A fully stirred peptide solid phase synthesis device

Abstract

The invention relates to the technical field of polypeptide synthesis, and in particular to a polypeptide solid phase synthesis device capable of being fully stirred, comprising a fully stirring device installed inside a stirring barrel, the fully stirring device comprising a turning base, a mixing sleeve, a self-priming transmission shaft and a solvent detection device, the self-priming transmission shaft being installed at the axial center position of the stirring barrel, the turning base being installed at the bottom of the stirring barrel, the turning base being transmission-connected with the self-priming transmission shaft, the turning base being used for mixing stirring materials, the mixing sleeve being installed at the axial center position of the turning base, the mixing sleeve being transmission-connected with the self-priming transmission shaft, a reflux gap being formed between the mixing sleeve and the turning base, the solvent detection device being installed on the self-priming transmission shaft, the solvent detection device being used for extraction detection, and the invention can effectively ensure the adequacy of stirring and improve work efficiency and work quality.

Description

Technical Field

[0001] The invention relates to the technical field of polypeptide synthesis, and in particular to a fully stirred polypeptide solid phase synthesis device. Background Art

[0002] The principle of solid phase synthesis of peptides is: first, covalently cross-link an amino-protected amino acid on a solid phase carrier, usually using a 20% piperidine N, N-dimethylformamide solution to remove the amino-protecting group to expose the amino group; then add the next amino-protected amino acid, a condensing agent, and an inhibitor, and the carboxyl group of the second amino acid condenses with the amino group of the first amino acid to form an amide bond; in this way, a dipeptide with an amino-protecting group is obtained on the solid phase carrier; repeat the above reaction operation to extend the peptide chain from the C-terminus to the N-terminus until the desired peptide sequence is obtained.

[0003] Chinese patent CN217997060U discloses a polypeptide solid phase synthesis device, which is designed to detect whether the resin is completely washed to avoid residual DMF solution containing alkali solution. Its technical solution is as follows: a polypeptide solid phase synthesis device, including a reaction tank, a stirring module is arranged in the reaction tank, an amino acid input pipe, a DMF solution input pipe, and an alkaline solvent input pipe are connected to the upper part of the reaction tank; a liquid outlet pipe is arranged at the bottom of the reaction tank, and the liquid outlet pipe is connected to a temporary storage tank, a pH online detector is connected to the temporary storage tank, and an emptying pipe is arranged on the temporary storage tank; a filter sieve plate is horizontally arranged in the reaction tank, and the stirring module is located above the filter sieve plate; valves are arranged on the amino acid input pipe, the DMF solution input pipe, the alkaline solvent input pipe, the liquid outlet pipe and the emptying pipe, which belongs to the technical field of polypeptide synthesis.

[0004] Although the above technical solution can detect the temporary storage tank to temporarily store the waste liquid, and determine whether the washing is qualified by analyzing the pH value of the waste liquid, the existing stirring resin washing is carried out by rotating the stirring blade in one direction. This stirring method is difficult to fully diffuse the resin to achieve a good washing effect, resulting in each resin washing needing to be repeatedly washed, affecting production efficiency and wasting washing solution. Summary of the invention

[0005] In view of the above problems, a fully stirred polypeptide solid phase synthesis device is provided, which can effectively ensure the adequacy of stirring through a fully stirring device, thereby improving work efficiency and work quality.

[0006] In order to solve the problems of the prior art, the present invention provides a fully stirred polypeptide solid phase synthesis device, comprising a fully stirring device installed inside a stirring barrel, the fully stirring device comprising a turning base, a mixing sleeve, a self-priming transmission shaft and a solvent detection device; the self-priming transmission shaft is installed at the axial position of the stirring barrel, the turning base is installed at the bottom of the stirring barrel, the turning base is connected to the self-priming transmission shaft, the turning base is used to mix and stir the materials, the mixing sleeve is installed at the axial position of the turning base, the mixing sleeve is connected to the self-priming transmission shaft, a reflux gap is formed between the mixing sleeve and the turning base, the solvent detection device is installed on the self-priming transmission shaft, and the solvent detection device is used for extraction detection.

[0007] Preferably, the twisting base includes a filter layer installed at the bottom of the mixing barrel, a scraper frame is installed on the filter layer, a rotating sleeve is also installed on the scraper frame, the rotating sleeve is in contact with the inner wall of the mixing barrel, and the inner wall of the rotating sleeve is provided with a plurality of first guide blades.

[0008] Preferably, the turning base further comprises a plurality of boosting nozzles installed on the inner wall of the rotating sleeve, and the boosting nozzles are connected to the self-priming transmission shaft.

[0009] Preferably, a plurality of stirring rods are provided inside the mixing sleeve, and the outer wall of the mixing sleeve is evenly spaced and covered with second guide blades.

[0010] Preferably, both upper and lower ends of the self-priming transmission shaft are provided with flow ports, driving blades are provided inside the flow ports, a suction pump is installed at the lower flow port of the self-priming transmission shaft, the liquid outlet end of the suction pump is connected with the upper flow port of the self-priming transmission shaft through a circulation pipe, a plurality of control valves are installed on the circulation pipe, a first liquid outlet is provided on the outside of the self-priming transmission shaft, the first liquid outlet is connected with the upper flow port of the self-priming transmission shaft, and a reverse transmission mechanism is also installed on the self-priming transmission shaft.

[0011] Preferably, the self-priming transmission shaft also includes an auxiliary driving device installed on the top of the mixing barrel, the auxiliary driving device includes a first rotary driver installed on the top of the mixing barrel, a driving gear is installed at the output end of the first rotary driver, and the auxiliary driving device also includes an adaptive transmission gear plate installed on the self-priming transmission shaft, and the adaptive transmission gear plate is meshed with the driving gear.

[0012] Preferably, a transmission cardan wheel is provided inside the adaptive transmission gear disc, the transmission cardan wheel is fixedly connected to the self-priming transmission shaft, the outer wall of the transmission cardan wheel is covered with cardan protrusions, and a plurality of adaptive interference blocks are installed between the transmission cardan wheels.

[0013] Preferably, the solvent detection device comprises a detection box connected to the circulation pipeline, a solvent detector is arranged inside the detection box, and a liquid inlet and a second liquid outlet are arranged on the detection box.

[0014] Preferably, the solvent detection device also includes an automatic cleaning device for cleaning the inside of the detection box, the automatic cleaning device includes a movable pushing frame, the movable end of the movable pushing frame is equipped with a rotating cleaning shaft, the rotating cleaning shaft extends toward the inside of the detection box, and a separating piston block is also installed at the extended end of the rotating cleaning shaft. The automatic cleaning device also includes a sewage pipe connected to the detection box.

[0015] Preferably, the outer wall of the rotating cleaning shaft is provided with a plurality of liquid spraying holes, and a rotating cleaning wheel is installed beside the liquid spraying holes. The rotating cleaning shaft also includes a rotating driving device, and the rotating driving device is used to drive the rotating cleaning shaft to rotate.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] 1. The resin needs to be washed in time to remove excess alkaline solution. After the washing solution enters the interior of the mixing barrel, the self-priming transmission shaft will suck the washing solution inside the mixing barrel to make the washing solution circulate. When the self-priming transmission shaft sucks the washing solution, it will rotate. When the self-priming transmission shaft rotates, it will drive the turning base and the mixing sleeve to rotate synchronously. When the turning base and the mixing sleeve rotate synchronously, the internal resin and the washing solution will be rotated and stirred synchronously. When the resin and the washing solution are rotated and stirred, the resin will sink to the bottom of the turning base due to gravity. When the turning base rotates, the precipitated resin will be continuously guided to the reflux gap. When the mixing sleeve and the turning base rotate, the reflux gap will form an upward suction force, so that the resin that rotates and enters the reflux gap will rise and move. When the resin rises, it will rub and collide with each other. After the resin passes through the reflux gap and rises to the upper layer of the washing solution, it enters the interior of the mixing sleeve. When the mixing sleeve rotates, the resin that enters will be further mixed and stirred, forming a flowing rotation cycle effect, which can effectively ensure the adequacy of stirring and improve work efficiency.

[0018] 2. The solvent detection device will detect the washing solution sucked and flowing by the self-priming transmission shaft in real time, and detect the alkalinity in the washing solution. If the alkalinity of the washing solution is high, the cleaning solvent can be replaced in time to continue cleaning until the alkalinity in the washing solution meets the standard. Through real-time detection, it can be effectively and quickly determined whether the resin is qualified for cleaning, thereby improving work efficiency and work quality. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a three-dimensional schematic diagram of a fully stirrable peptide solid phase synthesis device.

[0020] Figure 2 yes Figure 1 Partial view at point A in the middle.

[0021] Figure 3 The front view of a fully stirrable peptide solid phase synthesis device.

[0022] Figure 4 yes Figure 3 Cross-sectional view at section BB.

[0023] Figure 5 yes Figure 3 A sectional perspective view at section BB.

[0024] Figure 6 yes Figure 5 A partial enlarged view of point C in the middle.

[0025] Figure 7 yes Figure 5 A partial enlarged view of point D in the middle.

[0026] Figure 8 A three-dimensional schematic diagram of a solvent detection device in a fully stirred peptide solid phase synthesis device Figure 1 .

[0027] Fig. 9 A three-dimensional schematic diagram of a solvent detection device in a fully stirred peptide solid phase synthesis device Figure 2 .

[0028] Fig.10 The present invention is a planar cutaway stereoscopic diagram of a solvent detection device in a fully stirrable peptide solid phase synthesis device.

[0029] The numbers in the figure are:

[0030] 1. Mixing barrel; 2. Turning base; 21. Scraper rack; 22. Rotating sleeve; 23. First guide blade; 24. Boost nozzle; 241. Connecting pipe; 242. Inclined nozzle; 25. Filter layer; 3. Mixing sleeve; 31. Stirring rod; 32. Second guide blade; 4. Self-priming transmission shaft; 41. Flow port; 42. Suction pump; 43. First liquid outlet; 44. Driving blade; 45. Circulation pipe; 46. Control valve; 47. Reverse transmission mechanism; 471. Mounting shell; 472. First conduction bevel gear; 473. Second conduction bevel gear; 474. Third conduction bevel gear; 48. Auxiliary drive device; 481. First rotary Rotary drive; 482, driving gear; 483, adaptive transmission gear disc; 484, transmission clamping wheel; 485, clamping protrusion; 486, adaptive resistance block; 5, solvent detection device; 51, detection box; 52, liquid inlet; 53, second liquid outlet; 54, automatic cleaning device; 541, mobile pushing frame; 5411, linear drive; 5412, pushing connecting plate; 542, rotating cleaning shaft; 5421, spray hole; 5422, rotating cleaning wheel; 5423, driven wheel; 5424, transmission chain; 5426, second rotary drive; 5427, driving wheel; 543, sewage pipe; 544, separating piston block. DETAILED DESCRIPTION

[0031] In order to further understand the features, technical means, specific objectives and functions of the present invention, the present invention is further described in detail below in conjunction with the accompanying drawings and specific implementation methods.

[0032] See also Figures 1 to 10 As shown, a fully stirred polypeptide solid phase synthesis device includes a fully stirring device installed inside a stirring barrel 1, the fully stirring device includes a turning base 2, a mixing sleeve 3, a self-priming transmission shaft 4 and a solvent detection device 5, the self-priming transmission shaft 4 is installed at the axial position of the stirring barrel 1, the turning base 2 is installed at the bottom of the stirring barrel 1, the turning base 2 is connected to the self-priming transmission shaft 4, the turning base 2 is used to mix and stir the materials, the mixing sleeve 3 is installed at the axial position of the turning base 2, the mixing sleeve 3 is connected to the self-priming transmission shaft 4, a reflux gap is formed between the mixing sleeve 3 and the turning base 2, the solvent detection device 5 is installed on the self-priming transmission shaft 4, and the solvent detection device 5 is used for extraction detection.

[0033] During the solid phase synthesis of medical peptides, a solution containing alkali is added into the stirring barrel 1. The solution containing alkali will remove the amino protecting group of the resin, and then the solution containing alkali is discharged from the stirring barrel 1. Subsequently, the resin needs to be washed in time to remove excess alkali solution. After the alkali solution is discharged, the washing solution is transported to the stirring barrel 1. After the washing solution enters the stirring barrel 1, the self-priming transmission shaft 4 will suck the washing solution inside the stirring barrel 1 to make the washing solution circulate. When the self-priming transmission shaft 4 sucks the washing solution, it will rotate. When the self-priming transmission shaft 4 rotates, it will drive the turning base 2 and the mixing sleeve 3 to rotate synchronously. When the turning base 2 and the mixing sleeve 3 rotate synchronously, the internal resin and washing solution will be rotated and stirred synchronously. When the resin and the washing solution are rotated and stirred, the resin will be affected by gravity and will sink to the bottom of the turning base 2. When the twisting base 2 rotates, the precipitated resin will be continuously guided to the reflux gap. When the mixing sleeve 3 and the twisting base 2 rotate, the reflux gap will form an upward suction force, so that the resin that rotates and enters the reflux gap will rise and move. When the resin rises, they will rub and collide with each other. After the resin passes through the reflux gap and rises to the upper layer of the washing solution, it enters the interior of the mixing sleeve 3. When the mixing sleeve 3 rotates, the entered resin will be further mixed and stirred to form a flow-type rotation cycle effect, which can effectively improve the adequacy of stirring. At the same time, the solvent detection device 5 will detect the washing solution sucked and flowed by the self-priming transmission shaft 4 in real time, and detect the alkalinity in the washing solution. If the washing solution contains too much alkalinity, the cleaning solvent can be replaced in time to continue cleaning until the alkalinity in the washing solution meets the standard. Through real-time detection, it is effective to quickly determine whether the resin is qualified for cleaning, thereby improving work efficiency and work quality.

[0034] See also Figures 4 to 6As shown, the twisting base 2 includes a filter layer 25 installed at the bottom of the mixing barrel 1, a scraper frame 21 is installed on the filter layer 25, and a rotating sleeve 22 is also installed on the scraper frame 21. The rotating sleeve 22 is in contact with the inner wall of the mixing barrel 1, and a plurality of first guide blades 23 are provided on the inner wall of the rotating sleeve 22.

[0035] The filter layer 25 is arranged at the bottom of the stirring barrel 1 for filtering and separating the resin and the solution. When it is necessary to wash the resin in time and remove the excess alkaline solution, the washing solution is transported to the stirring barrel 1 after the alkaline solution is discharged. After the washing solution enters the stirring barrel 1, the self-priming transmission shaft 4 will suck the washing solution inside the stirring barrel 1 to make the washing solution circulate. When the self-priming transmission shaft 4 sucks the washing solution, it will rotate. When the washing solution rotates, it will drive the turning base 2 and the mixing sleeve 3 to rotate synchronously. When the turning base 2 and the mixing sleeve 3 rotate synchronously, the resin and the washing solution inside will be mixed. When the resin and the washing solution are stirred synchronously, the resin will sink to the filter layer 25 due to the influence of gravity. Then, when the scraper frame 21 rotates, it will drive the resin deposited on the filter layer 25 to gather and move toward the inner wall of the rotating sleeve 22. When the rotating sleeve 22 rotates, the first guide blade 23 on the inner wall will drive the gathered resin to rise along the first guide blade 23 and enter the reflux gap between the mixing sleeve 3 and the turning base 2. When the first guide blade 23 rotates, it will form an upward pushing spiral driving force, and the rotating mixing sleeve 3 can effectively drive the washing solution and resin in the reflux gap to spirally rise. It can effectively avoid resin precipitation and improve the adequacy of resin stirring.

[0036] See also Figures 4 to 6 As shown, the turning base 2 further includes a plurality of boosting nozzles 24 installed on the inner wall of the rotating sleeve 22 , and the boosting nozzles 24 are connected to the self-priming transmission shaft 4 .

[0037] The booster nozzle 24 is in a long strip shape and is covered with inclined nozzles 242 arranged obliquely upward. The booster nozzle 24 is connected to the self-priming transmission shaft 4 through a connecting pipe 241 .

[0038] The booster nozzles 24 are evenly installed on the inner wall of the rotating sleeve 22. When the self-priming transmission shaft 4 sucks the washing solution inside the stirring barrel 1 in a suction cycle, the self-priming transmission shaft 4 will transport the sucked washing solution to the connecting pipe 241. The connecting pipe 241 transports the washing solution to the booster nozzle 24. The booster nozzle 24 then transports the washing solution to the reflux gap through multiple inclined nozzles 242. When the turning base 2 cooperates with the mixing sleeve 3 to guide the resin deposited on the filter layer 25 to the reflux gap, the washing solution sprayed on the multiple inclined nozzles 242 will help the resin in the reflux gap to flow upward, effectively improving the resin rising and floating effect.

[0039] See also Figures 4 to 7 As shown, a plurality of stirring rods 31 are arranged inside the mixing sleeve 3, and the outer wall of the mixing sleeve 3 is evenly spaced and covered with second guide blades 32.

[0040] When the self-priming transmission shaft 4 sucks the washing solution, it will rotate. The self-priming transmission shaft 4 will drive the turning base 2 and the mixing sleeve 3 to rotate synchronously. When the turning base 2 and the mixing sleeve 3 rotate synchronously, the resin and the washing solution inside will rotate and stir synchronously. When the resin and the washing solution are rotated and stirred, the resin will sink to the bottom of the turning base 2 due to the influence of gravity. When the turning base 2 rotates, the precipitated resin will be continuously guided to the reflux gap. When the mixing sleeve 3 rotates, the second guide blade 32 on the outside will spirally rotate at the reflux gap. The rotation of the second guide blade 32 will form a spiral suction in the reflux gap. The spiral suction can effectively guide the resin to flow upward. When the resin floats to the top of the mixing sleeve 3, it will circulate into the interior of the mixing sleeve 3. When the resin enters the interior of the mixing sleeve 3, the stirring rod 31 inside the mixing sleeve 3 will further stir the resin, thereby effectively ensuring the stirring effect.

[0041] See also Figures 1 to 7 As shown, both upper and lower ends of the self-priming transmission shaft 4 are provided with flow ports 41, and driving blades 44 are provided inside the flow ports 41. A suction pump 42 is installed at the lower end flow port 41 of the self-priming transmission shaft 4, and the liquid outlet end of the suction pump 42 is connected with the upper end flow port 41 of the self-priming transmission shaft 4 through a circulation pipe 45. A plurality of control valves 46 are installed on the circulation pipe 45. A first liquid outlet 43 is provided on the outside of the self-priming transmission shaft 4, and the first liquid outlet 43 is communicated with the upper end flow port 41 of the self-priming transmission shaft 4. A reverse transmission mechanism 47 is also installed on the self-priming transmission shaft 4.

[0042] The reverse transmission mechanism 47 includes a mounting shell 471 installed inside the mixing barrel 1, and a first conduction bevel gear 472, a second conduction bevel gear 473 and a third conduction bevel gear 474 are installed inside the mounting shell 471. The first conduction bevel gear 472 is conduction-connected to the turning base 2, the second conduction bevel gear 473 is conduction-connected to the self-priming transmission shaft 4, and the third conduction bevel gear 474 is installed between the first conduction bevel gear 472 and the second conduction bevel gear 473.

[0043] When the self-priming transmission shaft 4 drives the second conduction bevel gear 473 to rotate, the second conduction bevel gear will drive the first conduction bevel gear 472 to rotate synchronously through the third conduction bevel gear 474, and the second conduction bevel gear will rotate in the opposite direction to the first conduction bevel gear 472. When the first conduction bevel gear 472 rotates in the opposite direction, it will drive the turning base 2 and the self-priming transmission shaft 4 to rotate in the opposite direction.

[0044] After the washing solution is added to the stirring barrel 1, it is necessary to drive the turning base 2 and the mixing sleeve 3 to rotate and stir the washing solution and resin in the stirring barrel 1, and the washing solution is sucked from the flow port 41 at the lower end of the self-priming transmission shaft 4 by the suction pump 42, and the washing solution is transported to the circulation pipe 45 through the suction pump 42, and the circulation pipe 45 transports the sucked washing solution to the flow port 41 at the upper end of the self-priming transmission shaft 4, and the washing solution passes through the flow port 41 at the upper end of the self-priming transmission shaft 4 into the interior of the self-priming transmission shaft 4, and the self-priming transmission shaft 4 then transports the washing solution through the first liquid outlet 43. To the boost nozzle 24, a circulation is formed. At the same time, when the washing solution passes through the flow ports 41 at the upper and lower ends of the self-priming transmission shaft 4, the driving blades 44 inside the flow ports 41 are affected by the water flow to form a hydraulic drive, so that the self-priming transmission shaft 4 rotates. When the self-priming transmission shaft 4 rotates, it drives the reverse transmission mechanism 47 and the mixing sleeve 3 to rotate the mixing barrel 1. When the reverse transmission mechanism 47 rotates, it drives the twisting base 2 to rotate in the direction, effectively making the twisting base 2 and the mixing sleeve 3 rotate in the opposite direction. The twisting base 2 and the mixing sleeve 3 rotate in the opposite direction to effectively improve the stirring effect. The control valve 46 on the circulation pipeline 45 is used to control the liquid delivery area.

[0045] See also Figures 1 to 5 As shown, the self-priming transmission shaft 4 also includes an auxiliary driving device 48 installed on the top of the mixing barrel 1, the auxiliary driving device 48 includes a first rotary driver 481 installed on the top of the mixing barrel 1, and a driving gear 482 is installed at the output end of the first rotary driver 481. The auxiliary driving device 48 also includes an adaptive transmission gear disc 483 installed on the self-priming transmission shaft 4, and the adaptive transmission gear disc 483 is meshed with the driving gear 482.

[0046] The first rotary driver 481 is preferably a servo motor. When the self-priming transmission shaft 4 needs to be started to rotate, due to the large amount of resin precipitation accumulation inside the mixing barrel 1, the turning base 2 and the mixing sleeve 3 will cause starting resistance, which will cause the self-priming transmission shaft 4 to be driven slowly by water pressure. In order to quickly drive the self-priming transmission shaft 4 to rotate, the servo motor drives the active gear 482 to rotate. When the active gear 482 rotates, it will drive the adaptive transmission gear plate 483 to rotate. The rotation of the adaptive transmission gear plate 483 can drive the self-priming transmission shaft 4 to start quickly. When the self-priming transmission shaft 4 rotates, it will drive the turning base 2 and the mixing sleeve 3 to rotate synchronously. The rotation of the turning base 2 and the mixing sleeve 3 will drive the resin inside the mixing barrel 1 to float, and the resin floating will reduce the rotation resistance. After the self-priming transmission shaft 4 reaches a certain speed, the servo motor will stop rotating, effectively assisting in starting the self-priming transmission shaft 4 and effectively ensuring the stirring speed.

[0047] See also Figure 2As shown, a transmission cardan wheel 484 is provided inside the adaptive transmission gear disc 483, and the transmission cardan wheel 484 is fixedly connected to the self-priming transmission shaft 4, and the outer wall of the transmission cardan wheel 484 is covered with cardan protrusions 485, and a plurality of adaptive resistance blocks 486 are installed between the transmission cardan wheels 484 and the transmission cardan wheels 484.

[0048] The transmission card-connecting wheel 484 is rotationally connected with the adaptive transmission toothed disc 483, and the transmission card-connecting wheel 484 is fixedly connected with the self-priming transmission shaft 4. When the servo motor drives the driving gear 482 to rotate, the driving gear 482 rotates, which will drive the adaptive transmission toothed disc 483 to rotate. The adaptive friction block 486 inside the adaptive transmission toothed disc 483 will synchronously contract and move under the influence of centrifugal force. When the adaptive friction block 486 contracts, it will conflict with the card-connecting protrusion 485 on the outer wall of the transmission card-connecting wheel 484. At this time, the rotation of the adaptive transmission toothed disc 483 will drive the transmission card-connecting wheel 484 to rotate synchronously, and the rotation of the transmission card-connecting wheel 484 will drive the self-priming transmission shaft 4 to rotate synchronously. When the self-priming transmission shaft 4 reaches a certain speed, the servo motor will stop rotating, and the adaptive transmission toothed disc 483 will stop rotating accordingly. When the adaptive transmission toothed disc 483 stops rotating, the adaptive friction block 486 will automatically disengage from the transmission card-connecting wheel 484, effectively realizing adaptive conduction and avoiding conduction resistance.

[0049] See also Figure 8 As shown, the solvent detection device 5 includes a detection box 51 connected to the circulation pipeline 45. A solvent detector is arranged inside the detection box 51. The detection box 51 is provided with a liquid inlet 52 and a second liquid outlet 53.

[0050] The liquid inlet 52 and the second liquid outlet 53 on the detection box 51 are used to connect to the circulation pipe 45. When the washing solution is applied to the resin inside the stirring barrel 1, the self-priming transmission shaft 4 will circulate and suck the washing solution. When it is necessary to detect the alkalinity in the washing solution, the circulating washing solution is transported to the inside of the detection box 51 through the control valve 46 on the circulation pipe 45. The detection box 51 will detect the alkalinity in the washing solution, so as to quickly judge whether the resin has been cleaned.

[0051] See also Figures 8 to 10 As shown, the solvent detection device 5 also includes an automatic cleaning device 54 for cleaning the inside of the detection box 51. The automatic cleaning device 54 includes a movable pushing frame 541. The movable end of the movable pushing frame 541 is equipped with a rotating cleaning shaft 542. The rotating cleaning shaft 542 extends toward the inside of the detection box 51. A separating piston block 544 is also installed at the extending end of the rotating cleaning shaft 542. The automatic cleaning device 54 also includes a sewage pipe 543 connected to the detection box 51.

[0052] The movable pushing frame 541 includes a linear driver 5411 , and a pushing connecting plate 5412 is installed at the output end of the linear driver 5411 . The pushing connecting plate 5412 is rotatably connected to the rotating cleaning shaft 542 .

[0053] The linear drive 5411 is preferably an electric push rod. After the inspection of the inspection box 51 is completed, when the inside of the inspection box 51 needs to be cleaned to ensure the accuracy of the next inspection, the electric push rod will push the movable pushing frame 541 to move. When the movable pushing frame 541 moves, it will drive the rotating cleaning shaft 542 to extend and move toward the inside of the inspection box 51. The movement of the rotating cleaning shaft 542 will drive the separating piston block 544 to move to squeeze out the residual washing solution inside the inspection box 51. When the rotating cleaning shaft 542 moves inside the inspection box 51, it will also drive the inside of the inspection box 51 to be cleaned. The sewage pipe 543 is the same as discharging the cleaning liquid inside the cleaning inspection box 51.

[0054] See also Figures 8 to 10 As shown, the outer wall of the rotating cleaning shaft 542 is provided with a plurality of liquid spraying holes 5421, and a rotating cleaning wheel 5422 is installed beside the liquid spraying holes 5421. The rotating cleaning shaft 542 also includes a rotating driving device, which is used to drive the rotating cleaning shaft 542 to rotate.

[0055] A limiting slide groove is also provided on the outer side of the rotating cleaning shaft 542, and the rotating cleaning shaft 542 is connected to the cleaning liquid delivery pipeline.

[0056] The rotary drive device includes a second rotary drive 5426 installed on the detection box 51, and a driving wheel 5427 is installed at the output end of the second rotary drive 5426. The rotary drive device also includes a driven wheel 5423 installed on the rotating cleaning shaft 542. A plurality of limit blocks are provided inside the driven wheel 5423, and the limit blocks are slidably connected to the limit slide grooves. A transmission chain 5424 is installed between the driven wheel 5423 and the driving wheel 5427.

[0057] A plurality of elastic push strips are disposed on the rotating cleaning wheel 5422 , and a conflict cleaning block is installed on each of the elastic push strips. The conflict cleaning block conflicts with the inner wall of the detection box 51 .

[0058] The second rotary driver 5426 is preferably a servo motor. When the electric push rod pushes the movable pushing frame 541 to move, the movable pushing frame 541 moves and drives the rotating cleaning shaft 542 to extend and move toward the inside of the detection box 51. When the rotating cleaning shaft 542 moves, the servo motor drives the driving wheel 5427 to rotate. When the driving wheel 5427 rotates, it drives the driven wheel 5423 to rotate through the transmission chain 5424. The rotation of the driven wheel 5423 drives the rotating cleaning shaft 542 to rotate. The cleaning liquid delivery pipeline delivers the cleaning liquid to the inside of the rotating cleaning shaft 542. The rotating cleaning shaft 542 sprays the cleaning liquid into the inside of the detection box 51 through the spray hole 5421. When the rotating cleaning shaft 542 rotates, it also drives the rotating cleaning wheel 5422 to rub and clean the inner wall of the detection box 51. The rotating cleaning wheel 5422 cooperates with the cleaning liquid to effectively clean the inside of the detection box 51.

[0059] Specific working principle:

[0060] During the solid phase synthesis of medical peptides, a solution containing alkali is added into the stirring barrel 1. The solution containing alkali will remove the amino protecting group of the resin, and then the solution containing alkali is discharged from the stirring barrel 1. Subsequently, the resin needs to be washed in time to remove excess alkali solution. After the alkali solution is discharged, the washing solution is transported to the stirring barrel 1. After the washing solution enters the stirring barrel 1, the self-priming transmission shaft 4 will suck the washing solution inside the stirring barrel 1 to make the washing solution circulate. When the self-priming transmission shaft 4 sucks the washing solution, it will rotate. When the self-priming transmission shaft 4 rotates, it will drive the turning base 2 and the mixing sleeve 3 to rotate synchronously. When the turning base 2 and the mixing sleeve 3 rotate synchronously, the internal resin and washing solution will be rotated and stirred synchronously. When the resin and the washing solution are rotated and stirred, the resin will be affected by gravity and will sink to the bottom of the turning base 2. When the twisting base 2 rotates, the precipitated resin will be continuously guided to the reflux gap. When the mixing sleeve 3 and the twisting base 2 rotate, the reflux gap will form an upward suction force, so that the resin that rotates and enters the reflux gap will rise and move. When the resin rises, they will rub and collide with each other. After the resin passes through the reflux gap and rises to the upper layer of the washing solution, it enters the interior of the mixing sleeve 3. When the mixing sleeve 3 rotates, the entered resin will be further mixed and stirred to form a flow-type rotation cycle effect, which can effectively improve the adequacy of stirring. At the same time, the solvent detection device 5 will detect the washing solution sucked and flowed by the self-priming transmission shaft 4 in real time, and detect the alkalinity in the washing solution. If the washing solution contains too much alkalinity, the cleaning solvent can be replaced in time to continue cleaning until the alkalinity in the washing solution meets the standard. Through real-time detection, it is effective to quickly determine whether the resin is qualified for cleaning, thereby improving work efficiency and work quality.

[0061] The above embodiments only express one or several implementation modes of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the present invention. It should be pointed out that, for those of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the attached claims.

Claims

1. A fully stirrable polypeptide solid phase synthesis device, comprising a fully stirring device installed inside a stirring barrel (1), characterized in that: The fully stirring device comprises a turning base (2), a mixing sleeve (3), a self-priming transmission shaft (4) and a solvent detection device (5); The self-priming transmission shaft (4) is installed at the axis center of the mixing barrel (1); The twisting base (2) is installed at the bottom of the mixing barrel (1), the twisting base (2) is in driving connection with the self-priming transmission shaft (4), and the twisting base (2) is used to mix the stirring material; The mixing sleeve (3) is installed at the axis center position of the turning base (2), the mixing sleeve (3) is connected to the self-priming transmission shaft (4) in a transmission manner, and a reflux gap is formed between the mixing sleeve (3) and the turning base (2); The solvent detection device (5) is installed on the self-priming transmission shaft (4), and the solvent detection device (5) is used for extraction detection; The twisting base (2) comprises a filter layer (25) mounted on the bottom of the mixing barrel (1), a scraper frame (21) is mounted on the filter layer (25), a rotating sleeve (22) is also mounted on the scraper frame (21), the rotating sleeve (22) is in contact with the inner wall of the mixing barrel (1), and a plurality of first guide blades (23) are provided on the inner wall of the rotating sleeve (22); The turning base (2) further comprises a plurality of boosting nozzles (24) mounted on the inner wall of the rotating sleeve (22), wherein the boosting nozzles (24) are connected to the self-priming transmission shaft (4); A plurality of stirring rods (31) are arranged inside the mixing sleeve (3), and the outer wall of the mixing sleeve (3) is evenly spaced and covered with second guide blades (32); The self-priming transmission shaft (4) is provided with flow openings (41) at both upper and lower ends, and drive blades (44) are provided inside the flow openings (41). A suction pump (42) is installed at the flow opening (41) at the lower end of the self-priming transmission shaft (4), and the liquid outlet end of the suction pump (42) is connected to the flow opening (41) at the upper end of the self-priming transmission shaft (4) through a circulation pipeline (45). A plurality of control valves (46) are installed on the circulation pipeline (45). A first liquid outlet (43) is provided on the outside of the self-priming transmission shaft (4), and the first liquid outlet (43) is connected to the flow opening (41) at the upper end of the self-priming transmission shaft (4). A reverse transmission mechanism (47) is also installed on the self-priming transmission shaft (4); The self-priming transmission shaft (4) further comprises an auxiliary driving device (48) mounted on the top of the mixing barrel (1), the auxiliary driving device (48) comprising a first rotating driver (481) mounted on the top of the mixing barrel (1), a driving gear (482) being mounted on the output end of the first rotating driver (481), and the auxiliary driving device (48) further comprises an adaptive transmission gear disc (483) mounted on the self-priming transmission shaft (4), the adaptive transmission gear disc (483) being meshed with the driving gear (482); A transmission clamping wheel (484) is provided inside the adaptive transmission gear disc (483); the transmission clamping wheel (484) is fixedly connected to the self-priming transmission shaft (4); the outer wall of the transmission clamping wheel (484) is covered with clamping protrusions (485); and a plurality of adaptive abutment blocks (486) are installed between the transmission clamping wheels (484); The solvent detection device (5) comprises a detection box (51) connected to the circulation pipeline (45), a solvent detector is provided inside the detection box (51), and a liquid inlet (52) and a second liquid outlet (53) are provided on the detection box (51); The solvent detection device (5) further comprises an automatic cleaning device (54) for cleaning the interior of the detection box (51). The automatic cleaning device (54) comprises a movable pushing frame (541). A rotating cleaning shaft (542) is mounted on the movable end of the movable pushing frame (541). The rotating cleaning shaft (542) extends toward the interior of the detection box (51). A separating piston block (544) is also mounted on the extended end of the rotating cleaning shaft (542). The automatic cleaning device (54) further comprises a sewage discharge pipe (543) connected to the detection box (51).

2. A fully stirrable polypeptide solid phase synthesis device according to claim 1, characterized in that: The outer wall of the rotating cleaning shaft (542) is provided with a plurality of liquid spray holes (5421), and a rotating cleaning wheel (5422) is installed beside the liquid spray hole (5421). The rotating cleaning shaft (542) also includes a rotating driving device, which is used to drive the rotating cleaning shaft (542) to rotate.

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