Polypeptide solid-phase synthesis device

Abstract

The present application provides a polypeptide solid-phase synthesis device. The polypeptide solid-phase synthesis device comprises a first circulation pipeline, a second circulation pipeline, a first switching valve, and a second switching valve. The first circulation pipeline comprises a synthesis column, a third switching valve, and a first pump body which are sequentially arranged from upstream to downstream. The second circulation pipeline comprises a fourth switching valve, a second pump body, and an activation reactor which are sequentially arranged from upstream to downstream. The technical solution provided by the present application can solve the problems in the related art of low synthesis efficiency, complex batch operations, and large amino acid usage amount of polypeptide solid-phase synthesis devices.

Description

Peptide solid phase synthesis apparatus

[0001] This application claims priority to the patent application submitted to the State Intellectual Property Office of China on November 15, 2023, with application number 202311524387.6 and invention name "Polypeptide Solid Phase Synthesis Device". Technical Field

[0002] The present application relates to the technical field of polypeptide synthesis devices, and in particular to a polypeptide solid-phase synthesis device. Background Art

[0003] Peptides are a class of compounds formed by multiple amino acids linked by peptide bonds. In recent years, with the development and maturity of peptide synthesis technology, peptide drugs have become a hot topic in drug research and development. Due to their broad indications, high safety profile, and significant efficacy, they have been widely used in the prevention, diagnosis, and treatment of diseases such as tumors, cardiovascular and cerebrovascular diseases, hepatitis, diabetes, and AIDS, and have broad development prospects.

[0004] With the rapid development of technologies related to peptide synthesis (such as the emergence of solid-phase peptide synthesis technology), equipment, and processes, the R&D and production costs of peptide drugs have been significantly reduced, and the development of peptide drugs continues to heat up. In the process of peptide solid-phase synthesis, peptide synthesizers are often used for synthesis.

[0005] However, the synthesis process of peptide solid-phase synthesizers in related technologies is batch synthesis, which is time-consuming and labor-intensive, mostly requires manual intervention, has low synthesis efficiency, and uses a large amount of amino acids.

[0006] Summary of the Invention

[0007] The present application provides a polypeptide solid-phase synthesis device to solve the problems of low synthesis efficiency, complex batch operation and large amount of amino acids used in polypeptide solid-phase synthesis devices in related technologies.

[0008] The present application provides a polypeptide solid phase synthesis device, which includes a first circulation pipeline, a second circulation pipeline, a first switching valve and a second switching valve. The first circulation pipeline includes a synthesis column, a third switching valve and a first pump body arranged in sequence from upstream to downstream. The second circulation pipeline includes a fourth switching valve, a second pump body and an activation reactor arranged in sequence from upstream to downstream; wherein the first switching valve has a switching inlet a1, a switching outlet a1 and a switching outlet a2, the second switching valve includes a switching inlet b1, a switching inlet b2, a switching outlet b1 and a switching outlet b2, the third switching valve has an injection port c1, a switching inlet c1 and a switching outlet c1, the fourth switching valve has an injection port d1, a switching inlet d1 and a switching outlet The switching outlet d1, the outlet of the first pump body and the outlet of the second pump body are all connected with the switching inlet a1 of the first switching valve, the switching outlet a1 of the first switching valve is connected with the switching inlet b1 of the second switching valve, the switching outlet b1 of the second switching valve is connected with the inlet of the synthesis column, the outlet of the synthesis column is connected with the switching inlet c1 of the third switching valve, the switching outlet c1 of the third switching valve is connected with the inlet of the first pump body, the switching outlet a2 of the first switching valve is connected with the inlet of the activation reactor, the outlet of the activation reactor is connected with the switching inlet b2 of the second switching valve, the switching outlet b2 of the second switching valve is connected with the switching inlet d1 of the fourth switching valve, and the switching outlet d1 of the fourth switching valve is connected with the inlet of the second pump body.

[0009] Furthermore, the first circulation pipeline also includes a fifth switching valve, which has a switching inlet e1, a first flushing inlet and a switching outlet e1. The outlet of the synthesis column is connected to the switching inlet e1 of the fifth switching valve, the switching outlet e1 of the fifth switching valve is connected to the switching inlet c1 of the third switching valve, and the switching outlet b2 of the second switching valve is also connected to the first flushing inlet of the fifth switching valve.

[0010] Furthermore, the fifth switching valve further has a second flushing inlet, and the first switching valve further has a switching outlet a3, and the switching outlet a3 of the first switching valve is connected to the second flushing inlet of the fifth switching valve.

[0011] Furthermore, the polypeptide solid phase synthesis device also includes a waste liquid pipeline, and the third switching valve also has a waste liquid outlet, and the waste liquid outlet of the third switching valve is connected to the inlet of the waste liquid pipeline.

[0012] Furthermore, a flow restrictor and a waste liquid outlet valve are provided on the waste liquid pipeline, and the waste liquid outlet valve is located downstream of the flow restrictor.

[0013] Furthermore, the polypeptide solid phase synthesis device also includes a detector capable of detecting synthesis parameters, and the detector is arranged on the first circulation pipeline.

[0014] Furthermore, the detector includes a UV detector, which is located between the synthesis column and the third switching valve; and / or the detector further includes a conductivity detector, which is located between the first pump body and the first switching valve.

[0015] Furthermore, the polypeptide solid phase synthesis device further comprises a controller, and the first pump body, the second pump body, and the detector are respectively connected to the controller by signal.

[0016] Furthermore, the polypeptide solid-phase synthesis apparatus further comprises two first injection valves, the outlets of the two first injection valves are both connected to the injection port d1 of the fourth switching valve; and / or, the polypeptide solid-phase synthesis apparatus further comprises a second injection valve, the outlet of the second injection valve is connected to the injection port c1 of the third switching valve.

[0017] Furthermore, the tube body of the first circulation pipeline is made of PEEK, FEP or stainless steel; and / or the tube body of the second circulation pipeline is made of PEEK, FEP or stainless steel.

[0018] Applying the technical solution of the present application, the polypeptide solid phase synthesis device includes a first circulation pipeline, a second circulation pipeline, a first switching valve and a second switching valve. The first circulation pipeline, the second circulation pipeline, the first switching valve and the second switching valve can form a deprotection cycle, an amino acid activation cycle and an amino acid coupling cycle according to their connection relationship. Wherein, in the deprotection cycle, after the deprotection reagent enters the third switching valve from the injection port c1, it is transported by the first pump body to the first switching valve and then enters the synthesis column through the second switching valve. At this time, the circulation pipeline of the synthesis column → the third switching valve → the first pump body → the first switching valve → the second switching valve → the synthesis column is opened, so that the deprotection reagent is fully contacted with the carrier in the synthesis column. In the amino acid activation cycle, the amino acid and the reagent are combined into one path through the first pump body and the second pump body to enter the first switching valve and then enter the activation reactor. Then, the circulation pipeline of the activation reactor → the second switching valve → the fourth switching valve → the second pump body → the first switching valve → the activation reactor is opened, so that the amino acid is fully contacted with the activator to achieve the effect of activating the amino acid. During the amino acid coupling cycle, after the amino acid is fully activated and enters the synthesis column, the circulation line (synthesis column → third switching valve → first pump → first switching valve → second switching valve → synthesis column) is opened to ensure full contact between the activated amino acid and the carrier. This structure enables continuous synthesis, maximizing the continuity of the synthesis, reducing the operation time between each step and between steps, improving production efficiency, and reducing the amount of amino acids used, thus saving costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The drawings that constitute part of this application are used to provide a further understanding of this application. The illustrative embodiments of this application and their descriptions are used to explain this application and do not constitute an improper limitation on this application. In the drawings:

[0020] FIG1 shows a schematic diagram of a polypeptide solid phase synthesis apparatus provided in an embodiment of the present application.

[0021] Among them, the above-mentioned drawings include the following figure marks: 100, first circulation pipeline; 200, second circulation pipeline; 300, waste liquid pipeline; 1, first injection valve; 2, fourth switching valve; 3, conductivity detector; 4, second injection valve; 5, third switching valve; 6, first switching valve; 7, fifth switching valve; 8, activation reactor; 9, synthesis column; 10, second switching valve; 11, UV detector; 13, flow restrictor; 14, waste liquid outlet valve; 15, first pump body; 16, second pump body. DETAILED DESCRIPTION

[0022] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is in no way intended to limit the present application and its application or use. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of this application.

[0023] As shown in Figure 1, an embodiment of the present application provides a polypeptide solid-phase synthesis device, which includes a first circulation pipeline 100, a second circulation pipeline 200, a first switching valve 6, and a second switching valve 10. The first circulation pipeline 100 includes a synthesis column 9, a third switching valve 5, and a first pump body 15 arranged in sequence from upstream to downstream. The second circulation pipeline 200 includes a fourth switching valve 2, a second pump body 16, and an activation reactor 8 arranged in sequence from upstream to downstream. Among them, the first switching valve 6 has a switching inlet a1, a switching outlet a1, and a switching outlet a2. The second switching valve 10 includes a switching inlet b1, a switching inlet b2, a switching outlet b1, and a switching outlet b2. The third switching valve 5 has an injection port c1, a switching inlet c1, and a switching outlet c1. The fourth switching valve 2 has an injection port d1, a switching inlet d1, and a switching outlet d1. The outlet of the first pump body 15 and the outlet of the second pump body 16 are both connected to the switching inlet a1 of the first switching valve 6. The switching outlet a1 of the first switching valve 6 is connected to the switching inlet b1 of the second switching valve 10. The switching outlet b1 of the second switching valve 10 is connected to the inlet of the synthesis column 9, the outlet of the synthesis column 9 is connected to the switching inlet c1 of the third switching valve 5, the switching outlet c1 of the third switching valve 5 is connected to the inlet of the first pump body 15, the switching outlet a2 of the first switching valve 6 is connected to the inlet of the activation reactor 8, the outlet of the activation reactor 8 is connected to the switching inlet b2 of the second switching valve 10, the switching outlet b2 of the second switching valve 10 is connected to the switching inlet d1 of the fourth switching valve 2, and the switching outlet d1 of the fourth switching valve 2 is connected to the inlet of the second pump body 16.

[0024] Using the peptide solid-phase synthesis apparatus provided in this embodiment, the first circulation line 100, the second circulation line 200, the first switching valve 6, and the second switching valve 10, based on their interconnectedness, can form a deprotection cycle, an amino acid activation cycle, and an amino acid coupling cycle. In the deprotection cycle, the deprotection reagent enters the third switching valve 5 through the injection port c1, is transported by the first pump 15 through the first switching valve 6, and then enters the synthesis column 9 through the second switching valve 10. At this point, the circulation line from synthesis column 9 → third switching valve 5 → first pump 15 → first switching valve 6 → second switching valve 10 → synthesis column 9 is opened to allow the deprotection reagent to fully contact the carrier in the synthesis column 9. In the amino acid activation cycle, the amino acid and reagent merge through the first pump 15 and second pump 16, enter the first switching valve 6, and then enter the activation reactor 8. The circulation line from activation reactor 8 → second switching valve 10 → fourth switching valve 2 → second pump 16 → first switching valve 6 → activation reactor 8 is then opened to allow the amino acid to fully contact the activating reagent, achieving the desired amino acid activation effect. During the amino acid coupling cycle, after the amino acid is fully activated and enters the synthesis column 9, the circulation line (synthesis column 9 → third switching valve 5 → first pump 15 → first switching valve 6 → second switching valve 10 → synthesis column 9) is opened to ensure full contact between the activated amino acid and the carrier. This structure enables continuous, fully automated synthesis, maximizing synthesis continuity. It also makes the synthesis intelligent, reducing operation time between steps and between steps, improving production efficiency, and reducing amino acid usage, thus saving costs.

[0025] It should be noted that the second switching valve 10 is a column valve, providing three passage functions to satisfy the function of material circulation or passage. The activation reactor 8 is an online activation reactor with a mixing core, and the synthesis column 9 is a polypeptide synthesis column.

[0026] As shown in Figure 1, in this embodiment, the first circulation pipeline 100 also includes a fifth switching valve 7, the fifth switching valve 7 has a switching inlet e1, a first flushing inlet and a switching outlet e1, the outlet of the synthesis column 9 is connected to the switching inlet e1 of the fifth switching valve 7, the switching outlet e1 of the fifth switching valve 7 is connected to the switching inlet c1 of the third switching valve 5, and the switching outlet b2 of the second switching valve 10 is also connected to the first flushing inlet of the fifth switching valve 7.

[0027] When the polypeptide solid phase synthesis device needs to be flushed, the following valves can be opened to achieve flushing: third switching valve 5 → first pump body 15 → first switching valve 6 → activation reactor 8 → second switching valve 10 → fifth switching valve 7 .

[0028] In this embodiment, the fifth switching valve 7 further has a second flushing inlet, and the first switching valve 6 further has a switching outlet a3 . The switching outlet a3 of the first switching valve 6 is connected to the second flushing inlet of the fifth switching valve 7 .

[0029] When the peptide solid phase synthesis device is put into use, it is necessary to pre-inject reagents into the pipeline to fill the pipeline with reagents, and it is best not to let the reagents pass through components other than the valves. Therefore, the following valves can be used to achieve the above purpose: third switching valve 5 → first pump body 15 → first switching valve 6 → fifth switching valve 7.

[0030] As shown in Figure 1, the polypeptide solid-phase synthesis device also includes a waste liquid pipeline 300, and the third switching valve 5 also has a waste liquid outlet. The waste liquid outlet of the third switching valve 5 is connected to the inlet of the waste liquid pipeline 300. The waste liquid is collected by the waste liquid pipeline to improve the environmental protection effect of the device.

[0031] Specifically, the waste liquid pipeline 300 is provided with a flow restrictor 13 and a waste liquid outlet valve 14, with the waste liquid outlet valve 14 located downstream of the flow restrictor 13. The flow restrictor 13 ensures pump accuracy by transmitting an electrical signal to the controller. The waste liquid outlet valve 14 separates the waste liquid into eight categories for collection and recycling, thus conserving energy.

[0032] It should be noted that the first switching valve 6 is a three-point selection valve, which can choose to circulate through the path of the activation reactor 8-the second pump body 16, or through the path of the synthesis column 9-the first pump body 15, or through the path of the fifth switching valve 7-the waste liquid outlet valve 14.

[0033] In this embodiment, the polypeptide solid phase synthesis apparatus further includes a detector capable of detecting synthesis parameters. The detector is disposed on the first circulation pipeline 100 to detect the synthesis effect.

[0034] Specifically, the detector includes a UV detector 11, which is located between the synthesis column 9 and the third switching valve 5. The UV detector 11 can detect ultraviolet absorption during the synthesis process online.

[0035] The detector further includes a conductivity detector 3, which is located between the first pump body 15 and the first switching valve 6. The conductivity detector 3 can be used to online test the conductivity signal during the synthesis process.

[0036] Specifically, the detector also includes a pressure detector (to detect the pressure of the synthesis process system) and a temperature detector (to detect the temperature of the synthesis process system) to further improve the detection precision and accuracy.

[0037] In this embodiment, the polypeptide solid phase synthesis device further includes a controller, and the first pump body 15, the second pump body 16, and the detector are respectively connected to the controller signal, thereby realizing automatic control operation of the device and improving production efficiency.

[0038] The serial port server is connected to the host computer via an Ethernet port. The serial port server is connected to multiple pumps and multiple detectors. Specifically, the controller includes a microcontroller unit, a communication module, a storage module, multiple communication interfaces connected to the microcontroller unit, and an injection valve module, a valve power control module, a mixing assembly control module, multiple detection modules, and a pressure acquisition module, each connected to the microcontroller unit. The microcontroller unit is connected to the serial port server via the communication module, enabling signal exchange with the host computer.

[0039] As shown in Figure 1, the peptide solid phase synthesis device also includes two first injection valves 1, the outlets of the two first injection valves 1 are connected to the injection port d1 of the fourth switching valve 2 to achieve amino acid injection. Specifically, the first injection valve 1 can provide the inlet of 13 kinds of amino acids.

[0040] As shown in Figure 1, the peptide solid phase synthesis apparatus further includes a second injection valve 4, the outlet of which is connected to the injection port c1 of the third switching valve 5 to enable reagent injection. Specifically, the second injection valve 4 can provide an inlet for six reagents and an inlet for flushing.

[0041] It should be noted that the third switching valve 5 is a two-point selection valve, which can select the path from the second injection valve 4 to the first pump body 15 or the path from the UV detector 11 to the first pump body 15 for coupled circulation.

[0042] The tube body of the first circulation pipeline 100 is made of PEEK (Poly ether ether ketone), FEP (Fluorinated ethylene propylene), or stainless steel, while the tube body of the second circulation pipeline 200 is made of PEEK (Poly ether ether ketone), FEP (Fluorinated ethylene propylene), or stainless steel. This makes the tube bodies of the first circulation pipeline 100 and the second circulation pipeline 200 both low in cost and long in service life.

[0043] In this embodiment, the tube body of the first circulation pipeline 100 and the tube body of the second circulation pipeline 200 are made of PEEK (Poly ether ether ketone) or FEP (Fluorinated ethylene propylene), with diameters of 1 / 8 inch and 1 / 16 inch respectively.

[0044] It should be noted that the valve bodies in this embodiment are all multi-channel control valves, and the execution operation of each valve is controlled by the execution motor driver to rotate and control the on-off, which drives the rotor fixed to the shaft end to rotate, switches to the channel on the required valve head, and then controls the on-off of the pipeline connected to the single valve body. Among them, the connection method of the valve body includes thread or sleeve, chuck, flange connection, etc. In other embodiments, the number of injection valves can be increased, the valve control method can be changed, electric valve or pneumatic valve. Alternatively, the number of pumps can be increased to meet the feeding demand, and the pump method can be changed to electric or pneumatic diaphragm pump, plunger, mechanical pump, magnetic pump, etc.

[0045] In this example, the inventors used a peptide solid phase synthesis device for testing. The amino acid sequence synthesized in this test was H-Val-Gln-Ala-Ala-IIe-Asp-Tyr-IIe-Asn-Gly-NH2.

[0046] The test process is as follows: (1) Equipment debugging: pre-loading to confirm that the equipment can operate normally; (2) Pre-preparation: mixing ingredients and loading columns; (3) Synthesis: according to the established synthesis order (deprotection, cleaning, activation, cleaning, synthesis, cleaning, end-capping, cleaning, and coupling each amino acid in this order until the target chain reaches the established length), automatic feeding is carried out for polypeptide synthesis; (4) Cutting: peeling off the complete polypeptide chain from the carrier.

[0047] The above is a general procedure for testing using a peptide solid-phase synthesis device. After cleavage, product post-processing and purity testing are required. The test results show that the purity of the polypeptide chain synthesized using the peptide solid-phase synthesis device of this embodiment is 91.32%, which is better than the purity of the related art (approximately 87.56%).

[0048] The device provided by this embodiment has the following beneficial effects:

[0049] (1) The existing problems of peptide synthesis equipment were optimized and a continuous over-current synthesis method was adopted to maximize the continuity of synthesis, reduce the operation time of each process and between processes, and greatly improve production efficiency.

[0050] (2) The existing peptide synthesis equipment is large and not suitable for R&D experiments. A reasonable pipeline layout is adopted (based on the overall layout, pipelines that need to pass materials and produce residues are optimized and shortened). The equipment and pipeline structure are simple, the dead volume is small, the material residue is reduced, the risk of cross-contamination between materials is reduced, and the effect of saving materials is achieved.

[0051] (3) Optimization was conducted to address the problem that mechanical stirring in existing peptide synthesis equipment can easily damage the product. Compared to traditional synthesis reactors, the peptide solid-phase synthesis device uses a material circulation method to replace the stirring device, reducing the shear force of mechanical stirring on the resin, reducing the risk of product damage, and improving the yield.

[0052] (4) Through the unique pipeline design, multiple circulation modes can be achieved without manual switching, saving costs while improving synthesis efficiency.

[0053] (5) In view of the lack of process monitoring instruments in existing peptide synthesis equipment, a pressure detector, a temperature detector, a UV detector 11 and a conductivity detector 3 are introduced to monitor part of the synthesis process in real time, which can judge part of the reaction process online, guide the correction during the synthesis process, and improve the purity of the product.

[0054] The foregoing description is merely a preferred embodiment of the present application and is not intended to limit the present application. Persons skilled in the art will readily appreciate that various modifications and variations are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present application shall be included within the scope of protection of the present application.

Claims

1. A polypeptide solid phase synthesis device, characterized in that: The polypeptide solid phase synthesis device comprises a first circulation pipeline (100), a second circulation pipeline (200), a first switching valve (6) and a second switching valve (10); the first circulation pipeline (100) comprises a synthesis column (9), a third switching valve (5) and a first pump body (15) which are arranged in sequence from upstream to downstream; the second circulation pipeline (200) comprises a fourth switching valve (2), a second pump body (16) and an activation reactor (8) which are arranged in sequence from upstream to downstream; The first switching valve (6) has a switching inlet a1, a switching outlet a1, and a switching outlet a2; the second switching valve (10) includes a switching inlet b1, a switching inlet b2, a switching outlet b1, and a switching outlet b2; the third switching valve (5) has an injection port c1, a switching inlet c1, and a switching outlet c1; the fourth switching valve (2) has an injection port d1, a switching inlet d1, and a switching outlet d1; the outlet of the first pump body (15) and the outlet of the second pump body (16) are both connected to the switching inlet a1 of the first switching valve (6); the switching outlet a1 of the first switching valve (6) is connected to the switching inlet b1 of the second switching valve (10); the second switching valve (10) is connected to the switching inlet b1 of the second switching valve (10); The switching outlet b1 of the valve (10) is connected to the inlet of the synthesis column (9), the outlet of the synthesis column (9) is connected to the switching inlet c1 of the third switching valve (5), the switching outlet c1 of the third switching valve (5) is connected to the inlet of the first pump body (15), the switching outlet a2 of the first switching valve (6) is connected to the inlet of the activation reactor (8), the outlet of the activation reactor (8) is connected to the switching inlet b2 of the second switching valve (10), the switching outlet b2 of the second switching valve (10) is connected to the switching inlet d1 of the fourth switching valve (2), and the switching outlet d1 of the fourth switching valve (2) is connected to the inlet of the second pump body (16).

2. The polypeptide solid phase synthesis device according to claim 1, characterized in that: The first circulation pipeline (100) also includes a fifth switching valve (7), the fifth switching valve (7) having a switching inlet e1, a first flushing inlet and a switching outlet e1, the outlet of the synthesis column (9) is connected to the switching inlet e1 of the fifth switching valve (7), the switching outlet e1 of the fifth switching valve (7) is connected to the switching inlet c1 of the third switching valve (5), and the switching outlet b2 of the second switching valve (10) is also connected to the first flushing inlet of the fifth switching valve (7).

3. The polypeptide solid phase synthesis device according to claim 2, characterized in that: The fifth switching valve (7) further has a second flushing inlet, and the first switching valve (6) further has a switching outlet a3, and the switching outlet a3 of the first switching valve (6) is connected to the second flushing inlet of the fifth switching valve (7).

4. The polypeptide solid phase synthesis device according to claim 1, characterized in that: The polypeptide solid phase synthesis device further comprises a waste liquid pipeline (300), and the third switching valve (5) further comprises a waste liquid outlet, and the waste liquid outlet of the third switching valve (5) is connected to the inlet of the waste liquid pipeline (300).

5. The polypeptide solid phase synthesis device according to claim 4, characterized in that: The waste liquid pipeline (300) is provided with a flow restrictor (13) and a waste liquid outlet valve (14), and the waste liquid outlet valve (14) is located downstream of the flow restrictor (13).

6. The polypeptide solid phase synthesis device according to claim 1, characterized in that: The polypeptide solid phase synthesis device further comprises a detector capable of detecting synthesis parameters, and the detector is arranged on the first circulation pipeline (100).

7. The polypeptide solid phase synthesis device according to claim 6, characterized in that: The detector comprises a UV detector (11), and the UV detector (11) is located between the synthesis column (9) and the third switching valve (5); and / or, The detector further comprises a conductivity detector (3), and the conductivity detector (3) is located between the first pump body (15) and the first switching valve (6).

8. The polypeptide solid phase synthesis device according to claim 6, characterized in that: The polypeptide solid phase synthesis device also includes a controller, and the first pump body (15), the second pump body (16), and the detector are respectively connected to the controller by signal.

9. The polypeptide solid phase synthesis device according to any one of claims 1 to 8, characterized in that: The polypeptide solid phase synthesis device further comprises two first injection valves (1), the outlets of the two first injection valves (1) are both connected to the injection port d1 of the fourth switching valve (2); and / or, The polypeptide solid phase synthesis device further comprises a second injection valve (4), the outlet of the second injection valve (4) being connected to the injection port c1 of the third switching valve (5).

10. The polypeptide solid phase synthesis device according to any one of claims 1 to 8, characterized in that: The pipe body of the first circulation pipeline (100) is made of PEEK, FEP or stainless steel; and / or, The pipe body of the second circulation pipeline (200) is made of PEEK, FEP or stainless steel.

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