Method and equipment for preparing calcipotriol bulk drug

Abstract

The invention provides a preparation method and equipment of a calcipotriol bulk drug, and belongs to the technical field of calcipotriol production. The manufacturing equipment of the calcipotriol bulk drug comprises a tank body, a tank cover is fixedly installed at the top of the tank body, a rotating sleeve is rotatably installed at the top of the tank cover, a regular polygon cylinder is installed in the rotating sleeve in a penetrating and sliding mode, a high-pressure water pump is arranged on one side of the tank body, and a water conveying pipe is fixedly installed on a water outlet of the high-pressure water pump. And one end of the water conveying pipe is fixedly connected with a first water drainage pipe, one end of the first water drainage pipe extends into the regular polygon cylinder, and a first three-dimensional cleaning ball is fixedly installed at one end of the first water drainage pipe. The manufacturing equipment of the calcipotriol bulk drug has the advantages that the automatic cleaning function is achieved, a stirring device does not need to be dismantled, the downtime can be shortened, the cleaning speed can be increased, and the cleaning effect can be improved. The manufacturing method of the calcipotriol bulk drug has the advantage that the production efficiency can be improved.

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 raw material drug. Background Art

[0002] Calcipotriol is an organic compound with the chemical formula C 27 H 40 O3, Calcipotriol is a derivative of vitamin D, which can inhibit the proliferation of skin cells (keratinocytes) and induce their differentiation, thereby correcting the abnormal proliferation and differentiation of psoriatic lesions. It can also be used to treat stable lesions caused by psoriatic arthritis. In the process of preparing calcipotriol using stigmasterol as a starting material, stigmasterol needs to be fermented by microorganisms such as Penicillium oxalicum or Aspergillus terreus to introduce an α-hydroxyl group, so biological fermentation equipment is needed. The commonly used biological fermentation equipment is a fermentation tank.

[0003] During the use of the biological fermentation tank, the inner tank needs to be cleaned regularly to prevent the original residual liquid from breeding harmful substances and affecting subsequent use. However, the biological fermentation tank in the prior art does not have a self-cleaning function. In order to complete the cleaning, in addition to the traditional manual cleaning, the most common method is to use a tank cleaning device to complete the cleaning. During cleaning, the cleaning pipe of the tank cleaning device needs to be extended into the inner tank of the fermentation tank through the manhole. In order to make the three-dimensional cleaning ball on the cleaning pipe be in the central position of the inner tank, sometimes the stirring device on the fermentation tank needs to be removed. Therefore, the cleaning of the fermentation tank is overall 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 material to solve the above technical problems. Summary of the invention

[0005] The technical problem solved by the present invention is to provide a manufacturing device for calcipotriol raw material drug 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 manufacturing method for calcipotriol raw material drug using the manufacturing device for calcipotriol raw material drug.

[0006] In order to solve the above technical problems, the present invention provides a manufacturing device for calcipotriol bulk drug, comprising a tank body, the tank body comprising an inner tank and a jacket, the jacket is fixedly sleeved on the outer wall of the inner tank, a tank cover is fixedly installed on the top of the inner tank, a rotating sleeve is rotatably installed on the top of the tank cover, a regular polygonal cylinder is penetrated and slidably installed in the rotating sleeve, the bottom end of the regular polygonal cylinder extends into the inner tank, and a stirrer is fixedly sleeved, a high-pressure water pump is arranged on one side of the tank body, a water pipe is fixedly installed on the water outlet of the high-pressure water pump, one end of the water pipe away from the high-pressure water pump is fixedly connected to a first drain pipe, the first drain pipe extends into the regular polygonal cylinder at one end away from the water pipe, and a first three-dimensional cleaning ball is fixedly installed, a first motor is fixedly installed on the top of the tank cover, the first motor is transmission-connected to the rotating sleeve, and a lifting mechanism for lifting the regular polygonal cylinder is also arranged on the top of the tank cover; A gyro-shaped blocking block is rotatably mounted on the inner wall of the bottom of the liner, the top of the gyro-shaped blocking block 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; 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, an air supply pipe is fixedly installed on the bottom of the aeration ring pipe, and one end of the air supply pipe away from the aeration ring pipe extends to the outside of the tank body.

[0007] 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.

[0008] Preferably, the lifting mechanism includes a collar, a fixed plate, a lifting arm, a filament rod and a second motor, the collar being rotatably mounted on the regular polygonal cylinder, the fixed plate being fixedly mounted on the top of the tank cover, the lifting arm being slidably mounted on an outer wall of one side of the fixed plate close to the regular polygonal cylinder, the lifting arm having one end away from the fixed plate being fixedly connected to the collar, two shaft seats being fixedly mounted on the fixed plate, the filament rod being rotatably mounted on the two shaft seats, the filament rod passing through the lifting arm and being threadedly connected to the lifting arm, the second motor being fixedly mounted on the shaft seat located above, and the output end of the second motor being fixedly connected to the top end of the filament rod.

[0009] Preferably, a reinforcing rod is fixedly mounted on the shaft seat located at the top, 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.

[0010] 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 one end of the two connecting hoses away from the corresponding second drain pipes is fixedly connected to the water pipe, and two sets of linked pressing mechanisms are provided on the fixed plate, and the linked pressing mechanisms are used to cooperate with the lifting arm to drive the second drain pipe to move downward.

[0011] 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.

[0012] Preferably, limiting grooves are provided on both sides of the inner rack, L-shaped sliders are slidably installed in the two limiting grooves, and one end of the two L-shaped sliders away from the inner rack is fixedly connected to the shaft seat located above.

[0013] 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 provided in the arc-shaped plate, a plurality of the arc-shaped locking rods all penetrate the corresponding arc-shaped locking holes and are slidably connected to the inner walls of the corresponding arc-shaped locking holes.

[0014] 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.

[0015] In order to solve the above problems, the present invention also provides a method for preparing a calcipotriol bulk drug, comprising the following steps: T1: placing a culture medium containing glucose, corn steep liquor and potassium dihydrogen phosphate into a manufacturing device for the calcipotriol API, introducing high-temperature steam into the interlayer for sterilization, and then inoculating a seed solution of Penicillium oxalicum, stirring under aeration, and culturing for two days, adding stigmasterol to a 0.1% Tween 80 solution to prepare a suspension, and adding the suspension to the manufacturing device for the calcipotriol API, continuing to ferment for three days, terminating the reaction, discharging the fermentation liquid, and then extracting the fermentation liquid with ethyl acetate, allowing the layers to stand and separate, and taking the organic layer and concentrating it under reduced pressure to obtain compound a; T2: Compound a is reacted with tert-butyldimethylsilyl chloride in an aprotic organic solvent in the presence of an acid-binding agent at 20 to 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: After photoisomerization reaction of compound e, calcipotriol raw material is obtained.

[0016] Compared with the related art, the method and equipment for manufacturing the calcipotriol API provided by the present invention have the following beneficial effects: The present invention provides a manufacturing device for a calcipotriol bulk drug. By setting components such as a rotating sleeve, a regular polygonal cylinder, a lifting mechanism, a high-pressure water pump, a water delivery pipe, a first drainage pipe and a first three-dimensional cleaning ball, during normal operation, the first three-dimensional cleaning ball is hidden in the regular polygonal cylinder and is located at the central position 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 make the first three-dimensional cleaning ball appear, and then the high-pressure water pump is started to pump cleaning liquid into the first drainage pipe. Under the action of water pressure, the cleaning liquid is sprayed from the nozzle on the first three-dimensional cleaning ball, and the rotating pipe and the nozzle on the first three-dimensional cleaning ball are rotated, so that the trajectory of the cleaning liquid spraying is spherical, so that the inner liner is cleaned in all directions. Through this setting, the manufacturing device for the calcipotriol bulk drug has an autonomous cleaning function, and can complete all-round cleaning of the inner liner without the aid of special cleaning equipment, and there is no need to remove the stirring device, so that the equipment can be stopped and cleaned at any time, reducing downtime, which is conducive to improving the production efficiency of the calcipotriol bulk drug. The present invention provides a manufacturing device for calcipotriol bulk drug. By arranging components such as a second drainage pipe, a second three-dimensional cleaning ball, a connecting hose, a linkage pressing mechanism, and a push block, during the process of lifting a regular polygonal cylinder, two second drainage pipes can be moved downward. After the lifting arm rises to the limit height position, the first three-dimensional cleaning ball is completely exposed, and at the same time, the second three-dimensional cleaning ball is completely entered into the inner tank under the drive of 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 spray water at the same time, which can effectively improve the cleaning speed, and also can improve the cleaning effect on the tank cover and the agitator, so that the overall cleaning speed and cleaning effect are significantly improved. The present invention provides a manufacturing device for a calcipotriol bulk drug. By arranging 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 the arc-shaped locking holes on the plurality of arc-shaped plates, so that the polygonal protective cover can be reliably locked. When it is necessary to inspect and repair the components in the polygonal protective cover, it is only necessary to rotate the circular ring counterclockwise so that the plurality of arc-shaped locking rods can all exit the corresponding arc-shaped locking holes, and the polygonal protective cover can be quickly unlocked. By means of this arrangement, the disassembly and installation time of the polygonal protective cover can be greatly reduced, and the inspection and repair efficiency can be effectively improved. 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 fermentation process. Since the calcipotriol API manufacturing equipment has a self-cleaning function, the time used for preparation and cleaning can be effectively saved, which is beneficial to improving the production efficiency of calcipotriol. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 A schematic structural diagram of a first embodiment of a manufacturing device for calcipotriol API provided by the present invention; Figure 2 for Figure 1 The schematic diagram of the structure of the manufacturing equipment of calcipotriol API after removing the polygonal protective cover; Figure 3 for Figure 2 An enlarged schematic diagram of the structure of part A is shown; Figure 4 for Figure 2 A schematic cross-sectional view of a manufacturing apparatus for calcipotriol API is shown; Figure 5 for Figure 4 The schematic diagram of the structure of the manufacturing equipment of calcipotriol API after the regular polygonal cylinder is lifted; Figure 6 for Figure 5 A schematic diagram of the connection between the first three-dimensional cleaning ball and the first drain pipe is shown; Figure 7 for Figure 4The structural schematic diagram of the gyro-shaped blocking block shown; Figure 8 for Figure 1 The schematic diagram of the structure in which the polygonal protective cover and the polygonal base are separated; Fig. 9 A schematic structural diagram of a second embodiment of the manufacturing equipment for calcipotriol bulk drug provided by the present invention; Fig.10 for Fig. 9 A partial cross-sectional structural schematic diagram of a manufacturing device for calcipotriol API is shown; Fig.11 for Fig.10 The structural schematic diagram of two sets of linkage pressing mechanisms shown; Fig.12 for Fig.11 An enlarged schematic diagram of the structure of part B is shown; Fig.13 A schematic structural diagram of a third embodiment of the manufacturing equipment for calcipotriol API provided by the present invention; Fig.14 for Fig.13 The enlarged structural diagram of the C part is shown; Fig.15 for Fig.13 A schematic diagram of the connection between the ring and the plurality of ear blocks shown; Fig.16 for Fig.13 Schematic diagram of the structure of the curved plate shown.

[0018] 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 rod; 11, second motor; 12, high-pressure water pump; 13, water pipe; 14, first drainage 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 rod; 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 locking rod; 37. Arc plate; 38. Magnet block. DETAILED DESCRIPTION

[0019] The present invention will be further described below in conjunction with the accompanying drawings and implementation modes.

[0020] First embodiment Please refer to Figure 1-Figure 8In the first embodiment of the present invention, the manufacturing equipment of calcipotriol raw material drug 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 arranged on the top of the tank cover 2, a steam inlet and a cooling water inlet are arranged on the outer wall of the jacket, a condensate outlet and a cooling water outlet are arranged at the bottom of the jacket, a discharge pipe is arranged 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 shaped like 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 arranged 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 with the rotating sleeve 3. Circular gears are fixedly sleeved on the outer wall of the regular polygonal cylinder 4 and on the output end of the first motor 7. The two circular gears are meshed. 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 tube 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 tube 4, a limited position slide is provided on the fixed plate 8, the lifting arm 9 is slidably mounted in the limited position slide, and 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 long lead screw 10 is rotatably mounted on the two shaft seats, the long lead screw 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 lead screw 10; 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. When the regular polygonal tube 4 rotates, the gyro-shaped blocking block 18 rotates with it. 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, a plurality of aeration plates distributed in a ring shape are fixedly installed on the top of the aeration ring pipe 16, and an air supply pipe 17 is fixedly installed on 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 externally connected to an air supply device.

[0021] In this embodiment, a polygonal base 20 is fixedly installed on the top of the tank body 1. A mounting groove is opened on the top of the polygonal base 20. A polygonal protective cover 21 is arranged 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.

[0022] 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 .

[0023] In this embodiment: In the initial state, the bottom of the regular polygonal tube 4 is in conflict with 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; 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 make the raw materials evenly mixed together. 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, so as to supply oxygen to the fermentation raw materials. After the fermentation is completed, the material valve on the discharge pipe can be opened to discharge the fermentation liquid; When the inside of the inner tank needs to be cleaned, the second motor 11 is started to drive the filament 10 to rotate in the opposite direction. During the reverse rotation of the filament 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 sleeve ring 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 pump cleaning liquid 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 the inner tank can be cleaned in all directions.

[0024] Compared with the related art, the manufacturing equipment of calcipotriol raw material provided by the present invention has the following beneficial effects: 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, in 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 expose the first three-dimensional cleaning ball 15, 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 cleaning liquid is discharged. Under the present invention, 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, so that the inner tank is cleaned in all directions. Through this arrangement, the manufacturing equipment of the calcipotriol raw material has an independent cleaning function, and can complete the all-round cleaning of the inner tank without the aid of special cleaning equipment, and there is no need to remove the stirring device, so that the equipment can be stopped and cleaned at any time, reducing the downtime, which is beneficial to improving the production efficiency of the calcipotriol raw material.

[0025] Second embodiment: The second embodiment of the present invention is further described below in conjunction with the accompanying drawings and implementation modes.

[0026] Please refer to Figure 9-12In the manufacturing equipment of calcipotriol raw material provided in this embodiment, two second drain pipes 22 are also slidably installed 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 second three-dimensional cleaning balls 23 are fixedly installed on both ends, and connecting hoses 24 are fixedly installed on the tops of the two second drain pipes 22. One end of the two connecting hoses 24 away from the corresponding second drain pipes 22 is fixedly connected to the water pipe 13, and two sets of linkage pressing mechanisms are arranged on the fixed plate 8. The linkage pressing mechanism is used to cooperate with the lifting arm 9 to drive the second drain pipe 22 to move downward. When it is necessary to clean the inside of the inner tank, in 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 drain pipes 22 to move downward, and allow the two second three-dimensional cleaning balls 23 to enter the inner tank.

[0027] Specifically, any one of the linkage pressing mechanisms includes a fixed block 25, two limit 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. The fixed block 25 is fixedly mounted on the fixed plate 8. The two limit slide bars 26 are both penetrated and slidably mounted on the fixed block 25. The bottom ends of the two limit 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. 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 limit slide bars 26 are fixedly mounted with 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. A limiting slide groove is provided, and L-shaped sliders are slidably installed in the two limiting slide grooves. The ends of the two L-shaped sliders away from the inner rack 31 are fixedly connected to 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 meshed with the gear 32. When the inner rack 31 is lifted, the gear 32 is driven to rotate, and the outer rack 29 is driven to move downward during the rotation of the gear 32. The two springs 30 are respectively mounted on the two limiting 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 rack 31, and then push the two inner racks 31 to move upward.

[0028] In this embodiment: When cleaning the inner tank, the second motor 11 is started to operate to lift the regular polygonal tube 4. 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 to move downward through the connecting frame 28, so that the second three-dimensional cleaning ball 23 enters the inner tank. 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 the cleaning liquid, which can improve the overall cleaning speed. In the case of using only the first three-dimensional cleaning ball 15, the force of the cleaning liquid sprayed upward due to gravity will be lower, 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, which improves the overall cleaning speed and significantly improves the overall cleaning effect. After cleaning is completed, the second motor 11 is started to drive the lifting arm 9 to move downward, and 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, and the outer rack 29 will rise with the upper connecting plate, so that the corresponding inner rack 31 moves 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 the initial height position; By arranging the second drain pipe 22, the second three-dimensional cleaning ball 23, the connecting hose 24, the linkage pressing 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 entered into the inner tank under the drive of 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.

[0029] Third embodiment: The third embodiment of the present invention is further described below in conjunction with the accompanying drawings and implementation modes.

[0030] Please refer to Figure 13-Figure 16 In the manufacturing equipment of calcipotriol raw material provided in this embodiment, the polygonal protective cover 21 is fixed in a quick fixing manner. Specifically, a plurality of ear blocks 34 are fixedly installed on the polygonal protective cover 21, and the ear blocks 34 are made of stainless steel. The same circular ring 35 is rotatably installed on the plurality of ear blocks 34, and 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 arc-shaped locking rods 36 distributed in rotational symmetry are fixedly installed on the bottom of the circular ring 35, and a plurality of arc-shaped plates 37 distributed in rotational symmetry are fixedly installed on the top of the tank cover 2. An arc-shaped locking hole is opened in the arc-shaped plate 37, and a 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.

[0031] 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 .

[0032] In this embodiment: When it is necessary to inspect the components in 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 are all withdrawn from the corresponding arc-shaped locking holes, thereby releasing the lock of the polygonal protective cover 21, and then it can be taken away; 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; By arranging components such as multiple ear blocks 34, circular rings 35, multiple arc-shaped locking rods 36, and multiple arc-shaped plates 37, 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 in 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 inspection efficiency can be effectively improved.

[0033] Fourth embodiment: This embodiment provides a method for producing a calcipotriol raw material drug, comprising the following steps: T1: placing a culture medium containing glucose, corn steep liquor and potassium dihydrogen phosphate into a manufacturing device for the calcipotriol API, introducing high-temperature steam into the interlayer for sterilization, and then inoculating a seed solution of Penicillium oxalicum, stirring under aeration, and culturing for two days, adding stigmasterol to a 0.1% Tween 80 solution to prepare a suspension, and adding the suspension to the manufacturing device for the calcipotriol API, continuing to ferment for three days, terminating the reaction, discharging the fermentation liquid, and then extracting the fermentation liquid with ethyl acetate, allowing the layers to stand and separate, and taking the organic layer and concentrating it under reduced pressure to obtain compound a; T2: Compound a is reacted with tert-butyldimethylsilyl chloride in an aprotic organic solvent in the presence of an acid-binding agent at 20 to 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: After photoisomerization reaction of compound e, calcipotriol raw material is obtained.

[0034] The method for manufacturing the calcipotriol API uses the above-mentioned calcipotriol API manufacturing equipment to carry out the front fermentation process. Since the calcipotriol API manufacturing equipment has a self-cleaning function, the time used for preparation and cleaning can be effectively saved, which is beneficial to improving the production efficiency of calcipotriol.

[0035] 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 specification 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 raw material drug, comprising a tank body (1), the tank body (1) comprising an inner liner and a jacket, the jacket is fixedly mounted on the outer wall of the inner liner, and a tank cover (2) is 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 arranged 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 drainage pipe (14), an end of the first drainage 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 on the top of the tank cover (2); 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 arranged 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) is in contact with 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 aeration plates distributed in an annular shape are fixedly mounted on the top of the aeration ring tube (16), and an air supply pipe (17) is fixedly mounted on the bottom of the aeration ring tube (16), and one end of the air supply pipe (17) away from the aeration ring tube (16) extends to the outside of the tank body (1).

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 arranged 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 2, characterized in that: The lifting mechanism comprises a collar (6), a fixed plate (8), a lifting arm (9), a filament rod (10) and a second motor (11); the collar (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 an outer wall of the fixed plate (8) close to the regular polygonal cylinder (4); one 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).

4. The manufacturing equipment of calcipotriol bulk drug according to claim 3, characterized in that: A reinforcing rod is fixedly mounted on the shaft seat located at the top, 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).

5. 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 are fixedly mounted with a second three-dimensional cleaning ball (23), the top ends of the two second drain pipes (22) are fixedly mounted with a connecting hose (24), the ends of the two connecting hoses (24) away from the corresponding second drain pipes (22) are fixedly connected to the water pipe (13), and two sets of linkage pressing mechanisms are arranged on the fixed plate (8), the linkage pressing mechanisms are used to cooperate with the lifting arm (9) to drive the second drain pipe (22) to move downward.

6. The manufacturing equipment of calcipotriol bulk drug according to claim 5, characterized in that: Any one of the linkage downward pressing mechanisms comprises a fixed block (25), two limit sliding rods (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 limit sliding rods (26) are both penetrated and slidably mounted on the fixed block (25), the bottom ends of the two limit sliding rods (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 one 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 meshed with the gear (32), the two springs (30) are respectively sleeved 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).

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

8. 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), a same circular ring (35) is rotatably mounted on the plurality of ear blocks (34), a plurality of arc-shaped locking rods (36) which are rotationally symmetrically distributed are fixedly mounted on the bottom of the circular ring (35), a plurality of arc-shaped plates (37) which are rotationally symmetrically distributed are fixedly mounted on the top of the tank cover (2), an arc-shaped locking hole is formed in the arc-shaped plate (37), and the plurality of arc-shaped locking rods (36) all penetrate the corresponding arc-shaped locking holes and are slidably connected to the inner walls of the corresponding arc-shaped locking holes.

9. The manufacturing equipment of calcipotriol bulk drug according to claim 8, 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).

10. A method for producing a calcipotriol API using the calcipotriol API production equipment according to any one of claims 1 to 9, characterized in that: The following steps are involved: T1: placing a culture medium containing glucose, corn steep liquor and potassium dihydrogen phosphate into a manufacturing device for the calcipotriol API, introducing high-temperature steam into the interlayer for sterilization, and then inoculating a seed solution of Penicillium oxalicum, stirring under aeration, and culturing for two days, adding stigmasterol to a 0.1% Tween 80 solution to prepare a suspension, and adding the suspension to the manufacturing device for the calcipotriol API, continuing to ferment for three days, terminating the reaction, discharging the fermentation liquid, and then extracting the fermentation liquid with ethyl acetate, allowing the layers to stand and separate, and taking the organic layer and concentrating it under reduced pressure to obtain compound a; T2: Compound a is reacted with tert-butyldimethylsilyl chloride in an aprotic organic solvent in the presence of an acid-binding agent at 20 to 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: After photoisomerization reaction of compound e, calcipotriol raw material is obtained.

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