Simethicone oral preparation composition as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a simethicone oral preparation composition as well as a preparation method and application thereof. The composition comprises simethicone, magnesium lauryl sulfate, an alkaline compound, starch, carboxymethyl cellulose, mannitol and water. According to the simethicone oral preparation composition, magnesium lauryl sulfate is added, so that the simethicone oral preparation composition is low in hygroscopicity and relatively good in stability; by limiting the addition amount of the magnesium lauryl sulfate, the angle of repose of the prepared simethicone oral preparation composition does not exceed 30 degrees, and the simethicone oral preparation composition has good fluidity. The simethicone oral preparation prepared from magnesium lauryl sulfate can be taken by using a small amount of water, the whole system is easy to form a uniform solution, the medication compliance of a patient is improved, the defoaming effect is better after the simethicone oral preparation is taken, and the result is clearer in the gastroscopy process.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an oral preparation composition of simethicone, a preparation method thereof, and an application thereof. Background Art

[0002] Gastroscopy is an effective method for diagnosing upper gastrointestinal diseases. However, foamy mucus adheres to the surface of the esophageal and gastric mucosa, resulting in unclear vision, affecting endoscopic observation, and even causing various false appearances, which is also the main reason for missed diagnosis and misdiagnosis.

[0003] Simethicone is often used as an antifoaming agent in endoscopic examinations. However, simethicone itself is insoluble in water. To exert its maximum antifoaming ability, the commonly used dosage forms in clinical practice are simethicone emulsion and its powder, etc. Although the emulsion has antifoaming ability, it has the characteristic of the emulsion dosage form - turbidity. Due to the extremely high requirement for the clarity of the vision during endoscopic examination, its turbid characteristic still affects the clarity of the vision during endoscopic examination. The simethicone powder is more stable than the liquid dosage form, has stronger antifoaming ability, is more convenient for storage and transportation, and can be made into oral granules or effervescent tablets.

[0004] For example, Chinese Patent Publication No. CN101836996A discloses an oral solid preparation mainly composed of loperamide hydrochloride and simethicone. It is a solid preparation made from loperamide hydrochloride, simethicone, and pharmaceutically acceptable excipients through pharmaceutical technology. The oral solid preparation of the present invention has stable quality, controllability, safety, and effectiveness. However, this solid preparation cannot solve the discomfort symptoms such as nausea in a small number of patients, and the simethicone and loperamide hydrochloride are prepared by ordinary processes. The antifoaming ability of simethicone in the oral solid preparation mainly composed of loperamide hydrochloride and simethicone is lower than that of simethicone alone.

[0005] Another Chinese Patent Publication No. CN107496363A discloses a solid composition of simethicone. The composition is composed of the following components in weight percentage: simethicone 8.0 - 12.0%, emulsifier 4.0 - 15.0%, pharmaceutically acceptable carrier material 73.0 - 88.0%, and the sum of the above components is 100%. The solid composition of simethicone has a high content of simethicone, few component types, good safety, good antifoaming ability, and good light transmittance of the solution obtained after dissolving in water. However, in actual clinical applications of the solid composition of simethicone of the present invention, turbidity is easily generated in the gastrointestinal tract of patients after administration, affecting the detection vision of gastroscopy and colonoscopy.

[0006] Another Chinese invention patent publication number CN117959256A discloses a simethicone powder and its preparation method and application. The simethicone powder includes simethicone, alkaline compounds, fillers, dispersants, and flavoring agents. This invention prepares a powder that can be used in combination, which is taken orally to treat gastric diseases such as gastric acid and abdominal flatulence, and can also be used as an antifoaming agent before gastroscopy examination. However, this invention uses colloidal silica as a dispersant, and colloidal silica is a water-insoluble substance, which will cause a sandy feeling in the patient's mouth when used, affecting the patient's compliance with taking medicine.

[0007] Due to its relatively high viscosity, simethicone has a problem of poor fluidity during the mixing process with solid excipients. Using silica as a dispersant can increase fluidity, but due to the poor solubility of silica after preparing the dispersant, there is a "sandy feeling" when taken orally; when using a general water-soluble dispersant, due to its water absorption, there is a problem of hygroscopicity, which will also lead to poor fluidity.

[0008] In view of this, there is an urgent need in the art to provide a simethicone oral preparation composition with better stability, fluidity, and defoaming effect, clearer results during gastroscopy examination, and can enhance the patient's compliance with taking medicine. Summary of the Invention

[0009] In view of the problems existing in the prior art, the present invention provides a simethicone oral preparation composition, its preparation method, and application.

[0010] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0011] A simethicone oral preparation composition, comprising the following components: simethicone, magnesium lauryl sulfate, alkaline compounds, starch, carboxymethyl cellulose, mannitol, and water.

[0012] Preferably, the particle size of the magnesium lauryl sulfate ≤ 30 μm.

[0013] Preferably, the alkaline compound is sodium bicarbonate, sodium hydroxide, or potassium hydroxide.

[0014] Preferably, the simethicone oral preparation composition further includes a flavoring agent.

[0015] Preferably, the flavoring agent is selected from one or more of strawberry essence, orange essence, and cherry essence.

[0016] Preferably, by mass, it comprises the following components: 6 - 12 parts of simethicone, 0.5 - 0.8 parts of magnesium lauryl sulfate, 5 - 20 parts of alkaline compounds, 25 - 35 parts of starch, 15 - 25 parts of carboxymethyl cellulose, 25 - 35 parts of mannitol, 0.2 - 0.5 parts of flavoring agent, and 80 - 120 parts of water.

[0017] More preferably, by mass parts, it includes the following components: 7-9 parts of simethicone, 0.5-0.6 parts of magnesium lauryl sulfate, 5-15 parts of alkaline compound, 30-32 parts of starch, 20-24 parts of carboxymethyl cellulose, 26-30 parts of mannitol, 0.3-0.4 parts of flavoring agent, and 80-120 parts of water.

[0018] Preferably, the type of the oral preparation is powder.

[0019] The present invention also provides a preparation method of the above-mentioned simethicone oral preparation composition, including the following steps:

[0020] (1) First, mix simethicone with part of the starch to obtain wet granule 1; mix the remaining starch, carboxymethyl cellulose with water to obtain wet granule 2; then mix wet granule 1 and wet granule 2 evenly to obtain a mixture;

[0021] (2) Dissolve the alkaline compound in the remaining water, prepare a solution and then add mannitol to obtain wet granule 3;

[0022] (3) Mix the mixture, wet granule 3 and the flavoring agent, grind, and then add magnesium lauryl sulfate and mix evenly to obtain the product.

[0023] Preferably, in step (3), after mixing, it is also necessary to pass through a 270-325 mesh sieve and dry. The grinding needs to reach a particle size of ≤30 μm, and after mixing evenly, it needs to pass through a 270-325 mesh sieve.

[0024] The present invention also provides the application of the above-mentioned simethicone oral preparation composition or the simethicone oral preparation composition prepared by the above-mentioned preparation method in the preparation of an oral dispersant for treating gastric acid and abdominal flatulence or an antifoaming agent for gastroscopy examination.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] (1) By adding magnesium lauryl sulfate in the present invention, the hygroscopicity of the simethicone oral preparation composition is not strong, and it has good stability under light conditions; by limiting the addition amount of magnesium lauryl sulfate, the angle of repose of the prepared simethicone oral preparation composition does not exceed 30°, and it has good fluidity.

[0027] (2) The simethicone oral preparation prepared by using magnesium lauryl sulfate in the present invention can be taken with less water, and the whole system is easy to form a homogeneous solution, which increases the compliance of patients taking medicine. After taking it, the antifoaming effect is better, and the result is clearer during gastroscopy examination. Description of the Drawings

[0028] Figure 1The gastroscopy examination image after a patient takes the simethicone oral preparation composition prepared according to Prescription 1-1.

[0029] Figure 2 The gastroscopy examination image after a patient takes the simethicone oral preparation composition prepared according to Prescription 5-4. Detailed implementation manners

[0030] It should be noted that the raw materials used in the present invention are all ordinary commercially available products. Among them, magnesium lauryl sulfate has a particle size of ≤30 μm.

[0031] Example 1

[0032] A simethicone oral preparation composition, by mass parts, its raw material composition is shown in Table 1:

[0033] Table 1 Raw material composition of Prescription 1-1 to Prescription 1-4

[0034] Composition Prescription 1-1 Prescription 1-2 Prescription 1-3 Prescription 1-4 Simethicone 8 parts 8 parts 8 parts 8 parts Sodium bicarbonate (alkaline compound) 10 parts 15 parts 5 parts 10 parts Starch 32 parts 30 parts 32 parts 32 parts Carboxymethyl cellulose 20 parts 20 parts 23.2 parts 20 parts Mannitol 29.2 parts 26.2 parts 28 parts 29.5 parts Strawberry essence (flavoring agent) 0.3 parts 0.3 parts 0.3 parts 0.3 parts Magnesium lauryl sulfate 0.5 parts 0.5 parts 0.5 parts 0.8 parts Purified water 100 parts 120 parts 80 parts 100 parts

[0035] The preparation method of this simethicone oral preparation composition is as follows:

[0036] (1) First, weigh the prescribed amount of simethicone, add 16 parts of starch to moisten it while stirring, mix evenly to obtain wet granules 1; then add the remaining starch and carboxymethyl cellulose to 60 parts of purified water, stir until non-loose wet granules 2 are formed; stir and mix the two kinds of wet granules to obtain mixture 1;

[0037] (2) Prepare an aqueous sodium bicarbonate solution with a mass concentration of 20% of the alkaline compound sodium bicarbonate, and add mannitol while stirring to mix evenly to obtain wet granules 3;

[0038] (3) Mix mixture 1 and wet granules 3 respectively, add the flavoring agent strawberry essence while stirring, mix evenly, pass through a 300-mesh sieve, place it in a vacuum drying oven for drying, grind it in a grinder until the particle size of the granules is below 30 μm; then add magnesium lauryl sulfate (particle size ≤30 μm), transfer it to a three-dimensional mixing device for sufficient mixing, and pass through a 300-mesh sieve to obtain.

[0039] Example 2

[0040] A simethicone oral preparation composition, by mass parts, its raw material composition is shown in Table 2:

[0041] Table 2 Raw material composition of Prescription 2-1 to Prescription 2-4

[0042] Composition Prescription 2-1 Prescription 2-2 Prescription 2-3 Prescription 2-4 Simethicone 8 parts 8 parts 8 parts 8 parts Sodium hydroxide (alkaline compound) 10 parts 15 parts 5 parts 10 parts Starch 32 parts 32 parts 30 parts 31.7 parts Carboxymethyl cellulose 20 parts 17.2 parts 26.2 parts 20 parts Mannitol 29.2 parts 27 parts 30 parts 29.2 parts Orange essence (flavoring agent) 0.3 parts 0.3 parts 0.3 parts 0.3 parts Magnesium lauryl sulfate 0.5 parts 0.5 parts 0.5 parts 0.8 parts Purified water 100 parts 120 parts 80 parts 100 parts

[0043] The preparation method of this simethicone oral preparation composition is as follows:

[0044] (1) First, weigh the prescribed amount of simethicone, add 16 parts of starch to wet the mixture while stirring, and mix well to obtain wet granules 1; then, add the remaining starch and carboxymethyl cellulose to 60 parts of purified water, and stir until non-loose wet granules 2 are formed; stir and mix the two wet granules to obtain a mixture 1;

[0045] (2) preparing an alkaline compound sodium hydroxide into a sodium hydroxide aqueous solution with a mass concentration of 20%, adding mannitol while stirring, and mixing to obtain wet granules 3;

[0046] (3) Mix the mixture 1 and the wet granules 3 respectively, add the flavoring agent orange essence while stirring, mix them evenly, sieve through a 300-mesh sieve, dry them in a vacuum drying oven, and grind them in a grinder until the particle size is less than 30 μm; then add magnesium lauryl sulfate (particle size ≤ 30 μm), transfer them to a three-dimensional mixing device for thorough mixing, and sieve through a 300-mesh sieve to obtain the product.

[0047] Example 3

[0048] A simethicone oral preparation composition, the raw material composition of which is shown in Table 3 by weight:

[0049] Table 3 Raw material composition of prescription 3-1 to prescription 3-3

[0050]

[0051]

[0052] The preparation method of the simethicone oral preparation composition comprises the following steps:

[0053] (1) First, weigh the prescribed amount of simethicone, add 16 parts of starch to wet the mixture while stirring, and mix well to obtain wet granules 1; then, add the remaining starch and carboxymethyl cellulose to 60 parts of purified water, and stir until non-loose wet granules 2 are formed; stir and mix the two wet granules to obtain a mixture 1;

[0054] (2) preparing an alkaline compound potassium hydroxide into a potassium hydroxide aqueous solution with a mass concentration of 20%, adding mannitol while stirring, and mixing to obtain wet granules 3;

[0055] (3) Mix the mixture 1 and the wet granules 3 respectively, add the flavoring agent cherry essence while stirring, mix them evenly, sieve through a 300-mesh sieve, dry them in a vacuum drying oven, and grind them in a grinder until the particle size is less than 30 μm; then add magnesium lauryl sulfate (particle size ≤ 30 μm), transfer them to a three-dimensional mixing device for thorough mixing, and sieve through a 300-mesh sieve to obtain the product.

[0056] Comparative Example 1

[0057] A simethicone oral preparation composition, by mass, its raw material composition is shown in Table 4:

[0058] Table 4 Raw material composition of Formulations 4-1 to 4-4

[0059]

[0060] The preparation method of this simethicone oral preparation composition is the same as that of Example 1.

[0061] Comparative Example 2

[0062] Compared with Formulation 1-1, Formulation 5-1 is only different in that magnesium lauryl sulfate is replaced by microcrystalline cellulose to prepare a simethicone oral preparation composition.

[0063] Compared with Formulation 1-1, Formulation 5-2 is only different in that magnesium lauryl sulfate is replaced by stearic acid to prepare a simethicone oral preparation composition.

[0064] Compared with Formulation 1-1, Formulation 5-3 is only different in that magnesium lauryl sulfate is replaced by sodium stearyl fumarate to prepare a simethicone oral preparation composition.

[0065] Compared with Formulation 1-1, Formulation 5-4 is only different in that magnesium lauryl sulfate is replaced by silicon dioxide to prepare a simethicone oral preparation composition.

[0066] The preparation methods of the simethicone oral preparation compositions of Formulations 5-1 to 5-4 are the same as that of Example 1.

[0067] Test Example 1

[0068] The simethicone oral preparation compositions prepared from Examples 1-3, Comparative Example 1 and Formulations 5-1 and 5-2 of Comparative Example 2 were respectively subjected to appearance, particle size and angle of repose detection. Appearance detection method: Take a small amount of solid and visually observe it in bright light; Particle size detection method: According to the Chinese Pharmacopoeia, use a laser particle size analyzer to measure the particle size of the sample; Angle of repose detection method: Use an FT-104B angle of repose measuring instrument. According to GB11986-89 "Determination of the Angle of Repose of Surfactant Powders and Particles", the products obtained from different examples are allowed to fall on a horizontal metal plate through a funnel to form a cone, and the angle between the conical surface and the bottom surface of the cone is measured to obtain the angle of repose.

[0069] The detection results are shown in Table 5. From the data of Examples 1-3, it can be seen that when the dosage of magnesium lauryl sulfate is 0.5-0.8 parts, the angle of repose of the prepared simethicone oral preparation composition does not exceed 30°, and it has good fluidity. Excessive or too little dosage of magnesium lauryl sulfate will affect the fluidity of the simethicone oral preparation composition.

[0070] Among them, the angle of repose of Formulations 5-1 and 5-2 is greater than 35°, indicating that different dispersants have a great influence on the hygroscopicity of the simethicone oral preparation composition. After absorbing moisture, particle agglomeration will occur, affecting fluidity. Only the simethicone oral preparation composition prepared with a specific dispersant (i.e., magnesium lauryl sulfate) has good fluidity.

[0071] Table 5 Results of Fluidity Detection

[0072]

[0073]

[0074] Test Example 2

[0075] The simethicone oral preparation compositions prepared from Formulations 1-1, 2-2, 3-3, 5-1, 5-2, and 5-3 were respectively subjected to stability investigation. The stability test conditions were as follows: placed at 60°C and 75% RH for 5 days, 10 days, and 30 days; irradiated with light at an intensity of 4500 ± 500 lx for 5 days and 10 days.

[0076] The experimental results are shown in Table 6. It can be seen from Table 6 that when magnesium lauryl sulfate is used as the dispersant, the prepared simethicone oral preparation composition does not have significant hygroscopicity and has good stability under light conditions.

[0077] Table 6 Results of Stability Experiment

[0078]

[0079]

[0080] Test Example 3

[0081] Animal efficacy experiments were respectively conducted on the simethicone oral preparation compositions prepared from Formulation 1-1, Formulation 2-1, Formulation 3-1, and Formulation 5-4.

[0082] Experimental method: Using SD rats as the experimental system, a 40% Triton X-100 solution at 2.0 μL / g was administered to establish a mouse gastric flatulence model. After modeling, it was divided into a normal group, a model control group, and an experimental group, with 10 rats in each group. The experimental group was respectively administered the simethicone oral preparation compositions prepared from 0.2 g / g of Formulation 1-1, Formulation 2-1, Formulation 3-1, and Formulation 5-4, and the number of hiccups of the mice was recorded within 30 minutes after administration.

[0083] After recording the number of hiccups, the mice were immediately sacrificed by cervical dislocation, dissected, the thoracic cavity was opened, the upper end of the cardia and the lower end of the pylorus were ligated with a thread, and then the stomach was completely removed. The drainage volume was measured using a toe plethysmograph, which was the total volume of the stomach with air bubbles. After puncturing to remove all the gas, the drainage volume was measured again using the toe plethysmograph, which was the volume of the solid stomach. The difference between the two was the volume of air bubbles in the stomach.

[0084] Experimental results: As shown in Table 7, it can be seen that the number of hiccups and the volume of air bubbles in the stomach of the mice in the model control group were significantly higher than those in the normal group (p < 0.01), indicating that the model was successfully established. Compared with the model control group, the number of hiccups in the groups of Prescription 1-1, Prescription 2-1, and Prescription 3-1 was significantly reduced (p < 0.01), while there was no significant difference in the Prescription 5-4 group; and the groups of Prescription 1-1, Prescription 2-1, and Prescription 3-1 had a significant effect on improving the volume of air bubbles in the stomach (p < 0.05).

[0085] Table 7 Results of animal pharmacodynamic experiments

[0086]

[0087]

[0088] Note: Compared with the normal group, && indicates p < 0.01; compared with the model control group, * indicates p < 0.05, ** indicates p < 0.01.

[0089] Test Example 4

[0090] The patients were respectively administered the simethicone oral preparation compositions prepared from Prescription 1-1 and Prescription 5-4 (calculated as simethicone: 8 mL / person) for gastroscopy examination. The results were respectively as Figure 1 - Figure 2 shown. It can be seen from the Figure 1 - Figure 2 examination results that the simethicone oral preparation compositions prepared from Prescription 1-1 ( Figure 1 ) and Prescription 5-4 ( Figure 2 ) could both play an antifoaming role during gastroscopy. However, when magnesium lauryl sulfate was used as the dispersant (i.e., Prescription 1-1), there were almost no air bubbles shown in the gastroscopy of the patients, making the test results clearer.

[0091] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the protection scope of the present invention. Any simple modification or equivalent replacement of the technical solution of the present invention by those of ordinary skill in the art shall not depart from the essence and scope of the technical solution of the present invention.

Claims

1. An oral preparation composition of simethicone, characterized in that, It comprises the following components: simethicone, magnesium lauryl sulfate, alkaline compound, starch, carboxymethyl cellulose, mannitol and water.

2. The simethicone oral preparation composition according to claim 1, characterized in that, The particle size of the magnesium lauryl sulfate is ≤30 μm.

3. The simethicone oral preparation composition according to claim 1, wherein The alkaline compound is sodium bicarbonate, sodium hydroxide or potassium hydroxide.

4. The simethicone oral preparation composition according to claim 1, wherein The simethicone oral preparation composition further comprises a flavoring agent.

5. The simethicone oral preparation composition according to claim 4, wherein The flavoring agent is selected from one or more of strawberry essence, orange essence and cherry essence.

6. The simethicone oral preparation composition according to claim 4 or 5, characterized in that, By mass, it comprises the following components: 6-12 parts of simethicone, 0.5-0.8 part of magnesium lauryl sulfate, 5-20 parts of alkaline compound, 25-35 parts of starch, 15-25 parts of carboxymethyl cellulose, 25-35 parts of mannitol, 0.2-0.5 part of flavoring agent and 80-120 parts of water.

7. The simethicone oral preparation composition according to claim 1, characterized in that, The type of the oral preparation is powder.

8. A method for preparing an oral preparation composition of simethicone as described in any one of claims 4-7, characterized in that, It comprises the following steps: (1) First, mix simethicone with part of the starch to obtain wet granule 1; mix the remaining starch, carboxymethyl cellulose with part of the water to obtain wet granule 2; then mix wet granule 1 and wet granule 2 evenly to obtain a mixture; (2) Dissolve the alkaline compound in the remaining water, prepare a solution and then add mannitol to obtain wet granule 3; (3) Mix the mixture, wet granule 3 and the flavoring agent, grind, and then add magnesium lauryl sulfate and mix evenly to obtain the product.

9. The preparation method according to claim 8, characterized in that, In step (3), after mixing, it is also necessary to pass through a 270-325 mesh sieve and dry. The grinding needs to reach a particle size of ≤30 μm, and after mixing evenly, it needs to pass through a 270-325 mesh sieve.

10. Use of a simethicone oral preparation composition as described in any one of claims 1-7 or a simethicone oral preparation composition prepared by the preparation method as described in any one of claims 8-9 in the preparation of an oral dispersant for treating gastric acid and abdominal flatulence or an antifoaming agent for gastrointestinal endoscopy examination.

Images