Nitrogen-excited ethanol fumigation device and method for high-activity raw material medicine

Abstract

The invention discloses a nitrogen-excited ethanol fumigation device and method for a high-activity raw material medicine, and relates to the technical field of medicine treatment. A nitrogen-excited ethanol fumigation device for high-activity bulk drugs comprises an ethanol nitrogen output unit used for storing ethanol and outputting 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 invention, the problem of reducing the amorphous content generated after the crushing treatment of the high-activity raw material medicine 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 invention relates to the technical field of drug processing, and in particular to a nitrogen-excited ethanol fumigation device and method for highly active raw materials. Background Art

[0002] In the pharmaceutical field, especially for the development and production of inhalation preparations, the particle size control of APIs is a key link to ensure the effectiveness and safety of drugs. Generally, the ideal particle size of APIs used in inhalation preparations needs to be less than 5μm to ensure that the drug particles can penetrate deep into the lungs, improve bioavailability and therapeutic effects. However, in the conventional process of API synthesis, even the final crystallization step is often difficult to directly achieve this particle size requirement.

[0003] In order to overcome this problem, the pharmaceutical industry widely uses physical methods such as air flow milling and mechanical grinding to destroy the lattice structure of API particles by applying external energy, thereby reducing the particle size. Although these technologies have achieved particle size reduction to a certain extent, they have also brought new problems. Long-term crushing or grinding treatment can easily transform some crystalline APIs into an amorphous state. This metastable state is very likely to recrystallize under humid, high temperature and other environmental conditions, resulting in adverse changes in the morphology, solubility and stability of the drug preparation, thereby affecting the efficacy of the drug and the safety of the patient's medication.

[0004] Especially for highly active pharmaceutical ingredients (API), the stability problem during the processing is more prominent. Highly active API usually has high biological activity and potential toxicity, and has extremely strict requirements on the production environment and processing technology. During physical processing such as crushing and grinding, 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 flying dust.

[0005] Therefore, how to ensure that the particle size of the API meets the requirements while avoiding the change of its crystal form after crushing and improving the stability of the preparation, and reducing the safety risk of patients' medication, has become a technical problem that the pharmaceutical industry needs to solve urgently. At present, although some technologies have tried to alleviate this problem by optimizing the crushing process and improving storage conditions, the results are not ideal and further exploration and innovation are still needed.

[0006] In this context, there is an urgent need to provide a new processing method that can reduce the amorphous content produced by high-activity APIs during the pulverization process, thereby improving the stability of the preparation and product quality, and ensuring the safety and effectiveness of patients' medication. Summary of the invention

[0007] The technical problem to be solved by the present invention is that the existing inhalation preparations such as high-activity API have problems of crystal transformation, decreased stability and poor product quality in the process of particle size refinement, resulting in the inability to ensure the safety and effectiveness of patients' medication. The purpose of the present invention is to provide a nitrogen-activated ethanol fumigation device and method for high-activity raw materials, which solves the problem of reducing the amorphous content of high-activity raw materials after pulverization, improves the stability of the preparations, reduces the safety risk of patients' medication, and at the same time reduces the safety risk and environmental pollution risk in the production process, providing a more reliable, efficient and EHS-compliant processing technology for the production of inhalation preparations.

[0008] The present invention is achieved through the following technical solutions:

[0009] A nitrogen-activated ethanol fumigation device for highly active raw materials, comprising:

[0010] An ethanol nitrogen output unit is used to store ethanol and also to output a mixed gas of anhydrous ethanol vapor and nitrogen;

[0011] The fumigation unit is connected to the ethanol nitrogen output unit and is used to fumigate highly active APIs using mixed gases;

[0012] The tail gas recovery and treatment unit is connected to the fumigation unit to receive and process the mixed gas after fumigation treatment and then discharge the tail gas.

[0013] As a possible design, the ethanol nitrogen output unit includes an ethanol storage container, a first nitrogen input pipe, a second nitrogen input pipe, an ethanol addition port, an ethanol discharge pipe and a transmission pipeline.

[0014] The ethanol storage container is used to store anhydrous ethanol and is connected to the transmission pipeline to output a mixed gas of anhydrous ethanol vapor and nitrogen;

[0015] The first nitrogen gas input pipe is connected to the bottom of the ethanol storage container and is used to introduce nitrogen gas into the ethanol storage container to stimulate the anhydrous ethanol to generate steam;

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

[0017] The ethanol adding port is connected to the ethanol storage container and is used to input anhydrous ethanol into the ethanol storage container;

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

[0019] The two ends of the transmission pipeline are respectively connected to the upper end of the ethanol storage container and the bottom of the fumigation unit, and are used for outputting a mixed gas of ethanol vapor and nitrogen to the fumigation unit.

[0020] As a possible design, the ethanol nitrogen output unit further includes 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 above device also includes a constant temperature unit, which includes a water tank, a liquid inlet pipe, a water return pipe, a self-priming water pump and a chiller.

[0023] The water tank is used to load purified water and regulate the temperature of the anhydrous ethanol evaporation and transmission process through the chiller;

[0024] The two ends of the liquid inlet pipe are respectively connected to the bottom of the water tank and the jacket of the ethanol storage container and the jacket of the transmission pipeline, so as to input the temperature-adjusted chilled water into the jacket of the ethanol storage container and the transmission pipeline, so as to adjust the temperature of the ethanol storage container and the transmission pipeline;

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

[0026] The self-priming water pump is installed on the liquid inlet pipe, and is used to extract the purified water that has been cooled in the water tank and input it into the jacket of the ethanol storage container and the jacket of the transmission pipeline through the liquid inlet pipe;

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

[0028] As a possible design, the above-mentioned chiller includes a temperature control container, a circulation pipeline and a circulation pump.

[0029] The temperature-controlled container is used to hold the temperature-controlled liquid;

[0030] The liquid inlet and outlet ends of the circulation pipeline are both connected to the temperature adjustment 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 control solution from the temperature control container.

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

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

[0034] There are multiple filter trays, and the multiple filter trays can be detachably stacked and snapped into the fumigation container. The filter trays are used to support highly active raw materials.

[0035] As a possible design, the exhaust gas recovery unit includes an exhaust pipe, a secondary filter, a fresh air duct, an exhaust pipe and an exhaust fan.

[0036] The two ends of the tail gas pipe are connected to the bottom of the secondary filter and the fumigation unit respectively, for conveying fumigation tail gas;

[0037] The secondary filter is connected to the exhaust pipe to input the filtered exhaust gas into the exhaust pipe;

[0038] The exhaust pipe is used to discharge filtered exhaust gas;

[0039] The exhaust fan is installed on the exhaust pipe to extract and filter the exhaust gas;

[0040] The fresh air duct is connected to the secondary filter and is used to provide fresh air to the secondary filter to balance the pressure difference between the secondary filter and the outside.

[0041] A nitrogen-stimulated ethanol fumigation method for highly active raw materials comprises the following steps:

[0042] Input ethanol into the ethanol nitrogen output unit, adjust the pressure of dry gas and wet gas in the ethanol nitrogen output unit, mix the dry gas and wet gas to form a mixed gas, the dry gas is nitrogen that has not passed through the ethanol solution, and the wet gas is nitrogen that has passed through the ethanol solution;

[0043] The highly active API is placed in a fumigation unit and fumigated with a mixed gas of nitrogen and nitrogen-excited ethanol vapor at 18 to 26° C. to obtain a crystallized highly active API.

[0044] As a possible design, the intake flow rate and ethanol vapor concentration of the above-mentioned mixed gas are specifically adjusted by inputting the pressure of wet gas and dry gas. The wet gas pressure of the ethanol nitrogen output unit is 0-0.40MPa, the dry gas pressure is 0-0.40MPa, and the nitrogen source pressure is 0.30-0.80MPa.

[0045] As a possible design, the mixed gas flow rate of the above-mentioned ethanol nitrogen output unit is 0-14L / min, and the ethanol vapor concentration is 0-5.5%VOL

[0046] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0047] The present invention uses pressurized nitrogen to excite anhydrous ethanol in an ethanol nitrogen output unit to form ethanol vapor, and then transports the ethanol vapor to a fumigation unit to cause API to undergo crystallization, thereby reducing amorphous, and further allowing the properties of the preparation to reach a stable state, thereby ensuring the quality of the preparation product. The tail gas is input into a tail gas recovery and treatment unit to achieve ethanol recovery, filtering and control of nitrogen carrying high-activity drug dust, purifying the tail gas before discharging, achieving reduction of amorphous bulk drug, and ensuring that the discharged gas does not carry any high-activity drug powder dust, thereby improving the stability of the preparation, and reducing the patient's medication safety risk and the safety risk and environmental pollution risk in the drug production process.

[0048] In the fumigation process, the present invention sets different wet gas pressures P1 (nitrogen pressure passing through an ethanol solution) to control the flow rate of nitrogen passing into the ethanol solution, thereby stimulating the ethanol liquid to generate ethanol vapor of different concentrations, and then controls the total air intake flow rate L of the formed mixed gas by adjusting the dry gas P2 (nitrogen pressure not passing through the ethanol solution) and P1 to control the concentration VOL of the ethanol vapor. The ethanol vapor passes through the raw material medicine on the stainless steel filter-type tray for fumigation treatment, thereby solving the problem of unstable preparation caused by high amorphous content after pulverization treatment, reducing the amorphous content of the raw material medicine, and finally the nitrogen ethanol vapor mixed gas passes through the tail gas treatment system. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] In order to more clearly illustrate the technical solutions of the exemplary embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments. It should be understood that the following drawings only illustrate certain embodiments of the present invention and should not be regarded as limiting the scope. For those of ordinary skill in the art, other relevant drawings can be obtained based on these drawings without creative work. In the drawings:

[0050] Figure 1 This is a schematic structural diagram of a nitrogen-activated ethanol fumigation device for a highly active API of the present invention;

[0051] Figure 2 This is a schematic cross-sectional structure diagram of a nitrogen-activated ethanol fumigation device for a highly active API of the present invention;

[0052] Figure 3 The present invention is a partial cross-sectional structural schematic diagram of a nitrogen-activated ethanol fumigation device for a highly active bulk drug.

[0053] Marks and corresponding parts names in the attached drawings:

[0054] 1-ethanol nitrogen output unit; 11-ethanol storage container; 12-first nitrogen input pipe; 13-ethanol addition port; 14-ethanol discharge pipe; 15-transmission pipeline; 16-ethanol concentration probe; 17-second nitrogen input pipe; 2-fumigation unit; 21-fumigation container; 22-filter tray; 3-exhaust gas recovery and treatment unit; 31-exhaust pipe; 32-secondary filter; 321-filter 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-priming water pump; 44-chiller; 441-temperature control container; 442-circulation pipeline; 443-circulation pump; 45-return 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 invention clearer, the present invention is further described in detail below in conjunction with examples and drawings. The illustrative embodiments of the present invention and their description are only used to explain the present invention and are not intended to limit the present invention. If specific conditions are not specified in the examples, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0056] In the first aspect, the present invention provides a nitrogen-activated ethanol fumigation device for highly active raw materials, referring to Figures 1 to 3 , including an ethanol nitrogen output unit 1, a fumigation unit 2 and an exhaust gas recovery and treatment unit 3. The ethanol nitrogen output unit 1 is used to store ethanol and also to output a mixed gas of anhydrous ethanol vapor and nitrogen; the fumigation unit 2 is connected to the ethanol nitrogen output unit 1 and is used to fumigate highly active APIs with a mixed gas; the exhaust gas recovery and treatment unit 3 is connected to the fumigation unit 2 and is used to receive and treat the mixed gas after fumigation treatment and then discharge the exhaust gas. Specifically, by injecting pressurized nitrogen into anhydrous ethanol, a compression effect is produced on the ethanol liquid. During the nitrogen injection process, heat exchange occurs with the ethanol, transferring heat to the ethanol, so that the increased temperature brings the ethanol liquid closer to its boiling point, thereby vaporizing; the injection of nitrogen will also produce disturbances and flows in the ethanol liquid, promoting the evaporation of the surface of the ethanol liquid. The final result is a mixed gas of nitrogen and ethanol vapor. The mixed gas is input into the fumigation unit 2 to fumigate the API, which can cause the API to crystallize. Ethanol vapor and a small amount of API powder may remain in the tail gas. The ethanol and API powder are recovered in turn through the tail gas recovery unit 3 to achieve the reduction of the amorphous form of the raw material, while ensuring that the exhausted gas does not carry any highly active drug powder dust.

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

[0058] In some embodiments of the present invention, reference Figure 2 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 addition port 13, an ethanol discharge pipe 14 and a transmission pipe 15. The ethanol storage container 11 is used to store anhydrous ethanol and is connected to the transmission pipe 15. When pressurized nitrogen is input into the container, the temperature and pressure of the nitrogen will cause the ethanol to vaporize, and the mixed gas of nitrogen and ethanol vapor will be output to the fumigation unit 2 along the transmission pipe 15 for API fumigation treatment; the first nitrogen input pipe 12 is connected to the bottom of the ethanol storage container 11, and is used to introduce nitrogen with a certain pressure and temperature into the ethanol storage container 11 to stimulate the anhydrous ethanol to produce steam (humidity); the second nitrogen input pipe 17 is connected to the upper end of the ethanol storage container (11). , which is used to directly input nitrogen into the transmission pipeline 15 without passing through anhydrous ethanol, thereby inputting dry gas into the transmission pipeline 15, which is used to increase the diffusion speed and uniformity of ethanol vapor; the ethanol addition port 13 is connected to the ethanol storage container 11, which is used to input anhydrous ethanol into the ethanol storage container 11; the ethanol discharge pipe 14 is connected to the bottom of the ethanol storage container 11, which is used to discharge anhydrous ethanol; the two ends of the transmission pipeline 15 are respectively connected to the upper end of the ethanol storage container 11 and the bottom of the fumigation unit 2, which are used to output ethanol vapor and nitrogen to the fumigation unit 2, and the two are mixed to form a mixed gas.

[0059] In some embodiments of the present invention, the ethanol nitrogen output unit 1 further comprises a first ethanol concentration probe 16, which is mounted on the transmission pipeline 15. The ethanol concentration probe 16 is preferably an online ethanol detector, which can obtain the ethanol vapor concentration through the nitrogen pressure and flow rate.

[0060] In some embodiments of the present invention, the above-mentioned device also includes a constant temperature unit 4, which includes a water tank 41, a liquid inlet pipe 42, a water return pipe 45, a self-priming water pump 43 and a water chiller 44. The water tank 41 is used to load purified water, and the temperature of the anhydrous ethanol is adjusted by the water chiller 44. When the temperature of the ethanol in the ethanol storage container 11 is too high, the purified water in the water tank 41 can be input into the interlayer of the ethanol storage container 11, and the temperature of the anhydrous ethanol can be reduced through heat exchange to maintain the temperature at a stable value; the two ends of the liquid inlet pipe 42 are respectively connected to the bottom of the water tank 41 and the jacket of the ethanol storage container 11, and are used to input the purified water after adjusting the temperature into the ethanol storage container 11; the water return pipe 45 is respectively connected to the upper end of the water tank 41, the jacket of the ethanol storage container 11 and the jacket of the transmission pipeline 15, It is used to input the cooled purified water into the water tank 41 for adjusting the temperature. The liquid inlet pipe 42, the water tank 41, the jacket of the ethanol storage container 11, the jacket of the transmission pipeline 15 and the return pipe 45 form a purified water circulation. During the continuous circulation, the ethanol is cooled by the chiller 44; the self-priming water pump 43 is installed on the liquid inlet pipe 42, and is used to provide power to extract the purified water in the water tank 41 and input it into the jacket of the ethanol storage container 11 through the liquid inlet pipe 42; the chiller 44 is installed in the water tank 41, and is used to adjust the temperature of the purified water in the water tank. Preferably, the purified water can be cooled by temperature exchange.

[0061] Preferably, a temperature sensor 61 is installed in the shell 6 and is electrically connected to the control and display unit 5 . When it is detected that the temperature in the shell 6 is too high, the constant temperature unit 4 can be started to cool down through the control and display unit 5 .

[0062] In some embodiments of the present invention, reference Figure 3 The water chiller 44 comprises a temperature regulating container 441, a circulation pipe 442 and a circulation pump 443. The temperature regulating container 441 is used to load a temperature regulating liquid, which can be any liquid with strong thermal conductivity; the liquid inlet and outlet of the circulation pipe 442 are both connected to the temperature regulating container 441, and the pipe body of the circulation pipe 442 is located in the water tank 41. When the liquid circulates in the circulation pipe 442, the temperature is exchanged with ethanol, which is used to regulate the temperature of the purified water in the water tank 41; the circulation pump 443 is installed on the circulation pipe 442, and is used to extract the temperature regulating solution from the temperature regulating container 441.

[0063] In some embodiments of the present invention, reference Figure 2The fumigation unit 2 includes a fumigation container 21 and a filter tray 22. The fumigation container 21 is a hollow furnace body, the bottom of which is connected to the ethanol nitrogen output unit 1, and the top is connected to the tail gas recovery unit 3; there are multiple filter trays 22, and multiple filter trays 22 can be detachably stacked and connected in the fumigation container 21. The filter tray 22 is used to support highly active APIs. 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 unit 3 through the fumigation container 21.

[0064] In some embodiments of the present invention, reference Figure 2 The exhaust gas recovery and treatment unit 3 includes an exhaust pipe 31, a secondary filter 32, a fresh air pipe 33, an exhaust pipe 36 and an exhaust fan 34. The two ends of the exhaust pipe 31 are respectively connected to the bottom of the secondary filter 32 and the fumigation unit 2 for conveying fumigation exhaust gas; the secondary filter 32 is connected to the exhaust pipe 36 for inputting the filtered exhaust gas into the exhaust pipe 36; the exhaust pipe 36 is used to discharge the filtered exhaust gas; the exhaust fan 34 is installed on the exhaust pipe 36 for extracting the filtered exhaust gas; the fresh air pipe 33 is connected to the secondary filter 32 for providing fresh air to the secondary filter 32 to balance the pressure difference between the secondary filter 32 and the outside.

[0065] Preferably, the exhaust fan 34 is connected to an online oxygen concentration probe 35. Since nitrogen in the exhaust gas is an asphyxiating emission, the online oxygen concentration probe 35 can be provided to monitor the ambient oxygen concentration. The purpose is to monitor that there is no nitrogen leakage in the environment and the oxygen content in the air is 21%, thereby ensuring that the environment in which the operator is located is safe.

[0066] Preferably, the above-mentioned secondary filter 32 includes 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 to the tail gas pipe 31 for receiving the tail gas, and the top is respectively connected to the exhaust pipe 36 and the fresh air duct 33; the water bath space 322 is located at the bottom of the filter container 321, and is used to absorb ethanol in the tail gas; the H14 high-efficiency filter 323 is stacked above the water bath space 322 and is located in the filter container 321, and is used to absorb residual raw materials in the tail gas.

[0067] Preferably, the above-mentioned device also includes a control display unit 5, and the control unit 5 is respectively connected to the first ethanol concentration probe 16 of the ethanol nitrogen output unit 1, the chiller 44 of the constant temperature unit 4, the online oxygen concentration probe 35 and the self-priming water pump 43, and the exhaust fan 34 of the tail gas recovery and treatment unit 3, for controlling the operation of each part.

[0068] In a second aspect, the present invention provides a method for nitrogen-stimulated ethanol fumigation of highly active APIs, comprising the following steps:

[0069] Input ethanol into the ethanol nitrogen output unit 1, adjust the pressure of dry gas and wet gas in the ethanol nitrogen output unit 1, and mix the dry gas, wet gas and ethanol vapor excited by the wet gas to form a mixed gas, wherein the dry gas is nitrogen that has not passed through the ethanol solution, and the wet gas is nitrogen that has passed through the ethanol solution;

[0070] The highly active API is placed in the fumigation unit 2 and fumigated with a mixed gas at 18 to 26° C. to obtain the crystallized highly active API.

[0071] In some embodiments of the present invention, the intake flow rate and ethanol vapor concentration of the above-mentioned mixed gas are specifically adjusted by inputting the pressure of wet gas and dry gas. The wet gas pressure of the ethanol nitrogen output unit 1 is 0-0.40MPa, the dry gas pressure is 0-0.40MPa, and the nitrogen gas source pressure is 0.30-0.80MPa.

[0072] The inventor found in actual research that during actual fumigation, several layers of trays are set for simultaneous fumigation, and the fumigation effects of the materials on the uppermost tray and the lowermost tray are inconsistent under the same process time. Since the ethanol concentration of the fumigation cannot be changed, an additional group of nitrogen (dry gas) is added to accelerate the upward diffusion of ethanol vapor and increase the diffusion speed of ethanol vapor. In addition to ensuring the fumigation effect of the upper and lower materials, the material processing time can also be saved.

[0073] In some embodiments of the present invention, the mixed gas flow rate of the ethanol nitrogen output unit 1 is 0-14 L / min, and the ethanol vapor concentration is 0-5.5% VOL.

[0074] The specific implementation methods described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific implementation method of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A nitrogen-activated ethanol fumigation device for highly active bulk drugs, characterized in that: include An ethanol nitrogen output unit (1) is used to store ethanol and also to output a mixed gas of anhydrous ethanol vapor and nitrogen; A fumigation unit (2) is connected to the ethanol nitrogen output unit (1) and is used for fumigating highly active APIs using a mixed gas; The tail gas recovery and processing unit (3) is connected to the fumigation unit (2) and is used to receive and process the mixed gas after fumigation and then discharge the tail gas.

2. The nitrogen-activated ethanol fumigation device for highly active bulk drugs according to claim 1, characterized in that: 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 addition port (13), an ethanol discharge pipe (14) and a transmission pipe (15). The ethanol storage container (11) is used to store anhydrous ethanol and is connected to the transmission pipeline (15) to output a mixed gas of anhydrous ethanol vapor and nitrogen; The first nitrogen gas input pipe (12) is connected to the bottom of the ethanol storage container (11) and is used to introduce nitrogen gas into the ethanol storage container (11) to stimulate the anhydrous ethanol to generate steam; The second nitrogen inlet pipe (17) is connected to the upper end of the ethanol storage container (11) and is used to directly input nitrogen into the transmission pipe (15) without passing through the anhydrous ethanol to increase the diffusion speed and uniformity of the ethanol vapor; The ethanol adding port (13) is connected to the ethanol storage container (11) and is used to input anhydrous ethanol into the ethanol storage container (11); The ethanol discharge pipe (14) is connected to the bottom of the ethanol storage container (11) and is used to discharge anhydrous ethanol; The two ends of the transmission pipeline (15) are respectively connected to the upper end of the ethanol storage container (11) and the bottom of the fumigation unit (2), and are used to output a mixed gas of ethanol vapor and nitrogen to the fumigation unit (2).

3. The nitrogen-activated ethanol fumigation device for highly active bulk drugs according to claim 1, characterized in that: 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) and is used to monitor the ethanol vapor concentration.

4. The nitrogen-activated ethanol fumigation device for highly active bulk drugs according to claim 2, characterized in that: It also includes a constant temperature unit (4), wherein the constant temperature unit (4) includes a water tank (41), a liquid inlet pipe (42), a water return pipe (45), a self-priming water pump (43) and a chiller (44). The water tank (41) is used to load purified water and to adjust the temperature of the anhydrous ethanol evaporation and transmission process through a water chiller (44); The two ends of the liquid inlet pipe (42) are respectively connected to the bottom of the water tank (41) and the jacket of the ethanol storage container (11), and are used to input chilled water into the jacket of the ethanol storage container (11), and are used to adjust the temperature of the ethanol storage container (11) and the transmission pipeline (15); The water return pipe (45) is respectively connected to the upper end of the water tank (41) and the jacket of the ethanol storage container (11), and is used to input the conditioned chilled water of the ethanol storage container (11) into the water tank (41); The self-priming water pump (43) is installed on the liquid inlet pipe (42) and is used to extract the purified water that has been cooled in the water tank (41) and input it 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 to the water tank (41) and is used to reduce the temperature of the purified water in the water tank (41).

5. The nitrogen-activated ethanol fumigation device for highly active bulk drugs according to claim 4, characterized in that: The water chiller (44) includes a temperature control container (441), a circulation pipeline (442) and a circulation pump (443). The temperature regulating container (441) is used for loading the temperature regulating liquid; The liquid inlet and liquid outlet of the circulation pipeline (442) are both connected to the temperature adjustment container (441) and are located in the water tank (41) for adjusting the temperature of the purified water in the water tank (41); The circulation pump (443) is installed on the circulation pipeline (442) and is used to extract the temperature-adjusting solution from the temperature-adjusting container (441).

6. The nitrogen-activated ethanol fumigation device for highly active API according to claim 1, characterized in that: The fumigation unit (2) comprises a fumigation container (21) and a filter tray (22). The bottom of the fumigation container (21) is connected to the ethanol nitrogen output unit (1), and the top is connected to the tail gas recovery and processing unit (3); There are a plurality of filter-type trays (22), and the plurality of filter-type trays (22) are detachably stacked and clamped in the fumigation container (21). The filter-type trays (22) are used to support highly active raw materials.

7. The nitrogen-activated ethanol fumigation device for highly active API according to claim 1, characterized in that: The tail gas recovery and treatment unit (3) comprises a tail gas pipe (31), a secondary filter (32), a fresh air duct (33), an exhaust pipe (36) and an exhaust fan (34). The two ends of the tail gas pipe (31) are respectively connected to the bottom of the secondary filter (32) and the fumigation unit (2) for conveying fumigation tail gas; The secondary filter (32) is connected to the exhaust pipe (36) to input the filtered exhaust gas into the exhaust pipe (36); The exhaust pipe (36) is used to discharge filtered exhaust gas; The exhaust fan (34) is installed on the exhaust pipe (36) and is used to extract and filter the exhaust gas; The fresh air duct (33) is connected to the secondary filter (32) and is used to provide fresh air to the secondary filter (32) to balance the pressure difference between the secondary filter (32) and the outside.

8. A nitrogen-activated ethanol fumigation method for highly active bulk drugs, characterized in that: The nitrogen-activated ethanol fumigation device for a highly active API according to any one of claims 1 to 7 is used, comprising the following steps: Inputting ethanol into the ethanol nitrogen output unit (1), adjusting the pressure of dry gas and wet gas in the ethanol nitrogen output unit (1), and mixing the dry gas and wet gas to form a mixed gas, wherein the dry gas is nitrogen that has not passed through the ethanol solution, and the wet gas is nitrogen that has passed through the ethanol solution; The highly active API is placed in a fumigation unit (2) and fumigated with a mixed gas of nitrogen and ethanol vapor excited by nitrogen at a temperature of 18 to 26° C. to obtain a crystallized highly active API.

9. The method for nitrogen-activated ethanol fumigation of a highly active API according to claim 8, characterized in that: The intake flow rate and ethanol vapor concentration of the mixed gas are specifically adjusted by inputting the pressure of wet gas and dry gas. The wet gas pressure of the ethanol nitrogen output unit (1) is 0-0.40 MPa, the dry gas pressure is 0-0.40 MPa, and the nitrogen gas source pressure is 0.30-0.80 MPa.

10. The method for nitrogen-activated ethanol fumigation of a highly active API according to claim 9, characterized in that: The mixed gas flow rate of the ethanol nitrogen output unit (1) is 0-14 L / min, and the ethanol vapor concentration is 0-5.5% VOL.

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