CN206635330U - A kind of virion antigen purifies concentrator - Google Patents

A kind of virion antigen purifies concentrator Download PDF

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Publication number
CN206635330U
CN206635330U CN201720289901.6U CN201720289901U CN206635330U CN 206635330 U CN206635330 U CN 206635330U CN 201720289901 U CN201720289901 U CN 201720289901U CN 206635330 U CN206635330 U CN 206635330U
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China
Prior art keywords
pipeline
fluid reservoir
micro
antigen
filtration
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Expired - Fee Related
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CN201720289901.6U
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Chinese (zh)
Inventor
孙爱喜
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Shanghai Hai Li Biotechnology Ltd
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Shanghai Hai Li Biotechnology Ltd
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Abstract

The utility model provides a kind of virion antigen purifying concentrator, and the equipment includes:Fluid reservoir, the fluid reservoir include the first fluid reservoir (1) and the second fluid reservoir (2);Micro-filtration (3), the micro-filtration are provided with micro-filtration hollow-fibre membrane;Ultrafiltration apparatus (4), the ultrafiltration apparatus are provided with ultra filtration hollow fiber membrane;And circulating pump.The equipment efficiently rapid concentration antigen and can remove the impurity in antigen, the non-purpose thing of foreign protein in the cell fragment, ovalbumin, production process in such as viral antigen, to meet that the large-scale production of high-quality vaccine purifies needs.

Description

A kind of virion antigen purifies concentrator
Technical field
The utility model belongs to biological technical field, in particular it relates to purify concentrator to a kind of virion antigen.
Background technology
Preparing large biological molecule and during various biogenetic products, often after extraction with concentrated before crystallization, particularly exist , it is necessary to carry out the effective content that concentration ensures each antigen of vaccine unit volume to vaccine antigen in vaccine connection seedling production process.Epidemic disease Seedling is widely used in healthy livestock and poultry, and because domestic livestock and poultry owning amount is huge, multi-joint seedling prevents for Animal diseases, reduces poultry feeders Labor intensity, mitigate livestock and poultry stress caused by vaccine injection and become clear day by day.The security requirement of vaccine product is first Position, it is lifting product competitiveness in the market to improve vaccine quality, reduce immune side reaction, occupies the key in high-grade market.I The demand growth of the various vaccines of state is rapid.And domestic production of vaccine scale is universal smaller, technological level is low, it is difficult to meets Gao Pin The demand of matter vaccine large-scale production.Domestic most live vaccine enterprises still use traditional production technology, such as spinner culture, thin,tough silk Cloth filtering etc., it is difficult to ensure the mass uniformity of different batches of products, while add the difficulty of process certification.
This area meets the large-scale production purifying of vaccine there is an urgent need to a kind of antigen purification concentrator rapidly and efficiently Need.
Utility model content
The purpose of this utility model is to provide a kind of antigen purification concentrator rapidly and efficiently, for concentrated antigen and goes Except the impurity in antigen, the non-purpose thing of foreign protein in the cell fragment, ovalbumin, production process in such as viral antigen, use To meet that the large-scale production of high-quality vaccine purifies needs.
A kind of virion antigen purifying concentrator described in the utility model, the equipment include:
Fluid reservoir, the fluid reservoir are used to store the antigen, and the fluid reservoir includes the first fluid reservoir (1) and the Two fluid reservoirs (2);
Micro-filtration (3), the micro-filtration is used to filter off to remove the impurity bigger than the virion antigen, and institute State micro-filtration and be provided with micro-filtration hollow-fibre membrane;
Ultrafiltration apparatus (4), the ultrafiltration apparatus are provided with ultra filtration hollow fiber membrane, and the ultrafiltration apparatus is used to filter off to remove The impurity smaller than the virion antigen, and the antigen is concentrated;
It is connected between the micro-filtration (3) and first fluid reservoir (1) by the first pipeline and second pipe, and shape Into micro-filtration circulation loop, circulating pump is provided with first pipeline and/or second pipe;
It is connected between the micro-filtration (3) and second fluid reservoir (2) by the 3rd pipeline;
It is connected between the ultrafiltration apparatus (4) and second fluid reservoir (2) by the 4th pipeline and the 5th pipeline, and shape Into ultrafiltration circulation loop, circulating pump is provided with the 4th pipeline and/or the 5th pipeline;
Wherein, the circulating pump is used in the apparatus be circulated the antigen.
In another preference, the equipment includes one or more micro-filtrations, and described multiple micro-filtrations are to go here and there The mode of connection/parallel connection connects, and the retention aperture of the micro-filtration doughnut is 0.45 μm of -0.65um.
In another preference, the equipment include one, two, three, four, five, six, seven, eight, nine Individual, ten micro-filtrations.
In another preference, the retention aperture of the micro-filtration doughnut is 0.50 μm of -0.60um.
In another preference, the equipment includes one or more ultrafiltration apparatus, and described multiple ultrafiltration apparatus are to go here and there The mode of connection/parallel connection connects, and the retention aperture of the ultrafiltration hollow fiber is 50kd-900kd.
In another preference, the equipment include one, two, three, four, five, six, seven, eight, nine Individual, ten ultrafiltration apparatus.
In another preference, the retention aperture of the ultrafiltration hollow fiber is 100kd-800kd.
In another preference, the retention aperture of the ultrafiltration hollow fiber is 300kd-500kd.
In another preference, the first Drainage pipe is also associated with first pipeline and the 4th pipeline, described first Drainage pipe is used to discharge the waste liquid being concentrated to give by purifying.
In another preference, the equipment also includes waste collection tank, and first Drainage pipe connects the waste liquid Collecting tank, the waste collection tank are used to handle the waste liquid.
In another preference, the ultrafiltration apparatus is also associated with the second Drainage pipe, and second Drainage pipe is used for Discharge the virion antigen of concentration.
In another preference, first fluid reservoir is also associated with a sample adding device, and the sample adding device is used for the Physiological saline is added in one fluid reservoir.
In another preference, the equipment also includes a feed pipe, and the feed pipe is used for first fluid reservoir The virion antigen of middle input concentration to be purified.
In another preference, first pipeline, and/or second pipe, and/or the 3rd pipeline, and/or the 4th pipe Road, and/or the 5th pipeline are provided with a valve, and the valve is used for the ON/OFF of pipeline;And/or
First pipeline, and/or second pipe, and/or the 3rd pipeline, and/or the 4th pipeline, and/or the 5th pipeline A pressure gauge is provided with, the pressure gauge is used to monitor the pressure in pipeline.
In another preference, the volume of first fluid reservoir is 100-3000L;And/or second fluid reservoir Volume is 100-3000L.
It should be understood that in the scope of the utility model, above-mentioned each technical characteristic of the present utility model and below (such as implementation Example) in specifically describe each technical characteristic between can be combined with each other, so as to form new or preferable technical scheme.It is limited to Length, no longer tire out one by one state herein.
Brief description of the drawings
Fig. 1 is that a kind of virion antigen of one preference of the utility model purifies the schematic diagram of concentrator;
In figure, 1 is the first fluid reservoir, and 2 be the second fluid reservoir, and 3 be micro-filtration, and 4 be ultrafiltration apparatus.
Embodiment
The present inventor by depth studying extensively, it has unexpectedly been found that, the micro-filtration with micro-filtration hollow-fibre membrane is filled Put and have the ultra-filtration filters device of ultra filtration hollow fiber membrane to be assembled, can quickly and efficiently concentrate and purify antigen, obtain The concentrated antigen of high quality, meet the large-scale production purifying needs of vaccine, realize multi-joint seedling production.On this basis, complete The utility model.
Virion antigen purifies concentrator
The utility model provides a kind of virion antigen purifying concentrator, and the equipment includes:Fluid reservoir, it is described Fluid reservoir is used to store the antigen, and the fluid reservoir includes the first fluid reservoir 1 and the second fluid reservoir 2;Micro-filtration 3, The micro-filtration is provided with micro-filtration hollow-fibre membrane, and the micro-filtration is used to filter off except bigger than the virion antigen Impurity;Ultrafiltration apparatus 4, the ultrafiltration apparatus are provided with ultra filtration hollow fiber membrane, the ultrafiltration apparatus be used to filtering off except than The small impurity of the virion antigen, and the antigen is concentrated;The micro-filtration 3 and first fluid reservoir 1 Between connected by the first pipeline with second pipe, and micro-filtration circulation loop is formed, in first pipeline and/or second pipe On be provided with circulating pump;Connected between the micro-filtration 3 and second fluid reservoir 2 by the 3rd pipeline;The ultrafiltration dress Put and connected between 4 and second fluid reservoir 2 by the 4th pipeline and the 5th pipeline, and form ultrafiltration circulation loop, described Circulating pump is provided with 4th pipeline and/or the 5th pipeline;Wherein, the circulating pump is used for the antigen in the apparatus Circulated.
In preferred embodiments, micro-filtration and the number of ultrafiltration apparatus have no particular limits in the equipment, According to the needs of real work, the micro-filtration and ultrafiltration apparatus of varying number can be set, can also be according to being actually needed with simultaneously Connection and/or the mode of series connection combine connection.The retention aperture of the micro-filtration doughnut and the retention aperture of ultrafiltration hollow fiber Also have no particular limits, the micro- of different retention apertures is selected according to the size of the virion antigen of required purifying concentration Filter doughnut and ultrafiltration hollow fiber.The retention aperture of micro-filtration doughnut is preferably 0.45 μm of -0.65um.Ultrafiltration is hollow The preferable molecular cut off in retention aperture of fiber is 100kd-900kd.
In preferred embodiments, the first Drainage pipe is also associated with first pipeline and the 4th pipeline, it is described First Drainage pipe is used to discharge the waste liquid filtered out.Preferably, the first Drainage pipe is connected to waste collection tank, and purifying is concentrated Obtained discharging of waste liquid does harmless treatment to waste collection tank.
In preferred embodiments, the ultrafiltration apparatus is also associated with the second Drainage pipe, second Drainage pipe For discharging the virion antigen of concentration, one of production process is carried out down.
In preferred embodiments, first fluid reservoir is also associated with a sample adding device, and the sample adding device is used for Physiological saline is added into the first fluid reservoir.
In preferred embodiments, the equipment also includes a feed pipe, and the feed pipe is used for the described first storage The virion antigen of concentration to be purified is inputted in flow container.
In preferred embodiments, settable valve is used for the stream for controlling antigen on all pipelines of whole equipment It is dynamic, or set pressure gauge to monitor the pressure change in pipeline.Preferably, first pipeline, and/or second pipe, and/or the Three pipelines, and/or the 4th pipeline, and/or the 5th pipeline are provided with a valve;And/or first pipeline, and/or the second pipe Road, and/or the 3rd pipeline, and/or the 4th pipeline, and/or the 5th pipeline are provided with a pressure gauge.
The volume of the fluid reservoir has no particular limits, and can be adjusted according to needs of production.Preferably, institute The volume for stating the first fluid reservoir is 100-3000L;And/or the volume of second fluid reservoir is 100-3000L.
Hollow-fibre membrane
Hollow-fibre membrane used in the utility model uses tangential flow filtration technology (Tangential Flow Filtration, TFF), also known as cross-flow filtration (Cross-Flow Filtration, CFF), feed liquid is with certain flow velocity in film Upper surface circulation, the material less than film retention aperture can pass through film to pass through end, and be more than the material meeting that film retains aperture It is rejected by, so as to realize that the classification of the concentration of target substance and different material separates.The film retention of micro-filtration hollow-fibre membrane Aperture is 0.45 μm of -0.65um, is used directly for the removal of cell and cell fragment in nutrient solution.Ultra filtration hollow fiber membrane Film retains aperture, i.e. molecular cut off is 100kd-900kd, is usually used in protein or virion and gently quickly concentrates.
The advantages of the utility model
A kind of virion antigen purifying concentrator described in the utility model, is extracted using slipstream membrane filtration technique The purpose thing virion needed, farthest remove without immune effect protein impurities, there is advantages below:
(1) purifying concentration one, handles the big efficiency high of amount of antigen, and the damage to virion is small, and antigen yield is high, quickly High power concentrated antigen is efficiently realized, antigen destination protein yield is high, and multi-joint seedling production can be achieved;
(2) can lead to for the hollow-fibre membrane in the different retention apertures of different size of virion selection, hollow-fibre membrane Inner pressed or the two-way on-line cleaning of external-compression type are crossed, autoclaving is easy to operate, and middle control fiber module filter area is big, and equipment accounts for It is small with space;
(3) impurity in nutrient solution, such as cell fragment, ovalbumin, microbial metabolic products, thermal source can effectively be removed Deng impurity, purifying antigen;
(4) tank body, pump are stainless steel, pipeline stainless steel or ABS tubing, do not pollute antigen;
(5) easy to operate, efficiency format high throughput is big, and large-scale production can be achieved, and lifts vaccine quality, and high-titer is low secondary anti- Should, service life of equipment is grown, and cost is low.
Below in conjunction with accompanying drawing, the utility model is further illustrated.It should be understood that following description be only it is of the present utility model most Preferred embodiment, and it is not construed as the limitation for scope of protection of the utility model.Fully understanding that this practicality is new On the basis of type, generally according to normal condition, or can be to this according to the condition proposed by manufacturer, those skilled in the art The technical scheme of utility model makes nonessential change, and such change should be considered as being included in protection of the present utility model Among scope.
The schematic diagram of virion antigen purifying concentrator described in the utility model is as shown in figure 1, the equipment bag Include:Fluid reservoir, the fluid reservoir is used to store the antigen, and the fluid reservoir includes the first fluid reservoir 1 and the second liquid storage Tank 2;The micro-filtration 3 being connected in parallel, the micro-filtration are provided with micro-filtration hollow-fibre membrane, and the micro-filtration is used to filter Remove the impurity bigger than the virion antigen;The ultrafiltration apparatus 4 being connected in parallel, it is hollow that the ultrafiltration apparatus is provided with ultrafiltration Tunica fibrosa, the ultrafiltration apparatus are used to filter off to remove the impurity smaller than the virion antigen, and the antigen are carried out dense Contracting;Connected between the micro-filtration 3 and first fluid reservoir 1 by the first pipeline and second pipe, and form micro-filtration and follow Loop back path, circulating pump is provided with first pipeline and/or second pipe;The micro-filtration 3 and second liquid storage Connected between tank 2 by the 3rd pipeline;Pass through the 4th pipeline and the 5th between the ultrafiltration apparatus 4 and second fluid reservoir 2 Pipeline is connected, and forms ultrafiltration circulation loop, and circulating pump is provided with the 4th pipeline and/or the 5th pipeline;Wherein, institute Circulating pump is stated to be used in the apparatus be circulated the antigen.
The first Drainage pipe is also associated with first pipeline and the 4th pipeline, first Drainage pipe is used to discharge The waste liquid filtered out.First Drainage pipe is connected to waste collection tank, by the discharging of waste liquid that purifying is concentrated to give to waste collection tank Do harmless treatment.The ultrafiltration apparatus is also associated with the second Drainage pipe, and second Drainage pipe is used to discharge concentration Virion antigen, carry out down one of production process.First fluid reservoir is also associated with a sample adding device, the sample adding device For adding physiological saline into the first fluid reservoir.The equipment also includes a feed pipe, and the feed pipe is used for described the The virion antigen of concentration to be purified is inputted in one fluid reservoir.
Enter fluid reservoir (1) by feed pipe by the virion antigen of preliminary purification, by micro-filtration (3), first Circulating pump on fluid reservoir (1), the first pipeline, second pipe and second pipe forms micro-filtration circulation loop, virion antigen As acting in micro-filtration circulation loop for circulating pump circulates.Material less than micro-filtration hollow-fibre membrane retention aperture can be with Through film to passing through end, and the material more than film retention aperture can be rejected by.Required antigen and less than the hollow fibre of micro-filtration The foreign protein in film retention aperture is tieed up through after micro-filtration hollow-fibre membrane, is entered by the 3rd pipeline in the second fluid reservoir (2). In actual production, the internal circulating load for the antigen that the needs in micro-filtration circulation loop purify concentration can taper into, in order to improve disease The yield of malicious particulate antigen by sample adding device, it is necessary to be used to add physiological saline into the first fluid reservoir (1), repeatedly injection is surplus Remaining 5-10 times of physiological saline of internal circulating load, continuing cycling through to minimal circulation amount, virion antigen content is seldom in remaining liquid, Discharged by the first Drainage pipe, waste collection tank can also be discharged into and do harmless treatment.
Virion antigen in second fluid reservoir (2) is further by ultrafiltration apparatus (4), the second fluid reservoir (2), the 4th Circulated in the ultrafiltration circulation loop that the circulating pump set on pipeline, the 5th pipeline and the 5th pipeline is formed.Required mesh Antigen retained by milipore filter, and less than milipore filter retention aperture other foreign proteins can then pass through ultrafiltration tunica fibrosa.Foreign protein Discharged also by the first Drainage pipe, or be discharged into waste collection tank and do harmless treatment.Circulated in ultrafiltration circulation loop straight To required virion antigen quantity is concentrated into, the virion antigen for discharging concentration is used for by the second Drainage pipe.
In Fig. 1, feed pipe, sample adding device, waste collection tank are not shown, and can be set on all pipelines of whole equipment The flowing that valve is used to control antigen is put, or sets pressure gauge to monitor the pressure change in pipeline, part is merely representative of out in figure Valve and pressure gauge.In addition, micro-filtration hollow-fibre membrane, ultra filtration hollow fiber membrane, the tool of the first fluid reservoir and the second fluid reservoir Body parameter is referring to this specification.
All it is incorporated as referring in this application in all documents that the utility model refers to, just as each document quilt It is individually recited as with reference to such.In addition, it is to be understood that after above-mentioned instruction content of the present utility model has been read, this area skill Art personnel can make various changes or modifications to the utility model, and these equivalent form of values equally fall within the application appended claims Book limited range.

Claims (10)

1. a kind of virion antigen purifies concentrator, it is characterised in that the equipment includes:
Fluid reservoir, the fluid reservoir is used to store the antigen, and the fluid reservoir includes the first fluid reservoir (1) and the second storage Flow container (2);
Micro-filtration (3), the micro-filtration are used to filter off to remove the impurity bigger than the virion antigen, and described micro- Filter device is provided with micro-filtration hollow-fibre membrane;
Ultrafiltration apparatus (4), the ultrafiltration apparatus are provided with ultra filtration hollow fiber membrane, and the ultrafiltration apparatus is used to filter off except than institute The small impurity of virion antigen is stated, and the antigen is concentrated;
It is connected, and is formed micro- by the first pipeline and second pipe between the micro-filtration (3) and first fluid reservoir (1) Circulation loop is filtered, circulating pump is provided with first pipeline and/or second pipe;
It is connected between the micro-filtration (3) and second fluid reservoir (2) by the 3rd pipeline;
It is connected, and is formed super by the 4th pipeline and the 5th pipeline between the ultrafiltration apparatus (4) and second fluid reservoir (2) Circulation loop is filtered, circulating pump is provided with the 4th pipeline and/or the 5th pipeline;
Wherein, the circulating pump is used in the apparatus be circulated the antigen.
2. equipment as claimed in claim 1, it is characterised in that the equipment includes one or more micro-filtrations, described Multiple micro-filtrations are connected in a manner of series/parallel, and the retention aperture of the micro-filtration doughnut is 0.45 μm of -0.65um.
3. equipment as claimed in claim 1, it is characterised in that the equipment includes one or more ultrafiltration apparatus, described Multiple ultrafiltration apparatus are connected in a manner of series/parallel, and the retention aperture of the ultrafiltration hollow fiber is 50kd-900kd.
4. equipment as claimed in claim 1, it is characterised in that be also associated with first row on first pipeline and the 4th pipeline Liquid pipe road, first Drainage pipe are used to discharge the waste liquid being concentrated to give by purifying.
5. equipment as claimed in claim 4, it is characterised in that the equipment also includes waste collection tank, first discharge opeing Pipeline connects the waste collection tank, and the waste collection tank is used to handle the waste liquid.
6. equipment as claimed in claim 1, it is characterised in that the ultrafiltration apparatus is also associated with the second Drainage pipe, described Second Drainage pipe is used for the virion antigen for discharging concentration.
7. equipment as claimed in claim 1, it is characterised in that first fluid reservoir is also associated with a sample adding device, described Sample adding device is used to add physiological saline into the first fluid reservoir.
8. equipment as claimed in claim 1, it is characterised in that the equipment also includes a feed pipe, and the feed pipe is used for The virion antigen of concentration to be purified is inputted into first fluid reservoir.
9. equipment as claimed in claim 1, it is characterised in that first pipeline, and/or second pipe, and/or the 3rd pipe Road, and/or the 4th pipeline, and/or the 5th pipeline are provided with a valve, and the valve is used for the ON/OFF of pipeline;And/or
First pipeline, and/or set on second pipe, and/or the 3rd pipeline, and/or the 4th pipeline, and/or the 5th pipeline There is a pressure gauge, the pressure gauge is used to monitor the pressure in pipeline.
10. equipment as claimed in claim 1, it is characterised in that the volume of first fluid reservoir is 100-3000L;And/or The volume of second fluid reservoir is 100-3000L.
CN201720289901.6U 2017-03-23 2017-03-23 A kind of virion antigen purifies concentrator Expired - Fee Related CN206635330U (en)

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Application Number Priority Date Filing Date Title
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110317832A (en) * 2018-03-28 2019-10-11 上海赛比曼生物科技有限公司 The method of the pure preparations of GMP grades of prepare with scale recombined lentivirus vectors
CN111979120A (en) * 2019-05-23 2020-11-24 比欧联科供应链管理(北京)有限公司 Rabies vaccine nucleic acid digestion removal device and experiment method

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110317832A (en) * 2018-03-28 2019-10-11 上海赛比曼生物科技有限公司 The method of the pure preparations of GMP grades of prepare with scale recombined lentivirus vectors
CN110317832B (en) * 2018-03-28 2022-07-05 西比曼生物科技(香港)有限公司 GMP (good manufacturing practice) scale preparation method of purified preparation of recombinant lentiviral vector
CN111979120A (en) * 2019-05-23 2020-11-24 比欧联科供应链管理(北京)有限公司 Rabies vaccine nucleic acid digestion removal device and experiment method
CN111979120B (en) * 2019-05-23 2022-09-27 比欧联科供应链管理(北京)有限公司 Rabies vaccine nucleic acid digestion removal device and experiment method

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