Multi-inactivation device for biopharmacy

Abstract

The invention relates to the technical field related to biopharmacy, in particular to a biopharmacy multiple inactivation device which comprises a pretreatment module and a multiple inactivation module. The multi-inactivation module comprises a supporting piece located at the lower end of the pretreatment module, and a pulsed electric field inactivation unit, a thermal inactivation unit and an ozone oxidation inactivation unit which are arranged on the supporting piece and are distributed in a circumferential array; and a flow path switching mechanism. The pulse electric field inactivation unit, the thermal inactivation unit and the ozone oxidation inactivation unit are adopted, corresponding inactivation treatment is carried out according to different classifications of liquid medicine, the functions are diversified, and the inactivation mode is not limited to a single inactivation mode; the flow path of the liquid medicine can be switched through the flow path switching mechanism, so that the pretreated liquid medicine is hermetically connected with any one of the pulsed electric field inactivation unit, the thermal inactivation unit and the ozone oxidation inactivation unit through the supporting piece, and corresponding liquid medicine inactivation treatment is carried out by using one inactivation unit in the multiple inactivation module as required.

Description

Technical Field

[0001] This invention relates to the field of biopharmaceutical technology, and in particular to a multiple inactivation device for biopharmaceuticals. Background Technology

[0002] The statements herein provide only background information in relation to this invention and do not necessarily constitute prior art.

[0003] In the biopharmaceutical industry, the inactivation of contaminants such as viruses and microorganisms is a core step in ensuring drug safety, and is directly related to patient medication safety and drug quality stability.

[0004] Currently, most inactivation devices used in the biopharmaceutical field employ a single inactivation method (such as thermal inactivation, chemical inactivation, or ultraviolet inactivation), which presents significant technical challenges: First, the inactivation efficiency is limited, and a single method is insufficient to completely inactivate stubborn viruses (such as retroviruses) or drug-resistant microorganisms, easily resulting in "inactivation dead zones" and the risk of drug contamination; second, compatibility is poor, thermal inactivation easily damages the active structure of protein drugs (such as monoclonal antibodies and vaccines), and ultraviolet inactivation has weak penetration into drug solutions with low transparency, making it difficult to adapt to the inactivation requirements of different types of biopharmaceutical products. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings mentioned above by providing a multiple inactivation device for biopharmaceuticals.

[0006] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: a multiple inactivation device for biopharmaceuticals, comprising a pretreatment module for drug solution treatment and a multiple inactivation module connected to the pretreatment module for inactivating the drug solution and used as needed, the multiple inactivation module comprising a support member located at the lower end of the pretreatment module, a pulsed electric field inactivation unit, a thermal inactivation unit and an ozone oxidation inactivation unit disposed on the support member and arranged in a circumferential array; A flow path switching mechanism is disposed within the support member and is sealed to any one of the pulse electric field inactivation unit, the thermal inactivation unit, and the ozone oxidation inactivation unit. It is used to switch the flow path of the pretreatment module and one of the inactivation units in the multiple inactivation modules as needed and to inactivate the drug solution accordingly.

[0007] Furthermore, the support member includes an upper support block and a lower support block that are stacked on top of each other and rotate relative to each other; The flow path switching mechanism includes a liquid inlet channel disposed inside the upper support block and extending outward at an angle; three liquid inlet channels arranged in a circular array at the inlets of the pulse electric field inactivation unit, the thermal inactivation unit, and the ozone oxidation inactivation unit, respectively, disposed on the lower support block; a servo motor disposed at the center of the upper support block, extending through the lower support block and fixed to the bottom surface of the lower support block; and the output shaft of the servo motor is connected to the upper support block via a coupling. The servo motor is started, driving the upper support block to rotate relative to the lower support block, so that the bottom of the liquid inlet channel penetrating the upper support block is sealed to any of the liquid inlet channels of the corresponding pulse electric field inactivation unit, the thermal inactivation unit and the ozone oxidation inactivation unit on the lower support block, forming a sealed flow path for the liquid.

[0008] Furthermore, the lower support block has a cavity at its center that is not connected to the three liquid inlet channels; The flow path switching mechanism also includes a cam disk disposed in the cavity and coaxially sleeved with the output shaft of the servo motor, and a gas pushing component on the side wall of each of the liquid inlet channels. The cam disk rotates periodically and cooperates with the gas pushing component at the corresponding position to open the flow path on one of the liquid inlet channels and correspondingly close the airflow path on the liquid inlet channel. The airflow paths on the remaining two liquid inlet channels are opened synchronously.

[0009] Furthermore, the edge of the cam disk is processed into a specific contour shape according to the push-broom logic; The gas pushing assembly includes a support block located inside the cavity and fixed to the inner side of each of the liquid inlet channels; two vertical airflow straight pipes arranged parallel to each other inside the support block; the top ends of the two airflow straight pipes converge to form a common air inlet pipe; the outer end of the air inlet pipe is provided with an air source interface; a valve stem is horizontally arranged in the middle section of the two airflow straight pipes; a movable groove is provided outside the valve stem and inside the support block; a spring a connected to the valve stem is provided in the movable groove; two parallel airflow channels are provided on the valve stem and are equidistant from the two airflow straight pipes; the outer end of the valve stem contacts the edge of the cam disc; and an inclined vent pipe communicating with the interior of the liquid inlet channel is provided at the lower end of the airflow straight pipe that is close to and inside the liquid inlet channel. The cam disk rotates, pressing or resetting the valve stem through the contour of the cam disk, thereby controlling the opening and closing of the airflow passage in the inner airflow straight pipe.

[0010] Furthermore, the pretreatment module includes an outer support groove rotatably mounted on the upper support block and a filter assembly disposed within the outer support groove. The filter assembly includes a microporous filter membrane disposed within the outer support groove and a porous support layer located within the microporous filter membrane and used to support the microporous filter membrane. The microporous filter membrane is used to trap impurities and bacterial fragments in the drug solution, and a drug solution inlet is provided at the center of the bottom surface of the microporous filter membrane. The pore size of the porous support layer is larger than that of the microporous filter membrane, and the interior of the porous support layer is provided with multiple interconnected and penetrating channels.

[0011] Furthermore, the output shaft of the servo motor is provided with a power shaft connected to the bottom surface of the upper support block and having a hollow cavity. The lower end of the straight airflow pipe, which is away from the liquid inlet channel and located on the outside, is provided with an annular pipe at the edge of the bottom surface of the cavity. A through pipe extending into the power shaft is provided on one side of the annular pipe. An annular channel communicating with the hollow cavity is provided on the circumference of the power shaft. A support ring plate communicating with the through pipe is rotatably provided at the annular channel.

[0012] Furthermore, the upper end of the hollow tube inside the power shaft extends to the top of the upper support block, and the top of the upper support block is provided with a backflush assembly that connects the microporous filter membrane and the upper end of the hollow tube. The backflush assembly includes a support ring frame located on top of the upper support block, and a top frame rotatably mounted on the support ring frame and connected to the outer support groove. The support ring frame has a plurality of spray nozzles arranged in a circumferential array and connected to the hollow tube cavity. The top frame has a through-hole at its center that communicates with the liquid inlet. The top frame also has a groove arranged in a circumferential array corresponding to the number of spray nozzles. The inner end of each groove has an opening for discharging the pre-treated liquid into the upper end of the liquid inlet channel.

[0013] Furthermore, the lower support block is also provided with spherical protrusions corresponding to the positions of the liquid inlet channels, and the bottom surface of the upper support block is provided with an annular semicircular track for the smooth passage of the spherical protrusions. An indicator frame that cooperates with the spherical protrusions is provided on one side of the top surface of the annular semicircular track, and springs b are provided on both sides of the indicator frame connected inside the upper support block.

[0014] Furthermore, the outlet side of the pulsed electric field inactivation unit is connected to the inlet side of the thermal inactivation unit via a conduit.

[0015] Furthermore, the top surface of the lower support block is provided with an opening that is inclined towards the upper opening of the liquid medicine inlet channel for guiding the flow.

[0016] The beneficial effects of this invention are reflected in: The pulsed electric field inactivation unit, thermal inactivation unit, and ozone oxidation inactivation unit employed in this invention perform corresponding inactivation treatments for different categories of drug solutions, offering diverse functions and not limited to a single inactivation mode. Furthermore, through a flow path switching mechanism, the flow path of the drug solution can be switched so that the pretreated drug solution is sealed and connected to any one of the pulsed electric field inactivation unit, thermal inactivation unit, or ozone oxidation inactivation unit via a support component, allowing for the use of one inactivation unit from the multiple inactivation modules to perform the corresponding drug solution inactivation treatment as needed. Attached Figure Description

[0017] Figure 1 This is a perspective view of the overall structure of an embodiment of the present invention. Figure 2 This is a partial cross-sectional view of an embodiment of the present invention; Figure 3 This is a partial cross-sectional view of a support member according to an embodiment of the present invention; Figure 4 This is a top plan sectional view of the lower support block according to an embodiment of the present invention; Figure 5 This is a front half-sectional view of a support member according to an embodiment of the present invention; Figure 6 for Figure 5 Enlarged view at point A in the middle; Figure 7 This is a perspective view of a microporous filter membrane according to an embodiment of the present invention. Figure 8 This is a perspective view of a microporous filter membrane according to an embodiment of the present invention. Figure 9 This is a top plan sectional view of a porous support layer according to an embodiment of the present invention; Figure 10 This is a perspective view of a backflush assembly according to an embodiment of the present invention; Figure 11 This is a perspective view of the top frame according to an embodiment of the present invention.

[0018] In the picture: 1. Pretreatment module; 11. Outer support groove; 12. Microporous filter membrane; 13. Porous support layer; 131. Pore; 2. Support component; 21. Upper support block; 211. Annular semi-circular track; 22. Lower support block; 221. Cavity; 3. Pulsed electric field inactivation unit; 4. Thermal inactivation unit; 5. Ozone oxidation inactivation unit; 6. Flow path switching mechanism; 61. Drug inlet channel; 62. Drug inlet channel; 63. Servo motor; 631. Power shaft; 631 1. Support ring plate; 64. Cam plate; 65. Gas pusher assembly; 651. Support vertical block; 652. Straight airflow pipe; 653. Inlet pipe; 654. Valve stem; 6541. Airflow channel; 655. Movable groove; 656. Ventilation pipe; 66. Ring pipe; 661. Through pipe; 7. Backflush assembly; 71. Support ring frame; 711. Spray nozzle; 72. Top frame; 721. Groove; 8. Spherical protrusion; 81. Indicator frame; 9. Inlet. Detailed Implementation

[0019] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Unless otherwise specified, the embodiments and features in the embodiments of this application can be combined with each other. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] Please see Figure 1-11 This invention discloses a multi-stage inactivation device for biopharmaceuticals, comprising a pretreatment module 1 for drug solution treatment and a multi-stage inactivation module connected to the pretreatment module 1 for inactivating the drug solution and used as needed. The multi-stage inactivation module includes a support member 2 located at the lower end of the pretreatment module 1, a pulsed electric field inactivation unit 3, a thermal inactivation unit 4, and an ozone oxidation inactivation unit 5 arranged in a circular array on the support member 2. The flow path switching mechanism 6 is disposed within the support member 2 and is sealed to any one of the pulse electric field inactivation unit 3, the thermal inactivation unit 4, and the ozone oxidation inactivation unit 5. It is used to switch the flow path of the pretreatment module 1 and one of the inactivation units in the multiple inactivation modules as needed and to inactivate the drug solution accordingly.

[0021] In practice, the pretreatment module 1 and the support component 2 are assembled and stacked sequentially from top to bottom. The pulse electric field inactivation unit 3, the thermal inactivation unit 4, and the ozone oxidation inactivation unit 5 are arranged in a circular array on the support component 2. The flow path switching mechanism 6 installed in the support component 2 can switch the flow path of the drug solution so that the pretreated drug solution passes through the support component 2 and is sealed to any one of the inactivation units of the pulse electric field inactivation unit 3, the thermal inactivation unit 4, and the ozone oxidation inactivation unit 5. This allows for the use of one inactivation unit from the multiple inactivation modules to perform the corresponding drug solution inactivation treatment as needed, achieving the switching of different inactivation modes. The operation is simple.

[0022] It should be noted that the pulsed electric field inactivation unit 3 adopts a parallel plate electrode structure, with the electrode material being 316L stainless steel. It can output a high-voltage pulsed electric field with an intensity of 10-80kV / cm and a pulse width of 1-100μs, achieving inactivation by disrupting the cell membrane potential of microorganisms and the capsid structure of viruses. The electrode spacing can be adjusted according to the drug flow rate (0.5-5cm adjustable) to ensure that the electric field uniformly covers the drug solution. The heat inactivation unit 4 uses a shell-and-tube heat exchanger to gently heat the drug solution with circulating hot water (the water temperature can be precisely controlled within the range of 56-121℃, with a temperature control accuracy of ±0.3℃). At the same time, a stir bar (adjustable speed of 50-300rpm) is set to ensure uniform temperature of the drug solution and avoid local overheating. The heating time can be set by the intelligent control module (adjustable from 1-60min) to adapt to the heat sensitivity of different viruses. The ozone oxidation inactivation unit 5 is equipped with a low-temperature plasma ozone generator (ozone output adjustable from 0.1 to 5 g / h). The ozone is uniformly integrated into the drug solution in the form of microbubbles (bubble diameter 10-50 μm) through a gas distributor. The strong oxidizing properties of ozone destroy viral nucleic acid and microbial enzyme systems. At the same time, an ozone concentration monitoring sensor (detection range 0-50 mg / L) is set up to adjust the ozone flow rate in real time and avoid excessive ozone leading to drug oxidation.

[0023] Additional notes: The pulsed electric field inactivation unit 3, the thermal inactivation unit 4, and the ozone oxidation inactivation unit 5 are subsequently equipped with conventionally used liquid treatment modules, including but not limited to residue detection modules, for the detection and feedback of the liquid.

[0024] In one embodiment, the support member 2 includes an upper support block 21 and a lower support block 22 that are stacked on top of each other and rotate relative to each other; The flow path switching mechanism 6 includes a liquid inlet channel 61 disposed inside the upper support block 21 and extending outward at an angle; three liquid inlet channels 62 arranged in a circular array at the inlets of the pulse electric field inactivation unit 3, the thermal inactivation unit 4 and the ozone oxidation inactivation unit 5, disposed on the lower support block 22; a servo motor 63 disposed at the center of the upper support block 21, extending through the lower support block 22 and fixed to the bottom surface of the lower support block 22; and the output shaft of the servo motor 63 is connected to the upper support block 21 via a coupling. The servo motor 63 is started, driving the upper support block 21 to rotate relative to the lower support block 22, so that the bottom of the liquid inlet channel 61 passing through the upper support block 21 is sealed to any of the liquid inlet channels 62 of the corresponding pulse electric field inactivation unit 3, the thermal inactivation unit 4 and the ozone oxidation inactivation unit 5 on the lower support block 22, forming a sealed flow path for the liquid. This design employs an upper support block 21 and a lower support block 22 that are stacked on top of each other and rotate relative to each other. A servo motor 63 is installed at the center of the bottom surface of the lower support block 22. The output shaft of the servo motor 63 passes through the lower support block 22 and connects to the upper support block 21. When the servo motor 63 is started, it drives the upper support block 21 to rotate relative to the lower support block 22. This causes the bottom opening of the liquid inlet channel 61, which is inclined outward from the inside of the upper support block 21, to connect with one of the liquid inlet channels 62 distributed in the circumferential array on the lower support block 22, which correspond to the pulse electric field inactivation unit 3, the thermal inactivation unit 4, and the ozone oxidation inactivation unit 5, respectively, forming a closed path for the liquid. This allows for switching of the liquid flow path and, in conjunction with the pulse electric field inactivation unit 3, the thermal inactivation unit 4, and the ozone oxidation inactivation unit 5, switches the inactivation mode for different types of liquids.

[0025] It should be noted that the servo motor 63 consists of three parts: the servo motor body, the encoder, and the driver. Its working principle is that the driver receives "position command pulses" from the controller (such as a PLC or microcontroller) and drives the motor to rotate. The encoder at the rear of the motor feeds back the actual position to the driver in real time. The driver compares the command position with the actual position and continuously adjusts the current and voltage to eliminate errors until the target position is reached and stabilized, thus driving the upper support block 21 to rotate to the designated position.

[0026] In one embodiment, the lower support block 22 has a cavity 221 at its center that is not connected to the three liquid inlet channels 62; The flow path switching mechanism 6 also includes a cam disk 64 disposed in the cavity 221 and coaxially sleeved with the output shaft of the servo motor 63, and a gas pushing component 65 on the side wall of each of the liquid inlet channels 62. The cam disk 64 rotates periodically and cooperates with the gas pushing component 65 at the corresponding position to open the flow path on one of the liquid inlet channels 62, thereby correspondingly closing the airflow path on that liquid inlet channel 62. The airflow paths on the remaining two liquid inlet channels 62 are opened synchronously. In this design, a cavity 221 is machined and reserved in the lower support block 22, and the cam disk 64 and the gas pushing component 65 are coaxially fixed on the output shaft of the servo motor 63. The cam disk 64 rotates with the servo motor 63 and cooperates with the gas pushing component 65 to open the flow path on one liquid inlet channel 62, thereby correspondingly closing the airflow path on that liquid inlet channel 62. The airflow paths on the remaining two liquid inlet channels 62 are opened synchronously.

[0027] In one embodiment, the edge of the cam disk 64 is machined into a specific contour shape according to the push-broom logic; The gas inlet assembly 65 includes a support block 651 located within the cavity 221 and fixed to the inner side of each of the liquid inlet channels 62; two vertical airflow straight pipes 652 arranged parallel to each other within the support block 651; a common air inlet pipe 653 is provided at the top ends of the two airflow straight pipes 652; an air source interface is provided at the outer end of the air inlet pipe 653; and a valve stem 654 is horizontally arranged in the middle section of the two airflow straight pipes 652. The support vertical block 651 is provided with a movable groove 655 inside. A spring a connected to the valve stem 654 is provided in the movable groove 655. The valve stem 654 is provided with two parallel airflow channels 6541 that are equidistant from the two airflow straight pipes 652. The outer end of the valve stem 654 contacts the edge of the cam disk 64. The lower end of the airflow straight pipe 652, which is close to the medicine inlet channel 62 and located on the inner side, is provided with an inclined vent pipe 656 that communicates with the inside of the medicine inlet channel 62. The rotation of the cam disk 64 presses or resets the valve stem 654 via its contour, controlling the opening and closing of the airflow passage of the inner airflow straight pipe 652. This design utilizes support blocks 651 welded to the inner sides of the corresponding drug inlet channels 62, and two vertically parallel airflow straight pipes 652 connected to each support block 651. The top ends of the two airflow straight pipes 652 converge and connect to the same air inlet pipe 653. Inert gas is simultaneously introduced into the two airflow straight pipes 652 through the air source interface at the outer end of the air inlet pipe 653. Since the gas supply process occurs during the early stage of drug inactivation, the passage of the corresponding inactivation unit is switched as needed. When the servo motor 63 drives the upper support block 21 to complete the passage switching, the cam disk 64, coaxially fixed on the output shaft of the servo motor 63, rotates accordingly. The recessed part of the outer contour edge of the cam disk 64 will contact the valve stem 654 at the selected corresponding inactivation unit, reset the valve stem 654 at that location, disconnect the air supply passage of the inner airflow straight pipe 652, and the valve stems 654 at the remaining two inactivation unit positions will be pressed into the protrusions on the edge of the cam disk 64, connecting the inner airflow straight pipe 652 with the airflow channel 6541 opened on the inner side of the valve stem 654, so that the air supply passage of the inner airflow straight pipe 652 is opened, "pushing" the liquid in the connecting pipe inside the corresponding inactivation unit towards the mainstream direction, entering the next stage or collection tank, so as to clean the connecting pipe inside the inactive inactivation unit and start a good post-cleaning procedure.

[0028] It should be noted that the lower end of the straight airflow pipe 652 located on the inner side is inclined and smoothly connected to the ventilation pipe 656, which is connected to the connecting pipe inside the liquid inlet channel 62 in the corresponding inactivation unit, and can push inert gas to clean the connecting pipe.

[0029] Nitrogen can be used as the inert gas; The gas source interface can be connected to an external nitrogen pipeline or gas supply equipment in the plant area.

[0030] In one embodiment, the pretreatment module 1 includes an outer support groove 11 rotatably disposed on the upper support block 21 and a filter assembly disposed within the outer support groove 11. The filter assembly includes a microporous filter membrane 12 disposed within the outer support groove 11 and a porous support layer 13 located within the microporous filter membrane 12 and used to support the microporous filter membrane 12. The microporous filter membrane 12 is used to intercept impurities and bacterial fragments in the drug solution, and a drug solution inlet is provided at the center of the bottom surface of the microporous filter membrane 12. The porous support layer 13 has a larger pore size than the microporous filter membrane 12, and the porous support layer 13 has multiple interconnected and penetrating channels 131 inside. This design, with the outer support groove 11 rotating relative to the slot on the upper support block 21, and the microporous filter membrane 12 horizontally installed within the outer support groove 11 and the porous support layer 13 contained within the microporous filter membrane 12, allows the microporous filter membrane 12 to effectively trap impurities and bacterial fragments in the drug solution. The porous support layer 13 provides mechanical support to the microporous filter membrane 12, preventing the extremely thin membrane from rupturing under pressure. Simultaneously, its open channels 131 greatly reduce fluid resistance.

[0031] It should be noted that the microporous filter membrane 12 is made of polyethersulfone, and the ether bonds and sulfonyl groups in its main chain give it good water flux, eliminating the need for surface hydrophilic modification, reducing the risk of extraction, and exhibiting excellent chemical and thermal stability.

[0032] In one embodiment, the output shaft of the servo motor 63 is provided with a power shaft 631 connected to the bottom surface of the upper support block 21 and having a hollow cavity. The lower end of the straight airflow pipe 652, which is away from the liquid inlet channel 62 and located on the outside, is provided with an annular pipe 66 at the edge of the bottom surface of the cavity 221. A through pipe 661 extending into the power shaft 631 is provided on one side of the annular pipe 66. The circumferential surface of the power shaft 631 is provided with an annular channel communicating with the hollow cavity. A support ring plate 6311 communicating with the through pipe 661 is rotatably provided at the annular channel. With this design, the lower end of the hollow cavity inside the power shaft 631 installed on the servo motor 63 is connected to the annular channel, and the support ring plate 6311 with grooves on the outer periphery of the annular channel and the hole opened on the support ring plate 6311 are connected to the inside of the through pipe 661. After the gas flows through the straight airflow pipe 652 located outside the liquid inlet channel 62, it enters the annular pipe 66 and is delivered to the hollow cavity through the through pipe 661, opening a new passage.

[0033] In one embodiment, the upper end of the hollow tube inside the power shaft 631 extends to the top of the upper support block 21, and the top of the upper support block 21 is provided with a backflush assembly 7 that connects the microporous filter membrane 12 and the upper end of the hollow tube. The backflush assembly 7 includes a support ring frame 71 located on top of the upper support block 21, and a top frame 72 rotatably mounted on the support ring frame 71 and connected to the outer support groove 11. The support ring frame 71 is circumferentially arranged with a plurality of spray nozzles 711 connected to the hollow cavity. The top frame 72 is provided with a through-hole communicating with the liquid inlet at its center. The top frame 72 is also circumferentially arranged with a number of slots 721 corresponding to the number of spray nozzles 711. The inner end of each slot 721 is provided with an opening for discharging the pre-treated liquid to the upper end of the liquid inlet channel 61. This design, through the support ring frame 71 installed with a groove on the top surface of the upper support block 21 and the top frame 72 welded to the bottom surface of the outer support groove 11, allows the outer support groove 11 to rotate relative to the upper support block 21, causing the multiple slots 721 in the circumferential array on the top frame 72 to be misaligned with the multiple spray nozzles 711 installed with a groove on the support ring frame 71. This enables the pre-treated liquid to be smoothly discharged downwards during the normal inactivation process of the liquid, while protecting the spray nozzles 711 from liquid entry. On the other hand, the rotation of the outer support groove 11 relative to the upper support block 21 causes the multiple slots 721 in the circumferential array on the top frame 72 to overlap with the multiple spray nozzles 711 installed with a groove on the support ring frame 71. At this time, during the cleaning of the connecting pipes inside the inactivation unit by pushing in gas, the liquid is simultaneously discharged from the spray nozzles 711 and passes through the channels 131 on the porous support layer 13 installed inside the microporous filter membrane 12 to back-flush and clean the impurities trapped in the pores of the microporous filter membrane 12.

[0034] In one embodiment, the lower support block 22 is further provided with spherical protrusions 8 corresponding to the positions of the liquid inlet channels 62, and the bottom surface of the upper support block 21 is provided with an annular semicircular track 211 for the spherical protrusions 8 to pass smoothly. An indicator frame 81 that cooperates with the spherical protrusions 8 is provided on one side of the inner top surface of the annular semicircular track 211, and springs b connected to the upper support block 21 are provided on both sides of the indicator frame 81. With this design, the spherical protrusions 8 installed on one side of the open side of each liquid inlet channel 62 on the lower support block 22, and the annular semicircular track 211 with grooves on the bottom surface of the upper support block 21 for the rotation of the spherical protrusions 8, after the upper support block 21 rotates to switch the corresponding liquid inlet channel, the spherical protrusions 8 installed at the corresponding channel position will contact the indicator frame 81 welded by spring b installed in the groove on the top surface of the annular semicircular track 211, and push the indicator frame 81 upward. At this time, the operator can know from the outside which of the pulse electric field inactivation unit 3, thermal inactivation unit 4, and ozone oxidation inactivation unit 5 is sealed to the liquid inlet channel 61 opened in the upper support block 21.

[0035] In one embodiment, the outlet side of the pulsed electric field inactivation unit 3 is connected to the inlet side of the thermal inactivation unit 4 via a conduit. This design, using a conduit to connect the outlet side of the pulsed electric field inactivation unit 3 to the inlet side of the thermal inactivation unit 4, enables protein drugs to undergo dual treatment of pulsed electric field inactivation and thermal inactivation sequentially, resulting in good inactivation effect.

[0036] It should be noted that ozone oxidation inactivation unit 5 is adapted for inactivation treatment of small molecule drugs; Solenoid valves are installed at both ends of the corresponding pulse electric field inactivation unit 3 and thermal inactivation unit 4 on the conduit to control the flow or cut-off of the conduit.

[0037] In one embodiment, the top surface of the lower support block 22 is provided with a spout 9 that is inclined to guide the liquid into the upper opening of the liquid inlet channel 61. With this design, the liquid can be gathered towards the upper opening of the centrally installed liquid inlet channel 62 and inclined out along the upper slope of the spout 9 by the spout 9 installed in a slot on the top surface of the lower support block 22.

[0038] The electrical components described in this article are controlled automatically by a controller. The controller circuit can be implemented by a person skilled in the art through simple programming. The power supply is also common knowledge in the field. Furthermore, since this application is mainly used to protect mechanical devices, the control method and circuit connection will not be explained in detail here.

[0039] It should be noted that if the embodiments of the present invention involve directional indicators (such as up, down, left, right, front, back, etc.), the directional indicators are only used to explain the relative positional relationship and movement of the components in a certain specific posture (as shown in the figure). If the specific posture changes, the directional indicators will also change accordingly.

[0040] Furthermore, if the embodiments of this invention involve descriptions such as "first" or "second," these descriptions are for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined with "first" or "second" may explicitly or implicitly include at least one of those features. Additionally, the technical solutions of the various embodiments can be combined with each other, but this must be based on the ability of those skilled in the art to implement them. If the combination of technical solutions is contradictory or impossible to implement, it should be considered that such a combination of technical solutions does not exist and is not within the scope of protection claimed by this invention.

[0041] Additionally, "multiple" refers to two or more.

[0042] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A multiple inactivation device for biopharmaceuticals, characterized in that: It includes a pretreatment module (1) for treating the drug solution and a multi-stage inactivation module connected to the pretreatment module (1) for inactivating the drug solution and used as needed. The multi-stage inactivation module includes a support member (2) located at the lower end of the pretreatment module (1), a pulse electric field inactivation unit (3), a thermal inactivation unit (4) and an ozone oxidation inactivation unit (5) arranged on the support member (2) in a circular array. The flow path switching mechanism (6) is disposed in the support (2) and is sealed to any one of the pulse electric field inactivation unit (3), the thermal inactivation unit (4) and the ozone oxidation inactivation unit (5). It is used to switch the path of the pretreatment module (1) and one of the inactivation units in the multiple inactivation modules as needed and to inactivate the drug solution accordingly.

2. The multiple inactivation device for biopharmaceutical manufacturing according to claim 1, characterized in that: The support member (2) includes an upper support block (21) and a lower support block (22) that are stacked on top of each other and rotate relative to each other. The flow path switching mechanism (6) includes a liquid inlet channel (61) disposed in the upper support block (21) and extending outward at an angle; three liquid inlet channels (62) arranged in a circular array are disposed on the lower support block (22) and corresponding to the inlets of the pulse electric field inactivation unit (3), the thermal inactivation unit (4) and the ozone oxidation inactivation unit (5); a servo motor (63) is disposed at the center of the upper support block (21) and extends through the lower support block (22) and is fixed on the bottom surface of the lower support block (22); the output shaft of the servo motor (63) is connected to the upper support block (21) via a coupling. Start the servo motor (63) to drive the upper support block (21) to rotate relative to the lower support block (22), so that the bottom of the liquid inlet channel (61) passing through the upper support block (21) is sealed to any of the liquid inlet channels (62) of the corresponding pulse electric field inactivation unit (3), thermal inactivation unit (4) and ozone oxidation inactivation unit (5) on the lower support block (22) and forms a sealed flow path for the liquid.

3. The multiple inactivation device for biopharmaceutical manufacturing according to claim 2, characterized in that: The lower support block (22) has a cavity (221) at its center that is not connected to the three liquid inlet channels (62). The flow path switching mechanism (6) further includes a cam disk (64) disposed in the cavity (221) and coaxially sleeved with the output shaft of the servo motor (63) and a gas pushing assembly (65) on the side wall of each of the liquid inlet channels (62). The cam disk (64) rotates periodically and cooperates with the gas pusher assembly (65) at the corresponding position to open the flow path on one of the liquid inlet channels (62) and close the airflow path on the liquid inlet channel (62) accordingly. The airflow paths on the remaining two liquid inlet channels (62) are opened synchronously.

4. The multiple inactivation device for biopharmaceutical manufacturing according to claim 3, characterized in that: The edge of the cam disk (64) is processed into a specific contour shape according to the push-broom logic; The gas inlet assembly (65) includes a support block (651) located within the cavity (221) and fixed to the inner side of each of the liquid inlet channels (62); two vertical airflow straight pipes (652) arranged parallel to each other within the support block (651); a common air inlet pipe (653) is provided at the top ends of the two airflow straight pipes (652); an air source interface is provided at the outer end of the air inlet pipe (653); a valve stem (654) is horizontally arranged in the middle section of the two airflow straight pipes (652); and the valve stem (654) is located outside the... The support vertical block (651) is provided with a movable groove (655), and a spring a connected to the valve stem (654) is provided in the movable groove (655). The valve stem (654) is provided with two parallel airflow channels (6541) that are equidistant from the two airflow straight pipes (652). The outer end of the valve stem (654) is in contact with the edge of the cam disk (64). The lower end of the airflow straight pipe (652) which is close to the liquid inlet channel (62) and located on the inner side is provided with an inclined vent pipe (656) that communicates with the inside of the liquid inlet channel (62). The cam disk (64) rotates, and the valve stem (654) is pressed into or reset by the contour of the cam disk (64), thereby controlling the opening and closing of the airflow passage of the airflow straight pipe (652) located on the inner side.

5. The multiple inactivation device for biopharmaceutical manufacturing according to claim 1, characterized in that: The pretreatment module (1) includes an outer support groove (11) rotatably mounted on the upper support block (21) and a filter assembly disposed in the outer support groove (11). The filter assembly includes a microporous filter membrane (12) disposed in the outer support groove (11) and a porous support layer (13) located in the microporous filter membrane (12) and used to support the microporous filter membrane (12). The microporous filter membrane (12) is used to intercept impurities and bacterial fragments in the drug solution. A drug solution inlet is provided at the center of the bottom surface of the microporous filter membrane (12). The pore size of the porous support layer (13) is larger than that of the microporous filter membrane (12), and the porous support layer (13) has multiple interconnected and penetrating channels (131) inside.

6. The multiple inactivation device for biopharmaceutical manufacturing according to claim 4, characterized in that: The output shaft of the servo motor (63) is provided with a power shaft (631) connected to the bottom surface of the upper support block (21) and having a hollow cavity. The lower end of the straight airflow pipe (652) located away from the liquid inlet channel (62) and on the outside is provided with an annular pipe (66) at the edge of the bottom surface of the cavity (221). A through pipe (661) extending into the power shaft (631) is provided on one side of the annular pipe (66). The circumferential surface of the power shaft (631) is provided with an annular channel communicating with the hollow cavity. A support ring plate (6311) communicating with the through pipe (661) is rotatably provided at the annular channel.

7. A multiple inactivation device for biopharmaceutical manufacturing according to claim 6 or 5, characterized in that: The upper end of the hollow tube inside the power shaft (631) extends to the top of the upper support block (21), and the top of the upper support block (21) is provided with a backflush assembly (7) that connects the microporous filter membrane (12) and the upper end of the hollow tube. The backflush assembly (7) includes a support ring frame (71) located on top of the upper support block (21) and a top frame (72) rotatably mounted on the support ring frame (71) and connected to the outer support groove (11). The support ring frame (71) is provided with a plurality of spray nozzles (711) connected to the hollow tube in a circumferential array. The top frame (72) is provided with a through-hole communicating with the liquid inlet in the center. The top frame (72) is also provided with a groove (721) in a circumferential array corresponding to the number of spray nozzles (711). Each groove (721) has an opening at its inner end, which is used to open and discharge the pre-treated liquid to the upper end of the liquid inlet channel (61).

8. The multiple inactivation device for biopharmaceutical manufacturing according to claim 2, characterized in that: The lower support block (22) is also provided with spherical protrusions (8) corresponding to the positions of the liquid inlet channels (62). The bottom surface of the upper support block (21) is provided with an annular semicircular track (211) for the spherical protrusions (8) to pass smoothly. An indicator frame (81) that cooperates with the spherical protrusions (8) is provided on one side of the inner top surface of the annular semicircular track (211). Springs b are provided on both sides of the indicator frame (81) and connected inside the upper support block (21).

9. The multiple inactivation device for biopharmaceutical manufacturing according to claim 1, characterized in that: The outlet side of the pulse electric field inactivation unit (3) is connected to the inlet side of the thermal inactivation unit (4) through a conduit.

10. The multiple inactivation device for biopharmaceutical manufacturing according to claim 2, characterized in that: The top surface of the lower support block (22) is provided with a hopper (9) that is inclined to guide the flow towards the upper end of the liquid inlet channel (61).

Images