A method and equipment for manufacturing calcipotriol raw material

Abstract

The present invention provides a method and equipment for manufacturing a calcipotriol API, belonging to the technical field of calcipotriol production. The manufacturing equipment for the calcipotriol API comprises a tank body, a tank cover fixedly mounted on the top of the tank body, a rotating sleeve rotatably mounted on the top of the tank cover, a regular polygonal cylinder passing through and slidably mounted in the rotating sleeve, a high-pressure water pump provided on one side of the tank body, a water pipe fixedly mounted on the water outlet of the high-pressure water pump, one end of the water pipe fixedly connected to a first drain pipe, one end of the first drain pipe extending into the regular polygonal cylinder and fixedly mounted with a first three-dimensional cleaning ball. The manufacturing equipment for the calcipotriol API provided by the present invention has an autonomous cleaning function, does not require the removal of a stirring device, can reduce downtime, and can improve the cleaning speed and cleaning effect. The manufacturing method for the calcipotriol API provided by the present invention has the advantage of improving production efficiency.

Description

Technical Field

[0001] The present invention relates to the technical field of calcipotriol production, and in particular to a method and equipment for manufacturing a calcipotriol bulk drug. Background Art

[0002] Calcipotriol is an organic compound with the chemical formula C 27 H 40 Calcipotriol is a vitamin D derivative that inhibits skin cell (keratinocyte) proliferation and induces differentiation, thereby correcting abnormal proliferation and differentiation in psoriatic lesions. It can also be used to treat stable lesions caused by psoriatic arthritis. The process for preparing calcipotriol using stigmasterol as a starting material requires fermentation with the microorganisms Penicillium oxalicum or Aspergillus terreus to introduce an α-hydroxyl group. This requires the use of fermentation equipment, currently commonly used in fermentation tanks.

[0003] During use, the inner tank of a biological fermentation tank needs to be cleaned regularly to prevent the original residual liquid from breeding harmful substances and affecting subsequent use. However, the biological fermentation tanks in the existing technology do not have a self-cleaning function. In addition to traditional manual cleaning, the most common method to complete cleaning is to use tank cleaning equipment. During cleaning, the cleaning pipe of the tank cleaning equipment needs to be extended into the inner tank of the fermentation tank through a manhole. In order to ensure that the three-dimensional cleaning ball on the cleaning pipe can be located in the center of the inner tank, the stirring device on the fermentation tank sometimes needs to be removed. Therefore, the cleaning of the fermentation tank is relatively troublesome and time-consuming, which in turn affects the production efficiency of calcipotriol.

[0004] Therefore, it is necessary to provide a method and equipment for manufacturing calcipotriol raw materials to solve the above technical problems. Summary of the Invention

[0005] The technical problem solved by the present invention is to provide a calcipotriol API manufacturing device with an autonomous cleaning function, which does not require the removal of a stirring device, can reduce downtime, and can improve the cleaning speed and cleaning effect, and proposes a calcipotriol API manufacturing method using the calcipotriol API manufacturing device.

[0006] To solve the above technical problems, the present invention provides a manufacturing device for calcipotriol raw material, comprising a tank body, the tank body comprising an inner liner and a jacket, the jacket fixedly sleeved on the outer wall of the inner liner, a tank cover fixedly mounted on the top of the inner liner, a rotating sleeve rotatably mounted on the top of the tank cover, a regular polygonal cylinder passing through and slidably mounted in the rotating sleeve, the bottom end of the regular polygonal cylinder extending into the inner liner, and a stirrer fixedly sleeved therein, a high-pressure water pump provided on one side of the tank body, a water pipe fixedly mounted on the water outlet of the high-pressure water pump, an end of the water pipe away from the high-pressure water pump fixedly connected to a first drain pipe, the first drain pipe extending into the regular polygonal cylinder away from the end of the water pipe and fixedly mounted with a first three-dimensional cleaning ball, a first motor fixedly mounted on the top of the tank cover, the first motor being transmission-connected to the rotating sleeve, and a lifting mechanism for lifting the regular polygonal cylinder further provided on the top of the tank cover;

[0007] A gyro-shaped blocking block is rotatably mounted on the inner wall of the bottom of the liner, the top of which extends into the regular polygonal tube, a sealing gasket is fixedly sleeved on the outer wall of the gyro-shaped blocking block, and the inner edge of the bottom opening of the regular polygonal tube contacts the sealing gasket;

[0008] An aeration ring pipe is fixedly installed on the inner wall of the bottom of the liner, a plurality of aeration plates distributed in a ring shape are fixedly installed on the top of the aeration ring pipe, and an air supply pipe is fixedly installed on the bottom of the aeration ring pipe. The air supply pipe extends to the outside of the tank body away from one end of the aeration ring pipe.

[0009] Preferably, a polygonal base is fixedly installed on the top of the tank body, a mounting groove is opened on the top of the polygonal base, a polygonal protective cover is arranged in the mounting groove, and the regular polygonal cylinder, the first motor, the first drain pipe and the lifting mechanism are all located in the polygonal protective cover.

[0010] Preferably, the lifting mechanism includes a collar, a fixed plate, a lifting arm, a screw rod and a second motor, the collar is rotatably mounted on the regular polygonal cylinder, the fixed plate is fixedly mounted on the top of the tank cover, the lifting arm is slidably mounted on the outer wall of the fixed plate on one side close to the regular polygonal cylinder, the lifting arm is fixedly connected to the collar at one end away from the fixed plate, two shaft seats are fixedly mounted on the fixed plate, the screw rod is rotatably mounted on the two shaft seats, the screw rod passes through the lifting arm and is threadedly connected to the lifting arm, the second motor is fixedly mounted on the shaft seat located above, and the output end of the second motor is fixedly connected to the top end of the screw rod.

[0011] Preferably, a reinforcing rod is fixedly mounted on the shaft seat located above, a hoop is fixedly mounted on one end of the reinforcing rod away from the fixing plate, and the hoop is fixedly sleeved on the first drain pipe.

[0012] Preferably, two second drain pipes are slidably installed on the top of the tank cover, the bottom ends of the two second drain pipes extend into the tank cover, and a second three-dimensional cleaning ball is fixedly installed on each of the two second drain pipes, and a connecting hose is fixedly installed on the top of each of the two second drain pipes, and the ends of the two connecting hoses away from the corresponding second drain pipes are fixedly connected to the water pipe, and two sets of linked downward pressing mechanisms are provided on the fixed plate, and the linked downward pressing mechanism is used to cooperate with the lifting arm to drive the second drain pipe to move downward.

[0013] The axle up and down groove at two ends embeds respectively in two guide rails up and down of being made up of the groove on the attachment piece, and the tooth on the attachment piece is meshed with tooth on upper sprocket wheel, the lower sprocket. The lower sprocket. The lower sprocket. The two guide rails are meshed with tooth on upper sprocket.

[0014] Preferably, limiting grooves are provided on both sides of the inner rack, and L-shaped sliders are slidably installed in the two limiting grooves, and the ends of the two L-shaped sliders away from the inner rack are fixedly connected to the shaft seat located above.

[0015] Preferably, a plurality of ear blocks are fixedly mounted on the polygonal protective cover, a same circular ring is rotatably mounted on the plurality of ear blocks, a plurality of arc-shaped locking rods which are rotationally symmetrically distributed are fixedly mounted on the bottom of the circular ring, a plurality of arc-shaped plates which are rotationally symmetrically distributed are fixedly mounted on the top of the tank cover, an arc-shaped locking hole is opened in the arc-shaped plate, and a plurality of the arc-shaped locking rods all pass through the corresponding arc-shaped locking holes and are slidably connected to the inner walls of the corresponding arc-shaped locking holes.

[0016] Preferably, a plurality of magnet blocks are fixedly sleeved on the circular ring, and the plurality of magnet blocks are attracted to the corresponding ear blocks.

[0017] To solve the above problems, the present invention also provides a method for producing a calcipotriol bulk drug, comprising the following steps:

[0018] T1: A culture medium containing glucose, corn steep liquor, and potassium dihydrogen phosphate is placed in a calcipotriol API manufacturing device. After sterilization by passing high-temperature steam into the interlayer, a seed solution of Penicillium oxalicum is inoculated and stirred under aeration. After two days of incubation, stigmasterol is added to a 0.1% Tween 80 solution to prepare a suspension, which is then added to the calcipotriol API manufacturing device. Fermentation is continued for three days. After terminating the reaction, the fermentation broth is discharged, and then the fermentation broth is extracted with ethyl acetate. The broth is allowed to stand and separate into layers. The organic layer is concentrated under reduced pressure to obtain compound a.

[0019] T2: reacting compound a with tert-butyldimethylsilyl chloride in an aprotic organic solvent in the presence of an acid-binding agent at 20-50°C to obtain compound b;

[0020] T3: In the presence of an organic base, compound b reacts with O3 in an aprotic organic solvent at -50°C to -10°C to obtain compound c;

[0021] T4: Compound c reacts with triphenylphosphine oxide in an aprotic organic solvent at 60°C to the reflux temperature of the solvent to obtain compound d;

[0022] T5: Compound d reacts with potassium borohydride in an organic solvent at 10-40°C to obtain compound e;

[0023] T6: Compound e undergoes photoisomerization reaction to obtain the calcipotriol raw material.

[0024] Compared with related technologies, the method and equipment for manufacturing the calcipotriol API provided by the present invention have the following beneficial effects:

[0025] The present invention provides a manufacturing device for a calcipotriol API. The device comprises a rotating sleeve, a regular polygonal cylinder, a lifting mechanism, a high-pressure water pump, a water pipe, a first drainage pipe, and a first three-dimensional cleaning ball. During normal operation, the first three-dimensional cleaning ball is hidden within the regular polygonal cylinder and located at the center of the inner liner of a tank body. When the inner liner of the tank body needs to be cleaned, the regular polygonal cylinder is lifted by the lifting mechanism to reveal the first three-dimensional cleaning ball. The high-pressure water pump is then activated to pump cleaning liquid into the first drainage pipe. Under the action of the water pressure, the cleaning liquid is sprayed from a nozzle on the first three-dimensional cleaning ball. Furthermore, the rotating pipe and the nozzle on the first three-dimensional cleaning ball rotate, so that the trajectory of the cleaning liquid spraying is spherical, thereby comprehensively cleaning the inner liner. This configuration enables the manufacturing device for the calcipotriol API to have an autonomous cleaning function. Comprehensive cleaning of the inner liner can be completed without the need for specialized cleaning equipment and without removing the stirring device. This allows the device to be stopped and cleaned at any time, reducing downtime and facilitating improved production efficiency of the calcipotriol API.

[0026] The present invention provides a manufacturing device for a calcipotriol bulk drug. By arranging components such as a second drainage pipe, a second three-dimensional cleaning ball, a connecting hose, a linkage downward pressure mechanism, and a push block, the two second drainage pipes can be caused to move downward during the process of lifting a regular polygonal cylinder. After the lifting arm rises to a maximum height position, the first three-dimensional cleaning ball is completely exposed, and simultaneously, the second three-dimensional cleaning ball is completely driven into the inner tank by the corresponding second drainage pipe. After the high-pressure water pump is started, the first three-dimensional cleaning ball and the two second three-dimensional cleaning balls can be caused to spray water simultaneously, thereby effectively increasing the cleaning speed and also improving the cleaning effect on the tank cover and the agitator, thereby significantly improving the overall cleaning speed and cleaning effect.

[0027] The present invention provides a manufacturing device for a calcipotriol bulk drug. The device comprises a plurality of ear blocks, a circular ring, a plurality of arc-shaped locking rods, a plurality of arc-shaped plates, and other components. The plurality of arc-shaped locking rods are respectively inserted into arc-shaped locking holes on the plurality of arc-shaped plates, thereby reliably locking a polygonal protective cover. When it is necessary to inspect and repair components within the polygonal protective cover, the circular ring is simply rotated counterclockwise to cause the plurality of arc-shaped locking rods to exit the corresponding arc-shaped locking holes, thereby quickly releasing the lock on the polygonal protective cover. This arrangement greatly reduces the time required for disassembly and installation of the polygonal protective cover, effectively improving inspection and repair efficiency.

[0028] The method for manufacturing the calcipotriol API provided by the present invention uses the above-mentioned calcipotriol API manufacturing equipment to carry out the front-end fermentation process. Since the calcipotriol API manufacturing equipment has a self-cleaning function, it can effectively save the time used for preparation and cleaning, which is conducive to improving the production efficiency of calcipotriol. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is a schematic structural diagram of a first embodiment of the manufacturing equipment for calcipotriol API provided by the present invention;

[0030] Figure 2 for Figure 1 The schematic diagram of the structure of the manufacturing equipment of calcipotriol API after removing the polygonal protective cover;

[0031] Figure 3 for Figure 2 A schematic diagram of the enlarged structure of part A shown;

[0032] Figure 4 for Figure 2 A schematic cross-sectional view of a manufacturing apparatus for calcipotriol API is shown;

[0033] Figure 5 for Figure 4 The manufacturing equipment of calcipotriol API shown is a schematic structural diagram after the regular polygonal cylinder is lifted;

[0034] Figure 6 for Figure 5 The schematic diagram of the connection between the first three-dimensional cleaning ball and the first drain pipe is shown;

[0035] Figure 7 for Figure 4 The schematic structural diagram of the gyro-shaped blocking block shown in FIG.

[0036] Figure 8 for Figure 1 The schematic structural diagram of the polygonal protective cover and the polygonal base in the separated state is shown;

[0037] Figure 9 This is a schematic structural diagram of a second embodiment of the manufacturing equipment for calcipotriol API provided by the present invention;

[0038] Figure 10 for Figure 9 A partial cross-sectional structural schematic diagram of the manufacturing equipment of calcipotriol raw material shown;

[0039] Figure 11 for Figure 10 The structural diagram of the two sets of linkage pressing mechanisms shown;

[0040] Figure 12 for Figure 11 A schematic diagram of the enlarged structure of part B is shown;

[0041] Figure 13 This is a schematic structural diagram of a third embodiment of the manufacturing equipment for calcipotriol API provided by the present invention;

[0042] Figure 14 for Figure 13The enlarged structural diagram of part C is shown;

[0043] Figure 15 for Figure 13 Schematic diagram of the connection between the ring and the multiple ear blocks shown;

[0044] Figure 16 for Figure 13 Schematic diagram of the structure of the curved plate shown.

[0045] Numbers in the figure: 1, tank body; 2, tank cover; 3, rotating sleeve; 4, regular polygonal cylinder; 5, agitator; 6, collar; 7, first motor; 8, fixed plate; 9, lifting arm; 10, long screw; 11, second motor; 12, high-pressure water pump; 13, water pipe; 14, first drain pipe; 15, first three-dimensional cleaning ball; 16, aeration ring pipe; 17, gas pipe; 18, gyro-shaped blocking block; 19, sealing gasket ; 20. Polygonal base; 21. Polygonal protective cover; 22. Second drain pipe; 23. Second three-dimensional cleaning ball; 24. Connecting hose; 25. Fixed block; 26. Limiting slide bar; 27. Driving rod; 28. Connecting frame; 29. ​​External rack; 30. Spring; 31. Internal rack; 32. Gear; 33. Push block; 34. Ear block; 35. Ring; 36. Arc-shaped locking rod; 37. Arc-shaped plate; 38. Magnet block. DETAILED DESCRIPTION

[0046] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0047] First embodiment

[0048] Please refer to Figures 1-8In the first embodiment of the present invention, the manufacturing equipment of calcipotriol raw material comprises: a tank body 1, the tank body 1 comprises an inner liner and a jacket, the jacket is fixedly sleeved on the outer wall of the inner liner, a tank cover 2 is fixedly installed on the top of the inner liner, a feed port, a sampling port and a hand hole are provided on the top of the tank cover 2, a steam inlet and a cooling water inlet are provided on the outer wall of the jacket, a condensate outlet and a cooling water outlet are provided at the bottom of the jacket, a discharge pipe is provided on the inner liner, and the bottom end of the discharge pipe extends to the bottom of the jacket, a rotating sleeve 3 is rotatably installed on the top of the tank cover 2, a regular polygon cylinder 4 is penetrated and slidably installed in the rotating sleeve 3, and the inner hole of the rotating sleeve 3 is a regular polygon, which is in the shape of a regular polygon. The regular polygonal cylinder 4 is adapted to the tank body 1. When the rotating sleeve 3 rotates, the regular polygonal cylinder 4 can be driven to rotate. The bottom end of the regular polygonal cylinder 4 extends into the inner tank, and a stirrer 5 is fixedly sleeved. A high-pressure water pump 12 is provided on one side of the tank body 1. A water pipe 13 is fixedly installed on the water outlet of the high-pressure water pump 12. The end of the water pipe 13 away from the high-pressure water pump 12 is fixedly connected to a first drain pipe 14. The end of the first drain pipe 14 away from the water pipe 13 extends into the regular polygonal cylinder 4, and a first three-dimensional cleaning ball 15 is fixedly installed. After the regular polygonal cylinder 4 is lifted, the first three-dimensional cleaning ball 15 will be exposed, and the high-pressure water pump 12 pumps clean water into the first drain pipe 14. Under the action of water pressure, the rotating tube and the nozzle on the first three-dimensional cleaning ball 15 rotate, and the interior of the liner can be fully rinsed. The top of the tank cover 2 is fixedly installed with a first motor 7, and the first motor 7 is transmission-connected to the rotating sleeve 3. Circular gears are fixedly sleeved on the outer wall of the regular polygonal cylinder 4 and the output end of the first motor 7. The two circular gears are meshed with each other. A lifting mechanism for lifting the regular polygonal cylinder 4 is also provided on the top of the tank cover 2. Specifically, the lifting mechanism includes a collar 6, a fixing plate 8, a lifting arm 9, a long screw rod 10 and a second motor 11. The ring 6 is rotatably sleeved on the regular polygonal cylinder 4, the fixed plate 8 is fixedly mounted on the top of the tank cover 2, the lifting arm 9 is slidably mounted on the outer wall of the fixed plate 8 close to the regular polygonal cylinder 4, the fixed plate 8 is provided with a limited slideway, the lifting arm 9 is slidably mounted in the limited slideway, the lifting arm 9 is fixedly connected to the collar 6 at one end away from the fixed plate 8, two shaft seats are fixedly mounted on the fixed plate 8, the long wire rod 10 is rotatably mounted on the two shaft seats, the long wire rod 10 passes through the lifting arm 9 and is threadedly connected to the lifting arm 9, the second motor 11 is fixedly mounted on the shaft seat located above, and the output end of the second motor 11 is fixedly connected to the top of the long wire rod 10;

[0049] In order to be able to block the bottom opening of the regular polygonal tube 4 without affecting its rotation, a tripod is fixedly installed on the inner wall of the bottom of the liner, and a gyro-shaped blocking block 18 is rotatably installed on the top of the tripod. The top end of the gyro-shaped blocking block 18 extends into the regular polygonal tube 4, and a sealing gasket 19 is fixedly sleeved on the outer wall of the gyro-shaped blocking block 18. The inner edge of the bottom opening of the regular polygonal tube 4 is in contact with the sealing gasket 19. During the rotation of the regular polygonal tube 4, the gyro-shaped blocking block 18 rotates with it.

[0050] In order to be able to input oxygen into the tank body 1 for aerobic fermentation, an aeration ring pipe 16 is fixedly installed on the inner wall of the bottom of the inner tank, and a plurality of aeration plates distributed in a ring shape are fixedly installed on the top of the aeration ring pipe 16. An air supply pipe 17 is fixedly installed at the bottom of the aeration ring pipe 16. One end of the air supply pipe 17 away from the aeration ring pipe 16 extends to the outside of the tank body 1, and the air supply pipe 17 is connected to an external air supply device.

[0051] In this embodiment, a polygonal base 20 is fixedly installed on the top of the tank body 1. A mounting groove is provided on the top of the polygonal base 20. A polygonal protective cover 21 is provided in the mounting groove. The regular polygonal cylinder 4, the first motor 7, the first drain pipe 14 and the lifting mechanism are all located in the polygonal protective cover 21. A plurality of tightening bolts are threadedly installed on the regular polygonal base 20, and the polygonal protective cover 21 is tightened and fixed by the plurality of tightening bolts.

[0052] In this embodiment, in order to improve the stability of the first drain pipe 14 , a reinforcing rod is fixedly installed on the upper shaft seat, and a hoop is fixedly installed on the end of the reinforcing rod away from the fixing plate 8 , and the hoop is fixedly sleeved on the first drain pipe 14 .

[0053] In this embodiment:

[0054] In the initial state, the bottom of the regular polygonal tube 4 contacts the sealing gasket 19 on the gyro-shaped blocking block 18; raw materials for fermentation can be added into the tank body 1 through the feeding port;

[0055] After the first motor 7 is started, it can drive the rotating sleeve 3 to rotate, the rotating sleeve 3 drives the regular polygonal cylinder 4 to rotate, and the regular polygonal cylinder 4 drives the stirrer 5 to rotate, so as to stir the raw materials and mix them evenly. According to the fermentation needs, steam can be introduced into the interlayer between the jacket and the inner tank through the steam inlet to heat the fermentation raw materials, and cooling water can be introduced into the interlayer through the cooling water inlet to cool the fermentation raw materials. In the case of aerobic fermentation, compressed air can be input into the aeration ring pipe 16 through the air supply pipe 17, and the compressed air is discharged through multiple aeration disks, thereby supplying oxygen to the fermentation raw materials. After fermentation is completed, the material valve on the discharge pipe can be opened to discharge the fermentation liquid;

[0056] When the inside of the liner needs to be cleaned, the second motor 11 is started to run, driving the long screw rod 10 to rotate in the opposite direction. During the reverse rotation of the long screw rod 10, the lifting arm 9 is driven to move upward, and the lifting arm 9 drives the regular polygonal cylinder 4 to slide upward through the collar 6. As the regular polygonal cylinder 4 continues to rise, the first three-dimensional cleaning ball 15 will gradually appear. When the lifting arm 9 rises to the limit height position, Figure 5 As shown, the first three-dimensional cleaning ball 15 is completely exposed, and then the high-pressure water pump 12 is started to run, and the cleaning liquid is pumped into the first drain pipe 14 through the water pipe 13. Under the action of water pressure, the rotating pipe and the nozzle on the first three-dimensional cleaning ball 15 rotate circumferentially, and the cleaning liquid is sprayed out from the nozzle. The flushing trajectory is spherical, so that the inner tank can be cleaned in all directions.

[0057] Compared with related technologies, the manufacturing equipment for calcipotriol API provided by the present invention has the following beneficial effects:

[0058] By rotating the sleeve 3, the regular polygonal cylinder 4, the lifting mechanism, the high-pressure water pump 12, the water pipe 13, the first drainage pipe 14 and the first three-dimensional cleaning ball 15, during normal operation, the first three-dimensional cleaning ball 15 is hidden in the regular polygonal cylinder 4 and is located at the center of the inner liner of the tank body 1. When the inner liner of the tank body 1 needs to be cleaned, the regular polygonal cylinder 4 is lifted by the lifting mechanism to make the first three-dimensional cleaning ball 15 appear, and then the high-pressure water pump 12 is started to pump cleaning liquid into the first drainage pipe 14. Under the action of water pressure, the first three-dimensional cleaning ball 15 is exposed. Under the above conditions, the cleaning liquid is sprayed out from the nozzle on the first three-dimensional cleaning ball 15, and the rotating tube and the nozzle on the first three-dimensional cleaning ball 15 will rotate, so that the trajectory of the cleaning liquid spraying is spherical, thereby making the inner liner cleaned in all directions. Through this arrangement, the manufacturing equipment of the calcipotriol raw material drug has an autonomous cleaning function, and can complete the all-round cleaning of the inner liner without the help of special cleaning equipment. There is no need to remove the stirring device, so that the equipment can be stopped and cleaned at the same time, reducing downtime, which is conducive to improving the production efficiency of the calcipotriol raw material drug.

[0059] Second embodiment:

[0060] The second embodiment of the present invention will be further described below with reference to the accompanying drawings and implementation plans.

[0061] Please refer to Figures 9-12In the manufacturing equipment of calcipotriol raw material provided in this embodiment, two second drainage pipes 22 are also slidably installed on the top of the tank cover 2. The bottom ends of the two second drainage pipes 22 extend into the tank cover 2 and are fixedly installed with second three-dimensional cleaning balls 23. The top ends of the two second drainage pipes 22 are fixedly installed with connecting hoses 24. The ends of the two connecting hoses 24 away from the corresponding second drainage pipes 22 are fixedly connected to the water pipe 13. Two sets of linkage pressing mechanisms are provided on the fixed plate 8. The linkage pressing mechanism is used to cooperate with the lifting arm 9 to drive the second drainage pipes 22 to move downward. When the inside of the inner tank needs to be cleaned, during the process of lifting the regular polygonal cylinder 4, after the lifting arm 9 rises to a certain height, it will trigger the linkage pressing mechanism to operate, drive the two second drainage pipes 22 to move downward, and allow the two second three-dimensional cleaning balls 23 to enter the inner tank.

[0062] Specifically, any one of the linked downward pressure mechanisms includes a fixed block 25, two limiting slides 26, a driving rod 27, a connecting frame 28, an outer rack 29, two springs 30, an inner rack 31 and a gear 32. The fixed block 25 is fixedly mounted on the fixed plate 8. The two limiting slides 26 are both penetrated and slidably mounted on the fixed block 25. The bottom ends of the two limiting slides 26 are fixedly mounted on the same lower connecting plate. The driving rod 27 is fixedly mounted on the bottom of the lower connecting plate. The connecting frame 28 is fixedly sleeved on the driving rod 27. The end of the connecting frame 28 away from the driving rod 27 is fixedly connected to the second drain pipe 22. The top ends of the two limiting slides 26 are fixedly mounted on the same upper connecting plate. The outer rack 29 is fixedly mounted on the top of the upper connecting plate. The inner rack 31 is slidably mounted on the shaft seat located above. Specifically, both sides of the inner rack 31 are open The two gears 32 are engaged with each other and the gear 32 is engaged with the gear 32. When the inner gear 31 is lifted, the gear 32 is driven to rotate, and when the gear 32 is rotated, the outer gear 29 is driven to move downward. The two springs 30 are respectively mounted on the two limit slide bars 26. The top ends of the two springs 30 are fixedly connected to the upper connecting plate, and the bottom ends are fixedly connected to the fixed block 25. Push blocks 33 are fixedly installed on the outer walls of both sides of the lifting arm 9. After the lifting arm 9 rises to a certain height, the two push blocks 33 will conflict with the bottom of the corresponding inner gear 31, and then push the two inner gears 31 to move upward.

[0063] In this embodiment:

[0064] When cleaning the inner tank, the second motor 11 is started to operate and the regular polygonal cylinder 4 is lifted. The lifting arm 9 gradually rises under the drive of the filament rod 10, and the two push blocks 33 rise with the lifting arm 9. When the lifting arm 9 rises to a certain height, the two push blocks 33 both conflict with the bottom of the corresponding inner rack 31. In the subsequent process of the lifting arm 9 continuing to rise, the two push blocks 33 will push the two inner racks 31 to slide upward. The inner rack 31 drives the gear 32 to rotate during the rising process. Driven by the gear 32, the outer rack 29 moves downward, and the outer rack 29 pushes the two limit slide bars 26 to move downward. The two springs 30 will be compressed. At the same time, the driving rod 27 moves downward, and the second drain pipe 22 is driven downward by the connecting frame 28, so that the second three-dimensional cleaning ball 23 enters the inner tank.

[0065] When the lifting arm 9 rises to the limit height position, the first three-dimensional cleaning ball 15 is completely exposed, and the two second three-dimensional cleaning balls 23 are completely in the inner tank and are located above the agitator 5. During flushing, after the high-pressure water pump 12 is running, the cleaning liquid is pumped into the first drain pipe 14 and the two second drain pipes 22. Under the action of water pressure, the first three-dimensional cleaning ball 15 and the two second three-dimensional cleaning balls 23 run at the same time and spray cleaning liquid, which can improve the overall cleaning speed. When only the first three-dimensional cleaning ball 15 is used, the upward force of the sprayed cleaning liquid will be lower due to the action of gravity, and the agitator 5 is blocked, so the cleaning effect on the upper half of the agitator 5 and the tank cover 2 will be relatively poor. After adding two second three-dimensional cleaning balls 23, the upper half of the agitator 5 and the inside of the tank cover 2 can be more fully cleaned, while improving the overall cleaning speed, the overall cleaning effect is also significantly improved.

[0066] After cleaning is completed, the second motor 11 is started to drive the lifting arm 9 to move downward. The ear block 34 moves downward with the lifting arm 9. After the thrust of the ear block 34 is lost, under the elastic force of the spring 30, the upper connecting plate and the lower connecting plate will move upward. The outer rack 29 rises along with the upper connecting plate, causing the corresponding inner rack 31 to move downward until it is reset. At the same time, the driving rod 27 drives the second drain pipe 22 to slide upward through the connecting frame 28, so that the second three-dimensional cleaning ball 23 rises to its initial height position.

[0067] Through the arrangement of the second drain pipe 22, the second three-dimensional cleaning ball 23, the connecting hose 24, the linkage downward pressure mechanism, the push block 33 and other components, in the process of lifting the regular polygonal cylinder 4, the two second drain pipes 22 can move downward, and after the lifting arm 9 rises to the limit height position, the first three-dimensional cleaning ball 15 is completely exposed, and at the same time, the second three-dimensional cleaning ball 23 is completely driven into the inner tank by the corresponding second drain pipe 22. After starting the high-pressure water pump 12, the first three-dimensional cleaning ball 15 and the two second three-dimensional cleaning balls 23 can spray water at the same time, which can effectively improve the cleaning speed, and also improve the cleaning effect of the tank cover 2 and the agitator 5, so that the overall cleaning speed and cleaning effect are significantly improved.

[0068] Third embodiment:

[0069] The third embodiment of the present invention will be further described below with reference to the accompanying drawings and implementation plans.

[0070] Please refer to Figure 13-16 In the manufacturing equipment for the calcipotriol API provided in this embodiment, the polygonal protective cover 21 is quickly fixed. Specifically, a plurality of ear blocks 34 are fixedly mounted on the polygonal protective cover 21. The ear blocks 34 are made of stainless steel. The same circular ring 35 is rotatably mounted on the plurality of ear blocks 34. A plurality of sponge sleeves are fixedly sleeved on the circular ring 35 to facilitate the rotation of the circular ring 35. A plurality of rotationally symmetrically distributed arc-shaped locking rods 36 are fixedly mounted on the bottom of the circular ring 35. A plurality of rotationally symmetrically distributed arc-shaped plates 37 are fixedly mounted on the top of the tank cover 2. Arc-shaped locking holes are opened in the arc-shaped plates 37. The plurality of arc-shaped locking rods 36 all pass through the corresponding arc-shaped locking holes and are slidably connected to the inner walls of the corresponding arc-shaped locking holes.

[0071] In this embodiment, in order to restrict the circular ring 35 and prevent it from rotating at will, a plurality of magnet blocks 38 are fixedly sleeved on the circular ring 35 , and the plurality of magnet blocks 38 are attracted to the corresponding ear blocks 34 .

[0072] In this embodiment:

[0073] When it is necessary to inspect the components inside the polygonal protective cover 21, the ring 35 is rotated counterclockwise, and the ring 35 drives the multiple arc-shaped locking rods 36 to move, so that the multiple arc-shaped locking rods 36 all exit the corresponding arc-shaped locking holes, thereby releasing the lock of the polygonal protective cover 21 and then removing it. After the inspection is completed, the polygonal protective cover 21 is placed in the installation groove on the polygonal base 20, and the ring 35 is rotated clockwise, and the ring 35 drives the multiple arc-shaped locking rods 36 to rotate clockwise, so that the arc-shaped locking rods 36 are reinserted into the arc-shaped locking holes, thereby locking the polygonal protective cover 21.

[0074] By arranging multiple ear blocks 34, circular rings 35, multiple arc-shaped locking rods 36, multiple arc-shaped plates 37 and other components, multiple arc-shaped locking rods 36 are respectively inserted into the arc-shaped locking holes on the multiple arc-shaped plates 37, so that the polygonal protective cover 21 can be reliably locked. When it is necessary to inspect and repair the components inside the polygonal protective cover 21, it is only necessary to rotate the circular ring 35 counterclockwise to make the multiple arc-shaped locking rods 36 withdraw from the corresponding arc-shaped locking holes, and quickly release the lock on the polygonal protective cover 21. Through this arrangement, the disassembly and installation time of the polygonal protective cover 21 can be greatly reduced, and the maintenance efficiency can be effectively improved.

[0075] Fourth embodiment:

[0076] This embodiment provides a method for producing a calcipotriol API, comprising the following steps:

[0077] T1: A culture medium containing glucose, corn steep liquor, and potassium dihydrogen phosphate is placed in a calcipotriol API manufacturing device. After sterilization by passing high-temperature steam into the interlayer, a seed solution of Penicillium oxalicum is inoculated and stirred under aeration. After two days of incubation, stigmasterol is added to a 0.1% Tween 80 solution to prepare a suspension, which is then added to the calcipotriol API manufacturing device. Fermentation is continued for three days. After terminating the reaction, the fermentation broth is discharged, and then the fermentation broth is extracted with ethyl acetate. The broth is allowed to stand and separate into layers. The organic layer is concentrated under reduced pressure to obtain compound a.

[0078] T2: reacting compound a with tert-butyldimethylsilyl chloride in an aprotic organic solvent in the presence of an acid-binding agent at 20-50°C to obtain compound b;

[0079] T3: In the presence of an organic base, compound b reacts with O3 in an aprotic organic solvent at -50°C to -10°C to obtain compound c;

[0080] T4: Compound c reacts with triphenylphosphine oxide in an aprotic organic solvent at 60°C to the reflux temperature of the solvent to obtain compound d;

[0081] T5: Compound d reacts with potassium borohydride in an organic solvent at 10-40°C to obtain compound e;

[0082] T6: Compound e undergoes photoisomerization reaction to obtain the calcipotriol raw material.

[0083] The method for manufacturing the calcipotriol API uses the aforementioned calcipotriol API manufacturing equipment to carry out the front-end fermentation process. Since the calcipotriol API manufacturing equipment has a self-cleaning function, it can effectively save the time used for preparation and cleaning, which is conducive to improving the production efficiency of calcipotriol.

[0084] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention description and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A manufacturing device for calcipotriol bulk drug, comprising a tank body (1), the tank body (1) comprising an inner liner and a jacket, the jacket being fixedly mounted on the outer wall of the inner liner, and a tank cover (2) being fixedly mounted on the top of the inner liner, characterized in that: A rotating sleeve (3) is rotatably mounted on the top of the tank cover (2), a regular polygonal cylinder (4) is penetrated and slidably mounted in the rotating sleeve (3), the bottom end of the regular polygonal cylinder (4) extends into the inner tank, and a stirrer (5) is fixedly mounted on the sleeve, a high-pressure water pump (12) is provided on one side of the tank body (1), a water pipe (13) is fixedly mounted on the water outlet of the high-pressure water pump (12), an end of the water pipe (13) away from the high-pressure water pump (12) is fixedly connected to a first drain pipe (14), an end of the first drain pipe (14) away from the water pipe (13) extends into the regular polygonal cylinder (4), and a first three-dimensional cleaning ball (15) is fixedly mounted, a first motor (7) is fixedly mounted on the top of the tank cover (2), the first motor (7) is transmission-connected to the rotating sleeve (3), and a lifting mechanism for lifting the regular polygonal cylinder (4) is also provided on the top of the tank cover (2); A gyro-shaped blocking block (18) is rotatably mounted on the inner wall of the bottom of the liner, the top of the gyro-shaped blocking block (18) extends into the regular polygonal tube (4), a sealing gasket (19) is fixedly sleeved on the outer wall of the gyro-shaped blocking block (18), and the inner edge of the bottom opening of the regular polygonal tube (4) contacts the sealing gasket (19); An aeration ring tube (16) is fixedly mounted on the inner wall of the bottom of the liner, a plurality of annularly distributed aeration disks are fixedly mounted on the top of the aeration ring tube (16), an air delivery pipe (17) is fixedly mounted on the bottom of the aeration ring tube (16), and one end of the air delivery pipe (17) away from the aeration ring tube (16) extends to the outside of the tank body (1); The lifting mechanism comprises a collar (6), a fixed plate (8), a lifting arm (9), a filament rod (10) and a second motor (11), wherein the collar (6) is rotatably mounted on the regular polygonal cylinder (4), the fixed plate (8) is fixedly mounted on the top of the tank cover (2), the lifting arm (9) is slidably mounted on the outer wall of the fixed plate (8) close to the regular polygonal cylinder (4), the end of the lifting arm (9) away from the fixed plate (8) is fixedly connected to the collar (6), two shaft seats are fixedly mounted on the fixed plate (8), the filament rod (10) is rotatably mounted on the two shaft seats, the filament rod (10) passes through the lifting arm (9) and is threadedly connected to the lifting arm (9), the second motor (11) is fixedly mounted on the shaft seat located above, and the output end of the second motor (11) is fixedly connected to the top end of the filament rod (10).

2. The manufacturing equipment of calcipotriol bulk drug according to claim 1, characterized in that: A polygonal base (20) is fixedly mounted on the top of the tank body (1), a mounting groove is provided on the top of the polygonal base (20), a polygonal protective cover (21) is provided in the mounting groove, and the regular polygonal cylinder (4), the first motor (7), the first drain pipe (14) and the lifting mechanism are all located in the polygonal protective cover (21).

3. The manufacturing equipment of calcipotriol bulk drug according to claim 1, characterized in that: A reinforcing rod is fixedly mounted on the shaft seat located above, and a hoop is fixedly mounted on one end of the reinforcing rod away from the fixing plate (8), and the hoop is fixedly sleeved on the first drain pipe (14).

4. The manufacturing equipment of calcipotriol bulk drug according to claim 3, characterized in that: Two second drain pipes (22) are slidably mounted on the top of the tank cover (2), the bottom ends of the two second drain pipes (22) extend into the tank cover (2), and a second three-dimensional cleaning ball (23) is fixedly mounted on each of the two second drain pipes (22), and a connecting hose (24) is fixedly mounted on the top of each of the two second drain pipes (22), and one end of each of the two connecting hoses (24) away from the corresponding second drain pipe (22) is fixedly connected to the water pipe (13), and two sets of linkage downward pressing mechanisms are provided on the fixed plate (8), and the linkage downward pressing mechanisms are used to cooperate with the lifting arm (9) to drive the second drain pipe (22) to move downward.

5. The manufacturing equipment of calcipotriol bulk drug according to claim 4, characterized in that: Any of the linkage downward pressing mechanisms comprises a fixed block (25), two limiting slide bars (26), a driving rod (27), a connecting frame (28), an outer rack (29), two springs (30), an inner rack (31) and a gear (32), wherein the fixed block (25) is fixedly mounted on the fixed plate (8), the two limiting slide bars (26) are both passed through and slidably mounted on the fixed block (25), the bottom ends of the two limiting slide bars (26) are fixedly mounted on the same lower connecting plate, the driving rod (27) is fixedly mounted on the bottom of the lower connecting plate, the connecting frame (28) is fixedly sleeved on the driving rod (27), and the end of the connecting frame (28) away from the driving rod (27) is connected to the second The drain pipe (22) is fixedly connected, the top ends of the two limit slide bars (26) are fixedly installed with the same upper connecting plate, the outer rack (29) is fixedly installed on the top of the upper connecting plate, the inner rack (31) is slidably installed on the shaft seat located above, the gear (32) is rotatably installed on the fixed plate (8), the outer rack (29) and the inner rack (31) are both engaged with the gear (32), the two springs (30) are respectively mounted on the two limit slide bars (26), the top ends of the two springs (30) are fixedly connected to the upper connecting plate, and the bottom ends are fixedly connected to the fixed block (25), and push blocks (33) are fixedly installed on the outer walls of both sides of the lifting arm (9).

6. The manufacturing equipment of calcipotriol bulk drug according to claim 5, characterized in that: Limiting slots are provided on both sides of the inner rack (31), and L-shaped sliders are slidably installed in the two limiting slots. The ends of the two L-shaped sliders away from the inner rack (31) are fixedly connected to the shaft seat located above.

7. The manufacturing equipment of calcipotriol bulk drug according to claim 2, characterized in that: A plurality of ear blocks (34) are fixedly mounted on the polygonal protective cover (21), and a same circular ring (35) is rotatably mounted on the plurality of ear blocks (34). A plurality of arc-shaped locking rods (36) that are distributed in rotational symmetry are fixedly mounted on the bottom of the circular ring (35). A plurality of arc-shaped plates (37) that are distributed in rotational symmetry are fixedly mounted on the top of the tank cover (2), and arc-shaped locking holes are opened in the arc-shaped plates (37). The plurality of arc-shaped locking rods (36) all pass through the corresponding arc-shaped locking holes and are slidably connected to the inner walls of the corresponding arc-shaped locking holes.

8. The manufacturing equipment of calcipotriol bulk drug according to claim 7, characterized in that: A plurality of magnet blocks (38) are fixedly sleeved on the circular ring (35), and the plurality of magnet blocks (38) are attracted to the corresponding ear blocks (34).

9. A method for producing a calcipotriol API using the calcipotriol API production equipment according to any one of claims 1 to 8, characterized in that: The following steps are involved: T1: A culture medium containing glucose, corn steep liquor, and potassium dihydrogen phosphate is placed in a calcipotriol API manufacturing device. After sterilization by passing high-temperature steam into the interlayer, a seed solution of Penicillium oxalicum is inoculated and stirred under aeration. After two days of incubation, stigmasterol is added to a 0.1% Tween 80 solution to prepare a suspension, which is then added to the calcipotriol API manufacturing device. Fermentation is continued for three days. After terminating the reaction, the fermentation broth is discharged, and then the fermentation broth is extracted with ethyl acetate. The broth is allowed to stand and separate into layers. The organic layer is concentrated under reduced pressure to obtain compound a. T2: reacting compound a with tert-butyldimethylsilyl chloride in an aprotic organic solvent in the presence of an acid-binding agent at 20-50°C to obtain compound b; T3: In the presence of an organic base, compound b reacts with O3 in an aprotic organic solvent at -50°C to -10°C to obtain compound c; T4: Compound c reacts with triphenylphosphine oxide in an aprotic organic solvent at 60°C to the reflux temperature of the solvent to obtain compound d; T5: Compound d reacts with potassium borohydride in an organic solvent at 10-40°C to obtain compound e; T6: Compound e undergoes photoisomerization reaction to obtain the calcipotriol raw material.

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