Aspirin sustained-release tablet and preparation method thereof

Abstract

The invention relates to an aspirin sustained-release tablet and a preparation method, belongs to the technical field of medicines, and adopts three dissolution modes for cooperative use to carry out gradient step-by-step controlled release. One group is composed of celery stem dry powder, xanthan gum and ethyl cellulose, and the acetylsalicylic acid with the mass percentage of 40%-50% is subjected to controlled release; the hydroxypropyl methylcellulose, the chitosan and the beta-cyclodextrin form a group and are used for simultaneously carrying out controlled release on 40-50% by mass of acetylsalicylic acid and the rest 50-60% by mass of acetylsalicylic acid; isomaltooligosacharide and resistant dextrin form a group, and the outermost layer of the group is coated with granules, so that the dissolution speed of all acetylsalicylic acid is delayed; in addition, the corn starch is added as a disintegrating component, and the proper addition of the corn starch can prevent the drug from being dissolved out too slowly, so that the drug dissolution amounts in the early and middle stages are ensured; all the components are matched for use, so that the stable controlled release speed of the medicine can be ensured, the problem that the dissolution speed is too high or too low in a certain time period is avoided, and the preparation is safer and more reliable.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and specifically relates to an aspirin sustained-release tablet and a preparation method thereof. Background Art

[0002] Aspirin, or acetylsalicylic acid, is a drug with a long history and is extremely important. Its discovery and application have had a profound impact on human health. As early as BC, people had discovered that willow bark had analgesic effects. Later, after continuous research and exploration, scientists extracted salicylic acid from willow bark. However, salicylic acid is highly irritating and has great side effects on the gastrointestinal tract. In order to solve this problem, scientists conducted a large number of experiments and improvements, and finally synthesized acetylsalicylic acid, which is aspirin.

[0003] Aspirin has multiple pharmacological effects. It has antipyretic, analgesic and anti-inflammatory effects, and can effectively relieve pain symptoms such as headache, toothache, joint pain, muscle pain, and fever. In addition, aspirin also has an antiplatelet aggregation effect, which can prevent and treat cardiovascular and cerebrovascular diseases.

[0004] With the continuous development of medical technology, the dosage form of aspirin is also constantly improving and innovating, including capsules, enteric-coated tablets, sustained-release tablets, etc. Capsules and enteric-coated tablets can prevent the drug from being destroyed by gastric acid in the stomach, thereby reducing irritation to the gastric mucosa. Sustained-release tablets control the dissolution rate of the drug, allowing the drug to dissolve slowly in the body, thereby prolonging the drug's duration of action. In addition, sustained-release tablets can also reduce the number of medications and improve patient compliance. At the same time, due to the slow dissolution rate of the drug, the blood drug concentration is more stable, which can reduce the side effects of the drug.

[0005] At present, the controlled release components of aspirin sustained-release tablets mainly include hydroxypropyl methylcellulose, ethyl cellulose, enteric coating materials (acrylic resin, etc.), and sustained-release coating materials (cellulose acetate, etc.). However, the controlled release of existing aspirin sustained-release tablets still has the problem of instability. Under different physiological conditions, such as different gastrointestinal pH values, digestive fluid secretion, gastrointestinal peristalsis speed, gastrointestinal food volume and other factors, the dissolution of the drug will fluctuate. In some cases, the drug dissolves too quickly and cannot continuously and stably exert a sustained-release effect. The blood drug concentration rises rapidly in a short period of time, increasing the risk of side effects; in other cases, the drug dissolves too slowly and cannot reach an effective therapeutic concentration in time, affecting the therapeutic effect. Therefore, it is necessary to develop a more stably dissolved aspirin sustained-release tablet to reduce interference from the gastrointestinal physiological environment and ensure dissolution progress and efficacy. Summary of the invention

[0006] The controlled release components of existing aspirin sustained-release tablets are easily affected by different physiological conditions, resulting in unstable controlled-release speed, increased risk of side effects when too fast, and weakened therapeutic effect when too slow. The present invention provides an aspirin sustained-release tablet and a preparation method, which adopts three dissolution methods for combined use to perform gradient controlled release. That is, celery stem powder, xanthan gum, and ethyl cellulose are a group to control the release of 40% to 50% of acetylsalicylic acid by mass; hydroxypropyl methylcellulose, chitosan, and β-cyclodextrin are a group to simultaneously control the release of 40% to 50% of acetylsalicylic acid and the remaining 50% to 60% of acetylsalicylic acid by mass; oligomaltolsaccharides and resistant dextrin are a group to wrap the granular material in the outermost layer to delay the dissolution rate of all acetylsalicylic acid; the combination of the components can ensure the stability of the controlled-release speed of the drug, and the problem of too fast or too slow dissolution speed in a certain period of time will not occur, which is safer and more reliable. The specific technical scheme is as follows:

[0007] A sustained-release aspirin tablet comprises the following raw materials in parts by weight: 30 to 50 parts of acetylsalicylic acid, 5 to 15 parts of celery stem powder, 0.01 to 0.03 parts of xanthan gum, 1 to 2.5 parts of ethyl cellulose, 1 to 3 parts of corn starch, 0.3 to 0.6 parts of hydroxypropyl methylcellulose, 0.1 to 0.5 parts of chitosan, 0.05 to 0.1 parts of beta-cyclodextrin, 0.3 to 0.5 parts of isomaltooligosaccharide and 0.5 to 1 parts of resistant dextrin.

[0008] In the above-mentioned sustained-release aspirin tablets, the median particle size of the celery stem dry powder is 20 μm to 50 μm.

[0009] The method for preparing the above-mentioned sustained-release aspirin tablets comprises the following steps:

[0010] S1: Prepare materials according to the mass fractions, dissolve xanthan gum in water to obtain glue solution A; take 40% to 50% of acetylsalicylic acid by mass, dissolve it in ethanol, then add celery stem powder, mix, and after evenly dispersing, add glue solution A and mix evenly, then evaporate to remove ethanol, to obtain extract B;

[0011] S2: Prepare materials according to mass fractions, dissolve ethyl cellulose in ethanol, and obtain mucus C;

[0012] S3: Mix the mucus C and the extract B evenly, evaporate and remove the ethanol and water, and obtain the inclusion compound D;

[0013] S4: preparing materials according to weight proportions, and dry-mixing the remaining 50% to 60% weight proportions of acetylsalicylic acid, corn starch, hydroxypropyl methylcellulose, chitosan and β-cyclodextrin to obtain a mixture E;

[0014] S5: mixing the inclusion compound D and the mixture E uniformly, and then adding water to wet-mix and granulate to obtain granular material F;

[0015] S6: Add isomaltooligosaccharide to the granular material F, mix evenly, then add resistant dextrin, mix evenly, and press into tablets to obtain aspirin sustained-release tablets.

[0016] In S1 of the above preparation method, the mass ratio of the components of the glue solution A is xanthan gum: water = 1: (100-120).

[0017] In S1 of the above preparation method, the amount of ethanol used is 10 to 15 times the mass of acetylsalicylic acid.

[0018] In S1 of the above preparation method, the evaporation temperature is 60° C. to 70° C., and the pressure is 0.06 MPa to 0.07 MPa.

[0019] In S2 of the above preparation method, the mass ratio of the components of the mucus C is ethanol:ethyl cellulose=100:(12-20).

[0020] In S3 of the above preparation method, the evaporation temperature is 75° C. to 80° C., and the pressure is 0.04 MPa to 0.06 MPa.

[0021] In S5 of the above preparation method, the amount of water added in the wet mixing granulation is 10% to 20% of the total mass of the inclusion compound D and the mixture E.

[0022] In S6 of the above preparation method, after tableting, sustained-release material coating is further performed.

[0023] Compared with the prior art, the aspirin sustained-release tablet and the preparation method of the present invention have the following beneficial effects:

[0024] 1. The present invention adopts three dissolution methods to carry out gradient controlled release. That is, celery stem powder, xanthan gum, and ethyl cellulose are a group to control the release of 40% to 50% of acetylsalicylic acid by mass; hydroxypropyl methylcellulose, chitosan, and β-cyclodextrin are a group to control the release of 40% to 50% of acetylsalicylic acid and the remaining 50% to 60% of acetylsalicylic acid by mass at the same time; oligomaltosaccharide and resistant dextrin are a group to wrap the granular material in the outermost layer to control the release of 40% to 50% of acetylsalicylic acid and the remaining 50% to 60% of acetylsalicylic acid by mass at the same time. Corn starch is used as a disintegrating component. The appropriate addition of corn starch can prevent the drug from dissolving too slowly and ensure the dissolution amount of the drug in the early and middle stages.

[0025] Second, xanthan gum is dissolved in water, acetylsalicylic acid is first thickened, and then celery stem powder is used for adsorption, so that acetylsalicylic acid can be well infiltrated into the internal pores of celery stem powder particles and adhered to the surface of celery stem powder particles to form a controlled release core, so that celery stem powder can play a controlled release role on acetylsalicylic acid. Then ethyl cellulose is used for wrapping to further play a sustained release role, so that 40% to 50% by mass of acetylsalicylic acid is slowly dissolved in the final stage.

[0026] 3. The remaining 50% to 60% by mass of acetylsalicylic acid is mixed with corn starch, hydroxypropyl methylcellulose, chitosan, and β-cyclodextrin, and then granulated with inclusion compound D. Hydroxypropyl methylcellulose, chitosan, and β-cyclodextrin can control the release of the remaining 50% to 60% by mass of acetylsalicylic acid, and can further assist in the controlled release of inclusion compound D, further delaying the dissolution of the drug in inclusion compound D, and forming a good progressive dissolution effect.

[0027] 4. Finally, granular material F is coated with isomaltooligosaccharide and resistant dextrin. On the one hand, it delays the dissolution of the drug. On the other hand, isomaltooligosaccharide and resistant dextrin, as prebiotics, can regulate the intestinal microbial environment, improve intestinal absorption capacity, promote drug absorption, and improve therapeutic efficacy. DETAILED DESCRIPTION

[0028] The present invention is further described below in conjunction with specific implementation cases, but the present invention is not limited to these embodiments.

[0029] Example 1

[0030] A sustained-release aspirin tablet comprises the following raw materials in parts by weight: 40 parts of acetylsalicylic acid, 10 parts of celery stem powder, 0.02 parts of xanthan gum, 1.2 parts of ethyl cellulose, 2 parts of corn starch, 0.5 parts of hydroxypropyl methylcellulose, 0.3 parts of chitosan, 0.08 parts of β-cyclodextrin, 0.4 parts of isomaltooligosaccharide, and 0.8 parts of resistant dextrin. The median particle size of the celery stem powder is 32.4 μm.

[0031] The method for preparing the above-mentioned sustained-release aspirin tablets comprises the following steps:

[0032] S1: Prepare materials according to mass fractions, dissolve xanthan gum in water, the mass ratio of xanthan gum: water = 1:110, and obtain glue solution A; take 45% of acetylsalicylic acid by mass, dissolve it in ethanol with the mass of 12 times of acetylsalicylic acid, then add celery stem powder, mix, disperse evenly, add glue solution A and mix evenly, then evaporate and remove ethanol at a temperature of 65°C and a pressure of 0.06MPa to obtain extract B;

[0033] S2: Prepare materials according to mass fractions, dissolve ethyl cellulose in ethanol, the mass ratio of ethanol:ethyl cellulose=100:16, and obtain mucus C;

[0034] S3: Mix the mucus C and the extract B evenly, and evaporate the ethanol and water at a temperature of 78°C and a pressure of 0.05MPa to obtain the inclusion compound D;

[0035] S4: preparing materials according to the mass proportions, and dry-mixing the remaining 55% of the mass proportions of acetylsalicylic acid, corn starch, hydroxypropyl methylcellulose, chitosan and β-cyclodextrin to obtain a mixture E;

[0036] S5: uniformly mixing the inclusion compound D and the mixture E, adding 15% of water of the total mass of the inclusion compound D and the mixture E, and wet-mixing and granulating to obtain granular material F;

[0037] S6: Add isomaltooligosaccharide to the granular material F, mix evenly, then add resistant dextrin, mix evenly, and press into tablets to obtain aspirin sustained-release tablets.

[0038] Example 2

[0039] A sustained-release aspirin tablet comprises the following raw materials in parts by weight: 30 parts of acetylsalicylic acid, 5 parts of celery stem powder, 0.01 parts of xanthan gum, 1 part of ethyl cellulose, 1 part of corn starch, 0.3 parts of hydroxypropyl methylcellulose, 0.1 parts of chitosan, 0.05 parts of β-cyclodextrin, 0.3 parts of isomaltooligosaccharide, and 0.5 parts of resistant dextrin. The median particle size of the celery stem powder is 20.0 μm.

[0040] The method for preparing the above-mentioned sustained-release aspirin tablets comprises the following steps:

[0041] S1: Prepare materials according to mass fractions, dissolve xanthan gum in water, the mass ratio is xanthan gum: water = 1:100, and obtain glue solution A; take 40% of acetylsalicylic acid by mass, dissolve it in ethanol with the mass of 10 times of acetylsalicylic acid, then add celery stem powder, mix, disperse evenly, add glue solution A and mix evenly, then evaporate and remove ethanol at a temperature of 60°C and a pressure of 0.06MPa to obtain extract B;

[0042] S2: Prepare materials according to mass fractions, dissolve ethyl cellulose in ethanol, the mass ratio of ethanol:ethyl cellulose=100:12, and obtain mucus C;

[0043] S3: Mix the mucus C and the extract B evenly, evaporate and remove ethanol and water at a temperature of 75°C and a pressure of 0.04 MPa to obtain inclusion compound D;

[0044] S4: preparing materials according to the mass proportions, and dry-mixing the remaining 60% of the mass proportions of acetylsalicylic acid, corn starch, hydroxypropyl methylcellulose, chitosan and β-cyclodextrin to obtain a mixture E;

[0045] S5: uniformly mixing the inclusion compound D and the mixture E, adding 10% of water of the total mass of the inclusion compound D and the mixture E, and wet mixing and granulating to obtain granular material F;

[0046] S6: Add isomaltooligosaccharide to the granular material F, mix evenly, then add resistant dextrin, mix evenly, and press into tablets to obtain aspirin sustained-release tablets.

[0047] Example 3

[0048] A sustained-release aspirin tablet comprises the following raw materials in parts by weight: 30 parts of acetylsalicylic acid, 15 parts of celery stem powder, 0.01 parts of xanthan gum, 2.5 parts of ethyl cellulose, 1 part of corn starch, 0.6 parts of hydroxypropyl methylcellulose, 0.1 parts of chitosan, 0.1 parts of β-cyclodextrin, 0.3 parts of isomaltooligosaccharide, and 1 part of resistant dextrin. The median particle size of the celery stem powder is 22.4 μm.

[0049] The method for preparing the above-mentioned sustained-release aspirin tablets comprises the following steps:

[0050] S1: Prepare materials according to mass fractions, dissolve xanthan gum in water, the mass ratio is xanthan gum: water = 1:100, and obtain glue solution A; take 50% of acetylsalicylic acid by mass, dissolve it in ethanol with the mass of 10 times of acetylsalicylic acid, then add celery stem powder, mix, disperse evenly, add glue solution A and mix evenly, then evaporate and remove ethanol at a temperature of 70°C and a pressure of 0.06MPa to obtain extract B;

[0051] S2: Prepare materials according to mass fractions, dissolve ethyl cellulose in ethanol, the mass ratio of ethanol:ethyl cellulose=100:20, and obtain mucus C;

[0052] S3: Mix the mucus C and the extract B evenly, and evaporate the ethanol and water at a temperature of 75°C and a pressure of 0.06MPa to obtain the inclusion compound D;

[0053] S4: preparing materials according to the weight proportions, and dry-mixing the remaining 50% weight proportions of acetylsalicylic acid, corn starch, hydroxypropyl methylcellulose, chitosan and β-cyclodextrin to obtain a mixture E;

[0054] S5: uniformly mixing the inclusion compound D and the mixture E, adding 14% of water of the total mass of the inclusion compound D and the mixture E, and wet mixing and granulating to obtain granular material F;

[0055] S6: Add isomaltooligosaccharide to the granular material F, mix evenly, then add resistant dextrin, mix evenly, and press into tablets to obtain aspirin sustained-release tablets.

[0056] Example 4

[0057] A sustained-release aspirin tablet comprises the following raw materials in parts by weight: 50 parts of acetylsalicylic acid, 5 parts of celery stem powder, 0.03 parts of xanthan gum, 1 part of ethyl cellulose, 3 parts of corn starch, 0.3 parts of hydroxypropyl methylcellulose, 0.5 parts of chitosan, 0.05 parts of β-cyclodextrin, 0.5 parts of isomaltooligosaccharide, and 0.5 parts of resistant dextrin. The median particle size of the celery stem powder is 45.3 μm.

[0058] The method for preparing the above-mentioned sustained-release aspirin tablets comprises the following steps:

[0059] S1: Prepare materials according to mass fractions, dissolve xanthan gum in water, the mass ratio of xanthan gum: water = 1:120, and obtain glue solution A; take 40% of acetylsalicylic acid by mass, dissolve it in ethanol with the mass of 15 times of acetylsalicylic acid, then add celery stem powder, mix, disperse evenly, add glue solution A and mix evenly, then evaporate and remove ethanol at a temperature of 60°C and a pressure of 0.07MPa to obtain extract B;

[0060] S2: Prepare materials according to mass fractions, dissolve ethyl cellulose in ethanol, the mass ratio of ethanol:ethyl cellulose=100:12, and obtain mucus C;

[0061] S3: Mix the mucus C and the extract B evenly, and evaporate the ethanol and water at a temperature of 80°C and a pressure of 0.04 MPa to obtain the inclusion compound D;

[0062] S4: preparing materials according to the mass proportions, and dry-mixing the remaining 60% of the mass proportions of acetylsalicylic acid, corn starch, hydroxypropyl methylcellulose, chitosan and β-cyclodextrin to obtain a mixture E;

[0063] S5: uniformly mixing the inclusion compound D and the mixture E, adding 16% of water of the total mass of the inclusion compound D and the mixture E, and wet mixing and granulating to obtain granular material F;

[0064] S6: Add isomaltooligosaccharide to the granular material F, mix evenly, then add resistant dextrin, mix evenly, and press into tablets to obtain aspirin sustained-release tablets.

[0065] Example 5

[0066] A sustained-release aspirin tablet comprises the following raw materials in parts by weight: 50 parts of acetylsalicylic acid, 15 parts of celery stem powder, 0.03 parts of xanthan gum, 2.5 parts of ethyl cellulose, 3 parts of corn starch, 0.6 parts of hydroxypropyl methylcellulose, 0.5 parts of chitosan, 0.1 parts of β-cyclodextrin, 0.5 parts of isomaltooligosaccharide, and 1 part of resistant dextrin. The median particle size of the celery stem powder is 29.6 μm.

[0067] The method for preparing the above-mentioned sustained-release aspirin tablets comprises the following steps:

[0068] S1: Prepare materials according to mass fractions, dissolve xanthan gum in water, the mass ratio of xanthan gum: water = 1:120, and obtain glue solution A; take 50% of acetylsalicylic acid by mass, dissolve it in ethanol with the mass of 15 times of acetylsalicylic acid, then add celery stem powder, mix, disperse evenly, add glue solution A and mix evenly, then evaporate and remove ethanol at a temperature of 70°C and a pressure of 0.07MPa to obtain extract B;

[0069] S2: Prepare materials according to mass fractions, dissolve ethyl cellulose in ethanol, the mass ratio of ethanol:ethyl cellulose=100:20, and obtain mucus C;

[0070] S3: Mix the mucus C and the extract B evenly, and evaporate the ethanol and water at a temperature of 80°C and a pressure of 0.06MPa to obtain the inclusion compound D;

[0071] S4: preparing materials according to the weight proportions, and dry-mixing the remaining 50% weight proportions of acetylsalicylic acid, corn starch, hydroxypropyl methylcellulose, chitosan and β-cyclodextrin to obtain a mixture E;

[0072] S5: uniformly mixing the inclusion compound D and the mixture E, adding 20% ​​water of the total mass of the inclusion compound D and the mixture E, and wet mixing and granulating to obtain granular material F;

[0073] S6: Add isomaltooligosaccharide to the granular material F, mix evenly, then add resistant dextrin, mix evenly, compress into tablets, and coat with sustained-release material to obtain sustained-release aspirin tablets.

[0074] Example 6

[0075] A sustained-release aspirin tablet comprises the following raw materials in parts by weight: 35 parts of acetylsalicylic acid, 8 parts of celery stem powder, 0.01 parts of xanthan gum, 1.5 parts of ethyl cellulose, 1.5 parts of corn starch, 0.6 parts of hydroxypropyl methylcellulose, 0.2 parts of chitosan, 0.06 parts of β-cyclodextrin, 0.3 parts of isomaltooligosaccharide, and 1 part of resistant dextrin. The median particle size of the celery stem powder is 50.0 μm.

[0076] The method for preparing the above-mentioned sustained-release aspirin tablets comprises the following steps:

[0077] S1: Prepare materials according to mass fractions, dissolve xanthan gum in water, the mass ratio is xanthan gum: water = 1:100, and obtain glue solution A; take 50% of acetylsalicylic acid by mass, dissolve it in ethanol with the mass of 15 times of acetylsalicylic acid, then add celery stem powder, mix, disperse evenly, add glue solution A and mix evenly, then evaporate and remove ethanol at a temperature of 70°C and a pressure of 0.06MPa to obtain extract B;

[0078] S2: Prepare materials according to mass fractions, dissolve ethyl cellulose in ethanol, the mass ratio of ethanol:ethyl cellulose=100:15, and obtain mucus C;

[0079] S3: Mix the mucus C and the extract B evenly, and evaporate the ethanol and water at a temperature of 80°C and a pressure of 0.04 MPa to obtain the inclusion compound D;

[0080] S4: preparing materials according to the weight proportions, and dry-mixing the remaining 50% weight proportions of acetylsalicylic acid, corn starch, hydroxypropyl methylcellulose, chitosan and β-cyclodextrin to obtain a mixture E;

[0081] S5: uniformly mixing the inclusion compound D and the mixture E, adding 15% of water of the total mass of the inclusion compound D and the mixture E, and wet-mixing and granulating to obtain granular material F;

[0082] S6: Add isomaltooligosaccharide to the granular material F, mix evenly, then add resistant dextrin, mix evenly, compress into tablets, and coat with sustained-release material to obtain sustained-release aspirin tablets.

[0083] Comparative Example 1

[0084] No celery stem powder is added to the raw materials, that is, no celery stem powder is added to S1; other parameters are the same as in Example 1.

[0085] Comparative Example 2

[0086] No xanthan gum is added to the raw materials, that is, S1 is omitted (glue A and extract B are not prepared), S2: prepare materials according to mass fractions, dissolve ethyl cellulose in ethanol, the mass ratio of ethanol: ethyl cellulose = 100: 16, and obtain mucus C; S3: mix mucus C and 45% by mass of acetylsalicylic acid evenly, evaporate and remove ethanol and water at a temperature of 78° C. and a pressure of 0.05 MPa to obtain inclusion compound D; other parameters are the same as in Example 1.

[0087] Comparative Example 3

[0088] No ethyl cellulose was added to the raw materials, that is, mucus C was not prepared in S2, inclusion compound D was not prepared in S3, and inclusion compound D in S5 was directly replaced by extract B; other parameters were the same as in Example 1.

[0089] Comparative Example 4

[0090] No isomaltooligosaccharide and no resistant dextrin are added to the raw materials, that is, no isomaltooligosaccharide and no resistant dextrin are added to S6, and the granular material F is directly tableted; other parameters are the same as those in Example 1.

[0091] Comparative Example 5

[0092] Acetylsalicylic acid, celery stem powder, xanthan gum, ethyl cellulose, corn starch, hydroxypropyl methylcellulose, chitosan, and β-cyclodextrin are directly mixed to obtain a mixture, and 15% of water of the total mass of the mixture is added to perform wet mixing and granulation to obtain granular material; oligomeric isomaltosaccharide is added to the granular material, mixed evenly, and then resistant dextrin is added, mixed evenly, and tableted to obtain aspirin sustained-release tablets. The mass fractions of the raw materials are the same as those in Example 1.

[0093] Comparative Example 6

[0094] Chitosan and β-cyclodextrin are not added to the raw materials, that is, chitosan and β-cyclodextrin are not added to S4; other parameters are the same as in Example 1.

[0095] The sustained-release properties of the aspirin sustained-release tablets prepared in the above-mentioned embodiments and comparative examples were tested.

[0096] 1. In vitro dissolution assay

[0097] The bare sample specifications of aspirin sustained-release tablets are: diameter 6.5 mm, thickness 3 mm, and weight 62 mg.

[0098] Take aspirin sustained-release tablets, refer to the dissolution determination method of the Chinese Pharmacopoeia, and use a dissolution tester for detection. Use a phosphate buffer with a pH value of 6.8 as the dissolution medium, stir at a speed of 100r / min, take the solution at 0.5h, 1h, 3h, 6h, and 8h, respectively, use a high-performance liquid chromatograph to detect the dissolution content of acetylsalicylic acid, and calculate the dissolution rate, dissolution rate = acetylsalicylic acid dissolution mass / acetylsalicylic acid mass in the tablet × 100%. Make 5 parallel samples for each, and the test results are shown in Table 1 below.

[0099] Table 1 In vitro dissolution test results (average value)

[0100]

[0101] As can be seen from the above results, the aspirin sustained-release tablets prepared by Examples 1 to 6 have a good and stable sustained-release effect, and the progress of sustained-release precipitation is stable, which can well balance the drug dissolution amount in each time period. As can be seen from the result of Comparative Example 1, after the celery stem powder participates in the preparation of the extract, it can play an obvious sustained-release effect on part of the acetylsalicylic acid and balance the dissolution rate of the acetylsalicylic acid. As can be seen from the results of Comparative Examples 3 and 4, xanthan gum and ethyl cellulose both have a controlled-release auxiliary effect on the celery stem powder, and not adding xanthan gum will affect the dissolution rate of the acetylsalicylic acid. As can be seen from the result of Comparative Example 4, adding oligomeric isomaltose and resistant dextrin in an appropriate amount can further improve the controlled-release effect and delay the early dissolution rate of the acetylsalicylic acid. As can be seen from the result of Comparative Example 5, simple mixing will affect the controlled-release level, and without the dissolution level, the dissolution of the acetylsalicylic acid will be irregular, too slow in the early stage, too fast in the later stage, and the absorption rate of the acetylsalicylic acid in different time periods will be affected. From the results of Comparative Example 6, it can be seen that chitosan and β-cyclodextrin help control the dissolution rate in the early stage of release, reduce the amount of drug dissolved in the early stage, and assist in balancing the overall dissolution process.

[0102] 2. In vivo drug metabolism assay

[0103] Aspirin sustained-release tablets were coated with conventional sustained-release materials and coated with a 120-micron-thick cellulose acetate material coating layer. Sample specifications: diameter 6.5 mm, thickness 3 mm, weight 66 mg.

[0104] A total of 72 subjects were selected and divided into 12 groups, with 6 people in each group. The age range of the 6 people was 2 people aged 16-20 years old (1 female and 1 male), 2 people aged 35-40 years old (1 female and 1 male), and 2 people aged 65-70 years old (1 female and 1 male).

[0105] Each group of subjects took one sustained-release aspirin tablet of each embodiment and each comparative example respectively; blood was collected at 0.5h, 1h, 2h, 4h, 6h, and 8h after taking the tablets, and the concentration of acetylsalicylic acid in the blood was determined by high performance liquid chromatography-tandem mass spectrometry. The test results are shown in Table 2 below.

[0106] Table 2 In vivo drug metabolism assay results (average value)

[0107]

[0108]

[0109] “ND” means below the minimum detection concentration; “ / ” means not detected.

[0110] As can be seen from the above results, the aspirin sustained-release tablets prepared by Examples 1 to 6 have a good and stable sustained-release effect, and the sustained-release precipitation progress is stable, which can well balance the drug dissolution amount and absorption amount in each time period. As can be seen from the result of Comparative Example 1, after the celery stem powder participates in the preparation of the extract, it can play an obvious sustained-release effect on part of the acetylsalicylic acid and balance the dissolution rate of the acetylsalicylic acid. As can be seen from the results of Comparative Examples 3 and 4, xanthan gum and ethyl cellulose both have a controlled-release auxiliary effect on the celery stem powder, and not adding xanthan gum will affect the dissolution rate of the acetylsalicylic acid. As can be seen from the result of Comparative Example 4, adding oligomeric isomaltose and resistant dextrin in an appropriate amount can further improve the controlled-release effect and delay the early dissolution rate of the acetylsalicylic acid. As can be seen from the result of Comparative Example 5, simple mixing will affect the controlled-release level, and without the dissolution level, the dissolution of the acetylsalicylic acid will be irregular, too slow in the early stage, too fast in the later stage, affecting the absorption rate of the acetylsalicylic acid in different time periods. From the results of Comparative Example 6, it can be seen that chitosan and β-cyclodextrin help control the dissolution rate in the early stage of release, reduce the amount of drug dissolved in the early stage, and assist in balancing the overall dissolution process.

Claims

1. An aspirin sustained-release tablet, characterized in that: The aspirin sustained-release tablets include the following raw materials in parts by weight: 30 to 50 parts of acetylsalicylic acid, 5 to 15 parts of celery stem powder, 0.01 to 0.03 parts of xanthan gum, 1 to 2.5 parts of ethyl cellulose, 1 to 3 parts of corn starch, 0.3 to 0.6 parts of hydroxypropyl methylcellulose, 0.1 to 0.5 parts of chitosan, 0.05 to 0.1 parts of β-cyclodextrin, 0.3 to 0.5 parts of isomaltooligosaccharide, and 0.5 to 1 parts of resistant dextrin.

2. The sustained-release aspirin tablet according to claim 1, characterized in that: The median particle size of the celery stem dry powder is 20 μm to 50 μm.

3. A method for preparing an aspirin sustained-release tablet according to claim 1 or 2, characterized in that: The preparation method comprises the following steps: S1: Prepare materials according to the mass fractions, dissolve xanthan gum in water to obtain glue solution A; take 40% to 50% of acetylsalicylic acid by mass, dissolve it in ethanol, then add celery stem powder, mix, and after evenly dispersing, add glue solution A and mix evenly, then evaporate to remove ethanol, to obtain extract B; S2: Prepare materials according to mass fractions, dissolve ethyl cellulose in ethanol, and obtain mucus C; S3: Mix the mucus C and the extract B evenly, evaporate and remove the ethanol and water, and obtain the inclusion compound D; S4: preparing materials according to weight proportions, and dry-mixing the remaining 50% to 60% weight proportions of acetylsalicylic acid, corn starch, hydroxypropyl methylcellulose, chitosan and β-cyclodextrin to obtain a mixture E; S5: mixing the inclusion compound D and the mixture E uniformly, and then adding water to wet-mix and granulate to obtain granular material F; S6: Add isomaltooligosaccharide to the granular material F, mix evenly, then add resistant dextrin, mix evenly, and press into tablets to obtain aspirin sustained-release tablets.

4. The method according to claim 3, characterized in that: In S1, the mass ratio of the components of the glue solution A is xanthan gum: water = 1: (100-120).

5. The manufacturing method according to claim 3, characterized in that: In S1, the amount of ethanol used is 10 to 15 times the mass of acetylsalicylic acid.

6. The method according to claim 3, characterized in that: In S1, the evaporation temperature is 60°C to 70°C, and the pressure is 0.06MPa to 0.07MPa.

7. The manufacturing method according to claim 3, characterized in that: In S2, the mass ratio of the components of the mucus C is ethanol:ethyl cellulose=100:(12-20).

8. The manufacturing method according to claim 3, characterized in that: In S3, the evaporation temperature is 75°C to 80°C, and the pressure is 0.04MPa to 0.06MPa.

9. The manufacturing method according to claim 3, characterized in that: In S5, the amount of water added in the wet mixing granulation is 10% to 20% of the total mass of the inclusion compound D and the mixture E.

10. The manufacturing method according to claim 3, characterized in that: In S6, after tableting, sustained-release material coating is further performed.

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