CN114247398A - Lipid nanoparticle preparation system and equipment - Google Patents
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- CN114247398A CN114247398A CN202111552157.1A CN202111552157A CN114247398A CN 114247398 A CN114247398 A CN 114247398A CN 202111552157 A CN202111552157 A CN 202111552157A CN 114247398 A CN114247398 A CN 114247398A
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0006—Controlling or regulating processes
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
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- B01D29/01—Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups B01D24/00 - B01D27/00; Filtering elements therefor with flat filtering elements
- B01D29/03—Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups B01D24/00 - B01D27/00; Filtering elements therefor with flat filtering elements self-supporting
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- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
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Abstract
The application discloses a lipid nanoparticle preparation system and equipment, and relates to the technical field of medicine preparation. The lipid nanoparticle preparation system comprises a mixing device, a first material supply unit, a second material supply unit and two filtering devices; the mixing device is respectively communicated with the first material supply unit and the second material supply unit and is used for mixing the carrier solution and the loaded solution to generate the lipid nanoparticle solution; one filtering device is communicated between the first material supply unit and the mixing device, and the other filtering device is communicated between the second material supply unit and the mixing device. The lipid nanoparticle preparation system provided by the present application can prevent the blockage of the mixing device.
Description
Technical Field
The application relates to the technical field of medicine preparation, in particular to a lipid nanoparticle preparation system and equipment.
Background
Lipid Nanoparticles (LNPs) are novel drug delivery systems that are formed by dissolving, coating or attaching drugs or other biologically active substances onto the surface of lipid nanoparticles, using biocompatible lipid materials as carriers. The lipid nanoparticles can improve drug absorption, have the advantages of slow release, controlled release, improved drug stability, enhanced curative effect, reduced toxic and side effects and the like, and are stable in vivo and in the storage process. The carrier system is widely applied to genetic drugs, antitumor drugs, proteins, polypeptides and other drugs.
However, the existing lipid nanoparticle processing equipment is easy to block in the lipid nanoparticle processing process, and has low production efficiency and influence on product quality.
Disclosure of Invention
The application provides a lipid nanoparticle preparation system and equipment, which can prevent a mixing device from being blocked.
The present application provides:
a lipid nanoparticle preparation system comprises a mixing device, a first material supply unit, a second material supply unit and two filtering devices;
wherein the mixing device is respectively communicated with the first material supply unit and the second material supply unit, the first material supply unit is used for supplying a carrier solution to the mixing device, the second material supply unit is used for supplying a carried solution to the mixing device, and the mixing device is used for mixing the carrier solution and the carried solution to generate a lipid nanoparticle solution;
one filtering device is communicated between the first material supply unit and the mixing device, and the other filtering device is communicated between the second material supply unit and the mixing device.
In some possible embodiments, the lipid nanoparticle preparation system further comprises an adapter device and a diluent supply device, the adapter device being in communication with the mixing device and the diluent supply device, respectively;
the diluent supply device is used for supplying diluent to the adapter device so as to dilute the lipid nanoparticle solution.
In some possible embodiments, the filter device comprises a material supply side, a material output side and a filter plate, the material supply side and the material output side are respectively arranged at two sides of the filter plate, the material supply side is communicated with a material supply unit connected with the filter device, and the material output side is communicated with the mixing device;
the lipid nanoparticle preparation system further comprises a cleaning solution supply device, and the cleaning solution supply device is respectively communicated with the material supply sides of the two filtering devices.
In some possible embodiments, the adapter device comprises a cleaning liquid delivery line and a dilution line;
wherein the dilution pipeline is respectively communicated with the mixing device and the diluent supply device;
the cleaning liquid conveying pipeline is respectively communicated with the cleaning liquid supply device and the material supply sides of the two filtering devices.
In some possible embodiments, the adapter device is further provided with an input pipeline, a switching valve core is further arranged in the adapter device, and the switching valve core comprises a first working state and a second working state;
when the switching valve core is in the first working state, the input pipeline is communicated between the dilution pipeline and the dilution liquid supply device;
when the switching valve core is in the second working state, the input pipeline is communicated between the cleaning liquid conveying pipeline and the cleaning liquid supply device.
In some possible embodiments, the lipid nanoparticle preparation system further includes a product receiving device, and an end of the dilution line, which is far from the mixing device, is communicated with the product receiving device.
In some possible embodiments, the filtration device comprises a first transfer port, a second transfer port, a third transfer port, and a fourth transfer port;
the first transmission port, the third transmission port and the fourth transmission port are communicated with the material supply side, the first transmission port is communicated with a material supply unit connected with the filtering device, the third transmission port is communicated with the cleaning liquid supply device, the fourth transmission port is communicated to a dirt recovery device, and valve bodies are arranged at the positions of the third transmission port and the fourth transmission port to control the opening and closing of the third transmission port and the fourth transmission port;
the second transmission port is communicated between the material output side and the mixing device.
In some possible embodiments, the mixing device includes a first distribution groove, a second distribution groove, a collection groove, and a plurality of mixed flow passages, the mixed flow passages are respectively communicated with the first distribution groove, the second distribution groove, and the collection groove;
the first distribution groove is communicated with the first material supply unit, the second distribution groove is communicated with the second material supply unit, and the collecting groove is used for collecting and outputting the lipid nanoparticle solution.
In some possible embodiments, the mixed flow channel comprises a first branch channel, a second branch channel and a confluence channel, and the first branch channel and the second branch channel are communicated with the same end of the confluence channel;
one end of the first branch channel, which is far away from the confluence channel, is communicated with the first distribution groove, one end of the second branch channel, which is far away from the confluence channel, is communicated with the second distribution groove, and one end of the confluence channel, which is far away from the first branch channel, is communicated with the collection groove;
the bus duct includes at least one S-bend segment.
In addition, the application also provides a lipid nanoparticle preparation device, which comprises the lipid nanoparticle preparation system provided by the application.
The beneficial effect of this application is: the application provides a lipid nanoparticle preparation system and equipment, wherein, lipid nanoparticle preparation system includes mixing arrangement, first material feed unit, second material feed unit and two filter equipment, and first material feed unit and second material feed unit all communicate with the mixing arrangement, and a filter equipment intercommunication is between first material feed unit and mixing arrangement, and another filter equipment intercommunication sets up between second material feed unit and mixing arrangement.
In use, the first material supply unit may supply the carrier solution to the mixing device, the second material supply unit may supply the loaded solution to the mixing device, and the carrier solution and the loaded solution may be mixed and reacted in the mixing device to generate the lipid nanoparticle solution. Wherein, filter equipment can filter carrier solution and the thing solution of being carried, avoids impurity to get into mixing arrangement and causes the jam to, also can ensure the smooth preparation of lipid nanoparticle, avoid influencing preparation efficiency.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are required to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present application and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained from the drawings without inventive effort.
Fig. 1 illustrates a schematic structural view of some example lipid nanoparticle preparation systems as they process lipid nanoparticles;
fig. 2 shows a schematic of the structure of the lipid nanoparticle preparation system when the filtration device is cleaned in some embodiments;
FIG. 3 shows a schematic structural diagram of a mixing device in some embodiments;
FIG. 4 shows a schematic cross-sectional view of a filter arrangement in some embodiments;
FIG. 5 shows a schematic diagram of the construction of a filter device in some embodiments;
fig. 6 shows a schematic internal structure of the adapter device in some embodiments.
Description of the main element symbols:
11-a first material supply unit; 111-a first storage device; 112-a first delivery pump; 12-a second material supply unit; 121-a second storage device; 122-a second delivery pump; 20-a mixing device; 21-a first material input port; 22-a second material input port; 23-a material outlet; 24-a first distribution groove; 25-a second distribution groove; 26-a collection tank; 27-a mixed flow channel; 271-a sink channel; 272-a first branch channel; 273-second branch channel; 28-a substrate; 30-a filtration device; 30 a-a first filter device; 30 b-a second filtration device; 31-a housing; 32-a filter plate; 33-a first transfer port; 34-a second transfer port; 35-a third transfer port; 36-a fourth transfer port; 301-material supply side; 302-material output side; 40-a switching device; 41-a first input port; 42-a second input port; 43-first output port; 44-a second output port; 45-dilution line; 46-cleaning liquid conveying pipeline; 47-transfer line; 48-input line; 51-a diluent supply; 52-a third delivery pump; 60-a product receiving device; 70-a dirt recovery device; 80-cleaning liquid supply means.
Detailed Description
Reference will now be made in detail to embodiments of the present application, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the drawings are exemplary only for the purpose of explaining the present application and are not to be construed as limiting the present application.
In the description of the present application, it is to be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," "counterclockwise," "axial," "radial," "circumferential," and the like are used in the orientations and positional relationships indicated in the drawings for convenience in describing the present application and for simplicity in description, and are not intended to indicate or imply that the referenced devices or elements must have a particular orientation, be constructed and operated in a particular orientation, and are therefore not to be considered limiting of the present application.
Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the present application, "a plurality" means two or more unless specifically limited otherwise.
In this application, unless expressly stated or limited otherwise, the terms "mounted," "connected," "secured," and the like are to be construed broadly and can include, for example, fixed connections, removable connections, or integral parts; can be mechanically or electrically connected; either directly or indirectly through intervening media, either internally or in any other relationship. The specific meaning of the above terms in the present application can be understood by those of ordinary skill in the art as appropriate.
In this application, unless expressly stated or limited otherwise, the first feature "on" or "under" the second feature may be directly contacting the first and second features or indirectly contacting the first and second features through intervening media. Also, a first feature "on," "over," and "above" a second feature may be directly or diagonally above the second feature, or may simply indicate that the first feature is at a higher level than the second feature. A first feature being "under," "below," and "beneath" a second feature may be directly under or obliquely under the first feature, or may simply mean that the first feature is at a lesser elevation than the second feature.
Example one
Embodiments provide a lipid nanoparticle preparation system, which can be used for preparing lipid nanoparticles.
As shown in fig. 1, the lipid nanoparticle preparation system may include a first material supply unit 11, a second material supply unit 12, a mixing device 20, and two filtering devices 30. In which two filtering devices 30, a first filtering device 30a and a second filtering device 30 b.
In the embodiment, the mixing device 20 may be respectively communicated with the first material supply unit 11 and the second material supply unit 12. In use, the first material supply unit 11 and the second material supply unit 12 may supply material to the mixing device 20 separately. For example, the first material supply unit 11 may supply a carrier solution, for example, an ethanol solution mixed with lipid, to the mixing device 20. The second material supply unit 12 may supply a solution to be loaded, for example, a solution mixed with a drug, a bioactive substance, or the like, to the mixing device 20.
The carrier solution and the solution to be carried can be mixed in the mixing device 20, so that the polarity of the solution is rapidly increased to supersaturate lipid molecules, and the lipid nanoparticles are self-assembled.
In an embodiment, a first filtering device 30a may be connected between the first material supply unit 11 and the mixing device 20, and the first filtering device 30a may filter the carrier solution flowing through. The second filtering device 30b may be connected between the second material supply unit 12 and the mixing device 20, and the second filtering device 30b may filter the loaded solution flowing through.
During the lipid nanoparticle processing, the first material supply unit 11 and the second material supply unit 12 can supply the carrier solution and the loaded solution to the mixing device 20 far and continuously as required, so that the carrier and the loaded solution are assembled into the lipid nanoparticles in the mixing device 20. The two filtering devices 30 can respectively take out impurities in the carrier solution and the loaded solution, so as to avoid the impurities from entering the mixing device 20 to cause blockage, thereby ensuring the smooth preparation of the lipid nanoparticles.
Example two
The embodiment provides a lipid nanoparticle preparation system, which can be used for preparing lipid nanoparticles of messenger Ribonucleic Acid (mRNA) vaccine drugs. It is understood that the present embodiment may be a further improvement on the first embodiment.
The mRNA vaccine raw material is messenger RNA single strand, does not need to enter cell nucleus, and has no risk of integrating exogenous gene segment into genome. However, since mRNA is very fragile and easily degraded by in vivo enzymes, the key to influence the potency of mRNA is the carrier and delivery technology.
Lipid nanoparticles can be formed by the self-assembly of particles of mRNA and lipid, formed by two liquids at appropriate flow rates and ratios. During the preparation process, the aqueous solution of mRNA and the ethanol solution of lipid are required to be rapidly mixed to rapidly increase the polarity of the solution, so that lipid molecules are supersaturated, and the lipid nanoparticles are subjected to self-assembly.
Accordingly, in an embodiment, the carrier solution may be a lipid ethanol solution, and the cargo solution may be an aqueous mRNA solution.
As shown in fig. 1, in some embodiments, the first material supply unit 11 may include a first stocker 111 and a first transfer pump 112. The first storage device 111 may be used to store the lipid ethanol solution. Accordingly, the first stock device 111 may be a barrel, box, or the like.
The input end of the first delivery pump 112 may be connected to the first storage device 111 through a hose, and the output end of the first delivery pump 112 may also be connected to the first filtering device 30a through a hose. In operation, the first delivery pump 112 may be used as a power source to continuously deliver the lipid ethanol solution in the first storage device 111 to the first filtering device 30a, and then deliver the lipid ethanol solution to the mixing device 20 after being filtered by the first filtering device 30 a. In some embodiments, the first delivery pump 112 can be a constant flow pump, and when in operation, the first delivery pump 112 delivers the lipid ethanol solution to the mixing device 20 at a set constant flow rate, wherein the flow rate of the lipid ethanol solution can be configured as desired.
Of course, in other embodiments, the first transfer pump 112 may also be a pump body structure such as a constant pressure pump.
In some embodiments, the second material supply unit 12 may include a second storage device 121 and a second delivery pump 122. Wherein, the second storing device 121 can be used for storing the mRNA aqueous solution. In the embodiment, the second stock device 121 may be a barrel-shaped, box-shaped, or the like structure.
The input end of the second delivery pump 122 may be connected to the second storage device 121 through a hose, and the output end of the second delivery pump 122 may also be connected to the second filtering device 30b through a hose. In operation, the second delivery pump 122 can be used as a power source for the second material supply unit 12 to continuously deliver the mRNA aqueous solution to the second filtering device 30b and further to the mixing device 20.
In some embodiments, the structures of the first and second filter devices 30a and 30b may be configured to be the same.
As shown in fig. 4 and 5, the filter device 30 may include a housing 31 and a filter plate 32. It is understood that the housing 31 may form a corresponding receiving chamber, and the filter plate 32 may be disposed in the housing 31 and divide the receiving chamber into two sub-receiving chambers separated from each other. One of the sub-receiving cavities may serve as a material supply side 301, communicating with a corresponding material supply unit. The other sub-receiving chamber may serve as a material output side 302 for receiving the filtered solution, and may be in communication with the mixing device 20.
In one embodiment, the housing 31 may be formed with a first transfer port 33 and a second transfer port 34, wherein the first transfer port 33 may be communicated with the material supply side 301, and the second transfer port 34 may be communicated with the material output side 302.
Referring also to fig. 1 and 3, in the first filter device 30a, the first transfer port 33 may be connected to the output end of the first transfer pump 112, and correspondingly, the second transfer port 34 may be connected to the mixing device 20. In the second filter device 30b, the first transfer port 33 may be connected to the output of the second transfer pump 122, and the second transfer port 34 may be connected to the mixing device 20. In use, the filter plate 32 of the first filtration device 30a can filter the lipid ethanol solution, and the filter plate 32 of the second filtration device 30b can filter the mRNA aqueous solution, so as to prevent impurities from entering the mixing device 20 and causing blockage.
As shown in fig. 3, the mixing device 20 includes a first material input port 21, a second material input port 22, and a material output port 23. The first material inlet 21 and the second material inlet 22 are both communicated with the material outlet 23. The first material inlet 21 is connected to the second transfer port 34 of the first filter device 30a, i.e. the first material inlet 21 is connected to the first material supply unit 11. The second material inlet port 22 may be in communication with the second transfer port 34 of the second filter device 30b and, correspondingly, the second material inlet port 22 may be in communication with the second material supply unit 12.
In an embodiment, the mixing device 20 may include a base plate 28, and a first distribution tank 24, a second distribution tank 25, and a collection tank 26 opening onto the base plate 28. Wherein the first material inlet 21 may be in communication with the first distribution chute 24, the second material inlet 22 may be in communication with the second distribution chute 25, and the material outlet 23 may be in communication with the collection chute 26. It will be appreciated that the first material inlet 21, the second material inlet 22 and the material outlet 23 may also all open onto the substrate 28.
The base plate 28 is further provided with a plurality of mixed flow passages 27 respectively communicating between the first distribution groove 24, the second distribution groove 25 and the collection groove 26. The mixed flow channel 27 may obtain the lipid ethanol solution from the first distribution tank 24 and the aqueous mRNA solution from the second distribution tank 25. The lipid ethanol solution and the mRNA aqueous solution may be combined in the mixed flow channel 27 and reacted to generate lipid nanoparticles. The resulting lipid nanoparticle solution may then enter holding tank 26 and be output through material output port 23.
In some embodiments, the mixed flow channels 27 may be provided with a plurality of sets, and accordingly, the first distribution groove 24 and the second distribution groove 25 may distribute the corresponding solutions to the plurality of mixed flow channels 27, and the generation of the lipid nanoparticles may be simultaneously performed within the plurality of mixed flow channels 27. For example, the mixed flow passages 27 may be provided in two, three, four, five, eight, etc. groups.
Of course, in other embodiments, the mixed flow passages 27 may be arranged in a group.
In the embodiment shown in fig. 3, the structure of each mixed flow passage 27 may be the same. The mixed flow passage 27 may include a first branch passage 272, a second branch passage 273, and a confluence passage 271. Wherein, the first branch passage 272 and the second branch passage 273 are both communicated with the confluence passage 271. An end of the first branch passage 272 remote from the confluence passage 271 may communicate with the first distribution groove 24, and an end of the second branch passage 273 remote from the confluence passage 271 may communicate with the second distribution groove 25. Correspondingly, an end of the converging passage 271 remote from the first branch passage 272 and the second branch passage 273 may communicate with the collecting groove 26.
In operation, the lipid ethanol solution may be distributed through the first distribution groove 24 into the first branch passage 272 of the plurality of mixed flow passages 27. The aqueous mRNA solution can be distributed to the second branch channel 273 of the plurality of mixed flow channels 27 through the second distribution groove 25. The lipid ethanol solution and the mRNA aqueous solution may be transferred into the confluent passage 271 through the first branch passage 272 and the second branch passage 273, respectively, and the lipid ethanol solution and the mRNA aqueous solution may be mixed in the confluent passage 271. It is understood that the lipid ethanol solution and the mRNA aqueous solution may have a flow rate by the first and second delivery pumps 112 and 122, and the lipid ethanol solution and the mRNA aqueous solution may be rapidly mixed in the confluence channel 271 such that the solution polarity is rapidly increased to supersaturate the lipid molecules, thereby allowing the lipid nanoparticles to complete self-assembly.
As shown in fig. 3, in some embodiments, the bus channel 271 may include at least one S-shaped curved segment, which may increase the extension length of the bus channel 271 on the substrate 28 with limited size, and at the same time, may also allow the lipid ethanol solution and the mRNA aqueous solution to be rapidly and uniformly mixed, thereby accelerating the generation of lipid nanoparticles. Illustratively, the bus duct 271 may include one, two, four, six, etc. S-shaped curved segments. The turning part of the S-shaped bending section can be right-angle turning or circular arc turning.
In use, a user can replace the mixing device 20 with different preparation efficiencies as needed to meet different production requirements. For example, in a pilot-scale validation of a drug, a less efficient preparation mixing device 20 may be selected. When mass production needs to be performed, the mixing device 20 with higher production efficiency can be replaced without replacing the whole system, so that the cost can be reduced. Wherein the mixing device 20 with larger preparation efficiency can have more mixed flow channels 27 than the mixing device 20 with smaller preparation efficiency to accelerate the generation of lipid nanoparticles.
As shown in fig. 1 and 6, in some embodiments, the lipid nanoparticle preparation system further includes a transfer device 40 and a diluent supply device 51. The switching device 40 may include a first input port 41, a second input port 42, a first output port 43, and a second output port 44. The first output port 43 communicates with the first input port 41, and the second output port 44 may communicate with the first input port 41 and the second input port 42, respectively.
In one embodiment, the material outlet 23 of the mixing device 20 may be connected to the second inlet 42 by a hose. The lipid nanoparticle solution with a higher concentration generated by the mixing device 20 can be delivered to the adapter device 40 through the second input port 42.
The diluent supply device 51 may be used to store diluent. The diluent supply device 51 may be configured in a barrel shape, a box shape, or the like. The diluent supply device 51 may be in communication with the first input port 41, and the diluent supply device 51 may supply a diluent into the adaptor device 40 to dilute the lipid nanoparticle solution with a higher concentration to form a lipid nanoparticle solution with a relatively lower concentration.
In an embodiment, the lipid nanoparticle preparation system further includes a product receiving device 60, and the second output port 44 may be connected to the product receiving device 60 through a hose. In operation, the adaptor device 40 may deliver the diluted lipid nanoparticle solution to the product receiving device 60 for storage. In embodiments, the product receiving device 60 may be a barrel, box, or the like.
As shown in fig. 1, the lipid nanoparticle preparation system further includes a third transfer pump 52. An input end of the third transfer pump 52 may be connected to the diluent supplier 51 through a hose, and an output end of the third transfer pump 52 may be connected to the first input port 41 through another hose. In operation, the third delivery pump 52 may be used as a power source to continuously supply the diluent in the diluent supply device 51 to the adaptor device 40 to dilute the lipid nanoparticle solution with relatively high concentration. In some embodiments, third transfer pump 52 may be a diaphragm pump.
Of course, in other embodiments, the third transfer pump 52 does not preclude the use of peristaltic, plunger, or other pump configurations.
As shown in fig. 2 and fig. 6, in some embodiments, the lipid nanoparticle preparation system further includes a cleaning solution supply device 80, and the cleaning solution supply device 80 can also be communicated to the material supply sides 301 of the two filtering devices 30 through the adapter device 40. Specifically, the cleaning liquid supply device 80 may also be communicated with the first input port 41 via the third transfer pump 52. The first outlet 43 may be in communication with the material supply side 301 of both filter devices 30 via a hose. In the embodiment, the input end of the third transfer pump 52 may be switched between the diluent supply device 51 and the cleaning liquid supply device 80, for example, by manual switching.
In the embodiment, the adapter 40 may be provided with a dilution line 45, a cleaning solution delivery line 46, an adapter line 47 and an input line 48. Wherein the second input port 42 and the second output port 44 are respectively disposed at two ends of the dilution line 45. The input pipeline 48 may be coaxial and in communication with the cleaning solution delivery pipeline 46, the first input port 41 may be disposed at a distal end of the input pipeline 48 away from the cleaning solution delivery pipeline 46, and the first output port 43 may be disposed at an end of the cleaning solution delivery pipeline 46 away from the input pipeline 48. The dilution line 45 can be connected to the input line 48 via a switching line 47, and in particular, an end of the switching line 47 remote from the dilution line 45 can be connected to a connection between the input line 48 and the cleaning solution delivery line 46.
In some embodiments, the connection between the switching line 47 and the cleaning liquid supply line 46 and the input line 48 may be provided with a switching valve (not shown) for switching the communication direction of the passage. Wherein the switching spool may include a first operating state and a second operating state. The first operating state is a state in which the switch valve element is in a state in which the input line 48 and the changeover line 47 are connected and the input line 48 and the cleaning liquid supply line 46 are disconnected. The second operating state is a state in which the switching valve element is in a state in which the input line 48 is in communication with the cleaning liquid delivery line 46 and the input line 48 is disconnected from the changeover line 47.
Accordingly, when the switching spool is in the first operating state, the input line 48 and the switching line 47 can be communicated, i.e., the diluent supply device 51 can be communicated with the diluent line 45. At the same time, the inlet line 48 is disconnected from the cleaning fluid delivery line 46.
When the switching valve is in the second state, the input line 48 can be made to communicate with the cleaning liquid delivery line 46, and the cleaning liquid supply device 80 can be made to communicate with the cleaning liquid delivery line 46. At the same time, the inlet line 48 is disconnected from the dilution line 45.
In some embodiments, the adapter 40 may be a multi-channel valve.
In use, the input end of the third transfer pump 52 may be communicated with the diluent supply device 51 and the input line 48 may be communicated with the transit line 47 when lipid nanoparticles are produced. The mixing device 20 may deliver the prepared lipid nanoparticle solution to the adaptor device 40, and at the same time, the diluent supply device 51 may supply a diluent to the adaptor device 40 to dilute the lipid nanoparticle solution, and the diluted lipid nanoparticle solution may be delivered to the product receiving device 60 through the second output port 44.
After a period of production, a certain amount of impurities are accumulated on the filter plates 32 in the filter device 30, and the filter plates 32 can be washed by the cleaning solution. When the filter plate 32 needs to be cleaned, the working state of the switching valve core can be adjusted, so that the input pipeline 48 is communicated with the cleaning liquid conveying pipeline 46, and the input pipeline 48 is disconnected with the switching pipeline 47. Meanwhile, the input end of the third transfer pump 52 may be communicated to the cleaning liquid supply device 80 through another hose. During the cleaning process, the third delivery pump 52 can be used as a power source for delivering the cleaning solution, so that the cleaning solution is continuously delivered to the material supply sides 301 of the two filter devices 30 through the switching device 40 to clean the filter plates 32.
Referring to fig. 5, the housing 31 of the filtering device 30 is further provided with a third transfer port 35 and a fourth transfer port 36, and both the third transfer port 35 and the fourth transfer port 36 can be communicated with the material supply side 301. Wherein the third transfer port 35 may communicate with the first output port 43 of the adapter device 40. The fourth transfer port 36 may be connected by piping to a waste recovery device 70. Wherein, the dirt recovery device can also be a box body, a barrel-shaped structure and the like.
In some embodiments, the third transfer port 35 may be positioned near the top of the filter device 30 and the fourth transfer port 36 may be positioned near the bottom of the filter device 30, i.e., the third transfer port 35 is positioned above the fourth transfer port 36.
During cleaning of the filter plates 32, cleaning liquid can enter the interior of the filter device 30 through the third transfer port 35 and can move in the direction of the fourth transfer port 36. During this time, the cleaning fluid may pass through the filter plate 32 and clean the filter plate 32. The soiled cleaning liquid may be output from the fourth transfer port 36 and delivered to the soil reclamation apparatus 70.
The third transfer port 35 and the fourth transfer port 36 may be provided with valves to control the opening and closing of the third transfer port 35 and the fourth transfer port 36. It is understood that the valves at the positions of the third transfer port 35 and the fourth transfer port 36 can be in a closed state during the processing of the lipid nanoparticles. When the filter plate 32 needs to be cleaned, the valves at the positions of the third transfer port 35 and the fourth transfer port 36 can be opened, and meanwhile, the connection between the second transfer port 34 and the mixing device 20 can be disconnected through the operation of pulling out a hose and the like, so that the cleaning liquid is prevented from entering the mixing device 20 and causing pollution. In some embodiments, the valves at the third transfer port 35 and the fourth transfer port 36 may be solenoid valves.
In an embodiment, the lipid nanoparticle preparation system further includes a controller, which is electrically connected to each electrical component in the lipid nanoparticle preparation system, so that the controller can control the operation of each electrical component, and the lipid nanoparticles can be automatically produced.
EXAMPLE III
Embodiments also provide a lipid nanoparticle preparation apparatus, which may include a main housing and the lipid nanoparticle preparation system provided in the embodiments. Wherein the lipid nanoparticle preparation system may be installed within the main chassis. In an embodiment, an operation interface may be disposed on the main housing, and the operation interface may be electrically connected to a controller in the lipid nanoparticle preparation system, so that a user may perform related operations.
In the description herein, reference to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the application. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, various embodiments or examples and features of different embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction.
Although embodiments of the present application have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present application, and that variations, modifications, substitutions and alterations may be made to the above embodiments by those of ordinary skill in the art within the scope of the present application.
Claims (10)
1. A lipid nanoparticle preparation system is characterized by comprising a mixing device, a first material supply unit, a second material supply unit and two filtering devices;
wherein the mixing device is respectively communicated with the first material supply unit and the second material supply unit, the first material supply unit is used for supplying a carrier solution to the mixing device, the second material supply unit is used for supplying a carried solution to the mixing device, and the mixing device is used for mixing the carrier solution and the carried solution to generate a lipid nanoparticle solution;
one filtering device is communicated between the first material supply unit and the mixing device, and the other filtering device is communicated between the second material supply unit and the mixing device.
2. The lipid nanoparticle preparation system according to claim 1, further comprising an adapter and a diluent supply, the adapter being in communication with the mixing device and the diluent supply, respectively;
the diluent supply device is used for supplying diluent to the adapter device so as to dilute the lipid nanoparticle solution.
3. The lipid nanoparticle preparation system according to claim 2, wherein the filtering device comprises a material supply side, a material output side, and a filter plate, the material supply side and the material output side are respectively provided at both sides of the filter plate, the material supply side is in communication with a material supply unit to which the filtering device is connected, and the material output side is in communication with the mixing device;
the lipid nanoparticle preparation system further comprises a cleaning solution supply device, and the cleaning solution supply device is respectively communicated with the material supply sides of the two filtering devices.
4. The lipid nanoparticle preparation system of claim 3, wherein the adapter comprises a wash fluid delivery line and a dilution line;
wherein the dilution pipeline is respectively communicated with the mixing device and the diluent supply device;
the cleaning liquid conveying pipeline is respectively communicated with the cleaning liquid supply device and the material supply sides of the two filtering devices.
5. The lipid nanoparticle preparation system according to claim 4, wherein the adapter device is further provided with an input pipeline, and a switching valve core is further arranged in the adapter device, and the switching valve core comprises a first working state and a second working state;
when the switching valve core is in the first working state, the input pipeline is communicated between the dilution pipeline and the dilution liquid supply device;
when the switching valve core is in the second working state, the input pipeline is communicated between the cleaning liquid conveying pipeline and the cleaning liquid supply device.
6. The lipid nanoparticle preparation system of claim 5, further comprising a product receiving device, wherein an end of the dilution line remote from the mixing device is in communication with the product receiving device.
7. The lipid nanoparticle preparation system of claim 3, wherein the filtration device comprises a first transfer port, a second transfer port, a third transfer port, and a fourth transfer port;
the first transmission port, the third transmission port and the fourth transmission port are communicated with the material supply side, the first transmission port is communicated with a material supply unit connected with the filtering device, the third transmission port is communicated with the cleaning liquid supply device, the fourth transmission port is communicated to a dirt recovery device, and valve bodies are arranged at the positions of the third transmission port and the fourth transmission port to control the opening and closing of the third transmission port and the fourth transmission port;
the second transmission port is communicated between the material output side and the mixing device.
8. The lipid nanoparticle preparation system according to claim 1, wherein the mixing device comprises a first distribution groove, a second distribution groove, a collection groove, and a plurality of mixed flow channels, the mixed flow channels being respectively communicated with the first distribution groove, the second distribution groove, and the collection groove;
the first distribution groove is communicated with the first material supply unit, the second distribution groove is communicated with the second material supply unit, and the collecting groove is used for collecting and outputting the lipid nanoparticle solution.
9. The lipid nanoparticle preparation system of claim 8, wherein the mixed flow channel comprises a first branch channel, a second branch channel and a confluence channel, and the first branch channel and the second branch channel are communicated with the same end of the confluence channel;
one end of the first branch channel, which is far away from the confluence channel, is communicated with the first distribution groove, one end of the second branch channel, which is far away from the confluence channel, is communicated with the second distribution groove, and one end of the confluence channel, which is far away from the first branch channel, is communicated with the collection groove;
the bus duct includes at least one S-bend segment.
10. A lipid nanoparticle production apparatus, comprising the lipid nanoparticle production system according to any one of claims 1 to 9.
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