Megestrol acetate process

Abstract

The invention relates to the technical field of medicine preparation, in particular to a megestrol acetate process which comprises the following steps: S1, extracting 316kg of absolute ethyl alcohol, adding the absolute ethyl alcohol into a reaction kettle through a head tank, injecting nitrogen into the reaction kettle, then feeding 2kg of cyclohexene into the reaction kettle through the head tank, starting the reaction kettle for stirring, then adding 20kg of methine into the reaction kettle through a feeding port, and stirring for 2 hours; heating the reaction kettle until the internal temperature is more than or equal to 70 DEG C, adding 4kg of palladium-carbon into the reaction kettle, stopping injecting nitrogen, continuously heating the reaction kettle for reaction, after the reaction is finished, filtering feed liquid in the reaction kettle into a new reaction kettle, flushing residual palladium-carbon in the reaction kettle by using 23.7 kg of absolute ethyl alcohol, filtering flushing liquid into the new reaction kettle by using the same filter, and after the filtration is finished, filtering to obtain the palladium-carbon composite material. Heating the new reaction kettle until the solution is clarified, starting sampling, and controlling the new reaction kettle to perform vacuum concentration, so that the problems that the existing megestrol acetate process is relatively complicated in operation flow and relatively low in yield of finished products can be effectively solved.

Description

Technical Field

[0001] The invention relates to the technical field of drug preparation, in particular to a megestrol acetate process. Background Art

[0002] Megestrol acetate is a white or off-white crystalline powder; odorless, easily soluble in chloroform, soluble in acetone or ethyl acetate, slightly soluble in ethanol, slightly soluble in ether, and insoluble in water. It is mainly used to treat irregular menstruation, functional uterine bleeding, endometriosis, advanced breast cancer and endometrial adenocarcinoma; it can also be used as the progestogen component of short-acting combined oral contraceptive tablets for contraception, and can also treat dysmenorrhea, functional uterine bleeding, endometriosis, etc. In addition, it is also suitable for palliative treatment of advanced breast cancer and endometrial cancer. Its structural formula is: However, the existing megestrol acetate process still has some shortcomings, specifically: the existing megestrol acetate process operation flow is relatively complicated and the finished product yield is low.

[0003] Therefore, a megestrol acetate process is needed to solve the problems raised in the above background technology. Summary of the invention

[0004] The object of the present invention is to provide a megestrol acetate process to solve the problems raised in the above-mentioned background technology.

[0005] To achieve the above object, the present invention provides the following technical solutions: A megestrol acetate process comprises the following steps: S1, extract 316kg of anhydrous ethanol and add it to the reactor through the header tank, inject nitrogen into the reactor, then send 2kg of cyclohexene into the reactor through the header tank, start the reactor to stir, then add 20kg of methine from the feed port into the reactor, heat the reactor to an internal temperature of ≥70°C, add 4kg of palladium carbon into the reactor and stop injecting nitrogen, continue heating the reactor for reaction, after the reaction is completed, filter the feed liquid in the reactor into a new reactor, rinse the residual palladium carbon in the reactor with 23.7kg of anhydrous ethanol, filter the rinse liquid into the new reactor through the same filter, after the filtration is completed, heat the new reactor until the solution is clear and start sampling, control the new reactor to perform reduced pressure concentration, after the concentration is completed, drain the remaining water from the reactor jacket and inject frozen brine, and cool to -2-2°C; S2, put the material in the new reactor into a centrifuge and centrifuge to filter out the mother liquor, the filtered mother liquor enters the storage tank, waits for the mother liquor to be recovered, washes the filter cake with 11.9 kg of anhydrous ethanol and spins dry, combines the washing liquid with the mother liquor, puts it into a barrel and hands over the three wastes, performs pulping on the filter cake, stops the centrifuge, collects the filter cake and weighs it to obtain the crude megestrol acetate wet product, evenly packs the crude megestrol acetate wet product into a drying tray, puts the drying tray into a vacuum dryer for drying, collects the material after drying, puts it into a double-layer plastic bag, and performs sampling inspection by QC. After passing the inspection, it enters the intermediate warehouse; S3, check the production equipment, extract 180-200kg of ethyl acetate and add it to the decolorization kettle through the header tank, then weigh 1.5kg of activated carbon and add it to the decolorization kettle through the feed port, start stirring, add all the crude megestrol acetate to the decolorization kettle through the feed port, heat the jacket of the decolorization kettle in a water bath to raise the internal temperature to 73-83°C, reflux for 60 minutes, filter the liquid in the decolorization kettle through a filter into a crystallization kettle, extract 20-40kg of ethyl acetate to rinse the decolorization kettle, and the washing liquid is filtered into the crystallization kettle. After the filtration is completed, distill and concentrate. After the concentration is completed, put the material in the crystallization kettle into a flat-plate closed centrifuge, centrifuge and filter, filter out the mother liquor, and put the filtered mother liquor into a storage tank, wash the filter cake with 20-40kg of ethyl acetate, dry it, combine the washing liquid with the mother liquor, stop the flat-plate closed centrifuge, wait for it to stop running, take samples for megestrol acetate centrifugal control, and collect the filter cake; S4, set the solenoid valve of the drying hot water tank to a hot water temperature of 60-70°C, start the hot water circulation, heat the vacuum dryer jacket with 60-70°C hot water, evenly pack the wet megestrol acetate in a drying tray, put it into the vacuum dryer, close the vacuum dryer cover, set the drying parameters for drying, and after drying for 4 hours, start sampling and testing the megestrol acetate drying central control, stop drying after the test is qualified, collect the dry material to obtain the megestrol acetate dry product.

[0006] As a preferred solution of the present invention, the process of the heating reaction in S1 is: heat the reaction kettle to reflux the liquid in the kettle to 76-80°C, switch the jacket of the reaction kettle to a water bath after reflux, and continue to maintain the original temperature reflux with a 90-95°C hot water bath, and keep the reaction for 60 minutes.

[0007] As a preferred solution of the present invention, during the reduced pressure concentration in S2, the temperature inside the reactor is ≤60°C, the vacuum degree is ≤-0.06MPa, the effluent is placed in a storage tank, and the concentration is stopped after the feed liquid becomes a paste.

[0008] As a preferred solution of the present invention, the specific steps of the drying treatment in S2 are: turn off the vacuum dryer, start the hot water circulation, set the hot water temperature of the solenoid valve of the drying hot water tank to 60-70°C, heat the vacuum dryer jacket with 60-70°C hot water, turn on the vacuum dryer, adjust the vacuum degree in the vacuum dryer to ≤-0.06 Mpa, and under the condition of hot water temperature of 60-70°C, control the internal temperature of the vacuum dryer to 48-54°C, the vacuum degree ≤-0.06Mpa, and dry for 24 hours.

[0009] As a preferred solution of the present invention, the pulping treatment step in S2 is: pulping the filter cake with 35-45°C warm water, washing the filter cake with 35-45°C warm water for 60 minutes under centrifugal state, drying, and sending the waste liquid to the factory waste liquid pool for centralized treatment.

[0010] As a preferred solution of the present invention, the specific method for checking the production equipment in S3 is: check the production conditions, fill in the "operation" status plate of the equipment decolorization kettle, filter, crystallization kettle, and flat-plate closed centrifuge, hang it in the specified position of the equipment, check whether the equipment is clean and dry, and confirm that the equipment is within the cleaning validity period.

[0011] As a preferred embodiment of the present invention, the distillation and concentration method in S4 is as follows: after the filtration is completed, check whether the solution is clear, start the crystallization kettle for stirring, heat in a water bath, control the internal temperature rise to ≤60°C, and the vacuum degree to ≤-0.06MPa for reduced pressure distillation, put the distillate into a storage tank, wait until the liquid in the concentrated crystallization kettle becomes slurry, stop distillation, and cool to -2-2°C.

[0012] As a preferred solution of the present invention, the parameter setting step of the vacuum dryer in S4 is: under the condition of hot water temperature of 60-70°C, the internal temperature of the vacuum dryer is controlled to be 40-46°C, and the vacuum degree is ≤-0.06Mpa.

[0013] Compared with the prior art, the present invention has the following beneficial effects: 1. In the present invention, cyclohexene, methine and palladium carbon are added to a reactor and heated for reaction. After the reaction is completed, the feed liquid in the reactor is filtered into a new reactor, the new reactor is controlled to be concentrated under reduced pressure, the material in the new reactor is placed in a centrifuge for centrifugal filtration, the filter cake is pulped, the centrifuge is stopped, the filter cake is collected and weighed to obtain a crude megestrol acetate wet product, the crude megestrol acetate wet product is dried, ethyl acetate, activated carbon and the crude megestrol acetate are added to the decolorization kettle from the feed port, the decolorization kettle jacket is heated in a water bath, and then The material liquid in the decolorization kettle is filtered through a filter into a crystallization kettle, and after the filtration is completed, distillation and concentration are carried out. After the concentration is completed, the material in the crystallization kettle is placed in a flat-plate closed centrifuge, centrifuged and filtered, and the filter cake is collected. The wet megestrol acetate product is evenly divided into a drying tray and placed in a vacuum dryer for drying. After the test is qualified, the drying is stopped, and the dry material is collected to obtain the megestrol acetate dry product. The operation process is relatively simple, the output rate of the crude megestrol acetate can reach 75%-85%, and the output of megestrol acetate can reach 68%-82%, and the output rate is relatively high. DETAILED DESCRIPTION

[0014] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0015] To facilitate understanding of the present invention, the present invention will be described more comprehensively below and several embodiments of the present invention are given. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, these embodiments are provided to make the disclosure of the present invention more thorough and comprehensive.

[0016] It should be noted that when an element is referred to as being "fixed on" another element, it may be directly on the other element or there may also be a central element. When an element is considered to be "connected to" another element, it may be directly connected to the other element or there may also be a central element. The terms "vertical", "horizontal", "left", "right" and similar expressions used in this article are for illustrative purposes only.

[0017] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by technicians in the technical field to which the present invention belongs. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more related listed items.

[0018] Embodiment, the present invention provides a technical solution: A megestrol acetate process comprises the following steps: S1, extract 316kg of anhydrous ethanol and add it to the reactor through the header tank, inject nitrogen into the reactor, then send 2kg of cyclohexene into the reactor through the header tank, start the reactor to stir, then add 20kg of methine from the feed port into the reactor, heat the reactor to an internal temperature of ≥70°C, add 4kg of palladium carbon into the reactor and stop injecting nitrogen, continue heating the reactor for reaction, after the reaction is completed, filter the feed liquid in the reactor into a new reactor, rinse the residual palladium carbon in the reactor with 23.7kg of anhydrous ethanol, filter the rinse liquid into the new reactor through the same filter, after the filtration is completed, heat the new reactor until the solution is clear and start sampling, control the new reactor to perform reduced pressure concentration, after the concentration is completed, drain the remaining water from the reactor jacket and inject frozen brine, and cool to -2-2°C; S2, put the material in the new reactor into a centrifuge and centrifuge to filter out the mother liquor, the filtered mother liquor enters the storage tank, waits for the mother liquor to be recovered, washes the filter cake with 11.9 kg of anhydrous ethanol and spins dry, combines the washing liquid with the mother liquor, puts it into a barrel and hands over the three wastes, performs pulping on the filter cake, stops the centrifuge, collects the filter cake and weighs it to obtain the crude megestrol acetate wet product, evenly packs the crude megestrol acetate wet product into a drying tray, puts the drying tray into a vacuum dryer for drying, collects the material after drying, puts it into a double-layer plastic bag, and performs sampling inspection by QC. After passing the inspection, it enters the intermediate warehouse; S3, check the production equipment, extract 180-200kg of ethyl acetate and add it to the decolorization kettle through the header tank, then weigh 1.5kg of activated carbon and add it to the decolorization kettle through the feed port, start stirring, add all the crude megestrol acetate to the decolorization kettle through the feed port, heat the jacket of the decolorization kettle in a water bath to raise the internal temperature to 73-83°C, reflux for 60 minutes, filter the liquid in the decolorization kettle through a filter into a crystallization kettle, extract 20-40kg of ethyl acetate to rinse the decolorization kettle, and the washing liquid is filtered into the crystallization kettle. After the filtration is completed, distill and concentrate. After the concentration is completed, put the material in the crystallization kettle into a flat-plate closed centrifuge, centrifuge and filter, filter out the mother liquor, and put the filtered mother liquor into a storage tank, wash the filter cake with 20-40kg of ethyl acetate, dry it, combine the washing liquid with the mother liquor, stop the flat-plate closed centrifuge, wait for it to stop running, take samples for megestrol acetate centrifugal control, and collect the filter cake; S4, set the solenoid valve of the drying hot water tank to a hot water temperature of 60-70°C, start the hot water circulation, heat the vacuum dryer jacket with 60-70°C hot water, evenly pack the wet megestrol acetate in a drying tray, put it into the vacuum dryer, close the vacuum dryer cover, set the drying parameters for drying, and after drying for 4 hours, start sampling and testing the megestrol acetate drying central control, stop drying after the test is qualified, collect the dry material to obtain the megestrol acetate dry product.

[0019] Furthermore, the process of the heating reaction in S1 is: heating the reactor to reflux the liquid in the reactor to 76-80°C, switching the jacket of the reactor to a water bath after reflux, and continuing to maintain the original temperature reflux with a 90-95°C hot water bath, and keeping the reaction for 60 minutes.

[0020] Furthermore, during the reduced pressure concentration in S2, the temperature inside the reactor is ≤60°C, the vacuum degree is ≤-0.06MPa, the effluent is placed in a storage tank, and the concentration is stopped after the feed liquid becomes a paste.

[0021] Furthermore, the specific steps of the drying treatment in S2 are: turn off the vacuum dryer, start the hot water circulation, set the hot water temperature of the solenoid valve of the drying hot water tank to 60-70°C, heat the vacuum dryer jacket with 60-70°C hot water, turn on the vacuum dryer, adjust the vacuum degree in the vacuum dryer to ≤-0.06 Mpa, and under the condition of hot water temperature of 60-70°C, control the internal temperature of the vacuum dryer to 48-54°C, the vacuum degree ≤-0.06Mpa, and dry for 24 hours.

[0022] Furthermore, the pulping treatment step in S2 is: pulping the filter cake with 35-45°C warm water, washing the filter cake with 35-45°C warm water for 60 minutes under centrifugal state, drying, and sending the waste liquid to the factory waste liquid pool for centralized treatment.

[0023] Furthermore, the specific method for checking the production equipment in S3 is: checking the production conditions, filling in the "operation" status plate of the equipment decolorization kettle, filter, crystallization kettle, and flat-plate closed centrifuge, hanging it in the specified position of the equipment, checking whether the equipment is clean and dry, and confirming that the equipment is within the cleaning validity period.

[0024] Furthermore, the distillation and concentration method in S4 is: after the filtration is completed, check whether the solution is clear, start the crystallization kettle for stirring, heat in a water bath, control the internal temperature rise to ≤60°C, and the vacuum degree to ≤-0.06MPa for reduced pressure distillation, put the distillate into a storage tank, wait until the liquid in the concentrated crystallization kettle becomes a slurry, stop distillation, and cool to -2-2°C.

[0025] Furthermore, the parameter setting step of the vacuum dryer in S4 is: under the condition of hot water temperature of 60-70°C, the internal temperature of the vacuum dryer is controlled to be 40-46°C, and the vacuum degree is ≤-0.06Mpa.

[0026] 316 kg of anhydrous ethanol was drawn and added to the reactor through the header tank, nitrogen was injected into the reactor, and then 2 kg of cyclohexene was sent into the reactor through the header tank, the reactor was started to stir, and then 20 kg of methine was added to the reactor from the feeding port, the reactor was heated to raise the temperature in the reactor to 70 ° C, 4 kg of palladium carbon was added to the reactor and the injection of nitrogen was stopped, the reactor was heated to reflux the liquid in the reactor to 80 ° C, and after reflux, the jacket of the reactor was switched to a water bath, and a 95 ° C hot water bath was used to continue to maintain the original temperature reflux, and the reaction was kept warm for 60 minutes; After the reaction is completed, the feed liquid in the reactor is filtered into a new reactor, and the residual palladium carbon in the reactor is rinsed with 23.7 kg of anhydrous ethanol. The rinse liquid is filtered into the new reactor through the same filter. After the filtration is completed, the new reactor is heated until the solution is clear and sampling begins. The new reactor is controlled to be concentrated under reduced pressure. The temperature in the reactor is 60°C and the vacuum degree is -0.06 MPa. The effluent is placed in a storage tank and concentrated until the feed liquid is in a paste state. After the concentration is completed, the remaining water is removed from the reactor jacket and frozen brine is injected and cooled to -2°C. The material in the new reactor is placed in a centrifuge for centrifugal filtration to filter out the mother liquor. The filtered mother liquor enters the storage tank and waits for the mother liquor to be recovered. The filter cake is washed with 11.9 kg of anhydrous ethanol and dried. The washing liquid is combined with the mother liquor and barreled for the three wastes. The filter cake is pulped with 45°C warm water. The filter cake is washed with 45°C warm water for 60 minutes under centrifugal state, and dried. The waste liquid is sent to the waste liquid pool in the factory for centralized treatment. The centrifuge is stopped, and the filter cake is collected and weighed to obtain the crude wet product of megestrol acetate; The crude wet product of megestrol acetate is evenly divided into a drying tray, the drying tray is placed in a vacuum dryer, the vacuum dryer is closed, the hot water circulation is turned on, the solenoid valve of the drying hot water tank is set to a hot water temperature of 70°C, the vacuum dryer jacket is heated with 70°C hot water, the vacuum dryer is turned on, the vacuum degree in the vacuum dryer is adjusted to -0.06 Mpa, and under the condition of a hot water temperature of 70°C, the internal temperature of the vacuum dryer is controlled to 54°C, the vacuum degree is controlled to -0.06Mpa, and the drying is carried out for 24 hours. After the drying is completed, the materials are collected and packed into double-layer plastic bags, and the materials are sampled and inspected by QC. After passing the inspection, the materials are put into the intermediate warehouse; Check the production conditions, fill in the "operation" status sign of the equipment decolorization kettle, filter, crystallization kettle, and flat-plate closed centrifuge, and hang it in the specified position of the equipment. Check whether the equipment is clean and dry, and confirm that the equipment is within the effective period of cleaning. Draw 200kg of ethyl acetate and add it to the decolorization kettle through the high-level tank, and then weigh 1.5kg of activated carbon and add it to the decolorization kettle through the feed port. Turn on the stirring, and add all the crude megestrol acetate to the decolorization kettle through the feed port. Heat the decolorization kettle jacket in a water bath to raise the internal temperature to 83°C, reflux for 60 minutes, filter the liquid in the decolorization kettle through the filter and transfer it to the crystallization kettle, draw 40kg of ethyl acetate to rinse the decolorization kettle, and the washing liquid is filtered into the crystallization kettle; After the filtration is completed, check whether the solution is clear, open the crystallization kettle for stirring, heat in a water bath, control the internal temperature to 60°C, and perform vacuum distillation at -0.06MPa. Put the distillate into the storage tank, wait for the concentrated crystallization kettle to be slurry, stop distillation, cool to -2°C, and after the concentration is completed, put the material in the crystallization kettle into a flat-plate sealed centrifuge, centrifuge and filter, filter out the mother liquor, and put the filtered mother liquor into the storage tank. Wash the filter cake with 40kg of ethyl acetate, dry it, combine the washing liquid with the mother liquor, stop the flat-plate sealed centrifuge, wait for it to stop running, take samples for centrifugal control of megestrol acetate, and collect the filter cake; The solenoid valve of the drying hot water tank is set to a hot water temperature of 70°C, and the hot water circulation is started. The vacuum dryer jacket is heated with 70°C hot water. The wet megestrol acetate product is evenly divided into a drying tray and placed in the vacuum dryer. The vacuum dryer cover is closed. Under the condition of a hot water temperature of 70°C, the internal temperature of the vacuum dryer is controlled to 46°C and the vacuum degree is controlled to -0.06Mpa for drying. After drying for 4 hours, the megestrol acetate drying central control starts sampling and testing. After the test is qualified, the drying is stopped, and the dried material is collected to obtain the megestrol acetate dry product.

[0027] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A megestrol acetate process, characterized in that: The following steps are involved: S1, extract 316kg of anhydrous ethanol and add it to the reactor through the header tank, inject nitrogen into the reactor, then send 2kg of cyclohexene into the reactor through the header tank, start the reactor to stir, then add 20kg of methine from the feed port into the reactor, heat the reactor to an internal temperature of ≥70°C, add 4kg of palladium carbon into the reactor and stop injecting nitrogen, continue heating the reactor for reaction, after the reaction is completed, filter the feed liquid in the reactor into a new reactor, rinse the residual palladium carbon in the reactor with 23.7kg of anhydrous ethanol, filter the rinse liquid into the new reactor through the same filter, after the filtration is completed, heat the new reactor until the solution is clear and start sampling, control the new reactor to perform reduced pressure concentration, after the concentration is completed, drain the remaining water from the reactor jacket and inject frozen brine, and cool to -2-2°C; S2, put the material in the new reactor into a centrifuge and centrifuge to filter out the mother liquor, the filtered mother liquor enters the storage tank, waits for the mother liquor to be recovered, washes the filter cake with 11.9 kg of anhydrous ethanol and spins dry, combines the washing liquid with the mother liquor, puts it into a barrel and hands over the three wastes, performs pulping on the filter cake, stops the centrifuge, collects the filter cake and weighs it to obtain the crude megestrol acetate wet product, evenly packs the crude megestrol acetate wet product into a drying tray, puts the drying tray into a vacuum dryer for drying, collects the material after drying, puts it into a double-layer plastic bag, and performs sampling inspection by QC. After passing the inspection, it enters the intermediate warehouse; S3, check the production equipment, extract 180-200kg of ethyl acetate and add it to the decolorization kettle through the header tank, then weigh 1.5kg of activated carbon and add it to the decolorization kettle through the feed port, start stirring, add all the crude megestrol acetate to the decolorization kettle through the feed port, heat the jacket of the decolorization kettle in a water bath to raise the internal temperature to 73-83°C, reflux for 60 minutes, filter the liquid in the decolorization kettle through a filter into a crystallization kettle, extract 20-40kg of ethyl acetate to rinse the decolorization kettle, and the washing liquid is filtered into the crystallization kettle. After the filtration is completed, distill and concentrate. After the concentration is completed, put the material in the crystallization kettle into a flat-plate closed centrifuge, centrifuge and filter, filter out the mother liquor, and put the filtered mother liquor into a storage tank, wash the filter cake with 20-40kg of ethyl acetate, dry it, combine the washing liquid with the mother liquor, stop the flat-plate closed centrifuge, wait for it to stop running, take samples for megestrol acetate centrifugal control, and collect the filter cake; S4, set the solenoid valve of the drying hot water tank to a hot water temperature of 60-70°C, start the hot water circulation, heat the vacuum dryer jacket with 60-70°C hot water, evenly pack the wet megestrol acetate in a drying tray, put it into the vacuum dryer, close the vacuum dryer cover, set the drying parameters for drying, and after drying for 4 hours, start sampling and testing at the megestrol acetate drying central control, stop drying after the test is qualified, collect the dry material to obtain the megestrol acetate dry product.

2. A megestrol acetate process according to claim 1, characterized in that: The process of the heating reaction in S1 is as follows: heating the reaction kettle to reflux the liquid in the kettle at 76-80°C, switching the jacket of the reaction kettle to a water bath after reflux, and continuing to reflux at the original temperature with a 90-95°C hot water bath, and keeping the temperature for reaction for 60 minutes.

3. A megestrol acetate process according to claim 1, characterized in that: During the reduced pressure concentration in S2, the temperature inside the reactor is ≤60°C, the vacuum degree is ≤-0.06MPa, the effluent is placed in a storage tank, and the concentration is stopped after the feed liquid becomes a paste.

4. A megestrol acetate process according to claim 1, characterized in that: The specific steps of the drying treatment in S2 are: turn off the vacuum dryer, start the hot water circulation, set the hot water temperature of the solenoid valve of the drying hot water tank to 60-70°C, heat the vacuum dryer jacket with 60-70°C hot water, turn on the vacuum dryer, adjust the vacuum degree in the vacuum dryer to ≤-0.06Mpa, control the internal temperature of the vacuum dryer to 48-54°C, the vacuum degree ≤-0.06Mpa under the condition of hot water temperature 60-70°C, and dry for 24 hours.

5. A megestrol acetate process according to claim 1, characterized in that: The pulping treatment step in S2 is: the filter cake is pulped with 35-45°C warm water, the filter cake is washed with 35-45°C warm water for 60 minutes under a centrifugal state, and the discarded waste liquid is sent to the factory waste liquid pool for centralized treatment.

6. A megestrol acetate process according to claim 1, characterized in that: The specific method for checking the production equipment in S3 is: check the production conditions, fill in the "operation" status plate of the equipment decolorization kettle, filter, crystallization kettle, and flat-plate closed centrifuge, hang it in the specified position of the equipment, check whether the equipment is clean and dry, and confirm that the equipment is within the cleaning validity period.

7. A megestrol acetate process according to claim 1, characterized in that: The distillation and concentration method in S4 is: after the filtration is completed, check whether the solution is clear, start the crystallization kettle for stirring, heat in a water bath, control the internal temperature rise to ≤60°C, and the vacuum degree to ≤-0.06MPa for reduced pressure distillation, put the distillate into a storage tank, wait until the liquid in the concentrated crystallization kettle becomes slurry, stop distillation, and cool to -2-2°C.

8. A megestrol acetate process according to claim 1, characterized in that: The parameter setting step of the vacuum dryer in S4 is: under the condition of hot water temperature of 60-70°C, the internal temperature of the vacuum dryer is controlled to be 40-46°C, and the vacuum degree is ≤-0.06Mpa.