Nitrogen-excited ethanol fumigation device for reducing amorphous content of high-activity bulk drug

Abstract

The utility model discloses a nitrogen-excited ethanol fumigation device for reducing the amorphous content of a high-activity raw material medicine, and relates to the technical field of medicine treatment. A nitrogen-excited ethanol fumigation device for reducing the amorphous content of a high-activity bulk drug comprises an ethanol nitrogen output unit used for storing ethanol and also used for outputting a mixed gas of absolute ethanol steam and nitrogen; the fumigation unit is in butt joint with the ethanol nitrogen output unit and is used for performing fumigation treatment on the high-activity raw material medicine through the mixed gas; and the tail gas recovery treatment unit is in butt joint with the fumigation unit and is used for receiving and treating the mixed gas subjected to fumigation treatment and then discharging tail gas. According to the utility model, the problem of reducing the amorphous content generated after the high-activity raw material medicine is crushed is solved, the stability of the preparation is improved, the medication safety risk of a patient is reduced, and a more reliable and efficient treatment technology is provided for the production of the inhalation preparation.

Description

TECHNICAL FIELD

[0001] The utility model relates to a kind of nitrogen excitation ethanol fumigation devices for reducing amorphous content of high-activity bulk drug. BACKGROUND

[0002] In the pharmaceutical field, especially for the development and production of inhalation preparations, the particle size control of bulk drug is a key link to ensure the effectiveness and safety of drugs. Generally, the ideal particle size of bulk drug used in inhalation preparations should be less than 5 μm to ensure that drug particles can reach the lungs, improve bioavailability and treatment effect. However, in the conventional process of bulk drug synthesis, even the final crystallization step, it is often difficult to directly meet this particle size requirement.

[0003] To overcome this problem, the pharmaceutical industry widely uses airflow pulverization, mechanical grinding and other physical methods to destroy the crystal lattice structure of bulk drug particles by applying external energy, thereby reducing the particle size. These techniques, although to some extent, achieve the reduction of particle size, but also bring new problems. Long-term pulverization or grinding treatment can easily convert part of the crystalline bulk drug to amorphous state, which is prone to recrystallization under humid, high temperature and other environmental conditions, leading to unfavorable changes in the morphology, solubility and stability of drug preparations, thereby affecting the efficacy of the drug and the safety of patients.

[0004] Especially for high active pharmaceutical ingredients (High Active Pharmaceutical Ingredient, high active API), the stability problem in the processing process is more prominent. High active API usually has high biological activity and potential toxicity, and has very strict requirements on production environment and processing technology. In the process of pulverization, grinding and other physical treatment, high active API is not only prone to crystal transformation, but also may increase the safety risk and environmental pollution risk in the production process due to dust flying.

[0005] Therefore, how to ensure that the particle size of bulk drug meets the requirements while avoiding the transformation of its crystal form after pulverization and improving the stability of the preparation and reducing the safety risk of patients, has become a technical problem to be solved in the pharmaceutical industry. At present, although some techniques have tried to optimize the pulverization process, improve the storage conditions and other means to alleviate this problem, the effect is not ideal, and further exploration and innovation are still needed.

[0006] Under this background, it is urgently needed to provide a new processing method that can reduce the generation of amorphous state of high active bulk drug in the pulverization process, thereby improving the stability of the preparation and the quality of the product, and ensuring the safety and effectiveness of patients. UTILITY MODEL CONTENT

[0007] The utility model wants to solve the technical problem of the current high active API and other inhalation preparations in the process of refining particle size, which has the problems of crystal form transformation, stability decline and poor product quality, which leads to the inability to guarantee the safety and effectiveness of patient medication, aims at providing a nitrogen excitation ethanol fumigation device for reducing the amorphous content of high active raw material medicine, solving the problem of reducing the amorphous content of high active raw material medicine after crushing treatment, improving the stability of preparation, reducing the safety risk of patient medication, and providing a more reliable and efficient processing technology for the production of inhalation preparations.

[0008] The utility model discloses the following technical scheme realizes:

[0009] A nitrogen excitation ethanol fumigation device for reducing the amorphous content of high active raw material medicine, comprising

[0010] The ethanol nitrogen output unit is used for storing ethanol and outputting mixed gas of ethanol vapor and nitrogen;

[0011] The fumigation unit is connected with the ethanol nitrogen output unit and is used for fumigation treatment of high active raw material by mixed gas;

[0012] The tail gas recovery treatment unit is connected with the fumigation unit and is used for receiving and treating mixed gas after fumigation treatment and then discharging tail gas.

[0013] As a possible design, the above-mentioned ethanol nitrogen output unit comprises an ethanol storage container, a first nitrogen input pipe, a second nitrogen input pipe, an ethanol adding port, an ethanol discharge pipe and a transmission pipeline,

[0014] The ethanol storage container is used for storing anhydrous ethanol and is connected with the transmission pipeline for outputting mixed gas of ethanol vapor and nitrogen;

[0015] The first nitrogen input pipe is connected with the bottom of the ethanol storage container and is used for introducing nitrogen into the ethanol storage container to excite anhydrous ethanol to generate steam;

[0016] The second nitrogen input pipe is connected with the upper end of the ethanol storage container and is used for directly inputting nitrogen into the transmission pipeline without passing through anhydrous ethanol to increase the diffusion speed and uniformity of ethanol vapor;

[0017] The ethanol adding port is connected with the ethanol storage container and is used for inputting anhydrous ethanol into the ethanol storage container;

[0018] The ethanol discharge pipe is connected with the bottom of the ethanol storage container and is used for discharging anhydrous ethanol;

[0019] The transmission pipeline is connected with the upper end of the ethanol storage container and the bottom of the fumigation unit at both ends respectively and is used for outputting mixed gas of ethanol vapor and nitrogen to the fumigation unit.

[0020] As a possible design, the ethanol nitrogen output unit further comprises a first ethanol concentration probe,

[0021] The ethanol concentration probe is installed on the transmission pipeline to monitor the ethanol vapor concentration.

[0022] As a possible design, the device further comprises a constant temperature unit, which comprises a water tank, an inlet pipe, a return pipe, a self-priming water pump and a water chiller,

[0023] The water tank is used to load purified water, and the evaporation and transmission process of anhydrous ethanol is temperature-adjusted by the water chiller;

[0024] The inlet pipe is connected with the bottom of the water tank and the jacket of the ethanol storage container and the jacket of the transmission pipeline respectively, and is used to input the temperature-adjusted purified water into the jacket of the ethanol storage container and the jacket of the transmission pipeline, so as to adjust the temperature of the ethanol storage container and the transmission pipeline;

[0025] The return pipe is connected with the upper end of the water tank and the jacket of the ethanol storage container respectively, and is used to input the chilled water for adjusting the temperature of the ethanol storage container and the transmission pipeline into the water tank to adjust the temperature;

[0026] The self-priming water pump is installed on the inlet pipe, and is used to extract the purified water in the water tank after temperature reduction to input into the jacket of the ethanol storage container and the jacket of the transmission pipeline through the inlet pipe;

[0027] The water chiller is connected with the water tank, and is used to reduce the temperature of the purified water in the water tank.

[0028] As a possible design, the water chiller comprises a temperature-adjusting container, a circulation pipeline and a circulation pump,

[0029] The temperature-adjusting container is used to load temperature-adjusting liquid;

[0030] The inlet end and the outlet end of the circulation pipeline are connected with the temperature-adjusting container, and are located in the water tank, and are used to adjust the temperature of the purified water in the water tank;

[0031] The circulation pump is installed on the circulation pipeline, and is used to extract the temperature-adjusting solution of the temperature-adjusting container.

[0032] As a possible design, the fumigation unit comprises a fumigation container and a filter screen type tray,

[0033] The bottom of the fumigation container is connected with the ethanol nitrogen output unit, and the top is connected with the tail gas recovery treatment unit;

[0034] The number of filter screen type trays is multiple, and multiple filter screen type trays can be detachably stacked and clamped in the fumigation container, and the filter screen type tray is used to support high-activity raw materials.

[0035] As a possible design, the tail gas recovery processing unit comprises a tail gas pipe, a secondary filter, a fresh air pipe, an exhaust pipe and an exhaust fan,

[0036] The tail gas pipe is connected with the bottom of the secondary filter and the fumigation unit respectively for conveying fumigation tail gas.

[0037] The secondary filter is connected with the exhaust pipe for inputting filtered tail gas into the exhaust pipe.

[0038] The exhaust pipe is used for discharging filtered tail gas.

[0039] The exhaust fan is installed on the exhaust pipe for extracting filtered tail gas.

[0040] The fresh air pipe is connected with the secondary filter for providing fresh air to the secondary filter to balance the pressure difference between the secondary filter and the outside.

[0041] As a possible design, the secondary filter comprises a filter container and a water bath space,

[0042] The filter container 321 is connected with the tail gas pipe at the bottom for inputting tail gas and connected with the exhaust pipe at the top.

[0043] The water bath space is located at the bottom of the filter container for absorbing ethanol in the tail gas.

[0044] As a possible design, the secondary filter further comprises an H14 high-efficiency filter,

[0045] The H14 high-efficiency filter is arranged above the water bath space in the filter container for absorbing residual raw material and ethanol in the tail gas.

[0046] As a possible design, the exhaust fan is connected with an online oxygen concentration probe.

[0047] Compared with the prior art, the utility model has the following advantages and beneficial effects:

[0048] The utility model discloses a nitrogen gas output unit is used to excite anhydrous ethanol with pressure nitrogen gas, thereby forming ethanol steam, conveying the ethanol steam to the fumigation unit to make API crystallize, reduce amorphous, and make the preparation property reach the stable state, thereby guaranteeing the quality of preparation product. BRIEF DESCRIPTION OF DRAWINGS

[0049] In order to more clearly illustrate the technical scheme in the example embodiments of the present application, the drawings needed in the embodiments will be briefly introduced as follows, and it should be understood that the following drawings only show some embodiments of the present application, and therefore should not be regarded as a limitation on the scope, and for those skilled in the art, other related drawings can also be obtained without creative labor on the basis of these drawings. In the drawings:

[0050] Fig. 1 A structure schematic view of the nitrogen excitation ethanol fumigation device for reducing amorphous content of high-activity raw medicine of the present application;

[0051] Fig. 2 A sectional structure schematic view of the nitrogen excitation ethanol fumigation device for reducing amorphous content of high-activity raw medicine of the present application;

[0052] Fig. 3 A partial sectional structure schematic view of the nitrogen excitation ethanol fumigation device for reducing amorphous content of high-activity raw medicine of the present application.

[0053] Markings in the drawings and corresponding names of parts:

[0054] 1-ethanol nitrogen output unit; 11-ethanol storage container; 12-first nitrogen input pipe; 13-ethanol adding port; 14-ethanol discharge pipe; 15-transport pipeline; 16-ethanol concentration probe; 17-second nitrogen input pipe; 2-fumigation unit; 21-fumigation container; 22-filter tray; 3-tail gas recovery treatment unit; 31-tail gas pipe; 32-secondary filter; 321-filtration container; 322-water bath space; 323-H14 high efficiency filter; 33-fresh air duct; 34-exhaust fan; 35-online oxygen concentration probe; 36-exhaust pipe; 4-constant temperature unit; 41-water tank; 42-liquid inlet pipe; 43-self-suction water pump; 44-chiller; 441-temperature adjusting container; 442-circulation pipeline; 443-circulation pump; 45-backwater pipe; 5-control display unit; 6-housing; 61-temperature sensor. DETAILED DESCRIPTION

[0055] In order to make the purpose, technical scheme and advantages of the present application more clear, the present application will be further described in detail in combination with embodiments and drawings, and the illustrative embodiments and the description thereof are only used to explain the present application, and should not be regarded as a limitation on the present application. The specific conditions not mentioned in the embodiments are carried out according to the conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments not mentioned by the manufacturer are all conventional products that can be purchased on the market.

[0056] The utility model provides a nitrogen excitation ethanol fumigation device for reducing amorphous content of high-activity raw medicine, referring to Figs. 1-3 , comprising ethanol nitrogen output unit 1, fumigation unit 2 and tail gas recovery processing unit 3.Ethanol nitrogen output unit 1 is used for storing ethanol and also for outputting mixed gas of anhydrous ethanol steam and nitrogen; fumigation unit 2 is connected with ethanol nitrogen output unit 1 and is used for fumigation treatment of high-activity raw medicine by mixed gas; tail gas recovery processing unit 3 is connected with fumigation unit 2 and is used for receiving and processing mixed gas after fumigation treatment and then discharging tail gas.Specifically, by injecting nitrogen with pressure into anhydrous ethanol, compression effect is generated on ethanol liquid, heat exchange occurs between nitrogen and ethanol during nitrogen injection, heat is transferred to ethanol, temperature is thus increased, which makes ethanol liquid closer to its boiling point, thus vaporization; nitrogen injection also generates disturbance and flow in ethanol liquid, which promotes evaporation of ethanol liquid surface.Finally, the result shows mixed gas of nitrogen and ethanol steam, mixed gas is input into fumigation unit 2 for API fumigation, which can make API crystallize, and ethanol steam and a small amount of API powder may remain in tail gas, ethanol and API powder are recovered by tail gas recovery processing unit 3 in turn, which realizes reduction of raw medicine amorphous content and ensures that discharged gas does not carry any high-activity medicine powder dust.

[0057] Preferably, the above device further comprises a shell 6, ethanol nitrogen output unit 1 and constant temperature unit 4 are installed in the shell 6, and fumigation unit 2 and tail gas recovery processing unit 3 are fixed on the shell 6.

[0058] In some embodiments of the utility model, referring to Fig. 2The ethanol-nitrogen output unit 1 comprises an ethanol storage container 11, a first nitrogen input pipe 12, a second nitrogen input pipe 17, an ethanol adding port 13, an ethanol discharge pipe 14 and a transmission pipe 15. The ethanol storage container 11 is used for storing anhydrous ethanol and is connected with the transmission pipe 15. When the nitrogen gas with pressure is input into the ethanol storage container 11, the temperature and pressure of the nitrogen gas will promote the ethanol to be vaporized. The mixed gas of the nitrogen gas and the ethanol vapor will be output to the fumigation unit 2 along the transmission pipe 15 for the API fumigation treatment. The first nitrogen input pipe 12 is connected with the bottom of the ethanol storage container 11 and is used for inputting the nitrogen gas with certain pressure and temperature into the ethanol storage container 11 to stimulate the anhydrous ethanol to generate the steam (moisture). The second nitrogen input pipe 17 is connected with the upper end of the ethanol storage container 11 and is used for directly inputting the nitrogen gas into the transmission pipe 15 without passing through the anhydrous ethanol, so that the dry gas is input into the transmission pipe 15, which is used for increasing the diffusion speed and uniformity of the ethanol vapor. The ethanol adding port 13 is connected with the ethanol storage container 11 and is used for inputting the anhydrous ethanol into the ethanol storage container 11. The ethanol discharge pipe 14 is connected with the bottom of the ethanol storage container 11 and is used for discharging the anhydrous ethanol. The transmission pipe 15 is connected with the upper end of the ethanol storage container 11 and the bottom of the fumigation unit 2 respectively and is used for outputting the ethanol vapor and the nitrogen gas to the fumigation unit 2. After the ethanol vapor and the nitrogen gas are mixed, the mixed gas is formed.

[0059] In some embodiments of the utility model, the ethanol-nitrogen output unit 1 further comprises a first ethanol concentration probe 16. The ethanol concentration probe 16 is installed on the transmission pipe 15. The ethanol concentration probe 16 is preferably an online ethanol detector. The ethanol vapor concentration can be obtained through the nitrogen gas pressure and flow.

[0060] In some embodiments of the utility model, the device further includes constant temperature unit 4, constant temperature unit 4 includes water tank 41, liquid inlet pipe 42, backwater pipe 45, self-priming water pump 43 and water chiller 44. Water tank 41 is used to load purified water, and the temperature of anhydrous ethanol is adjusted through water chiller 44, when the temperature of ethanol in ethanol storage container 11 is too high, the purified water in water tank 41 can be input into the interlayer of ethanol storage container 11, through heat exchange, the temperature of anhydrous ethanol is reduced, and the temperature is maintained at a stable value, liquid inlet pipe 42 is connected with the bottom of water tank 41 and the jacket of ethanol storage container 11 respectively, and is used to input the purified water after temperature adjustment into ethanol storage container 11, backwater pipe 45 is connected with the upper end of water tank 41, the jacket of ethanol storage container 11 and the jacket of transmission pipeline 15 respectively, and is used to input the purified water after temperature reduction into water tank 41 to adjust the temperature, liquid inlet pipe 42, water tank 41, the jacket of ethanol storage container 11, the jacket of transmission pipeline 15 and backwater pipe 45 form a purified water circulation, in the process of continuous circulation, the ethanol is cooled by water chiller 44, self-priming water pump 43 is installed on liquid inlet pipe 42, and is used to provide power to extract the purified water in water tank 41 into ethanol storage container 11 through liquid inlet pipe 42, water chiller 44 is installed in water tank 41, and is used to adjust the temperature of the purified water in water tank, preferably, the ethanol can be cooled through temperature exchange.

[0061] Preferably, temperature sensor 61 is installed in shell 6, which is electrically connected with control display unit 5, when detecting that the temperature in shell 6 is too high, constant temperature unit 4 can be started to cool down through control display unit 5.

[0062] In some embodiments of the utility model, refer to Fig. 3 The water chiller 44 includes a temperature adjustment container 441, a circulation pipeline 442, and a circulation pump 443. The temperature adjustment container 441 is used to load a temperature adjustment liquid, which can be any liquid with strong thermal conductivity. The circulation pipeline 442 has an inlet end and an outlet end connected to the temperature adjustment container 441. The pipeline body of the circulation pipeline 442 is located in the water tank 41. When the liquid circulates in the circulation pipeline 442, it exchanges temperature with the ethanol, thereby adjusting the temperature of the purified water in the water tank 41. The circulation pump 443 is installed on the circulation pipeline 442 to extract the temperature adjustment solution from the temperature adjustment container 441.

[0063] In some embodiments of the utility model, refer to Fig. 2The fumigation unit 2 comprises a fumigation container 21 and a filter tray 22. The fumigation container 21 is a hollow furnace body, the bottom of which is connected with the ethanol nitrogen output unit 1, and the top of which is connected with the tail gas recovery treatment unit 3; the filter tray 22 is detachably stacked in the fumigation container 21, and is used for supporting high-activity raw medicine, and the mixed gas moves from bottom to top to continuously fumigate the API, and the fumigated tail gas is transported to the tail gas recovery treatment unit 3 through the fumigation container 21.

[0064] In some embodiments of the utility model, refer to Fig. 2 The tail gas recovery treatment unit 3 comprises a tail gas pipe 31, a secondary filter 32, a fresh air pipe 33, an exhaust pipe 36 and an exhaust fan 34. The tail gas pipe 31 is connected with the bottom of the secondary filter 32 and the fumigation unit 2 respectively, and is used for transporting fumigation tail gas; the secondary filter 32 is connected with the exhaust pipe 36, and is used for inputting filtered tail gas into the exhaust pipe 36; the exhaust pipe 36 is used for discharging filtered tail gas; the exhaust fan 34 is installed on the exhaust pipe 36, and is used for extracting filtered tail gas; and the fresh air pipe 33 is connected with the secondary filter 32, and is used for providing fresh air to the secondary filter 32 to balance the pressure difference between the secondary filter 32 and the outside.

[0065] In some embodiments of the utility model, the exhaust fan 34 is connected with an online oxygen concentration probe 35. Since the nitrogen in the tail gas is a suffocating emission, the online oxygen concentration probe 35 can be used to monitor the oxygen concentration in the environment, so as to monitor that there is no nitrogen leakage in the environment and the oxygen content in the air is 21%, and thus the environment for the operator is safe.

[0066] In some embodiments of the utility model, the secondary filter 32 comprises a filter container 321, a water bath space 322 and an H14 high-efficiency filter 323. The bottom of the filter container 321 is connected with the tail gas pipe 31, and is used for connecting with tail gas; the top is connected with the exhaust pipe 36 and the fresh air pipe 33 respectively; the water bath space 322 is located at the bottom of the filter container 321, and is used for absorbing ethanol in the tail gas; and the H14 high-efficiency filter 323 is stacked above the water bath space 322 and located in the filter container 321, and is used for absorbing residual raw medicine and ethanol in the tail gas.

[0067] In some embodiments of the utility model, the device further comprises a control display unit 5, which is connected with the first ethanol concentration probe 16 of the ethanol nitrogen output unit 1, the water chiller 44 of the constant temperature unit 4, the online oxygen concentration probe 35 and the self-suction water pump 43, and the exhaust fan 34 of the tail gas recovery treatment unit 3, and is used for controlling the work of each part.

[0068] The above specific embodiments explain the purpose, technical scheme and beneficial effects of the present application in further detail, and it should be understood that the above description is only a specific embodiment of the present application and is not used to limit the protection scope of the present application, and any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the protection scope of the present application.

Claims

1. A nitrogen sparged ethanol fumigation device for reducing the amorphous content of a highly active drug substance, characterized by, The utility model relates to a high active raw material fumigation device, which comprises an ethanol nitrogen output unit (1) for storing ethanol and outputting mixed gas of ethanol vapor and nitrogen, a fumigation unit (2) for fumigation treatment of high active raw material by the mixed gas, and a tail gas recovery treatment unit (3) for receiving and treating the mixed gas after fumigation treatment and then discharging tail gas. The ethanol nitrogen output unit (1) comprises an ethanol storage container (11), a first nitrogen input pipe (12), a second nitrogen input pipe (17), an ethanol adding port (13), an ethanol discharge pipe (14) and a transmission pipeline (15). The ethanol storage container (11) is used for storing anhydrous ethanol and is connected with the transmission pipeline (15) for outputting the mixed gas of ethanol vapor and nitrogen. The first nitrogen input pipe (12) is connected with the bottom of the ethanol storage container (11) for inputting nitrogen into the ethanol storage container (11) to stimulate anhydrous ethanol to generate vapor.

2. The nitrogen sparging ethanol fumigation device for reducing the amorphous content of a highly active drug substance according to claim 1, characterized in that, The second nitrogen input pipe (17) is connected with the upper end of the ethanol storage container (11) for directly inputting nitrogen into the transmission pipeline (15) without passing through anhydrous ethanol to increase the diffusion speed and uniformity of ethanol vapor. The ethanol adding port (13) is connected with the ethanol storage container (11) for inputting anhydrous ethanol into the ethanol storage container (11). The ethanol discharge pipe (14) is connected with the bottom of the ethanol storage container (11) for discharging anhydrous ethanol. The transmission pipeline (15) is connected with the upper end of the ethanol storage container (11) and the bottom of the fumigation unit (2) respectively for outputting the mixed gas of ethanol vapor and nitrogen to the fumigation unit (2). The ethanol nitrogen output unit (1) further comprises a first ethanol concentration probe (16). The ethanol concentration probe (16) is installed on the transmission pipeline (15) for monitoring the concentration of ethanol vapor. The utility model further comprises a constant temperature unit (4) which comprises a water tank (41), a liquid inlet pipe (42), a backwater pipe (45), a self-suction water pump (43) and a water chiller (44).

3. The nitrogen sparging ethanol fumigation device for reducing the amorphous content of a highly active drug substance according to claim 1, characterized in that, The water tank (41) is used for loading purified water and adjusting the temperature in the evaporation and transmission process by the water chiller (44). The liquid inlet pipe (42) is connected with the bottom of the water tank (41) and the jacket of the ethanol storage container (11) respectively for inputting chilled water into the jacket of the ethanol storage container (11) and the transmission pipeline (15) to adjust the temperature of the ethanol storage container (11) and the transmission pipeline (15).

4. The nitrogen sparging device for reducing the amorphous content of highly active drug substance according to claim 2, wherein, The backwater pipe (45) is connected with the upper end of the water tank (41) and the jacket of the ethanol storage container (11) respectively for inputting the chilled water adjusted in the ethanol storage container (11) into the water tank (41) to adjust the temperature. The self-suction water pump (43) is installed on the liquid inlet pipe (42) for pumping the purified water in the water tank (41) after temperature reduction to be input into the jacket of the ethanol storage container (11) and the jacket of the transmission pipeline (15) through the liquid inlet pipe (42). The water chiller (44) is connected with the water tank (41) for reducing the temperature of the purified water in the water tank (41). ​ ​ ​ 5. A nitrogen sparging device for reducing the amorphous content of a highly active drug substance according to claim 4, characterized in that The cold water machine (44) comprises a temperature adjusting container (441), a circulating pipeline (442) and a circulating pump (443), The temperature adjusting container (441) is used for loading temperature adjusting liquid; The circulating pipeline (442) is connected with the temperature adjusting container (441) at the liquid inlet end and the liquid outlet end and is located in the water tank (41) and used for adjusting the temperature of the purified water in the water tank (41); The circulating pump (443) is installed on the circulating pipeline (442) and used for extracting the temperature adjusting solution of the temperature adjusting container (441).

6. A nitrogen sparged ethanol fumigation device for reducing the amorphous content of a highly active drug substance according to claim 1, characterized in that, The fumigation unit (2) comprises a fumigation container (21) and a filter screen type tray (22), The bottom of the fumigation container (21) is connected with the ethanol nitrogen gas output unit (1), and the top is connected with the tail gas recovery treatment unit (3); The filter screen type tray (22) is detachably stacked and clamped in the fumigation container (21), and the filter screen type tray (22) is used for supporting the high-activity raw material medicine.

7. A nitrogen sparged ethanol fumigation device for reducing the amorphous content of a highly active drug substance according to claim 1, characterized in that, The tail gas recovery treatment unit (3) comprises a tail gas pipeline (31), a secondary filter (32), a fresh air pipeline (33), an exhaust pipeline (36) and an exhaust fan (34), The tail gas pipeline (31) is connected with the bottom of the secondary filter (32) and the fumigation unit (2) at both ends, respectively, and is used for conveying fumigation tail gas; The secondary filter (32) is connected with the exhaust pipeline (36) and is used for inputting filtered tail gas into the exhaust pipeline (36); The exhaust pipeline (36) is used for discharging filtered tail gas; The exhaust fan (34) is installed on the exhaust pipeline (36) and is used for extracting filtered tail gas; The fresh air pipeline (33) is connected with the secondary filter (32) and is used for providing fresh air to the secondary filter (32) to balance the pressure difference between the secondary filter (32) and the outside.

8. A nitrogen sparged ethanol fumigation device for reducing the amorphous content of a highly active drug substance according to claim 7, characterized in that, The secondary filter (32) comprises a filtering container (321) and a water bath space (322), The bottom of the filtering container (321) is connected with the tail gas pipeline (31) and is used for connecting with tail gas, and the top is connected with the exhaust pipeline (36); The water bath space (322) is located at the bottom of the filtering container (321) and is used for absorbing ethanol in the tail gas.

9. A nitrogen sparged ethanol fumigation apparatus for reducing the amorphous content of a highly active drug substance according to claim 8, characterized in that, The secondary filter (32) further comprises an H14 high-efficiency filter (323), The H14 high-efficiency filter (323) is stacked above the water bath space (322) and is located in the filtering container (321) and is used for absorbing residual raw material medicine in the tail gas.

10. A nitrogen sparged ethanol fumigation device for reducing the amorphous content of a highly active drug substance according to claim 7, characterized in that, The exhaust fan (34) is connected with an online oxygen concentration probe (35).

Images