic buffered environment; calcium lactate gluconate, calcium citrate malate, calcium glycinate chelate, magnesium glycinate chelate, magnesium malate and zinc glycinate chelate are then sequentially added, and stirring is continued until uniform dispersion is achieved; the sweetener and the edible flavor are added, and purified water is supplemented to 30 mL; the pH is adjusted to 3.8-4.3, and after homogenization treatment, coarse particles are removed by filtration through an 80-120 mesh screen, followed by filling to obtain the uniformly dispersible oral liquid.

[0118] The preparation method of the oral liquid does not simply add all powders into water at one time, but first allows inulin, gum arabic and hydroxypropyl methylcellulose to swell in water, then adds citric acid, malic acid and sodium citrate to form a weakly acidic buffered environment, and finally adds the calcium source, magnesium source and zinc source stepwise. This can reduce precipitation formation from mineral sources under locally high-concentration conditions, and is also conducive to reducing metallic astringency.

[0119] Embodiment 5: Granule or Solid Beverage

[0120] Using the mineral matrix obtained in Embodiment 1 as the main raw material, granules or a solid beverage are prepared. Each recommended daily dosage comprises the following components:

[0121] mineral matrix 2183 mg;

[0122] erythritol 500 mg;

[0123] maltodextrin 250 mg;

[0124] lemon fruit powder or another food flavoring powder 100 mg;

[0125] silicon dioxide 15 mg.

[0126] The preparation method is as follows:

[0127] The mineral matrix, erythritol, maltodextrin and food flavoring powder are mixed, an appropriate amount of purified water is added to prepare a soft mass, the

[0128] itDESCRIPTION

[0129] soft mass is passed through an 18-24 mesh sieve for granulation, dried at 50-60°C, sized, and then mixed with silicon dioxide to obtain granules or a solid beverage.

[0130] The obtained granules or solid beverage may be packaged as one sachet per day. When used, they may be added into water and stirred or shaken before drinking. Because the mineral matrix contains the organic acid buffer system and the ternary aqueous dispersion stabilization system, a relatively uniform dispersion system can be formed under weakly acidic conditions after reconstitution.

[0131] Embodiment 6: General Preparation Method for Solid Dosage Forms When preparing tablets, hard capsules, granules or a solid beverage, the weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix obtained in Embodiment 1 may be subjected to wet granulation or dry granulation. The obtained granules have a D50 particle size controlled at 80-280 pm and a loss on drying not higher than 5.0%. Subsequently, excipients acceptable in the field of food or nutritional supplements are added according to the target dosage form, followed by tableting, capsule filling or packaging.

[0132] When the target dosage form is a tablet, microcrystalline cellulose, maltodextrin, croscarmellose sodium, silicon dioxide and magnesium stearate may be added followed by tableting.

[0133] When the target dosage form is a hard capsule, microcrystalline cellulose, silicon dioxide and magnesium stearate may be added followed by capsule filling.

[0134] When the target dosage form is granules or a solid beverage, erythritol, maltodextrin, food flavoring powder and silicon dioxide may be added followed by packaging.

[0135] By controlling the D50 particle size and loss on drying of the granules, moisture absorption, caking and flowability decline in solid dosage forms during storage can be reduced, while stability of capsule filling, tableting or packaging can be ensured.

[0136] Comparative Example Settings

[0137] In order to verify the synergistic effect of the composite system of the present invention, the following comparative examples are provided. On the basis of keepingDESCRIPTION

[0138] the contents of elemental calcium, elemental magnesium and elemental zinc close to those of Embodiment 1, each comparative example is supplemented with maltodextrin to the same dry-basis mass as Embodiment 1, and is tested under the same pH, same sample addition amount, same stirring time, same standing time or same dissolution conditions.

[0139] Comparative Example 1: Conventional inorganic mineral salt composition. Calcium carbonate, magnesium oxide and zinc oxide are respectively used as the calcium source, magnesium source and zinc source, such that the elemental calcium, elemental magnesium and elemental zinc provided thereby are close to those of Embodiment 1. Except for different mineral sources, the amounts of the organic acid buffer system and the ternary aqueous dispersion stabilization system are set with reference to Embodiment 1.

[0140] Comparative Example 2: Ordinary organic acid salt composition. Calcium citrate, magnesium citrate and zinc gluconate are respectively used as the calcium source, magnesium source and zinc source, such that the elemental calcium, elemental magnesium and elemental zinc provided thereby are close to those of Embodiment 1. Except for different mineral sources, the amounts of the organic acid buffer system and the ternary aqueous dispersion stabilization system are set with reference to Embodiment 1.

[0141] Comparative Example 3: Composition lacking the ternary aqueous dispersion stabilization system. A composition is prepared according to the mineral source and organic acid buffer system composition of Embodiment 1, but inulin, gum arabic and hydroxypropyl methylcellulose are not added, and maltodextrin is used to make up the dry-basis mass.

[0142] Comparative Example 4: Composition lacking the organic acid buffer system. A composition is prepared according to the mineral source and ternary aqueous dispersion stabilization system composition of Embodiment 1, but citric acid, malic acid and sodium citrate are not added, and maltodextrin is used to make up the dry-basis mass.DESCRIPTION

[0143] Comparative Example 5: Single calcium lactate gluconate system. Calcium lactate gluconate is used as the main calcium source such that the elemental calcium provided thereby is close to that of Embodiment 1, and calcium citrate malate and calcium glycinate chelate are not added. The magnesium source, zinc source, organic acid buffer system and ternary aqueous dispersion stabilization system adopt the same compositions as in Embodiment 1, and maltodextrin is used to make up the dry-basis mass.

[0144] Comparative Example 6: Composition with a replaced zinc source. A composition is prepared according to the calcium source, magnesium source, organic acid buffer system and ternary aqueous dispersion stabilization system of Embodiment 1, but the zinc glycinate chelate is replaced with zinc gluconate having an equal elemental zinc content, and maltodextrin is used to make up the dry-basis mass.

[0145] Comparative Example 7: Composition with a replaced magnesium source. A composition is prepared according to the calcium source, zinc source, organic acid buffer system and ternary aqueous dispersion stabilization system of Embodiment 1, but the magnesium glycinate chelate is replaced with magnesium citrate having an equal elemental magnesium content, and maltodextrin is used to make up the dry-basis mass.

[0146] Comparative Example 8: Composition lacking magnesium malate. A composition is prepared according to the calcium source, magnesium glycinate chelate, zinc source, organic acid buffer system and ternary aqueous dispersion stabilization system of Embodiment 1, but magnesium malate is not added, the magnesium content is made up with magnesium glycinate chelate having an equal elemental magnesium content, and maltodextrin is used to make up the dry-basis mass.

[0147] Comparative Example 9: Conventional liquid cal cium-magnesium -zinc organic salt system. Calcium lactate, calcium gluconate and calcium citrate malate are used as calcium sources, magnesium gluconate and magnesium citrate are used as magnesiumDESCRIPTION

[0148] sources, and zinc gluconate is used as a zinc source, such that the elemental calcium, elemental magnesium and elemental zinc provided thereby are close to those of Embodiment 1. The amounts of the organic acid buffer system and the ternary aqueous dispersion stabilization system are set with reference to Embodiment 1, and maltodextrin is used to make up the dry-basis mass.

[0149] Experimental Example 1: Evaluation of Mineral Element Precipitation Rate in a Weakly Acidic Aqueous System

[0150] Samples of Embodiment 1, Embodiment 4 and Comparative Examples 1-9 are tested respectively at 2.183 g of dry-basis sample added per 30 mL of a pH 4.0 citric acid-sodium citrate aqueous system. After the sample is added, the system is stirred for 5 minutes and allowed to stand for 24 hours. After standing is completed, centrifugation is carried out at 4000 rpm for 15 minutes, and the precipitate is collected. The precipitate is washed with a small amount of pH 4.0 buffer solution, dried at 60°C to constant weight, and then the contents of calcium, magnesium and zinc elements in the precipitate are measured by inductively coupled plasma optical emission spectrometry or atomic absorption spectrophotometry. Each sample is measured in parallel three times, and the results are expressed as mean ± standard deviation.

[0151] The mineral element precipitation rate is calculated as follows:

[0152] mineral element precipitation rate = total amount of calcium, magnesium and zinc elements in precipitate / total amount of calcium, magnesium and zinc elements in sample x 100%.

[0153] The test results are as follows:

[0154] The 24-hour mineral element precipitation rate of Embodiment 1 in the pH 4.0 weakly acidic aqueous system is 2.4 ± 0.3%, and the appearance is uniformly dispersed with a small amount of fine sediment at the bottom.

[0155] The 24-hour mineral element precipitation rate of the uniformly dispersible oral liquid prepared in Embodiment 4 in the pH 4.0 weakly acidic aqueous system is 2.1 ± 0.2%, and the appearance is uniformly dispersed without obvious hard precipitation.DESCRIPTION

[0156] The precipitation rate of Comparative Example 1 is 13.8 ± 0.7%, with obvious precipitation and bottom hard caking; the precipitation rate of Comparative Example 2 is 7.6 ± 0.5%, with relatively obvious precipitation; the precipitation rate of Comparative Example 3 is 8.9 ± 0.6%, with flocculent precipitation; the precipitation rate of Comparative Example 4 is 10.5 ± 0.8%, with obvious precipitation and a non-uniform system; the precipitation rate of Comparative Example 5 is 5.8 ± 0.4%; the precipitation rate of Comparative Example 6 is 6.4 ± 0.5%; the precipitation rate of Comparative Example 7 is 7.1 ± 0.6%; the precipitation rate of Comparative Example 8 is 6.8 ± 0.5%; and the precipitation rate of Comparative Example 9 is 8.2 ± 0.6%.

[0157] It can be seen from the above results that the 24-hour mineral element precipitation rate of the embodiments of the present invention in the pH 4.0 weakly acidic aqueous system is lower than 3.5% and is significantly lower than those of the comparative examples, indicating that the combined cooperation of the composite calcium source, the dual magnesium source, the zinc glycinate chelate, the organic acid buffer system and the ternary aqueous dispersion stabilization system can improve dispersion stability of the calcium-magnesium-zinc composite minerals in the weakly acidic aqueous system.

[0158] Experimental Example 2: Evaluation of Dissolution Rate in Low-Acid Simulated Gastric Fluid

[0159] Samples of Embodiment 1, Embodiment 2, Embodiment 3 and Comparative Examples 1-9 are tested respectively at 2.183 g of dry-basis sample added per 30 mL of a pH 4.5 low-acid simulated gastric fluid. The low-acid simulated gastric fluid contains 2.0 g / L sodium chloride and 3.2 g / L pepsin, and is adjusted to pH 4.5 with hydrochloric acid. Each sample is shaken at 37°C and 100 rpm, and sampled at 30 minutes. After filtration, the contents of calcium, magnesium and zinc are measured by inductively coupled plasma optical emission spectrometry or atomic absorption spectrophotometry, and the 30-minute dissolution rate is calculated. Each sample is measured in parallel three times, and the results are expressed as mean ± standardDESCRIPTION

[0160] deviation.

[0161] The dissolution rate is calculated as follows:

[0162] dissolution rate = amount of dissolved element at 30 minutes / total amount of corresponding element in sample x 100%.

[0163] The test results show that, in Embodiment 1, the 30-minute calcium dissolution rate is 86.3 ± 1.8%, the 30-minute magnesium dissolution rate is 83.7 ± 1.5%, and the 30-minute zinc dissolution rate is 88.5 ± 1.6%.

[0164] In the hard capsule of Embodiment 2, the 30-minute calcium dissolution rate is 84.9 ± 1.6%, the 30-minute magnesium dissolution rate is 82.1 ± 1.7%, and the 30-minute zinc dissolution rate is 87.2 ± 1.4%.

[0165] In the tablet of Embodiment 3, the 30-minute calcium dissolution rate is 82.6 ± 1.9%, the 30-minute magnesium dissolution rate is 80.4 ± 1.6%, and the 30-minute zinc dissolution rate is 85.8 ± 1.5%.

[0166] By contrast, in Comparative Example 1, the 30-minute dissolution rates of calcium, magnesium and zinc are 48.6 ± 2.4%, 41.2 ± 2.5% and 58.4 ± 2.2%, respectively; in Comparative Example 2, the 30-minute dissolution rates of calcium, magnesium and zinc are 71.8 ± 1.9%, 66.9 ± 2.0% and 75.2 ± 1.8%, respectively; and the dissolution rates of the other comparative examples are also lower than those of the embodiments of the present invention.

[0167] It can be seen from the above results that, in the pH 4.5 low-acid simulated gastric fluid, the mineral matrix of the present invention has an elemental calcium dissolution rate at 30 minutes not lower than 80.0%, an elemental magnesium dissolution rate not lower than 78.0%, and an elemental zinc dissolution rate not lower than 82.0%, indicating that the formulation system of the present invention can improve the dissolution performance of calcium, magnesium and zinc under low-acid conditions.

[0168] Experimental Example 3: Evaluation of Metallic Astringency

[0169] The uniformly dispersible oral liquid sample prepared in Embodiment 4 and oral liquid or aqueous dispersion samples prepared from Comparative Examples 1-9 at theDESCRIPTION

[0170] same elemental contents are subjected to blind evaluation by 10 evaluators who have undergone basic screening. The scoring standard is 0-10 points, wherein a higher score indicates a more obvious metallic astringency. After evaluating each sample, the evaluator rinses the mouth with water, and then evaluates the next sample after an interval of 5 minutes. Results are expressed as the mean ± standard deviation of scores by the 10 evaluators.

[0171] The results show that the average metallic astringency score of Embodiment 4 is 2.3 ± 0.5 points, and the mouthfeel is moderately sweet and sour with a slight mineral sensation. Comparative Example 1 scores 6.8 ± 0.8 points, exhibiting roughness, obvious powdery sensation and astringency; Comparative Example 2 scores 4.9 ± 0.7 points, with obvious mineral sour-astringent sensation; and Comparative Example 6 scores 5.1 ± 0.7 points, with relatively obvious zinc astringency.

[0172] It can be seen from the above results that the present invention, through combined cooperation of the composite calcium source, the dual magnesium source, the zinc glycinate chelate and the organic acid buffer system, helps to reduce metallic astringency generated by ordinary mineral salt combinations and conventional calcium-magnesium-zinc liquid systems.

[0173] Experimental Example 4: Evaluation of Powder Flowability

[0174] The mineral matrix obtained in Embodiment 1 and samples of Comparative Examples 1-9 are respectively tested for angle of repose, bulk density and Carr index. The angle of repose is determined by a fixed funnel method; the bulk density and tapped density are determined according to a conventional powder technology method, and the Carr index is calculated. Each sample is measured in parallel three times, and the results are expressed as mean ± standard deviation.

[0175] The Carr index is calculated as follows:

[0176] Carr index = (tapped density - bulk density) / tapped density x 100%.

[0177] The results show that the mineral matrix of Embodiment 1 has an angle of repose of 37.6 ± 1.1°, a bulk density of 0.61 ± 0.02 g / mL and a Carr index of 18.4 ± 1.2%. Comparative Example 1 has an angle of repose of 45.8 ± 1.4° and a Carr index of 25.7DESCRIPTION

[0178] ± 1.5%; and Comparative Example 3 has an angle of repose of 46.1 ± 1.5° and a Can¬ index of 27.2 ± 1.6%.

[0179] It can be seen from the above results that the mineral matrix of the present invention is not only suitable for a weakly acidic uniformly dispersible oral liquid, but also can meet the requirements of hard capsule filling and tablet compression for powder flowability.

[0180] Experimental Example 5: Evaluation of Accelerated Stability

[0181] The contents of the hard capsule of Embodiment 2, the tablet granules of Embodiment 3, the granules of Embodiment 5 and the samples of Comparative Examples 1-9 are placed at 40°C and 75% relative humidity for 30 days. Before and after placement, the moisture content is respectively measured, and caking, discoloration and abnormal odor are observed. The caking rate is calculated by sieving through a 20-mesh sieve and calculating the mass proportion of sample unable to pass through the sieve. Each sample is measured in parallel three times, and the results are expressed as mean ± standard deviation.

[0182] The caking rate is calculated as follows:

[0183] caking rate = mass of sample unable to pass through a 20-mesh sieve / total mass of sample x 100%.

[0184] The results show that, after 30 days, the moisture increase of the hard capsule contents of Embodiment 2 is 1.2 ± 0.2%, the caking rate is 2.6 ± 0.4%, and there is no obvious caking or obvious discoloration; after 30 days, the moisture increase of the tablet granules of Embodiment 3 is 1.3 ± 0.2%, the caking rate is 3.1 ± 0.5%, and there is slight loose agglomeration without obvious discoloration; after 30 days, the moisture increase of the granules of Embodiment 5 is 1.3 ± 0.2%, the caking rate is 3.4 ± 0.5%, and there is slight loose agglomeration without obvious abnormal odor.

[0185] The moisture increase and caking rate of the comparative example samples are significantly increased under the same conditions, wherein the caking rate of Comparative Example 3 is 13.2 ± 1.0%, with obvious caking.

[0186] It can be seen from the above results that the mineral matrix of the presentDESCRIPTION

[0187] invention has good accelerated stability in solid dosage forms, and can reduce moisture absorption agglomeration and caking problems.

[0188] Experimental Example 6: Evaluation of Placement Stability of Uniformly Dispersible Oral Liquid

[0189] The uniformly dispersible oral liquid of Embodiment 4 and the oral liquid or aqueous dispersion samples prepared from Comparative Examples 1-9 at the same elemental contents are respectively placed at 25°C and 40°C for 30 days, and crystallization, precipitation, layering and pH changes are observed. The precipitate is treated according to the method described in Experimental Example 1, and the contents of calcium, magnesium and zinc elements are measured to calculate the mineral element precipitation rate. Each sample is measured in parallel three times, and the results are expressed as mean ± standard deviation.

[0190] The results show that the mineral element precipitation rate of Embodiment 4 after placement at 25°C for 30 days is 2.6 ± 0.3%, the mineral element precipitation rate after placement at 40°C for 30 days is 3.3 ± 0.4%, the pH variation range is 4.02-4.18, and the appearance shows no obvious crystallization, with only slight fine sediment at the bottom.

[0191] The mineral element precipitation rates of Comparative Example 1 after placement at 25°C and 40°C for 30 days are 15.2 ± 0.8% and 18.6 ± 1.0%, respectively, with obvious precipitation and bottom hard caking; the mineral element precipitation rates of Comparative Example 4 after placement at 25°C and 40°C for 30 days are 11.8 ± 0.7% and 14.7 ± 0.9%, respectively, with an unstable system and obvious precipitation.

[0192] It can be seen from the above results that the mineral matrix of the present invention is suitable for preparing a weakly acidic uniformly dispersible oral liquid and has good placement stability.

[0193] Experimental Example 7: Evaluation of Adaptability to Different Oral Dosage Forms

[0194] The hard capsule of Embodiment 2, the tablet of Embodiment 3 and the granulesDESCRIPTION

[0195] of Embodiment 5 are respectively evaluated for dosage-form adaptability. The hard capsule is evaluated in terms of fill weight variation and flowability of contents; the tablet is evaluated in terms of tablet weight variation, hardness, disintegration time limit and tableting sticking / punching conditions; and the granules are evaluated in terms of reconstitution dispersibility and mineral element precipitation rate.

[0196] The results show that the No. 00 hard capsule of Embodiment 2 has a daily dosage of 4 capsules, the RSD of fill weight variation is 2.1%, and the filling process is smooth without obvious bridging.

[0197] The tablet of Embodiment 3 has a daily dosage of 2 tablets, the RSD of tablet weight variation is 1.8%, the hardness is 75-92 N, the disintegration time limit is 18 minutes, no obvious sticking / punching occurs during tableting, and the tablet surface is intact.

[0198] The granules of Embodiment 5 have a daily dosage of 1 sachet, are substantially uniformly dispersed after reconstitution for 30 seconds, and have a 24-hour mineral element precipitation rate of 3.0% in a pH 4.0 system.

[0199] It can be seen from the above results that the mineral matrix of the present invention can be adapted to the preparation of No. 00 hard capsules, tablets and granules, and can be used for reconstitution in a weakly acidic aqueous system.

[0200] Comprehensive Analysis

[0201] The above embodiments demonstrate that the present invention does not merely use one calcium source, one magnesium source or one zinc source, but rather forms a calcium-magnesium-zinc mineral matrix suitable for a weakly acidic uniformly dispersible oral system through combined cooperation of a composite calcium source, a dual magnesium source, a zinc glycinate chelate, an organic acid buffer system and a ternary aqueous dispersion stabilization system.

[0202] Compared with a conventional inorganic mineral salt combination, the present invention can significantly reduce the mineral element precipitation rate in a weakly acidic aqueous system, and improve the dissolution rates of calcium, magnesium and zinc in a pH 4.5 low-acid simulated gastric fluid.DESCRIPTION

[0203] Compared with an ordinary organic acid salt combination, the present invention does not simply replace inorganic salts with organic salts, but through cooperation among multiple calcium sources, multiple magnesium sources, a chelated zinc source, a buffer system and a dispersion stabilization system, takes into account both dispersion stability of a weakly acidic oral liquid and processing adaptability of solid dosage forms.

[0204] Compared with a composition lacking the ternary aqueous dispersion stabilization system, the present invention demonstrates that inulin, gum arabic and hydroxypropyl methylcellulose play an important role in lowering the mineral element precipitation rate, improving powder flowability and enhancing storage stability.

[0205] Compared with a composition lacking the organic acid buffer system, the present invention demonstrates that citric acid, malic acid and sodium citrate play an important role in maintaining the stability of a weakly acidic system, reducing local precipitation and improving mouthfeel.

[0206] Compared with compositions in which zinc glycinate chelate or magnesium glycinate chelate is replaced, the present invention demonstrates that zinc glycinate chelate and magnesium glycinate chelate have positive effects in reducing metallic astringency, improving low-acid dissolution performance and maintaining dispersion stability.

[0207] Compared with a composition lacking magnesium malate, the present invention demonstrates that, when magnesium malate and magnesium glycinate chelate are jointly used as a dual magnesium source, they are conducive to balancing low-acid dissolution performance, dispersion stability and solid powder adaptability.

[0208] Therefore, the weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix of the present invention can not only be used for supplementing calcium, magnesium and zinc, but also improve problems of ordinary calcium-magnesium-zinc composite products in oral dosage forms such as uniformly dispersible oral liquids, tablets, hard capsules, granules and solid beverages, includingDESCRIPTION

[0209] precipitation, astringency, low-acid dissolution, powder flowability and stability.

[0210] The above has shown and described the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments, and the above embodiments and description merely describe the principles of the present invention. Various changes and improvements may be made to the present invention without departing from the spirit and scope of the present invention, and these changes and improvements all fall within the scope of the present invention sought to be protected. The scope of protection sought by the present invention is defined by the appended claims and equivalents thereof.

Claims

CLAIMS1. A weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix, characterized in that the mineral matrix consists of a composite calcium source, a dual magnesium source, a zinc glycinate chelate, an organic acid buffer system and a ternary aqueous dispersion stabilization system;wherein the composite calcium source consists of calcium citrate malate, calcium lactate gluconate and a calcium glycinate chelate;the dual magnesium source consists of a magnesium glycinate chelate and magnesium malate;the organic acid buffer system consists of citric acid, malic acid and sodium citrate;the ternary aqueous dispersion stabilization system consists of inulin, gum arabic and hydroxypropyl methylcellulose;based on the total dry-basis mass of the mineral matrix, the composite calcium source is present in a mass percentage of 55.0-65.0%, the dual magnesium source is present in a mass percentage of 24.0-31.0%, the zinc glycinate chelate is present in a mass percentage of 1.0-2.0%, the organic acid buffer system is present in a mass percentage of 4.5-6.5%, and the ternary aqueous dispersion stabilization system is present in a mass percentage of 7.0-10.5%;when the mineral matrix is added at 2.0-2.4 g per 30 mL of a pH 4.0 citric acid-sodium citrate aqueous system, after stirring for 5 minutes and standing for 24 hours, a precipitation rate of mineral elements is not higher than 3.5%;when the mineral matrix is added at 2.0-2.4 g per 30 mL of a pH 4.5 low-acid simulated gastric fluid, after treatment at 37°C and 100 rpm for 30 minutes, an elemental calcium dissolution rate is not lower than 80.0%, an elemental magnesium dissolution rate is not lower than 78.0%, and an elemental zinc dissolution rate is not lower than 82.0%.

2. The weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix according to claim 1, characterized in that, based on a recommended daily dosage, the recommended daily dosage of the mineral matrix is 2.0-2.4 g, andCLAIMSprovides 180-260 mg of elemental calcium, 70-110 mg of elemental magnesium and 4-8 mg of elemental zinc.

3. The weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix according to claim 1, characterized in that a mass ratio of the calcium citrate malate, the calcium lactate gluconate and the calcium glycinate chelate is 1:0.51-0.70:0.13-0.20.

4. The weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix according to claim 1, characterized in that a mass ratio of the magnesium glycinate chelate to the magnesium malate is 1.35-1.80:1; a mass ratio of the citric acid, the malic acid and the sodium citrate is 1:1.20-1.80:0.50-0.85; and a mass ratio of the inulin, the gum arabic and the hydroxypropyl methylcellulose is 1:0.45-0.75:0.12-0.24.

5. The weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix according to claim 1, characterized in that the mineral matrix comprises the following components in parts by weight:calcium citrate malate 650-760 parts;calcium lactate gluconate 390-510 parts;calcium glycinate chelate 100-140 parts;magnesium glycinate chelate 320-400 parts;magnesium malate 200-260 parts;zinc glycinate chelate 25-35 parts;citric acid 30-45 parts;malic acid 45-65 parts;sodium citrate 18-32 parts;inulin 85-115 parts;gum arabic 45-75 parts;hydroxypropyl methylcellulose 12-24 parts.

6. The weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix according to claim 1, characterized in that an elemental calciumCLAIMScontent in the calcium citrate malate is 20.0-26.0%, an elemental calcium content in the calcium lactate gluconate is 12.0-14.5%, and an elemental calcium content in the calcium glycinate chelate is 13.0-20.0%; an elemental magnesium content in the magnesium glycinate chelate is 10.0-16.0%, an elemental magnesium content in the magnesium malate is 10.0-16.0%, and an elemental zinc content in the zinc glycinate chelate is 18.0-22.0%.

7. An oral composition, characterized in that the oral composition comprises a mineral matrix and excipients;wherein the mineral matrix is the weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix according to any one of claims 1 to 6;the excipients are excipients acceptable in the field of food or nutritional supplements;a dosage form of the oral composition is a uniformly dispersible oral liquid, tablet, hard capsule, granule or solid beverage;when the oral composition is a uniformly dispersible oral liquid, each 30 mL of the uniformly dispersible oral liquid contains 2.0-2.4 g of the mineral matrix and has a pH of 3.6-4.6;when the oral composition is a solid dosage form, the mineral matrix accounts for 70-95% of the dry-basis mass of the oral composition;when the oral composition is a hard capsule, the hard capsule is a No. 00 hard capsule and a recommended daily dosage is 4 capsules, or the hard capsule is a No. 0 hard capsule and a recommended daily dosage is 5-6 capsules;when the oral composition is a tablet, a recommended daily dosage is 2 tablets, and each tablet has a mass of 1.1 -1.4 g.

8. A preparation method of a weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix, for preparing the weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix according to any one of claims 1 to 6, characterized in that the method comprises the following steps:SI, sieving the calcium citrate malate, the calcium lactate gluconate and theCLAIMScalcium glycinate chelate respectively, and then mixing same to obtain a composite calcium source mixture;52, sieving the magnesium glycinate chelate, the magnesium malate and the zinc glycinate chelate respectively, and then mixing same to obtain a magnesium-zinc source mixture;53, mixing the citric acid, the malic acid, the sodium citrate, the inulin, the gum arabic and the hydroxypropyl methylcellulose to obtain a weakly acidic aqueous dispersion stabilization matrix;54, mixing the composite calcium source mixture, the magnesium-zinc source mixture and the weakly acidic aqueous dispersion stabilization matrix to obtain the weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix;55, according to a target product form, performing subsequent processing on the weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix obtained in step S4 or on the raw materials used for preparing the mineral matrix, wherein the target product form comprises a uniformly dispersible oral liquid, tablets, hard capsules, granules or a solid beverage.

9. The preparation method of a weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix according to claim 8, characterized in that, in step S5, when the target product form is a uniformly dispersible oral liquid, the citric acid, the malic acid, the sodium citrate, the inulin, the gum arabic and the hydroxypropyl methylcellulose are first added into water and stirred for swelling at 35-55°C, and then the calcium lactate gluconate, the calcium citrate malate, the calcium glycinate chelate, the magnesium glycinate chelate, the magnesium malate and the zinc glycinate chelate are sequentially added, the pH is adjusted to 3.6-4.6, and after homogenization treatment and filtration through an 80-120 mesh screen, filling is carried out to obtain the uniformly dispersible oral liquid.

10. The preparation method of a weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix according to claim 8, characterized in that, in step S5, when the target product form is tablets, hard capsules, granules or a solidCLAIMSbeverage, the weakly acidic uniformly dispersible oral calcium-magnesium-zinc mineral matrix obtained in step S4 is subjected to wet granulation or dry granulation, the resulting granules have a D50 particle size of 80-280 pm and a loss on drying not higher than 5.0%, and then, after adding excipients acceptable in the field of food or nutritional supplements, tableting, capsule filling or packaging is carried out.

Images