Immobilized enzyme reactor for bisoprolol synthesis

Abstract

The utility model relates to the technical field of reactors, and particularly discloses an immobilized enzyme reactor for bisoprolol synthesis, which comprises a reaction tank, a tank cover mounted at the top of the reaction tank and a bottom support mounted at the bottom of the reaction tank, a feed pipe is mounted at the top of the tank cover, a discharge pipe is mounted at the bottom of the bottom support, and the bottom support is fixed at the bottom of the reaction tank through a fastener. A plurality of positioning rods extending into the reaction tank are mounted at the top of the bottom support, a group of packed columns are mounted among the plurality of positioning rods, and limiting rings abutting against the tops of the packed columns are mounted on the inner wall of the reaction tank; the bottom support is fixed at the bottom of the reaction tank through the fastener, the packed column can be taken out by moving out the bottom support, the reaction tank does not need to be disassembled, the immobilized enzyme in the regenerated packed column is easily and quickly replaced, and the influence on the productivity in the synthesis of the sololol is reduced.

Description

Technical Field

[0001] This invention relates to the field of reactor technology, specifically to an immobilized enzyme reactor for bisoprolol synthesis. Background Technology

[0002] Bisoprolol, with the molecular formula C18H31NO4, is a yellow, oily liquid and a β-receptor blocker. It selectively works by blocking the binding of adrenaline to β1-receptors without affecting β2-receptors, making it a β1-blocker with high affinity and selectivity for cardiac β1-receptors. S-(-)-bisoprolol is the levorotatory isomer, and its synthesis involves multiple steps, including the introduction of a chiral center, potentially using chiral auxiliaries or asymmetric catalysis. For example, a packed-bed reactor or microchannel reactor can be used, filled with immobilized lipases (such as CAL-B) or ketone reductases, to catalyze an asymmetric reduction reaction, producing an S-configuration alcohol with a high ee value. A reactor is required in this process.

[0003] A fixed-bed reactor disclosed in existing patent publication number CN219377077U includes a fixed-bed reactor body, a fixed bed layer inside the fixed-bed reactor body, positioning rings at the upper and lower ends of the fixed bed layer, a support plate at the bottom of the fixed bed layer, a support rod at the bottom of the support plate, an electric heating bend inside the fixed bed layer, heating boxes on both sides of the fixed-bed reactor body, a fixed seat inside the heating box, an electric heating tube inside the fixed seat, and an end cap at the top of the fixed-bed reactor body. Raw materials are added to the fixed-bed reactor body through a feed hopper, filtered through a filter screen in the feed hopper, and then enter the feed pipe. The raw material gas flow in the feed pipe is ejected from the strip-shaped holes, dispersed by the wire mesh, and then enters the fixed bed layer, thereby ensuring that the raw material gas enters the fixed bed layer uniformly.

[0004] The aforementioned reactor uses a fixed bed for reaction, which is secured inside the reactor by support rods, support plates, and positioning rings. Disassembly requires complete removal of the end cap, heating box, and heating tubes, making the operation complex and time-consuming. Furthermore, the catalyst regeneration or replacement cycle is long, impacting production capacity. Therefore, an immobilized enzyme reactor for bisoprolol synthesis is proposed. Utility Model Content

[0005] The purpose of this invention is to provide an immobilized enzyme reactor for bisoprolol synthesis to solve the problems mentioned in the background art.

[0006] To achieve the above objectives, this utility model provides the following technical solution:

[0007] An immobilized enzyme reactor for bisoprolol synthesis includes a reaction vessel, a lid mounted on top of the reaction vessel, and a base mounted at the bottom of the reaction vessel. A feed pipe is installed on the top of the lid, and a discharge pipe is installed on the bottom of the base. The base is fixed to the bottom of the reaction vessel by fasteners. A plurality of positioning rods extending into the reaction vessel are installed on the top of the base. A set of filling columns is installed between the plurality of positioning rods. A limiting ring that abuts against the top of the filling columns is installed on the inner wall of the reaction vessel.

[0008] The reaction vessel is equipped with a partition plate on the top, which has a feed hole. The bottom of the partition plate is equipped with a material feeding device to spray the material output from the feed hole onto the filling column. The top of the vessel cover is equipped with a drive unit for driving the material feeding device.

[0009] In one alternative embodiment: the fastener includes a rotating seat and a rotating rod rotatably connected to the end of the rotating seat. The end of the rotating seat away from the rotating rod is fixedly connected to the bottom of the outer ring of the top of the base. The end of the rotating rod away from the rotating seat is threadedly connected to a threaded sleeve. A rotating handle is connected to the threaded sleeve. A groove for inserting the rotating rod is provided at the bottom outer ring of the reaction vessel.

[0010] In one alternative: the top of the reaction vessel is provided with an annular groove for installing a separator plate, the outer wall of the separator plate is in contact with the annular groove, the outer diameter of the separator plate is larger than the inner diameter of the reaction vessel, and the reaction vessel is connected to the vessel cover by fastening bolts.

[0011] In one alternative: the feeding component includes a central rod and a spiral blade connected to the central rod. The top of the spiral blade is provided with an arc-shaped isolation plate mounted on the central rod. The top of the arc-shaped isolation plate is slidably engaged with the bottom of the separator plate. The arc-shaped isolation plate is provided with a notch corresponding to the feed hole.

[0012] In one alternative: the drive unit includes a drive unit mounted on the top of the can lid, the power output end of the drive unit is connected to the top of the center rod, and the partition plate is provided with a rotating hole that rotatably engages with the center rod.

[0013] In one alternative: the outer wall of the reaction vessel is connected to three sets of support frames, which are evenly arranged around the circumference of the reaction vessel's axis.

[0014] In one alternative: a heating layer is provided between the inner and outer walls of the reaction vessel.

[0015] Compared with the prior art, the beneficial effects of this utility model are:

[0016] In this invention, the base is fixed to the bottom of the reaction vessel with fasteners. The base can be removed to take out the packing column without disassembling the reaction vessel. This allows for easy and quick replacement of the immobilized enzyme in the regenerated packing column, reducing the impact on the production capacity in the synthesis of bisoprolol.

[0017] In this invention, the material is dispersed by rotating the feeding component, so that the material evenly covers the surface of the filling column, reducing mass transfer resistance and optimizing the uniformity of fluid and enzyme distribution. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the structure of this utility model.

[0019] Figure 2 This is a schematic diagram of the internal structure of the reaction vessel in this utility model.

[0020] Figure 3 This is a schematic diagram of the structure of the separator disk and the spiral blade in this utility model.

[0021] Figure 4 In this utility model Figure 3 A schematic diagram of the split structure.

[0022] Figure 5 This is a partial structural schematic diagram of the present invention.

[0023] In the diagram: 1. Reaction vessel; 2. Vessel lid; 3. Base; 4. Support frame; 5. Drive unit; 6. Feed pipe; 7. Center rod; 8. Spiral blade; 9. Separator plate; 10. Feed hole; 11. Arc-shaped isolation plate; 12. Rotating seat; 13. Rotating rod; 14. Threaded sleeve; 15. Rotating handle; 16. Groove; 17. Limiting ring; 18. Filling column; 19. Positioning rod; 20. Discharge pipe. Detailed Implementation

[0024] In this utility model, unless otherwise explicitly specified and limited, the terms "installation," "connection," "joining," and "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components, unless otherwise explicitly limited. Those skilled in the art can understand the specific meaning of the above terms in this utility model according to the specific circumstances.

[0025] The technical solutions of the present utility model will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Obviously, the described embodiments are only some embodiments of the present utility model, and not all embodiments. Based on the embodiments of the present utility model, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the protection scope of the present utility model.

[0026] Please see Figures 1-5In this embodiment, an immobilized enzyme reactor for bisoprolol synthesis includes a reaction vessel 1, a lid 2 installed on top of the reaction vessel 1, and a base 3 installed at the bottom of the reaction vessel 1. A feed pipe 6 is installed on the top of the lid 2, and a discharge pipe 20 is installed on the bottom of the base 3. The base 3 is fixed to the bottom of the reaction vessel 1 by fasteners. A plurality of positioning rods 19 extending into the reaction vessel 1 are installed on the top of the base 3, and a set of packing columns 18 are installed between the plurality of positioning rods 19. A limiting ring 17 that abuts against the top of the packing columns 18 is installed on the inner wall of the reaction vessel 1. The immobilized enzyme carrier is loaded in the packing columns 18, and the substrate comes into contact with the enzyme and undergoes a catalytic reaction when flowing through the packing columns. The product after the reaction is discharged from the discharge pipe 20 at the bottom of the base 3, completing the continuous flow process.

[0027] The top of the reaction vessel 1 is equipped with a partition plate 9, the partition plate 9 is provided with a feed hole 10, and the bottom of the partition plate 9 is provided with a material feeding device for sprinkling the material output from the feed hole 10 to the filling column 18. The top of the vessel cover 2 is equipped with a drive unit 5 for driving the material feeding device to work.

[0028] Using the above scheme, the material enters the reaction tank 1 through the feed pipe 6 at the top of the tank cover 2, and flows into the interior of the reaction tank 1 through the feed hole 10 of the partition plate 9. The drive component 5 drives the feeding component to work. As the feeding component rotates, it sprinkles the material onto the surface of the filling column 18, thereby improving the uniformity of the material distribution on the surface of the filling column 18.

[0029] Please see Figure 5 The fastener includes a rotating seat 12 and a rotating rod 13 rotatably connected to the end of the rotating seat 12. The end of the rotating seat 12 away from the rotating rod 13 is fixedly connected to the bottom of the top outer ring of the base 3. The end of the rotating rod 13 away from the rotating seat 12 is threadedly connected to a threaded sleeve 14. A rotating handle 15 is connected to the threaded sleeve 14. A groove 16 for inserting the rotating rod 13 is provided at the bottom outer ring of the reaction vessel 1. Specifically, by rotating the handle 15 to loosen the threaded sleeve 14, the rotating rod 13 can be moved away from the groove 16, and the base 3 can be quickly disassembled to replace or regenerate the immobilized enzyme in the filling column 18.

[0030] Furthermore, the top of the reaction vessel 1 is provided with an annular groove for installing the partition plate 9. The outer wall of the partition plate 9 is in contact with the annular groove. The outer diameter of the partition plate 9 is larger than the inner diameter of the reaction vessel 1. The reaction vessel 1 is connected to the vessel cover 2 by fastening bolts.

[0031] Please see Figures 2 to 4The feeding component includes a central rod 7 and a spiral blade 8 connected to the central rod 7. The top of the spiral blade 8 is provided with an arc-shaped isolation plate 11 installed on the central rod 7. The top of the arc-shaped isolation plate 11 is slidably engaged with the bottom of the separator plate 9. The arc-shaped isolation plate 11 is provided with a notch corresponding to the feed hole 10. When the spiral blade 8 rotates, the substrate is evenly dispersed to the surface of the filling column 18 by centrifugal force to avoid excessive local concentration.

[0032] Please see Figure 2 The driving component 5 includes a driving component 5 installed on the top of the can lid 2. The power output end of the driving component 5 is connected to the top of the center rod 7. The partition plate 9 is provided with a rotating hole that rotates with the center rod 7.

[0033] Please see Figure 1 The outer wall of the reaction vessel 1 is connected to three sets of support frames 4, which are evenly arranged around the axis of the reaction vessel 1. The support frames 4 provide support and enhance the stability of the equipment.

[0034] Furthermore, a heating layer is provided between the inner and outer walls of the reaction vessel 1; in practical applications, electric heating or a circulating water bath can be used to maintain a constant temperature environment to ensure stable enzyme catalytic activity.

[0035] The working principle of this utility model is as follows: the material enters the reaction tank 1 through the feed pipe 6 at the top of the tank cover 2, and flows into the interior of the reaction tank 1 through the feed hole 10 of the partition plate 9. The driving component 5 drives the central rod 7 to rotate, and the spiral blade 8 rotates. Due to the notch setting of the arc-shaped isolation plate 11, the material enters the spiral blade 8 intermittently. As the spiral blade 8 rotates, it sprinkles the material onto the surface of the packed column 18, improving the uniformity of the material distribution on the surface of the packed column 18. The material flows through the immobilized enzyme area of ​​the packed column 18, where the enzyme combines with the substrate and catalyzes the generation of products (such as chiral alcohols). The reaction liquid flows out of the reactor, and the immobilized enzyme is retained in the reactor for recycling. This method can be applied to the asymmetric reduction step of S-(-)-bisoprolol.

[0036] The above description is merely a preferred embodiment of the present utility model and is not intended to limit the present utility model in any other way. Any person skilled in the art may make changes or modifications to the above-disclosed technical content to create equivalent embodiments for application in other fields. However, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present utility model without departing from the technical solution of the present utility model shall still fall within the protection scope of the technical solution of the present utility model.

Claims

1. An immobilized enzyme reactor for bisoprolol synthesis, comprising a reaction vessel (1), a lid (2) mounted on top of the reaction vessel (1), and a base (3) mounted on the bottom of the reaction vessel (1). Its features are: The top of the tank cover (2) is equipped with a feed pipe (6), the bottom of the base (3) is equipped with a discharge pipe (20), the base (3) is fixed to the bottom of the reaction tank (1) by fasteners, the top of the base (3) is equipped with a number of positioning rods (19) extending into the reaction tank (1), a set of filling columns (18) is installed between the number of positioning rods (19), and the inner wall of the reaction tank (1) is equipped with a limiting ring (17) that abuts against the top of the filling column (18). The reaction vessel (1) is equipped with a partition plate (9) on top, and a feed hole (10) is provided on the partition plate (9). A material feeding device is provided at the bottom of the partition plate (9) to sprinkle the material output from the feed hole (10) to the filling column (18). A drive device (5) is installed on the top of the tank cover (2) to drive the material feeding device to work.

2. The immobilized enzyme reactor for bisoprolol synthesis according to claim 1, characterized in that: The fastener includes a rotating seat (12) and a rotating rod (13) rotatably connected to the end of the rotating seat (12). The end of the rotating seat (12) away from the rotating rod (13) is fixedly connected to the bottom of the top outer ring of the base (3). The end of the rotating rod (13) away from the rotating seat (12) is threadedly connected to a threaded sleeve (14). A rotating handle (15) is connected to the threaded sleeve (14). A groove (16) for inserting the rotating rod (13) is provided at the bottom outer ring of the reaction vessel (1).

3. The immobilized enzyme reactor for bisoprolol synthesis according to claim 1, characterized in that: The top of the reaction vessel (1) is provided with an annular groove for installing a partition plate (9). The outer wall of the partition plate (9) is in contact with the annular groove. The outer diameter of the partition plate (9) is larger than the inner diameter of the reaction vessel (1). The reaction vessel (1) is connected to the vessel cover (2) by fastening bolts.

4. The immobilized enzyme reactor for bisoprolol synthesis according to claim 3, characterized in that: The feeding component includes a central rod (7) and a spiral blade (8) connected to the central rod (7). The top of the spiral blade (8) is provided with an arc-shaped isolation plate (11) installed on the central rod (7). The top of the arc-shaped isolation plate (11) is slidably engaged with the bottom of the separator plate (9). The arc-shaped isolation plate (11) is provided with a notch corresponding to the feed hole (10).

5. The immobilized enzyme reactor for bisoprolol synthesis according to claim 4, characterized in that: The drive unit (5) includes a drive unit (5) installed on the top of the can lid (2). The power output end of the drive unit (5) is connected to the top of the center rod (7). The partition plate (9) is provided with a rotating hole that rotates with the center rod (7).

6. The immobilized enzyme reactor for bisoprolol synthesis according to claim 1, characterized in that: The outer wall of the reaction vessel (1) is connected to three sets of support frames (4), which are evenly arranged around the circumference of the reaction vessel (1) with the axis of the reaction vessel (1) as the center.

7. The immobilized enzyme reactor for bisoprolol synthesis according to claim 1, characterized in that: A heating layer is provided between the inner and outer walls of the reaction vessel (1).

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