Filtering reaction kettle for polypeptide synthesis

Abstract

The utility model discloses a filtering reaction kettle for polypeptide synthesis. The filtering reaction kettle comprises a reaction kettle body, the bottom of the reaction kettle body is fixedly connected with a communicated discharge pipe; the first filtering transverse cylinder and the second filtering transverse cylinder are both of a cylindrical structure; rotating shafts are rotationally connected to the centers in the first filtering transverse cylinder and the second filtering transverse cylinder; a cross-shaped partition plate is fixedly connected to the rotating shaft, then the adjusting shifting block is rotated to drive the cross-shaped partition plate to rotate and switch, and the standby filter element group enters a working position, so that the time period for maintaining the optimal filtering efficiency of the system is effectively prolonged, and when a failed filter element needs to be replaced, the used filter element can be rotated to a fan-shaped notch to be pulled and replaced; by means of the design, the online filter element replacement function is achieved, continuous and efficient operation of a reaction kettle filtering system is guaranteed, the continuous production operation duration of the polypeptide synthesis reaction kettle is prolonged, and the downtime caused by filter element replacement is remarkably shortened.

Description

Technical Field

[0001] This utility model belongs to the technical field of polypeptide synthesis equipment, specifically, it relates to a filter reaction vessel for polypeptide synthesis. Background Technology

[0002] Peptide synthesis is divided into two chemical synthesis methods: solid-phase synthesis and liquid-phase synthesis. The basic principle is to link amino acids one by one into a polypeptide chain through chemical reactions. It is widely used in drug development, antibacterial and anticancer applications, food health, and biomaterials, and is an important biochemical technology. In peptide synthesis (especially solid-phase synthesis), separating the solid-phase support (such as resin) from the liquid-phase reactants, byproducts, or solvents ensures efficient reaction and improves product purity. Since each step in solid-phase synthesis (deprotection → washing → coupling → washing) requires cyclic operation, filtration is fundamental to achieving multi-step automation, ensuring that the reaction conditions at each step are independently controllable.

[0003] Patent CN222567720U discloses a peptide synthesis device, including a reaction vessel, a first filtration device, and a second filtration device. By integrating the peptide synthesis reaction and filtration into the same peptide synthesis device, continuous operation of peptide synthesis reaction and filtration is achieved, improving processing efficiency and production efficiency. Furthermore, through two stages of filtration with different precision, a product solution of better quality is obtained.

[0004] In the above-mentioned patent's technical solution, continuous operation of peptide synthesis reaction and filtration is achieved through the first and second filtration devices. However, after the filter elements of the first and second filtration devices have been performing filtration functions for a long time, they will inevitably become clogged, the filtration effect will gradually deteriorate or filtration will no longer be possible, and the machine needs to be stopped to replace the filter elements. This prolongs the continuous operation capability of the peptide synthesis reactor and has certain shortcomings. Utility Model Content

[0005] To address the technical problem in existing technologies where filter cartridges become clogged during peptide synthesis, requiring significant time for replacement and thus limiting the continuous operation of the peptide synthesis reactor, this invention provides a filter reactor for peptide synthesis.

[0006] The objective of this utility model can be achieved through the following technical solutions:

[0007] A filtration reactor for peptide synthesis includes a reactor body; a discharge pipe is fixedly connected to the bottom of the reactor body; it also includes a first filter cylinder and a second filter cylinder, both of which are cylindrical in shape; a rotating shaft is rotatably connected to the center of the first and second filter cylinders; a cross-shaped partition is fixedly connected to the rotating shaft, dividing the internal space of the first or second filter cylinder into four equal independent spaces; staggered partitions are fixedly connected to the rotating shaft at positions corresponding to the cross-shaped partitions, further dividing each of the four equal independent spaces into a filtration zone space and a feed passage zone space; a filter element is provided inside the filtration zone.

[0008] Furthermore, the outer edge of the cross-shaped partition abuts against the inner wall of the first or second filter cylinder; rubber ribs are fitted onto the outer edge of the cross-shaped partition.

[0009] Furthermore, the filtration accuracy of the filter element inside the first filter cylinder is less than that inside the second filter cylinder.

[0010] Furthermore, a first connecting pipe is fixedly connected to the middle of the upper part of the first filter cylinder; the first filter cylinder and the second filter cylinder are connected by a second connecting pipe, and one end of the second connecting pipe is connected to the filter area of ​​the first filter cylinder, and the other end is connected to the material passage area of ​​the second filter cylinder.

[0011] Furthermore, multiple discharge pipes are fixedly connected to the second filter cylinder along the axial direction, and each discharge pipe is equipped with a solenoid valve.

[0012] Furthermore, an adjustment hole is provided at one end of the rotating shaft; an adjustment rod is inserted inside the adjustment hole; both the adjustment rod and the adjustment hole are hexagonal structures that fit together.

[0013] Furthermore, an adjusting block is fixedly connected to the end of the adjusting rod. The adjusting block consists of a rod body and a circular block, wherein the circular block is fixedly connected to the adjusting rod.

[0014] Furthermore, a fan-shaped slit is provided on one end face of both the first and second filter cylinders; a fan-shaped cover is detachably provided on the fan-shaped slit.

[0015] Furthermore, the cross-shaped partition and the staggered partition are fixed with limiting blocks at the positions corresponding to the filtration zone, so that a gap is formed between the filter element and the first filter cylinder or between the filter element and the second filter cylinder.

[0016] The beneficial effects of this utility model are as follows: When a filter element becomes clogged or its filtration efficiency decreases, the operator can first pull the adjusting rod out of the adjusting hole a suitable distance to avoid the limiting constraint of the U-shaped locking block. Then, by rotating the adjusting lever, the cross partition is driven to rotate and switch, allowing the spare filter element group to enter the working position. This effectively extends the time period during which the system maintains optimal filtration efficiency. When it is necessary to replace a failed filter element, the used filter element can be rotated to the fan-shaped cut position for extraction and replacement. This design realizes the online filter element replacement function, ensuring the continuous and efficient operation of the reactor filtration system, increasing the continuous production operation time of the peptide synthesis reactor, and significantly reducing downtime caused by filter element replacement. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the overall structure of this utility model;

[0018] Figure 2 This is a schematic diagram showing the cooperation between the first and second filter cylinders in this utility model;

[0019] Figure 3 This is a cross-sectional view of the first and second filter cylinders in this utility model.

[0020] Figure 4 This is an exploded view of the first and second filter cylinders in this utility model.

[0021] The attached diagram lists the components represented by each number as follows:

[0022] 1. Reactor body; 2. Discharge pipe; 3. First connecting pipe; 4. First filter cylinder; 5. Second filter cylinder; 6. Rotating shaft; 7. Cross partition; 8. Staggered partition; 9. Filter element; 10. Limiting block; 11. Through hole; 12. Filtration zone; 13. Feed passage zone; 14. Second connecting pipe; 15. Discharge pipe; 16. Solenoid valve; 17. Adjustment hole; 18. Adjustment lever; 19. Adjustment rod; 20. U-shaped locking block; 21. Fan-shaped cut; 22. Fan-shaped cover. Detailed Implementation

[0023] 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.

[0024] This embodiment uses a reaction vessel for solid-phase synthesis of peptides to prepare the antitumor drug leuprorelin as an example to introduce the filtration reaction vessel for peptide synthesis provided in this application.

[0025] Please see Figure 1 As shown, a filtration reactor for peptide synthesis includes a reactor body 1; a discharge pipe 2 is fixedly connected to the bottom of the reactor body 1, and the synthesis product inside the reactor body 1 is discharged by negative pressure suction; it also includes a first filter cylinder 4 and a second filter cylinder 5 disposed on the side of the reactor body 1, both of which are cylindrical structures and their bottoms are fixed to the ground by support legs.

[0026] Please refer to it again. Figures 3-4 As shown, a rotating shaft 6 is rotatably connected to the center of both the first filter cylinder 4 and the second filter cylinder 5. The two ends of the rotating shaft 6 are rotatably connected to the two ends of the first filter cylinder 4 or the second filter cylinder 5, respectively. A cross-shaped partition 7 is fixedly connected to the rotating shaft 6. The outer edge of the cross-shaped partition 7 abuts against the inner wall of the first filter cylinder 4 or the second filter cylinder 5 to improve the airtightness between the cross-shaped partition 7 and the reactor body 1, and to divide the internal space of the first filter cylinder 4 or the second filter cylinder 5 into four equal independent spaces. A staggered partition 8 is fixedly connected to the rotating shaft 6 at the position between the cross-shaped partitions 7. The staggered partition 8 further divides each of the four equal independent spaces into a filtration zone 12 space and a material passage zone 13 space. The staggered partition 8 has evenly distributed through holes 11. A filter element 9 is provided inside the filtration zone 12, and the filtration accuracy of the filter element 9 inside the first filter cylinder 4 is less than that inside the second filter cylinder 5. Accordingly, the filter elements 9 inside the two can be selected from filter elements 9 of different materials and different precision to perform filtration operations. For example, the filter element 9 inside the first filter cylinder 4 can be a glass fiber filter element 9 or a stainless steel sintered filter element 9 (coarse filtration), and the filter element 9 inside the second filter cylinder 5 can be a ceramic membrane or a polyethersulfone membrane (fine filtration), etc.

[0027] Rubber ribs 23 are fitted on the outer edge of the cross partition 7 to further improve the airtightness between the cross partition 7 and the reactor body 1; the cross partition 7 and the staggered partition 8 are fixed with limit blocks 10 at the positions corresponding to the filtration zone 12 to fix the filter element 9, so that a gap is formed between the filter element 9 and the first filter cylinder 4 or between the filter element 9 and the second filter cylinder 5.

[0028] Please refer to it again. Figures 1-3 As shown, a first connecting pipe 3 is fixedly connected to the middle of the upper part of the first filter cylinder 4. The first connecting pipe 3 is connected to the discharge pipe 2 through a connector, which can transport the material inside the reactor body 1 to the inside of the first filter cylinder 4. The first filter cylinder 4 and the second filter cylinder 5 are connected by a second connecting pipe 14, and one end of the second connecting pipe 14 is connected to the filter area 12 of the first filter cylinder 4, and the other end is connected to the material passage area 13 of the second filter cylinder 5. Multiple discharge pipes 15 are fixedly connected to the second filter cylinder 5 along the axial direction. Each discharge pipe 15 is equipped with a solenoid valve 16 to control the opening and closing of each discharge pipe 15.

[0029] Please refer to it again. Figure 4 As shown, an adjustment hole 17 is provided at one end of the rotating shaft 6; an adjustment rod 19 is inserted inside the adjustment hole 17; both the adjustment rod 19 and the adjustment hole 17 are hexagonal structures that fit together; an adjustment lever 18 is fixedly connected to the end of the adjustment rod 19, which is composed of a rod body and a round block, wherein the round block is fixedly connected to the adjustment rod 19; U-shaped locking blocks 20 are fixedly provided at the positions of the first filter cylinder 4 and the second filter cylinder 5 corresponding to the adjustment rod 19.

[0030] Please refer to it again. Figure 4 As shown, a fan-shaped cutout 21 is provided on one end face of the first filter cylinder 4 and the second filter cylinder 5. The fan-shaped cutout 21 is used for replacing the filter element 9. A fan-shaped cover 22 is detachably provided on the fan-shaped cutout 21. The fan-shaped cover 22 and the fan-shaped cutout 21 can be connected by a spring clip to protect the internal components of the first filter cylinder 4 and the second filter cylinder 5.

[0031] To facilitate understanding of the above-mentioned technical solution of this utility model, the working principle or operation method of this utility model in actual process will be described in detail below:

[0032] When preparing the antitumor drug leuprorelin using a reaction vessel for solid-phase synthesis of peptides, the following steps can be specifically performed:

[0033] S1: 2-Chlorotriphenylmethyl chloride resin solid support, protected amino acids such as Fmoc-Arg(Pbf)-OH, Fmoc-Leu-OH, and Fmoc-D-Leu-OH, coupling agents such as HBTU / HOBt / DIPEA or DIC / HOBt, and deprotection agent 20% piperidine / DMF solution are added to the reaction vessel body 1. Then, under stirring and temperature control conditions, the amino acids are gradually coupled to form a fully protected polypeptide chain through solid-phase synthesis. The resulting mixture contains the resin support, unreacted amino acids, coupling agent byproducts (such as HOBt), deprotected groups (such as Fmoc decomposition products), and solvent (DMF or DCM).

[0034] S2: Under the action of the pump, the raw materials (the mixture after the coupling reaction) inside the reactor are discharged into the first filter cylinder 4 through the cooperation of the discharge pipe 2 and the first connecting pipe 3.

[0035] S3: The raw material (the mixture generated after the coupling reaction) first enters the feed zone 13 inside one of the four independent spaces. After the feed zone 13 is full, it first enters the filter zone 12 through the through hole 11, and then precipitates out from the filter element 9 inside the filter zone 12. The resin fragments and undissolved amino acids are left inside the feed zone 13 inside the first filter cylinder 4, while the intermediate containing the target polypeptide, solvent and small molecule by-products (such as the DIC by-product urea) are precipitated out, completing the initial coarse-precision filtration.

[0036] The material flow direction is as follows: material passage zone 13 → through hole 11 → filtration zone 12 (filter element 9) → gap → discharge pipe 15.

[0037] S4: The filtered raw material (containing the target polypeptide intermediate, solvent and small molecule byproducts) enters the feed zone 13 inside the second filter cylinder 5 under the action of the second connecting tube 14. After the feed zone 13 is full, the small molecule byproducts (such as HOBt residue and salt ions) and the incompletely coupled short peptide chains remain in the filter zone 12 inside the second filter cylinder 5. The finely filtered raw material (purified fully protected polypeptide chains) enters the gap between the filter element 9 and the second filter cylinder 5 separated by the limiting block 10.

[0038] S5: Because the gap between the discharge pipe 15 and the filter element 9 and the second filter cylinder 5 is connected, the final filtered raw material (fully protected polypeptide solution, such as crude leuprolide peptide) can be discharged by controlling the solenoid valve 16 to open several of the discharge pipes 15.

[0039] S6: The fully protected peptide solution (leuprorelin crude peptide) proceeds to the subsequent cleavage and purification steps.

[0040] The reactor filtration system features a structure with four equally divided independent spaces inside the first and second filter cylinders 4 and 5. Each independent space is equipped with a set of filter elements 9 to achieve coarse / fine filtration. When a set of filter elements 9 becomes clogged or its filtration efficiency decreases, the operator can first pull the adjusting rod 19 out of the adjusting hole 17 a suitable distance to avoid the limiting constraint of the U-shaped locking block 20. Then, by rotating the adjusting lever 18, the cross partition 7 is rotated to switch the system, allowing the spare set of filter elements 9 to enter the working position, thereby effectively extending the time period during which the system maintains optimal filtration efficiency. When it is necessary to replace a failed filter element 9, the failed filter element 9 is rotated to the fan-shaped cut 21 position. At this time, the equipment operation can be briefly stopped, or during equipment operation, the filter element 9 can be pulled out and replaced along the axial direction of the rotating shaft. After the operation is completed, the sealing state is restored by installing the fan-shaped cover 22, and the adjusting rod 19 is locked back into the U-shaped locking block 20. This design enables online filter element replacement, ensuring the continuous and efficient operation of the reactor filtration system, increasing the continuous production time of the peptide synthesis reactor, and significantly reducing downtime caused by filter element replacement.

[0041] It should be noted that, in this document, terms such as “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[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.

Claims

1. A filtration reactor for polypeptide synthesis, comprising a reactor body (1); a discharge pipe (2) is fixedly connected to the bottom of the reactor body (1); characterized in that: It also includes a first filter cylinder (4) and a second filter cylinder (5), both of which are cylindrical structures; the first filter cylinder (4) and the second filter cylinder (5) are rotatably connected to the center of their interiors by a rotating shaft (6); a cross partition (7) is fixedly connected to the rotating shaft (6) to divide the interior space of the first filter cylinder (4) or the second filter cylinder (5) into four independent spaces. The rotating shaft (6) is fixed with an interlaced partition (8) at the position between the cross partitions (7). The interlaced partition (8) divides each of the four equal parts of the independent space into a filtration zone (12) space and a material passage zone (13) space. The interlaced partition (8) has evenly distributed through holes (11). A filter element (9) is provided inside the filtration zone (12).

2. The filtration reactor for polypeptide synthesis according to claim 1, characterized in that: The outer edge of the cross partition (7) abuts against the inner wall of the first filter cylinder (4) or the second filter cylinder (5); the outer edge of the cross partition (7) is fitted with rubber ribs (23).

3. The filtration reactor for polypeptide synthesis according to claim 1, characterized in that: The filtration accuracy of the filter element (9) inside the first filter cylinder (4) is less than that inside the second filter cylinder (5).

4. The filtration reactor for polypeptide synthesis according to claim 1, characterized in that: The first filter cylinder (4) is fixedly connected to the middle of the upper part of the first connecting pipe (3); the first filter cylinder (4) and the second filter cylinder (5) are connected by the second connecting pipe (14), and one end of the second connecting pipe (14) is connected to the filter area (12) of the first filter cylinder (4), and the other end is connected to the material passage area (13) of the second filter cylinder (5).

5. The filtration reactor for polypeptide synthesis according to claim 1, characterized in that: Multiple discharge pipes (15) are fixedly connected to the second filter cylinder (5) along the axial direction, and each discharge pipe (15) is equipped with a solenoid valve (16).

6. The filtration reactor for polypeptide synthesis according to claim 1, characterized in that: An adjustment hole (17) is provided at one end of the rotating shaft (6); an adjustment rod (19) is inserted inside the adjustment hole (17); the adjustment rod (19) and the adjustment hole (17) are both regular hexagonal structures that fit each other.

7. The filtration reactor for polypeptide synthesis according to claim 6, characterized in that: An adjusting block (18) is fixedly connected to the end of the adjusting rod (19). The adjusting block (18) is composed of a rod body and a round block, wherein the round block is fixedly connected to the adjusting rod (19). U-shaped locking blocks (20) are fixedly provided on the first filter cylinder (4) and the second filter cylinder (5) at positions corresponding to the adjusting rod (19).

8. The filtration reactor for polypeptide synthesis according to claim 1, characterized in that: The first filter cylinder (4) and the second filter cylinder (5) each have a fan-shaped cut (21) on one end face; a fan-shaped cover (22) is detachably provided on the fan-shaped cut (21).

9. A filtration reactor for polypeptide synthesis according to claim 1, characterized in that: The cross-shaped partition (7) and the staggered partition (8) are fixed with limiting blocks (10) at the positions corresponding to the filter zone (12), so that a gap is formed between the filter element (9) and the first filter cylinder (4) or between the filter element (9) and the second filter cylinder (5).

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