Vacuum airtight sampling device, sampling method and application

Abstract

The invention provides a vacuum airtight sampling device, a sampling method and application, and belongs to the technical field of raw material medicine production. The device comprises a sampling inlet pipeline and a sampling outlet pipeline which are parallel to each other and are horizontally arranged, and the tail ends of the sampling inlet pipeline and the sampling outlet pipeline are vertically and hermetically connected with a sampling pipeline; the upstream of the joint of the sampling pipeline and the sampling inlet pipeline is hermetically connected with a gas phase pipeline through a vacuum nitrogen balance pipe; a sampling needle is hermetically mounted at the lower end of the sampling pipeline, a gas-phase needle is hermetically mounted at the lower end of the gas-phase pipeline, and the sampling needle and the gas-phase needle are both inserted into the sampling bottle. By arranging the sampling needle and the sampling bottle, the sampling leakproofness is ensured; by adopting the nitrogen pipe and the gas phase pipe, a vacuum pump in a process pipeline can be utilized to realize a vacuum state of a sampling pipeline, so that the sampling investment cost is reduced; according to the invention, the convenience, timeliness and simplicity of sampling are ensured, and the practicability of vacuum closed sampling of pipeline liquid in a small-scale production device of bulk pharmaceutical chemicals is improved.

Description

Technical Field

[0001] The invention belongs to the technical field of raw material drug production, and specifically relates to a vacuum-sealed sampling device, a sampling method and an application thereof. Background Art

[0002] In the production of APIs, processes that require a vacuum environment are generally involved, such as vacuum concentration, vacuum distillation, vacuum crystallization, and drying. In small-scale production facilities, in order to track operating parameters and analyze sample components at any time, it is very necessary to conduct vacuum-sealed sampling and analysis on the pipeline conveniently, flexibly, and in a timely manner.

[0003] Many of the currently disclosed vacuum sampling devices have certain technical problems when applied to sampling in small-scale production devices of raw materials. Chinese patent publication CN203490092U discloses a vacuum sampling system, and Chinese patent publication CN208076219U discloses a closed sampling device, both of which are used for sampling devices of vacuum reactors, but they are used for direct sampling in reactors and require an additional vacuum pump. Chinese patent publication CN203053745U discloses a new type of liquid vacuum sampling device for pipeline liquid vacuum sampling, but the device is not airtight, and the subsequent vacuum breaking operation of the sampling device is not considered, which is a challenge for subsequent analysis. Chinese patent publication CN212988924U discloses a vacuum sampling valve, which uses a valve stem and a sampling port to open and close, avoiding excessive medium residue at the sampling point, is environmentally friendly, and greatly improves the inspection accuracy of the sample, but the sampling valve is relatively expensive. Chinese patent publication CN211553425U discloses a vacuum sampling system, which has a relatively complex process and long pipelines and is not suitable for simple vacuum sampling of small-scale production equipment.

[0004] The factors that need to be considered for vacuum sampling of pipelines in small-scale production facilities of raw materials are: first, most of them involve flammable, explosive and toxic media, and the sampling process needs to be closed; second, in small-scale production facilities, the volume of reactors and containers is generally 5L-50L, and the sampling pipelines and sampling devices require smaller volumes to avoid large losses to the product during the sampling process. Summary of the invention

[0005] The purpose of the present invention is to solve the problems existing in the above-mentioned prior art and to provide a vacuum-sealed sampling device, a sampling method and an application thereof.

[0006] The present invention is achieved through the following technical solutions:

[0007] In a first aspect, the present invention provides a vacuum-sealed sampling device, comprising a sampling inlet pipeline and a sampling outlet pipeline which are arranged parallel to each other and horizontally, wherein the sampling inlet pipeline and the sampling outlet pipeline are vertically and sealedly connected to the sampling pipeline at their ends;

[0008] The upstream of the connection between the sampling pipeline and the sampling inlet pipeline is sealed with a gas phase pipeline through a vacuum nitrogen balance pipe;

[0009] A sampling needle is sealed at the lower end of the sampling pipeline, and a gas phase needle is sealed at the lower end of the gas phase pipeline. Both the sampling needle and the gas phase needle are inserted into the sampling bottle.

[0010] A further improvement of the present invention is:

[0011] The sampling inlet pipeline is sealed and connected to the upstream of the process pipeline, and the sampling outlet pipeline is sealed and connected to the downstream of the process pipeline;

[0012] The process pipeline is provided with a process valve, and the process valve is located between the sampling inlet pipeline and the sampling outlet pipeline.

[0013] A further improvement of the present invention is:

[0014] The sampling inlet pipeline is provided with a sampling inlet cut-off valve;

[0015] The sampling outlet pipeline is provided with a second sampling outlet cut-off valve.

[0016] A further improvement of the present invention is:

[0017] A sampling cut-off valve is provided at the upper part of the sampling pipeline, and the sampling cut-off valve is located between the connection between the sampling pipeline and the sampling inlet pipeline and the connection between the sampling pipeline and the vacuum nitrogen balance pipe;

[0018] A first sampling outlet cut-off valve is arranged at the lower part of the sampling pipeline, and the first sampling outlet cut-off valve is located between the connection between the sampling pipeline and the sampling outlet pipeline and the sampling needle.

[0019] A further improvement of the present invention is:

[0020] The gas phase pipeline is arranged in parallel with the sampling pipeline, and a second gas phase cut-off valve, a pressure gauge and a third gas phase cut-off valve are arranged on the gas phase pipeline in sequence from top to bottom.

[0021] A further improvement of the present invention is:

[0022] A gas phase pipe is provided upstream of the connection between the sampling pipeline and the vacuum nitrogen balance pipe, and a first gas phase cut-off valve is provided on the gas phase pipe;

[0023] A nitrogen pipe is arranged upstream of the connection between the gas phase pipeline and the vacuum nitrogen balance pipe, and a nitrogen shut-off valve is arranged on the nitrogen pipe.

[0024] A further improvement of the present invention is:

[0025] The lengths of the sampling inlet pipeline and the sampling outlet pipeline are 15 times the diameter of the process pipeline.

[0026] A further improvement of the present invention is:

[0027] The lengths of the gas phase pipe, the nitrogen pipe, the sampling pipeline, and the gas phase pipeline are 10-20 times the diameter of the process pipeline.

[0028] The second aspect of the present invention provides a vacuum-sealed sampling method, which uses the vacuum-sealed sampling device described above to perform sampling, and the specific steps include:

[0029] (1) Startup: First close the process valve, open the sampling inlet shut-off valve and the second sampling outlet shut-off valve;

[0030] (2) Rinsing: The liquid to be sampled flows through the sampling inlet pipeline, the sampling pipeline, and the sampling outlet pipeline in sequence, and the sampling pipeline is rinsed after a certain period of time to ensure that the liquid to be sampled that finally enters the sampling bottle is fresh;

[0031] (3) Breaking the vacuum: Close the sampling inlet shut-off valve and the second sampling outlet shut-off valve, open the process valve, sampling shut-off valve, the second gas phase shut-off valve, and the nitrogen shut-off valve to break the vacuum state of the sampling pipeline. When the pressure gauge shows 0 MPaG, close the nitrogen shut-off valve;

[0032] (4) Sampling: After breaking the vacuum, insert the sampling needle and the gas phase needle into the sampling bottle, open the first gas phase cut-off valve, the first sampling outlet cut-off valve, and the third gas phase cut-off valve. After the required amount of sampling is achieved, close the first sampling outlet cut-off valve and the third gas phase cut-off valve to complete the sampling;

[0033] (5) Unloading the sampling bottle: Pull out the sampling needle and gas phase needle from the sampling bottle, and send the sampling bottle to the analytical sampling room for sampling and analysis;

[0034] (6) Re-establishing the vacuum state: close the process valve, the first gas phase shut-off valve, and the nitrogen shut-off valve, open the sampling inlet shut-off valve and the second sampling outlet shut-off valve. After a certain period of time, a vacuum state is established in the sampling pipeline. Close the sampling inlet shut-off valve and the second sampling outlet shut-off valve, and open the process valve to prepare for the next sampling.

[0035] The third aspect of the present invention provides an application of a vacuum-tight sampling device in vacuum-tight sampling of pipeline liquids in a small-scale production device for raw materials.

[0036] Compared with the prior art, the present invention has the following beneficial effects:

[0037] The present invention ensures the practicality of sampling of a small-scale production device by adopting a sleeve pipeline, reducing the length of the sampling pipeline, reducing the volume of the sampling pipeline, and reducing the loss of products on the sampling pipeline; by adopting the configuration of a sampling needle and a sampling bottle, the airtightness of sampling is ensured; by adopting a nitrogen tube and a gas phase tube, the configuration of an additional vacuum pump with a higher vacuum degree is reduced, and the investment in sampling is reduced; by reducing the configuration of pipelines and valves, the convenience, timeliness and simplicity of sampling are ensured, and the convenience of studying the vacuum operation parameters of a small-scale production device of a bulk drug is improved. The present invention improves the practicality of vacuum-tight sampling of pipeline liquid in a small-scale production device of a bulk drug, and achieves better technical effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 It is a schematic structural diagram of the vacuum-sealed sampling device of the present invention.

[0039] In the figure, 1. process pipeline, 2. process valve, 3. sampling inlet pipeline, 4. sampling inlet cut-off valve, 5. gas phase pipe, 6. nitrogen pipe, 7. first gas phase cut-off valve, 8. nitrogen cut-off valve, 9. vacuum nitrogen balance pipe, 10. second gas phase cut-off valve, 11. sampling cut-off valve, 12. pressure gauge, 13. gas phase pipeline, 14. sampling pipeline, 15. third gas phase cut-off valve, 16. gas phase needle, 17. sampling bottle, 18. sampling needle, 19. first sampling outlet cut-off valve, 20. sampling outlet pipeline, 21. second sampling outlet cut-off valve. DETAILED DESCRIPTION

[0040] The present invention is further described in detail below in conjunction with the accompanying drawings:

[0041] [Example 1]

[0042] This embodiment provides a vacuum-sealed sampling device, which is suitable for vacuum-sealed sampling of pipeline liquids in a small-scale production device of raw materials. Figure 1 As shown, the device comprises a sampling inlet pipeline 3 and a sampling outlet pipeline 20 which are arranged parallel to each other and horizontally, and the ends of the sampling inlet pipeline 3 and the sampling outlet pipeline 20 are vertically sealed and connected with a sampling pipeline 14;

[0043] The upstream of the connection between the sampling pipeline 14 and the sampling inlet pipeline 3 is sealedly connected to the gas phase pipeline 13 through a vacuum nitrogen balance pipe 9;

[0044] A sampling needle 18 is sealed at the lower end of the sampling pipeline 14 , and a gas phase needle 16 is sealed at the lower end of the gas phase pipeline 13 . Both the sampling needle 18 and the gas phase needle 16 are inserted into a sampling bottle 17 .

[0045] Further, the sampling inlet pipeline 3 is sealed and connected to the upstream of the process pipeline 1, the sampling outlet pipeline 20 is sealed and connected to the downstream of the process pipeline 1, and a process valve 2 is provided on the process pipeline 1, and the process valve 2 is located between the sampling inlet pipeline 3 and the sampling outlet pipeline 20. When sampling is required, the process valve 2 is closed, and the sample liquid in the process pipeline 1 flows into the sampling inlet pipeline 3, and flows into the sampling bottle 17 through the sampling pipeline 14.

[0046] The process pipeline 1 is arranged vertically, and the fluid in the process pipeline 1 flows from top to bottom.

[0047] Furthermore, a sampling inlet cut-off valve 4 is provided on the sampling inlet pipeline 3, and a second sampling outlet cut-off valve 21 is provided on the sampling outlet pipeline 20, and the sampling inlet cut-off valve 4 and the second sampling outlet cut-off valve 21 are both arranged as close to the process pipeline 1 as possible, and as short as possible to reduce the dead zone between the sampling inlet cut-off valve 4, the second sampling outlet cut-off valve 21 and the process pipeline 1, and can reduce the rinsing time and the influence of the liquid dead zone in the sampling pipeline on the process pipeline liquid.

[0048] Furthermore, a sampling cut-off valve 11 is provided at the upper part of the sampling pipeline 14, and the sampling cut-off valve 11 is located between the connection between the sampling pipeline 14 and the sampling inlet pipeline 3 and the connection between the sampling pipeline 14 and the vacuum nitrogen balance pipe 9; a first sampling outlet cut-off valve 19 is provided at the lower part of the sampling pipeline 14, and the first sampling outlet cut-off valve 19 is located between the connection between the sampling pipeline 14 and the sampling outlet pipeline 20 and the sampling needle 18.

[0049] Furthermore, the gas phase pipeline 13 is arranged in parallel with the sampling pipeline 14, and the gas phase pipeline 13 is provided with a second gas phase shut-off valve 10, a pressure gauge 12 and a third gas phase shut-off valve 15 in sequence from top to bottom. The vacuum nitrogen balance pipe 9 connects the sampling pipeline 14 and the gas phase pipeline 13 in a sealed manner, and is located upstream of the sampling shut-off valve 11 and the second gas phase shut-off valve 10. The vacuum nitrogen balance pipe 9 is mainly used to maintain the same pressure in the sampling pipeline 14 and the gas phase pipeline 13.

[0050] Furthermore, a gas phase pipe 5 is provided upstream of the connection between the sampling pipeline 14 and the vacuum nitrogen balance pipe 9 , and a first gas phase cut-off valve 7 is provided on the gas phase pipe 5 . The function of the gas phase pipe 5 is to discharge excess gas through the gas phase pipe 5 .

[0051] A nitrogen pipe 6 is provided upstream of the connection between the gas phase pipeline 13 and the vacuum nitrogen balance pipe 9, and a nitrogen shut-off valve 8 is provided on the nitrogen pipe 6. The end of the nitrogen pipe 6 is connected to an external nitrogen pipeline, and nitrogen enters the downstream pipeline through the nitrogen pipe 6.

[0052] Preferably, the sampling inlet pipeline 3, the sampling outlet pipeline 20, the gas phase pipe 5, the nitrogen pipe 6, the sampling pipeline 14, and the gas phase pipeline 13 are all made of ferrules with a diameter not greater than 1 / 4 inch (about 0.63 cm), and the pipelines are as short as possible.

[0053] The length of the sampling inlet pipeline 3 and the sampling outlet pipeline 20 is 14.5 to 15.5 times the diameter of the process pipeline 1, preferably 15 times. Here, it is mainly considered that the sampling inlet pipeline 3 and the sampling outlet pipeline 20 need to be provided with a branch pipe platform and a tee, and the pipe fittings and valves thereon need to be connected by a ferrule. If it is too short, mechanical connection cannot be achieved due to the existence of pipe fittings, valves, and ferrule connections; if it is too long, the sampling pipeline is too long, which increases the amount of liquid in the sampling pipeline and the rinsing time, and is not suitable for small-scale sampling scenarios.

[0054] The lengths of the gas phase pipe 5, nitrogen pipe 6, sampling pipeline 14, and gas phase pipeline 13 are 10-20 times the diameter of the process pipeline 1. Since a branch pipe and a tee are required on the pipeline, the pipe fittings and valves need to be connected by a ferrule. If they are too short, mechanical connection cannot be achieved due to the existence of pipe fittings, valves, and ferrule connections; if they are too long, the sampling pipeline is too long, which increases the amount of liquid in the sampling pipeline and the space occupied by the sampling system, and is not suitable for small-scale sampling scenarios.

[0055] Furthermore, the sampling inlet cut-off valve 4, the second sampling outlet cut-off valve 21, the first gas phase cut-off valve 7, and the nitrogen cut-off valve 8 are needle valves.

[0056] Furthermore, the sampling needle 18 and the gas phase needle 16 are respectively welded to the end tube walls of the sampling pipeline 14 and the gas phase pipeline 13. When sampling is required, the sampling needle 18 and the gas phase needle 16 are respectively inserted into the ends of the sampling pipeline 14 and the gas phase pipeline 13, and inserted into the sampling bottle 17. After sampling is completed, they can be pulled out.

[0057] Preferably, the volume of the sampling bottle 17 is less than 2 mL.

[0058] In the present invention, since the sampling inlet pipeline 3 and the sampling outlet pipeline 20 are respectively connected to the process pipeline 1 to form a loop, the nitrogen pipe 6 and the gas phase pipe 5 are used, so that the vacuum pump provided in the process pipeline 1 can be used to achieve the vacuum state of the sampling pipeline 14. Therefore, there is no need to set a vacuum pump in the device of the present invention, thereby reducing the sampling investment cost.

[0059] When establishing a vacuum state, the present invention closes the process valve 2, the first gas phase cut-off valve 7, the nitrogen cut-off valve 8, the third gas phase cut-off valve 15 and the first sampling outlet cut-off valve 19, opens the sampling inlet cut-off valve 4, the third gas phase cut-off valve 10, the sampling cut-off valve 11 and the second sampling outlet cut-off valve 21. After a certain period of time, a vacuum state is established in the sampling pipeline 14, the sampling inlet cut-off valve 4 and the second sampling outlet cut-off valve 21 are closed, and the process valve 2 is opened to prepare for sampling.

[0060] The present invention ensures the practicality of sampling of a small-scale production device by adopting a sleeve pipeline, reducing the length of the sampling pipeline, reducing the volume of the sampling pipeline, and reducing the loss of products on the sampling pipeline; by adopting the configuration of a sampling needle and a sampling bottle, the airtightness of sampling is ensured; by adopting a nitrogen tube and a gas phase tube, the configuration of an additional vacuum pump with a higher vacuum degree is reduced, and the investment in sampling is reduced; by reducing the configuration of pipelines and valves, the convenience, timeliness and simplicity of sampling are ensured, and the convenience of studying the vacuum operation parameters of a small-scale production device of a bulk drug is improved. The present invention improves the practicality of vacuum-tight sampling of pipeline liquid in a small-scale production device of a bulk drug, and achieves better technical effects.

[0061] [Example 2]

[0062] This embodiment provides a vacuum-tight sampling method, which uses the vacuum-tight sampling device described in Example 1 for sampling. Before sampling, the sampling inlet cut-off valve 4, the second sampling outlet cut-off valve 21, the first gas phase cut-off valve 7, the nitrogen cut-off valve 8, the second gas phase cut-off valve 10, the sampling cut-off valve 11, the third gas phase cut-off valve 15, and the first sampling outlet cut-off valve 19 are all in a closed state, and the process valve 2 is in an open state; the specific steps of sampling include:

[0063] (1) Startup: first close the process valve 2, and open the sampling inlet cut-off valve 4 and the second sampling outlet cut-off valve 21;

[0064] (2) Rinsing: The liquid to be sampled flows through the sampling inlet pipeline 3, the sampling pipeline 14, and the sampling outlet pipeline 20 in sequence, and the sampling pipeline is rinsed after a certain period of time to ensure that the liquid to be sampled that finally enters the sampling bottle 17 is fresh;

[0065] (3) Breaking the vacuum: close the sampling inlet shut-off valve 4 and the second sampling outlet shut-off valve 21, open the process valve 2, the sampling shut-off valve 11, the second gas phase shut-off valve 10, and the nitrogen shut-off valve 8, break the vacuum state of the sampling pipeline, and when the pressure gauge shows 0 MPaG, close the nitrogen shut-off valve 8;

[0066] (4) Sampling: After breaking the vacuum, insert the sampling needle 18 and the gas phase needle 16 into the sampling bottle 17, open the first gas phase shut-off valve 7, the first sampling outlet shut-off valve 19, and the third gas phase shut-off valve 15, and when the sampling reaches the required amount, close the first sampling outlet shut-off valve 19 and the third gas phase shut-off valve 15 to complete the sampling; during the sampling process, as the liquid sample enters the sampling pipeline, the gas in the pipeline will be discharged from the gas phase pipe 15;

[0067] (5) Unloading the sampling bottle: Pull out the sampling needle 18 and the gas phase needle 16 from the sampling bottle 17, and send the sampling bottle 17 to the analytical sampling room for sampling and analysis;

[0068] (6) Re-establishing the vacuum state: close the process valve 2, the first gas phase shut-off valve 7, and the nitrogen shut-off valve 8, open the sampling inlet shut-off valve 4 and the second sampling outlet shut-off valve 21. After a certain period of time, a vacuum state is established in the sampling pipeline 14, close the sampling inlet shut-off valve 4 and the second sampling outlet shut-off valve 21, and open the process valve 2 to prepare for the next sampling.

[0069] When studying the vacuum operation process parameters of a small-scale production device in a certain API factory, it is necessary to regularly sample and analyze the composition of the condensed liquid, and the batch processing volume is 10L. Using the vacuum-sealed sampling device and sampling method of the present invention, the following data are obtained:

[0070] Operating time: intermittent

[0071] Work section personnel setting: 1 operator.

[0072] During the operation, the sampling pipeline has a small volume, the product loss in the rinsing and sampling pipelines is small, the sampling is convenient and timely, the vacuum sampling can be carried out well, and the component analysis of the sample in the vacuum operation is completed.

[0073] [Example 3]

[0074] Referring to the sampling method of Example 2, a small-scale production device of a certain raw material pharmaceutical factory was studying vacuum operation process parameters, with a batch processing volume of 20L and a vacuum degree of 500Pa. Vacuum-tight sampling was used to regularly analyze the liquid components. The following data were obtained by using the vacuum-tight sampling device and sampling method of the present invention:

[0075] Operating time: intermittent

[0076] Work section personnel setting: 1 operator.

[0077] During the operation, the sampling pipeline is small in size, and the product loss in the rinsing and sampling pipelines is small, which avoids the use of a vacuum pump (100Pa) with a higher vacuum degree for sampling, reduces investment, and makes sampling convenient and timely. It can better perform vacuum sampling and complete the component analysis of the product refined by vacuum distillation.

[0078] [Comparative Example 1]

[0079] When studying the vacuum operation process parameters of a small-scale production device in a raw material pharmaceutical factory, it is necessary to regularly sample and analyze the composition of the condensed liquid, with a batch processing volume of 10L. Using a traditional vacuum-sealed sampling box (for details, see Chinese patent publication CN116399650A), the following data was obtained:

[0080] Operating time: intermittent

[0081] During the operation, the sampling pipeline is long, the product loss during rinsing and sampling is large, and the operation process is complicated, which affects the final product collection volume and the convenience of sampling.

[0082] [Comparative Example 2]

[0083] When studying the vacuum operation process parameters of a small-scale production unit of a certain API factory, the batch processing volume was 20L, the vacuum degree was 500Pa, and vacuum-sealed sampling was used to regularly analyze the liquid components. Using a traditional vacuum-sealed sampling box, the following data were obtained:

[0084] Operating time: intermittent

[0085] During the operation, the sampling pipeline is long and a vacuum pump with a higher vacuum degree is required for sampling, which increases the sampling investment and affects the final product collection volume and sampling convenience.

[0086] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "connected" and "connection" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0087] In the description of the present invention, unless otherwise specified, the terms "upper", "lower", "left", "right", "inside", "outside", etc. indicate directions or positional relationships based on the directions or positional relationships shown in the accompanying drawings. They are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific direction, be constructed and operated in a specific direction. Therefore, they cannot be understood as limitations on the present invention.

[0088] The above technical solution is only one implementation mode of the present invention. For those skilled in the art, it is easy to make various types of improvements or modifications based on the principles disclosed in the present invention, and it is not limited to the technical solution described in the above specific embodiments of the present invention. Therefore, the above description is only preferred and does not have a restrictive meaning.

Claims

1. A vacuum-sealed sampling device, characterized in that: It comprises a sampling inlet pipeline and a sampling outlet pipeline which are arranged parallel to each other and horizontally, and the ends of the sampling inlet pipeline and the sampling outlet pipeline are vertically sealed and connected with the sampling pipeline; The upstream of the connection between the sampling pipeline and the sampling inlet pipeline is sealed with a gas phase pipeline through a vacuum nitrogen balance pipe; A sampling needle is sealed at the lower end of the sampling pipeline, and a gas phase needle is sealed at the lower end of the gas phase pipeline. Both the sampling needle and the gas phase needle are inserted into the sampling bottle.

2. The vacuum-sealed sampling device according to claim 1, characterized in that: The sampling inlet pipeline is sealed and connected to the upstream of the process pipeline, and the sampling outlet pipeline is sealed and connected to the downstream of the process pipeline; The process pipeline is provided with a process valve, and the process valve is located between the sampling inlet pipeline and the sampling outlet pipeline.

3. The vacuum-sealed sampling device according to claim 1 or 2, characterized in that: The sampling inlet pipeline is provided with a sampling inlet cut-off valve; The sampling outlet pipeline is provided with a second sampling outlet cut-off valve.

4. The vacuum-sealed sampling device according to claim 1, characterized in that: A sampling cut-off valve is provided at the upper part of the sampling pipeline, and the sampling cut-off valve is located between the connection between the sampling pipeline and the sampling inlet pipeline and the connection between the sampling pipeline and the vacuum nitrogen balance pipe; A first sampling outlet cut-off valve is arranged at the lower part of the sampling pipeline, and the first sampling outlet cut-off valve is located between the connection between the sampling pipeline and the sampling outlet pipeline and the sampling needle.

5. The vacuum-sealed sampling device according to claim 1, characterized in that: The gas phase pipeline is arranged in parallel with the sampling pipeline, and a second gas phase cut-off valve, a pressure gauge and a third gas phase cut-off valve are arranged on the gas phase pipeline in sequence from top to bottom.

6. The vacuum-sealed sampling device according to claim 1, characterized in that: A gas phase pipe is provided upstream of the connection between the sampling pipeline and the vacuum nitrogen balance pipe, and a first gas phase cut-off valve is provided on the gas phase pipe; A nitrogen pipe is arranged upstream of the connection between the gas phase pipeline and the vacuum nitrogen balance pipe, and a nitrogen shut-off valve is arranged on the nitrogen pipe.

7. The vacuum-sealed sampling device according to claim 2, characterized in that: The lengths of the sampling inlet pipeline and the sampling outlet pipeline are 15 times the diameter of the process pipeline.

8. The vacuum-sealed sampling device according to claim 6, characterized in that: The lengths of the gas phase pipe, the nitrogen pipe, the sampling pipeline, and the gas phase pipeline are 10-20 times the diameter of the process pipeline.

9. A vacuum-sealed sampling method, characterized in that: Sampling is performed using the vacuum sampling sealing device as described in any one of claims 1 to 8, and the specific steps include: (1) Startup: First close the process valve, open the sampling inlet shut-off valve and the second sampling outlet shut-off valve; (2) Rinsing: The liquid to be sampled flows through the sampling inlet pipeline, the sampling pipeline, and the sampling outlet pipeline in sequence, and the sampling pipeline is rinsed after a certain period of time to ensure that the liquid to be sampled that finally enters the sampling bottle is fresh; (3) Breaking the vacuum: Close the sampling inlet shut-off valve and the second sampling outlet shut-off valve, open the process valve, sampling shut-off valve, the second gas phase shut-off valve, and the nitrogen shut-off valve to break the vacuum state of the sampling pipeline. When the pressure gauge shows 0 MPaG, close the nitrogen shut-off valve; (4) Sampling: After breaking the vacuum, insert the sampling needle and the gas phase needle into the sampling bottle, open the first gas phase cut-off valve, the first sampling outlet cut-off valve, and the third gas phase cut-off valve. After the required amount of sampling is achieved, close the first sampling outlet cut-off valve and the third gas phase cut-off valve to complete the sampling; (5) Unloading the sampling bottle: Pull out the sampling needle and gas phase needle from the sampling bottle, and send the sampling bottle to the analytical sampling room for sampling and analysis; (6) Re-establishing the vacuum state: close the process valve, the first gas phase shut-off valve, and the nitrogen shut-off valve, open the sampling inlet shut-off valve and the second sampling outlet shut-off valve. After a certain period of time, a vacuum state is established in the sampling pipeline. Close the sampling inlet shut-off valve and the second sampling outlet shut-off valve, and open the process valve to prepare for the next sampling.

10. Use of the vacuum-tight sampling device according to any one of claims 1 to 8 in vacuum-tight sampling of pipeline liquids in a small-scale production device for bulk drugs.

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