Mesalazine colon-targeted controlled-release tablet and preparation method thereof

Abstract

The invention belongs to the technical field of mesalazine controlled-release preparations, and particularly relates to mesalazine colon-targeted controlled-release tablets and a preparation method thereof.The mesalazine colon-targeted controlled-release tablets comprise a tablet core layer and a controlled-release layer, the controlled-release layer wraps the tablet core layer, the tablet core layer is composed of mesalazine and an auxiliary material pyrodextrin, and the auxiliary material pyrodextrin is a mixture of mesalazine and pyrodextrin. The controlled release layer consists of pyrodextrin, a plasticizer and a pore-foaming agent. By arranging the power assembly, the two efficient stirring assemblies and the two cleaning assemblies can be driven at the same time, attachments on the inner wall of the equipment can be treated while efficient stirring is achieved, by arranging the efficient stirring assemblies, a starch aqueous solution and hydrochloric acid can be mixed more sufficiently and evenly, and the efficiency of the equipment is improved. And through the arrangement of the cleaning assembly, materials attached to the inner wall of the equipment can be scraped away, resources are saved, waste is reduced, and meanwhile the labor intensity of follow-up equipment cleaning is reduced.

Description

Technical Field

[0001] The invention belongs to the technical field of mesalazine controlled-release preparations, and in particular relates to a mesalazine colon-targeted controlled-release tablet and a preparation method thereof. Background Art

[0002] Mesalazine colon targeted controlled-release tablets are a new type of drug preparation designed to accurately deliver mesalazine to the colon to improve the drug's therapeutic effects and reduce side effects. Through colon targeted drug delivery, the drug can directly act on the diseased tissue in the colon, increase the local concentration of the drug, and enhance the therapeutic effect. For diseases in the colon such as inflammatory bowel disease, it can more effectively relieve inflammation.

[0003] Regarding the stirring equipment required in the production process of mesalazine colon targeted controlled-release tablets, the stirring efficiency of the existing technology is not high, and it is not convenient to clean the inside of the equipment. Since the starch aqueous solution and hydrochloric acid need to be fully mixed during the preparation of pyrodextrin, and the starch aqueous solution has a certain viscosity, efficient stirring measures are required during stirring to ensure that the ingredients are mixed sufficiently evenly. After the stirring is completed, a large amount of material will be adhered to the inner wall of the stirring equipment, and corresponding treatment measures are also required. Summary of the invention

[0004] The purpose of the present invention is to provide a mesalazine colon targeted controlled-release tablet and a preparation method thereof, which can improve the stirring efficiency and have a measure for scraping off the attached materials, in order to solve the above-mentioned problems of insufficient stirring efficiency and a large amount of material adhering to the inner wall of the stirring device.

[0005] To achieve the above object, the present invention adopts the following technical scheme: a mesalazine colon targeted controlled-release tablet, comprising a core layer and a controlled-release layer, wherein the controlled-release layer is wrapped around the outside of the core layer, the core layer is composed of mesalazine and auxiliary material pyrodextrin, the controlled-release layer is composed of pyrodextrin, a plasticizer and a pore-forming agent, the auxiliary material pyrodextrin of the core layer and the pyrodextrin in the controlled-release layer are both made of starch as raw materials, and are prepared by hydrochloric acid acid hydrolysis, pre-drying and baking, the auxiliary material pyrodextrin in the core layer retains part of the crystalline structure and most of the α-1,4 glycosidic bonds of starch, and its structure has glucan and some irregular branched structures, and there is a certain steric hindrance in the molecule, the intermediate product obtained by decomposition and hydrolysis of pyrodextrin starch in the controlled-release layer under certain conditions, and its main structure retains the structure in which glucose residues of some starch are connected by glycosidic bonds, and the basic structural unit of starch is α-D-pyranose glucose, which is connected by α-1,4-glycosidic bonds to form a straight chain, and a small amount of α-1,6-glycosidic bonds form branches.

[0006] Preferably, the mass ratio of mesalazine in the tablet core layer is 80%, the mass ratio of the auxiliary material pyrodextrin in the tablet core layer is 20%, the mass ratio of the pyrodextrin in the controlled release layer is 80%, the mass ratio of the plasticizer in the controlled release layer is 10%, the mass ratio of the pore-forming agent in the controlled release layer is 10%, the mass ratio of the tablet core layer to the controlled release layer is 1:0.5-1:2, and the weight ratio of the auxiliary material pyrodextrin in the tablet core layer to the pyrodextrin in the controlled release layer is 1:2-1:3.

[0007] Preferably, the auxiliary materials pyrodextrin and pyrodextrin are both made from starch as raw materials, and the raw materials of the auxiliary materials pyrodextrin and pyrodextrin can be one or more of corn starch, wheat starch, rice starch, tapioca starch and potato starch.

[0008] Preferably, the plasticizer is wrapped in the outer layer of the tablet core layer following the controlled release layer, and the component of the plasticizer is triethyl citrate.

[0009] Preferably, the pore-forming agent is wrapped in the outer layer of the tablet core layer following the controlled release layer, and the pore-forming agent can be any one of lactose, mannitol and povidone.

[0010] A method for preparing mesalazine colon targeted controlled-release tablets, the specific preparation method is as follows:

[0011] S1: First, prepare the core layer material. Add hydrochloric acid to a starch aqueous solution with a mass concentration of 50%-60%, adjust the pH value to 2.5-3.5, stir at a speed of 300-400 rpm for 20-40 minutes, and then pre-dry, bake, wash and dry to obtain the core layer material;

[0012] S2: The preparation of the controlled release layer material is basically the same as the preparation method of the core layer material, except that the baking temperature is 125-150°C and the time is 1-5h, while the auxiliary material pyrodextrin in the core layer is baked at a temperature of 175-190°C for 2-4h;

[0013] S3: Grinding and sieving: Grinding the core layer material and the controlled release layer material separately and passing through a 100-120 mesh sieve;

[0014] S4: Finally, mesalazine and the auxiliary material pyrodextrin are evenly mixed and pressed into a tablet core layer, and then a controlled-release layer material is added for tableting, so as to obtain mesalazine colon-targeted controlled-release tablets with a double-layer tablet structure.

[0015] The preparation process of the above-mentioned mesalazine colon targeted controlled-release tablets also involves a stirring device, including a body, wherein the upper surface of the body is provided with a feed inlet, the bottom surface of the body is provided with a discharge port, and the feed inlet and the discharge port are both provided with sealing covers;

[0016] A stirring mechanism, the stirring mechanism includes a power component, two high-efficiency stirring components and two cleaning components, the power component includes a motor fixedly connected to the upper surface of the body through a bracket, the output end of the motor is fixedly connected to a No. 1 rotating shaft, the No. 1 rotating shaft is rotatably connected to the inner top surface of the body through a bearing, the inner bottom surface of the body is rotatably connected to a sleeve through a bearing, the inner bottom surface of the body is fixedly connected to a support column, and the bottom end of the No. 1 rotating shaft is fixedly connected to the upper surface of the sleeve.

[0017] Preferably, the high-efficiency stirring assembly includes a No. 1 bevel gear fixedly connected to the support column in the circumferential direction, and two No. 2 rotating shafts are arranged in the sleeve, and the two No. 2 rotating shafts are rotatably connected to the side wall of the sleeve through bearings, and the side ends of the two No. 2 rotating shafts are fixedly connected to the No. 2 bevel gears, and the two No. 2 bevel gears are meshed with the No. 1 bevel gear, and a plurality of stirring rods are fixedly connected to the two No. 2 rotating shafts at equal intervals in the circumference.

[0018] Preferably, the cleaning assembly includes a mounting plate fixedly connected to the side wall of the No. 1 rotating shaft, the bottom surface of the mounting plate is fixedly connected to a fixing plate, the side wall of the fixing plate is provided with a threaded through groove, a threaded rod is threadedly connected to the inner surface of the threaded through groove, the side end of the threaded rod is rotatably connected to a movable plate via a bearing, a scraper is provided on the side of the movable plate, the side wall of the scraper is fixedly connected to two No. 1 guide rods, both of the No. 1 guide rods are penetrated and slidably connected to the side wall of the movable plate, two springs are fixedly connected between the scraper and the movable plate, the side wall of the movable plate is fixedly connected to a No. 2 guide rod, and the No. 2 guide rod is penetrated and slidably connected to the side wall of the fixed plate.

[0019] Compared with the prior art, the advantages of the present invention are:

[0020] 1. The present invention provides a power component. When preparing the pyrodextrin required for the mesalazine colon targeted controlled-release tablets, the power component can simultaneously drive two high-efficiency stirring components and two cleaning components. Therefore, while achieving high-efficiency stirring, it can also process the attachments on the inner wall of the equipment, saving resources and reducing the power output required for the operation of the equipment, which is more in line with actual usage scenarios.

[0021] 2. The present invention provides a high-efficiency stirring component. When preparing the pyrodextrin required for the mesalazine colon targeted controlled-release tablets, the high-efficiency stirring component can make the starch aqueous solution and the hydrochloric acid mix more fully and evenly, thereby improving the stirring efficiency and saving the stirring time, and also helping to improve the quality of the pyrodextrin.

[0022] 3. The present invention provides a cleaning component. When preparing the pyrodextrin required for the mesalazine colon targeted controlled-release tablets, the power of the power component is used to scrape off the material attached to the inner wall of the equipment. While saving resources and reducing waste, it is also beneficial to reduce the labor intensity of subsequent equipment cleaning. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a schematic flow diagram of the preparation method of the present invention;

[0024] Figure 2 It is a schematic diagram of the three-dimensional structure analysis of the present invention;

[0025] Figure 3 It is a schematic diagram of a three-dimensional structural analysis from another viewing angle of the present invention;

[0026] Figure 4 It is a three-dimensional structural schematic diagram of the present invention;

[0027] Figure 5 for Figure 2 The enlarged view of point A in the middle;

[0028] Figure 6 for Figure 3 Enlarged view of point B in the middle.

[0029] In the figure, 1 is the machine body; 2 is the feed port; 3 is the discharge port; 4 is the motor; 5 is the first rotating shaft; 6 is the sleeve; 7 is the support column; 8 is the first bevel gear; 9 is the second rotating shaft; 10 is the second bevel gear; 11 is the stirring rod; 12 is the mounting plate; 13 is the fixed plate; 14 is the threaded rod; 15 is the moving plate; 16 is the scraper; 17 is the first guide rod; 18 is the spring; and 19 is the second guide rod. DETAILED DESCRIPTION

[0030] The following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[0031] A mesalazine colon-targeted controlled-release tablet comprises a core layer and a controlled-release layer, wherein the controlled-release layer is wrapped around the outside of the core layer, the core layer is composed of mesalazine and auxiliary material pyrodextrin, the controlled-release layer is composed of pyrodextrin, a plasticizer and a pore-forming agent, the auxiliary material pyrodextrin of the core layer and the pyrodextrin in the controlled-release layer are both made of starch as raw materials, and are prepared by hydrochloric acid acid hydrolysis, pre-drying and baking, the auxiliary material pyrodextrin in the core layer retains part of the crystalline structure and most of the α-1,4 glycosidic bonds of starch, and its structure has glucan and some irregular branched structures, and there is a certain steric hindrance in the molecule, the intermediate product obtained by decomposition and hydrolysis of pyrodextrin starch in the controlled-release layer under certain conditions, and its main structure retains the structure in which glucose residues of some starch are connected by glycosidic bonds, and the basic structural unit of starch is α-D-pyranose glucose, which is connected by α-1,4-glycosidic bonds to form a straight chain, and there is also a small amount of α-1 ,6-glycosidic bonds form branches, mesalazine accounts for 80% of the mass proportion of the core layer, the auxiliary material pyrodextrin accounts for 20% of the mass proportion of the core layer, the mass proportion of pyrodextrin in the controlled release layer is 80%, the mass proportion of the plasticizer in the controlled release layer is 10%, the mass proportion of the pore-forming agent in the controlled release layer is 10%, the mass ratio of the core layer to the controlled release layer is 1:0.5-1:2, the weight ratio of the auxiliary material pyrodextrin in the core layer to the pyrodextrin in the controlled release layer is 1:2-1:3, the auxiliary materials pyrodextrin and pyrodextrin are both made from starch, the raw materials of the auxiliary materials pyrodextrin and pyrodextrin can be one or more of corn starch, wheat starch, rice starch, cassava starch and potato starch, the plasticizer follows the controlled release layer and is wrapped in the outer layer of the core layer, the component of the plasticizer is triethyl citrate, the pore-forming agent follows the controlled release layer and is wrapped in the outer layer of the core layer, the pore-forming agent can be any one of lactose, mannitol and povidone.

[0032] like Figure 1-Figure 6 As shown, a method for preparing mesalazine colon targeted controlled-release tablets, the specific preparation method is as follows:

[0033] S1: First, prepare the core layer material. Add hydrochloric acid to a starch aqueous solution with a mass concentration of 50%-60%, adjust the pH value to 2.5-3.5, stir at a speed of 300-400 rpm for 20-40 minutes, and then pre-dry, bake, wash and dry to obtain the core layer material;

[0034] S2: The preparation of the controlled release layer material is basically the same as the preparation method of the core layer material, except that the baking temperature is 125-150°C and the time is 1-5h, while the auxiliary material pyrodextrin in the core layer is baked at a temperature of 175-190°C for 2-4h;

[0035] S3: Grinding and sieving: Grinding the core layer material and the controlled release layer material separately and passing through a 100-120 mesh sieve;

[0036] S4: Finally, mesalazine and the auxiliary material pyrodextrin are evenly mixed and pressed into a tablet core layer, and then a controlled-release layer material is added for tableting, so as to obtain mesalazine colon-targeted controlled-release tablets with a double-layer tablet structure.

[0037] The preparation process of the above-mentioned mesalazine colon targeted controlled-release tablets also involves a stirring device, including a body 1, a feed port 2 is provided on the upper surface of the body 1, a discharge port 3 is provided on the bottom surface of the body 1, and sealing covers are provided outside the feed port 2 and the discharge port 3.

[0038] A stirring mechanism, the stirring mechanism includes a power component, two high-efficiency stirring components and two cleaning components. The power component includes a motor 4 fixedly connected to the upper surface of the body 1 through a bracket, the output end of the motor 4 is fixedly connected to a No. 1 rotating shaft 5, the No. 1 rotating shaft 5 is rotatably connected to the inner top surface of the body 1 through a bearing, the inner bottom surface of the body 1 is rotatably connected to a sleeve 6 through a bearing, the inner bottom surface of the body 1 is fixedly connected to a support column 7, the bottom end of the No. 1 rotating shaft 5 is fixedly connected to the upper surface of the sleeve 6, the high-efficiency stirring component includes a No. 1 bevel gear 8 fixedly connected to the support column 7 in the circumferential direction, two No. 2 rotating shafts 9 are arranged in the sleeve 6, the two No. 2 rotating shafts 9 are both rotatably connected to the side wall of the sleeve 6 through bearings, the side ends of the two No. 2 rotating shafts 9 are fixedly connected to No. 2 bevel gears 10, and the two No. 2 bevel gears 10 are connected to a The No. 1 bevel gears 8 are meshed with each other, and a plurality of stirring rods 11 are fixedly connected to the two No. 2 rotating shafts 9 at equidistant intervals in the circumferential direction. The cleaning assembly includes a mounting plate 12 fixedly connected to the side wall of the No. 1 rotating shaft 5, and a fixing plate 13 is fixedly connected to the bottom surface of the mounting plate 12. The side wall of the fixing plate 13 is provided with a threaded through groove, and a threaded rod 14 is threadedly connected to the inner thread of the threaded through groove. The side end of the threaded rod 14 is rotatably connected to a movable plate 15 through a bearing, and a scraper 16 is provided on the side of the movable plate 15. Two No. 1 guide rods 17 are fixedly connected to the side wall of the scraper 16, and the two No. 1 guide rods 17 are both penetrated and slidably connected to the side wall of the movable plate 15. Two springs 18 are fixedly connected between the scraper 16 and the movable plate 15, and a No. 2 guide rod 19 is fixedly connected to the side wall of the movable plate 15, and the No. 2 guide rod 19 penetrates and is slidably connected to the side wall of the fixed plate 13.

[0039] The working principle of the present invention is as follows:

[0040] When preparing pyrodextrin, starch aqueous solution and hydrochloric acid are added into the machine body 1 through the feed port 2, and then the motor 4 is started. The motor 4 drives the No. 1 rotating shaft 5 to rotate, and then drives the sleeve 6 to rotate. When the sleeve rotates, it drives multiple No. 2 rotating shafts 9 to revolve around the No. 1 rotating shaft 5. The multiple No. 2 rotating shafts 9 will drive multiple No. 2 bevel gears 10 to revolve around the No. 1 rotating shaft 5. The multiple revolving No. 2 bevel gears 10 will mesh with the No. 1 bevel gear 8 to rotate themselves. The multiple No. 2 bevel gears 10 will drive the multiple No. 2 rotating shafts 9 to rotate, and then drive the multiple stirring rods 11 to rotate while revolving. In this way, the stirring efficiency is improved, and efficient stirring is achieved, so that the starch aqueous solution and the hydrochloric acid are mixed more evenly.

[0041] When the No. 1 rotating shaft 5 rotates, it will drive the mounting plate 12 to revolve. Here, taking a cleaning component as an example, the mounting plate 12 rotates through the fixed plate 13, the movable plate 15, and the two No. 1 guide rods 17 to drive the scraper 16 to revolve. Under the action of the two springs 18, the scraper 16 will always be in contact with the inner wall of the body 1, and thus during the revolution, the material attached to the inner wall of the body 1 can be scraped off. The threaded rod 14 is used to adjust the scraping force. By rotating the threaded rod 14, the threaded rod 14 will engage with the threaded through hole, thereby driving the movable plate 15 to move. The closer the movable plate 15 is to the scraper 16, the more the spring 18 will be compressed. At this time, the greater the scraping force is, which is more suitable for materials with high viscosity. On the contrary, controlling the movable plate 15 to move away from the scraper 16 can reduce the scraping force, which can be adjusted according to specific circumstances.

[0042] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A mesalazine colon targeted controlled-release tablet, comprising a core layer and a controlled-release layer, characterized in that: The controlled release layer is wrapped around the outside of the tablet core layer, the tablet core layer is composed of mesalazine and auxiliary material pyrodextrin, the controlled release layer is composed of pyrodextrin, a plasticizer and a pore-forming agent, the auxiliary material pyrodextrin of the tablet core layer and the pyrodextrin in the controlled release layer are both made of starch as raw material, and are prepared by hydrochloric acid acid hydrolysis, pre-drying and baking, the auxiliary material pyrodextrin in the tablet core layer retains part of the crystalline structure and most of the α-1,4 glycosidic bonds of starch, its structure has glucan and some irregular branched structures, and there is a certain steric hindrance in the molecule, the intermediate product obtained by decomposition and hydrolysis of pyrodextrin starch in the controlled release layer under certain conditions, its main structure retains the structure in which glucose residues of some starch are connected by glycosidic bonds, the basic structural unit of starch is α-D-pyranose glucose, which is connected by α-1,4-glycosidic bonds to form a straight chain, and a small amount of α-1,6-glycosidic bonds form branches.

2. A mesalazine colon targeted controlled-release tablet according to claim 1, characterized in that: The mass ratio of mesalazine in the tablet core layer is 80%, the mass ratio of the auxiliary material pyrodextrin in the tablet core layer is 20%, the mass ratio of the pyrodextrin in the controlled release layer is 80%, the mass ratio of the plasticizer in the controlled release layer is 10%, the mass ratio of the pore-forming agent in the controlled release layer is 10%, the mass ratio of the tablet core layer to the controlled release layer is 1:0.5-1:2, and the weight ratio of the auxiliary material pyrodextrin in the tablet core layer to the pyrodextrin in the controlled release layer is 1:2-1:

3.

3. A mesalazine colon targeted controlled-release tablet according to claim 1, characterized in that: The auxiliary materials pyrodextrin and pyrodextrin are both made from starch as raw materials, and the raw materials of the auxiliary materials pyrodextrin and pyrodextrin can be one or more of corn starch, wheat starch, rice starch, cassava starch and potato starch.

4. A mesalazine colon targeted controlled-release tablet according to claim 1, characterized in that: The plasticizer is wrapped in the outer layer of the tablet core layer following the controlled release layer, and the component of the plasticizer is triethyl citrate.

5. A mesalazine colon targeted controlled-release tablet according to claim 1, characterized in that: The pore-forming agent is wrapped in the outer layer of the tablet core layer following the controlled release layer, and the pore-forming agent can be any one of lactose, mannitol and povidone.

6. A method for preparing the mesalazine colon targeted controlled-release tablets as claimed in claim 1, characterized in that: The specific preparation method is as follows: S1: First, prepare the core layer material. Add hydrochloric acid to a starch aqueous solution with a mass concentration of 50%-60%, adjust the pH value to 2.5-3.5, stir at a speed of 300-400 rpm for 20-40 minutes, and then pre-dry, bake, wash and dry to obtain the core layer material; S2: The preparation of the controlled release layer material is basically the same as the preparation method of the core layer material, except that the baking temperature is 125-150°C and the time is 1-5h, while the auxiliary material pyrodextrin in the core layer is baked at a temperature of 175-190°C for 2-4h; S3: Grinding and sieving: Grinding the core layer material and the controlled release layer material separately and passing through a 100-120 mesh sieve; S4: Finally, mesalazine and the auxiliary material pyrodextrin are evenly mixed and pressed into a tablet core layer, and then a controlled-release layer material is added for tableting, so as to obtain mesalazine colon-targeted controlled-release tablets with a double-layer tablet structure. The preparation process of the above-mentioned mesalazine colon targeted controlled-release tablets also involves a stirring device, comprising a body (1), wherein the upper surface of the body (1) is provided with a feed port (2), the bottom surface of the body (1) is provided with a discharge port (3), and the feed port (2) and the discharge port (3) are both provided with sealing covers. A stirring mechanism, the stirring mechanism comprising a power component, two high-efficiency stirring components and two cleaning components, the power component comprising a motor (4) fixedly connected to the upper surface of a body (1) via a bracket, the output end of the motor (4) being fixedly connected to a first rotating shaft (5), the first rotating shaft (5) being rotatably connected to the inner top surface of the body (1) via a bearing, the inner bottom surface of the body (1) being rotatably connected to a sleeve (6) via a bearing, the inner bottom surface of the body (1) being fixedly connected to a support column (7), the bottom end of the first rotating shaft (5) being fixedly connected to the upper surface of the sleeve (6).

7. The method for preparing a mesalazine colon targeted controlled-release tablet according to claim 6, characterized in that: The high-efficiency stirring assembly comprises a first bevel gear (8) fixedly connected to the support column (7) in the circumferential direction, two second rotating shafts (9) are arranged in the sleeve (6), the two second rotating shafts (9) are rotatably connected to the side wall of the sleeve (6) through bearings, the side ends of the two second rotating shafts (9) are fixedly connected to the second bevel gears (10), the two second bevel gears (10) are meshed with the first bevel gear (8), and the two second rotating shafts (9) are fixedly connected to a plurality of stirring rods (11) at equal intervals in the circumferential direction.

8. The method for preparing a mesalazine colon targeted controlled-release tablet according to claim 6, characterized in that: The cleaning assembly comprises a mounting plate (12) fixedly connected to the side wall of the first rotating shaft (5); a fixing plate (13) is fixedly connected to the bottom surface of the mounting plate (12); a side wall of the fixing plate (13) is provided with a threaded through groove; a threaded rod (14) is threadedly connected to the inner surface of the threaded through groove; a side end of the threaded rod (14) is rotatably connected to a movable plate (15) via a bearing; a scraper (16) is provided on the side of the movable plate (15); two first guide rods (17) are fixedly connected to the side wall of the scraper (16); the two first guide rods (17) are both slidably connected to the side wall of the movable plate (15); two springs (18) are fixedly connected between the scraper (16) and the movable plate (15); a second guide rod (19) is fixedly connected to the side wall of the movable plate (15); the second guide rod (19) is slidably connected to the side wall of the fixing plate (13).

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