Sulphated aluminium tablet and its preparation method

Abstract

The application relates to the technical field of veterinary drugs, in particular to a sucralfate tablet and a preparation method thereof. The sucralfate tablet comprises the following components in parts by weight: sucralfate 30-60 parts, a filler 30-60 parts, dextrin 5-20 parts, microcrystalline cellulose 5-20 parts and a lubricant 0.1-0.5 parts, wherein the filler comprises more than 95% of corn starch and not less than 1.5% of an amino acid composition. According to the technical scheme, the amino acid composition is added into the filler in a proper amount, so that the sucralfate tablet can be uniformly dispersed in the stomach, the coverage of the stomach mucosa is improved, and the sucralfate tablet has better treatment and repair effects on gastric ulcers.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of veterinary medicine, in particular, relates to a sucralfate tablet and a preparation method thereof. BACKGROUND

[0002] Gastric ulcer is a common digestive system disease of pets such as domestic dogs and cats, and is a type of peptic ulcer. When the gastric mucosa is damaged, an ulcer is likely to occur at the site, i.e., a gastric ulcer is formed, which further affects the diet and health status of pets.

[0003] Sucralfate is a commonly used drug for treating gastric ulcer, which is an aluminum salt of sucrose acid ester containing 8 sulfate radicals. It is insoluble in water and most organic solvents, and only soluble in acid or alkali solution. Sucralfate can dissociate into sucrose sulfate complex ions in an acidic environment, and the complex ions polymerize into insoluble negatively charged colloids, which combine with the positively charged protein exudate on the ulcer surface to form a protective film covering the ulcer surface, promoting ulcer healing.

[0004] However, in the prior art, the sucralfate preparation, especially the sucralfate tablet, has the problem of uneven dispersion. When the gastric peristalsis of pets is fast, the treatment effect of the sucralfate preparation is poor.

[0005] Therefore, there is an urgent need in the art for a sucralfate tablet and a preparation method thereof, and thus the present application is proposed. SUMMARY

[0006] The present application aims to provide a sucralfate tablet and a preparation method thereof to solve at least one technical problem in the background art.

[0007] Specifically, the first aspect of the present application provides a sucralfate tablet, which comprises the following components in parts by weight:

[0008] 30-60 parts of sucralfate,

[0009] 30-60 parts of a filler,

[0010] 5-20 parts of dextrin,

[0011] 5-20 parts of microcrystalline cellulose,

[0012] 0.1-0.5 parts of a lubricant,

[0013] wherein the filler comprises more than 95% of corn starch and not less than 1.5% of an amino acid composition.

[0014] By adding an appropriate amount of amino acid composition to the filler, the sucralfate tablet can be more uniformly dispersed in the stomach after entering the stomach, thereby improving its coverage of the gastric mucosa and further playing a better role in treating and repairing gastric ulcers.

[0015] Preferably, the sucralfate tablet comprises, by weight parts, the following components:

[0016] Sucralfate 45-55 parts,

[0017] Filling agent 45-55 parts,

[0018] Dextrin 8-15 parts,

[0019] Microcrystalline cellulose 8-12 parts,

[0020] Lubricant 0.15-0.25 parts.

[0021] More preferably, the sucralfate tablet comprises, by weight parts, the following components:

[0022] Sucralfate 50 parts,

[0023] Filling agent 50 parts,

[0024] Dextrin 10 parts,

[0025] Microcrystalline cellulose 9.8 parts,

[0026] Lubricant 0.2 parts.

[0027] Preferably, the amino acid composition is histidine and cystine in a weight ratio of 1:1-1:0.5.

[0028] Preferably, the lubricant is one or a combination of several of talc, micronized silica gel, and magnesium stearate.

[0029] More preferably, the lubricant is magnesium stearate.

[0030] Preferably, the sucralfate tablet further comprises 1-3 parts of component A, which comprises 30% by weight of polyethylene glycol 4000 and 70% by weight of sucrose.

[0031] By adding component A to the sucralfate tablet, the product's residence time in the stomach can be effectively increased, and the product's therapeutic effect on gastric ulcers can be enhanced.

[0032] In a second aspect, the present application provides a preparation method of the sucralfate tablet according to the first aspect of the present application, comprising the steps of:

[0033] Preparation of starch paste: an appropriate amount of corn starch is weighed and added to purified water in an amount of 5-15 times the weight of the starch, heated to 90-120℃, and stirred while adding to prepare a starch paste. After cooling, the amino acid composition is added and stirred until uniform, and then set aside;

[0034] Granulation, take the right amount of dextrin, sucralfate, microcrystalline cellulose in turn into the high-speed wet granulator, add starch paste; turn on the high-speed wet granulator, 3000-5000 rpm / min, granulation 5-10 minutes;

[0035] Drying, the intermediate product obtained in the previous step is sucked into the fluidized bed dryer, dried at a temperature of 60-90℃ for 30-90 minutes, then taken out to obtain sucralfate granules.

[0036] The above technical scheme can make the obtained sucralfate tablets have better stability and improve the effective period of the product.

[0037] Preferably, the preparation method of the sucralfate tablets further comprises the step of:

[0038] Granulation, add sucralfate granules into the lifting granulator and sieve with a 20-mesh sieve for granulation, and then reserve.

[0039] Tabletting, suck the sucralfate granules into the mixer and add lubricant, turn on the mixer, mix for 20-50 minutes, and then take the qualified sucralfate granules for tabletting.

[0040] Preferably, in the step of preparing starch paste, the weight of the purified water is 9 times that of the starch.

[0041] Preferably, in the step of preparing starch paste, when the temperature cools down to not higher than 100℃, the amino acid composition is added and stirred until the starch paste cools down to room temperature.

[0042] Preferably, the sucralfate granules obtained in the drying step have a water content of not higher than 8%.

[0043] In summary, the present application has the following beneficial effects:

[0044] 1. The sucralfate tablets provided by the present application can realize more uniform dispersion in the stomach by adding an appropriate amount of amino acid composition to the filler, thereby improving the coverage of the stomach mucosa and further playing a better therapeutic and repair role on gastric ulcers.

[0045] 2. The sucralfate tablets provided by the present application can effectively improve the residence time of the product in the stomach by adding component A containing polyethylene glycol 4000 and sucrose to the sucralfate tablets, thereby enhancing the therapeutic effect of the product on gastric ulcers.

[0046] 3. The preparation method of the sucralfate tablets provided by the present application can make the obtained sucralfate tablets have better stability and improve the effective period of the product. DETAILED DESCRIPTION

[0047] The exemplary embodiments will be described in detail herein with reference to the attached drawings. The following description is made with reference to the accompanying drawings in which like reference numerals represent like elements or similar elements, unless otherwise indicated. The following exemplary embodiments described herein represent only some embodiments consistent with the present application. Conversely, the exemplary embodiments are only examples of apparatuses and methods consistent with some aspects of the present application as detailed in the appended claims.

[0048] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising," when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0049] The present application will be described in detail herein with reference to the following examples.

[0050] The prior art sucralfate preparation, especially sucralfate tablets, has uneven dispersion. When the pet's gastric peristalsis is fast, the sucralfate preparation can not achieve good therapeutic effect. In view of this, the present application provides a sucralfate tablet that can solve one of the above technical problems. The sucralfate tablet comprises, by weight: 30-60 parts of sucralfate, 30-60 parts of filler, 5-20 parts of dextrin, 5-20 parts of microcrystalline cellulose, and 0.1-0.5 parts of lubricant. The filler comprises more than 95% of corn starch and not less than 1.5% of amino acid composition. By adding an appropriate amount of amino acid composition to the filler, the sucralfate tablet can be more uniformly dispersed in the stomach, improving its coverage of the gastric mucosa, and thus playing a better role in treating and repairing gastric ulcers.

[0051] In order to better understand the above technical solution, the above technical solution will be described in detail in combination with specific embodiments. It should be noted that the components not specifically emphasized in the present application can be purchased on the market.

[0052] Experimental Example 1 Uniform Distribution

[0053] The applicant found in the research that the existing sucralfate tablets are not uniformly dispersed when dissolved in the stomach, resulting in low bioavailability.

[0054] Based on this, the applicant simulated the gastric environment in this experimental example to conduct a sucralfate tablet dispersion experiment.

[0055] Take 20 cm x 20 cm x 20 cm experimental vessel, add hydrochloric acid with pH = 1, and stir at 10 r / min, add 5 pieces of 0.5 g sucralfate tablets, weigh the weight of the tablet core after 10 min.

[0056] Formula 1

[0057] The components are weighed as follows:

[0058] Sucralfate 50 parts,

[0059] Corn starch 50 parts,

[0060] Dextrin 10 parts,

[0061] Microcrystalline cellulose 10 parts,

[0062] Magnesium stearate 0.2 parts,

[0063] The above components are prepared into tablets as follows:

[0064] Prepare starch slurry, weigh corn starch and add 10 times its weight of purified water, heat to 100℃, stir while adding to prepare starch slurry, ready for use;

[0065] Granulation, weigh dextrin, sucralfate, and microcrystalline cellulose in turn into a high-speed wet granulator, add starch slurry; turn on the high-speed wet granulator at 4000 rpm, granulate for 8 minutes;

[0066] Drying, the intermediate product obtained in the previous step is sucked into a fluidized bed dryer, and after drying at a temperature of 80℃ for 60 minutes, it is taken out to obtain sucralfate granules;

[0067] Granulation, tabletting to obtain finished product.

[0068] Formula 2

[0069] The components are weighed as follows:

[0070] Sucralfate 50 parts,

[0071] Filler 50 parts,

[0072] Dextrin 10 parts,

[0073] Microcrystalline cellulose 10 parts,

[0074] Magnesium stearate 0.2 parts,

[0075] Among them, the filler includes 95% corn starch and 5% histidine.

[0076] The above components are prepared into tablets as follows:

[0077] Preparation of starch slurry, corn starch is weighed and added into 10 times of purified water by weight, heated to 100℃, stirred while adding to prepare starch slurry, cooled and then added with histidine, stirred uniformly and reserved;

[0078] Granulation, dextrin, sucralfate and microcrystalline cellulose are weighed and sequentially sucked into a high-speed wet granulator, and the starch slurry is added; the high-speed wet granulator is started, at 4000 rpm, and granulation is performed for 8 minutes;

[0079] Drying, the intermediate product obtained in the previous step is sucked into a fluidized bed dryer, dried at a temperature of 80℃ for 60 minutes, and then taken out to obtain sucralfate granules;

[0080] Granulation and tabletting to obtain finished products.

[0081] Formula 3

[0082] Each component is weighed as follows:

[0083] Sucralfate 50 parts,

[0084] Filling agent 50 parts,

[0085] Dextrin 10 parts,

[0086] Microcrystalline cellulose 10 parts,

[0087] Magnesium stearate 0.2 parts,

[0088] Among them, the filling agent includes 95% corn starch and 5% cystine.

[0089] The above components are prepared into tablets as follows:

[0090] Preparation of starch slurry, corn starch is weighed and added into 10 times of purified water by weight, heated to 100℃, stirred while adding to prepare starch slurry, cooled and then added with cystine, stirred uniformly and reserved;

[0091] Granulation, dextrin, sucralfate and microcrystalline cellulose are weighed and sequentially sucked into a high-speed wet granulator, and the starch slurry is added; the high-speed wet granulator is started, at 4000 rpm, and granulation is performed for 8 minutes;

[0092] Drying, the intermediate product obtained in the previous step is sucked into a fluidized bed dryer, dried at a temperature of 80℃ for 60 minutes, and then taken out to obtain sucralfate granules;

[0093] Granulation and tabletting to obtain finished products.

[0094] Formula 4

[0095] Each component is weighed as follows:

[0096] Sucralfate 50 parts,

[0097] filler 50 parts,

[0098] dextrin 10 parts,

[0099] microcrystalline cellulose 10 parts,

[0100] magnesium stearate 0.2 parts,

[0101] The filler includes 95% corn starch and 5% amino acid composition. The amino acid composition is composed of histidine and cystine in a weight ratio of 1:1.

[0102] The above components are prepared into tablets by the following steps:

[0103] A starch slurry is prepared. Corn starch is weighed and added to 10 times its weight of purified water. The mixture is heated to 100°C while stirring to prepare the starch slurry. After cooling, the amino acid composition is added and stirred uniformly for standby use;

[0104] Granulation: dextrin, sucralfate, and microcrystalline cellulose are weighed and sequentially sucked into a high-speed wet granulator. The starch slurry is added. The high-speed wet granulator is turned on at 4000 rpm for 8 minutes.

[0105] Drying: the intermediate product obtained in the previous step is sucked into a fluidized bed dryer. The temperature is controlled at 80°C for drying for 60 minutes. Then, the sucralfate granules are obtained.

[0106] Granulation and tabletting to obtain the finished product.

[0107] Formula 5

[0108] Each component is weighed as follows:

[0109] sucralfate 50 parts,

[0110] filler 50 parts,

[0111] dextrin 10 parts,

[0112] microcrystalline cellulose 10 parts,

[0113] magnesium stearate 0.2 parts,

[0114] The filler includes 95% corn starch and 5% amino acid composition. The amino acid composition is composed of histidine and cystine in a weight ratio of 1:1.

[0115] The above components are prepared into tablets by the following steps:

[0116] A starch slurry is prepared. Corn starch is weighed and added to 10 times its weight of purified water. The mixture is heated to 100°C while stirring to prepare the starch slurry. After cooling, the amino acid composition is added and stirred uniformly for standby use;

[0117] Granulation, take dextrin, sucralfate, microcrystalline cellulose in turn into the high-speed wet granulator, add starch paste; turn on the high-speed wet granulator, 4000 rpm / min, granulate for 8 minutes;

[0118] Drying, the intermediate product obtained in the previous step is sucked into the fluidized bed dryer, and the temperature is controlled at 80°C for drying for 60 minutes, and then taken out to obtain sucralfate granules;

[0119] Granulation, tabletting to obtain finished products.

[0120] Among them, the components selected in formula 1-5 are all from the same batch. The sucralfate tablets prepared according to the above formula 1-5 are detected for the weight of the tablet core according to the method in this experimental example.

[0121] Table 1 tablet core weight after dissolution of formula 1-5

[0122] Group Tablet Core Weight (mg) Formulation 1 192 Formulation 2 166 Formulation 3 204 Formulation 4 133 Formulation 5 180

[0123] According to the results in Table 1, compared with the initial mass of the tablet 500mg, the mass of the tablet core of formula 1-formula 5 is significantly reduced after the experiment. The reduction of the mass of the tablet core indicates that the tablet has faster dispersion capacity in this environment, which is more conducive to exerting the pharmaceutical effect of protecting the gastric mucosa.

[0124] But among them, the tablet core mass of formula 4 is the lowest. This indicates that:

[0125] (1) The selection of the filler component in the sucralfate tablet provided by the present application is relatively important. When the filler is composed of corn starch and amino acid composition, the tablet has better dispersion performance;

[0126] (2) If formula 5 is used, corn starch is replaced by potato starch, and the technical effect is significantly reduced;

[0127] (3) If formula 2 and formula 3 are used, the filler is prepared from corn starch and histidine and cystine respectively, and the technical effect of formula 4 cannot be obtained.

[0128] Therefore, this experiment shows that in the present application, the filler component is composed of specific corn starch, histidine and cystine components, which can achieve better technical effect of tablet dispersion.

[0129] Experimental example 2 discharge rate

[0130] The applicant found in the research that the existing sucralfate tablets have a shorter residence time in the stomach, resulting in lower bioavailability.

[0131] Based on this, the applicant simulates the gastric environment in this experimental example to conduct a sucralfate tablet residence experiment.

[0132] Take the stomach of the gastric ulcer model rats, isolate the gastric mucosa, dissolve the sucralfate tablets in hydrochloric acid with pH = 1, evenly smear on the surface of the gastric mucosa, place in the constant temperature and humidity box with environmental temperature 37±2℃, relative humidity 90±2%, take out after 20min, measure the in vitro bioadhesion force with pressure 200g and compression time 15min.

[0133] Formula 6

[0134] The components are weighed as follows:

[0135] Sucralfate 50 parts,

[0136] Filling agent 50 parts,

[0137] Dextrin 10 parts,

[0138] Microcrystalline cellulose 10 parts,

[0139] Magnesium stearate 0.2 parts,

[0140] Component A 2 parts,

[0141] Among them, the filling agent includes 95% corn starch and 5% amino acid composition. The amino acid composition is composed of histidine and cystine in a weight ratio of 1:1;

[0142] Component A is polyethylene glycol 4000.

[0143] The above components are prepared into tablets according to the following steps:

[0144] Prepare starch slurry, weigh corn starch and add 10 times its weight of purified water, heat to 100℃, stir while adding to prepare starch slurry, after cooling, add amino acid composition, stir uniformly and reserve;

[0145] Granulation, weigh dextrin, sucralfate, microcrystalline cellulose and component A in turn into a high-speed wet granulator, add starch slurry; start the high-speed wet granulator at 4000rpm / min, granulate for 8 minutes;

[0146] Drying, the intermediate product obtained in the previous step is sucked into a fluidized bed dryer, dried at a temperature of 80℃ for 60 minutes, then taken out to obtain sucralfate granules;

[0147] Granulation and tabletting to obtain finished products.

[0148] Formula 7

[0149] The components are weighed as follows:

[0150] Sucralfate 50 parts,

[0151] Filling agent 50 parts,

[0152] Dextrin 10 parts,

[0153] Microcrystalline cellulose 10 parts,

[0154] Magnesium stearate 0.2 parts,

[0155] Component A 2 parts,

[0156] The filler includes 95% corn starch and 5% amino acid composition. The amino acid composition is composed of histidine and cystine in a weight ratio of 1:1.

[0157] Component A is sucrose.

[0158] The above components are prepared into tablets according to the following steps:

[0159] A starch slurry is prepared. Corn starch is weighed and added to 10 times its weight of purified water. The mixture is heated to 100°C while stirring to prepare the starch slurry. After cooling, the amino acid composition is added and stirred uniformly for standby use.

[0160] Granulation. Dextrin, sucralfate, microcrystalline cellulose, and component A are weighed and sequentially sucked into a high-speed wet granulator. The starch slurry is added. The high-speed wet granulator is turned on at 4000 rpm for 8 minutes.

[0161] Drying. The intermediate product obtained in the previous step is sucked into a fluidized bed dryer. The temperature is controlled at 80°C for drying for 60 minutes. Then, the sucralfate granules are obtained.

[0162] The granules are made and tablets are pressed to obtain the finished product.

[0163] Formula 8

[0164] Each component is weighed according to the following weight parts:

[0165] Sucralfate 50 parts,

[0166] Filler 50 parts,

[0167] Dextrin 10 parts,

[0168] Microcrystalline cellulose 10 parts,

[0169] Magnesium stearate 0.2 parts,

[0170] Component A 2 parts,

[0171] The filler includes 95% corn starch and 5% amino acid composition. The amino acid composition is composed of histidine and cystine in a weight ratio of 1:1.

[0172] Component A is composed of 70% by weight of polyethylene glycol 4000 and 30% by weight of sucrose.

[0173] The above components are prepared into tablets by the following steps:

[0174] A starch slurry is prepared by adding corn starch into purified water with 10 times the weight of the corn starch, heated to 100°C, and stirred while adding to form the starch slurry. After cooling, the amino acid composition is added, and stirred until uniform, and then set aside;

[0175] Granulation: The dextrin, sucralfate, microcrystalline cellulose, and component A are sequentially sucked into a high-speed wet granulator, and the starch slurry is added. The high-speed wet granulator is turned on, and the granulation is performed at 4000 rpm for 8 minutes.

[0176] Drying: The intermediate product obtained in the previous step is sucked into a fluidized bed dryer, and dried at a temperature of 80°C for 60 minutes. The sucralfate granules are obtained after being removed from the dryer.

[0177] The granules are filled and compressed into tablets to obtain the finished product.

[0178] Formulation 9

[0179] The components are weighed as follows:

[0180] Sucralfate 50 parts,

[0181] Filling agent 50 parts,

[0182] Dextrin 10 parts,

[0183] Microcrystalline cellulose 10 parts,

[0184] Magnesium stearate 0.2 parts,

[0185] Component A 2 parts,

[0186] The filling agent includes 95% corn starch and 5% amino acid composition. The amino acid composition is composed of histidine and cystine in a weight ratio of 1:1.

[0187] Component A is composed of 30% by weight of polyethylene glycol 4000 and 70% by weight of sucrose.

[0188] The above components are prepared into tablets by the following steps:

[0189] A starch slurry is prepared by adding corn starch into purified water with 10 times the weight of the corn starch, heated to 100°C, and stirred while adding to form the starch slurry. After cooling, the amino acid composition is added, and stirred until uniform, and then set aside;

[0190] Granulation: The dextrin, sucralfate, microcrystalline cellulose, and component A are sequentially sucked into a high-speed wet granulator, and the starch slurry is added. The high-speed wet granulator is turned on, and the granulation is performed at 4000 rpm for 8 minutes.

[0191] Drying, the intermediate product obtained in the previous step is sucked into a fluidized bed dryer, and after drying for 60 minutes at a temperature of 80°C, the product is taken out to obtain sucralfate granules;

[0192] Granulation and tabletting to obtain the finished product.

[0193] Formulation 10

[0194] The components are weighed as follows:

[0195] Sucralfate 50 parts,

[0196] Filling agent 50 parts,

[0197] Dextrin 10 parts,

[0198] Microcrystalline cellulose 10 parts,

[0199] Magnesium stearate 0.2 parts,

[0200] Component A 2 parts,

[0201] Among them, the filling agent includes 95% corn starch and 5% amino acid composition. Among them, the amino acid composition is composed of histidine and cystine in a weight ratio of 1:1;

[0202] Component A is composed of 30% by weight of polyethylene glycol 4000 and 70% by weight of maltose.

[0203] The above components are prepared into tablets as follows:

[0204] Prepare starch slurry, weigh corn starch and add 10 times its weight of purified water, heat to 100°C, stir while adding to prepare starch slurry, and after cooling, add amino acid composition, stir until uniform, and reserve;

[0205] Granulation, weigh dextrin, sucralfate, microcrystalline cellulose, and component A in turn into a high-speed wet granulator, and add the starch slurry; start the high-speed wet granulator at 4000 rpm, and granulate for 8 minutes;

[0206] Drying, the intermediate product obtained in the previous step is sucked into a fluidized bed dryer, and after drying for 60 minutes at a temperature of 80°C, the product is taken out to obtain sucralfate granules;

[0207] Granulation and tabletting to obtain the finished product.

[0208] Among them, the components selected in Formulations 6-10 are all from the same batch. The sucralfate tablets prepared according to Formulations 6-10 above are detected for in vitro bioadhesion according to the method in this experimental example.

[0209] Table 2 In vitro bioadhesion of Formulations 6-10

[0210]

[0211]

[0212] According to the results of Table 2, compared with other formulations, the adhesion of formulation 9 is the highest in the experiment. The higher the adhesion index of the tablet, the stronger the ability of the tablet to adhere to the gastric mucosa after the tablet is dispersed in the stomach, the longer the tablet stays in the stomach, and the more beneficial it is to exert the efficacy of the product in protecting the gastric mucosa.

[0213] Among them, the adhesion of formulation 9 is the highest, which shows that:

[0214] (1) In the components of the sucralfate tablet provided in the present application, the selection of the components of component A is important. When the filler is composed of 30% by weight of polyethylene glycol 4000 and 70% by weight of sucrose, the tablet has stronger adhesion to the gastric mucosa;

[0215] (2) As in formulations 6 and 7, when component A is composed of only polyethylene glycol 4000 or sucrose, respectively, the technical effect of formulation 9 cannot be achieved;

[0216] (3) As in formulation 8, when the component ratio of polyethylene glycol 4000 and sucrose is significantly changed, the technical effect is significantly reduced;

[0217] (4) As in formulation 10, when the sucrose in component A is replaced by maltose, which is also a disaccharide, the technical effect is significantly reduced;

[0218] Therefore, the experiment shows that in the present application, when component A is composed of polyethylene glycol 4000 and sucrose in a specific ratio, the adhesion of the tablet to the gastric mucosa can be significantly improved.

[0219] Example 1

[0220] The components are weighed as follows:

[0221] Sucralfate 30 parts, filler 30 parts, dextrin 5 parts, microcrystalline cellulose 5 parts, and magnesium stearate 0.1 part, wherein the filler includes 98.5% corn starch and 1.5% amino acid composition. The amino acid composition is composed of histidine and cystine in a weight ratio of 1:1.

[0222] The above components are prepared into tablets according to the following steps:

[0223] Prepare starch slurry, weigh corn starch and add 5 times its weight of purified water, heat to 90°C, stir while adding, and add amino acid composition and stir until the starch slurry cools to room temperature;

[0224] Granulation, take dextrin, sucralfate, microcrystalline cellulose in turn into high-speed wet granulator, add starch paste; open high-speed wet granulator, 3000 rpm / min, granulation 5 minutes;

[0225] Drying, the intermediate product obtained in the previous step is sucked into the fluidized bed dryer, and the temperature is controlled at 60°C for drying for 30 minutes, and then taken out to obtain sucralfate granules, wherein the water content of the sucralfate granules is not higher than 8%;

[0226] Granulation, the sucralfate granules are added into the lifting granulator for granulation with a 20-mesh sieve, and the granulation is ready for use.

[0227] Tablet preparation, the sucralfate granules are sucked into a mixer and lubricant is added, the mixer is opened, and mixing is performed for 20 minutes, and the qualified sucralfate granules are pressed into tablets.

[0228] Example 2

[0229] The components are weighed as follows:

[0230] Sucralfate 50 parts, filler 50 parts, dextrin 10 parts, microcrystalline cellulose 9.8 parts, and magnesium stearate 0.2 parts, wherein the filler comprises 97% corn starch and 3% amino acid composition. The amino acid composition is composed of histidine and cystine in a weight ratio of 1:0.75.

[0231] The above components are prepared into tablets by the following steps:

[0232] Preparation of starch paste, corn starch is weighed and added into purified water with a weight of 9 times that of the corn starch, heated to 100°C, and stirred while adding to prepare the starch paste, and the amino acid composition is added and stirred until the starch paste is cooled to room temperature;

[0233] Granulation, take dextrin, sucralfate, microcrystalline cellulose in turn into high-speed wet granulator, add starch paste; open high-speed wet granulator, 4000 rpm / min, granulation 8 minutes;

[0234] Drying, the intermediate product obtained in the previous step is sucked into the fluidized bed dryer, and the temperature is controlled at 80°C for drying for 60 minutes, and then taken out to obtain sucralfate granules, wherein the water content of the sucralfate granules is not higher than 8%;

[0235] Granulation, the sucralfate granules are added into the lifting granulator for granulation with a 20-mesh sieve, and the granulation is ready for use.

[0236] Tablet preparation, the sucralfate granules are sucked into a mixer and lubricant is added, the mixer is opened, and mixing is performed for 30 minutes, and the qualified sucralfate granules are pressed into tablets.

[0237] Example 3

[0238] The components are weighed as follows:

[0239] Sulfolactose 60 parts, filler 60 parts, dextrin 20 parts, microcrystalline cellulose 20 parts, magnesium stearate 0.5 parts, wherein the filler includes 95% corn starch and 5% amino acid composition. The amino acid composition is composed of histidine and cystine in a weight ratio of 1:0.5.

[0240] The above components are prepared into tablets by the following steps:

[0241] Prepare a starch slurry, weigh the corn starch and add it to 15 times its weight of purified water, heat to 120°C, and stir while adding to prepare the starch slurry. When the temperature cools to 100°C, add the amino acid composition and stir until the starch slurry cools to room temperature.

[0242] Granulation: Weigh the dextrin, sulfolactose, and microcrystalline cellulose and sequentially suck them into a high-speed wet granulator. Add the starch slurry. Turn on the high-speed wet granulator at 5000 rpm and granulate for 10 minutes.

[0243] Drying: Suck the intermediate product obtained in the previous step into a fluidized bed dryer. Control the temperature at 90°C and dry for 90 minutes. Then take out the sulfolactose granules. The water content of the sulfolactose granules is not higher than 8%.

[0244] Granulation: Add the sulfolactose granules to a lifting granulator and use a 20-mesh sieve for granulation. The granulation is ready for use.

[0245] Tablet preparation: Suck the sulfolactose granules into a mixer and add a lubricant. Turn on the mixer and mix for 50 minutes. Take the qualified sulfolactose granules and press them into tablets.

[0246] Example 4

[0247] The technical solution of Example 4 is similar to that of Example 2, except that the sulfolactose tablet components include:

[0248] Sulfolactose 45 parts, filler 45 parts, dextrin 8 parts, microcrystalline cellulose 8 parts, lubricant 0.15 parts.

[0249] Example 5

[0250] The technical solution of Example 5 is similar to that of Example 2, except that the sulfolactose tablet components include:

[0251] Sulfolactose 55 parts, filler 55 parts, dextrin 15 parts, microcrystalline cellulose 12 parts, lubricant 0.25 parts.

[0252] Example 6

[0253] Weigh each component by the following weight parts:

[0254] Sucralfate 30 parts, filler 30 parts, dextrin 5 parts, microcrystalline cellulose 5 parts, magnesium stearate 0.1 part, component A

[0255] 1 part. Among them, the filler includes 98.5% of corn starch, and 1.5% of amino acid composition. Among them, the amino acid composition is composed of histidine and cystine with a weight ratio of 1:1. Among them, the component A includes 30% by weight of polyethylene glycol 4000, and 70% by weight of sucrose.

[0256] The above components are prepared into tablets according to the following steps:

[0257] Prepare starch slurry, take corn starch and add 5 times its weight of purified water, heat to 90℃, stir while adding to prepare starch slurry, add amino acid composition and stir until the starch slurry cools to room temperature;

[0258] Granulation, take dextrin, sucralfate, microcrystalline cellulose, and component A in turn into a high-speed wet granulator, add starch slurry; start the high-speed wet granulator at 3000 rpm, granulate for 5 minutes;

[0259] Drying, the intermediate product obtained in the previous step is sucked into a fluidized bed dryer, and the temperature is controlled at 60℃ for drying for 30 minutes, then taken out to obtain sucralfate granules, the water content of the sucralfate granules is not higher than 8%;

[0260] Granulation, add sucralfate granules to a lifting granulator and sieve with a 20-mesh sieve for granulation, and then reserve.

[0261] Tablet preparation, suck the sucralfate granules into a mixer and add a lubricant, start the mixer and mix for 20 minutes, and then take the qualified sucralfate granules for tabletting.

[0262] Example 7

[0263] Take each component according to the following weight parts:

[0264] Sucralfate 50 parts, filler 50 parts, dextrin 10 parts, microcrystalline cellulose 9.8 parts, magnesium stearate 0.2 parts, component A 2 parts. Among them, the filler includes 97% of corn starch, and 3% of amino acid composition. Among them, the amino acid composition is composed of histidine and cystine with a weight ratio of 1:0.75. Among them, the component A includes 30% by weight of polyethylene glycol 4000, and 70% by weight of sucrose.

[0265] The above components are prepared into tablets according to the following steps:

[0266] Prepare starch slurry, take corn starch and add 9 times its weight of purified water, heat to 100℃, stir while adding to prepare starch slurry, add amino acid composition and stir until the starch slurry cools to room temperature;

[0267] Granulation, take dextrin, sucralfate, microcrystalline cellulose, component A in turn into the high-speed wet granulator, add starch paste; turn on the high-speed wet granulator, 4000 rpm / min, granulation for 8 minutes;

[0268] Drying, take the intermediate product obtained in the previous step into the fluidized bed dryer, control the temperature at 80℃, dry for 60 minutes, then take out, obtain sucralfate granules, the water content of the sucralfate granules is not higher than 8%;

[0269] Granulation, add sucralfate granules into the lifting granulator and sieve with 20 meshes for granulation, and then reserve for use.

[0270] Tablet preparation, take sucralfate granules into the mixer and add lubricant, turn on the mixer, mix for 30 minutes, and then take the qualified sucralfate granules for tabletting.

[0271] Example 8

[0272] Take each component by weight as follows:

[0273] Sucralfate 60 parts, filler 60 parts, dextrin 20 parts, microcrystalline cellulose 20 parts, magnesium stearate 0.5 parts, and component A 3 parts. Among them, the filler includes 95% corn starch and 5% amino acid composition. Among them, the amino acid composition is composed of histidine and cystine with a weight ratio of 1:0.5. Among them, the component A includes 30% by weight of polyethylene glycol 4000 and 70% by weight of sucrose.

[0274] Prepare the above components into tablets by the following steps:

[0275] Prepare starch paste, take corn starch and add purified water with 15 times the weight of the corn starch, heat to 120℃, stir while adding to prepare starch paste, when the temperature cools to 100℃, add amino acid composition and stir until the starch paste cools to room temperature;

[0276] Granulation, take dextrin, sucralfate, microcrystalline cellulose, component A in turn into the high-speed wet granulator, add starch paste; turn on the high-speed wet granulator, 5000 rpm / min, granulation for 10 minutes;

[0277] Drying, take the intermediate product obtained in the previous step into the fluidized bed dryer, control the temperature at 90℃, dry for 90 minutes, then take out, obtain sucralfate granules, the water content of the sucralfate granules is not higher than 8%;

[0278] Granulation, add sucralfate granules into the lifting granulator and sieve with 20 meshes for granulation, and then reserve for use.

[0279] Tablet preparation, take sucralfate granules into the mixer and add lubricant, turn on the mixer, mix for 50 minutes, and then take the qualified sucralfate granules for tabletting.

[0280] Comparative Example 1

[0281] Comparative Example 1 is substantially the same as the technical solution of Example 2, the only difference is that the filler is potato starch.

[0282] Comparative Example 2

[0283] Comparative Example 2 is substantially the same as the technical solution of Example 2, the only difference is that in the drying step, the water content of the sucralfate particles is 10%.

[0284] Comparative Example 3

[0285] Comparative Example 3 is substantially the same as the technical solution of Example 3, the only difference is that in the step of preparing the starch slurry, the cooling is not performed before adding the amino acid composition and stirring.

[0286] Comparative Example 4

[0287] Comparative Example 4 is substantially the same as the technical solution of Example 7, the only difference is that in component A, the polyethylene glycol 4000 is replaced by polyethylene glycol 6000.

[0288] Comparative Example 5

[0289] Comparative Example 5 is substantially the same as the technical solution of Example 7, the only difference is that in component A, the polyethylene glycol 4000 is replaced by polyethylene glycol 2000.

[0290] Comparative Example 6

[0291] Comparative Example 6 is substantially the same as the technical solution of Example 7, the only difference is that in component A, the sucrose is replaced by maltose.

[0292] Comparative Example 7

[0293] Comparative Example 7 is substantially the same as the technical solution of Example 8, the only difference is that in the step of preparing the starch slurry, the cooling is not performed before adding the amino acid composition and stirring.

[0294] Test Example 1

[0295] The sucralfate tablets prepared according to the methods of Examples 1-8 and Comparative Examples 1-7 are tested for inhibition rate of gastric ulcer according to the method of this test example. It is understood that the same batch of product is selected for experiments in the same group.

[0296] The experimental method is as follows:

[0297] Take rats that have been fasted for 24 hours (feeding conditions: room temperature, 12h light / dark cycle, free drinking water), and make a gastric ulcer model SD rat by gavage with 0.1ml / 10g anhydrous ethanol.

[0298] After operation, the rats were allowed to eat and drink freely. The next day, the SD rats with gastric ulcer model were grouped, with 10 rats in each group. Twelve experimental groups (Examples 1-8 and Comparative Examples 1-7) and one blank group (normal saline) were prepared. The experimental groups were administered with 1 ml of distilled water, and the dose was 20 mg / kg each time. The animals were executed by cervical dislocation at 24 h after administration, and the gastric tissue was taken.

[0299] The gastric contents were washed with normal saline, and the stomach was fixed in 1% formaldehyde solution. After 15 min, the stomach was flattened on the surface of a glass dish, and the long and short diameters of the ulcer surface were measured. The ulcer inhibition rate was calculated as follows:

[0300] Ulcer inhibition rate = (ulcer area of blank group - ulcer area of experimental group) / ulcer area of blank group x 100%

[0301] The experimental results are shown in Table 3.

[0302] Table 3: Gastric ulcer inhibition rate experiment of Examples 1-8 and Comparative Examples 1-7

[0303] Group Ulcer Inhibition Rate (%) Example 1 56.6％ Example 2 55.0％ Example 3 58.2％ Example 4 57.6％ Example 5 56.8％ Example 6 60.5％ Example 7 60.9％ Example 8 61.7 Comparative Example 1 50.4 Comparative Example 2 45.8 Comparative Example 3 45.4 Comparative Example 4 55.4 Comparative Example 5 56.0 Comparative Example 6 56.3 Comparative Example 7 50.1

[0304] According to the results in Table 3, it can be seen that:

[0305] First, Comparative Examples 1-5 and Comparative Example 1-2, the ulcer inhibition rate of Comparative Example 1-2 was significantly lower than that of Example 1-5. In combination with Experimental Example 1 of the present application, the selection of corn starch in the filler can affect the dispersion ability of the product, and thus affect the final efficacy.

[0306] Second, Comparative Examples 6-8 and Comparative Examples 4-5, the ulcer inhibition rate of Comparative Examples 4-5 was significantly lower than that of Examples 6-8. In combination with Experimental Example 2 of the present application, the selection of the type of polyethylene glycol in Component A can affect the adhesion of the product to the gastric mucosa, and thus affect the final efficacy.

[0307] Third, Comparative Examples 6-8 and Comparative Example 6, the ulcer inhibition rate of Comparative Example 6 was significantly lower than that of Examples 6-8. In combination with Experimental Example 2 of the present application, the selection of sucrose in Component A can affect the adhesion of the product to the gastric mucosa, and thus affect the final efficacy.

[0308] Fourth, Comparative Examples 3 and 8 and Comparative Examples 3 and 7, the ulcer inhibition rate of Comparative Examples 3 and 7 was significantly lower than that of Examples 3 and 8. This indicates that, in the preparation of the starch slurry step, if the amino acid composition is added at a temperature above 100°C, the quality of the final product will be affected, and thus the effect of the product on treating gastric ulcer will be affected.

[0309] For those skilled in the art, the technical features in the above examples can be freely combined, and the technical solutions formed thereby also belong to the embodiments disclosed in the present application.

[0310] Further, various modifications and changes can be made to the application without departing from the spirit thereof, and it is intended to cover in the appended claims all such modifications and changes that fall within the scope of the application.

Claims

1. A tablet of sucralfate, characterized in that: By weight parts, including components: Sucralfate 30-60 parts, Filler 30-60 parts, Dextrin 5-20 parts, Microcrystalline cellulose 5-20 parts, Lubricant 0.1-0.5 parts, The filler is composed of corn starch and amino acid composition, and includes more than 95% corn starch and not less than 1.5% amino acid composition; the amino acid composition is histidine and cystine, and the weight ratio of the two is 1:1-1:0.5; The preparation method of the sucralfate tablet includes the following steps: Preparation of starch slurry, corn starch is weighed and added into purified water with 5-15 times the weight of the starch, heated to 100-120℃, and stirred while adding to prepare the starch slurry. When the temperature cools down to not higher than 100℃, the amino acid composition is added and stirred until the starch slurry cools down to room temperature; Granulation, dextrin, sucralfate, and microcrystalline cellulose are weighed and sequentially sucked into a high-speed wet granulator, and the starch slurry is added. The high-speed wet granulator is started, and the rotation speed is 3000-5000 rpm / min. Granulation is performed for 5-10 minutes. Drying, the intermediate product obtained in the previous step is sucked into a fluidized bed dryer, and the temperature is controlled at 60-90℃ for drying for 30-90 minutes. After the water content is measured to be not higher than 8%, the product is taken out, and sucralfate granules are obtained. Whole granulation, the sucralfate granules are added into a lifting whole granulator and whole granulated with a 20-mesh sieve. The whole granulation is ready for use. Tablet preparation, the sucralfate granules are sucked into a mixer and the lubricant is added. The mixer is started, and the mixture is mixed for 20-50 minutes. The qualified sucralfate granules are taken out and pressed into tablets.

2. The sucralfate tablet according to claim 1, wherein: By weight parts, including components: Sucralfate 45-55 parts, Filler 45-55 parts, Dextrin 8-15 parts, Microcrystalline cellulose 8-12 parts, Lubricant 0.15-0.25 parts.

3. The sucralfate tablet according to claim 1, wherein: The lubricant is one or a combination of several of talc, micronized silica gel, and magnesium stearate.

4. The suifated aluminium tablet according to claim 3, wherein: The lubricant is magnesium stearate.

5. The sucralfate tablet according to claim 1, wherein: The sucralfate tablet further includes 1-3 parts of component A, and the component A includes 30% by weight of polyethylene glycol 4000 and 70% by weight of sucrose.

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