Preparation containing oyster calcium particles and preparation method thereof

Abstract

The invention belongs to the technical field of calcium tablet preparation, and particularly relates to a preparation containing oyster calcium particles and a preparation method thereof. The preparation comprises an inner particle phase and an outer particle phase, the particle inner phase comprises oyster calcium powder, a diluent and an adhesive; the particle external phase comprises essence, a sweetening agent, a disintegrating agent and a lubricating agent. According to the preparation method, the adding mode of the essence in the total mixing process is improved, generally, the essence is added in one step in the total mixing process, the essence is dispersed in the particles prepared from the particle inner phase in a specific proportion and then participates in the total mixing, the essence can be dispersed more uniformly, and the taste of the preparation is greatly improved. Meanwhile, in order to further improve the taste, a sweetening agent in a specific proportion is added, so that the whole preparation is fragrant in smell, and the whole preparation is crisp and sweet in taste and free of gravel feeling when being chewed.

Description

Technical Field

[0001] The present application belongs to the technical field of calcium tablet preparation, and specifically relates to a preparation containing oyster calcium particles and a preparation method thereof. Background Art

[0002] Calcium plays a potentially important role and influence in maintaining the normal physiological functions of human bones, muscles, nerves, and cardiovascular health. Oysters are the world's largest farmed shellfish and one of my country's four largest farmed shellfish. At present, the development of oysters in China is mainly focused on the edible part, while the inedible shells are discarded as garbage, which not only causes environmental pollution, but also wastes resources.

[0003] Oyster shell is a multi-layer microstructure with calcium carbonate as the main component, which is formed by natural mineralization under the regulation of biological organic macromolecules such as proteins and polysaccharides. Organic matter such as proteins and polysaccharides only accounts for about 5%, while calcium carbonate accounts for 90%-95% of the total mass of oyster shell. The calcium content is about 40%, which is a good natural biological calcium source. The research on preparing various food and drug grade calcium supplements using oyster shell as raw material has attracted wide attention.

[0004] The daily intake of calcium is large, and oyster calcium accounts for a large proportion in the preparation. In terms of tableting properties, the compressibility is poor, and the large amount makes the taste astringent. In addition, the oyster calcium chewable tablets currently on the market have a long disintegration time and there is a risk of blocking the pyloric sphincter in the stomach.

[0005] Therefore, there is an urgent need for a new type of oyster calcium preparation and a preparation method thereof, which can improve the tablet compressibility of the oyster calcium preparation, improve the taste, and increase the disintegration time. Summary of the invention

[0006] The purpose of the present invention is to solve the deficiencies of the prior art and provide a preparation containing oyster calcium particles and a preparation method thereof, which specifically adopts the following technical scheme: In a first aspect, a preparation containing oyster calcium particles, the preparation comprising: The particle inner phase comprises oyster calcium powder, a diluent and a binder; The outer phase of the particle is wrapped around the inner phase of the particle. The granular outer phase includes flavors, sweeteners, disintegrants and lubricants; The ingredients in the preparation are calculated by weight percentage and include: Oyster calcium powder 70wt%-80wt%, diluent 10wt%-30wt%, binder 1wt%-3wt%, flavor 0.1wt%-0.5wt%, sweetener 0.01wt%-0.05wt%, disintegrant 0.25wt%-3wt%, lubricant 0.3wt%-1.0wt%.

[0007] The present invention prepares oyster calcium particles into an inner phase and an outer phase, wherein the inner phase contains oyster calcium powder, a diluent and a binder. The oyster calcium powder is ground to control a certain particle size, and then mixed with a special diluent and a binder. The flavor is first dispersed in the inner phase of the particles to obtain particles, and then mixed with other auxiliary materials. A disintegrant is added to the outer phase of the particles, which can not only significantly improve the compressibility of the preparation, but also improve the taste of the preparation, making it fragrant in smell, and having a crisp and sweet taste when chewed without any gravel feeling, and shorten the disintegration time of the preparation.

[0008] As a further preferred embodiment, the diluent comprises mannitol; The binder includes at least one of corn starch, povidone K30, hypromellose and hydroxypropyl cellulose.

[0009] As a further preferred embodiment, the flavor includes at least one of sweet orange oil flavor, strawberry flavor, vanilla flavor, mint flavor, and raspberry flavor.

[0010] As a further preferred embodiment, the sweetener includes at least one of aspartame, acesulfame potassium, and sucralose.

[0011] As a further preferred embodiment, the disintegrant includes at least one of cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, and calcium carboxymethyl cellulose.

[0012] As a further preferred embodiment, the lubricant includes at least one of magnesium stearate, stearic acid, micro-powder silica gel, talc, and sodium stearyl fumarate.

[0013] As a further preferred embodiment, the preparation comprises granules, microgranules, capsules or chewable tablets.

[0014] In a second aspect, the present invention provides a method for preparing the above-mentioned preparation containing oyster calcium particles, comprising the following steps: S1. Grinding oyster shells by water milling to prepare oyster calcium powder; the particle size of the oyster calcium powder is D90≤100 μm; S2, adding oyster calcium powder and diluent into a wet mixing granulator, stirring, shearing, mixing, then adding adhesive slurry, granulating, drying, granulating, sieving, and obtaining a particle inner phase; the concentration of the adhesive slurry is 5wt%-10wt%; S3, placing part of the inner phase of the granules in a high-efficiency wet granulator for stirring and shearing, and then adding essence to make it evenly dispersed to obtain a first material; the weight ratio of the essence to the part of the inner phase of the granules is 1: (5-20); S4, placing the first material, the remaining part of the granular internal phase, the sweetener and the disintegrant in a mixer and mixing them uniformly to obtain a second material; S5. Place the lubricant in a high-efficiency wet granulator and mix it with the second material to obtain a total mixed material, press the tablets, and coat the tablets to obtain the preparation containing oyster calcium particles.

[0015] As a further preferred embodiment, the mixing time in S1 is 0.5 min-1.5 min; the time for adding the binder slurry is 1.5 min-2.5 min; the granulation time is 1 s-10 s; and the specific parameters of drying are as follows: The inlet air temperature is 145-155℃, the fan frequency is 45-55Hz, the steam pressure is 0.4-0.6MPa, the outlet air temperature is 60-75℃, and the moisture content is ≤1.0%; The speed of the mixer in S4 is 5 rpm-10 rpm, and the time is 10 min-20 min.

[0016] As a further preferred embodiment, the coating comprises the following steps: The gastric soluble coating premix is ​​prepared into a coating solution with a concentration of 10wt%-15wt%, and a high-efficiency coating machine is used to coat the compressed plain tablets; the coating weight gain is 0.5wt%-2.0wt%.

[0017] The present invention has at least the following beneficial effects: (1) The present invention prepares oyster calcium powder by water-flying grinding, controls its particle size, and adds a diluent and an adhesive of a specific type and proportion. After wet granulation and drying, granules with good compressibility can be obtained, and chewable tablets can be obtained after tabletting.

[0018] (2) The present invention improves the way of adding flavors during the total mixing process. Usually, flavors are prepared by adding them in one step during the total mixing process. The present invention first disperses the flavors in the particles prepared by the particle internal phase in a specific proportion, and then participates in the total mixing, so that the flavors can be dispersed more evenly and the taste of the preparation is greatly improved. At the same time, in order to further improve the taste, a specific proportion of sweetener is added to make the whole preparation fragrant in terms of smell, and the whole preparation tastes crispy and sweet when chewed, without any gritty feeling.

[0019] (3) In order to improve the disintegration time of conventional preparations, the present invention increases the use of disintegrants in the granular outer phase, thereby improving the disadvantage of the long disintegration time of chewable tablets under the prior art conditions. DETAILED DESCRIPTION

[0020] The following will be combined with the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0021] In the following examples, the gastric soluble coating premix is ​​Opadry, product brand: 290F620179-CN.

[0022] Example 1 A preparation containing oyster calcium particles, the preparation method of which is as follows: The chewable tablets (100,000 tablets) contain oyster calcium granules according to the ratio in Table 1 below. The content of active ingredient in the chewable tablets is 1.3 g / tablet as calculated as oyster calcium powder, and the calcium content is ≥300 mg / tablet.

[0023] Table 1 In Table 1 above, the weight ratio of oyster calcium powder to diluent is approximately 1:0.24, wherein the diluent is spray-dried mannitol, model 200SD, and its particle size D90 is 200 μm; the weight ratio of oyster calcium powder to diluent is approximately 1:0.022.

[0024] The preparation process comprises the following steps: S1: Pretreatment: oyster shells are ground by water jet method to prepare oyster calcium powder, and the particle size is controlled to be D90≤30μm for later use; S2: Preparation of adhesive slurry: Take adhesive corn starch and prepare the adhesive slurry with purified water to a concentration of 8wt%; S3: Granulation of the internal phase of the granules: Add oyster calcium powder and diluent spray-dried mannitol into a wet mixing granulator, set the parameters as follows: stirring at low speed, shearing at low speed, mixing time for 1 min, then slowly and evenly add the prepared adhesive slurry through the valve funnel, slurry addition time for 2 min, granulation time for 5 s, and obtain wet granules; S4: Drying: The wet granules are sucked into a boiling granulation dryer by vacuum for drying. The inlet air temperature is set at 150°C, the fan frequency is set at 50Hz, and the steam pressure is 0.5MPa. When the outlet air temperature reaches 70°C, the moisture content is ≤1.0%, and the material is discharged to obtain dry granules. S5: Granulation: The dry granules are sized using a sieving machine, and the granulation sieve has a mesh number of 14 stainless steel sieves to obtain granules; S6: total mixing, wherein the total mixing comprises the following steps: A1: Take part of the granules after granulation and place them in a high-efficiency wet granulator, set low stirring and low shear parameters for operation, and then slowly add the essence to make it evenly dispersed. The flavoring time is 1 min, and the mixing time after adding is 10 s, wherein the weight ratio of the essence to the part of the granules after granulation in step S5 is 1:13, so as to obtain material 1; A2: Material 1, the remaining granules after granulation, the sweetener and the disintegrant are placed in a mixer at a mixing speed of 8 rpm for 15 min to obtain material 2; A3: Place the lubricant in a mixer and mix it with material 2 at a speed of 8 rpm for 5 minutes to obtain a total mixed material; S7: Tabletting: The total mixed material is tableted using an 18mm×7.5mm oval punch to obtain plain tablets. The average tablet weight of 10 tablets is within the range of 1.285±2.0%, and the average hardness is controlled within the range of 10~20kg; S8: Coating: The gastric soluble coating premix is ​​prepared into a coating solution with a concentration of 12wt%, and the obtained plain tablets are coated with a high-efficiency coating machine, and the coating weight gain is 0.5wt%-2.0wt%, so as to obtain coated chewable tablets.

[0025] Example 2 A preparation containing oyster calcium particles. The difference between this embodiment and embodiment 1 is that the weight ratio of oyster calcium powder to diluent is about 1:0.13, and the rest of the preparation method is the same as that of embodiment 1.

[0026] The chewable tablets (100,000 tablets) contain oyster calcium granules according to the ratio in Table 2 below. The content of active ingredient in the chewable tablets is 1.3 g / tablet as calculated as oyster calcium powder, and the calcium content is ≥300 mg / tablet.

[0027] Table 2 Example 3 A preparation containing oyster calcium particles, the formula of this embodiment is different from that of embodiment 1 in that the weight ratio of oyster calcium powder to diluent is about 1:0.41. The preparation method is the same as that of embodiment 1.

[0028] The chewable tablets (100,000 tablets) contain oyster calcium granules according to the ratio in Table 3 below. The content of active ingredient in the chewable tablets is 1.3 g / tablet as oyster calcium powder, and the calcium content is ≥300 mg / tablet.

[0029] Table 4 Example 4 A preparation containing oyster calcium particles, the prescription of this embodiment differs from that of embodiment 1 in that: The weight ratio of oyster calcium powder to adhesive is about 1:0.013, wherein the adhesive is corn starch.

[0030] The difference between the preparation method and Example 1 is that: Step S2: Preparation of adhesive slurry: Take adhesive corn starch and use purified water to prepare an adhesive slurry concentration of 5wt%; The chewable tablets (100,000 tablets) contain oyster calcium granules according to the ratio in Table 4 below. The content of active ingredient in the chewable tablets is 1.3 g / tablet as oyster calcium powder, and the calcium content is ≥300 mg / tablet.

[0031] Table 4 Example 5 A preparation containing oyster calcium particles, the prescription of this embodiment differs from that of embodiment 1 in that: The weight ratio of oyster calcium powder to adhesive is about 1:0.041, wherein the adhesive is corn starch.

[0032] The difference between the preparation method and Example 1 is that: Step S2: Preparation of adhesive slurry: Take adhesive corn starch and use purified water to prepare an adhesive slurry concentration of 10wt%; The chewable tablets (100,000 tablets) contain oyster calcium granules according to the ratio in Table 5 below. The content of active ingredient in the chewable tablets is 1.3 g / tablet as calculated as oyster calcium powder, and the calcium content is ≥300 mg / tablet.

[0033] Table 5 Example 6 A preparation containing oyster calcium particles, the prescription of this embodiment is the same as that of embodiment 1, except that the preparation method is: The material 1 is obtained, that is, the weight ratio of the flavor in step A1 in the total mixing of step S6 to the part of the granules after granulation in step S5 is 1:5.

[0034] The chewable tablets (100,000 tablets) contain oyster calcium granules according to the ratio in Table 6 below. The content of active ingredient in the chewable tablets is 1.3 g / tablet as calculated as oyster calcium powder, and the calcium content is ≥300 mg / tablet.

[0035] Table 6 Example 7 A preparation containing oyster calcium particles, the prescription of this embodiment is the same as that of embodiment 1, except that the preparation method is: The material 1 is obtained, that is, the weight ratio of the flavor in step A1 in the total mixing of step S6 to the part of the granules after granulation in step S5 is 1:20.

[0036] The chewable tablets (100,000 tablets) contain oyster calcium granules according to the ratio in Table 7 below. The content of active ingredient in the chewable tablets is 1.3 g / tablet as calculated as oyster calcium powder, and the calcium content is ≥300 mg / tablet.

[0037] Table 7 Example 8 A preparation containing oyster calcium particles. The formulation of this embodiment is the same as that of Example 1, except that the particle size of the oyster calcium powder is 30 μm ≤ D90 ≤ 50 μm, and the rest of the preparation method is the same as that of Example 1.

[0038] Example 9 A preparation containing oyster calcium particles, the formulation of this embodiment is the same as that of embodiment 1, except that the particle size of the oyster calcium powder is 50 μm≤D90≤100 μm. The preparation method is the same as that of embodiment 1.

[0039] Comparative Example 1 A preparation containing oyster calcium particles, the prescription of this embodiment differs from that of embodiment 1 in that: The weight ratio of oyster calcium powder to diluent is about 1:0.1, and a lower amount of diluent is used. The preparation method is the same as that of Example 1.

[0040] The chewable tablets (100,000 tablets) contain oyster calcium granules according to the ratio in Table 8 below. The content of active ingredient in the chewable tablets is 1.3 g / tablet as calculated as oyster calcium powder, and the calcium content is ≥300 mg / tablet.

[0041] Table 8 Comparative Example 2 A preparation containing oyster calcium particles, this embodiment is different from embodiment 1 in that: The weight ratio of oyster calcium powder to diluent is about 1:0.45, and a higher amount of diluent is used. The preparation method is the same as that of Example 1.

[0042] The chewable tablets (100,000 tablets) contain oyster calcium granules according to the ratio in Table 9 below. The content of active ingredient in the chewable tablets is 1.3 g / tablet as calculated as oyster calcium powder, and the calcium content is ≥300 mg / tablet.

[0043] Table 9 Comparative Example 3 A preparation containing oyster calcium particles, this embodiment is different from embodiment 1 in that: The weight ratio of oyster calcium powder to binder is about 1:0.01, and a lower amount of binder is used.

[0044] The difference between the preparation method and Example 1 is that: Step S2: Preparation of adhesive slurry: Take adhesive corn starch and use purified water to prepare an adhesive slurry with a concentration of 3wt%; The chewable tablets (100,000 tablets) contain oyster calcium granules according to the ratio in Table 10 below. The content of active ingredient in the chewable tablets is 1.3 g / tablet as oyster calcium powder, and the calcium content is ≥300 mg / tablet.

[0045] Table 10 Comparative Example 4 A preparation containing oyster calcium particles, this embodiment is different from embodiment 1 in that: The weight ratio of oyster calcium powder to binder is about 1:0.045, and a higher amount of binder is used.

[0046] The difference between the preparation method and Example 1 is that: Step S2: Preparation of adhesive slurry: Take adhesive corn starch and use purified water to prepare an adhesive slurry with a concentration of 12wt%; The chewable tablets (100,000 tablets) contain oyster calcium granules according to the ratio in Table 11 below. The content of active ingredient in the chewable tablets is 1.3 g / tablet as calculated as oyster calcium powder, and the calcium content is ≥300 mg / tablet.

[0047] Table 11 Comparative Example 5 A preparation containing oyster calcium particles, the difference between this comparative example and Example 1 is the preparation method: The material 1 is obtained, i.e., step A1 in the total mixing of step S6: the weight ratio of the flavor to the part of the granules after granulation in step S5 is 1:3.

[0048] Comparative Example 6 A preparation containing oyster calcium particles, the difference between this comparative example and Example 1 is the preparation method: The material 1 is obtained, that is, the weight ratio of the flavor in step A1 in the total mixing of step S6 to the part of the granules after granulation in step S5 is 1:22.

[0049] Comparative Example 7 A preparation containing oyster calcium particles, the difference between this comparative example and Example 1 is that ordinary powdered mannitol (D90 < 25 μm) is used. The preparation method is the same as that of Example 1.

[0050] Comparative Example 8 A preparation containing oyster calcium particles, the difference between this comparative example and Example 1 is that the particle size of the oyster calcium powder is 100 μm<D90≤150 μm. The preparation method is the same as that of Example 1.

[0051] Comparative Example 9 A preparation containing oyster calcium particles. The difference between this comparative example and Example 1 is that the diluent used is sucrose powder, and the preparation method is the same as that of Example 1.

[0052] Comparative Example 10 The difference between this comparative example and Example 1 is that the adhesive used is gum arabic, and the preparation method is the same as that of Example 1.

[0053] Comparative Example 11 A preparation containing oyster calcium particles. The difference between this comparative example and Example 1 is that the preparation method is different. In step S6, the granules obtained in step S5 are placed in a mixer together with flavor, sweetener and disintegrant, and mixed at a speed of 8 rpm for 15 min. Subsequently, the lubricant is placed in the mixer and mixed together with material 2 at a speed of 8 rpm for 5 min to obtain a total mixed material.

[0054] Example 10 This example performs compressibility testing on the above examples 1-9 and comparative examples 1-11, and the specific testing method is as follows: The hardness of the chewable tablets was tested by hardness tester (TianDa TianFa YD-35 intelligent tablet hardness tester), and the appearance of the chewable tablets was tested by visual inspection. The chewable tablets were compressed under the same tableting main pressure and observed for signs of capping.

[0055] Testing standard: The average hardness of the prepared chewable tablets is controlled at 10~20kg, and the appearance is glossy, without top cracks or waist cracks.

[0056] According to the above-mentioned detection method, the compressibility of the total mixed material obtained by the total mixing in step S6 prepared in Examples 1 to 9 and Comparative Examples 1 to 11 was detected. The detection results are shown in Table 12 below.

[0057] Table 12 Compressibility test of different embodiments Note: The above tablets are all prepared under the same tableting main pressure, which is 22-27KN.

[0058] From the above test results, we can know that: The chewable tablets prepared in Examples 1-9 have suitable hardness, tablet gloss and no capping, and the average hardness of the chewable tablets is controlled within the range of 10-20 kg, and the tablet gloss has no cracking phenomenon, which meets the standards.

[0059] The amount of diluent used, whether too high or too low, affects the compressibility of the chewable tablets. In Example 1, a lower amount of diluent is used, and the tablet hardness is relatively small. Some tablets have capping cracks, and the hardness is less than 10kg. In Example 2, a higher amount of diluent is used, and the tablet surface is glossy, without capping cracks or waist cracks, but its hardness range exceeds 20kg. The chewable tablet has too high a hardness that affects the chewing taste.

[0060] The amount of adhesive used, whether too high or too low, affects the compressibility of the chewable tablets. Comparative Example 3 uses a lower amount of adhesive, the tablet surface is rough, the top cracks are serious, the scrap rate is high, and the hardness is less than 5kg; Comparative Example 4 uses a higher amount of adhesive, the tablet surface is glossy, there is no top crack or waist crack phenomenon, but its hardness range exceeds 20kg, and the chewable tablet hardness is too high to affect the chewing taste.

[0061] Compared with Examples 1-9, Comparative Examples 5-6 have different flavor dispersion ratios, but the chewable tablets prepared in Comparative Examples 4-5 have glossy surface, no top cracks or waist cracks, and the hardness is controlled within the range of 10-20 kg, which meets the standard, that is, different flavor dispersion ratios have little effect on the compressibility of the tablets.

[0062] Compared with Examples 1-9, in Comparative Example 7, ordinary powdered mannitol was used as a diluent, and the chewable tablets prepared were glossy, but some tablets had capping phenomenon; in Comparative Example 9, sucrose powder was used as a diluent, and the chewable tablets prepared were glossy, some tablets had capping phenomenon, and the hardness range exceeded 20 kg. Therefore, the choice of diluent has a certain influence on the compressibility of the tablets.

[0063] Compared with Examples 1-9, in Comparative Example 8, the particle size D90 of the active ingredient oyster calcium powder is greater than 100 μm, and the chewable tablets prepared have a rough surface, severe top cracks, a high scrap rate, and a hardness of less than 5 kg, with a large reduction in hardness. Therefore, the particle size of the active ingredient has a greater influence on the compressibility.

[0064] Compared with Examples 1-9, in Comparative Example 10, gum arabic was used as the adhesive, and the chewable tablets prepared were glossy, some tablets had capping, and the hardness was controlled within the range of 10-20 kg. Therefore, the choice of adhesive had a certain influence on the compressibility of the tablets.

[0065] Compared with Examples 1-9, in Comparative Example 11, the mixing order in step S6 was changed, and the chewable tablets prepared had glossy surface, no top cracks or waist cracks, and the hardness was controlled within the range of 10-20 kg, which met the standards. That is, the mixing order of the excipients in the total mixing step had little effect on the compressibility of the tablets.

[0066] In summary, for the chewable tablets prepared in the present application, the preferred particle size of the active ingredient oyster calcium powder, the selection of the diluent and the adhesive, and the preferred ratio have a great influence on the compressibility and hardness of the chewable tablets, but the flavor and the particle dispersion ratio prepared in step S5, and the order of mixing the total mixed excipients in step S6 have little effect on the compressibility and hardness of the chewable tablets.

[0067] Embodiment 11 This example tests the taste of the above examples 1-9 and comparative examples 1-11, as follows: The mouthfeel of the chewable tablets prepared in Examples 1 to 9 and Comparative Examples 1 to 11 was tested, and the test results are shown in Table 13 below.

[0068] Table 13 Taste test of examples and comparative examples Note: The above conclusion is the weighted average description after testing 20 people.

[0069] From the taste results in the table above, we can see that: In Example 1-2, the chewable tablets prepared have a good taste; in Example 3, a larger amount of diluent is used, and the weight ratio of oyster calcium powder to diluent is within 1: (0.13-0.41), and the chewable tablets prepared have a harder chewing hardness, but acceptable; in Example 4, a smaller amount of diluent is used, and the weight ratio of oyster calcium powder to binder is about 1: 0.013, and the chewable tablets prepared have a softer chewing hardness, which is acceptable; in Example 5, a larger amount of binder is used, and the weight ratio of oyster calcium powder to binder is about 1: 0.041, and the chewable tablets prepared have a harder chewing hardness, which is acceptable; The dispersion ratios of the flavors in Examples 6-7 are different. The weight ratio of the flavor of step A1 in the total mixing of step S6 of Example 6 to the part of the particles after granulation in step S5 is 1:5, and the weight ratio of the flavor of step A1 in the total mixing of step S6 of Example 7 to the part of the particles after granulation in step S5 is 1:20. The prepared chewable tablets have uneven aroma, but the aroma is acceptable. The particle size of the active ingredient oyster calcium powder in Examples 8-9 is different. The particle size of the oyster calcium powder in Example 1 is 30μm≤D90≤50μm, and the particle size of the oyster calcium powder in Example 2 is 50μm≤D90≤100μm. The prepared chewable tablets have a sandy feeling, but the taste is acceptable.

[0070] Comparative Examples 1-2 used different amounts of diluents. Comparative Example 1 used a lower amount of diluent, and the chewable tablets prepared had a soft mouthfeel, and the crispness and coolness were not obvious; Comparative Example 2 used a higher amount of diluent, and the chewable tablets prepared had a harder mouthfeel, were not easy to chew, and were not acceptable to the subjects. Comparative Examples 3-4 used different amounts of binders. Comparative Example 3 used a lower amount of binder, and the chewable tablets prepared had a soft mouthfeel; Comparative Example 4 used a higher amount of binder, and the chewable tablets prepared had a too hard mouthfeel, were difficult to chew, and were not acceptable to the subjects. The dispersion ratio of flavors in Comparative Examples 5-6 is different. The weight ratio of the flavor of step A1 in the total mixing of step S6 in Comparative Example 5 to the part of the granules after granulation in step S5 is 1:3. The weight ratio of the flavor of step A1 in the total mixing of step S6 in Comparative Example 6 to the part of the granules after granulation in step S5 is 1:22, which exceeds the range of Examples 1-9. The chewing hardness of the prepared chewable tablets is appropriate, the aroma is uneven, the aroma of some tablets is too heavy, and some tablets have no aroma, which is not accepted by the subjects and has no gritty feeling. Comparative Example 7 uses ordinary powdered mannitol to prepare chewable tablets with good taste. Comparative Example 8 uses oyster calcium powder with larger particle size to prepare chewable tablets with heavy gritty taste and are not accepted by the subjects. Comparative Example 9 uses sucrose powder as the diluent, and the chewable tablets prepared have too hard chewing hardness at the entrance, are difficult to chew, and are not accepted by the subjects. Comparative Example 10, when the adhesive uses gum arabic, the chewable tablets prepared have good taste. In comparative example 11, in the total mixing step, the flavor was not dispersed in the granules prepared in step S5 first, and the prepared chewable tablets had uneven aroma, some tablets had too strong aroma, some tablets had no aroma, and had moderate sweetness and a cool feeling.

[0071] In summary, for the chewable tablets prepared in the present application, the optimization of the particle size of the active ingredient oyster calcium powder, the selection of the amount of diluent and adhesive, the proportion of flavor dispersion in the total mixing step, and the mixing order of excipients in the total mixing step have a greater impact on the taste of the chewable tablets, but the material selection of the diluent and adhesive has little effect on the taste of the chewable tablets.

[0072] Example 12 This example tests the disintegration time of the above examples 1-9 and comparative examples 1-11, and the specific test method is as follows: According to the disintegration time test method (General Rules 0921 of Part IV of the Chinese Pharmacopoeia 2020 Edition), the disintegration time should be ≤15min.

[0073] The test results are shown in the following Table 12. The disintegration time of the chewable tablets prepared in Examples 1 to 9 and Comparative Examples 1 to 11 was tested.

[0074] Table 14 Disintegration time test of examples and comparative examples Note: The disintegration time in the above table is the average disintegration time of 6 tablets tested.

[0075] From the disintegration time results in the above table, we can see that: In Examples 1-9, the disintegrant was added to the outer phase of the granules, and the disintegration time was less than 15 min, which met the standard, and the disintegration time of different Examples was slightly different. In Comparative Examples 1-11, except for Comparative Examples 2, 4 and 9, the disintegration time of the remaining Comparative Examples was less than 15 min.

[0076] Comparative Example 2 uses a higher amount of diluent, and the weight ratio of oyster calcium powder to diluent is about 1:0.45. Comparative Example 4 uses a higher amount of adhesive, and the weight ratio of oyster calcium powder to adhesive is about 1:0.045. The diluent used in Comparative Example 9 is sucrose powder. The disintegration time of the chewable tablets prepared in the above comparative examples is greater than 15 minutes.

[0077] In summary, for the chewable tablets prepared in the present application, the selection of the amount of diluent and binder and the selection of diluent have a great influence on the disintegration time of the chewable tablets.

[0078] The embodiments of the present application are described above. Specific examples are used herein to illustrate the principles and implementation methods of the present application. The description of the above embodiments is only used to help understand the core idea of ​​the present application, but the present application is not limited to the above-mentioned specific implementation methods. The above-mentioned specific implementation methods are merely illustrative and not restrictive. Under the guidance of the present application, ordinary technicians in this field can also make many forms without departing from the scope of protection of the purpose of the present application and the claims, all of which are within the protection of the present application.

Claims

1. A preparation containing oyster calcium particles, characterized in that: The preparation comprises: The particle inner phase comprises oyster calcium powder, a diluent and a binder; The outer phase of the particle is wrapped around the inner phase of the particle. The granular outer phase includes flavors, sweeteners, disintegrants and lubricants; The ingredients in the preparation are calculated by weight percentage and include: Oyster calcium powder 70wt%-80wt%, diluent 10wt%-30wt%, binder 1wt%-3wt%, flavor 0.1wt%-0.5wt%, sweetener 0.01wt%-0.05wt%, disintegrant 0.25wt%-3wt%, lubricant 0.3wt%-1.0wt%.

2. The preparation according to claim 1, characterized in that The diluent includes mannitol; The adhesive comprises at least one of corn starch, povidone K30, hydroxypropyl methylcellulose and hydroxypropyl cellulose.

3. The preparation according to claim 1, characterized in that The flavor includes at least one of sweet orange oil flavor, strawberry flavor, vanilla flavor, mint flavor, and raspberry flavor.

4. The preparation according to claim 1, characterized in that The sweetener is selected from at least one of aspartame, acesulfame potassium and sucralose.

5. The preparation according to claim 1, characterized in that The disintegrant is selected from at least one of cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, and calcium carboxymethyl cellulose.

6. The preparation according to claim 1, characterized in that The lubricant is selected from at least one of magnesium stearate, stearic acid, micro-powder silica gel, talc, and sodium stearyl fumarate.

7. The preparation according to any one of claims 1 to 6, characterized in that The preparations include granules, microgranules, capsules or chewable tablets.

8. A method for preparing a preparation containing oyster calcium particles according to any one of claims 1 to 7, characterized in that: The following steps are involved: S1. Grinding oyster shells by water milling to prepare oyster calcium powder; the particle size of the oyster calcium powder is D90≤100 μm; S2, adding oyster calcium powder and diluent into a wet mixing granulator, stirring, shearing, mixing, then adding adhesive slurry, granulating, drying, granulating, sieving, and obtaining a particle inner phase; the concentration of the adhesive slurry is 5wt%-10wt%; S3, placing part of the inner phase of the granules in a high-efficiency wet granulator for stirring and shearing, and then adding essence to make it evenly dispersed to obtain a first material; the weight ratio of the essence to the part of the inner phase of the granules is 1: (5-20); S4, placing the first material, the remaining part of the granular internal phase, the sweetener and the disintegrant in a mixer and mixing them uniformly to obtain a second material; S5. Place the lubricant in a high-efficiency wet granulator and mix it with the second material to obtain a total mixed material, press the tablets, and coat the tablets to obtain the preparation containing oyster calcium particles.

9. The preparation method according to claim 8, characterized in that: The mixing time in S1 is 0.5 min-1.5 min; the time for adding the binder slurry is 1.5 min-2.5 min; the granulation time is 1 s-10 s; the specific parameters of drying are as follows: The inlet air temperature is 145-155℃, the fan frequency is 45-55Hz, the steam pressure is 0.4-0.6MPa, the outlet air temperature is 60-75℃, and the moisture content is ≤1.0%; The speed of the mixer in S4 is 5 rpm-10 rpm, and the time is 10 min-20 min.

10. The preparation method according to claim 8, characterized in that: The coating comprises the following steps: The gastric soluble coating premix is ​​prepared into a coating solution with a concentration of 10wt%-15wt%, and a high-efficiency coating machine is used to coat the compressed plain tablets; the coating weight gain is 0.5wt%-2.0wt%.

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