A composition, a drug, and a method for preparing the same for treating stomach acid and bloating.

Abstract

This invention relates to the field of pharmaceutical preparations, and more particularly to a composition, its preparation method, and its application. The composition comprises simethicone and magnesium aluminum carbonate, with propionate, mannitol, sucrose, sorbitol, menthol, and magnesium stearate as excipients. Stability testing results show that, compared to combinations of other raw materials and excipients, the chewable tablets prepared by this invention using magnesium aluminum carbonate as the active ingredient and appropriate excipients exhibit good stability. Under accelerated conditions for 6 months, the defoaming and antacid abilities showed no significant change, still meeting the requirements, ensuring efficacy against gastric acid, bloating, and related gastrointestinal discomfort and pain, thereby reducing the frequency of patient medication and improving patient compliance.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical formulation technology, and in particular to a composition, a drug, and a method for preparing the same for treating gastric acid and bloating. Background Technology

[0002] Simethicone chewable tablets were developed and marketed by BERLIN-CHEMIE AG in Germany under the brand name EspumisanKautabletten. Their indications include: symptomatic treatment of gas-related gastrointestinal discomfort, such as bloating; and as an adjunct medication before abdominal endoscopy.

[0003] Aluminum magnesium carbonate is a compound of aluminum hydroxide, magnesium hydroxide, carbonate, and water. It is a novel, long-acting antacid. Its active ingredients are arranged in a layered lattice structure, forming a unique network structure with dual effects. On one hand, it rapidly brings gastric juice to the optimal pH range of 3-5, inhibiting excessive pepsin activity and promoting ulcer healing. On the other hand, it reversibly binds to bile acids and pepsin, eliminating the damage of bile acids to the gastric mucosa. It is used for hyperacidity, acute and chronic gastritis, bile reflux gastritis, reflux esophagitis, duodenal bulb ulcers, gastric ulcers, and non-ulcer dyspepsia and gastrointestinal discomfort caused by various factors such as excessive consumption of coffee, alcohol, strong tea, nicotine, and the use of nonsteroidal anti-inflammatory drugs (NSAIDs).

[0004] Existing studies have shown that the combined use of simethicone and aluminum magnesium carbonate is more effective than using either drug alone in treating flatulence, peptic ulcers, and reflux esophagitis, demonstrating a good synergistic effect. However, the dosage form of the combined use is mainly a suspension, which is not very stable. Its defoaming and acid-neutralizing abilities decrease after a period of storage. Therefore, it is of great significance to provide a dosage form with better stability, stronger defoaming and acid-neutralizing abilities to further improve the efficacy against gastric acid and flatulence, reduce the frequency of medication for patients, and improve compliance. Summary of the Invention

[0005] In view of this, the present invention provides a composition, a medicine, and a method for preparing the same for treating gastric acid and bloating.

[0006] This invention uses simethicone and magnesium aluminum carbonate as active ingredients, and rationally combines them with excipients. The resulting composition exhibits strong acid-neutralizing and defoaming abilities, showing significant differences compared to other combinations of raw materials and excipients. This indicates that the tablets prepared from the optimized raw materials and excipients obtained in this invention are more effective in treating gastric acid and bloating.

[0007] In this invention, the composition comprises the following raw materials in parts by weight:

[0008]

[0009] In some specific embodiments, the composition comprises, by weight, parts of:

[0010]

[0011] In some specific embodiments, the composition comprises, by weight, parts of:

[0012]

[0013]

[0014] In some specific embodiments, the composition comprises, by weight, parts thereof.

[0015]

[0016] The present invention also provides the use of the composition in the preparation of a medicament for treating gastric acid and flatulence.

[0017] The present invention also provides a medicine for treating stomach acid and bloating, the raw materials of which include the composition described in the present invention.

[0018] The present invention also provides a method for preparing the drug, wherein the drug is a tablet, and the method for preparing the drug includes the following steps:

[0019] S1. Mix magnesium aluminum carbonate with simethicone oil and then granulate to obtain the first material;

[0020] S2. The first material is mixed with sorbitol, propionate, sucrose, mannitol and povidone and granulated to obtain the second material;

[0021] S3. Mix the second material with menthol and magnesium stearate to obtain an intermediate;

[0022] S4. Compress the intermediate into tablets.

[0023] In this invention, before step S1, the aluminum magnesium carbonate and menthol are pretreated. The pretreatment includes: sieving the aluminum magnesium carbonate and pulverizing and sieving the menthol. The mesh size of the sieve is 60 to 100 mesh, specifically 60, 70, 80, 90, or 100 mesh.

[0024] In this invention, in step S1, both the first granulation and the second granulation are performed under stirring and cutting conditions. The stirring speed is 190 rpm to 210 rpm, specifically 190 rpm, 200 rpm, or 210 rpm. The cutting speed is 990 rpm to 1010 rpm, specifically 990 rpm, 1000 rpm, or 1010 rpm. The granulation time is 3 min to 7 min, specifically 3 min, 4 min, 5 min, 6 min, or 7 min.

[0025] Furthermore, step S2 includes: mixing the first material and sorbitol and granulating for 5 minutes; then adding propionate, sucrose, mannitol and povidone and mixing and granulating for 10 minutes.

[0026] In this invention, in step S3, the mixing is carried out at a rotation speed of 5 rpm to 8 rpm, specifically 5 rpm, 6 rpm, 7 rpm, or 8 rpm. The mixing time is 10 minutes.

[0027] This invention also provides a medicament for treating gastric acid and bloating prepared by the above-described preparation method. A composition, its preparation method, and its application are also described. The composition comprises simethicone, magnesium aluminum carbonate, and excipients including propionate, mannitol, sucrose, sorbitol, menthol, and magnesium stearate. Stability testing results show that, compared to combinations of other raw materials and excipients, the chewable tablets prepared by this invention with magnesium aluminum carbonate as the active ingredient and appropriate excipients exhibit good stability. Under accelerated conditions for 6 months, the defoaming ability and antacid capacity showed no significant change, still meeting the requirements, ensuring efficacy against gastric acid, bloating, and related gastrointestinal discomfort and pain, thereby reducing the frequency of medication use and improving patient compliance. Detailed Implementation

[0028] This invention provides a composition, a drug, and a method for preparing the same for treating gastric acid and bloating. Those skilled in the art can refer to this description and appropriately modify the process parameters to achieve the desired results. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The methods and applications of this invention have been described through preferred embodiments, and those skilled in the art can clearly modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit, and scope of this invention to implement and apply the technology of this invention.

[0029] The test materials used in this invention are all common commercial products and can be purchased on the market.

[0030] The present invention will be further illustrated below with reference to the embodiments:

[0031] Example 1

[0032] 1. Prescription:

[0033] Table 1

[0034]

[0035]

[0036] 2. Process steps:

[0037] Step 1: Pass the aluminum magnesium carbonate through an 80-mesh sieve; Crush the menthol and pass it through an 80-mesh sieve;

[0038] Step 2: Weighing Ingredients: Weigh each raw and auxiliary material according to the table above;

[0039] Step 3: Add magnesium aluminum carbonate and simethicone to a wet granulator and mix. Set the stirring speed to 200 rpm and the cutting speed to 1000 rpm. Run the machine for 5 minutes to allow the magnesium aluminum carbonate to fully absorb the simethicone.

[0040] Step 4: Premix the raw materials under the stirring and cutting conditions of Step 3: Add sorbitol to the wet granulator of Step 3, start running for 5 minutes, then add propionate, sucrose, mannitol and povidone, and run for 10 minutes;

[0041] Step 5: Mixing: Transfer the material obtained in Step 4 to a hopper mixer, add menthol and magnesium stearate, set the speed to 6 rpm, and run for 10 minutes to obtain the intermediate.

[0042] Step 6: Tableting: The intermediate is compressed into tablets to obtain simethicone aluminum magnesium carbonate chewable tablets.

[0043] Example 2

[0044] 1. Prescription:

[0045] Table 2

[0046]

[0047]

[0048] 2. Process steps:

[0049] Step 1: Pass the aluminum magnesium carbonate through an 80-mesh sieve; Crush the menthol and pass it through an 80-mesh sieve;

[0050] Step 2: Weighing Ingredients: Weigh each raw and auxiliary material according to the table above;

[0051] Step 3: Add magnesium aluminum carbonate and simethicone to a wet granulator and mix. Set the stirring speed to 200 rpm and the cutting speed to 1000 rpm. Run the machine for 5 minutes to allow the magnesium aluminum carbonate to fully absorb the simethicone.

[0052] Step 4: Premix the raw materials under the stirring and cutting conditions of Step 3: Add sorbitol to the wet granulator of Step 3, start running for 5 minutes, then add propionate, sucrose, mannitol and povidone, and run for 10 minutes;

[0053] Step 5: Mixing: Transfer the material obtained in Step 4 to a hopper mixer, add menthol and magnesium stearate, set the speed to 6 rpm, and run for 10 minutes to obtain the intermediate.

[0054] Step 6: Tableting: The intermediate is compressed into tablets to obtain simethicone aluminum magnesium carbonate chewable tablets.

[0055] Example 3

[0056] 1. Prescription:

[0057] Table 3

[0058]

[0059]

[0060] 2. Process steps:

[0061] Step 1: Pass the aluminum magnesium carbonate through an 80-mesh sieve; Crush the menthol and pass it through an 80-mesh sieve;

[0062] Step 2: Weighing Ingredients: Weigh each raw and auxiliary material according to the table above;

[0063] Step 3: Add magnesium aluminum carbonate and simethicone to a wet granulator and mix. Set the stirring speed to 200 rpm and the cutting speed to 1000 rpm. Run the machine for 5 minutes to allow the magnesium aluminum carbonate to fully absorb the simethicone.

[0064] Step 4: Premix the raw materials under the stirring and cutting conditions of Step 3: Add sorbitol to the wet granulator of Step 3, start running for 5 minutes, then add propionate, sucrose, mannitol and povidone, and run for 10 minutes;

[0065] Step 5: Mixing: Transfer the material obtained in Step 4 to a hopper mixer, add menthol and magnesium stearate, set the speed to 6 rpm, and run for 10 minutes to obtain the intermediate.

[0066] Step 6: Tableting: The intermediate is compressed into tablets to obtain simethicone aluminum magnesium carbonate chewable tablets.

[0067] Compare with Example 1

[0068] 1. Prescription:

[0069] Table 4

[0070] name Dosage Simethicone 40g Aluminum magnesium carbonate 500g Mannitol 80g sucrose 184g Sorbitol 150g Povidone 30g Menthol 1g magnesium stearate 15g Made 1000 pieces

[0071] 2. Process steps:

[0072] Step 1: Pass the aluminum magnesium carbonate through an 80-mesh sieve; Crush the menthol and pass it through an 80-mesh sieve;

[0073] Step 2: Weighing Ingredients: Weigh each raw and auxiliary material according to the table above;

[0074] Step 3: Add magnesium aluminum carbonate and simethicone to a wet granulator and mix. Set the stirring speed to 200 rpm and the cutting speed to 1000 rpm. Run the machine for 5 minutes to allow the magnesium aluminum carbonate to fully absorb the simethicone.

[0075] Step 4: Premix the raw materials under the stirring and cutting conditions of Step 3: Add sorbitol to the wet granulator of Step 3, start running for 5 minutes, then add sucrose, mannitol and povidone, and run for 10 minutes;

[0076] Step 5: Mixing: Transfer the material obtained in Step 4 to a hopper mixer, add menthol and magnesium stearate, set the speed to 6 rpm, and run for 10 minutes to obtain the intermediate.

[0077] Step 6: Tableting: The intermediate is compressed into tablets to obtain simethicone aluminum magnesium carbonate chewable tablets.

[0078] Compare with Example 2

[0079] 1. Prescription:

[0080] Table 5

[0081] name Dosage Simethicone 40g Aluminum magnesium carbonate 500g Mannitol 100g sucrose 162g Sorbitol 153g Povidone 30g Menthol 1g magnesium stearate 15g Made 1000 pieces

[0082] 2. Process steps:

[0083] Step 1: Pass the aluminum magnesium carbonate through an 80-mesh sieve; Crush the menthol and pass it through an 80-mesh sieve;

[0084] Step 2: Weighing Ingredients: Weigh each raw and auxiliary material according to the table above;

[0085] Step 3: Add magnesium aluminum carbonate and simethicone to a wet granulator and mix. Set the stirring speed to 200 rpm and the cutting speed to 1000 rpm. Run the machine for 5 minutes to allow the magnesium aluminum carbonate to fully absorb the simethicone.

[0086] Step 4: Premix the raw materials under the stirring and cutting conditions of Step 3: Add sorbitol to the wet granulator of Step 3, start running for 5 minutes, then add sucrose, mannitol and povidone, and run for 10 minutes;

[0087] Step 5: Mixing: Transfer the material obtained in Step 4 to a hopper mixer, add menthol and magnesium stearate, set the speed to 6 rpm, and run for 10 minutes to obtain the intermediate.

[0088] Step 6: Tableting: The intermediate is compressed into tablets to obtain simethicone aluminum magnesium carbonate chewable tablets.

[0089] Example 4

[0090] The samples prepared in Examples 1-3 and Control Examples 1-2 were subjected to accelerated testing (conditions: 40℃±2℃, RH 75%±5%) for 6 months. The results are as follows:

[0091] Table 6: Accelerated test results of the samples from Example 1

[0092]

[0093]

[0094] Table 7: Accelerated test results of the samples from Example 2

[0095]

[0096] Table 8: Accelerated test results of the samples from Example 3

[0097]

[0098]

[0099] Table 9: Results of accelerated testing of the control sample 1

[0100]

[0101]

[0102] Table 10: Results of accelerated testing of the control sample 2

[0103]

[0104] Results: After 6 months of accelerated testing, no significant changes were observed in the quality indicators of the samples from Examples 1, 2, and 3. The acid-producing power of the control samples 1 and 2 failed to meet the requirements after 3 and 6 months of accelerated testing, respectively, and their defoaming power was close to the lower limit. This indicates that the samples prepared according to the formulation and process of this invention have stable quality.

[0105] Example 5: Acid-generating capacity test

[0106] To simulate the chewing process of a patient taking medication, the experimental samples (Examples 1, 2, and 3) were processed into 20-mesh particles and used as test samples. Using the Rossett-Rice in vitro acid-fastness test, 30 ml of water and 70 ml of 0.1 mol·L⁻¹ hydrochloric acid solution were added to a reaction vessel. The reaction solution was maintained at 37°C using a magnetic stirrer and a contact thermometer, and the magnetic stirring speed was 400 rpm. -1 The pH change in the reaction vessel was measured using a pH meter equipped with a glass electrode and a calomel electrode, and a constant flow pump was used at a rate of (2.0 ± 0.1) ml / min. -1 0.1 mol·L⁻¹ solution at a constant temperature of 37°C was pumped into the reaction vessel at a rate that was maintained at a constant temperature. -1 Hydrochloric acid solution. After adding the antacid to be tested, immediately turn on the constant flow pump and magnetic stirrer, and record the time and pH value simultaneously.

[0107] Table 11: Results of Dynamic Acid Production Capacity Study

[0108]

[0109] Results: The samples in Examples 1, 2, and 3 reached pH 3 in a time close to that of Daxin (a brand of magnesium carbonate tablets), much faster than domestically produced magnesium aluminum carbonate chewable tablets, and maintained pH 3-5 for a longer period, indicating that the magnesium aluminum carbonate tablets prepared according to this invention have a fast disintegration and dispersion rate and a rapid onset of action. The samples in Control Examples 1 and 2 reached pH 3 in a longer time than Daxin and domestically produced magnesium aluminum carbonate chewable tablets, and maintained pH 3-5 for a shorter period. This indicates that the samples prepared according to this invention have strong acid-neutralizing power.

[0110] Example 6: Evaluation of Defoaming Ability

[0111] Defoaming ability test method: Take two 50ml portions of 1.0% Triton X-100 solution without foam and carefully inject them into two clean 250ml stoppered graduated cylinders. Take an appropriate amount of the product powder (approximately equivalent to 40mg of polydimethylsiloxane) and place it in one of the graduated cylinders. Seal both graduated cylinders tightly, shake them vigorously 5 times, let them stand for 1 minute, and measure the foam height. Divide the height of the reduced foam in the graduated cylinder with the product added by the height of the foam in the graduated cylinder without the product added (100%) to calculate the defoaming ability. It should not be less than 80%.

[0112] Table 12: Defoaming ability

[0113]

[0114] Results: The defoaming ability of the samples from Examples 1, 2, and 3 of this invention was consistent with that of the simethicone emulsion, and significantly better than that of the simethicone chewable tablets. However, the defoaming ability of the samples from Control Examples 1 and 2 was significantly lower than that of the simethicone emulsion and the simethicone chewable tablets. This indicates that the chewable tablets of this invention have excellent defoaming ability, effectively relieving bloating, and are significantly more effective than Control Examples 1-2 and existing simethicone chewable tablets.

[0115] The above are merely preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A composition, characterized in that, It includes simethicone, magnesium aluminum carbonate, propionate, mannitol, sucrose, sorbitol, povidone, menthol, and magnesium stearate.

2. The composition according to claim 1, characterized in that, The raw materials include the following parts by weight:

3. The composition according to any one of claims 1 to 2, characterized in that, The composition comprises, by weight, parts of: Or include: Or include:

4. Use of the composition according to any one of claims 1 to 3 in the preparation of a medicament for treating gastric acid and flatulence.

5. A medication for treating stomach acid and bloating, characterized in that, Its raw materials include the composition described in any one of claims 1 to 3.

6. The method for preparing the drug as described in claim 5, characterized in that, The drug is a tablet, and the preparation method of the tablet includes the following steps: S1. After mixing aluminum magnesium carbonate with simethicone oil, the mixture is subjected to first granulation to obtain the first material; S2. The first material is mixed with sorbitol, propionate, sucrose, mannitol and povidone, and then subjected to a second granulation to obtain the second material. S3. Mix the second material with menthol and magnesium stearate to obtain an intermediate; S4. Compress the intermediate into tablets.

7. The preparation method according to claim 6, characterized in that, In step S1, the first granulation includes granulating for 5 minutes under the conditions of stirring speed of 190 rpm to 210 rpm and cutting speed of 990 rpm to 1010 rpm.

8. The preparation method according to claim 6, characterized in that, The second granulation in step S2 includes: mixing and granulating the first material and sorbitol for 5 minutes under the conditions of stirring speed of 190 rpm to 210 rpm and cutting speed of 990 rpm to 1010 rpm, and then adding propionate, sucrose, mannitol and povidone and mixing and granulating for 10 minutes.

9. The preparation method according to claim 6, characterized in that, In step S3, the mixing is carried out at a rotation speed of 5 rpm to 8 rpm and the mixing time is 10 min.

10. The preparation method according to any one of claims 6 to 9, characterized in that, Before performing step S1, the process also includes sieving magnesium aluminum carbonate, crushing menthol, and sieving it.

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