Process for reducing content of bromofluoromethane in fluticasone furoate bulk drug

Abstract

The invention provides a process for reducing the content of bromofluoromethane in a fluticasone furoate bulk drug, and relates to the technical field of biological medicine and separation and purification processes, and the process comprises the following steps: adding pure water into an original solution, oscillating and mixing, and standing for layering; separating an organic phase; concentrating the extracted solution to a semi-solid state, adding a crystallization solvent, and cooling; the wet crystals are placed in vacuum drying and purifying equipment, and the temperature in a drying tank is increased; according to the invention, the power assembly drives the external drying tank to rotate, so that the internal solution can be in direct contact with the inner wall of the drying tank in a larger area, and along with the rotation of the drying tank, the solution at the bottom layer is partially adhered and lifted to form a thinner state; the volatilization process is accelerated, the volatilization and purification efficiency is improved, the volatilization uniformity is improved, and the caking phenomenon of the generated medicine powder part can be reduced.

Description

Technical Field

[0001] This invention relates to the fields of biomedicine and separation and purification technology, and in particular to a process for reducing the content of fluorobromomethane in fluticasone furoate raw material. Background Technology

[0002] In the processing of fluticasone furoate raw materials, it is necessary to thoroughly remove or control this harmful impurity below a safe threshold through targeted optimization of the synthesis and purification process. Because fluorobromomethane has hepatotoxic and nephrotoxic risks and carcinogenic potential, strict control can prevent adverse reactions caused by impurity accumulation during long-term medication use, which is especially crucial for patients with asthma / rhinitis. On the other hand, fluorobromomethane is volatile and chemically reactive; its residue may lead to degradation of the raw material. Removal can significantly extend the drug's shelf life and maintain consistent efficacy. Therefore, reducing the fluorobromomethane content in fluticasone furoate raw materials is an extremely important step.

[0003] In existing technologies, methods to reduce the fluorobromomethane content in fluticasone furoate raw materials include low-temperature vacuum drying and nitrogen purging. However, in conventional methods, the fluorobromomethane crystals are placed directly on a tray, vacuumed, and heated. Although this can achieve the volatilization process, the volatilization effect is mainly affected by the surface area, which limits the volatilization efficiency. Furthermore, during the separation and purification process, the dried powder may clump together, making it difficult to collect the powder later. This results in cumbersome processing steps and makes it difficult to meet the needs of large-scale production. Summary of the Invention

[0004] The present invention aims to at least partially solve one of the technical problems in the related art.

[0005] Therefore, the purpose of this invention is to provide a process for reducing the fluorobromomethane content in fluticasone furoate raw material. This invention uses a power component to drive the external drying tank to rotate, thereby enabling a larger area of ​​direct contact between the internal solution and the inner wall of the drying tank. As the drying tank rotates, the bottom layer of solution adheres and rises, forming a thinner layer, which accelerates the evaporation process, improves the efficiency of evaporation and purification, improves the uniformity of evaporation, and also reduces the occurrence of agglomeration in the resulting powder.

[0006] To achieve the above objectives, the present invention provides a process for reducing the content of fluorobromomethane in fluticasone furoate raw material, comprising the following steps: S1. Add the original solution to pure water, shake to mix, and let stand to separate the layers; separate the organic phase, repeat the extraction 2-3 times, dissolve and remove some of the fluorobromomethane impurities; S2. Concentrate the extracted solution to a semi-solid state, add crystallization solvent, slowly cool to 0-5℃, and stir to crystallize for 12-24 hours. S3. Filter and collect the crystals, and wash with a cold solvent to elute the fluorobromomethane; S4. Place the wet crystals in a vacuum drying and purification device. The vacuum drying and purification device includes a drying tank, a power component, a transmission component, and a scraping component. The wet crystals are dropped into the interior of the drying tank through the opening on the surface of the drying tank. An electric heating wire is embedded in the inner wall of the drying tank. After the electric heating wire is turned on, the temperature inside the drying tank is increased. The temperature is set to 30-40℃ and the vacuum degree is ≤10 mbar. S5. One end of the drying tank is connected to an air inlet pipe. An air filling mechanism is set at one end of the inner wall of the drying tank. Nitrogen gas from the outside is delivered to the interior of the air filling mechanism through the air inlet pipe to purge the drying tank with nitrogen gas. The air filling mechanism triggers the transmission component and drives the scraping component to move horizontally. The scraping component locks with the drying tank and rotates synchronously. The scraping component agitates the solvent, accelerates solvent evaporation, and ensures that the residual fluorobromomethane is reduced to the target level. S6. Stop the nitrogen supply, reset the gas filling mechanism, and reset the transmission component and scraping assembly synchronously. Use the internal scraping assembly, which is locked to the drying tank, to scrape the powder adhering to the inside of the vacuum drying and purification equipment, so that the powder accumulates in the bottom area of ​​the drying tank. After scraping is completed, open the drying tank and take out the collected powder.

[0007] Further, in step S1, the mixture after the synthesis reaction is completed is transferred to a separatory funnel and mixed with pure water at a 1:1 ratio. After sealing, the mixture is shaken at 120-150 times / minute for 3 minutes to transfer fluorobromomethane from the aqueous phase to the organic phase. Then, the mixture is allowed to stand for 15-20 minutes to separate into layers. After the interface is clear, the lower aqueous phase is slowly released from the lower separation valve, while the upper organic phase is retained. This extraction is repeated until gas chromatography shows that the residual amount of fluorobromomethane has decreased by >90%. If an emulsion layer appears in the shaken solution, add saturated sodium chloride solution to eliminate the emulsion.

[0008] Furthermore, after crystallization is completed in step S3, the suspension containing fluticasone furoate crystals is poured into a pre-cooled Buchner funnel, the temperature is controlled at 0-5℃, a vacuum pump is started for filtration, the negative pressure is ≥0.08 MPa, and the mother liquor is quickly removed; then the crystals are washed three times with a low-temperature mixed solvent of ethanol and water, the ratio of ethanol to water being 8:2.

[0009] Furthermore, in step S4, the wet crystals are introduced into the interior of the drying tank from the preset inlet on the surface of the drying tank, and form a volatile solvent after being heated by the inner wall of the drying tank. The dispensing port is located at one end of the drying tank. A power assembly at the end of the drying tank is used to control the entire drying tank to rotate. A sealing cover is installed at the end of the dispensing port. After the power assembly drives the drying tank to rotate, the dispensing port and the sealing cover rotate synchronously around the power assembly.

[0010] Furthermore, the drying tank is connected to an inlet pipe and an exhaust pipe at both ends. The inlet pipe is used to transport nitrogen into the interior of the drying tank, and the exhaust pipe is used to blow out the nitrogen and entrained solvent volatile gases inside the drying tank. The process of controlling the drying tank using the power unit includes: Support frames are welded to the surfaces of both the intake and exhaust pipes to support the entire drying tank. A motor is screwed onto the support frame of the exhaust pipe. After the motor is started, the drive shaft at the output end of the motor is rotated, and the drive shaft drives the active gear on the surface to move synchronously. A driven gear is welded to the end of the drying tank. The active gear and the driven gear work together to rotate the entire drying tank. During the rotation of the drying tank, the solvent inside the drying tank comes into direct contact with different areas of the inner wall of the drying tank and is continuously heated by the changing contact areas.

[0011] Furthermore, nitrogen is delivered to the filling mechanism inside the drying tank through the air inlet pipe. The nitrogen is kept at high pressure. In the initial state, the filling mechanism is pulled by the second spring, which drives the telescopic sleeve to move to one end of the telescopic groove closer to the air inlet pipe. High-pressure nitrogen pushes the telescopic sleeve, and the second spring stretches it. The telescopic sleeve and the top sleeve move synchronously toward the exhaust pipe at the other end under high pressure. An exhaust plate is integrally formed on the inner side of the drying tank near the exhaust pipe, and a central column is screwed into the middle of the exhaust plate.

[0012] Furthermore, the nitrogen pusher sleeve is fitted onto the end of the central column and abuts against the end of the sliding sleeve, applying a thrust to the sliding sleeve and controlling the sliding sleeve to move toward the other end. The sliding sleeve pushes and compresses the first spring at the end, and simultaneously drives the first docking plate on the side to move. The first docking plate, the connecting frame, and the second docking plate are all integrally formed. When the sliding sleeve moves, it directly drives the first docking plate, the connecting frame, and the second docking plate to move. The first insertion post on the first docking plate and the second docking plate is always embedded in the receiving hole on the scraping component, while the second insertion post on the second docking plate is embedded in the groove opened at one end of the inner wall of the drying tank during the translation process, which is used to keep the scraping component and the drying tank locked together.

[0013] Furthermore, after the motor is started, the drying tank rotates through the power component, which, together with the groove and the second plug-in post, directly drives the entire scraping component to rotate synchronously with the drying tank. A scraping blade is provided at the end of the scraping component, and the edge of the scraping blade is in contact with the inner wall of the drying tank, so that the scraping component and the drying tank are locked in a relatively stationary state between the scraping blade and the drying tank. The heating process of the inner wall of the drying tank is started, and with the rotation of the scraper assembly and the drying tank, the solvent at the bottom is scooped up and stirred by the scraper blades. A counterweight rod is connected to the side of the sliding sleeve through an extension rod. The counterweight rod is pressed against the inner wall of the drying tank. As the counterweight rod rotates, the powder generated after the solvent evaporates is crushed.

[0014] Furthermore, in step S6, after the solvent evaporates, the external nitrogen supply is stopped, the pressure inside the inflation mechanism is reduced, and during the reset of the second spring, the telescopic sleeve is pulled along the inside of the telescopic groove toward one end of the air inlet pipe, and the top sleeve is pulled to reset synchronously. The top sleeve and the sliding sleeve separate, and the sliding sleeve, under the reset push of the first spring, pulls the scraping component to move synchronously toward the position of the air inlet pipe. After the sliding sleeve is reset, it drives the first docking plate, the connecting frame and the second docking plate to reset synchronously. The second insertion post on the second docking plate moves out of the groove, and the scraping component and the drying tank are unlocked. The weight of the counterweight rod on one side of the sliding sleeve is greater than the entire scraping component, and the first spring and the sliding sleeve are movably connected. At this time, the power component is started to carry out the subsequent powder collection process.

[0015] Furthermore, the powder collection process includes: the power component controls the drying tank to rotate continuously, the transmission component hangs down through the side counterweight rod to pull the scraping component on the other side of the sliding sleeve, and controls the scraping blade to always keep in a fixed angle position. After the drying tank rotates, the inner wall of the drying tank and the scraping blade generate relative movement. As the drying tank rotates, the scraping blade scrapes off the powder adhering to different areas on the inner wall of the drying tank.

[0016] The technical solution provided by this invention may include the following beneficial effects: 1. The process for reducing the fluorobromomethane content in fluticasone furoate raw material uses a power unit to drive the external drying tank to rotate, thereby enabling a larger direct contact area between the internal solution and the inner wall of the drying tank. As the drying tank rotates, the bottom layer of solution is partially adhered and lifted, forming a thinner state, which accelerates the evaporation process and improves the efficiency of evaporation and purification.

[0017] 2. In this process for reducing the fluorobromomethane content in fluticasone furoate raw material, a certain pressure is generated by injecting nitrogen gas. This pressure can be used to directly control the movement of the transmission components, allowing the sliding assembly to embed into the inner wall of the drying tank. This achieves the locking purpose between the scraping assembly and the drying tank. Subsequently, the internal solution can be stirred by the synchronous rotation of the scraping assembly and the drying tank, which further improves the uniformity of volatilization and reduces the occurrence of agglomeration of the generated powder.

[0018] 3. After the volatilization is completed, the process of reducing the content of fluorobromomethane in fluticasone furoate raw material only requires stopping the injection of nitrogen, but still starting the power unit. The first spring on the transmission component can release the locking effect between the scraping component and the drying tank. At this time, the scraping component can scrape off the powder adhering to the drying tank by means of the weight of the transmission component and the scraping component, so as to achieve the purpose of powder aggregation and facilitate the subsequent removal of powder.

[0019] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0020] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the following description of the embodiments taken in conjunction with the accompanying drawings, wherein: Figure 1 This is a flowchart of a process for reducing the content of fluorobromomethane in fluticasone furoate raw material according to an embodiment of the present invention; Figure 2 This is a schematic diagram of the vacuum drying and purification equipment used in the process of reducing the content of fluorobromomethane in fluticasone furoate raw material according to an embodiment of the present invention. Figure 3 This is a schematic diagram of the internal structure of the drying tank in a vacuum drying and purification device according to an embodiment of the present invention; Figure 4 This is a side sectional view of the drying tank in a vacuum drying and purification device according to an embodiment of the present invention; Figure 5 This is the present invention. Figure 4 Enlarged view of region A in the middle; Figure 6 This is a schematic diagram showing the connection between the transmission component and the scraping assembly in a vacuum drying and purification device according to an embodiment of the present invention; Figure 7 This is a schematic diagram of the scraping component in a vacuum drying and purification device according to an embodiment of the present invention; Figure 8 This is a schematic diagram of the power component in a vacuum drying and purification device according to an embodiment of the present invention; As shown in the figure: 1. Support frame; 2. Power assembly; 3. Dryer; 4. Air inlet pipe; 5. Transmission component; 6. Scraper assembly; 7. Inflation mechanism; 8. Front end plate; 9. Rear end plate; 10. Groove; 11. Exhaust pipe; 12. Exhaust disc; 13. Center column; 14. Air inlet disc; 15. Telescopic sleeve; 16. Air inlet; 17. Top sleeve; 18. Second spring; 19. Sliding sleeve; 20. First spring; 21. Extension rod; 22. Counterweight rod; 23. First docking plate; 24. Connecting frame; 25. First insertion post; 26. Second docking plate; 27. Linkage plate; 28. Receiver hole; 29. ​​Scraper; 30. Motor; 31. Drive shaft; 32. Drive gear; 33. Driven gear; 34. Second insertion post; 35. Exhaust port; 36. Dating slip ring; 37. Telescopic groove. Detailed Implementation

[0021] Embodiments of the present invention are described in detail below, examples of which are illustrated in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the invention, and should not be construed as limiting the invention. Rather, embodiments of the invention include all variations, modifications, and equivalents falling within the spirit and scope of the appended claims.

[0022] like Figures 1 to 8 As shown in the figure, this invention proposes a process for reducing the fluorobromomethane content in fluticasone furoate raw material, comprising the following steps: S1. Add the original solution to pure water, shake to mix, and let stand to separate the layers; separate the organic phase, repeat the extraction 2-3 times, dissolve and remove some of the fluorobromomethane impurities; After the synthesis reaction is completed, the mixture is transferred to a separatory funnel and mixed with pure water at a ratio of 1:1. After sealing, the mixture is shaken at 120-150 times / minute for 3 minutes to transfer fluorobromomethane from the aqueous phase to the organic phase. Then, the mixture is allowed to stand for 15-20 minutes to separate the layers. After the interface is clear, the lower aqueous phase is slowly released from the lower separation valve, while the upper organic phase is retained. The extraction is repeated until gas chromatography shows that the residual amount of fluorobromomethane has decreased by >90%.

[0023] S2. Concentrate the extracted solution to a semi-solid state, add crystallization solvent, slowly cool to 0-5℃, and stir to crystallize for 12-24 hours. S3. Filter and collect the crystals, and wash with a cold solvent to elute the fluorobromomethane; After crystallization, the suspension containing fluticasone furoate crystals was poured into a pre-cooled Buchner funnel, and the temperature was controlled at 0-5℃. The vacuum pump was started for filtration, with a negative pressure ≥0.08 MPa, and the mother liquor was quickly removed. Subsequently, the crystals were washed three times with a low-temperature mixed solvent of ethanol and water, with the ratio of ethanol to water being 8:2.

[0024] S4. In this step, a vacuum drying and purification device is used. A docking slip ring 36 is set at both ends of the drying tank 3, and the docking slip ring 36 is movably connected to the air inlet pipe 4 and the exhaust pipe 11 respectively. The power component 2 includes a motor 30, a drive shaft 31, a drive gear 32 and a driven gear 33. The output end of the motor 30 is welded to the drive shaft 31, and the end of the drive shaft 31 is keyed to the drive gear 32. A driven gear 33 is set at one end of the drying tank 3. The drive gear 32 and the driven gear 33 are fitted together. The motor 30 is screwed onto one of the support frames 1. Both ends of the drying tank 3 are placed through the support frames 1. An exhaust plate 12 is integrally formed on one end of the inner wall of the drying tank 3, and an exhaust hole 35 is provided on the surface of the exhaust plate 12.

[0025] The wet crystals are placed in a vacuum drying and purification device, which includes a drying tank 3, a power component 2, a transmission component 5, and a scraping component 6. The wet crystals are dropped into the interior of the drying tank 3 through the opening on the surface of the drying tank 3. An electric heating wire is embedded in the inner wall of the drying tank 3. After the electric heating wire is activated, the temperature inside the drying tank 3 is increased. The temperature is set to 30-40℃ and the vacuum degree is ≤10 mbar. Wet crystals are introduced into the interior of the drying tank 3 from the pre-set inlet on the surface of the drying tank 3, and form a volatile solvent after being heated by the inner wall of the drying tank 3; The dispensing port is located at one end of the drying tank 3. The power assembly 2 located at the end of the drying tank 3 is used to control the entire drying tank 3 to rotate. A sealing cover is installed at the end of the dispensing port. After the power assembly 2 drives the drying tank 3 to rotate, the dispensing port and the sealing cover rotate synchronously around the power assembly 2.

[0026] The drying tank 3 is connected to an air inlet pipe 4 and an exhaust pipe 11 at its two ends respectively. The air inlet pipe 4 is used to transport nitrogen into the interior of the drying tank 3, and the exhaust pipe 11 is used to blow out the nitrogen and entrained solvent volatile gas inside the drying tank 3. The process by which the power unit 2 controls the drying tank 3 includes: Support frames 1 are welded to the surfaces of both the intake pipe 4 and the exhaust pipe 11 to support the entire drying tank 3. A motor 30 is screwed onto the support frame 1 of the exhaust pipe 11. After the motor 30 is started, the drive shaft 31 at the output end of the motor 30 is controlled to rotate, and the drive shaft 31 drives the active gear 32 on the surface to move synchronously. A driven gear 33 is welded to the end of the drying tank 3. The active gear 32 is linked with the driven gear 33 until the entire drying tank 3 is rotated. During the rotation of the drying tank 3, the solvent inside the drying tank 3 comes into direct contact with different areas of the inner wall of the drying tank 3 and is continuously heated by the contact areas.

[0027] The power unit 2 drives the external drying tank 3 to rotate, thereby enabling the internal solution to have a larger direct contact area with the inner wall of the drying tank 3. As the drying tank 3 rotates, the bottom layer of solution is adhered and lifted, forming a thinner state, which accelerates the evaporation process and improves the efficiency of evaporation and purification.

[0028] S5. In this step, an inflation mechanism 7, a transmission component 5, and a scraping component 6 are used. The inflation mechanism 7 includes a telescopic sleeve 15, an air inlet 16, a top sleeve 17, and a second spring 18. One end of the telescopic sleeve 15 is connected to the second spring 18. An air inlet plate 14 is integrally formed on the other end of the inner wall of the drying tank 3. A telescopic groove 37 is opened on the inner side of the air inlet plate 14. A second spring 18 is welded to one end of the telescopic groove 37. The other end of the second spring 18 is connected to the telescopic sleeve 15. Multiple air inlets 16 are opened on the surface of the telescopic sleeve 15. The top sleeve 17 is in the form of a ring structure, and the inner ring of the top sleeve 17 is flush with the surface of the central column 13. The transmission component 5 includes a sliding sleeve 19, a first spring 20, an extension rod 21, and a counterweight rod 22. The extension rod 21 is welded to the side of the sliding sleeve 19, and the counterweight rod 22 is welded to the end of the extension rod 21. The end of the sliding sleeve 19 abuts against one end of the first spring 20, and the sliding sleeve and the first spring 20 are kept separated. The end of the first spring 20 is welded to the surface of the exhaust plate 12. Nitrogen gas is blown out from the air inlet 16 on the inflation side, passes through the inside of the drying tank 3, and then blown out from the inside of the exhaust port 35 towards the outside. The scraping assembly 6 includes a linkage plate 27, a receiving hole 28, and a scraping blade 29. The linkage plate 27 is welded to one edge of the scraping blade 29. The receiving hole 28 is opened on the surface of the linkage plate 27. A first docking plate 23 is also welded to the side of the sliding sleeve 19. A connecting frame 24 is welded to the side of the first docking plate 23. A second docking plate 26 is welded to the other end of the connecting frame 24. A first insertion post 25 is welded to the same side of the first docking plate 23 and the second docking plate 26. There are four first insertion posts 25. A second docking post is also welded to the other side of the second docking plate 26. There are two second docking posts.

[0029] One end of the drying tank 3 is connected to an air inlet pipe 4. An air filling mechanism 7 is provided on one end of the inner wall of the drying tank 3. Nitrogen gas from the outside is delivered to the interior of the air filling mechanism 7 through the air inlet pipe 4 to purge the drying tank 3 with nitrogen gas. The air filling mechanism 7 triggers the transmission component 5 and drives the scraping component 6 to move horizontally. The scraping component 6 is locked to the drying tank 3 and rotates synchronously. The solvent is stirred by the scraping component 6 to accelerate solvent evaporation and ensure that the residual fluorobromomethane is reduced to the target level. Nitrogen gas is delivered to the filling mechanism 7 inside the drying tank 3 through the air inlet pipe 4. The nitrogen gas is kept at high pressure. In the initial state, the filling mechanism 7 is pulled by the second spring 18, which drives the telescopic sleeve 15 to move to one end of the telescopic groove 37 close to the air inlet pipe 4. High-pressure nitrogen pushes the telescopic sleeve 15, and the second spring 18 is stretched. The telescopic sleeve 15 and the top sleeve 17 move synchronously towards the exhaust pipe 11 at the other end under high pressure. An exhaust plate 12 is integrally formed on the inner side of the drying tank 3 near the exhaust pipe 11, and a central column 13 is screwed into the middle of the exhaust plate 12.

[0030] The nitrogen pusher sleeve is fitted onto the end of the central column 13 and abuts against the end of the sliding sleeve 19, applying a thrust to the sliding sleeve 19 and controlling the sliding sleeve 19 to move toward the other end. The sliding sleeve 19 pushes and compresses the first spring 20 at the end, and simultaneously drives the first docking plate 23 on the side to move. The first docking plate 23, the connecting frame 24, and the second docking plate 26 are all integrally formed. When the sliding sleeve 19 moves, it directly drives the first docking plate 23, the connecting frame 24, and the second docking plate 26 to move. The first insertion post 25 on the first docking plate 23 and the second docking plate 26 is always embedded in the receiving hole 28 on the scraping component 6, while the second insertion post 34 on the second docking plate 26 is embedded in the groove 10 opened at one end of the inner wall of the drying tank 3 during the translation process, which is used to keep the scraping component 6 and the drying tank 3 locked and linked.

[0031] After the motor 30 is started, the drying tank 3 rotates through the power component 2. In conjunction with the groove 10 and the second insertion post 34, the entire scraping component 6 rotates synchronously with the drying tank 3. A scraping blade 29 is provided at the end of the scraping component 6. The edge of the scraping blade 29 is in contact with the inner wall of the drying tank 3, so that the scraping component 6 and the drying tank 3 are locked in a relatively stationary state between the scraping blade 29 and the drying tank 3. The heating process of the inner wall of the drying tank 3 is started, and with the rotation of the scraper assembly 6 and the drying tank 3, the solvent at the bottom is scooped up and stirred by the scraper blade 29. The counterweight rod 22 is connected to the side of the sliding sleeve 19 by the extension rod 21. The counterweight rod 22 is pressed on the inner wall of the drying tank 3. As the counterweight rod 22 rotates, the powder generated after the solvent evaporates is crushed.

[0032] The injected nitrogen gas generates a certain pressure, which directly controls the movement of the transmission component 5, allowing the sliding component to be embedded in the inner wall of the drying tank 3. This achieves the locking purpose between the scraping component 6 and the drying tank 3. Subsequently, the scraping component 6 can be rotated synchronously with the drying tank 3 to agitate the internal solution, further improving the uniformity of evaporation and reducing the occurrence of clumping in the generated powder.

[0033] S6. Stop the nitrogen supply, reset the gas filling mechanism 7, and reset the transmission component 5 and the scraping component 6 synchronously. With the help of the internally released scraping component 6 which is locked to the drying tank 3, scrape the powder adhering to the inside of the vacuum drying and purification equipment, so that the powder accumulates in the bottom area of ​​the drying tank 3. After the scraping is completed, open the drying tank 3 and take out the collected powder.

[0034] After the solvent evaporates, the external nitrogen supply is stopped, the pressure inside the inflation mechanism 7 is reduced, and during the reset of the second spring 18, the telescopic sleeve 15 is pulled along the inside of the telescopic groove 37 toward one end of the air inlet pipe 4, and the top sleeve 17 is pulled to reset synchronously. The top sleeve 17 and the sliding sleeve 19 are separated. Under the reset push of the first spring 20, the sliding sleeve 19 pulls the scraping component 6 to move synchronously toward the position of the air inlet pipe 4. After the sliding sleeve 19 is reset, it drives the first docking plate 23, the connecting frame 24 and the second docking plate 26 to reset synchronously. The second insertion post 34 on the second docking plate 26 moves out of the inside of the groove 10, and the locking state between the scraping assembly 6 and the drying tank 3 is released. The weight of the counterweight rod 22 on one side of the sliding sleeve 19 is greater than the entire scraping assembly 6, and the first spring 20 is movably connected to the sliding sleeve 19. At this time, the power assembly 2 is started to carry out the subsequent powder collection process.

[0035] The powder collection process includes: the power unit 2 controls the drying tank 3 to rotate continuously, the transmission component 5 hangs down through the side counterweight rod 22, and pulls the scraping component 6 on the other side of the sliding sleeve 19, controlling the scraping blade 29 to always maintain a fixed angle position. After the drying tank 3 rotates, the inner wall of the drying tank 3 and the scraping blade 29 generate relative movement. As the drying tank 3 rotates, the scraping blade 29 scrapes off the powder adhering to different areas on the inner wall of the drying tank 3.

[0036] After evaporation is complete, simply stop the injection of nitrogen, but still start the power component 2. The first spring 20 on the transmission component 5 can release the locking effect between the scraping component 6 and the drying tank 3. At this time, the scraping component 6 can scrape off the powder adhering to the drying tank 3 by means of the weight of the transmission component 5 and the scraping component 6, so as to achieve the purpose of powder aggregation and facilitate the subsequent removal of powder.

[0037] The terms "first," "second," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance. Furthermore, in the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0038] Any process or method description in the flowchart or otherwise herein can be understood as representing a module, segment, or portion of code comprising one or more executable instructions for implementing a particular logical function or process, and the scope of the preferred embodiments of the invention includes additional implementations in which functions may be performed not in the order shown or discussed, including substantially simultaneously or in reverse order depending on the functions involved, as will be understood by those skilled in the art to which embodiments of the invention pertain.

[0039] In the description of this specification, references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0040] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. A process for reducing the content of fluorobromomethane in fluticasone furoate raw material, characterized in that, Includes the following steps: S1. Add the original solution to pure water, shake to mix, and let stand to separate the layers; separate the organic phase, repeat the extraction 2-3 times, dissolve and remove some of the fluorobromomethane impurities; S2. Concentrate the extracted solution to a semi-solid state, add crystallization solvent, slowly cool to 0-5℃, and stir to crystallize for 12-24 hours. S3. Filter and collect the crystals, and wash with a cold solvent to elute the fluorobromomethane; S4. Place the wet crystals in a vacuum drying and purification device. The vacuum drying and purification device includes a drying tank, a power component, a transmission component, and a scraping component. The wet crystals are dropped into the interior of the drying tank through the opening on the surface of the drying tank. An electric heating wire is embedded in the inner wall of the drying tank. After the electric heating wire is activated, the temperature inside the drying tank is increased. The temperature is set to 30-40℃ and the vacuum degree is ≤10mbar. S5. One end of the drying tank is connected to an air inlet pipe. An air filling mechanism is set at one end of the inner wall of the drying tank. Nitrogen gas from the outside is delivered to the interior of the air filling mechanism through the air inlet pipe to purge the drying tank with nitrogen gas. The air filling mechanism triggers the transmission component and drives the scraping component to move horizontally. The scraping component locks with the drying tank and rotates synchronously. The scraping component agitates the solvent, accelerates the evaporation of the solvent, and reduces the residual fluorobromomethane to the target level. S6. Stop the nitrogen supply, reset the gas filling mechanism, and reset the transmission component and scraping assembly synchronously. Use the internal scraping assembly, which is locked to the drying tank, to scrape the powder adhering to the inside of the vacuum drying and purification equipment, so that the powder accumulates in the bottom area of ​​the drying tank. After scraping is completed, open the drying tank and take out the collected powder.

2. The process for reducing the fluorobromomethane content in fluticasone furoate raw material according to claim 1, characterized in that, In step S1, the mixture after the synthesis reaction is completed is transferred to a separatory funnel and mixed with pure water at a 1:1 ratio. After sealing, the mixture is shaken at 120-150 times / minute for 3 minutes to transfer fluorobromomethane from the aqueous phase to the organic phase. The mixture is then allowed to stand for 15-20 minutes to separate the layers. Once the interface is clear, the lower aqueous phase is slowly released from the lower separation valve, while the upper organic phase is retained. This extraction process is repeated until gas chromatography shows a decrease in fluorobromomethane residue of >90%. If an emulsion layer appears in the shaken solution, add saturated sodium chloride solution to eliminate the emulsion.

3. The process for reducing the content of fluorobromomethane in fluticasone furoate raw material according to claim 2, characterized in that, After crystallization is completed in step S3, the suspension containing fluticasone furoate crystals is poured into a pre-cooled Buchner funnel, the temperature is controlled at 0-5℃, the vacuum pump is started for filtration, the negative pressure is ≥0.08 MPa, and the mother liquor is quickly removed; then the crystals are washed three times with a low-temperature mixed solvent of ethanol and water, the ratio of ethanol to water is 8:

2.

4. The process for reducing the fluorobromomethane content in fluticasone furoate raw material according to claim 1, characterized in that, In step S4, the wet crystals are introduced into the interior of the drying tank from the preset inlet on the surface of the drying tank, and form a volatile solvent after being heated by the inner wall of the drying tank. The dispensing port is located at one end of the drying tank. A power assembly at the end of the drying tank is used to control the entire drying tank to rotate. A sealing cover is installed at the end of the dispensing port. After the power assembly drives the drying tank to rotate, the dispensing port and the sealing cover rotate synchronously around the power assembly.

5. The process for reducing the fluorobromomethane content in fluticasone furoate raw material according to claim 4, characterized in that, The drying tank is connected to an inlet pipe and an exhaust pipe at both ends. The inlet pipe is used to deliver nitrogen into the interior of the drying tank, and the exhaust pipe is used to blow out the nitrogen and entrained solvent volatile gases from the interior of the drying tank. The process of controlling the drying tank using the power unit includes: Support frames are welded to the surfaces of both the intake and exhaust pipes to support the entire drying tank. A motor is screwed onto the support frame of the exhaust pipe. After the motor is started, the drive shaft at the output end of the motor is rotated, and the drive shaft drives the active gear on the surface to move synchronously. A driven gear is welded to the end of the drying tank. The active gear and the driven gear work together to rotate the entire drying tank. During the rotation of the drying tank, the solvent inside the drying tank comes into direct contact with different areas of the inner wall of the drying tank and is continuously heated by the changing contact areas.

6. The process for reducing the content of fluorobromomethane in fluticasone furoate raw material according to claim 4, characterized in that, Nitrogen gas is delivered to the filling mechanism inside the drying tank through the air inlet pipe. The nitrogen gas is kept at high pressure. In the initial state, the filling mechanism is pulled by the second spring, which moves the telescopic sleeve inside the telescopic groove to one end close to the air inlet pipe. High-pressure nitrogen pushes the telescopic sleeve, and the second spring stretches it. The telescopic sleeve and the top sleeve move synchronously toward the exhaust pipe at the other end under high pressure. An exhaust plate is integrally formed on the inner side of the drying tank near the exhaust pipe, and a central column is screwed into the middle of the exhaust plate.

7. The process for reducing the content of fluorobromomethane in fluticasone furoate raw material according to claim 6, characterized in that, The nitrogen pusher sleeve is fitted onto the end of the central column and abuts against the end of the sliding sleeve, applying a thrust to the sliding sleeve and controlling the sliding sleeve to move toward the other end. The sliding sleeve pushes and compresses the first spring at the end, and simultaneously drives the first docking plate on the side to move. The first docking plate, the connecting frame, and the second docking plate are all integrally formed. When the sliding sleeve moves, it directly drives the first docking plate, the connecting frame, and the second docking plate to move. The first insertion post on the first docking plate and the second docking plate is always embedded in the receiving hole on the scraping component, while the second insertion post on the second docking plate is embedded in the groove opened at one end of the inner wall of the drying tank during the translation process, which is used to keep the scraping component and the drying tank locked together.

8. The process for reducing the fluorobromomethane content in fluticasone furoate raw material according to claim 7, characterized in that, After the motor is started, the drying tank rotates through the power component. The groove and the second plug-in post directly drive the entire scraping component to rotate synchronously with the drying tank. A scraping blade is provided at the end of the scraping component. The edge of the scraping blade is in contact with the inner wall of the drying tank, so that the scraping component and the drying tank are locked in a relatively stationary state between the scraping blade and the drying tank. The heating process of the inner wall of the drying tank is started, and with the rotation of the scraper assembly and the drying tank, the solvent at the bottom is scooped up and stirred by the scraper blades. A counterweight rod is connected to the side of the sliding sleeve through an extension rod. The counterweight rod is pressed against the inner wall of the drying tank. As the counterweight rod rotates, the powder generated after the solvent evaporates is crushed.

9. The process for reducing the content of fluorobromomethane in fluticasone furoate raw material according to claim 6, characterized in that, In step S6, after the solvent evaporates, the external nitrogen supply is stopped, the pressure inside the inflation mechanism is reduced, and during the reset of the second spring, the telescopic sleeve is pulled along the inside of the telescopic groove toward one end of the air inlet pipe, and the top sleeve is pulled to reset synchronously. The top sleeve and the sliding sleeve separate, and the sliding sleeve, under the reset push of the first spring, pulls the scraping component to move synchronously toward the position of the air inlet pipe. After the sliding sleeve is reset, it drives the first docking plate, the connecting frame and the second docking plate to reset synchronously. The second insertion post on the second docking plate moves out of the groove, and the scraping component and the drying tank are unlocked. The weight of the counterweight rod on one side of the sliding sleeve is greater than the entire scraping component, and the first spring and the sliding sleeve are movably connected. At this time, the power component is started to carry out the subsequent powder collection process.

10. The process for reducing the content of fluorobromomethane in fluticasone furoate raw material according to claim 9, characterized in that, The powder collection process includes: the power unit controls the drying tank to rotate continuously, the transmission component hangs down through the side counterweight rod to pull the scraping component on the other side of the sliding sleeve, and controls the scraping blade to always keep in a fixed angle position. After the drying tank rotates, the inner wall of the drying tank and the scraping blade generate relative movement. As the drying tank rotates, the scraping blade scrapes off the powder adhering to different areas on the inner wall of the drying tank.

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