A high-efficiency continuous flow reaction device for synthesis of bulk drug

Abstract

The utility model relates to continuous flow reaction device technical field, concretely relates to a kind of high-efficiency continuous flow reaction device for raw material medicine synthesis, including mixing block, reaction component and reaction box, mixing block is fixedly installed with reaction component side face, reaction component is fixedly installed in reaction box;Reaction component includes microchannel pipe, No. 1 fixed plate, No. 2 fixed plate and heat conduction layer, microchannel pipe is bently arranged, the inner side surface of No. 1 fixed plate and No. 2 fixed plate is uniformly provided with the arc-shaped recess of bending trend consistent with microchannel pipe, and heat conduction layer is fixedly connected with the inner side wall of arc-shaped recess.The utility model microchannel pipe and mixing block adopt the material that satisfies the corrosion resistance and compliance requirement of raw material medicine synthesis, and No. 1 fixed plate and No. 2 fixed plate adopt carbon steel material, cooperate the processing mode that microchannel pipe is separated from fixed plate, avoid the case that the price of overall structure material is higher, to reduce cost.

Description

Technical Field

[0001] This utility model relates to the technical field of continuous flow reaction devices, specifically a high-efficiency continuous flow reaction device for the synthesis of active pharmaceutical ingredients. Background Technology

[0002] In the field of active pharmaceutical ingredient (API) synthesis, continuous flow reaction technology is widely used because it can achieve precise temperature control and improve reaction efficiency. As a core device, the microchannel reactor's structural design is crucial. Most existing continuous flow reactors adopt an integral structure, with reaction channels etched into a single piece of material. When the internal pipelines are partially blocked or damaged, the entire reactor needs to be replaced, resulting in high maintenance costs. In addition, to meet the requirements of API synthesis for material corrosion resistance and compliance, existing reactors mostly use high-priced materials, such as 316L stainless steel and Hastelloy, which increases material costs. If low-cost materials are used to reduce costs, the contact between the raw materials and the low-cost materials will affect the reaction safety and product purity.

[0003] Therefore, a high-efficiency continuous flow reactor for the synthesis of active pharmaceutical ingredients is proposed to solve the problems mentioned above. Utility Model Content

[0004] To address the shortcomings of existing technologies, this invention provides a high-efficiency continuous flow reaction device for the synthesis of active pharmaceutical ingredients (APIs). The microchannel tubes and mixing blocks are made of materials that meet the requirements for corrosion resistance and compliance in API synthesis, while the first and second fixing plates are made of carbon steel. By processing the microchannel tubes and fixing plates separately, the high cost of integral structure materials is avoided, thereby reducing costs and solving the problems mentioned in the background technology.

[0005] To achieve the above objectives, the present invention provides the following technical solution: including a mixing block, a reaction component, and a reaction chamber, wherein the mixing block is fixedly installed on the side of the reaction component, and the reaction component is fixedly installed inside the reaction chamber;

[0006] The reaction assembly includes a microchannel tube, a first fixing plate, a second fixing plate, and a heat-conducting layer. The microchannel tube is bent, and the inner surfaces of the first and second fixing plates are provided with arc-shaped grooves that are consistent with the bending direction of the microchannel tube. The heat-conducting layer is fixedly connected to the inner wall of the arc-shaped groove.

[0007] Preferably, the microchannel tube is divided into a connecting section and a mixing section, which are arranged alternately. The microchannel tube is bent at the connection between the connecting section and the mixing section, and the angle between the connecting section and the mixing section is less than 10 degrees.

[0008] Preferably, a semi-spinning cone cavity is provided at the position corresponding to the mixing section of the arc-shaped groove, and the two semi-spinning cone cavities are combined into a spinning cone cavity. An exhaust hole is provided on the surface of the semi-spinning cone cavity, and the exhaust hole penetrates the first fixing plate and the second fixing plate.

[0009] Preferably, the diameter of the middle part of the mixing section is larger than the diameters of both ends, and the outer surface of the microchannel tube is in contact with the inner surface of the heat-conducting layer.

[0010] Preferably, the inner side of the first fixing plate is provided with a positioning pin, the second fixing plate is provided with a positioning hole corresponding to the positioning pin, the contact surface of the first fixing plate and the second fixing plate is a precision machined surface, and the first fixing plate and the second fixing plate are fixed together by bolts.

[0011] Preferably, the mixing block has an F-shaped channel inside, and one end of the microchannel tube is inserted into the F-shaped channel and fits against the inner surface of the F-shaped channel.

[0012] Preferably, the bottom of the reaction chamber is provided with a plurality of slots that are adapted to the width of the bottom of the reaction component, and a top cover is fixedly installed on the top of the reaction chamber, and the bottom surface of the top cover is provided with a groove that is adapted to the width of the top of the reaction component.

[0013] Preferably, the top cover has a feeding pipe interface on its upper surface, which is connected to the two interfaces of the F-shaped channel, and the top cover has a discharge pipe interface on its side, which is connected to the microchannel tube.

[0014] Preferably, the first and second fixing plates are provided with heat dissipation fins on the side away from the microchannel tube, and the opposite sides of the reaction chamber are provided with inlet and outlet for conveying coolant.

[0015] Compared with the prior art, this utility model provides a high-efficiency continuous flow reaction device for the synthesis of active pharmaceutical ingredients, which has the following beneficial effects:

[0016] 1. The microchannel tubes and mixing blocks are made of materials that meet the requirements for corrosion resistance and compliance in the synthesis of active pharmaceutical ingredients, while the No. 1 and No. 2 fixing plates are made of carbon steel. The microchannel tubes and fixing plates are processed separately to avoid the high cost of integral structural materials, thereby reducing costs.

[0017] 2. The F-shaped channel allows the two raw materials to be initially mixed before entering the microchannel tube. The microchannel tube is curved and the diameter in the middle of the mixing section is larger than that at both ends. Combined with the spindle cavity structure, strong turbulence is formed during the flow, which improves the mixing effect and promotes complete reaction.

[0018] 3. The heat-conducting layer is made of copper. Taking advantage of its relatively soft texture, after the No. 1 and No. 2 fixing plates are positioned by positioning pins and bolts, they are tightly attached to the outer side of the microchannel tube by interference fit. Combined with the heat dissipation fins and the circulation of coolant in the reaction chamber, the heat dissipation efficiency is improved.

[0019] 4. The microchannel tubes can be disassembled and installed individually. When a single microchannel tube is damaged, there is no need to replace the entire device, reducing maintenance costs. Multiple reaction components are installed in parallel through slots. During use, different numbers of reaction components can be connected as needed to improve efficiency and meet different production capacity requirements. Attached Figure Description

[0020] The accompanying drawings, which are included to provide a further understanding of this application and form part of this application, illustrate exemplary embodiments of this application and are used to explain this application, but do not constitute an undue limitation of this application. In the drawings:

[0021] Figure 1 An isometric structural schematic diagram of the high-efficiency continuous flow reactor for the synthesis of active pharmaceutical ingredients according to this utility model;

[0022] Figure 2 A schematic diagram of the internal structure of the reaction chamber provided for the high-efficiency continuous flow reaction apparatus for the synthesis of active pharmaceutical ingredients of this utility model;

[0023] Figure 3 A schematic cross-sectional view of the connection between the mixing block and the reaction components in the high-efficiency continuous flow reaction apparatus for the synthesis of active pharmaceutical ingredients of this utility model.

[0024] Figure 4 A schematic diagram of the reaction components provided for the high-efficiency continuous flow reaction apparatus for the synthesis of active pharmaceutical ingredients according to this utility model;

[0025] Figure 5 This is a schematic diagram of the exploded structure of the reaction components provided for the high-efficiency continuous flow reaction apparatus for the synthesis of active pharmaceutical ingredients according to this utility model.

[0026] In the diagram: 1. Mixing block; 2. Reaction assembly; 3. Reaction chamber; 4. Arc-shaped groove; 5. Connecting section; 6. Mixing section; 7. Semi-spindle conical cavity; 8. Exhaust port; 9. Positioning pin; 10. Positioning hole; 11. F-shaped channel; 12. Slot; 13. Top cover; 14. Feed pipe interface; 15. Discharge pipe interface; 16. Heat dissipation fins; 201. Microchannel tube; 202. Fixing plate No. 1; 203. Fixing plate No. 2; 204. Thermal conductive layer. Detailed Implementation

[0027] 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. Example

[0028] Please see Figure 1 - Figure 5 This embodiment discloses a high-efficiency continuous flow reaction apparatus for the synthesis of active pharmaceutical ingredients, comprising a mixing block 1, a reaction assembly 2, and a reaction chamber 3. The mixing block 1 is fixedly installed on the side of the reaction assembly 2, and the reaction assembly 2 is fixedly installed inside the reaction chamber 3. The reaction assembly 2 includes a microchannel tube 201, a first fixing plate 202, a second fixing plate 203, and a heat-conducting layer 204. The microchannel tube 201 is bent. The inner surfaces of the first fixing plate 202 and the second fixing plate 203 are provided with arc-shaped grooves 4 that are consistent with the bending direction of the microchannel tube 201. The heat-conducting layer 204 is fixedly connected to the inner wall of the arc-shaped grooves 4. The cavity and the outer wall of the microchannel tube 201 are interference fit. After the first fixing plate 202 and the second fixing plate 203 are locked, the inner side of the heat-conducting layer 204 is attached to the outer side of the microchannel tube 201. The microchannel tube 201 is made of 316 stainless steel, the mixing block 1 is made of 316 stainless steel, the first fixing plate 202 and the second fixing plate 203 are made of carbon steel, and the heat-conducting layer 204 is made of copper. Taking advantage of the relatively soft nature of copper, when the first fixing plate 202 and the second fixing plate 203 are locked, the copper heat-conducting layer 204 can undergo slight deformation to fill the small imperfections on the outer side of the microchannel tube 201 and ensure a tight fit.

[0029] The microchannel tube 201 is divided into a connecting section 5 and a mixing section 6, which are staggered. The microchannel tube 201 is bent at the connection between the connecting section 5 and the mixing section 6, and the angle between the connecting section 5 and the mixing section 6 is less than 90 degrees, so that the microchannel tube 201 is folded more tightly, and a longer pipe length is bent within the same area, which prolongs the reaction time of the raw materials and improves the reaction conversion rate. The diameter of the middle part of the mixing section 6 is larger than the diameters at both ends. The outer side of the microchannel tube 201 is in contact with the inner side of the heat-conducting layer 204. The variable diameter design of the mixing section 6 creates a velocity difference in the raw materials during the flow process, which, together with the bending path, enhances the turbulence effect and improves the mixing uniformity.

[0030] A semi-spindle cavity is provided at the corresponding position of the arc-shaped groove 4 and the mixing section 6. The two semi-spindle cavities are merged into a spindle cavity. An exhaust hole 8 is provided on the surface of the semi-spindle cavity. The exhaust hole 8 passes through the first fixing plate 202 and the second fixing plate 203. A positioning pin 9 is provided on the inner side of the first fixing plate 202. A positioning hole 10 corresponding to the positioning pin 9 is provided on the second fixing plate 203. The contact surface of the first fixing plate 202 and the second fixing plate 203 is a precision machined surface. The first fixing plate 202 and the second fixing plate 203 are fixed by bolts. The positioning pin 9 and the positioning hole 10 ensure that the arc-shaped groove 4 is precisely aligned. The precision machined surface is locked with the bolts to make the copper heat-conducting layer 204 fit tightly against the outer side of the microchannel tube 201.

[0031] The mixing block 1 has an F-shaped channel 11 inside. One end of the microchannel tube 201 is inserted into the F-shaped channel 11 and fits against the inner surface of the F-shaped channel 11. The other two interfaces of the F-shaped channel 11 are connected to the feeding pipe interface 14 on the upper surface of the top cover 13. The two interfaces are connected to different raw materials respectively. The two raw materials are initially mixed in the overlapping part of the pipeline and then fed into the microchannel tube 201. The bottom of the reaction box 3 is provided with multiple slots 12 that are adapted to the width of the bottom of the reaction component 2. The top cover 13 is fixedly installed on the top of the reaction box 3. The bottom surface of the top cover 13 has a groove that is adapted to the width of the top of the reaction component 2. Through the cooperation of the slots 12 and the groove, the reaction component 2 can be quickly positioned and stably installed.

[0032] The top surface of the top cover 13 is provided with a feeding pipe interface 14, which is connected to two interfaces of the F-shaped channel 11. The side of the reaction chamber 3 is provided with a discharge pipe interface 15, which is connected to the microchannel tube 201 to form a raw material conveying and product discharge path. The first fixing plate 202 and the second fixing plate 203 are provided with heat dissipation fins 16 on the side away from the microchannel tube 201. The two opposite sides of the outside of the reaction chamber 3 are provided with inlet and outlet for conveying coolant. The heat dissipation fins 16 increase the heat dissipation area and, together with the coolant, can quickly dissipate the heat generated by the reaction and maintain a stable reaction temperature.

[0033] By processing the microchannel tube 201 and the fixing plate separately, the cost is reduced by taking advantage of the material difference between 316 stainless steel and carbon steel. At the same time, the heat transfer efficiency is improved by the interference fit design of the copper heat-conducting layer 204. While meeting the usage requirements, the cost is reduced by avoiding the high price of materials in the integral structure.

[0034] Based on the above embodiments, the application and effect of the water expansion method are expanded: After the microchannel tube 201 is fixed by the fixing plate, the water expansion method is used to make the microchannel tube 201 fit with the heat-conducting layer 204 in the spindle cavity. The specific operation is as follows: the first fixing plate 202 and the second fixing plate 203, which are equipped with the microchannel tube 201, are positioned by the positioning pin 9 and the bolts are pre-locked. High-pressure water is introduced into the microchannel tube 201, so that the outer side of the mixing section 6 undergoes plastic deformation and gradually fits with the copper heat-conducting layer 204 in the spindle cavity. During this process, the air inside the spindle cavity is discharged through the exhaust hole 8 (the hole diameter is less than 0.2 mm). Since copper is relatively soft, under the action of water expansion pressure, the copper heat-conducting layer 204 will undergo adaptive deformation with the deformation of the microchannel tube 201 and further fit, so that the outer side of the mixing section 6 is tightly fitted with the heat-conducting layer 204 in the spindle cavity.

[0035] The mixed liquid forms turbulence in the spindle cone, which increases the mixing effect of the mixed liquid and further increases the reaction rate. The water-swollen mixing section 6 cooperates with the spindle cavity to make the raw materials form radial mixing during the flow process, thereby improving the mixing efficiency.

[0036] Because it is difficult to process high-precision cavities with varying diameters in pipelines, it is difficult to ensure that the outer side of the pipeline fits the groove in the fixed plate during direct processing. The microchannel tube 201 is processed by water expansion method to make the outer side of the mixing section 6 fit the heat-conducting layer 204 in the spindle cone cavity, which effectively solves the problem of precision processing and reduces processing costs.

[0037] Based on the above embodiments, the application of multiple reaction components 2 in parallel is expanded: multiple reaction components 2 are connected in parallel and fixedly installed in the reaction chamber 3. Multiple reaction components 2 are installed side by side in the slot 12 at the bottom of the reaction chamber 3. The top cover 13 is fixed to the reaction chamber 3 by bolts. The groove on the bottom surface of the top cover 13 fits with the top of each reaction component 2 to ensure stable installation. The reaction chamber 3 is provided with flowing coolant to continuously cool down. The coolant enters from the inlet, flows through the gaps of the heat dissipation fins 16 of each reaction component 2, and is discharged from the outlet to keep the temperature of each reaction component 2 consistent.

[0038] Multiple reaction components 2 connected in parallel increase efficiency, and the continuous cooling is achieved by heat dissipation fins 16 and flowing coolant. Compared with a single reaction component 2, the production capacity is increased, and the output can be flexibly adjusted by increasing or decreasing the number of connected reaction components 2 to meet the production needs of different batches of active pharmaceutical ingredients.

[0039] The working principle of the above embodiment is as follows: Two raw materials enter the F-shaped channel 11 of the mixing block 1 through the feeding pipe interface 14 on the top cover 13. After preliminary mixing, they flow into the microchannel tube 201 and flow along the curved connecting section 5 and the mixing section 6. Under the action of the variable diameter structure of the mixing section 6, turbulence is formed to achieve a full mixing reaction. The heat generated by the reaction is transferred to the copper heat-conducting layer 204 through the microchannel tube 201, and is discharged by the coolant circulation system through the first fixing plate 202, the second fixing plate 203 and the heat dissipation fins 16. The reaction products are discharged through the discharge pipe interface 15. If the microchannel tube 201 is blocked or damaged, the bolts can be loosened to remove the fixing plate and replace the microchannel tube 201 separately. When it is necessary to adjust the production capacity, the number of connected reaction components 2 can be increased or decreased.

[0040] The installation, connection, or setting methods disclosed in this embodiment are all common mechanical connection methods. As long as they can achieve their beneficial effects, they can be implemented. Therefore, this embodiment will not elaborate on their specific structural composition and working principle.

[0041] If certain terms are used in the specification and claims to refer to specific components, those skilled in the art will understand that hardware manufacturers may use different names to refer to the same component. This specification and claims do not distinguish components based on differences in name, but rather on differences in function. The term "comprising" as used throughout the specification and claims is an open-ended term and should be interpreted as "comprising but not limited to".

[0042] Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the present invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A high-efficiency continuous flow reaction device for synthesis of bulk drug, characterized in that: It includes a mixing block (1), a reaction component (2), and a reaction chamber (3). The mixing block (1) is fixedly installed on the side of the reaction component (2), and the reaction component (2) is fixedly installed inside the reaction chamber (3). ​ The reaction assembly (2) includes a microchannel tube (201), a first fixing plate (202), a second fixing plate (203), and a heat-conducting layer (204). The microchannel tube (201) is bent. The inner surfaces of the first fixing plate (202) and the second fixing plate (203) are provided with arc-shaped grooves (4) that are consistent with the bending direction of the microchannel tube (201). The heat-conducting layer (204) is fixedly connected to the inner wall of the arc-shaped groove (4).

2. The high-efficiency continuous-flow reaction device for synthesis of bulk drugs according to claim 1, characterized in that: The microchannel tube (201) is divided into a connecting section (5) and a mixing section (6). The connecting section (5) and the mixing section (6) are arranged alternately. The microchannel tube (201) is bent at the connection between the connecting section (5) and the mixing section (6). The angle between the connecting section (5) and the mixing section (6) is less than (90) degrees.

3. The high-efficiency continuous-flow reaction device for synthesis of bulk drug according to claim 2, characterized in that: The arc-shaped groove (4) and the mixing section (6) are provided with a semi-spinning cone cavity (7), and the two semi-spinning cone cavities (7) are combined into a spinning cone cavity. The surface of the semi-spinning cone cavity (7) is provided with an exhaust hole (8), and the exhaust hole (8) penetrates the first fixing plate (202) and the second fixing plate (203).

4. The high-efficiency continuous-flow reaction device for synthesis of bulk drug according to claim 2, characterized in that: The diameter of the middle part of the mixing section (6) is larger than the diameter of both ends, and the outer side of the microchannel tube (201) is in contact with the inner side of the heat-conducting layer (204).

5. The high-efficiency continuous-flow reaction device for synthesis of a bulk drug according to claim 1, characterized in that: The inner side of the first fixing plate (202) is provided with a positioning pin (9), and the second fixing plate (203) is provided with a positioning hole (10) corresponding to the positioning pin (9). The contact surface between the first fixing plate (202) and the second fixing plate (203) is a precision machined surface. The first fixing plate (202) and the second fixing plate (203) are fixed together by bolts.

6. The high-efficiency continuous-flow reaction device for synthesis of a bulk drug according to claim 1, characterized in that: The mixing block (1) has an F-shaped channel (11) inside, and one end of the microchannel tube (201) is inserted into the F-shaped channel (11) and fits against the inner surface of the F-shaped channel (11).

7. The high-efficiency continuous-flow reaction device for synthesis of a bulk drug according to claim 6, characterized in that: The bottom of the reaction chamber (3) is provided with multiple slots (12) that are adapted to the bottom width of the reaction component (2). The top of the reaction chamber (3) is fixedly installed with a top cover (13). The bottom surface of the top cover (13) is provided with a groove that is adapted to the top width of the reaction component (2).

8. The high-efficiency continuous flow reactor for the synthesis of active pharmaceutical ingredients according to claim 7, characterized in that: The top cover (13) is provided with a feeding pipe interface (14) on its upper surface. The feeding pipe interface (14) is connected to the two interfaces of the F-shaped channel (11). The top cover (13) is provided with a discharge pipe interface (15) on its side. The discharge pipe interface (15) is connected to the microchannel tube (201).

9. The high-efficiency continuous flow reactor for the synthesis of active pharmaceutical ingredients according to claim 1, characterized in that: The first fixing plate (202) and the second fixing plate (203) are provided with heat dissipation fins (16) on the side away from the microchannel tube (201), and the two opposite sides of the reaction box (3) are provided with inlet and outlet for conveying coolant.

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