Calcium carbonate dimeticone chewable tablet and preparation method thereof

Abstract

The invention belongs to the technical field of chemicals, and particularly provides a preparation method of calcium carbonate dimeticone chewable tablets, which comprises the following steps: 1) mixing dimeticone and superfine silica powder, adding calcium carbonate, uniformly mixing, adding aspartame, essence, mannitol, corn starch and hydroxy propyl cellulose, sieving, and uniformly mixing to obtain a base material; (2) adding ethylene glycol chitosan and guar gum into a buffer solution, uniformly stirring, adding a galactose oxidase solution and a catalase solution, reacting at room temperature, adding compound polysaccharide, and continuously uniformly mixing to obtain slurry; and 3) adding the slurry and magnesium stearate into the base material, uniformly mixing to prepare a soft material, and then granulating and tabletting to obtain the calcium carbonate dimeticone chewable tablet. The calcium carbonate dimeticone chewable tablet prepared by the invention has the advantages of stable drug release, long drug effect duration and small adverse reaction.

Description

Technical Field

[0001] This application belongs to the field of chemical pharmaceutical technology, and in particular relates to a calcium carbonate dimethicone chewable tablet and its preparation method. Background Technology

[0002] Gastric ulcer is a common digestive system disease in clinical practice, often occurring in the antrum, cardia, esophagus, and gastric angle. The cause is excessive gastric acid secretion that erodes the gastric mucosa, leading to peptic ulcers, significant inflammatory foci, stomach pain, and in severe cases, even gastric perforation. Therefore, timely and effective treatment is necessary.

[0003] Currently, commonly used clinical treatments include esomeprazole enteric-coated tablets, calcium carbonate and simethicone chewable tablets, magnesium aluminum simethicone chewable tablets, and antibiotics. Among these, calcium carbonate and simethicone chewable tablets have fewer adverse reactions and are suitable for long-term use. Their active ingredients mainly include calcium carbonate and simethicone. Calcium carbonate neutralizes stomach acid, acting as a buffer to relieve symptoms caused by excessive stomach acid. Simethicone can eliminate foamy mucus in the gastrointestinal tract and relieve abdominal bloating, resulting in overall good therapeutic effects.

[0004] For the clinical stages of gastric ulcers—active, healing, and scarring—technologists have been continuously improving the drug components of chewable tablets to enhance their adaptability and efficacy. For example, application publication number CN102018721A discloses a formulation and preparation method for calcium carbonate and dimethicone chewable tablets. The main components are: calcium carbonate, dimethicone, micronized silica gel, aspartame, powdered flavoring, mannitol, corn starch, low-substituted hydroxypropyl cellulose, and magnesium stearate. This is used to treat peptic ulcers, including gastric and duodenal ulcers, and to relieve various discomfort symptoms caused by excessive gastric acid. Besides the two active pharmaceutical ingredients, calcium carbonate and dimethicone, the excipients in chewable tablets also play an important role in regulating the drug's disintegration and dissolution rate, which has a positive effect on therapeutic efficacy. Therefore, how to regulate and improve the drug release rate of chewable tablets is an urgent problem to be solved. Summary of the Invention

[0005] To address the aforementioned issues and further improve the retention effect of the active pharmaceutical ingredient, prolong the release time in the stomach, and enhance the therapeutic effect of chewable tablets on gastric ulcers, this application provides a calcium carbonate dimethicone chewable tablet and its preparation method.

[0006] This application first provides a method for preparing calcium carbonate dimethicone chewable tablets, comprising the following steps: 1) Mix dimethicone and micronized silica gel, then add calcium carbonate and mix evenly. Next, add aspartame, flavoring, mannitol, corn starch and hydroxypropyl cellulose, sieve and mix evenly to obtain the base material. 2) Add ethylene glycol chitosan and guar gum to the buffer solution, stir well, then add galactose oxidase solution and catalase solution, react at room temperature, then add the complex polysaccharide and continue to mix to obtain the slurry. 3) Add slurry and magnesium stearate to the base material, mix evenly to form a soft material, and then granulate and compress to obtain the final product.

[0007] Furthermore, in step 1), the mass ratio of dimethicone oil to micronized silica gel is 20:1.

[0008] Furthermore, in step 1), the hydroxypropyl cellulose is a low-substituted hydroxypropyl cellulose.

[0009] Furthermore, in step 1), the mass ratio of dimethicone to calcium carbonate is 420:20.

[0010] Furthermore, in step 2), the mass ratio of ethylene glycol chitosan to guar gum is (2.4-2.6):1.

[0011] Furthermore, in step 2), the amount of the complex polysaccharide added is 15-25% of the mass of ethylene glycol chitosan.

[0012] Furthermore, in step 2), the buffer solution is PBS buffer.

[0013] Furthermore, in step 2), the complex polysaccharide is prepared using the following steps: S1: Prepare the base solution by uniformly mixing aluminum lactate, corn soluble protein and deionized water; S2: Add protease to the flaxseed gum solution to react, then centrifuge to remove the precipitate, then add Sevage reagent, shake and centrifuge to obtain the supernatant; S3: Take the supernatant and base liquid and mix them evenly to obtain the final product.

[0014] Furthermore, in step S2, the protease is a proteolytic enzyme.

[0015] This application also provides a calcium carbonate dimethicone chewable tablet, which is prepared by the above-described method.

[0016] Compared with the prior art, this application has the following beneficial effects: This application first mixes dimethicone with micronized silica gel to improve the dispersibility of dimethicone. Then, after adding the slurry, the ethylene glycol chitosan and guar gum in the slurry can form a Schiff base gel system. Simultaneously, the complex polysaccharides can further construct a multi-layered network structure within the gel system, multi-encapsulating the base material. When the patient takes the tablet, the chewed tablet enters the gastrointestinal system and comes into contact with gastric juice. The multi-layered encapsulation allows calcium carbonate and dimethicone to achieve a stable drug release rate. Furthermore, over time, the Schiff base gel system gradually disintegrates under acidic conditions, making the overall release rate more stable over time and maximizing the therapeutic effect. Attached Figure Description

[0017] Figure 1 This is a schematic diagram illustrating the simulated drug release of calcium carbonate dimethicone chewable tablets in Examples 1-2 and Control Groups 1-2 of this application. Detailed Implementation

[0018] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0019] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0020] When using “including,” “having,” and “contains” as described herein, the intention is to cover non-exclusive inclusion, unless an explicit qualifying term such as “only,” “consisting of,” etc., is used, in which case another component may be added.

[0021] The terms "preferred," "more preferably," "better," and "even better" used in this application refer to embodiments of this application that provide certain beneficial effects under certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the description of one or more preferred embodiments does not imply that other embodiments are unavailable, nor is it intended to exclude other embodiments from the scope of this application. That is, in this application, "preferred," "more preferably," "better," and "even better" are merely descriptions of implementations or embodiments with better effects, but do not constitute a limitation on the scope of protection of this application.

[0022] In this application, terms such as "further," "even more," and "particularly" are used for descriptive purposes and to indicate differences in content, but should not be construed as limiting the scope of protection of this application.

[0023] In this application, "at least one" means one or more, such as one, two, or more. "Multiple" or "several" means at least two, such as two, three, etc., and "multi-layered" means at least two layers, such as two layers, three layers, etc., unless otherwise explicitly specified. In the description of this application, "several" means at least one, such as one, two, etc., unless otherwise explicitly specified.

[0024] When a numerical range is disclosed herein, the range is considered continuous and includes the minimum and maximum values ​​of the range, as well as every value between the minimum and maximum values. Furthermore, when the range refers to integers, it includes every integer between the minimum and maximum values ​​of the range. Additionally, when multiple ranges are provided to describe a feature or characteristic, the ranges may be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges to which they are incorporated.

[0025] Unless otherwise specified, all steps in this application may be performed sequentially or randomly. For example, the method comprising steps (a) and (b) indicates that the method may include steps (a) and (b) performed sequentially, or it may include steps (b) and (a) performed sequentially. For example, the mention that the method may also include step (c) indicates that step (c) may be added to the method in any order; for example, the method may include steps (a), (b), and (c), or it may include steps (a), (c), and (b), or it may include steps (c), (a), and (b), etc. Unless otherwise stated, singular terms may include plural forms and should not be construed as having a quantity of one.

[0026] In this application, "above" or "below" includes the number itself. For example, "below 1" includes 1.

[0027] In this application, room temperature refers to 0~40℃, including but not limited to 10~40℃, or further to 20~30℃.

[0028] Based on extensive experimental research, this application provides a method for preparing calcium carbonate dimethicone chewable tablets, comprising the following steps: 1) Mix dimethicone and micronized silica gel, then add calcium carbonate and mix evenly. Next, add aspartame, flavoring, mannitol, corn starch and hydroxypropyl cellulose, sieve and mix evenly to obtain the base material. 2) Add ethylene glycol chitosan and guar gum to the buffer solution, stir well, then add galactose oxidase solution and catalase solution, react at room temperature, then add the complex polysaccharide and continue to mix to obtain the slurry. 3) Add slurry and magnesium stearate to the base material, mix evenly to form a soft material, and then granulate and compress to obtain the final product.

[0029] Furthermore, in step 1), the mass ratio of dimethicone oil to micronized silica gel is 20:1.

[0030] Furthermore, in step 1), the hydroxypropyl cellulose is a low-substituted hydroxypropyl cellulose.

[0031] Furthermore, in step 1), the mass ratio of dimethicone to calcium carbonate is 420:20.

[0032] Furthermore, in step 2), the mass ratio of ethylene glycol chitosan to guar gum is (2.4-2.6):1.

[0033] In some specific embodiments, in step 2), the mass ratio of ethylene glycol chitosan to guar gum can be 2.4:1, 2.45:1, 2.5:1, 2.55:1, or 2.6:1. More preferably, under normal circumstances, a mass ratio of ethylene glycol chitosan to guar gum of 2.5:1 in step 2) yields better experimental results.

[0034] Furthermore, in step 2), the amount of the complex polysaccharide added is 15-25% of the mass of ethylene glycol chitosan.

[0035] In some specific embodiments, in step 2), the amount of the complex polysaccharide added can be 15%, 15.5%, 16%, 16.5%, 17%, 17.5%, 18%, 18.5%, 19%, 19.5%, 20%, 20.5%, 21%, 21.5%, 22%, 22.5%, 23%, 23.5%, 24%, 24.5%, or 25% of the mass of ethylene glycol chitosan. More preferably, under normal circumstances, when the amount of the complex polysaccharide added in step 2) is 20%, 21%, or 22% of the mass of ethylene glycol chitosan, better experimental results can be obtained.

[0036] Furthermore, in step 2), the buffer solution is PBS buffer.

[0037] Furthermore, in step 2), the complex polysaccharide is prepared using the following steps: S1: Prepare the base solution by uniformly mixing aluminum lactate, corn soluble protein and deionized water; S2: Add protease to the flaxseed gum solution to react, then centrifuge to remove the precipitate, then add Sevage reagent, shake and centrifuge to obtain the supernatant; S3: Take the supernatant and base liquid and mix them evenly to obtain the final product.

[0038] Furthermore, in step S2, the protease is a proteolytic enzyme.

[0039] The present application will be further illustrated by the following examples, but these examples do not limit the scope of the present application.

[0040] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in this application, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. All reagents or instruments whose manufacturers are not specified are conventional products that can be purchased commercially. In addition to the specific methods, equipment, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description in this application, any prior art methods, equipment, and materials similar to or equivalent to those described, used, or made by the methods, equipment, and materials in the embodiments of this application may be used to implement this application. Example 1

[0041] The preparation method of the calcium carbonate dimethicone chewable tablets in this embodiment includes the following steps: 1) Take 20g of dimethicone oil and 1g of micronized silica gel, mix them together, then add 420g of calcium carbonate and mix evenly. Pass the mixture through a 40-mesh sieve. Next, add 3g of aspartame, 3g of flavoring, 200g of mannitol, 13.5g of corn starch and 15g of low-substituted hydroxypropyl cellulose. Pass the mixture through an 80-mesh sieve and mix evenly to obtain the base material. 2) Add 1.2g of ethylene glycol chitosan and 0.5g of guar gum to 50mL of PBS buffer, stir well, then add 2mL of galactose oxidase solution and 2mL of catalase solution. After reacting at room temperature, add 0.24g of complex polysaccharide and continue mixing to obtain a slurry. 3) Add slurry to the base material, the amount of slurry added is 5% of the base material mass and 4g of magnesium stearate, mix evenly to make soft material, then granulate and compress to obtain tablets, each tablet contains 20mg of dimethicone oil.

[0042] The complex polysaccharide in this embodiment is a flaxseed gum solution with a solid content of 25% and PBS buffer as the solvent.

[0043] The galactose oxidase solution in this embodiment uses PBS buffer as the solvent and contains 15 mg / mL, or 7.2 U of galactose oxidase.

[0044] The catalase solution in this embodiment uses PBS buffer as the solvent and has a catalase content of 20 mg / mL, 750 U. Example 2

[0045] The preparation method of the calcium carbonate dimethicone chewable tablets in this embodiment includes the following steps: 1) Take 20g of dimethicone oil and 1g of micronized silica gel, mix them together, then add 420g of calcium carbonate and mix evenly. Pass the mixture through a 40-mesh sieve. Next, add 3g of aspartame, 3g of flavoring, 200g of mannitol, 13.5g of corn starch and 15g of low-substituted hydroxypropyl cellulose. Pass the mixture through an 80-mesh sieve and mix evenly to obtain the base material. 2) Add 1.2g of ethylene glycol chitosan and 0.5g of guar gum to 50mL of PBS buffer, stir well, then add 2mL of galactose oxidase solution and 2mL of catalase solution. After reacting at room temperature, add 0.24g of complex polysaccharide and continue mixing to obtain a slurry. 3) Add slurry to the base material, the amount of slurry added is 5% of the base material mass and 4g of magnesium stearate, mix evenly to make soft material, then granulate and compress to obtain tablets, each tablet contains 20mg of dimethicone oil.

[0046] The galactose oxidase solution in this embodiment uses PBS buffer as the solvent and contains 15 mg / mL, or 7.2 U of galactose oxidase.

[0047] The catalase solution in this embodiment uses PBS buffer as the solvent and has a catalase content of 20 mg / mL, 750 U.

[0048] The complex polysaccharide in this embodiment was prepared using the following steps: S1: Mix 0.5g aluminum lactate, 1g corn lysate, and 30mL PBS buffer to prepare the base solution; S2: Add 0.5g of protease hydrolase to 100g of flaxseed gum solution and react at 50℃ for 2h. After the reaction is complete, raise the temperature to 80℃ and hold for 10min to inactivate papain. Then cool to room temperature, centrifuge to remove the precipitate, add an equal volume of Sevage reagent, shake and centrifuge to obtain the supernatant. Distill the supernatant under reduced pressure to make the solid content of the supernatant 25%. S3: Take the supernatant and base liquid at a mass ratio of 1:0.35 and mix them evenly to obtain the final product.

[0049] The flaxseed gum solution in this embodiment has a solid content of 10% and uses PBS buffer as the solvent.

[0050] The proteolytic enzyme in this embodiment is papain.

[0051] Control group 1 The preparation method of the calcium carbonate dimethicone chewable tablets in this control group includes the following steps: 1) Take 20g of dimethicone oil and 1g of micronized silica gel, mix them together, then add 420g of calcium carbonate and mix evenly. Pass the mixture through a 40-mesh sieve. Next, add 3g of aspartame, 3g of flavoring, 200g of mannitol, 13.5g of corn starch and 15g of low-substituted hydroxypropyl cellulose. Pass the mixture through an 80-mesh sieve and mix evenly to obtain the base material. 2) Add 10% corn starch slurry and 4g magnesium stearate to the base material, mix evenly to form a soft material, then granulate and compress to obtain the product. Each tablet contains 20mg of dimethicone.

[0052] In this control group, the amount of corn starch slurry added was 5% of the base material mass.

[0053] Control group 2 The preparation method of the calcium carbonate dimethicone chewable tablets in this control group includes the following steps: 1) Take 20g of dimethicone oil and 1g of micronized silica gel, mix them together, then add 420g of calcium carbonate and mix evenly. Pass the mixture through a 40-mesh sieve. Next, add 3g of aspartame, 3g of flavoring, 200g of mannitol, 13.5g of corn starch and 15g of low-substituted hydroxypropyl cellulose. Pass the mixture through an 80-mesh sieve and mix evenly to obtain the base material. 2) Add 1.2g of ethylene glycol chitosan and 0.5g of guar gum to 50mL of PBS buffer, stir well, then add 2mL of galactose oxidase solution and 2mL of catalase solution, and react at room temperature to obtain a slurry; 3) Add slurry and 4g magnesium stearate to the base material, mix evenly to form a soft material, then granulate and compress to obtain tablets, each tablet containing 20mg of dimethicone.

[0054] The galactose oxidase solution in this embodiment uses PBS buffer as the solvent and contains 15 mg / mL, or 7.2 U of galactose oxidase.

[0055] The catalase solution in this embodiment uses PBS buffer as the solvent and has a catalase content of 20 mg / mL, 750 U.

[0056] The amount of slurry added to this control group was 5% of the mass of the base material.

[0057] Performance testing The release rate of dimethicone was tested using an infrared photometer under simulated gastric fluid conditions. The test results are as follows: Figure 1 As shown. The specific test method is as follows: 1. Accurately weigh chromatographically pure dimethicone and prepare standard solutions with toluene at concentrations of approximately 0.05 mg / mL, 0.10 mg / mL, 0.20 mg / mL, 0.30 mg / mL, 0.40 mg / mL, and 0.50 mg / mL. Inject the standard solutions into the potassium bromide liquid cell. Set the scan count to 32 and the resolution to 4 cm⁻¹. -1 Wavenumber range 2000-400cm -1 The characteristic wavenumber was measured to be 1261 cm⁻¹. -1 Linear regression was performed with concentration C on the x-axis and absorbance A on the y-axis. The regression equation was A = 0.2512C + 0.002, and R = 0.9993, indicating a good linear relationship between concentration and absorbance in the range of 0-0.5 mg / mL.

[0058] 2. Test samples: Take 10 calcium carbonate dimethicone chewable tablets from Examples 1-2 and Control Groups 1-2, crush them, and add them to a beaker containing 500 mL of simulated gastric fluid. Stir magnetically at room temperature at a stirring speed of 200 r / min. Take 2 mL of the release solution at intervals and measure its absorbance with an infrared spectrophotometer. Then, add the same volume of simulated gastric fluid to the release solution to keep the volume of the solution in the beaker constant at 500 mL.

[0059] analyze Figure 1 It can be seen that the chewable tablets of this application have a very stable and effective drug dissolution state, which can reduce side effects, prolong the duration of drug effect, and give full play to the therapeutic effect.

[0060] Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A method for preparing calcium carbonate dimethicone chewable tablets, characterized in that: Includes the following steps: 1) Mix dimethicone and micronized silica gel, then add calcium carbonate and mix evenly. Next, add aspartame, flavoring, mannitol, corn starch and hydroxypropyl cellulose, sieve and mix evenly to obtain the base material. 2) Add ethylene glycol chitosan and guar gum to the buffer solution, stir evenly, then add galactose oxidase solution and catalase solution, react at room temperature, then add the complex polysaccharide and continue to mix to obtain the slurry. 3) Add slurry and magnesium stearate to the base material, mix evenly to form a soft material, and then granulate and compress to obtain the final product.

2. The method for preparing calcium carbonate dimethicone chewable tablets according to claim 1, characterized in that: In step 1), the mass ratio of dimethicone oil to micronized silica gel is 20:

1.

3. The method for preparing calcium carbonate dimethicone chewable tablets according to claim 1, characterized in that: In step 1), the hydroxypropyl cellulose is a low-substituted hydroxypropyl cellulose.

4. The method for preparing calcium carbonate dimethicone chewable tablets according to claim 1, characterized in that: In step 1), the mass ratio of dimethicone to calcium carbonate is 420:

20.

5. The method for preparing calcium carbonate dimethicone chewable tablets according to claim 1, characterized in that: In step 2), the mass ratio of ethylene glycol chitosan to guar gum is (2.4-2.6):

1.

6. The method for preparing calcium carbonate dimethicone chewable tablets according to claim 1, characterized in that: In step 2), the amount of the complex polysaccharide added is 15-25% of the mass of ethylene glycol chitosan.

7. The method for preparing calcium carbonate dimethicone chewable tablets according to claim 1, characterized in that: In step 2), the buffer solution is PBS buffer.

8. The method for preparing calcium carbonate dimethicone chewable tablets according to claim 1, characterized in that: In step 2), the complex polysaccharide is prepared using the following steps: S1: Prepare the base solution by uniformly mixing aluminum lactate, corn soluble protein and deionized water; S2: Add protease to the flaxseed gum solution to react, then centrifuge to remove the precipitate, then add Sevage reagent, shake and centrifuge to obtain the supernatant; S3: Take the supernatant and base liquid and mix them evenly to obtain the final product.

9. The method for preparing calcium carbonate dimethicone chewable tablets according to claim 8, characterized in that: In step S2, the protease is a proteolytic enzyme.

10. A calcium carbonate dimethicone chewable tablet, characterized in that: It is prepared by any one of the preparation methods described in claims 1-9.

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