Synthetic reaction device

Abstract

The utility model provides a synthetic reaction device. The synthesis reaction device comprises a supporting frame, a synthesis column is rotatably arranged on the supporting frame, the synthesis column is provided with a containing cavity, a liquid inlet and a liquid outlet, the liquid inlet and the liquid outlet are communicated with the containing cavity, the liquid inlet is located in the bottom of the synthesis column, and the liquid outlet is located in the top of the synthesis column; a sampling opening communicated with the containing cavity is formed in the bottom of the synthesis column, the synthesis reaction device further comprises a sealing piece, and the sealing piece is provided with a sealing position filled in the sampling opening in a sealing mode and a sealing releasing position separated from the sampling opening. The technical scheme provided by the utility model solves the problems that the synthesis column of a closed system in the prior art needs to be integrally disassembled during sampling operation, so that time is consumed, the synthesis efficiency is influenced, reagents are possibly wasted, a sealing ring is damaged, and the health of operators is harmed due to volatilization of the reagents in the disassembly process.

Description

Technical Field

[0001] The utility model relates to the technical field of chemical synthesis, in particular to a synthesis reaction device. Background Art

[0002] As a type of biologically active molecule formed by multiple amino acids connected by peptide bonds, peptides have shown great potential in the field of drug research and development in recent years. They have a wide range of applications, including the prevention, diagnosis and treatment of diseases such as tumors, cardiovascular and cerebrovascular diseases, hepatitis, diabetes, and AIDS. Due to their high safety, significant efficacy and adaptability to a variety of diseases, peptide drugs have become one of the focuses of drug research and development. The clinical value of peptide drugs is widely recognized, and many drugs are recommended for use by international and domestic treatment guidelines and expert consensus, showing their important position in modern medicine.

[0003] With the advancement of solid-phase peptide synthesis technology and the innovation of related equipment and processes, the development and production costs of peptide drugs have been significantly reduced, which has promoted the continued popularity of peptide drug research and development. However, technical challenges in the peptide synthesis process still exist, especially in improving synthesis efficiency and product quality.

[0004] At present, peptide synthesis is mainly carried out in a stirred tank or a fully automated synthesis tank. The stirred tank relies on mechanical stirring to make the resin fully contact with the solvent, but this stirring method easily destroys the resin and the peptide chain structure, affecting the synthesis quality. The fully automated synthesis tank is mixed by 180-degree flipping. Although it avoids the direct damage of mechanical stirring, the resin is easily attached to the inner wall of the tank, resulting in unstable coupling reaction efficiency. In order to solve these problems, the applicant has previously developed a peptide solid phase synthesis device, which uses a synthesis column and replaces stirring by circulating in the system to ensure that the resin is completely immersed in the reaction solution during the synthesis process, thereby improving the sufficiency of the reaction and the synthesis efficiency, while reducing reagent consumption. However, this closed system synthesis column has many inconveniences when performing sampling operations. For example, the sampling operation for sampling to detect the coupling effect or retaining samples for analysis of some nodes (such as decapeptides, 15-peptides, etc.) is relatively complicated, and the synthesis column needs to be disassembled as a whole, which is not only time-consuming and affects the synthesis efficiency, but also may cause reagent waste and damage the sealing ring, and the volatilization of reagents during the disassembly process will cause harm to the health of the operator. Utility Model Content

[0005] The main purpose of the utility model is to provide a synthesis reaction device to solve the problem that the synthesis column of the closed system in the prior art needs to be disassembled as a whole when performing sampling operations, which is not only time-consuming and affects the synthesis efficiency, but also may cause reagent waste and damage the sealing ring. In addition, the volatilization of the reagent during the disassembly process may cause harm to the health of the operator.

[0006] In order to achieve the above-mentioned purpose, the utility model provides a synthesis reaction device, including a support frame, a synthesis column rotatably arranged on the support frame, the synthesis column having a accommodating cavity and a liquid inlet and a liquid outlet connected with the accommodating cavity, the liquid inlet is located at the bottom of the synthesis column, and the liquid outlet is located at the top of the synthesis column; a sampling port connected with the accommodating cavity is provided on the bottom of the synthesis column, and the synthesis reaction device also includes a sealing member, the sealing member having a sealing position for sealing and filling in the sampling port and a sealing release position for detaching from the sampling port.

[0007] Furthermore, the support frame includes a base and two support members, the composite column is located between the two support members, one end of each support member is connected to the base, and the composite column is rotatably arranged relative to the other end of each support member.

[0008] Furthermore, the synthesis reaction device also includes a mounting frame for mounting the synthesis column; along the radial direction of the synthesis column, pivot members are provided on both sides of the mounting frame, and each support member is provided with a pivot hole, and the two pivot members are rotatably matched with the two pivot holes.

[0009] Furthermore, the pivot hole is a through hole, and at least part of the outer periphery of the pivot member is provided with threads. The synthetic reaction device also includes a locking member, one end of the pivot member is connected to the mounting frame, and the other end of the pivot member extends out of the through hole and cooperates with the locking member thread.

[0010] Furthermore, the pivot member includes a connecting block and a rotating shaft connected to the connecting block, the cross-sectional area of ​​the connecting block is larger than the cross-sectional area of ​​the rotating shaft, the connecting block is connected to the mounting frame, and the rotating shaft is rotatably matched with the pivot hole.

[0011] Furthermore, each support member is a support rod, and the support rod extends along the axial direction of the synthetic column.

[0012] Furthermore, the sealing member is a sealing rubber plug or a metal sealing cover or a magnetic sealing member.

[0013] Furthermore, a temperature-controlling jacket is provided on the periphery of the synthesis column, and the temperature-controlling jacket has a heat exchange cavity and a medium inlet and a medium outlet communicated with the heat exchange cavity.

[0014] Furthermore, the synthesis reaction device also includes a temperature sensor, which is located in the heat exchange cavity and is configured to be connected to the controller.

[0015] Furthermore, the bottom of the synthetic column is spaced apart from the base.

[0016] By applying the technical solution of the utility model, a sampling port is provided at the bottom of the synthesis column, and the synthesis column is rotatably provided on the support frame, so that the sampling process becomes simple and quick, and there is no need to disassemble the synthesis column as a whole. In this way, on the one hand, a single person can complete the sampling operation, which greatly improves the operation efficiency and convenience; on the other hand, the frequent disassembly and assembly of the synthesis column can be avoided, which not only reduces the influence of the sampling operation on the synthesis efficiency, maintains the continuity of the synthesis process and the reaction stability, but also effectively reduces the consumption of reagents during frequent disassembly, and reduces the physical stress on the sealing ring, thereby extending the service life of the sealing ring and ensuring the sealing performance of the synthesis column for long-term operation; on the other hand, by additionally arranging a sampling port for sampling, the sampling process is more closed and controllable, which effectively reduces the volatilization of reagents and protects the safety of operators. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The drawings constituting part of the present application are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation on the present invention. In the drawings:

[0018] Figure 1 A schematic structural diagram of an embodiment of a synthetic reaction device of the utility model is shown;

[0019] Figure 2 Shows Figure 1 A structural schematic diagram of the synthesis reaction device from another perspective.

[0020] The above drawings include the following reference numerals:

[0021] 1. Connecting block; 2. Support member; 3. Base; 4. Synthetic column; 5. Sampling port; 6. Liquid inlet; 7. Liquid outlet; 9. Mounting frame; 10. Support frame; 11. Pivot member; 12. Locking member; 15. Rotating shaft. DETAILED DESCRIPTION

[0022] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present utility model will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0023] like Figure 1 and Figure 2As shown, an embodiment of the utility model provides a synthesis reaction device. The synthesis reaction device comprises: a support frame 10; a synthesis column 4, which is rotatably arranged on the support frame 10, and the synthesis column 4 has a receiving cavity and a liquid inlet 6 and a liquid outlet 7 connected to the receiving cavity, wherein the liquid inlet 6 is located at the bottom of the synthesis column 4, and the liquid outlet 7 is located at the top of the synthesis column 4; wherein a sampling port 5 connected to the receiving cavity is provided on the bottom of the synthesis column 4, and the synthesis reaction device further comprises a sealing member, wherein the sealing member has a sealing position for sealing and filling in the sampling port 5 and a sealing release position for separating from the sampling port 5.

[0024] In the above technical scheme, by setting a sampling port at the bottom of the synthesis column 4, and rotatably setting the synthesis column 4 on the support frame 10, sampling can be achieved by turning over the synthesis column 4 and removing the seal, so that the sampling process becomes simple and quick, and there is no need to disassemble the synthesis column 4 as a whole. In this way, on the one hand, a single person can complete the sampling operation, which greatly improves the operation efficiency and convenience; on the other hand, the frequent disassembly and assembly of the synthesis column 4 can be avoided, which not only reduces the impact of the sampling operation on the synthesis efficiency, maintains the continuity of the synthesis process and the reaction stability, but also effectively reduces the consumption of reagents during frequent disassembly, and also reduces the physical stress on the sealing ring on the upper side of the synthesis column 4, thereby extending the service life of the sealing ring and ensuring the sealing performance of the synthesis column 4 for long-term operation; on the other hand, by additionally setting a sampling port 5 for sampling, the sampling process is more closed and controllable, which effectively reduces the volatilization of reagents and protects the safety of operators.

[0025] like Figure 2 As shown, in an embodiment of the utility model, the support frame 10 includes: a base 3; two support members 2, a composite column 4 is located between the two support members 2, one end of each support member 2 is connected to the base 3, and the composite column 4 is rotatably arranged relative to the other end of each support member 2.

[0026] Through the above-mentioned arrangement, the combination of the base 3 and the two support members 2 provides a more stable support for the synthesis column 4, ensuring the stability of the synthesis column under various operating conditions, that is, the synthesis column 4 will not accidentally move or tip over during the flipping process, thereby ensuring the safety and reliability of the synthesis process; and when the operator is performing sampling operations, he can easily flip the synthesis column 4 to a suitable angle to ensure that the sampling port 5 can be accurately aligned, reducing the difficulty of operation and time consumption.

[0027] like Figure 1 As shown, in the embodiment of the utility model, the synthesis reaction device also includes a mounting frame 9 for mounting the synthesis column 4; along the radial direction of the synthesis column 4, pivot members 11 are provided on both sides of the mounting frame 9, and each support member 2 is provided with a pivot hole, and the two pivot members 11 are rotatably matched with the two pivot holes.

[0028] In the above technical solution, through the cooperation of the pivot hole and the pivot member 11, the synthetic column 4 can be easily rotated between the two support members 2, which makes the sampling operation more convenient. Without additional tools or manpower, the operator can complete the flipping of the synthetic column with one hand, thereby quickly opening the sampling port 5 for sampling.

[0029] like Figure 1 and Figure 2 As shown, in the embodiment of the utility model, the pivot hole is a through hole, and at least part of the outer periphery of the pivot member 11 is provided with a thread. The synthetic reaction device also includes a locking member 12, one end of the pivot member 11 is connected to the mounting frame 9, and the other end of the pivot member 11 extends out of the through hole and is threadedly matched with the locking member 12.

[0030] In the above technical solution, the pivot member 11 can be unlocked by rotating the locking member 12, so that the synthetic column 4 can be flipped over to make the sampling port 5 face upward, and then the synthetic column 4 can be fixed by tightening the locking member 12 to ensure that the operator can take samples when the synthetic column 4 is stable, thereby reducing the risk of accidents that may occur during operation.

[0031] Preferably, in the embodiment of the present invention, the locking member 12 is a nut.

[0032] like Figure 1 As shown, in an embodiment of the utility model, the pivot member 11 includes a connecting block 1 and a rotating shaft 15 connected to the connecting block 1, the cross-sectional area of ​​the connecting block 1 is larger than the cross-sectional area of ​​the rotating shaft 15, the connecting block 1 is connected to the mounting frame 9, and the rotating shaft 15 is rotatably matched with the pivot hole.

[0033] Through the above arrangement, the larger cross-sectional area of ​​the connection block 1 can abut against the support member 2, and by screwing the locking member 12, the two support members 2 can be pressed against the two connection blocks 1, so that the synthetic column 4 can be fixed.

[0034] like Figure 1 As shown, in the embodiment of the utility model, each support member 2 is a support rod, and the support rod extends along the axial direction of the synthetic column 4. In this way, the two support rods can support the synthetic column 4, so that the synthetic column 4 can be suspended on the support frame 10, thereby facilitating the flipping of the synthetic column 4.

[0035] Preferably, in the embodiment of the utility model, the sealing member is a sealing rubber plug or a metal cover or a magnetic plug. In this way, the sealing of the sampling port 5 can be ensured when not in use to prevent leakage of the reaction liquid, and at the same time, moisture and impurities in the air can be prevented from entering the reaction system and affecting the purity and efficiency of polypeptide synthesis.

[0036] Preferably, in the embodiment of the utility model, a temperature control jacket is provided on the periphery of the synthesis column 4, and the temperature control jacket has a heat exchange cavity and a medium inlet and a medium outlet communicated with the heat exchange cavity. In this way, by adjusting the temperature of the temperature control jacket, the reaction conditions can be optimized, the resin and the solvent can be more fully contacted and reacted, the occurrence of side reactions can be reduced, and the purity and yield of peptide chain synthesis can be improved.

[0037] Preferably, in an embodiment of the utility model, the synthesis reaction device further comprises a temperature sensor, the temperature sensor is located in the heat exchange chamber, and the temperature sensor is configured to be connected to the controller. The polypeptide synthesis reaction has strict requirements on temperature conditions, and the addition of the temperature sensor enables the synthesis column 4 to accurately control the reaction temperature, ensuring that the synthesis reaction is carried out at the optimal temperature, thereby improving the reaction efficiency and the quality consistency of the polypeptide product.

[0038] like Figure 1 As shown, in the embodiment of the utility model, the bottom of the synthesis column 4 is spaced apart from the base 3. In this way, the synthesis column 4 can be flexibly turned over in a limited operating space for sampling.

[0039] It should be noted that the synthesis reaction device of the embodiment of the utility model slightly reduces the sieve plate at the bottom of the traditional synthesis column, adds a sampling port 5 next to it, and designs the synthesis column to be flippable. At the node where sampling is required, the column is flipped upside down, the nuts at both ends are tightened, and the seal of the sampling port is unscrewed for sampling. The operation is simple and convenient, and a single person can complete the sampling operation. At the same time, the added sampling port 5 does not affect the function of the synthesis column piston to move freely to adjust the column volume.

[0040] It should be noted that since there is a piston rod on the top of the synthesis column for adjusting the volume inside the column, it is difficult to place it upside down. The utility model makes the synthesis column into a flip-over design, so that a single person can complete the sampling work of a larger synthesis column; in addition, in addition to being used in laboratory-type polypeptide synthesis, it can also be promoted and applied in production.

[0041] It should be noted that the size of the bottom sieve plate of the synthesis column of the present invention, the position and size of the sampling port 5, etc. can all be changed;

[0042] In one embodiment, the synthetic column may also be a column whose volume cannot be changed.

[0043] In order to verify the feasibility and effect of the utility model, an implementation case was carried out: the synthesis column of the synthesis reaction device was used to synthesize the polypeptide chain acyl carrier protein ACP65-74, and each amino acid was sampled to test the deprotection and coupling effects during synthesis, which was convenient to operate and save time. After sampling 5 peptides and 10 peptides, the cleavage treatment was performed to analyze the purity. The final crude peptide purities were 98.96% and 94.67%, respectively. It took 20 hours to synthesize the entire peptide chain, that is, the instrument was turned on for synthesis on the first day, and the crude peptide sample was obtained on the second day.

[0044] From the above description, it can be seen that the above-mentioned embodiments of the utility model achieve the following technical effects: by setting a sampling port at the bottom of the synthesis column and rotatably setting the synthesis column on the support frame, the sampling process becomes simple and quick, and there is no need to disassemble the synthesis column as a whole. In this way, on the one hand, a single person can complete the sampling operation, which greatly improves the operating efficiency and convenience; on the other hand, the frequent disassembly and assembly of the synthesis column can be avoided, which not only reduces the impact of the sampling operation on the synthesis efficiency, maintains the continuity of the synthesis process and the reaction stability, but also effectively reduces the consumption of reagents during frequent disassembly, and reduces the physical stress on the sealing ring, thereby extending the service life of the sealing ring and ensuring the sealing performance of the synthesis column for long-term operation; on the other hand, by additionally setting a sampling port for sampling, the sampling process is more closed and controllable, which effectively reduces the volatilization of reagents and protects the safety of operators.

[0045] The above description is only the preferred embodiment of the utility model, and is not intended to limit the utility model. For those skilled in the art, the utility model can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the utility model shall be included in the protection scope of the utility model.

Claims

1. A synthesis reaction device, characterized in that: include: Support frame (10); A synthesis column (4) rotatably arranged on the support frame (10), the synthesis column (4) having a receiving cavity and a liquid inlet (6) and a liquid outlet (7) communicated with the receiving cavity, the liquid inlet (6) being located at the bottom of the synthesis column (4), and the liquid outlet (7) being located at the top of the synthesis column (4); Wherein, a sampling port (5) communicating with the accommodating chamber is provided at the bottom of the synthesis column (4), and the synthesis reaction device further comprises a sealing member, wherein the sealing member has a sealing position for sealing and filling in the sampling port (5) and a sealing release position for separating from the sampling port (5).

2. The synthesis reaction device according to claim 1, characterized in that: The support frame (10) comprises: Base (3); Two support members (2), the synthetic column (4) being located between the two support members (2), one end of each support member (2) being connected to the base (3), and the synthetic column (4) being rotatably arranged relative to the other end of each support member (2).

3. The synthesis reaction device according to claim 2, characterized in that: The synthesis reaction device further comprises a mounting frame (9) for mounting the synthesis column (4); Along the radial direction of the synthetic column (4), pivot members (11) are provided on both sides of the mounting frame (9), and each of the support members (2) is provided with a pivot hole, and the two pivot members (11) are rotatably matched with the two pivot holes.

4. The synthesis reaction device according to claim 3, characterized in that: The pivot hole is a through hole, and at least part of the outer periphery of the pivot member (11) is provided with a thread. The synthetic reaction device further comprises a locking member (12), one end of the pivot member (11) is connected to the mounting frame (9), and the other end of the pivot member (11) extends out of the through hole and is threadedly engaged with the locking member (12).

5. The synthesis reaction device according to claim 4, characterized in that: The pivot member (11) comprises a connecting block (1) and a rotating shaft (15) connected to the connecting block (1); the cross-sectional area of ​​the connecting block (1) is larger than the cross-sectional area of ​​the rotating shaft (15); the connecting block (1) is connected to the mounting frame (9); and the rotating shaft (15) is rotatably matched with the pivot hole.

6. The synthesis reaction device according to any one of claims 2 to 5, characterized in that: Each of the support members (2) is a support rod, and the support rod extends along the axial direction of the synthetic column (4).

7. The synthesis reaction device according to any one of claims 1 to 5, characterized in that: The sealing member is a sealing rubber plug or a metal sealing cover or a magnetic sealing plug.

8. The synthesis reaction device according to any one of claims 1 to 5, characterized in that: The outer periphery of the synthesis column (4) is provided with a temperature control jacket, and the temperature control jacket has a heat exchange cavity and a medium inlet and a medium outlet communicated with the heat exchange cavity.

9. The synthesis reaction device according to claim 8, characterized in that: The synthetic reaction device further comprises a temperature sensor, which is located in the heat exchange cavity and is configured to be connected to a controller.

10. The synthesis reaction device according to any one of claims 2 to 5, characterized in that: The bottom of the synthesis column (4) is spaced apart from the base (3).

Images