Sodium butyrate enteric sustained-release pellet capsule and preparation method thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, and discloses a sodium butyrate enteric-coated and sustained-release pellet capsule and a preparation method thereof.The capsule comprises, by weight, 0.55%-0.88% of sodium butyrate raw materials, 0.55%-0.88% of filling agents, 0.35%-0.88% of binding agents, 0.20%-0.30% of lubricating agents, 0.20%-0.30% of enteric coating materials, 0.20%-0.30% of pigments, 0.20%-0.30% of solvents, 0.20%-0.30% of dispersion media, 0.20%-0.30% of 40%-46% of a filling agent; 9%-10% of an adhesive; 1%-1.2% of a lubricant; 23%-28% of an enteric coating material; 0.07%-0.09% of a pigment; 7%-9% of a solvent; 5-10% of a dispersion medium; 2%-6% of a release regulator; due to the design of enteric solubility, the capsule can release medicine in the intestinal tract after passing through the stomach, the medicine can be slowly and continuously released in the body, the curative effect is improved, side effects are reduced, it is ensured that the medicine cannot be damaged in gastric acid, meanwhile, turmeric and carthamin yellow in pigment can bring warm properties to the capsule, and the capsule has the advantages of being free of toxic and side effects, safe and reliable. The cold and cool feeling in the body can be balanced, and the cold and cool symptom of the stomach can be relieved.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a sodium butyrate enteric-coated sustained-release micropellet capsule and a preparation method thereof. Background Art

[0002] In the field of pharmaceutical formulation technology, traditional drug release methods often face many challenges. Traditional pills often encounter problems such as unstable drug release and poor patient compliance. The drug release rate may be fast, resulting in large fluctuations in blood drug concentrations, requiring multiple doses to maintain efficacy, which may affect patient compliance. The design and preparation method of enteric-coated sustained-release micropellet capsules is precisely to overcome the limitations of these traditional dosage forms and provide patients with more optimized treatment options. Summary of the invention

[0003] In view of the deficiencies in the prior art, the present invention provides a sodium butyrate enteric-coated sustained-release micropellet capsule and a preparation method thereof, which has the advantages of drug mildness, stable solubility and improved patient compliance, and solves the problems of unstable drug release and poor patient compliance.

[0004] To achieve the above object, the present invention provides the following technical solution: a sodium butyrate enteric sustained-release micropellet capsule, wherein the capsule components include a sodium butyrate inner core layer material, including a sodium butyrate raw material, a filler, a binder and a lubricant; and an enteric coating layer material, including an enteric coating material, a pigment, a solvent, a dispersion medium, a release regulator and a pH regulator; The capsule ingredients include: sodium butyrate raw material 0.55%-0.88%; filler 40%-46%; binder 9%-10%; lubricant 1%-1.2%; enteric coating material 23%-28%; pigment 0.07%-0.09%; solvent 7%-9%; dispersion medium 5%-10%; release regulator 2%-6%; pH regulator 3%-5%.

[0005] Preferably, the filler is composed of cassava starch, sodium starch octenyl succinate and microcrystalline cellulose in a ratio of 3:1:1; the binder is composed of lactose and gelatin in a ratio of 5:1; the lubricant is composed of silica fluoride and magnesium stearate in a ratio of 1:4; the enteric coating material is composed of hydroxypropyl methylcellulose phthalate; the pigment is composed of turmeric and safflower yellow in a ratio of 1:1; the solvent is composed of ethanol, purified water and ethyl acetate in a ratio of 1:3:6; the dispersion medium is composed of TNWDIS; the release regulator is composed of acrylic resin; and the pH regulator is composed of 30% hydrochloric acid and 10% sodium bicarbonate in a ratio of 2:1.

[0006] Preferably, the preparation process of the tapioca starch is: S1.1, Raw material selection and processing: Select fresh cassava in the middle stage of maturity as raw material; S1.2, peeling: after washing, use a cassava peeling machine to peel the cassava to remove the outer skin; S1.3, crushing: using a hammer crusher, setting the speed to 1480 rpm, hammering, filing, cutting and squeezing the cassava for 30 min, using water with a volume of 150% of the cassava starch as a medium, processing the crushed cassava into starch pulp, and in the process of adding water and stirring, passing the cassava starch pulp through a 6.0 mm sieve, and then crushing it for the second time, and stirring continuously after passing through a 1.2-1.4 mm sieve; S1.4, screening and separation: Use a 120 pressure curved screen to screen the thin starch slurry after crushing and stirring, and then use a vertical centrifugal screen to separate the starch milk and fiber. The screening and separation process is carried out 3-5 times; S1.5, bleaching: use 0.1 kg / t of starch potassium permanganate for bleaching, add the diluted potassium permanganate solution evenly into the separated starch milk, stir thoroughly for 1 hour and then let stand for 1 hour; S1.6, sand removal: the bleached starch slurry is pumped into the vortex by a pressure pump, the bottom flow removes sand, and the top flow passes through the slurry; S1.7, Separation: Use a disc separator to wash, refine and concentrate the starch slurry; S1.8, Dehydration: Use a scraper centrifuge to dehydrate the starch slurry by overflow method, and ensure that the moisture content of wet starch after dehydration is 30%-35%; S1.9, Drying: The wet starch dehydrated by the scraper centrifuge is transported to the air flow dryer for drying for 1 hour. The steam pressure of the air flow dryer is set to 0.8Mpa. The moisture content of the finished starch product after drying is 9.5%-10.5%.

[0007] Preferably, the preparation process of the sodium starch octenyl succinate is: S2.1, esterification reaction: corn starch and octenyl succinic anhydride are mixed in a ratio of 1:5, the pH value is controlled at 9-10, the temperature is controlled at 30-40°C, and the reaction time is controlled at 7-9h to obtain a preliminary product of sodium octenyl succinate starch; S2.2, washing: after the reaction is completed, the sodium starch octenyl succinate formed product is washed three times with 75% ethanol; S2.3, drying: after washing, the wet sodium octenyl succinate starch is obtained, which is dried for 1 hour using a drum drying device at a drying temperature of 110-120° C. to obtain sodium octenyl succinate starch.

[0008] Preferably, the preparation process of turmeric is: S3.1. Screening: Screen the fresh turmeric to remove stones, dirt and mechanical impurities; S3.2, crushing: After the screened turmeric slices are exposed to the sun for 10 days, they are crushed using a crusher to a particle size of 2 mm to 4 mm; S3.3, extraction: the crushed turmeric is put into an extraction tank, 90% ethanol is added for high temperature extraction at 120°C, the extraction time is 2h, and after repeating twice, the two extracts are combined; S3.4, Concentration: The concentrate is transferred to a centrifugal evaporator, and the extract is concentrated to a concentration of 1 / 20 of the volume before concentration at a temperature of 55-65°C, with the evaporation time set to 30-40 minutes, and the remaining ethanol is recovered; S3.5. Drying: The concentrated turmeric extract is dried using spray drying technology, the inlet temperature is set to 195°C, the drying time is set to 1h, and the finished product after drying is a powdered turmeric extract, which is stored at a temperature of 0-5°C.

[0009] Preferably, the preparation process of safflower yellow is: S4.1. Material selection: Select fresh, early-ripening safflower, wash and set aside; S4.2, soaking: mix safflower and pure water in a ratio of 1:5 in a glass beaker, place the glass beaker in a water bath, set the temperature to 40°C, and soak for 0.1 to 4.5 hours; S4.3, extrusion: use a manual screw press to squeeze the soaked safflower for 10 minutes; S4.4, collecting liquid: mix the squeezed safflower and pure water in a ratio of 1:4 in a glass beaker, place the glass beaker in a water bath, set the temperature to 45°C, soak for 2.0h to 6.0h, squeeze again after soaking, and collect the secondary extracted yellow pigment liquid; S4.5, purification: the yellow pigment liquid obtained from the secondary extraction is fully mixed with AB-8 macroporous resin, the mixed resin is loaded into a column, and 95% ethanol is used as an eluent to elute the adsorbed yellow pigment from the resin; S4.6, Concentrated drying: Use spray drying technology to dry the adsorbed yellow pigment, set the inlet temperature to 200°C, set the drying time to 40 minutes, the finished product after drying is powdered safflower yellow, and is stored at a temperature of 0-5°C.

[0010] Based on solving the above technical problems, the present invention provides a second technical solution as follows: a method for preparing a sodium butyrate enteric-coated sustained-release micropellet capsule, which is prepared according to the capsule components of the above sodium butyrate enteric-coated sustained-release micropellet capsule, comprising the following steps: Step 1, preparation of sodium butyrate inner core layer; Step 2: spraying an enteric coating layer to obtain sodium butyrate enteric-coated sustained-release micropellet capsules.

[0011] Preferably, the preparation process of the sodium butyrate inner core layer in step 1 is: S5.1. Raw material pretreatment: crush the sodium butyrate raw material of the formula ratio into 20-30 microns using a hammer mill; S5.2. Preparation of auxiliary materials: weigh fillers, adhesives and lubricants according to the formula ratio; S5.3, Mixing process: Select a V-type mixer, add the pretreated sodium butyrate and filler into the mixer and mix for 10 minutes in an environment with a temperature of 20°C and a humidity of 44%. After all components are evenly distributed, add the adhesive and lubricant and stir thoroughly for 20 minutes; S5.4, coating treatment: the mixed materials are coated using a fluidized bed coater. During the coating process, the temperature is controlled at 20°C-25°C and the spray rate is controlled at 50-60mL / min.

[0012] Preferably, the process of spraying the enteric coating layer in step 2 to obtain the sodium butyrate enteric coated sustained-release pellet capsules is: S6.1. Selection of coating materials: enteric coating materials, pigments, solvents, dispersion media, release regulators and pH regulators; S6.2, spray coating: set the temperature of the fluidized bed coater to 30°C, the humidity to 45%, and the spraying rate to 60 mL / min, and evenly spray a layer of 80 μm coating material on the surface of the sodium butyrate inner core layer prepared in step 1 to form micropellets; S6.3, coating and curing: after spraying, the micropellets are cured at a temperature of 40-50°C for 6 minutes to obtain sodium butyrate enteric-coated sustained-release micropellets capsules; S6.4, Quality Inspection: Sodium butyrate enteric-coated sustained-release microcapsules are tested for appearance, particle size distribution, coating integrity and in vitro release.

[0013] Preferably, in the quality inspection of step S6.4, the qualified sodium butyrate enteric-coated sustained-release microcapsules are packaged and stored in a cool and dry place.

[0014] Compared with the prior art, the present invention provides a sodium butyrate enteric-coated sustained-release micropellet capsule and a preparation method thereof, which has the following beneficial effects: 1. The pigment in the present invention is composed of turmeric and safflower yellow in a ratio of 1:1. Turmeric has the properties of pungent, dispersing, warming and unblocking, can enter the blood and qi, effectively activate blood circulation and promote qi circulation, help improve blood circulation, and relieve pain and discomfort caused by poor qi and blood circulation. Combined with the administration properties of safflower yellow, it can bring a warming property to the capsule, help balance the cold feeling in the body, and relieve the symptoms of cold stomach.

[0015] 2. The preparation steps of the present invention enable the drug to be released slowly and continuously in the body to maintain a stable blood drug concentration, improve efficacy and reduce side effects. The enteric-coated design enables the capsule to release the drug in the intestine after passing through the stomach to ensure that the drug will not be destroyed in gastric acid.

[0016] 3. The filler composed of cassava starch, sodium starch octenyl succinate and microcrystalline cellulose in the present invention can form a porous structure, increase the contact area between the drug and the filler, and help release the drug. Sodium starch octenyl succinate can adjust the viscosity and fluidity of the filler, so that the drug is evenly distributed in the filler to improve the stability and plasticity of the drug. The filler using the above three raw materials can slowly release the drug, prolong the action time of the drug, reduce the dosage and frequency of the drug, and solve the problems of unstable drug release and poor patient compliance. In addition, the combination of the filler can be adjusted within a specified range according to the properties of the drug and the requirements of the preparation, thereby further improving the efficacy of the drug and the compliance of the patient. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 A flow chart was prepared for the present invention. DETAILED DESCRIPTION

[0018] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0019] See also Figure 1 , a sodium butyrate enteric-coated sustained-release micropellet capsule, the capsule components include a sodium butyrate inner core layer material, including a sodium butyrate raw material, a filler, a binder and a lubricant; and an enteric coating layer material, including an enteric coating material, a pigment, a solvent, a dispersion medium, a release regulator and a pH regulator; The proportions of capsule ingredients include: sodium butyrate raw material 0.55%-0.88%; filler 40%-46%; binder 9%-10%; lubricant 1%-1.2%; enteric coating material 23%-28%; pigment 0.07%-0.09%; solvent 7%-9%; dispersion medium 5%-10%; release regulator 2%-6%; pH regulator 3%-5%.

[0020] The filler consists of tapioca starch, sodium starch octenylsuccinate and microcrystalline cellulose in a ratio of 3:1:1; the binder consists of lactose and gelatin in a ratio of 5:1; the lubricant consists of argon silica and magnesium stearate in a ratio of 1:4; the enteric coating material consists of hydroxypropyl methylcellulose phthalate; the pigment consists of turmeric and safflower yellow in a ratio of 1:1; the solvent consists of ethanol, purified water and ethyl acetate in a ratio of 1:3:6; the dispersion medium consists of TNWDIS (TNWDIS is a specific carbon nanotube dispersant suitable for improving the dispersibility of carbon nanotubes in aqueous media); the release regulator consists of acrylic resin; and the pH regulator consists of 30% hydrochloric acid and 10% sodium bicarbonate in a ratio of 2:1.

[0021] The preparation process of cassava starch is: S1.1, Raw material selection and processing: Select fresh cassava in the middle stage of maturity as raw material; S1.2, peeling: after washing, use a cassava peeling machine to peel the cassava to remove the outer skin; S1.3, crushing: using a hammer crusher, setting the speed to 1480 rpm, hammering, filing, cutting and squeezing the cassava for 30 min, using water with a volume of 150% of the cassava starch as a medium, processing the crushed cassava into starch pulp, and in the process of adding water and stirring, passing the cassava starch pulp through a 6.0 mm sieve, and then crushing it for the second time, and stirring continuously after passing through a 1.2-1.4 mm sieve; S1.4, screening and separation: Use a 120 pressure curved screen to screen the thin starch slurry after crushing and stirring, and then use a vertical centrifugal screen to separate the starch milk and fiber. The screening and separation process is carried out 3-5 times; S1.5, bleaching: use 0.1 kg / t of starch potassium permanganate for bleaching, add the diluted potassium permanganate solution evenly into the separated starch milk, stir thoroughly for 1 hour and then let stand for 1 hour; S1.6, sand removal: the bleached starch slurry is pumped into the vortex by a pressure pump, the bottom flow removes sand, and the top flow passes through the slurry; S1.7, Separation: Use a disc separator to wash, refine and concentrate the starch slurry; S1.8, Dehydration: Use a scraper centrifuge to dehydrate the starch slurry by overflow method, and ensure that the moisture content of wet starch after dehydration is 30%-35%; S1.9, Drying: The wet starch dehydrated by the scraper centrifuge is transported to the air flow dryer for drying for 1 hour. The steam pressure of the air flow dryer is set to 0.8Mpa. The moisture content of the finished starch product after drying is 9.5%-10.5%.

[0022] The preparation process of sodium starch octenylsuccinate is as follows: S2.1, esterification reaction: corn starch and octenyl succinic anhydride are mixed in a ratio of 1:5, the pH value is controlled at 9-10, the temperature is controlled at 30-40°C, and the reaction time is controlled at 7-9h to obtain a preliminary product of sodium octenyl succinate starch; S2.2, washing: after the reaction is completed, the sodium starch octenyl succinate formed product is washed three times with 75% ethanol; S2.3, drying: after washing, the wet sodium octenyl succinate starch is obtained, which is dried for 1 hour using a drum drying device at a drying temperature of 110-120° C. to obtain sodium octenyl succinate starch.

[0023] The preparation process of turmeric is: S3.1, Screening: Screen the fresh turmeric to remove stones, dirt and mechanical impurities to ensure that the extraction process is not interfered by foreign substances; S3.2, crushing: After the selected turmeric slices are exposed to the sun for 10 days, they are crushed using a crusher. The crushed particles are between 2mm and 4mm to increase the contact area with the extraction solvent and improve the extraction rate of the active ingredients. The particle size after crushing should be moderate. Too coarse or too fine will affect the subsequent extraction effect. S3.3, extraction: the crushed turmeric is put into an extraction tank, and 90% ethanol is added for high temperature extraction at 120°C for 2 hours. After being repeated twice, the two extracts are combined. This step aims to fully extract the active ingredients in turmeric, such as curcuminoids; S3.4, Concentration: The concentrate is transferred to a centrifugal evaporator, and the evaporation time is set to 30min-40min at a temperature of 55-65°C, and the extract is concentrated to a concentration of 1 / 20 of the volume before concentration, and the remaining ethanol is recovered. Concentration not only increases the concentration of the active ingredients, but also facilitates subsequent drying and other applications; S3.5. Drying: The concentrated turmeric extract is dried using spray drying technology, the inlet temperature is set to 195°C, the drying time is set to 1h, and the finished product after drying is a powdered turmeric extract, which is stored at a temperature of 0-5°C.

[0024] The preparation process of safflower yellow is as follows: S4.1. Material selection: Select fresh, early-ripening safflower, wash and set aside; S4.2, soaking: mix safflower and pure water in a ratio of 1:5 in a glass beaker, place the glass beaker in a water bath, set the temperature to 40°C, and soak for 0.1 to 4.5 hours; S4.3, squeezing: use a manual screw press to squeeze the soaked safflower for 10 minutes to fully extract the yellow pigment; S4.4, collecting liquid: mix the squeezed safflower and pure water in a ratio of 1:4 in a glass beaker, place the glass beaker in a water bath, set the temperature to 45°C, soak for 2.0h to 6.0h, squeeze again after soaking, and collect the secondary extracted yellow pigment liquid; S4.5, purification: the yellow pigment liquid obtained from the secondary extraction is fully mixed with AB-8 macroporous resin, the mixed resin is loaded into a column, and 95% ethanol is used as an eluent to elute the adsorbed yellow pigment from the resin; S4.6, Concentrated drying: Use spray drying technology to dry the adsorbed yellow pigment, set the inlet temperature to 200°C, set the drying time to 40 minutes, the finished product after drying is powdered safflower yellow, and is stored at a temperature of 0-5°C.

[0025] A method for preparing a sodium butyrate enteric-coated sustained-release micropellet capsule is prepared according to the capsule components of the above-mentioned sodium butyrate enteric-coated sustained-release micropellet capsule, comprising the following steps: Step 1, preparation of sodium butyrate inner core layer; Step 2: spraying an enteric coating layer to obtain sodium butyrate enteric-coated sustained-release micropellet capsules.

[0026] The preparation process of the sodium butyrate inner core layer in step 1 is: S5.1. Raw material pretreatment: crush the sodium butyrate raw material of the formula ratio into 20-30 microns using a hammer mill; S5.2. Preparation of auxiliary materials: weigh fillers, adhesives and lubricants according to the formula ratio; S5.3, Mixing process: Select a V-type mixer, add the pretreated sodium butyrate and filler into the mixer and mix for 10 minutes in an environment with a temperature of 20°C and a humidity of 44%. After ensuring that all components are evenly distributed, add the adhesive and lubricant and stir thoroughly for 20 minutes; S5.4, coating treatment: The mixed materials are coated using a fluidized bed coating machine. During the coating process, the temperature is controlled at 20℃-25℃, and the spray rate is controlled at 50-60mL / min to ensure that the coating is uniform and complete. Through the coating treatment, a stable inner layer is formed, that is, the sodium butyrate core is evenly wrapped by the auxiliary material layer, thus laying the foundation for the subsequent enteric coating.

[0027] The process of spraying the enteric coating layer in step 2 to obtain the sodium butyrate enteric coated sustained-release pellet capsules is as follows: S6.1. Selection of coating materials: enteric coating materials, pigments, solvents, dispersion media, release regulators and pH regulators; S6.2, spray coating: set the temperature of the fluidized bed coater to 30°C, the humidity to 45%, and the spraying rate to 60 mL / min, and evenly spray a layer of 80 μm coating material on the surface of the sodium butyrate inner core layer prepared in step 1 to form micropellets; S6.3, coating and curing: after spraying, the micropellets are cured at a temperature of 40-50°C for 6 minutes to obtain sodium butyrate enteric-coated sustained-release micropellets capsules; S6.4, Quality Inspection: Sodium butyrate enteric-coated sustained-release microcapsules are tested for appearance, particle size distribution, coating integrity and in vitro release.

[0028] In step S6.4 quality inspection, qualified sodium butyrate enteric-coated sustained-release microcapsules are packaged and stored in a cool and dry place. Example

[0029] The capsule components include: 0.58% sodium butyrate raw material; 46% filler; 9% binder; 1.2% lubricant; 25% enteric coating material; 0.08% pigment; 8% solvent; 8% dispersion medium; 4% release regulator; 4% pH regulator. The above raw material formula is used to prepare sodium butyrate enteric sustained-release microcapsule capsules using the preparation steps of the present invention.

[0030] Step 1: Preparation of sodium butyrate inner core layer, the preparation process is as follows: S5.1. Raw material pretreatment: crush the sodium butyrate raw material of the formula ratio into 20-30 microns using a hammer mill; S5.2. Preparation of auxiliary materials: weigh fillers, adhesives and lubricants according to the formula ratio; S5.3, Mixing process: Select a V-type mixer, add the pretreated sodium butyrate and filler into the mixer and mix for 10 minutes in an environment with a temperature of 20°C and a humidity of 44%. After ensuring that all components are evenly distributed, add the adhesive and lubricant and stir thoroughly for 20 minutes; S5.4, coating treatment: The mixed materials are coated using a fluidized bed coating machine. During the coating process, the temperature is controlled at 20℃-25℃, and the spray rate is controlled at 50-60mL / min to ensure that the coating is uniform and complete. Through the coating treatment, a stable inner layer is formed, that is, the sodium butyrate core is evenly wrapped by the auxiliary material layer, thus laying the foundation for the subsequent enteric coating.

[0031] Step 2: spraying an enteric coating layer to obtain sodium butyrate enteric coated sustained-release pellet capsules, the preparation process of which is as follows: S6.1. Selection of coating materials: enteric coating materials, pigments, solvents, dispersion media, release regulators and pH regulators; S6.2, spray coating: set the temperature of the fluidized bed coater to 30°C, the humidity to 45%, and the spraying rate to 60 mL / min, and evenly spray a layer of 80 μm coating material on the surface of the sodium butyrate inner core layer prepared in step 1 to form micropellets; S6.3, coating and curing: after spraying, the micropellets are cured at a temperature of 40-50°C for 6 minutes to obtain sodium butyrate enteric-coated sustained-release micropellets capsules; S6.4, Quality Inspection: Sodium butyrate enteric-coated sustained-release microcapsules are tested for appearance, particle size distribution, coating integrity and in vitro release.

[0032] In step S6.4 quality inspection, qualified sodium butyrate enteric-coated sustained-release microcapsules are packaged and stored in a cool and dry place. Example

[0033] The capsule components include: 0.80% sodium butyrate raw material; 43% filler; 10% binder; 1.2% lubricant; 26% enteric coating material; 0.09% pigment; 8% solvent; 8% dispersion medium; 3% release regulator; 4.5% pH regulator. The above raw material formula is used to prepare sodium butyrate enteric sustained-release microcapsule capsules using the preparation steps of the present invention. Example

[0034] The capsule components include: 0.80% sodium butyrate raw material; 43% filler; 10% binder; 1.2% lubricant; 26% enteric coating material; 0.09% pigment; 8% solvent; 8% dispersion medium; 3% release regulator; 4.5% pH regulator. The above raw material formula is used to prepare sodium butyrate enteric sustained-release microcapsule capsules using the preparation steps of the present invention.

[0035] Comparative Example 1 The capsule components include: 0.58% sodium butyrate raw material; 46% filler; 9% binder; 1.2% lubricant; 25% enteric coating material; 0.08% colorant; 8% solvent; 8% dispersion medium; 4% release regulator; 4% pH regulator. The raw material pigment of the above formula is changed into the colorant, and the above raw material formula is used to prepare the sodium butyrate enteric sustained-release microcapsule capsule using the preparation steps of the present invention.

[0036] Comparative Example 2 The capsule components include: 0.80% sodium butyrate raw material; 43% filler; 10% binder; 1.2% lubricant; 26% enteric coating material; 0.09% pigment; 8% solvent; 8% dispersion medium; 3% release regulator; 4.5% pH regulator. The cassava starch in the raw material filler of the above formula is replaced with corn starch, and the above raw material formula is used to prepare sodium butyrate enteric sustained-release micropellet capsules using the preparation steps of the present invention.

[0037] Comparative Example 3 The capsule components include: 0.80% sodium butyrate raw material; 43% filler; 10% binder; 1.2% lubricant; 26% enteric coating material; 0.09% pigment; 8% solvent; 8% dispersion medium; 3% release regulator; 4.5% pH regulator. The above raw material formula is compared with the preparation steps of Example 3, and S6.3, coating and curing step is removed to prepare sodium butyrate capsules.

[0038] The difference between Example 1 and Comparative Example 1 lies in the use of pigments and toners. Pigments are used in Example 1, while pigments are replaced by toners in Comparative Example 1. The pigments in the present invention are composed of turmeric and safflower yellow in a ratio of 1:1. Turmeric has the properties of pungent, dispersing, warming and unblocking, can enter the blood and qi, effectively activate blood circulation and promote qi circulation, help improve blood circulation, and relieve pain and discomfort caused by poor qi and blood circulation. Combined with the dosing properties of safflower yellow, it can bring warm properties to the capsule, help balance the cold feeling in the body, and relieve the symptoms of cold stomach.

[0039] The difference between Example 2 and Comparative Example 2 lies in the selection of fillers. In Example 2, cassava starch is used as a filler, while in Comparative Example 2, it is replaced by corn starch. By selecting cassava starch as a filler, the corn starch in Comparative Example 2 cannot form a porous structure with microcrystalline cellulose, while the cassava starch and microcrystalline cellulose in Example 2 can form a porous structure, thereby increasing the contact area between the drug and the filler, which helps to release the drug, so that when the finished capsule is used, the drug release characteristics, capsule mechanical strength and formulation stability are improved, which helps to improve the overall efficacy of the drug and the patient's medication experience.

[0040] The difference between Example 3 and Comparative Example 3 lies in the preparation steps. Example 3 adopts the preparation steps of the present invention, while Comparative Example 3 removes S6.3 and coating and curing steps of the preparation steps of the present invention to prepare sodium butyrate capsules, resulting in differences in coating quality, drug release rate and formulation stability between the two finished capsules. Example 3 adopts the preparation steps of the present invention, and adds S6.3 and coating and curing steps to prepare sodium butyrate capsules, so that the drug can be slowly and continuously released in the body, further maintaining a stable blood drug concentration, improving efficacy and reducing side effects. The enteric design enables the capsule to release the drug in the intestine after passing through the stomach to ensure that the drug is not destroyed in gastric acid.

[0041] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A sodium butyrate enteric-coated sustained-release pellet capsule, characterized in that: The capsule components include sodium butyrate inner core layer materials, including sodium butyrate raw materials, fillers, adhesives and lubricants; and enteric coating layer materials, including enteric coating materials, pigments, solvents, dispersion media, release regulators and pH regulators; The capsule ingredients include: sodium butyrate raw material 0.55%-0.88%; filler 40%-46%; binder 9%-10%; lubricant 1%-1.2%; enteric coating material 23%-28%; pigment 0.07%-0.09%; solvent 7%-9%; dispersion medium 5%-10%; release regulator 2%-6%; pH regulator 3%-5%.

2. The sodium butyrate enteric-coated sustained-release micropellet capsule according to claim 1, characterized in that: The filler is composed of cassava starch, sodium starch octenyl succinate and microcrystalline cellulose in a ratio of 3:1:1; the binder is composed of lactose and gelatin in a ratio of 5:1; the lubricant is composed of silica fluoride and magnesium stearate in a ratio of 1:4; the enteric coating material is composed of hydroxypropyl methylcellulose phthalate; the pigment is composed of turmeric and safflower yellow in a ratio of 1:1; the solvent is composed of ethanol, purified water and ethyl acetate in a ratio of 1:3:6; the dispersion medium is composed of TNWDIS; the release regulator is composed of acrylic resin; and the pH regulator is composed of 30% hydrochloric acid and 10% sodium bicarbonate in a ratio of 2:

1.

3. The sodium butyrate enteric-coated sustained-release micropellet capsule according to claim 2, characterized in that: The preparation process of the tapioca starch is: S1.1, Raw material selection and processing: Select fresh cassava in the middle stage of maturity as raw material; S1.2, peeling: after washing, use a cassava peeling machine to peel the cassava to remove the outer skin; S1.3, crushing: using a hammer crusher, setting the speed to 1480 rpm, hammering, filing, cutting and squeezing the cassava for 30 min, using water with a volume of 150% of the cassava starch as a medium, processing the crushed cassava into starch pulp, and in the process of adding water and stirring, passing the cassava starch pulp through a 6.0 mm sieve, and then crushing it for the second time, and stirring continuously after passing through a 1.2-1.4 mm sieve; S1.4, screening and separation: Use a 120 pressure curved screen to screen the thin starch slurry after crushing and stirring, and then use a vertical centrifugal screen to separate the starch milk and fiber. The screening and separation process is carried out 3-5 times; S1.5, bleaching: use 0.1 kg / t of starch potassium permanganate for bleaching, add the diluted potassium permanganate solution evenly into the separated starch milk, stir thoroughly for 1 hour and then let stand for 1 hour; S1.6, sand removal: the bleached starch slurry is pumped into the vortex by a pressure pump, the bottom flow removes sand, and the top flow passes through the slurry; S1.7, Separation: Use a disc separator to wash, refine and concentrate the starch slurry; S1.8, Dehydration: Use a scraper centrifuge to dehydrate the starch slurry by overflow method, and ensure that the moisture content of wet starch after dehydration is 30%-35%; S1.9, Drying: The wet starch dehydrated by the scraper centrifuge is transported to the air flow dryer for drying for 1 hour. The steam pressure of the air flow dryer is set to 0.8Mpa. The moisture content of the finished starch product after drying is 9.5%-10.5%.

4. The sodium butyrate enteric-coated sustained-release micropellet capsule according to claim 2, characterized in that: The preparation process of the sodium starch octenyl succinate is as follows: S2.1, esterification reaction: corn starch and octenyl succinic anhydride are mixed in a ratio of 1:5, the pH value is controlled at 9-10, the temperature is controlled at 30-40°C, and the reaction time is controlled at 7-9h to obtain a preliminary product of sodium octenyl succinate starch; S2.2, washing: after the reaction is completed, the sodium starch octenyl succinate formed product is washed three times with 75% ethanol; S2.3, drying: after washing, the wet sodium octenyl succinate starch is obtained, which is dried for 1 hour using a drum drying device at a drying temperature of 110-120° C. to obtain sodium octenyl succinate starch.

5. The sodium butyrate enteric-coated sustained-release micropellet capsule according to claim 2, characterized in that: The preparation process of turmeric is as follows: S3.

1. Screening: Screen the fresh turmeric to remove stones, dirt and mechanical impurities; S3.2, crushing: After the screened turmeric slices are exposed to the sun for 10 days, they are crushed using a crusher to a particle size of 2 mm to 4 mm; S3.3, extraction: the crushed turmeric is put into an extraction tank, 90% ethanol is added for high temperature extraction at 120°C, the extraction time is 2h, and after repeating twice, the two extracts are combined; S3.4, Concentration: The concentrate is transferred to a centrifugal evaporator, and the extract is concentrated to a concentration of 1 / 20 of the volume before concentration at a temperature of 55-65°C, with the evaporation time set to 30-40 minutes, and the remaining ethanol is recovered; S3.

5. Drying: The concentrated turmeric extract is dried using spray drying technology, the inlet temperature is set to 195°C, the drying time is set to 1h, and the finished product after drying is a powdered turmeric extract, which is stored at a temperature of 0-5°C.

6. The sodium butyrate enteric-coated sustained-release micropellet capsule according to claim 2, characterized in that: The preparation process of safflower yellow is as follows: S4.

1. Material selection: Select fresh, early-ripening safflower, wash and set aside; S4.2, soaking: mix safflower and pure water in a ratio of 1:5 in a glass beaker, place the glass beaker in a water bath, set the temperature to 40°C, and soak for 0.1 to 4.5 hours; S4.3, extrusion: use a manual screw press to squeeze the soaked safflower for 10 minutes; S4.4, collecting liquid: mix the squeezed safflower and pure water in a ratio of 1:4 in a glass beaker, place the glass beaker in a water bath, set the temperature to 45°C, soak for 2.0h to 6.0h, squeeze again after soaking, and collect the secondary extracted yellow pigment liquid; S4.5, purification: the yellow pigment liquid obtained from the secondary extraction is fully mixed with AB-8 macroporous resin, the mixed resin is loaded into a column, and 95% ethanol is used as an eluent to elute the adsorbed yellow pigment from the resin; S4.6, Concentrated drying: Use spray drying technology to dry the adsorbed yellow pigment, set the inlet temperature to 200°C, set the drying time to 40 minutes, the finished product after drying is powdered safflower yellow, and is stored at a temperature of 0-5°C.

7. A method for preparing a sodium butyrate enteric-coated sustained-release micropellet capsule, which is prepared according to the capsule components of the sodium butyrate enteric-coated sustained-release micropellet capsule according to claim 1, characterized in that: The following steps are involved: Step 1, preparation of sodium butyrate inner core layer; Step 2: spraying an enteric coating layer to obtain sodium butyrate enteric-coated sustained-release micropellet capsules.

8. The method for preparing a sodium butyrate enteric-coated sustained-release micropellet capsule according to claim 7, characterized in that: The preparation process of the sodium butyrate inner core layer in step 1 is as follows: S5.

1. Raw material pretreatment: crush the sodium butyrate raw material of the formula ratio into 20-30 microns using a hammer mill; S5.

2. Preparation of auxiliary materials: weigh fillers, adhesives and lubricants according to the formula ratio; S5.3, Mixing process: Select a V-type mixer, add the pretreated sodium butyrate and filler into the mixer and mix for 10 minutes in an environment with a temperature of 20°C and a humidity of 44%. After all components are evenly distributed, add the adhesive and lubricant and stir thoroughly for 20 minutes; S5.4, coating treatment: the mixed materials are coated using a fluidized bed coater. During the coating process, the temperature is controlled at 20°C-25°C and the spray rate is controlled at 50-60mL / min.

9. The method for preparing a sodium butyrate enteric-coated sustained-release micropellet capsule according to claim 8, characterized in that: The process of spraying the enteric coating layer in step 2 to obtain the sodium butyrate enteric coated sustained-release pellet capsules is as follows: S6.

1. Selection of coating materials: enteric coating materials, pigments, solvents, dispersion media, release regulators and pH regulators; S6.2, spray coating: set the temperature of the fluidized bed coater to 30°C, the humidity to 45%, and the spraying rate to 60 mL / min, and evenly spray a layer of 80 μm coating material on the surface of the sodium butyrate inner core layer prepared in step 1 to form micropellets; S6.3, coating and curing: after spraying, the micropellets are cured at a temperature of 40-50°C for 6 minutes to obtain sodium butyrate enteric-coated sustained-release micropellets capsules; S6.4, Quality Inspection: Sodium butyrate enteric-coated sustained-release microcapsules are tested for appearance, particle size distribution, coating integrity and in vitro release.

10. The method for preparing a sodium butyrate enteric-coated sustained-release micropellet capsule according to claim 9, characterized in that: In the quality inspection of step S6.4, the qualified sodium butyrate enteric-coated sustained-release microcapsules are packaged and stored in a cool and dry place.

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