Virus inactivation method for liquid biological product

Abstract

A continuous virus inactivation method for a liquid biological product. A virus inactivation device is used to perform virus inactivation on a liquid biological product. The virus inactivation device comprises a feeding part, a centrifugal part, and a discharging part. The centrifugal part is provided with an ultraviolet lamp (23). The liquid biological product is continuously introduced into the centrifugal part through the feeding part; the liquid biological product is thinned by means of the centrifugal effect to form a liquid layer having a thickness of 0.01-0.2 cm; the ultraviolet lamp (23) is used to perform virus inactivation by means of ultraviolet irradiation; the liquid biological product subjected to the virus inactivation is continuously discharged from the centrifugal part to the discharging part by means of the centrifugal effect, and is discharged from the virus inactivation device through the discharging part; the retention time of the liquid biological product in the centrifugal part is controlled to be 5-60 s; the irradiation intensity of the ultraviolet lamp (23) is 500-10,000 μW / cm2, and the irradiation wavelength of the ultraviolet lamp (23) is 254-280 nm.

Description

Method for virus inactivation of liquid biological products TECHNICAL FIELD

[0001] The present application belongs to the technical field of virus inactivation, and particularly relates to a method for virus inactivation of liquid biological products. BACKGROUND

[0002] In the biotechnology industry, with the gradual increase of various biological products, the use of people is expanding, and the risk of animal-derived virus infection of humans and potential nosocomial infection is increasingly prominent. The Drug Registration Management Method requires that biological products increase virus inactivation process verification data. Virus inactivation / removal verification research should use a method that simulates the production process, and should try to design a virus inactivation / removal verification research plan that is related to the actual production process and reasonable.

[0003] Traditional virus inactivation / removal processes include low-pH methods, organic solvent / detergent (S / D) methods, nanofiltration methods, chromatography methods, and pasteurization methods. These methods more or less have the disadvantages of high cost, good effect on lipid envelope viruses only, genetic toxicity, and optimal inactivation conditions changing with the composition of biological products. Compared with the above methods, ultraviolet disinfection is a pure physical disinfection method, which has the advantages of simplicity, convenience, broad-spectrum efficiency, no secondary pollution, easy management, and automation. The principle of ultraviolet disinfection is to use ultraviolet light to cause abnormal chemical bonds between adjacent pyrimidine molecules in viral DNA or RNA, thereby hindering the replication of DNA or RNA, and achieving virus inactivation.

[0004] However, ultraviolet disinfection has been widely used in disinfection of tap water and space, but its application in the field of biological products is not very common. According to the traditional method, when directly using ultraviolet light to irradiate the biological products, the biological products (such as proteins) themselves have an optical absorption coefficient, which will absorb part of the ultraviolet light. Therefore, only the virus inactivation effect of the surface layer of the biological products is good. With the increase of the amount of biological products, the liquid layer thickness receiving ultraviolet irradiation is larger, and the virus inactivation effect is poorer. Even if the stirring operation is increased, it will not bring much improvement. In addition, the larger the liquid layer thickness, the longer the ultraviolet irradiation time, and the effective substances of the upper layer of the biological products will be wasted due to excessive ultraviolet irradiation. Moreover, the above traditional method is not suitable for virus inactivation of large-scale biological products in the production process. When developing a virus inactivation method suitable for large-scale biological products in the production process, not only the virus inactivation effect and the degree of biological product activity loss need to be considered, but also the inactivation efficiency and energy consumption need to be considered, so as to achieve the purpose of obtaining better inactivation effect at lower cost. SUMMARY

[0005] The problem to be solved by the present application is to provide a continuous liquid biological product virus inactivation method.

[0006] To solve the above technical problems, the present application adopts the following technical solutions:

[0007] The present application provides a virus inactivation method for liquid biological products, which does not use nucleic acid as an effective component. The method uses a virus inactivation device to inactivate viruses in the liquid biological products. The virus inactivation device includes a feeding part, a centrifugal part, and a discharging part. The centrifugal part is equipped with an ultraviolet lamp. The liquid biological products are continuously fed into the centrifugal part through the feeding part. Under the action of centrifugation, the liquid biological products are thinned to a liquid layer thickness of 0.01 cm to 0.2 cm (for example, 0.01 cm, 0.02 cm, 0.03 cm, 0.04 cm, 0.05 cm, 0.06 cm, 0.07 cm, 0.08 cm, 0.09 cm, 0.1 cm, 0.11 cm, 0.12 cm, 0.13 cm, 0.14 cm, 0.15 cm, 0.16 cm, 0.17 cm, 0.18 cm, 0.19 cm, 0.2 cm). At the same time, the liquid biological products are inactivated by ultraviolet irradiation through the ultraviolet lamp. The liquid biological products after virus inactivation are continuously discharged from the centrifugal part to the discharging part under the action of centrifugation. The liquid biological products are discharged from the virus inactivation device through the discharging part. The retention time of the liquid biological products in the centrifugal part is controlled to be 5 to 60 seconds (for example, 5 seconds, 10 seconds, 15 seconds, 20 seconds, 25 seconds, 30 seconds, 35 seconds, 40 seconds, 45 seconds, 50 seconds, 55 seconds, 60 seconds). The irradiation intensity of the ultraviolet lamp is 500 to 10000 μW / cm 2 (for example, 500 μW / cm 2 , 1000 μW / cm 2 , 1500 μW / cm 2 , 2000 μW / cm 2 , 2500 μW / cm 2 , 3000 μW / cm 2 , 3500 μW / cm 2 , 4000 μW / cm 2 , 4500 μW / cm 2 , 5000 μW / cm 2 , 5500 μW / cm 2 , 6000 μW / cm 2 , 6500 μW / cm 2 , 7000 μW / cm 2 , 7500 μW / cm 2 , 8000 μW / cm 2 , 8500 μW / cm 2 , 9000 μW / cm 2 , 9500 μW / cm 2 , 10000 μW / cm2 ), and the irradiation wavelength of the ultraviolet lamp is 254-280 nm (for example, 254 nm, 255 nm, 256 nm, 257 nm, 258 nm, 259 nm, 260 nm, 261 nm, 262 nm, 263 nm, 264 nm, 265 nm, 266 nm, 267 nm, 268 nm, 269 nm, 270 nm, 271 nm, 272 nm, 273 nm, 274 nm, 275 nm, 276 nm, 277 nm, 278 nm, 279 nm, 280 nm).

[0008] Preferably, the liquid layer thickness is controlled to be 0.02-0.08 cm, the retention time of the liquid biological product in the centrifugal part is controlled to be 5-60 s, and the irradiation intensity of the ultraviolet lamp is 2000-2500 μW / cm 2 , and the irradiation wavelength of the ultraviolet lamp is 254-280 nm.

[0009] Further preferably, the liquid layer thickness is controlled to be 0.02-0.06 cm, the retention time of the liquid biological product in the centrifugal part is controlled to be 10-30 s, and the irradiation intensity of the ultraviolet lamp is 2000-2500 μW / cm 2 , and the irradiation wavelength of the ultraviolet lamp is 254-265 nm.

[0010] According to some specific embodiments, the irradiation wavelength of the ultraviolet lamp is 254 nm.

[0011] According to some embodiments, the outlet part comprises a first container, which comprises a body with a hollow cavity with an open upper end and a baffle cover detachably arranged on the body, and an outlet arranged at the bottom of the body and communicating with the outside. The centrifugal part comprises a second container, a driving assembly and an ultraviolet lamp. The second container is arranged in the first container and has a hollow structure of a circular truncated cone shape with an open upper end. The inner diameter of the second container gradually increases from bottom to top. The inner radius of the bottom of the second container is 10-200 cm. The included angle between the inner side wall and the inner bottom surface of the second container is 90-135°, excluding 90°. There is a gap between the upper end of the second container and the baffle cover. The driving assembly comprises a rotating shaft penetrating through the bottom of the first container and connected with the second container and capable of driving the second container to rotate around its axis, a motor connected with the rotating shaft and used to drive the rotating shaft to rotate. The rotating shaft is coaxial with the second container. The ultraviolet lamp is inserted on the baffle cover and suspended in the second container. The length direction of the ultraviolet lamp is parallel to the axial direction of the second container. There is a gap between the ultraviolet lamp and the inner wall of the second container. The feeding part comprises a feeding pipe and a peristaltic pump. One end of the feeding pipe penetrates through the baffle cover and extends into the second container. The other end of the feeding pipe is connected with the peristaltic pump and communicates with the peristaltic pump. The liquid biological product is continuously fed into the second container. Under the action of centrifugal force, the liquid biological product is thinned on the side wall of the second container, pushed upward from the bottom of the second container, and thrown out from the upper edge of the second container to the first container under the action of centrifugal force.

[0012] According to some specific embodiments, the included angle between the inner side wall and the inner bottom surface of the second container is 100°.

[0013] According to some embodiments, the feeding pipe comprises a first part connected with the peristaltic pump and a funnel-shaped second part connected with the first part. The upper end of the second part is an open or closed interface. The vertical projection of the lower end of the second part on the bottom surface of the second container is close to the center of the bottom surface of the second container.

[0014] According to some embodiments, the bottom of the first container is a slope, and the outlet is arranged at the lower end of the slope.

[0015] According to some embodiments, the virus inactivation device further comprises a control console, and a rotating speed adjusting button is arranged on the control console.

[0016] According to some embodiments, the virus inactivation device further comprises a detection device, a collection device or a collection / detection integrated device connected with the outlet.

[0017] Further, the virus inactivation device further comprises a temperature detection device, a humidity detection device, a luminosity detection device, a rotation speed detection device, a leakage detection device, etc.

[0018] According to some embodiments, the inactivation method comprises the steps of selecting a centrifugal speed and selecting a feed flow rate, in particular as follows:

[0019] selecting a centrifugal speed in the range of 100-2000 rpm;

[0020] obtaining the surface area of the inner side wall of the second container, measuring the mass of the liquid biological product in the second container when the feed amount and the discharge amount of the second container are equal under the selected centrifugal speed, the measuring method being: under the selected centrifugal speed, feeding the liquid biological product into the second container at a constant feed flow rate, stopping the feeding and closing the upper end opening of the second container to stop the discharging when the second container rotates to the weight remaining constant, and measuring the mass of the liquid biological product in the second container,

[0021] calculating the liquid layer thickness according to the calculation formula of the liquid layer thickness: liquid layer thickness = mass of the liquid biological product in the second container ÷ surface area of the inner side wall of the second container, testing the liquid layer thickness under different feed flow rates, and constructing the functional relationship between the feed flow rate and the liquid layer thickness,

[0022] calculating the retention time according to the calculation formula of the retention time: retention time = mass of the liquid biological product in the second container ÷ feed flow rate, testing the retention time under different feed flow rates, and constructing the functional relationship between the feed flow rate and the retention time,

[0023] selecting the feed flow rate that can make the liquid layer thickness and the retention time both be in the range to be controlled according to the functional relationship between the feed flow rate and the liquid layer thickness and the functional relationship between the feed flow rate and the retention time.

[0024] Further, selecting the centrifugal speed in the range of 200-1000 rpm.

[0025] Further, when the inner radius of the bottom of the second container is 10-20 cm, selecting the centrifugal speed in the range of 500-1000 rpm.

[0026] Still further, when the inner radius of the bottom of the second container is 10-15 cm, selecting the centrifugal speed in the range of 600-800 rpm.

[0027] Further, the ratio of the inner radius of the bottom of the second container to the inner radius of the top of the second container is 1:(1.05~1.5), for example 1:1.05, 1:1.10, 1:1.15, 1:1.20, 1:1.25, 1:1.30, 1:1.35, 1:1.40, 1:1.45, 1:1.50.

[0028] Further, the ratio of the inner radius of the bottom of the second container to the inner radius of the top of the second container is 1:(1.05~1.5), for example 1:1.05, 1:1.10, 1:1.15, 1:1.20, 1:1.25, 1:1.30, 1:1.35, 1:1.40, 1:1.45, 1:1.50.

[0029] According to some embodiments, the power of the ultraviolet lamp is 15~30W, for example 15W, 16W, 17W, 18W, 19W, 20W, 21W, 22W, 23W, 24W, 25W, 26W, 27W, 28W, 29W, 30W.

[0030] According to some specific and preferred embodiments, the inner radius of the bottom of the second container is 10~11.5cm, the inner radius of the top of the second container is 11.8~13cm, and the height of the second container is 18~20cm.

[0031] Further preferably, the feeding speed of the liquid biological product is 0.1~5mL / s, and the rotation speed of the centrifugation is 600~800rpm.

[0032] Further preferably, the feeding speed of the liquid biological product is 1~5mL / s.

[0033] In the embodiments of the present application, the effective component of the liquid biological product is protein.

[0034] Preferably, the total protein content of the liquid biological product is 0.01~50mg / mL.

[0035] Preferably, the virus includes one or more of the members of the Reoviridae family, the Rhabdoviridae family, the Orthomyxoviridae family, the Filoviridae family, the Coronaviridae family, the Bunyaviridae family, the Phenuiviridae family, the Flaviviridae family, the Paramyxoviridae family, the Togaviridae family, the Arenaviridae family, the Picornaviridae family, the Caliciviridae family, the Retroviridae family, the Poxviridae family, the Herpesviridae family, the Iridoviridae family, the Papovaviridae family, the Parvoviridae family.

[0036] According to some embodiments, the virus includes encephalomyocarditis virus, porcine parvovirus, murine parvovirus, and heterophilic mouse virus.

[0037] In the embodiments of the present application, the liquid biological product is a vaccine preparation, a toxin preparation, a toxoid preparation, an immune serum, a blood product, an immunoglobulin preparation, an antigen preparation, an allergen preparation, a cytokine preparation, a hormone preparation, an enzyme product, a fermentation broth, a monoclonal antibody preparation, or an in vitro immunodiagnostic product.

[0038] Compared with the prior art, the present application has the following advantages:

[0039] The present application provides a continuous viral inactivation method for liquid biological products, which thins the feed liquid to 0.01 cm to 0.2 cm through centrifugation, and controls the liquid biological product to be irradiated under ultraviolet light with an irradiation intensity of 500 to 10000 μW / cm 2 2 for 5 to 60 seconds under the centrifugal action, which shows unexpectedly better effects in balancing the viral inactivation effect and the activity loss of the liquid biological product compared with the prior art. According to the existing experimental results, for the viral inactivation of the liquid biological product with protein as the effective substance, the inactivation effect of reducing the viral titer (log10) by ≥4 logs and retaining the protein titer by >80% can be achieved in a shorter ultraviolet irradiation time, which is suitable for large-scale industrial processing and has lower energy consumption compared with the prior art. BRIEF DESCRIPTION OF DRAWINGS

[0040] Fig. 1 is a structural schematic diagram of the viral inactivation device used in Examples 1 to 8 and Comparative Examples 4 and 5;

[0041] Fig. 2 is a graph of the function relationship between the feed flow rate and the liquid layer thickness;

[0042] Fig. 3 is a graph of the function relationship between the feed flow rate and the retention time;

[0043] Fig. 4 is a microscope observation diagram of the ST cells inoculated with the FIIa solution treated in Example 1 and cultured;

[0044] Fig. 5 is a microscope observation diagram of the ST cells inoculated with the FIIa solution to be treated in Example 1 and cultured;

[0045] Fig. 6 is a microscope observation diagram of the Vero cells inoculated with the FIIa solution treated in Example 2 and cultured;

[0046] Fig. 7 is a microscope observation diagram of the Vero cells inoculated with the FIIa solution to be treated in Example 2 and cultured;

[0047] Fig. 8 is a microscope observation diagram of the ST cells inoculated with the FIIa solution treated in Example 3 and cultured;

[0048] Fig. 9 is a microscope observation diagram of the ST cells inoculated with the FIIa solution to be treated in Example 3 and cultured;

[0049] Figure 10 is a photomicrograph of Vero cells inoculated with and incubated in the treated FIIa solution of Example 4;

[0050] Figure 11 is a photomicrograph of Vero cells inoculated with and incubated in the untreated FIIa solution of Example 4;

[0051] Figure 12 is a photomicrograph of ST cells inoculated with and incubated in the treated LZM solution of Example 5;

[0052] Figure 13 is a photomicrograph of ST cells inoculated with and incubated in the untreated LZM solution of Example 5;

[0053] Figure 14 is a photomicrograph of Vero cells inoculated with and incubated in the treated LZM solution of Example 6;

[0054] Figure 15 is a photomicrograph of Vero cells inoculated with and incubated in the untreated LZM solution of Example 6;

[0055] Figure 16 is a photomicrograph of ST cells inoculated with and incubated in the treated LZM solution of Example 7;

[0056] Figure 17 is a photomicrograph of ST cells inoculated with and incubated in the untreated LZM solution of Example 7;

[0057] Figure 18 is a photomicrograph of Vero cells inoculated with and incubated in the treated LZM solution of Example 8;

[0058] Figure 19 is a photomicrograph of Vero cells inoculated with and incubated in the untreated LZM solution of Example 8;

[0059] Figure 20 is a photomicrograph of ST cells inoculated with and incubated in the treated FIIa solution of Comparative Example 1;

[0060] Figure 21 is a photomicrograph of ST cells inoculated with and incubated in the treated FIIa solution of Comparative Example 2;

[0061] Figure 22 is a photomicrograph of ST cells inoculated with and incubated in the treated FIIa solution of Comparative Example 3;

[0062] Figure 23 is a photomicrograph of ST cells inoculated with and incubated in the untreated FIIa solution of Comparative Example 3;

[0063] In Fig. 1, 11, first container; 111, body; 112, baffle cover; 113, discharge port; 21, second container; 22, driving assembly; 23, ultraviolet lamp; 311, first part; 312, second part; 32, peristaltic pump; 4, control console; 5, collection / detection integrated device. DETAILED DESCRIPTION

[0064] In order to develop a virus inactivation method suitable for large-scale biological products in the production process, the present inventors have conducted a large number of studies on virus inactivation methods in combination with existing devices capable of thinning biological products. For example, in order to be able to thin biological products for ultraviolet irradiation, patent CN108524969A discloses a centrifugal device that uses centrifugal action to thin biological products for ultraviolet irradiation, but it cannot achieve continuous inactivation and is not suitable for the inactivation of large-scale biological products in the production process. Patents CN218132575U and CN219943241U also use centrifugal action to thin biological products for ultraviolet irradiation while achieving continuous inactivation. However, after a large number of biological product virus sterilization experiments using the devices of patents CN218132575U and CN219943241U, no particularly satisfactory results were obtained. Therefore, the present inventors further adjusted the virus inactivation device and optimized the adjustment of the virus inactivation conditions to improve the virus inactivation effect while improving the virus inactivation efficiency.

[0065] Specifically, the technical solution adopted by the present application is: a virus inactivation device is used to inactivate viruses in liquid biological products, the virus inactivation device includes a feeding part, a centrifugal part and a discharge part, the centrifugal part is provided with an ultraviolet lamp, the liquid biological products are continuously fed into the centrifugal part through the feeding part, the liquid biological products are thinned to a liquid layer thickness of 0.01 cm to 0.2 cm under the action of centrifugation, and at the same time, ultraviolet irradiation is performed through the ultraviolet lamp to inactivate viruses, the liquid biological products after virus inactivation are continuously discharged from the centrifugal part to the discharge part under the action of centrifugation, and are discharged from the virus inactivation device through the discharge part, the retention time of the liquid biological products in the centrifugal part is controlled to be 5 to 60 s, the irradiation intensity of the ultraviolet lamp is 500 to 10000 μW / cm 2 , and the irradiation wavelength of the ultraviolet lamp is 254 to 280 nm.

[0066] The virus inactivation device comprises a feeding part, a centrifugal part, a discharging part, a control console and a collection / detection integrated device. The discharging part comprises a first container, which comprises a body with a hollow cavity with an open upper end and a baffle cover detachably arranged on the body, and a discharging port arranged at the bottom of the body and communicating with the outside. The centrifugal part comprises a second container, a driving assembly and an ultraviolet lamp. The second container is arranged in the first container and has a hollow structure of a circular truncated cone shape with an open upper end. The inner diameter of the second container gradually increases from bottom to top. The inner radius of the bottom of the second container is 10-200 cm. The included angle between the inner side wall and the inner bottom surface of the second container is 90-135°, excluding 90°. There is a gap between the upper end of the second container and the baffle cover. The driving assembly comprises a rotating shaft penetrating through the bottom of the first container and connected with the second container and capable of driving the second container to rotate around its axis, a motor connected with the rotating shaft and used for driving the rotating shaft to rotate, and the rotating shaft is coaxial with the second container. The ultraviolet lamp is inserted on the baffle cover and suspended in the second container. The length direction of the ultraviolet lamp is parallel to the axis direction of the second container. There is a gap between the ultraviolet lamp and the inner wall of the second container. The feeding part comprises a feeding pipe and a peristaltic pump. One end of the feeding pipe penetrates through the baffle cover and extends into the second container. The other end of the feeding pipe is connected with the peristaltic pump and communicates with the peristaltic pump. The liquid biological product is continuously fed into the second container. Under the centrifugal action, the liquid biological product is thinned on the side wall of the second container, at the same time, is pushed upward from the bottom of the second container, and is thrown out from the upper edge of the second container to the first container under the centrifugal action. The feeding pipe comprises a first part connected with the peristaltic pump and a second part connected with the first part and in the shape of a funnel. The upper end of the second part is open. The vertical projection of the lower end of the second part on the bottom surface of the second container is close to the center of the bottom surface of the second container. The bottom of the first container is a slope, and the discharging port is arranged at the lower end of the slope. The control console is provided with a rotating speed adjusting button.

[0067] Before formal continuous virus sterilization is performed using the virus inactivation device of the present application, the centrifugal speed and the feed flow rate are selected as follows: the centrifugal speed is selected in the range of 100-2000 rpm; the surface area of the inner side wall of the second container is obtained, and the mass of the liquid biological product in the second container when the feed amount and the discharge amount of the second container are equal is measured under the selected centrifugal speed, by the following method: under the selected centrifugal speed, the liquid biological product is fed into the second container at a constant feed flow rate, and when the second container rotates to a constant weight, the feeding and the discharge of the upper end opening of the second container are stopped, the mass of the liquid biological product in the second container is measured, the liquid layer thickness is calculated according to the formula: liquid layer thickness = mass of the liquid biological product in the second container ÷ surface area of the inner side wall of the second container, the liquid layer thickness under different feed flow rates is tested, and the functional relationship between the feed flow rate and the liquid layer thickness is constructed; the retention time is calculated according to the formula: retention time = mass of the liquid biological product in the second container ÷ feed flow rate, the retention time under different feed flow rates is tested, and the functional relationship between the feed flow rate and the retention time is constructed; and according to the functional relationship between the feed flow rate and the liquid layer thickness and the functional relationship between the feed flow rate and the retention time, the feed flow rate that can make the liquid layer thickness and the retention time both be in the range to be controlled is selected.

[0068] After a large number of experimental attempts and verifications, when the inner radius of the bottom of the second container is 10-20 cm, the centrifugal speed is preferably selected in the range of 500-1000 rpm. When the inner radius of the bottom of the second container is 10-15 cm, the centrifugal speed is preferably selected in the range of 600-800 rpm.

[0069] Some specific embodiments of the present application show that the virus inactivation method of the present application has unexpectedly better effects at least for protein products, can achieve an inactivation effect of viral titer reduction (log10) ≥4 logs and protein titer retention >80% in a shorter ultraviolet irradiation time, is suitable for large-scale industrial processing of protein biological products, and has lower energy consumption compared with the prior art.

[0070] The present application is further described below in conjunction with examples. However, the present application is not limited to the following examples. The implementation conditions used in the examples can be further adjusted according to different requirements of specific use, and the implementation conditions not mentioned are conventional conditions in the industry. The technical features involved in each embodiment of the present application can be combined with each other as long as they do not conflict with each other.

[0071] The virus inactivation device used in Examples 1-8 and Comparative Examples 4 and 5 below is shown in FIG. 1, which includes a feeding part, a centrifugal part, a discharging part, a control console and a collection / detection integrated device 5.

[0072] Specifically, the discharging part comprises a first container 11, the first container 11 comprises a body 111 with a hollow cavity with an open upper end and a baffle cover 112 detachably arranged on the body 111, and the bottom of the body 111 is provided with a discharging port 113 in communication with the outside. The centrifugal part comprises a second container 21, a driving assembly 22 and a UV lamp 23, the second container 21 is arranged in the first container 11, the second container 21 is a hollow structure of a circular truncated cone shape with an open upper end, the inner diameter of the second container 21 gradually increases from bottom to top, the inner radius of the bottom of the second container 21 is 11 cm, the inner radius of the top of the second container 21 is 12 cm, the height of the second container 21 (the vertical height from the inner bottom surface to the top surface of the second container) is 19 cm, the slant height is 19.03 cm, and there is a gap between the upper end of the second container 21 and the baffle cover 112. The driving assembly 22 comprises a rotating shaft penetrating through the bottom of the first container 11 and connected with the second container 21 and capable of driving the second container 21 to rotate around its own axis, a motor connected with the rotating shaft and used for driving the rotating shaft to rotate, and the rotating shaft is coaxial with the second container 21. The UV lamp 23 is inserted on the baffle cover 112 and is suspended in the second container 21, the length direction of the UV lamp 23 is parallel to the axis direction of the second container 21, there is a gap between the UV lamp 23 and the inner wall of the second container 21, the distance between the UV lamp 23 and the axis of the second container 21 is 6 cm, and the irradiation intensity of the UV lamp 23 is 3500 μW / cm 2 . The feeding part comprises a feeding pipe and a peristaltic pump 32, one end of the feeding pipe penetrates through the baffle cover 112 and extends into the second container 21, the other end of the feeding pipe is in communication with the peristaltic pump 32, and the liquid biological product is continuously fed into the second container 21. Under the action of centrifugal force, the liquid biological product is thinned on the side wall of the second container 21, at the same time, the liquid biological product is pushed upward from the bottom of the second container 21, and under the action of centrifugal force, the liquid biological product is thrown out from the upper edge of the second container 21 to the first container 11.

[0073] The feeding pipe comprises a first part 311 connected with the peristaltic pump 32 and a second part 312 in the shape of a funnel connected with the first part 311, the upper end of the second part 312 is open, and the vertical projection of the lower end of the second part 312 on the bottom surface of the second container 21 is close to the center of the bottom surface of the second container 21. The bottom of the first container 11 is a slope, and the discharging port 113 is arranged at the lower end of the slope. A rotating speed adjusting button is arranged on the control panel 4.

[0074] After a large number of experimental attempts and verifications, when the inactivation device is used, the centrifugal speed is preferably selected in the speed range of 600-800 rpm. The function relationship between the feed flow rate and the liquid layer thickness and the function relationship between the feed flow rate and the retention time are respectively constructed according to the method described above. For example, when the centrifugal speed is selected as 600 rpm and 800 rpm, the function relationship between the feed flow rate and the liquid layer thickness is shown in FIG. 2, and the function relationship between the feed flow rate and the retention time is shown in FIG. 3.

[0075] The wavelength of ultraviolet irradiation in the following examples and comparative examples is 254 nm.

[0076] The raw materials or reagents not specifically stated in the following examples and comparative examples are all commercially available products commonly used in the art; and the experimental or testing methods not specifically stated are all experimental conditions or detection instruments commonly used in the art. Example 1

[0077] This example provides a method for inactivating porcine parvovirus (PPV) in a thrombin (FIIa) solution, which is specifically as follows:

[0078] (1) Take the FIIa solution (self-made) to be treated, the total protein content of which is 10 mg / mL, the initial titer of FIIa is 10 IU / mL, and the PPV virus titer is 7.25 logs.

[0079] (2) Turn on the ultraviolet lamp and balance for 10 min; turn on the centrifuge until the speed is balanced at 800 rpm; select the feed flow rate according to the function relationship under the condition of 800 rpm in FIG. 2 and FIG. 3, which is 4 mL / s in this example, the liquid layer thickness is 0.053 cm (according to the function relationship under the condition of 800 rpm in FIG. 2), and the ultraviolet irradiation time is 10.41 s (according to the function relationship under the condition of 800 rpm in FIG. 3).

[0080] (3) Turn on the peristaltic pump, and pass the FIIa solution to be treated into the centrifugal part at a feed flow rate of 4 mL / s. Under the action of centrifugal force, a thin liquid layer is formed on the inner side wall of the second container and moves upward, and the FIIa solution at the top is thrown out from the upper edge of the second container to the first container, and finally flows out from the discharge port.

[0081] The treated FIIa solution and the FIIa solution to be treated are inoculated into ST cells respectively, and after 5 days of culture, the cytopathic effect of ST cells is observed under a microscope, and the virus titer is calculated according to the determination results using the Karber method (8 holes / dilution), which is expressed by the median cell infective dose (TCID 50 ).

[0082] Figure 4 shows that the ST cells in the treated FIIa solution are normal and have normal morphology, and no cytopathic effect is observed. Figure 5 shows that the ST cells in the FIIa solution to be treated have obvious cytopathic effect. The virus titer result shows that the EMCV virus titer decreases by 5.38 logs. It is detected that the FIIa titer of the FIIa solution after inactivation treatment is 84.7% of the initial FIIa titer. Example 2

[0083] This example provides a method for inactivating Encephalomyocarditis virus (EMCV) in a thrombin (FIIa) solution, which is specifically as follows:

[0084] (1) Take the FIIa solution to be treated (self-made), the total protein content is 10 mg / mL, the initial FIIa titer is 10 IU / mL, and the EMCV virus titer is 8.06 logs.

[0085] (2) Turn on the ultraviolet lamp and balance for 10 min; turn on the centrifuge until the speed is balanced at 800 rpm; select the feed flow rate according to the function relationship under the condition of 800 rpm in Figures 2 and 3, which is 2.5 mL / s in this example, the liquid layer thickness is 0.039 cm (according to the function relationship under the condition of 800 rpm in Figure 2), and the ultraviolet irradiation time (retention time) is 14.4 s (according to the function relationship under the condition of 800 rpm in Figure 3).

[0086] (3) Turn on the peristaltic pump, and pass the FIIa solution to be treated into the centrifugal part at a feed flow rate of 4 mL / s. Under the action of centrifugal force, a thin liquid layer is formed on the inner side wall of the second container and moves upward. The FIIa solution at the top is thrown out from the upper edge of the second container into the first container, and finally flows out from the discharge port.

[0087] Take the treated FIIa solution and the FIIa solution to be treated, respectively inoculate Vero cells, and culture for 5 days. Under a microscope, observe the cytopathic effect of the Vero cells, and use the Karber method (8 holes / dilution) to calculate the virus titer according to the determination result, which is expressed by the median cell infective dose (TCID 50 ).

[0088] Figure 6 shows that the Vero cells in the treated FIIa solution are normal and have normal morphology, and no cytopathic effect is observed. Figure 7 shows that the Vero cells in the FIIa solution to be treated have obvious cytopathic effect. The virus titer result shows that the EMCV virus titer decreases by 4.38 logs. It is detected that the FIIa titer of the FIIa solution after inactivation treatment is 80.9% of the initial FIIa titer. Example 3

[0089] This embodiment provides another embodiment of a method for inactivating porcine parvovirus (PPV) in a thrombin (FIIa) solution, which is basically the same as that in Embodiment 1, except that the centrifugal speed is selected to be 600 rpm, and the feed flow rate selected in this embodiment is 4 mL / s, the liquid layer thickness is 0.064 cm (according to the functional relationship under the condition of 600 rpm in FIG. 2), and the UV irradiation time (retention time) is 11.68 s (according to the functional relationship under the condition of 600 rpm in FIG. 3).

[0090] FIG. 8 shows that the ST cells in the treated FIIa solution are normal and good in shape, and no cell lesions are observed. FIG. 9 shows that the ST cells in the FIIa solution to be treated have obvious lesions. The virus titer result shows that the decrease in the PPV virus titer is 4.62 logs. It is detected that the FIIa titer of the FIIa solution after inactivation treatment is 85.5% of the initial FIIa titer. Embodiment 4

[0091] This embodiment provides another embodiment of a method for inactivating encephalomyocarditis virus (EMCV) in a thrombin (FIIa) solution, which is basically the same as that in Embodiment 2, except that the centrifugal speed is selected to be 600 rpm, and the feed flow rate selected in this embodiment is 2.5 mL / s, the liquid layer thickness is 0.047 cm (according to the functional relationship under the condition of 600 rpm in FIG. 2), and the UV irradiation time (retention time) is 18.17 s (according to the functional relationship under the condition of 600 rpm in FIG. 3).

[0092] FIG. 10 shows that the Vero cells in the treated FIIa solution are normal and good in shape, and no cell lesions are observed. FIG. 11 shows that the Vero cells in the FIIa solution to be treated have obvious lesions. The virus titer result shows that the decrease in the EMCV virus titer is 4.13 logs. It is detected that the FIIa titer of the FIIa solution after inactivation treatment is 83.6% of the initial FIIa titer. Embodiment 5

[0093] This embodiment provides a method for inactivating porcine parvovirus (PPV) in a lysozyme (LZM) solution, which is as follows:

[0094] (1) Take the LZM solution (self-made) to be treated, the total protein content of which is 10 mg / mL, the initial LZM titer is 400 U / mL, and the PPV virus titer is 7.25 logs.

[0095] (2) Turn on the ultraviolet lamp and balance for 10 min; turn on the centrifuge until the speed is balanced at 800 rpm; select the feed flow rate according to the function relationship under the condition of 800 rpm in FIG. 2 and FIG. 3, which is 4 mL / s in this embodiment, the liquid layer thickness is 0.053 cm (according to the function relationship under the condition of 800 rpm in FIG. 2), and the ultraviolet irradiation time (retention time) is 10.41 s (according to the function relationship under the condition of 800 rpm in FIG. 3).

[0096] (3) Turn on the peristaltic pump, and pass the LZM solution to be treated into the centrifugal part at a feed flow rate of 4 mL / s. Under the action of centrifugal force, a thin liquid layer is formed on the inner side wall of the second container and moves upward. The LZM solution at the top is thrown out of the upper edge of the second container into the first container, and finally flows out from the discharge port.

[0097] The treated LZM solution and the LZM solution to be treated are inoculated with ST cells, respectively. After 5 days of culture, the cytopathic effect of the ST cells is observed under a microscope. The virus titer is calculated according to the determination results using the Karber method (8 holes / dilution), and is expressed by the median tissue culture infectious dose (TCID 50 ).

[0098] FIG. 12 shows that the ST cells in the treated LZM solution are normal and good, and the morphology is normal, and no cytopathic effect is observed. FIG. 13 shows that the ST cells in the LZM solution to be treated have obvious cytopathic effect. The virus titer result shows that the decrease of the PPV virus titer is 5.26 logs. It is detected that the LZM titer of the inactivated LZM solution is 93.2% of the initial LZM titer. Example 6

[0099] This embodiment provides a method for inactivating Encephalomyocarditis virus (EMCV) in a lysozyme (LZM) solution, which is specifically as follows:

[0100] (1) Take the LZM solution to be treated (self-made), and the total protein content is 10 mg / mL. The initial LZM titer is 400 U / mL, and the EMCV virus titer is 8.06 logs.

[0101] (2) Turn on the ultraviolet lamp and balance for 10 min; turn on the centrifuge until the speed is balanced at 800 rpm; select the feed flow rate according to the function relationship under the condition of 800 rpm in FIG. 2 and FIG. 3, which is 4 mL / s in this embodiment, the liquid layer thickness is 0.053 cm (according to the function relationship under the condition of 800 rpm in FIG. 2), and the ultraviolet irradiation time (retention time) is 10.41 s (according to the function relationship under the condition of 800 rpm in FIG. 3).

[0102] (3) Turn on the peristaltic pump, and pass the LZM solution to be treated into the centrifugal part at a feed flow rate of 4 mL / s. Under the action of the centrifugal force, a thin liquid layer is formed on the inner side wall of the second container and moves upward. The LZM solution at the top is thrown out of the upper edge of the second container into the first container, and finally flows out of the discharge port.

[0103] The treated LZM solution and the LZM solution to be treated were inoculated with Vero cells, respectively. After 5 days of culture, the cytopathic effect of the ST cells was observed under a microscope. The virus titer was calculated according to the determination results using the Karber method (8 wells / dilution), and expressed as the median tissue culture infectious dose (TCID 50 ).

[0104] Figure 14 shows that the Vero cells in the treated LZM solution are normal and good, and the morphology is normal, and no cytopathic effect is observed. Figure 15 shows that the Vero cells in the LZM solution to be treated have obvious cytopathic effect. The virus titer result shows that the EMCV virus titer decreases by 4.25 logs. It is detected that the LZM titer of the inactivated LZM solution is 91.6% of the initial LZM titer. Example 7

[0105] This embodiment provides another embodiment of a method for inactivating porcine parvovirus (PPV) in lysozyme (LZM). The method is basically the same as that in Example 5, except that the centrifugal speed is selected to be 600 rpm. In this embodiment, the feed flow rate is selected to be 4 mL / s, the liquid layer thickness is 0.064 cm (according to the functional relationship under the condition of 600 rpm in Figure 2), and the ultraviolet irradiation time (retention time) is 11.68 s (according to the functional relationship under the condition of 600 rpm in Figure 3).

[0106] Figure 16 shows that the ST cells in the treated LZM solution are normal and good, and the morphology is normal, and no cytopathic effect is observed. Figure 17 shows that the ST cells in the LZM solution to be treated have obvious cytopathic effect. The virus titer result shows that the PPV virus titer decreases by 4.88 logs. It is detected that the LZM titer of the inactivated LZM solution is 95.4% of the initial LZM titer. Example 8

[0107] The present embodiment provides another embodiment of the method for inactivating Encephalomyocarditis virus (EMCV) in lysozyme (LZM), which is basically the same as that in Embodiment 6, except that the centrifugal speed is selected as 600 rpm. In the present embodiment, the feed flow rate is selected as 2.5 mL / s, and the liquid layer thickness is 0.047 cm (according to the functional relationship under the condition of 600 rpm in FIG. 2), and the ultraviolet irradiation time (retention time) is 18.17 s (according to the functional relationship under the condition of 600 rpm in FIG. 3).

[0108] FIG. 18 shows that the Vero cells in the treated LZM solution are normal and normal in shape, and no cytopathic effect is observed. FIG. 19 shows that the Vero cells in the LZM solution to be treated exhibit obvious cytopathic effect. The virus titer result shows that the EMCV virus titer decreases by 4.08 logs. The detection shows that the LZM titer of the LZM solution after inactivation treatment is 92.5% of the initial LZM titer.

[0109] Comparative Example 1

[0110] The present comparative example provides another method for inactivating Porcine parvovirus (PPV) in thrombin (FⅡa) solution. The present comparative example is basically the same as Embodiment 1, except that the centrifugal device in patent CN218132575U is used for virus inactivation. The bottom radius of the body of the centrifugal device is 13 cm, the top radius is 17 cm, the height is 20 cm, the inclined height is 20.39 cm, and the rotation speed is 800 rpm. When the feed flow rate is 2.5 ml / s, the feed flow rate and the liquid layer thickness functional relationship, the feed flow rate and the retention time functional relationship of the present application are used to construct the feed flow rate and the liquid layer thickness of the present comparative example, and the retention time in the body is 16.9 s. It is measured that only the FⅡa solution reaches the top layer when it can accept a relatively strong ultraviolet intensity of about 5000 μW / cm 2 , and the actual ultraviolet irradiation time is significantly lower than the retention time in the body. FIG. 20 shows that the ST cells in the treated FⅡa solution exhibit obvious cytopathic effect. The virus titer result shows that the PPV virus titer decreases by 0.39 logs, and almost no inactivation effect is achieved.

[0111] The present comparative example is only an example of using the centrifugal device in CN218132575U for virus inactivation. During the research and development stage, the working parameters (including feed flow rate and centrifugal speed) of the centrifugal device are systematically adjusted, and the technical effect comparable to Comparative Example 1 cannot be achieved within a retention time of 5-60 s. Compared with Embodiment 1, the virus inactivation efficiency of the present comparative example is low, the energy consumption is higher, and the cost is higher.

[0112] Comparative Example 2

[0113] This comparative example provides another method for inactivating porcine parvovirus (PPV) in a thrombin (FIIa) solution. The FIIa solution to be treated in this comparative example is the same as in Example 1, except that a flat plate centrifuge of patent CN219943241U is used for virus inactivation. The flat plate radius of the centrifuge is 20 cm, and the rotation speed is 300 rpm. When the feed flow rate is 0.5 ml / s, the liquid layer thickness is 0.1 cm, and the UV irradiation time is 1.2 s, the UV intensity reaches 10000 μW / cm 2 The virus titer results show that the PPV virus titer decreases by 0.77 logs, and there is almost no inactivation effect. Figure 21 shows that the ST cells in the treated FIIa solution have obvious lesions.

[0114] This comparative example is only an example of using the flat plate centrifuge of CN219943241U for virus inactivation. During the research and development stage, the working parameters (including feed flow rate and centrifugal rotation speed) of the flat plate centrifuge were systematically adjusted, but the virus inactivation effect was not as good as that of Example 1.

[0115] Comparative Example 3

[0116] This comparative example provides another method for inactivating porcine parvovirus (PPV) in a thrombin (FIIa) solution. The FIIa solution to be treated in this comparative example is the same as in Example 1. This comparative example uses the method described in the national standard (HJ 2522-2012) parallel light UV irradiation instrument for UV irradiation. This method is not continuous liquid feeding, and cannot meet the needs of large-scale production. It is only used as a comparative reference for virus inactivation effect and protein activity retention. 49 mL of FIIa solution is placed in a 90 mm petri dish, the irradiation area and the dish bottom area are 49 cm 2 , and the liquid layer thickness is 1 cm. However, due to the action of the magnetic stirrer, the bottom liquid can still receive UV irradiation. The UV irradiation intensity is 2000 μW / cm 2 , and the irradiation time is 15 s. Figure 22 shows that the ST cells in the treated FIIa solution have obvious lesions, and Figure 23 shows that the lesion degree of the ST cells in the FIIa solution to be treated is greater than that in the treated FIIa solution. The virus titer results show that the PPV virus titer decreases by 1.80 logs. The FIIa titer of the inactivated FIIa solution is 77.5% of the initial FIIa titer.

[0117] Comparative Example 4

[0118] This example provides another embodiment of the method for inactivating porcine parvovirus (PPV) in a thrombin (FIIa) solution, which is substantially the same as Example 1, except that the feed flow rate selected in this example is 20 mL / s, the liquid layer thickness is 0.198 cm, and the UV irradiation time is 3.16 s. The viral titer results show that the PPV viral titer decreased by 2.05 logs, which is less than the viral reduction (logio) of >4 logs that is conventionally required in the art, indicating that the ability of this step to remove / inactivate viruses is less than the standard for effectiveness.

[0119] Comparative Example 5

[0120] This example provides another embodiment of the method for inactivating porcine parvovirus (PPV) in a thrombin (FIIa) solution, which is substantially the same as Example 1, except that the feed flow rate selected in this example is 0.2 mL / s, the liquid layer thickness is 0.019 cm, and the UV irradiation time is 140.2 s. The viral titer results show that the PPV viral titer decreased by 5.38 logs, and the FIIa potency of the FIIa solution after inactivation treatment is 69.4% of the initial FIIa potency. For the same treatment volume, the treatment time in this example is significantly longer than in Example 1.

[0121] The foregoing detailed description of the application has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the application to the precise form disclosed, and obviously many modifications and variations are possible in light of the above teaching. The described embodiments were chosen in order to best explain the principles of the application and its practical application to thereby enable others skilled in the art to best utilize the application.

Claims

1. A method for viral inactivation of a liquid biological product, which is not effective in nucleic acids, characterized by: The liquid biological product is inactivated by a virus inactivation device, the virus inactivation device comprises a feeding part, a centrifugal part and a discharging part, the centrifugal part is provided with an ultraviolet lamp, the liquid biological product is continuously introduced into the centrifugal part through the feeding part, the liquid biological product is thinned to a liquid layer thickness of 0.01cm~0.2cm under the centrifugal action, and the liquid biological product is inactivated by ultraviolet irradiation through the ultraviolet lamp, the liquid biological product after virus inactivation is continuously discharged from the centrifugal part to the discharging part under the centrifugal action, and the liquid biological product is discharged from the virus inactivation device through the discharging part, the retention time of the liquid biological product in the centrifugal part is controlled to be 5~60s, the irradiation intensity of the ultraviolet lamp is 500~10000μW / cm 2 , and the irradiation wavelength of the ultraviolet lamp is 254~280nm.

2. The method for virus inactivation of a liquid biological according to claim 1, characterized in that: The liquid layer thickness is controlled to be 0.02-0.08 cm, the retention time of the liquid biological product in the centrifugal part is controlled to be 5-60 s, and the irradiation intensity of the ultraviolet lamp is 2000-2500 μW / cm 2 .

3. The method for virus inactivation of a liquid biological according to claim 1, characterized in that: The discharging part comprises a first container, the first container comprises a body with a hollow cavity with an open upper end and a baffle cover detachably arranged on the body, the bottom of the body is provided with a discharging port in communication with the outside, The centrifugal part comprises a second container, a driving assembly and an ultraviolet lamp, the second container is arranged in the first container, the second container is a hollow structure of a circular truncated cone with an open upper end, the inner diameter of the second container gradually increases from bottom to top, the inner radius of the bottom of the second container is 10-200 cm, the included angle between the inner side wall and the inner bottom surface of the second container is 90-135°, the gap exists between the upper end of the second container and the baffle cover, the driving assembly comprises a rotating shaft penetrating through the bottom of the first container and connected with the second container and capable of driving the second container to rotate around its axis, a motor connected with the rotating shaft and used for driving the rotating shaft to rotate, the rotating shaft is coaxial with the second container, the ultraviolet lamp is inserted on the baffle cover and suspended in the second container, the length direction of the ultraviolet lamp is parallel to the axial direction of the second container, and the gap exists between the ultraviolet lamp and the inner wall of the second container, The feeding part comprises a feeding pipe and a peristaltic pump, one end of the feeding pipe penetrates through the baffle cover and extends into the second container, and the other end of the feeding pipe is in communication with the peristaltic pump, The liquid biological product is continuously fed into the second container, under the centrifugal action, the liquid biological product is thinned on the side wall of the second container, at the same time, the liquid biological product is pushed upward from the bottom of the second container, and under the centrifugal action, the liquid biological product is thrown out from the upper edge of the second container into the first container.

4. The method for virus inactivation of a liquid biological according to claim 3, characterized in that: The inactivation method comprises the steps of selecting a centrifugal speed and selecting a feeding flow, and specifically as follows: The centrifugal speed is selected in the range of 100-2000 rpm; The surface area of the inner side wall of the second container is obtained, the mass of the liquid biological product in the second container is measured when the feeding amount and the discharging amount of the second container are equal under the selected centrifugal speed, the measurement method is that under the selected centrifugal speed, the liquid biological product is fed into the second container at a constant feeding flow, when the second container rotates to keep the weight constant, the feeding and the closing of the upper opening of the second container are stopped to stop the discharging, and the mass of the liquid biological product in the second container is measured, The liquid layer thickness is calculated according to the calculation formula of the liquid layer thickness: liquid layer thickness=mass of the liquid biological product in the second container÷surface area of the inner side wall of the second container, the liquid layer thickness under different feeding flows is tested, and the functional relationship between the feeding flow and the liquid layer thickness is constructed, The retention time is calculated according to the calculation formula of the retention time: retention time=mass of the liquid biological product in the second container÷feeding flow, the retention time under different feeding flows is tested, and the functional relationship between the feeding flow and the retention time is constructed, According to the functional relationship between the feeding flow and the liquid layer thickness and the functional relationship between the feeding flow and the retention time, the feeding flow capable of making the liquid layer thickness and the retention time in the range to be controlled is selected.

5. The method for virus inactivation of a liquid biological according to claim 4, characterized in that: The centrifugal speed is selected from the range of 200-1000 rpm.

6. The method for virus inactivation of a liquid biological according to claim 3, characterized in that: The ratio of the inner radius of the bottom to the inner radius of the top of the second container is 1: (1.05-1.5).

7. The method for virus inactivation of a liquid biological according to claim 6, characterized in that: The ratio of the inner radius of the bottom to the inner radius of the top of the second container is 1: (1.05-1.2).

8. The method for virus inactivation of a liquid biological according to claim 3, characterized in that: The inner radius of the bottom of the second container is 10-11.5 cm, the inner radius of the top is 11.8-13 cm, and the height is 18-20 cm, and the power of the ultraviolet lamp is 15-30 W.

9. The method for virus inactivation of a liquid biological according to claim 6, characterized in that: The feeding speed of the liquid biological product is 0.1-5 mL / s, and the centrifugal speed is 600-800 rpm.

10. The method for virus inactivation of a liquid biological according to claim 9, characterized in that: The feeding speed of the liquid biological product is 1-5 mL / s.

11. The method of virus inactivation according to claim 1, characterized in that: The effective component of the liquid biological product is protein, and / or the total protein content of the liquid biological product is 0.01-50 mg / mL, and / or the virus includes one or more of the members of the Reoviridae, Rhabdoviridae, Orthomyxoviridae, Filoviridae, Coronaviridae, Bunyaviridae, Phenuiviridae, Flaviviridae, Paramyxoviridae, Togaviridae, Arenaviridae, Picornaviridae, Caliciviridae, Retroviridae, Poxviridae, Herpesviridae, Iridoviridae, Papovaviridae, Parvoviridae.

12. The method for virus inactivation of a liquid biological according to claim 11, characterized in that: The virus includes encephalomyocarditis virus, porcine parvovirus, murine parvovirus, and xenotropic murine virus.

13. The method for virus inactivation of a liquid biological according to claim 1, characterized in that: The liquid biological product is a vaccine preparation, a toxin preparation, a toxoid preparation, immune serum, a blood product, an immunoglobulin preparation, an antigen preparation, an allergen preparation, a cytokine preparation, a hormone preparation, an enzyme preparation, a fermentation broth, a monoclonal antibody preparation, or an in vitro immunodiagnostic preparation.

14. The method of virus inactivation according to claim 3, characterized in that: The feeding pipe includes a first part connected to the peristaltic pump and a funnel-shaped second part connected to the first part, the upper end of the second part is open, and the vertical projection of the lower end of the second part on the bottom surface of the second container is close to the center of the bottom surface of the second container. The bottom of the first container is a slope, and the discharge port is arranged at the lower end of the slope.

15. The method of virus inactivation according to claim 3, characterized in that: The virus inactivation device further comprises a control console, and the control console is provided with a speed adjusting button.

16. The method of virus inactivation according to claim 3, characterized in that: The virus inactivation device further comprises a detection device, a collection device, or a collection / detection integrated device connected to the discharge port.

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