Polypeptide reactor and polypeptide production system
By designing an integrated peptide reactor and buffer tank, the problems of complexity and low efficiency in existing systems were solved, achieving efficient and simplified multi-process integration in peptide production.
Patent Information
- Application Number
- CN202422668475.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-01
- Publication Date
- 2025-12-02
- Estimated Expiration
- 2034-11-01
AI Technical Summary
Existing peptide synthesis systems are complex in composition, have low production efficiency, and involve cumbersome processes.
Design a peptide reactor comprising a tank and a cover to form a reaction chamber, with a sieve plate dividing it into a first chamber and a second chamber. The sieve plate is used to separate solid and liquid substances. A temperature control unit, a stirring mechanism, and an anti-corrosion coating are provided to achieve uniform reaction between amino acid liquid and resin layer, and to connect with a buffer tank for precipitation reaction.
It simplifies the structure of peptide production systems, improves reaction uniformity and production efficiency, reduces the need for specialized equipment, and enables integrated production across multiple processes.
Smart Images
Figure CN223615856U_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of peptide production technology, and more specifically, to a peptide reactor and a peptide production system. Background Technology
[0002] Polypeptides are bioactive substances that are related to various cellular functions in organisms. Their molecular structure is between that of amino acids and proteins. They are compounds formed by multiple amino acids linked together by peptide bonds in a certain sequence.
[0003] Peptide synthesis is a repetitive process of adding amino acids. Solid-phase synthesis typically proceeds from the C-terminus (carboxyl terminus) to the N-terminus (amino terminus) to synthesize resin peptides. First, the carboxyl group of the terminal amino acid of the desired peptide chain is covalently linked to an insoluble polymeric resin. Then, this amino acid, bound to the solid support, acts as the amino component, undergoing deamino protection and reaction with an excess of activated carboxyl components to lengthen the peptide chain. This process can be repeated multiple times: coupling → washing → deprotection → neutralization and washing → next round of condensation, until the desired resin peptide chain length is achieved. The resin peptide is then cleaved, and the resulting buffer solution is used for precipitation. The precipitate is washed and dried to obtain the crude peptide.
[0004] Specifically, in existing production processes, resin peptides are vacuum dried, then pyrolyzed with a pyrolysis buffer. After the pyrolysis reaction, the liquid is collected, concentrated under vacuum, and then a precipitant is added to the concentrate for precipitation. After the precipitation reaction, the precipitate is filtered, washed, and dried to obtain crude peptide powder. Existing peptide synthesis systems typically include peptide synthesizers, vacuum drying ovens, pyrolyzers, and centrifuge systems. In other words, existing peptide synthesis systems have a dedicated device for each step, making the production system complex and cumbersome, and resulting in low production efficiency. Utility Model Content
[0005] The purpose of this application is to provide a peptide reactor and a peptide production system to reduce the composition of the production system and improve production efficiency.
[0006] The embodiments of this application are implemented as follows:
[0007] In a first aspect, embodiments of this application provide a polypeptide reactor, including a tank and a cover, the tank and the cover being connected to form a reaction chamber, a sieve plate being disposed inside the tank, the sieve plate dividing the reaction chamber into a first chamber located above the sieve plate and a second chamber located below the sieve plate; the sieve plate is configured to separate solid substances in the production process into the first chamber, and liquid substances in the production process can pass through the sieve plate;
[0008] The first chamber is provided with a feed inlet for adding amino acid liquid; the sieve plate is used to form a resin layer and react with the added amino acid liquid; the tank is provided with a first air inlet, which is connected to the second chamber and can be connected to an air supply device to make the amino acid liquid in the second chamber move upward and re-contact the resin layer on the sieve plate.
[0009] When the peptide reactor provided by the above technical solution is used in peptide production, the sieve plate can serve as a carrier of reactants. During the reaction, amino acids fall from the top of the first chamber and react with the resin layer. Amino acids that have not yet reacted can pass through the sieve plate to the second chamber and move upward under the action of the gas supply device connected to the first air inlet and re-contact the resin layer on the sieve plate, thereby reacting with the resin layer.
[0010] It is easy to understand that the peptide reactor provided in this application can enable the amino acid solution in the second chamber to move upward and re-contact the resin layer, so that the amino acid solution reacts with the resin layer from the bottom of the resin layer. In other words, the amino acid solution can contact the resin layer from more directions to achieve the reaction, so the reaction is more uniform and the production efficiency is higher.
[0011] Furthermore, since the sieve plate can separate solid substances in the production process into the first chamber and liquid substances in the production process can pass through the sieve plate, it is easy to understand that the final peptide cannot pass through the sieve plate. Therefore, the process of cleaning the precipitate obtained after the pyrolysis and precipitation process can also be carried out in the peptide reactor provided in this application. The peptide production system using the peptide reactor provided in this application does not need to set up other special washing equipment, which simplifies the composition of the peptide production system.
[0012] In conjunction with the first aspect, in some alternative embodiments, a temperature control unit is also provided for regulating the temperature within the first chamber so that the reaction to form the peptide takes place at a constant temperature.
[0013] In the above technical solution, the temperature inside the first chamber can be changed by setting a temperature control unit to maintain a stable temperature inside the first chamber. Therefore, some processes that require heating or cooling can also be carried out in the peptide reactor provided in this application.
[0014] In conjunction with the first aspect, in some optional embodiments, the temperature control unit includes a pipe surrounding the outside of the tank body of the first chamber, and a cooling component and a heating component; the pipe is used to provide a heat exchange medium, and the cooling component and the heating component are used to change the temperature of the heat exchange medium; an insulation layer is provided on the side of the pipe away from the tank body.
[0015] In conjunction with the first aspect, in some alternative embodiments, a stirring mechanism is provided in the first chamber for stirring the resin layer.
[0016] In the above technical solution, by setting up a stirring mechanism, the amino acid liquid and the resin layer can be mixed more evenly during the production process, thereby making the reaction more efficient and improving the reaction efficiency.
[0017] In conjunction with the first aspect, in some alternative embodiments, a support assembly is also included, to which the tank is rotatably connected, the tank being configured to rotatably oriented so that the opening of the tank faces downward.
[0018] In the above technical solution, the tank can be rotated to a position where the opening of the tank faces downwards to pour out the material inside the tank.
[0019] In conjunction with the first aspect, in some alternative embodiments, the inner wall of the tank is provided with an anti-corrosion coating.
[0020] In the above technical solution, since the inner wall of the tank is provided with an anti-corrosion coating, the peptide reactor provided by the above technical solution can be used in processes that require the use of corrosive materials, such as the process of pyrolyzing the obtained resin peptides. That is, by adding an anti-corrosion coating to the peptide reactor, the above technical solution can eliminate the need for a pyrolyzer in the peptide production system, thereby reducing the composition of the production system.
[0021] In conjunction with the first aspect, in some alternative embodiments, the anti-corrosion coating is an ETFE structural component or a PTFE structural component.
[0022] In the above technical solution, etfe and ptfe will not react with trifluoroacetic acid added in the pyrolysis process, so as to avoid the peptide reactor being corroded by trifluoroacetic acid and reduce the contamination of the obtained product.
[0023] In conjunction with the first aspect, in some alternative embodiments, an air extraction port is provided above the first chamber, the air extraction port being used to connect a vacuum pumping device to reduce the air pressure inside the first chamber.
[0024] The peptide reactor provided by the above technical solution can reduce the gas pressure in the first chamber, enabling the peptide reactor to concentrate the feed liquid obtained after pyrolysis under reduced pressure.
[0025] Secondly, embodiments of this application provide a peptide production system, including a peptide reactor as provided in the first aspect and a buffer tank for precipitation reaction, wherein the volume of the buffer tank is larger than the volume of the tank body; a second chamber is connected to the buffer tank; and a liquid extraction device is connected to the upper end of the buffer tank.
[0026] In the above technical solution, the buffer tank has a larger volume, making it more suitable for precipitation reactions that require the addition of large amounts of organic solvents for precipitation compared to a peptide reactor. Since the second chamber is connected to the buffer tank, the buffer solution obtained from the lysis process in the peptide reactor can be transferred into the buffer tank for precipitation. The supernatant formed after precipitation can be extracted using a pumping device connected to the upper end of the buffer tank, thus separating the solid and liquid phases.
[0027] In conjunction with the second aspect, in some optional embodiments, the first air inlet is connected to an air supply device via a first air supply line; the cover is connected to a second air supply line, which is used to supply air to the first chamber so that the liquid in the second chamber is transferred to the buffer tank under air pressure.
[0028] In the above technical solution, air can be supplied to the second chamber through the first air supply line, giving the bottom of the peptide reactor a bubbling function. This allows the amino acid feed solution in the second chamber to move upwards and re-contact the resin layer on the sieve plate. Supplying air to the first chamber through the second air supply line also facilitates the transfer of the liquid (i.e., buffer solution) in the second chamber to the buffer tank, making operation convenient. Attached Figure Description
[0029] To more clearly illustrate the technical solutions of the embodiments of this application, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of this application and should not be regarded as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.
[0030] Figure 1 A schematic diagram of the peptide production system provided in the embodiments of this application;
[0031] Figure 2 This is a schematic diagram of a peptide reactor provided in an embodiment of this application.
[0032] Icons: 100-Peptide reactor; 110-Tank body; 111-First chamber; 112-Second chamber; 113-First air inlet; 120-Cover; 121-Feed inlet; 130-Sieve plate; 140-Support assembly; 150-Temperature control unit; 160-Stirring mechanism; 161-Motor; 162-Impeller; 170-Spray ball; 200-Buffer tank; 310-First air supply line; 320-Second air supply line. Detailed Implementation
[0033] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. The components of the embodiments of this application described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.
[0034] Therefore, the following detailed description of the embodiments of this application provided in the accompanying drawings is not intended to limit the scope of the claimed application, but merely to illustrate selected embodiments of the application. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.
[0035] It should be noted that similar labels and letters in the following figures indicate similar items. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.
[0036] In the description of this application, it should be noted that the terms "center," "upper," "lower," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship commonly used when the product is in use. They are used only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this application. In addition, the terms "first," "second," and "third," etc., are used only to distinguish descriptions and should not be construed as indicating or implying relative importance.
[0037] Furthermore, terms such as "horizontal," "vertical," and "sag" do not imply that components must be absolutely horizontal or suspended, but rather that they can be slightly tilted. For example, "horizontal" simply means that its direction is more horizontal relative to "vertical," and does not mean that the structure must be completely horizontal, but can be slightly tilted.
[0038] In the description of this application, it should also be noted that, unless otherwise expressly specified and limited, the terms "set up," "install," "connect," and "link" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.
[0039] This application provides a polypeptide production system, such as... Figure 1As shown, the system includes an interconnected peptide reactor 100 and a buffer tank 200. The peptide reactor 100 provided in this application can realize multiple steps in peptide production, including reacting a resin layer with an amino acid feed solution, and cleaning the precipitate obtained from the precipitation reaction in the buffer tank 200. Because the peptide reactor 100 provided in this application can realize multiple steps, the peptide production system provided in this application can have a relatively simple structure.
[0040] like Figure 1 and Figure 2 As shown, the peptide reactor 100 includes a tank 110 and a cover 120, with the cover 120 covering the opening at the top of the tank 110 to form a reaction chamber. A sieve plate 130 is disposed inside the tank 110, on which a resin layer is deposited. The sieve plate 130 divides the reaction chamber into a first chamber 111 located above the sieve plate 130 and a second chamber 112 located below the sieve plate 130. The sieve plate 130 separates solid substances during the production process into the first chamber 111, while liquid substances can pass through it. The solid substances during the production process include added solid reactants, such as the resin layer, and solid substances obtained from the reaction, such as precipitates obtained in precipitation reactions. An inlet 121 for adding amino acid solution is provided above the first chamber 111. It is easy to understand that after the amino acid solution falls, it can contact and react with the resin layer on the sieve plate 130 to obtain resin peptides. After the resin peptides are cleaved, a precipitation reaction is carried out. The precipitate is then washed and dried to obtain crude peptides. The washing process of the precipitate can also be carried out within the peptide reactor 100. During the washing process, the precipitate is located above the sieve plate 130, and the waste liquid generated after washing flows into the second chamber 112. Furthermore, a drain port can be provided in the tank 110 to discharge the waste liquid from the second chamber 112.
[0041] In some embodiments, the inlet 121 can be located on the cover 120; in other embodiments, the inlet 121 can also be located on the tank 110. In order to make the liquid material more evenly distributed after entering the first chamber 111, in some embodiments, a spray ball 170 can be provided on the cover 120 or the tank 110, with the inlet 121 located on the spray ball 170. By setting the spray ball 170 to add amino acid liquid material into the first chamber 111, the amino acid liquid material can be sprayed more evenly on the resin layer, so that the amino acid liquid material reacts more evenly, fully and efficiently with the resin layer, and the heat of reaction can also be controlled to a certain extent.
[0042] Furthermore, in some embodiments, the tank 110 is also provided with a first air inlet 113, which is connected to the second chamber 112. The peptide production system also includes an air supply device connected to the first air inlet 113 to supply air to the second chamber 112. During the process of adding amino acid solution to the first chamber 111, some amino acid solution may flow into the second chamber 112 before reacting with the resin layer. By supplying air to the second chamber 112 through the air supply device, the amino acid solution in the second chamber 112 can move upward and re-contact the resin layer on the sieve plate 130, thereby reacting with the resin layer. In this embodiment, the amino acid solution can react with the resin layer from the bottom, that is, the amino acid solution can contact the resin layer from more directions to achieve reaction, thus the reaction is more uniform and the production efficiency is higher.
[0043] In some embodiments, the peptide reactor 100 is further provided with a temperature control unit 150 for regulating the temperature within the first chamber 111, so that the peptide formation process is carried out at a constant temperature. Further, the temperature control unit 150 includes a pipe surrounding the outside of the tank body 110 of the first chamber 111, as well as a cooling component and a heating component. A heat exchange medium is disposed within the pipe, and the cooling and heating components are used to change the temperature of the heat exchange medium, thereby regulating the temperature within the first chamber 111. The cooling component can employ existing cooling methods, such as those used in air conditioners or refrigerators; the heating component can employ electric heating. Furthermore, an insulation layer can be provided on the side of the pipe furthest from the tank body 110 to reduce heat exchange between the heat exchange medium within the pipe and the atmospheric environment.
[0044] During peptide production, the peptide coupling reaction releases a large amount of heat. Therefore, a cooling component can be used to lower the temperature inside the first chamber 111. After washing the precipitate, it needs to be dried to obtain crude peptides; therefore, a heating component can be used for drying. It is easy to understand that the peptide reactor 100 can not only cool the coupling reaction process but also dry the precipitate. The peptide reactor 100 can perform multiple processes, thus simplifying the structure of the production system.
[0045] In some embodiments, a stirring mechanism 160 is also provided in the first chamber 111. The stirring mechanism 160 is used to stir the resin layer, which can make the amino acid solution and the resin layer more uniformly mixed during the production process, thereby making the reaction more efficient and improving the reaction efficiency. Furthermore, the stirring mechanism 160 is disposed on the cover 120 so that after the cover 120 is removed, the stirring mechanism 160 is also removed from the first chamber 111 to facilitate the removal of the material from the first chamber 111. In some embodiments, the stirring mechanism 160 includes a motor 161 and a blade 162 connected to the output shaft of the motor 161; wherein the motor 161 is disposed on the cover 120, and the blade 162 is located in the first chamber 111. In other embodiments, the stirring mechanism 160 may also adopt other structures.
[0046] In some embodiments, the inner wall of the tank 110 is provided with an anti-corrosion coating. Furthermore, both the first chamber 111 and the second chamber 112 are provided with anti-corrosion coatings. The anti-corrosion coating is resistant to trifluoroacetic acid corrosion; for example, the anti-corrosion coating can be an ETFE (ethylene-tetrafluoroethylene copolymer) structural component or a PTFE (polytetrafluoroethylene) structural component. In the peptide production process, the resin peptide needs to be cleaved. The cleavage process requires the addition of trifluoroacetic acid to the obtained resin peptide to detach the peptide from the resin peptide. In this embodiment, since the anti-corrosion coating inside the tank 110 is resistant to trifluoroacetic acid corrosion, the peptide reactor 100 provided in this embodiment can also be used for the cleavage process of peptide production. This eliminates the need for a separate cleavage unit in the peptide production system provided in this application, simplifying the structure of the peptide production system.
[0047] Furthermore, in some embodiments, an extraction port is provided above the first chamber 111. The extraction port is used to connect a vacuum device to reduce the air pressure inside the first chamber 111. The extraction port can be located on the cover 120 or on the tank 110. The peptide reactor 100 provided in this embodiment can obtain a buffer solution after cleaving the resin peptide, and concentrate the buffer solution by evacuating the first chamber 111. A precipitation reaction can be achieved by adding a precipitant to the concentrated buffer solution.
[0048] Since the precipitation reaction requires the addition of a large amount of precipitant, the peptide production system provided in this application includes a separate buffer tank 200 for the precipitation reaction. The volume of the buffer tank 200 is larger than the volume of the tank body 110 of the peptide reactor 100, so that the buffer tank 200 can meet the requirements of the precipitation reaction to accommodate the buffer solution and a large amount of organic solvent as the precipitant. The buffer tank 200 is also equipped with a liquid extraction device, which is used to extract the supernatant formed by the precipitation reaction. The liquid extraction device is preferably located at the upper end of the first chamber 111, specifically it can be located at the cover 120 or at the upper end of the tank body 110. The liquid extraction device can be an existing water pump or a device that manually uses the principle of negative pressure to achieve the suction function.
[0049] Furthermore, to facilitate the transfer of the buffer solution from the peptide reactor 100 to the buffer tank 200 for precipitation, in some embodiments, the second chamber 112 is also connected to the buffer tank 200. It is easy to understand that the buffer solution is a liquid, and the liquid in the production process can pass through the sieve plate 130. Therefore, the buffer solution will enter the lower second chamber 112. By connecting the second chamber 112 to the buffer tank 200, the buffer solution can be easily transferred to the buffer tank 200. The second chamber 112 and the buffer tank 200 can be connected via piping.
[0050] Furthermore, the cover 120 is also connected to a second air supply line 320 for supplying air to the first chamber 111, so that the liquid in the second chamber 112 can be transferred to the buffer tank 200 under air pressure. It is easy to understand that the air pressure in the first chamber 111 can also enter the second chamber 112. When the air pressure in the first chamber 111 increases, the buffer solution in the second chamber 112 can enter the buffer tank 200, making the process of transferring the buffer solution to the buffer tank 200 very simple and efficient. Furthermore, the air source connected to the second air supply line 320 can be from the air supply device connected to the first air supply line 310.
[0051] In some implementations, such as Figure 2 As shown, it also includes a support assembly 140, and the tank 110 is rotatably connected to the support assembly 140. The tank 110 is rotatable so that the opening of the tank 110 faces downward. It is easy to understand that by rotating the tank 110 to face downward, the material in the first chamber 111 can be poured out.
[0052] The production process of the polypeptide production system provided in this application includes:
[0053] S1: Add a resin layer and amino acid solution to the first chamber 111 to react and obtain resin peptides until a resin peptide of a specified length is synthesized; during the reaction, gas is introduced into the second chamber 112 through the first gas supply pipe 310.
[0054] S2: Trifluoroacetic acid is added to the first chamber 111 to release the polypeptide from the resin peptide; the resin after polypeptide release and the buffer containing polypeptide are obtained.
[0055] S3: Transfer the buffer solution into the buffer tank 200 through the tubing between the second chamber 112 and the buffer tank 200; then pour out the resin in the peptide reactor 100;
[0056] S4: Transfer the buffer solution in buffer tank 200 to peptide reactor 100, and use a vacuum device to evacuate the tank 110 to concentrate the buffer solution.
[0057] S5: Transfer the concentrated buffer solution to buffer tank 200 and add precipitant; extract the supernatant using a pumping device and transfer the resulting precipitate to peptide reactor 100;
[0058] S6: The precipitate is filtered and washed in the peptide reactor 100, and the first chamber 111 is heated by the temperature control unit 150 to dry the precipitate and obtain crude peptide; finally, the tank 110 of the peptide reactor 100 is rotated to the position with the opening facing downward to pour out the obtained crude peptide.
[0059] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.
Claims
1. A polypeptide reactor, characterized in that, The device includes a tank and a cover, which are connected to form a reaction chamber. A sieve plate is provided inside the tank, which divides the reaction chamber into a first chamber located above the sieve plate and a second chamber located below the sieve plate. The sieve plate is configured to separate solid substances in the production process into the first chamber, while liquid substances in the production process can pass through the sieve plate. The first chamber is provided with a feed inlet for adding amino acid liquid; the sieve plate is used to form a resin layer and react with the added amino acid liquid; the tank is provided with a first air inlet, which is connected to the second chamber and can be connected to an air supply device to make the amino acid liquid in the second chamber move upward and re-contact the resin layer on the sieve plate.
2. The polypeptide reactor according to claim 1, characterized in that, It is also equipped with a temperature control unit for regulating the temperature in the first chamber so that the process of forming peptides is carried out at a constant temperature.
3. The polypeptide reactor according to claim 2, characterized in that, The temperature control unit includes a pipe surrounding the outside of the tank body in the first chamber, as well as a refrigeration component and a heating component; the pipe is used to provide a heat exchange medium, and the refrigeration component and the heating component are used to change the temperature of the heat exchange medium; an insulation layer is provided on the side of the pipe away from the tank body.
4. The polypeptide reactor according to claim 1, characterized in that, The first chamber is equipped with a stirring mechanism for stirring the resin layer.
5. The polypeptide reactor according to claim 1, characterized in that, It also includes a support assembly to which the tank is rotatably connected, the tank being configured to rotate so that the opening of the tank faces downward.
6. The polypeptide reactor according to claim 1, characterized in that, The inner wall of the tank is provided with an anti-corrosion coating.
7. The polypeptide reactor according to claim 6, characterized in that, The anti-corrosion coating is an ETFE structural component or a PTFE structural component.
8. The polypeptide reactor according to claim 6, characterized in that, An air extraction port is provided above the first chamber, which is used to connect a vacuum pumping device to reduce the air pressure inside the first chamber.
9. A polypeptide production system, characterized in that, The apparatus includes a peptide reactor as described in any one of claims 1-8, and a buffer tank for precipitation reaction, wherein the volume of the buffer tank is greater than the volume of the tank body; the second chamber is in communication with the buffer tank; and a pumping device is connected to the upper end of the buffer tank.
10. The polypeptide production system according to claim 9, characterized in that, The first air inlet is connected to an air supply device via a first air supply pipeline; the cover is connected to a second air supply pipeline, which is used to supply air to the first chamber so that the liquid in the second chamber is transferred to the buffer tank under air pressure.