Equipment for industrially precipitating antigen by PEG (Polyethylene Glycol)

Abstract

The utility model provides industrial PEG (Polyethylene Glycol) antigen precipitation equipment which is characterized in that the required PEG amount is prepared according to the antigen amount, a PEG solution is transferred into a PEG preparation tank and is measured by a radar type liquid level meter, and the PEG solution is poured back and forth between the PEG preparation tank and a PEG precipitation tank through a PEG transfer pipeline after being sterilized, so that the PEG is accurately added; after the antigen is precipitated by PEG, the supernatant contains impurities, a sterile supernatant discarding device is additionally arranged in the PEG precipitation tank, the precipitation and supernatant layering condition is observed through a test mirror on the tank body, the supernatant is discarded, the volume of the treated antigen is reduced, only the antigen of the precipitation part is purified, and the purity of the antigen is improved; the PEG precipitation tank adopts magnetic stirring under low shear force, the PEG preparation tank adopts magnetic stirring under high shear force, and compared with mechanical stirring, the magnetic stirring can ensure that the inside of the tank is sterile; the sterile supernatant discarding device can sterilize on line, and the device and the interior of the tank are sterile.

Description

Technical Field

[0001] The utility model relates to the technical field of pharmaceutical equipment, in particular to an industrialized PEG antigen precipitation device. Background Art

[0002] In the field of separation and purification in the pharmaceutical industry, PEG (polyethylene glycol) is often used for the separation and purification of proteins, nucleic acids, etc., namely, PEG precipitation method. PEG has good water solubility. The target substance of PEG precipitation is called antigen. PEG is prepared into a solution, and the antigen is also in the solution. After PEG is added to the antigen and fully stirred, it will naturally precipitate. In the precipitate, the supernatant and the precipitate are obviously stratified. The supernatant is discarded and the precipitate is further purified. Therefore, in this process, the key is to accurately add PEG as required, achieve the best PEG precipitation antigen effect (obvious stratification between the supernatant and the precipitate), discard all the supernatant (the supernatant contains foreign proteins, which can increase the purity of the antigen) and ensure the sterility of the product.

[0003] In the current PEG precipitation method, the equipment used cannot observe the precipitation stratification after the supernatant and precipitate are separated, the supernatant discarding device has the risk of contamination, and the PEG precipitation antigen effect is not optimal.

[0004] Patent document CN117229369A discloses a method for preparing high-purity antigens for industrial foot-and-mouth disease vaccines, in which the discarded supernatant is discharged by a rotary discharging mechanism, the volume is measured by weighing, and the stirring is mechanical stirring. The patent has the following shortcomings: the discarded supernatant rotary discharging mechanism has the risk of contamination, the manufacturing cost is high, and the supernatant rotary discharging mechanism has liquid accumulation in the horizontal direction; it does not explain how to accurately add PEG; the conical sedimentation tank has poor sedimentation effect; it is impossible to observe the sedimentation stratification effect; the supernatant and sediment are easily disturbed when the device rotates in the device.

[0005] Patent document CN213315060U discloses a supernatant extraction device. The patent has the following shortcomings: there is no complete device, and the sedimentation and stratification effect cannot be observed; the manufacturing cost is high; there is liquid accumulation in the horizontal direction of the device; the supernatant and sediment are easily disturbed when the device rotates in the device.

[0006] Patent document CN214597404U discloses a supernatant extraction device. The patent has the following shortcomings: there is no complete equipment, and the precipitation and stratification effect cannot be observed; there is a risk of bacterial contamination; and the manufacturing cost is high. Utility Model Content

[0007] In view of the defects in the prior art, the purpose of the utility model is to provide an industrialized PEG precipitation antigen equipment.

[0008] The equipment for industrial PEG antigen precipitation provided by the utility model comprises: a sterile supernatant discarding device, a sight glass, a first sight glass lamp and a manhole, a first respirator, a material inlet, a first pressure sensor, a first pressure gauge, a first radar-type liquid level gauge, a first cleaning inlet and a pure steam inlet, a sampling valve, a first chilled water inlet, a second chilled water return port, magnetic stirring under low shear, an antigen outlet, a first temperature sensor, a first baffle, magnetic stirring under high shear, a PEG material transfer pipeline, a second temperature sensor, a second chilled water inlet, a second chilled water return port, an industrial steam inlet, an industrial steam condensate drain, a PEG solution feeding port, a second pressure sensor, a second pressure gauge, a second radar-type liquid level gauge, a second cleaning inlet and a pure steam inlet, a second sight glass lamp and a manhole, a second respirator, and a second baffle;

[0009] The sterile supernatant discarding device is installed in the PEG precipitation tank;

[0010] The test mirror, the first cleaning inlet and the pure steam inlet, the sampling valve, the first chilled water inlet, and the second chilled water return port are installed in the middle of the outer part of the PEG precipitation tank;

[0011] The first sight glass lamp and the manhole, the first respirator, the material inlet, the first pressure sensor, the first pressure gauge, and the first radar level gauge are installed on the top of the PEG sedimentation tank;

[0012] The low shear magnetic stirring, antigen outlet, and first temperature sensor are installed at the outer bottom of the PEG precipitation tank;

[0013] The first baffle is closely attached to the inner wall of the PEG precipitation tank;

[0014] The high shear magnetic stirring, PEG transfer pipeline, and second temperature sensor are installed on the outer bottom of the PEG preparation tank;

[0015] The second chilled water inlet, the second chilled water return port, the industrial steam inlet, the second cleaning inlet and the pure steam inlet are installed in the middle of the outer part of the PEG preparation tank;

[0016] The industrial steam condensate row is installed between the second chilled water inlet and the PEG preparation tank;

[0017] The PEG solution feeding port, the second pressure sensor, the second pressure gauge, the second radar level gauge, the second sight glass lamp and the manhole, and the second respirator are installed on the outer top of the PEG preparation tank;

[0018] The second baffle is closely attached to the inner wall of the PEG preparation tank.

[0019] Preferably, the aseptic supernatant discarding device is composed of a float, a hose, a center rod, and a fulcrum;

[0020] The floating ball is installed on the central rod;

[0021] One end of the hose is fixed to the float, and the other end is fixed to the connection point between the hose and the 316L stainless steel pipe;

[0022] The upper and lower ends of the central rod are respectively fixed to the upper and lower heads of the PEG precipitation tank body;

[0023] The fulcrum is arranged on the central rod.

[0024] Preferably, the liquid inlet of the hose is on the same horizontal line as the float.

[0025] Preferably, the fulcrum is arranged on the central rod 10 cm away from the bottom of the PEG precipitation tank.

[0026] Preferably, a third cleaning inlet and a pure steam inlet are installed on the 316L stainless steel pipe connected to the hose.

[0027] Preferably, the first sight glass lamp and the manhole are composed of a trial lamp and a manhole, and the manhole is installed with tempered glass resistant to high temperature and high pressure, and the trial lamp emits light into the tank through the manhole.

[0028] Preferably, the PEG transfer pipeline connects the PEG preparation tank and the PEG precipitation tank, and the PEG transfer pipeline is at the same horizontal line as the sampling valve.

[0029] Preferably, the second sight glass lamp and the manhole are composed of a trial lamp and a manhole, and the manhole is installed with tempered glass resistant to high temperature and high pressure, and the trial lamp emits light into the tank through the manhole.

[0030] Preferably, the height-to-diameter ratio of the PEG precipitation tank is 1:1 to 1.2:1.

[0031] Preferably, the float and the center rod are made of 316L stainless steel, and the center hole diameter of the float is smaller than the outer diameter of the center rod.

[0032] Compared with the prior art, the utility model has the following beneficial effects:

[0033] (1) PEG precipitation has the best effect on antigens: The antigen precipitation effect is related to the height-to-diameter ratio of the PEG precipitation tank. The optimal height-to-diameter ratio is 1:1 to 1.2:1, which achieves the best precipitation effect.

[0034] (2) Improving antigen purity: After PEG precipitation of antigen, the supernatant contains impurities. The PEG precipitation tank uses a sterile supernatant discarding device to observe the stratification of precipitation and supernatant through the test mirror on the tank body, discard the supernatant, reduce the volume of processed antigen, purify only the precipitated antigen, and improve the antigen purity;

[0035] (3) Ensure sterility in all aspects: The PEG precipitation tank uses magnetic stirring under low shear force, and the PEG preparation tank uses magnetic stirring under high shear force. Compared with mechanical stirring, magnetic stirring can ensure sterility in the tank; the sterile supernatant discarding device can be sterilized online to ensure sterility of the device itself and the tank. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Other features, objects and advantages of the present invention will become more apparent by reading the detailed description of non-limiting embodiments with reference to the following drawings:

[0037] Figure 1 This is a schematic diagram of the equipment structure for industrial PEG precipitation of antigens;

[0038] Figure 2 It is a schematic diagram of the structure of the sterile supernatant discarding device;

[0039] Reference numerals:

[0040]

[0041] DETAILED DESCRIPTION

[0042] The utility model is described in detail below in conjunction with specific embodiments. The following embodiments will help those skilled in the art to further understand the utility model, but do not limit the utility model in any form. It should be pointed out that for those of ordinary skill in the art, several changes and improvements can be made without departing from the concept of the utility model. These all belong to the protection scope of the utility model.

[0043] Example

[0044] The utility model provides an industrial PEG antigen precipitation device, which ensures sterility in many aspects such as precise addition of PEG, regulation of the height-to-diameter ratio of the PEG precipitation tank, aseptic supernatant discarding device, equipment hardware, etc., effectively solves the shortcomings of current equipment and is a highly efficient and easy-to-operate industrial PEG antigen precipitation device.

[0045] The utility model provides an industrialized PEG antigen precipitation device, comprising: a sterile supernatant discarding device 1, a sight glass 2, a first sight glass lamp and a manhole 3, a first respirator 4, a material inlet 5, a first pressure sensor 6, a first pressure gauge 7, a first radar level gauge 8, a first cleaning inlet and a pure steam inlet 9, a sampling valve 10, a first chilled water inlet 11, a first chilled water return port 12, a low shear magnetic stirring 13, an antigen outlet 14, a first temperature sensor 15, a first baffle 16, a high shear magnetic stirring 17, and a PEG material transfer pipeline 18. , second temperature sensor 19, second chilled water inlet 20, second chilled water return port 21, industrial steam inlet 22, industrial steam condensate drain 23, PEG solution feeding port 24, second pressure sensor 25, second pressure gauge 26, second radar level gauge 27, second cleaning inlet and pure steam inlet 28, second sight glass lamp and manhole 29, second respirator 30, second baffle 31, float 32, hose 33, center rod 34, third cleaning inlet and pure steam inlet 35, fulcrum 36, hose and 316L stainless steel pipe connection point 37;

[0046] The sterile supernatant discarding device 1 is installed in the PEG precipitation tank;

[0047] The test mirror 2, the first cleaning inlet and the pure steam inlet 9, the sampling valve 10, the first chilled water inlet 11, and the first chilled water return port 12 are installed in the middle of the outer part of the PEG precipitation tank;

[0048] The first sight glass lamp and the manhole 3, the first respirator 4, the material inlet 5, the first pressure sensor 6, the first pressure gauge 7, and the first radar level gauge 8 are installed on the top of the PEG sedimentation tank;

[0049] The low shear magnetic stirring 13, the antigen outlet 14, and the first temperature sensor 15 are installed at the outer bottom of the PEG precipitation tank;

[0050] The first baffle 16 is closely attached to the inner wall of the PEG precipitation tank;

[0051] The high shear magnetic stirring 17, PEG transfer pipeline 18, and second temperature sensor 19 are installed on the outer bottom of the PEG preparation tank;

[0052] The second chilled water inlet 20, the second chilled water return port 21, the industrial steam inlet 22, the second cleaning inlet and the pure steam inlet 28 are installed in the middle of the outer part of the PEG preparation tank;

[0053] The industrial steam condensate row 23 is installed between the second chilled water inlet 20 and the PEG preparation tank;

[0054] The PEG solution feeding port 24, the second pressure sensor 25, the second pressure gauge 26, the second radar level gauge 27, the second sight glass lamp and the manhole 29, and the second respirator 30 are installed on the outer top of the PEG preparation tank;

[0055] The second baffle 31 is closely attached to the inner wall of the PEG preparation tank.

[0056] The aseptic supernatant discarding device 1 is composed of a float 32, a hose 33, a center rod 34, and a fulcrum 36;

[0057] The float 32 is mounted on a center rod 34;

[0058] One end of the hose 33 is fixed to the float 32, and the other end is fixed to the connection point 37 between the hose and the 316L stainless steel pipe, and the liquid inlet is on the same horizontal line as the float 32;

[0059] The center rod 34 is fixed to the upper and lower heads of the tank body;

[0060] The fulcrum 36 is arranged at a position 10 cm from the center rod 34 to the bottom of the tank;

[0061] The first sight glass lamp and manhole 3 are composed of a trial mirror lamp and a manhole. The manhole is provided with high temperature and high pressure resistant tempered glass. The trial mirror lamp emits light into the tank through the manhole. The trial mirror 2 is a high temperature and high pressure resistant tempered glass, which can be used to observe the sedimentation and stratification in the tank. The trial mirror 2 is installed on the tank wall;

[0062] The first respirator 4 is used for the intake of clean compressed air and exhaust of clean compressed air or pure steam of the PEG precipitation tank;

[0063] The material inlet 5, the antigen is transferred from the upstream to the inlet of the PEG precipitation tank;

[0064] The first pressure sensor 6 and the first pressure gauge 7 jointly monitor the pressure of the PEG precipitation tank to ensure that the pressure vessel is used safely and reliably;

[0065] The first radar level meter 8 measures the liquid level of the PEG sedimentation tank;

[0066] The first cleaning inlet and the pure steam inlet 9 are used to clean and sterilize the PEG precipitation tank;

[0067] The sampling valve 10 is used to sample the PEG precipitation tank;

[0068] The first chilled water inlet 11 and the first chilled water return port 12 control the temperature of the PEG precipitation tank;

[0069] The first temperature sensor 15 monitors the temperature of the PEG precipitation tank;

[0070] After the supernatant is discarded, the antigen is transferred to the next purification process through the antigen outlet 14.

[0071] When PEG and antigen need to be fully stirred, the magnetic stirring 13 under low shear force is turned on, and the direction of the liquid flow can be changed through the first baffle 16 to prevent the formation of vortex flow in the center of the liquid surface.

[0072] The third cleaning inlet and pure steam inlet 35 clean and sterilize the hose 33;

[0073] The PEG transfer pipeline 18 is a PEG transmission pipeline from the bottom of the PEG preparation tank to the PEG precipitation tank (on the same horizontal line as the sampling valve 10);

[0074] The second temperature sensor 19 monitors the temperature of the PEG preparation tank;

[0075] The second chilled water inlet 20 and the second chilled water return port 21 control the temperature of the PEG preparation tank;

[0076] The PEG solution feed port 24 is used to add PEG solution, and when the PEG is sterilized in the PEG preparation tank, the industrial steam is jacketed in through the industrial steam inlet 22, and the industrial steam condensate discharge 23 is used to discharge condensed water;

[0077] The second pressure sensor 25 and the second pressure gauge 26 jointly monitor the pressure of the PEG preparation tank to ensure that the pressure vessel is used safely and reliably;

[0078] The second radar level meter 27 measures the liquid level of the PEG preparation tank;

[0079] The second cleaning inlet and the pure steam inlet 28 are used to clean and sterilize the PEG preparation tank;

[0080] The second sight glass lamp and manhole 29 is composed of a trial lamp and a manhole, and the manhole is provided with high temperature and high pressure resistant tempered glass, and the trial lamp emits light into the tank through the manhole, and the operation condition in the tank can be observed;

[0081] The second respirator 30 is used for the clean compressed air intake and exhaust of clean compressed air or pure steam and the sterilized cold air exhaust of the PEG preparation tank;

[0082] PEG is sterilized in the PEG preparation tank. During the inactivation process, magnetic stirring 17 under high shear force needs to be turned on. The direction of the PEG solution can be changed by the second baffle 31 to prevent the formation of a vortex flow in the center of the liquid surface.

[0083] Working principle:

[0084] PEG precipitation tank structure: the first cleaning inlet and pure steam inlet 9 are the inlets of cleaning liquid and pure steam respectively; the antigen enters the tank through the antigen inlet 5; the tank pressure is monitored by the first pressure sensor 6 and the first pressure gauge 7 to ensure correctness; the tank liquid level is measured by the first radar level gauge 8; sampling is performed through the sampling valve 10; the tank and antigen temperatures are monitored by the temperature sensor 15 and controlled by the jacket first chilled water inlet 11 and the first chilled water return port 12; the PEG precipitation tank has a height-to-diameter ratio of 1:1 to 1.2:1, and the precipitation effect is the best. After PEG and antigen are fully stirred and uniformly precipitated by magnetic stirring 13 under low shear, the test mirror light is turned on, the test mirror 2 observes the solution stratification, the first respirator 4 is pressurized, and the sterile supernatant discarding device 1 discards the supernatant.

[0085] Aseptic supernatant discarding device 1: It is composed of a central rod 34, a floating ball 32, a hose 33, and a fulcrum 36; the central rod 34 is made of 316L stainless steel and is fixed to the upper and lower heads of the tank body; the hose 33 is a silicone hose, which is resistant to high temperatures, one end of which is fixed to the floating ball 32, and the other end is fixed to the connection point 37 between the hose and the 316L stainless steel pipe, and the liquid inlet is at the same horizontal line as the floating ball 32; the floating ball 32 is made of 316L stainless steel, and the central aperture is slightly smaller than the outer diameter of the central rod 34, and is installed on the central rod 34 to play a left and right fixing role; the central rod 34 has a fulcrum 36 10 cm away from the bottom of the tank, and when there is no antigen in the tank, the floating ball 32 is placed at the fulcrum 36; the floating ball 32 floats on the liquid surface in the tank and moves up and down with the liquid surface; the third cleaning inlet and the pure steam inlet 35 clean and sterilize the hose 33; the cleaning and sterilization of the floating ball 32 and the central rod 34 are completed by the first cleaning inlet and the pure steam inlet 9.

[0086] PEG preparation tank structure: the second cleaning inlet and pure steam inlet 28 are the inlets of cleaning liquid and pure steam respectively; PEG solution enters the tank body through the PEG solution feeding port 24; the tank body pressure is monitored jointly by the second pressure sensor 25 and the second pressure gauge 26; the tank body liquid level is measured by the second radar level gauge 27; the tank body and PEG temperature are monitored by the temperature sensor 19 and controlled by the jacket second chilled water inlet 20 and the second chilled water return port 21; PEG real tank sterilization is carried out through the jacket industrial steam inlet 22, and the jacket condensate is discharged through the industrial steam condensate drain 23.

[0087] In order to accurately add PEG, first prepare the required amount of PEG according to the amount of antigen, then measure it with the second radar level meter 27, and finally add PEG to the PEG precipitation tank through the PEG transfer pipeline 18. First add it to the PEG precipitation tank, and after it is fully stirred, transfer the antigen in the PEG precipitation tank to the PEG preparation tank to the same volume of PEG. After it is stirred again in the PEG preparation tank, transfer the antigen to the PEG precipitation tank for precipitation.

[0088] In the description of the present application, it should be understood that the terms "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present application.

[0089] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art can make various changes or modifications within the scope of the claims, which does not affect the essence of the present invention. In the absence of conflict, the embodiments of the present application and the features in the embodiments can be combined with each other at will.

Claims

1. An industrial PEG precipitation antigen device, characterized in that: include: Aseptic supernatant discarding device (1), first sight glass lamp and manhole (3), first respirator (4), material inlet (5), first cleaning inlet and pure steam inlet (9), sampling valve (10), first chilled water inlet (11), first chilled water return port (12), magnetic stirring under low shear (13), antigen outlet (14), first baffle (16), magnetic stirring under high shear (17), PEG material transfer pipeline (18), second chilled water inlet (20), second chilled water return port (21), industrial steam inlet (22), industrial steam condensate drain (23), PEG solution feeding port (24), second cleaning inlet and pure steam inlet (28), second sight glass lamp and manhole (29), second respirator (30), second baffle (31); The sterile supernatant discarding device (1) is installed in a PEG precipitation tank; The first cleaning inlet and pure steam inlet (9), the sampling valve (10), the first chilled water inlet (11), and the first chilled water return port (12) are installed in the middle of the outer part of the PEG precipitation tank; The first sight glass lamp, the manhole (3), the first respirator (4), and the material inlet (5) are installed on the outer top of the PEG precipitation tank; The low shear magnetic stirring (13) and the antigen outlet (14) are installed at the outer bottom of the PEG precipitation tank; The first baffle (16) is closely attached to the inner wall of the PEG precipitation tank; The high shear magnetic stirring (17) and the PEG transfer pipeline (18) are installed at the outer bottom of the PEG preparation tank; The second chilled water inlet (20), the second chilled water return port (21), the industrial steam inlet (22), the second cleaning inlet and the pure steam inlet (28) are installed in the middle of the outer part of the PEG preparation tank; The industrial steam condensate drain (23) is installed between the second chilled water inlet (20) and the PEG preparation tank; The PEG solution feed port (24), the second sight glass lamp and the manhole (29), and the second respirator (30) are installed on the outer top of the PEG preparation tank; The second baffle (31) is in close contact with the inner wall of the PEG preparation tank.

2. The equipment for industrial PEG precipitation of antigens according to claim 1, characterized in that: The aseptic supernatant discarding device (1) is composed of a floating ball (32), a hose (33), a central rod (34), and a fulcrum (36); The floating ball (32) is mounted on a central rod (34); One end of the hose (33) is fixed to the float (32), and the other end is fixed to the connection point (37) between the hose and the 316L stainless steel pipe; The upper and lower ends of the central rod (34) are respectively fixed to the upper and lower heads of the PEG precipitation tank body; The fulcrum (36) is arranged on the central rod (34).

3. The equipment for industrial PEG precipitation of antigens according to claim 2, characterized in that: Installing a test mirror (2), a first pressure sensor (6), a first pressure gauge (7), a first radar level gauge (8) and a first temperature sensor (15) on the PEG precipitation tank; A second temperature sensor (19), a second pressure sensor (25), a second pressure gauge (26) and a second radar level gauge (27) are installed on the PEG preparation tank.

4. The equipment for industrial PEG precipitation of antigens according to claim 2, characterized in that: The liquid inlet of the hose (33) and the float (32) are on the same horizontal line.

5. The equipment for industrial PEG precipitation of antigens according to claim 2, characterized in that: The fulcrum (36) is arranged on the central rod (34) at a distance of 10 cm from the bottom of the PEG precipitation tank.

6. The equipment for industrial PEG precipitation of antigens according to claim 2, characterized in that: A third cleaning inlet and a pure steam inlet (35) are installed on the 316L stainless steel pipe connected to the hose (33).

7. The equipment for industrial PEG precipitation of antigens according to claim 1, characterized in that: The first sight glass lamp and manhole (3) is composed of a trial mirror lamp and a manhole, and the manhole is equipped with high temperature and high pressure resistant tempered glass, and the trial mirror lamp emits light into the tank through the manhole; The second sight glass lamp and manhole (29) is composed of a trial lamp and a manhole, and the manhole is provided with high temperature and high pressure resistant tempered glass, and the trial lamp emits light into the tank through the manhole.

8. The equipment for industrial PEG precipitation of antigens according to claim 1, characterized in that: The PEG transfer pipeline (18) connects the PEG preparation tank and the PEG precipitation tank, and the PEG transfer pipeline (18) is on the same horizontal line as the sampling valve (10).

9. The equipment for industrial PEG precipitation of antigens according to claim 1, characterized in that: The height-to-diameter ratio of the PEG precipitation tank is 1:1 to 1.2:

1.

10. The equipment for industrial PEG precipitation of antigens according to claim 2, characterized in that: The floating ball (32) and the center rod (34) are made of 316L stainless steel, and the center hole diameter of the floating ball (32) is smaller than the outer diameter of the center rod (34).

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