CN112500997A - Auxiliary device for online culture solution supplementation of antibacterial drug in-vitro PK/PD model and use method of auxiliary device - Google Patents
Auxiliary device for online culture solution supplementation of antibacterial drug in-vitro PK/PD model and use method of auxiliary device Download PDFInfo
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- CN112500997A CN112500997A CN202011508071.4A CN202011508071A CN112500997A CN 112500997 A CN112500997 A CN 112500997A CN 202011508071 A CN202011508071 A CN 202011508071A CN 112500997 A CN112500997 A CN 112500997A
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
- C12M23/08—Flask, bottle or test tube
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/38—Caps; Covers; Plugs; Pouring means
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/04—Filters; Permeable or porous membranes or plates, e.g. dialysis
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/06—Nozzles; Sprayers; Spargers; Diffusers
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
Abstract
The invention provides an auxiliary device for online culture solution supplementation of an antibacterial in-vitro PK/PD model, and belongs to the technical field of antibacterial in-vitro efficacy research. The auxiliary device comprises a donor bottle cap for covering a donor bottle in a PK/PD model and a receptor bottle cap for covering a receptor bottle in the PK/PD model; a donor bottle gas inlet pipeline and a donor bottle liquid outlet pipeline are hermetically penetrated through the bottle cap of the donor bottle, one ends of the gas inlet pipeline and the donor bottle liquid outlet pipeline, which extend out of the donor bottle, are respectively provided with a first luer connector and a second luer connector, and a first filter is arranged on the first luer connector; a receptor bottle liquid leading-in pipeline, a receptor bottle gas leading-out pipeline and a receptor bottle liquid leading-out pipeline are hermetically penetrated through the receptor bottle cap, a third luer connector and a fourth luer connector are respectively arranged at one ends of the receptor bottle liquid leading-in pipeline and the receptor bottle gas leading-out pipeline, which extend out of the receptor bottle, and a second filter is arranged on the fourth luer connector. The auxiliary device for online culture solution supplementation of the antibacterial drug in-vitro PK/PD model can realize online culture solution supplementation for a fresh culture solution storage container of the in-vitro PK/PD model.
Description
Technical Field
The invention relates to the technical field of antibacterial drug in-vitro efficacy research, in particular to an auxiliary device for online culture solution supplementation of an antibacterial drug in-vitro PK/PD model and a using method thereof.
Background
The in-vitro PK/PD technology of the antibacterial drug is a research technology which simulates the pharmacokinetic process of the drug in a human body in an in-vitro device and observes the killing effect of the antibacterial drug on bacteria in the process, thereby integrating the pharmacokinetic factors and the antibacterial activity of the drug. The technology can be used for carrying out PK/PD research on the antibacterial drugs, and further provides reference for the establishment of clinical schemes of the antibacterial drugs.
At present, the technology is adopted internationally and domestically, and the technology needs to be completed based on a set of special equipment. The hardware architecture of the in vitro PK/PD model generally includes: fresh culture medium container, central authorities room, waste liquid storage container, peristaltic pump, agitator etc. several parts constitute, wherein connect through the silicone tube between fresh culture medium container, central authorities room, the waste liquid storage container and constitute the liquid way, and the peristaltic pump is as liquid way drive with fresh culture solution from storage container pump-in to central authorities room, need keep liquid volume stable in the central authorities room, consequently will have equivalent liquid in step and pump out to waste liquid storage container from the central authorities indoor. In the process, the medicament introduced into the central chamber can form exponential decay, the pharmacokinetics process of the medicament in the body can be simulated through the adjustment of the liquid flow rate, and meanwhile, if bacteria are inoculated into the central chamber, the antibacterial effect of the medicament on the bacteria in the dynamic change of concentration can be investigated.
The in vitro PK/PD model requires a larger volume of fresh medium to be used during the run, especially when the administration period to be investigated is longer or the frequency of administration is higher, a larger volume of culture fluid is consumed. Secondly, when multiple models are operated synchronously, the multiple models are connected to the same fresh medium storage container for simplifying the structure and increasing the controllability. Therefore, the in vitro PK/PD model technology puts a great demand on the volume of a fresh culture medium storage container. Researchers often choose to purchase high temperature resistant large volume plastic drums from the market and configure special caps to meet this requirement. However, large volume storage vessels require the addition and autoclaving of large volumes of broth at a time during use, and the broth requires a pre-heat treatment prior to pumping into the central chamber, which can be inconvenient due to excessive volume and weight.
Disclosure of Invention
In view of the above, the present invention provides an auxiliary device for online supplementing a culture solution to an antimicrobial drug PK/PD model and a method for using the same, so as to solve the problems in the prior art that a large amount of culture solution needs to be added at one time and autoclaved during the use of a large-volume storage container, the culture solution needs to be preheated before being pumped into a central chamber, and the excessive volume and weight cause great inconvenience to the processes or the operation processes.
In order to achieve the above purpose, the invention provides the following technical scheme:
an auxiliary device for online culture solution supplementation of an antibacterial drug in-vitro PK/PD model comprises a donor bottle cap for covering a donor bottle in the PK/PD model and a receptor bottle cap for covering a receptor bottle in the PK/PD model;
a donor bottle gas introduction pipeline and a donor bottle liquid discharge pipeline are hermetically penetrated through the donor bottle cap, a first luer connector and a second luer connector are respectively arranged at one ends of the gas introduction pipeline and the donor bottle liquid discharge pipeline, which extend out of the donor bottle, and a first filter is arranged on the first luer connector;
a receptor bottle liquid leading-in pipeline, a receptor bottle gas leading-out pipeline and a receptor bottle liquid leading-out pipeline are hermetically penetrated through the receptor bottle cap, a third luer connector and a fourth luer connector are respectively arranged at one ends of the receptor bottle liquid leading-in pipeline and the receptor bottle gas leading-out pipeline, which extend out of the receptor bottle, and a second filter is arranged on the fourth luer connector.
Preferably, the donor bottle cap and the recipient bottle cap are integrally formed.
Preferably, the first and second filters are 0.22 micron filters.
Preferably, the donor bottle gas introduction pipeline, the donor bottle liquid discharge pipeline, the acceptor bottle liquid introduction pipeline, the acceptor bottle gas discharge pipeline and the acceptor bottle liquid discharge pipeline are made of silica gel or rubber.
The invention also provides a use method of the auxiliary device for online culture solution supplementation of the antibacterial drug in-vitro PK/PD model, which comprises the following steps:
s1, covering the bottle cap of the donor bottle on the donor bottle with culture solution prepared inside, connecting the first luer connector and the second luer connector, and then carrying out overall disinfection treatment;
s2, plugging the third luer connector and the fourth luer connector by using a first luer plug and a second luer plug respectively, disinfecting the bottle cap of the receptor bottle, covering the sterilized receptor bottle after the disinfection, and connecting the liquid lead-out pipeline to a central chamber in the PK/PD model;
s3, respectively removing the first and second luer plugs, connecting the second and third luer plugs, respectively connecting the first and second filters at the first and fourth luer plugs, and connecting the first filter to a syringe;
s4 Rapid injection of air into a donor vial in a PK/PD model using the syringe.
Compared with the prior art, the invention has the following beneficial effects:
the auxiliary device for the antibacterial drug in-vitro PK/PD model to supplement the culture solution on line and the use method thereof provided by the invention can realize the purpose of supplementing the culture solution on line for the fresh culture solution storage container of the in-vitro PK/PD model, and simultaneously greatly facilitate the processing processes of preparation, disinfection, preheating and the like of the culture solution due to the fact that the culture solution can be prepared by bottle separation. In addition, convenient butt joint measures and filtering measures can achieve good sterile control.
Drawings
FIG. 1 is a schematic structural diagram of an auxiliary device for online culture solution supplementation of an antibacterial in-vitro PK/PD model provided by the invention;
FIG. 2 is a schematic diagram of a standby state of an auxiliary device for online culture solution supplementation of an antibacterial in-vitro PK/PD model provided by the invention;
FIG. 3 is a schematic diagram of an activated state of an auxiliary device for online culture solution supplementation of an antibacterial in-vitro PK/PD model provided by the invention;
FIG. 4 is a schematic diagram of an intravenous administration of an in vitro PK/PD model fluid supplement;
FIG. 5 is a schematic view of an intravenous infusion administration of an in vitro PK/PD model fluid supplement;
in the figure, 1, a donor bottle cap, 2, a donor bottle gas introduction pipeline, 3, a donor bottle liquid discharge pipeline, 4, a first luer connector, 5, a second luer connector, 6, a third luer connector, 7, a fourth luer connector, 8, a receptor bottle gas discharge pipeline, 9, a receptor bottle liquid discharge pipeline, 10, a receptor bottle liquid introduction pipeline, 11, a donor bottle, 12, a receptor bottle, 13, a luer connector butt joint body, 14, a second luer plug, 15, a syringe, 16, a first filter, 17, a medicine feeding bottle, 18, a peristaltic pump, 19, a central chamber, 20, a stirrer, 21, a stirrer, 22, a waste liquid bottle, 23, a sampling hole channel, 24, a receptor bottle cap, 25, a waste liquid discharge pipeline, 26, a first luer plug, 27 and a second filter are arranged.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be described clearly and completely with reference to the accompanying drawings of the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be obtained by a person skilled in the art without inventive step based on the embodiments of the present invention, are within the scope of the present invention. Thus, the following detailed description of the embodiments of the present invention, presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention.
As shown in fig. 1, the present invention provides an auxiliary device for online supplementing a culture solution for an antimicrobial drug in vitro PK/PD model, comprising a donor bottle cap 1 for covering a donor bottle 11 in the PK/PD model and a recipient bottle cap 24 for covering a recipient bottle 12 in the PK/PD model;
a donor bottle gas inlet pipeline 2 and a donor bottle liquid outlet pipeline 3 are hermetically penetrated through the donor bottle cap 1, a first luer connector 4 and a second luer connector 5 are respectively arranged at one ends of the donor bottle gas inlet pipeline 2 and the donor bottle liquid outlet pipeline 3, which extend out of the donor bottle 11, and a first filter 16 is arranged on the first luer connector 4;
a receptor bottle liquid leading-in pipeline 10, a receptor bottle gas leading-out pipeline 8 and a receptor bottle liquid leading-out pipeline 9 are hermetically penetrated through the receptor bottle cap 24, a third luer connector 6 and a fourth luer connector 7 are respectively arranged at one ends of the receptor bottle liquid leading-in pipeline 10 and the receptor bottle gas leading-out pipeline 8, which extend out of the receptor bottle 12, and a second filter 27 is arranged on the fourth luer connector 7.
The above technical solution of the present invention is explained as follows, as shown in fig. 1 to 3:
firstly, preferably, round holes corresponding to the donor bottle gas leading-in pipeline 2 and the donor bottle liquid leading-out pipeline 3 are arranged on the donor bottle cap 1, the diameter of the round holes can penetrate through the donor bottle gas leading-in pipeline 2 and the donor bottle liquid leading-out pipeline 3, and the sufficient tightness between the donor bottle gas leading-in pipeline 2 and the donor bottle liquid leading-out pipeline 3 and the hole wall is ensured to ensure the tightness of the top end of the donor bottle cap 1, therefore, the aperture is required to be smaller than the diameters of the donor bottle gas leading-in pipeline 2 and the donor bottle liquid leading-out pipeline 3, the diameter difference is ensured to be more than 0.1mm in order to ensure the tightness, the donor bottle cap and the receptor bottle cap can be manufactured by an integral forming process, and guarantee that the pipeline is sealed to run through the bottle lid can, the preferred mode of seting up the round hole that adopts to run through the round hole with the pipeline is sealed, adopt this kind of mode can guarantee to change the pipeline conveniently.
Secondly, the donor bottle gas leading-in pipeline 2 and the donor bottle liquid leading-out pipeline 3 are arranged above the donor bottle cap 1 to have proper lengths so as to ensure convenient operation;
thirdly, both the donor bottle gas leading-in pipeline 2 and the donor bottle liquid leading-out pipeline 3 can be used as donor bottle liquid leading-out pipelines, in the invention, the reference numeral 3 in fig. 1 is taken as a liquid leading-out pipeline for illustration, and the length of the donor bottle liquid leading-out pipeline 3 below the bottle cap is preferably that the bottom of the donor bottle 11 can be touched;
the donor bottle gas introduction pipeline 2 and the donor bottle liquid lead-out pipeline 3 can be used as pipelines for introducing donor bottle gas, in the invention, the reference numeral 2 in fig. 1 is taken as the donor bottle gas introduction pipeline 2 as an example, the length of the donor bottle gas introduction pipeline 2 below the donor bottle cap 1 can be any length, but is preferably 2-10cm, so that the lower end of the pipeline is preferably not contacted with the liquid level in the donor bottle 11;
fifthly, preferably, round holes corresponding to the receptor bottle liquid leading-in pipeline 10, the receptor bottle gas leading-out pipeline 8 and the receptor bottle liquid leading-out pipeline 9 are formed in the top of the receptor bottle cap 24, the diameter of each round hole can penetrate through the receptor bottle liquid leading-in pipeline 10, the receptor bottle gas leading-out pipeline 8 and the receptor bottle liquid leading-out pipeline 9, enough tightness among the receptor bottle liquid leading-in pipeline 10, the receptor bottle gas leading-out pipeline 8, the receptor bottle liquid leading-out pipeline 9 and the hole wall is ensured to ensure the sealing performance of the top end of the receptor bottle cap 24, therefore, the hole diameter needs to be smaller than the diameters of the receptor bottle liquid leading-in pipeline 10, the receptor bottle gas leading-out pipeline 8 and the receptor bottle liquid leading-out pipeline 9, and the diameter difference needs to be ensured to be more than 0.1mm in order to ensure the sealing performance;
sixthly, as shown in fig. 1, at least 3 sections of pipelines on the bottle cap 24 of the receiving bottle are needed, wherein one pipeline is responsible for introducing liquid, the invention is described by taking a reference numeral 10 in fig. 1 as an example of a liquid introducing pipeline of the receiving bottle, and the other pipeline is responsible for leading out gas, the invention is described by taking a reference numeral 8 in fig. 1 as an example of a gas leading-out pipeline of the receiving bottle, and the other pipeline is responsible for leading out liquid, the invention is described by taking a reference numeral 9 in fig. 1 as an example of a liquid leading-out pipeline of the receiving bottle, and the pipelines can be selected according to actual needs, for example: the liquid outlet pipeline 9 of the receiver bottle shown by reference numeral 9 in fig. 1 can also be used as a liquid inlet pipeline 10 of the receiver bottle, and the like, and is not described again;
seventh, the length of the above-mentioned recipient bottle gas outlet line 8 for gas discharge below the recipient bottle cap 24 is preferably such that the lower end of the line does not touch the liquid surface in the recipient bottle 12, the above-mentioned recipient bottle liquid inlet line 10 for liquid introduction should touch the bottom of the bottle as much as possible to form the effective liquid surface difference between the donor bottle 11 and the recipient bottle 12 as much as possible, and the above-mentioned recipient bottle liquid outlet line 9 for liquid discharge should touch the bottom of the bottle as much as possible to discharge the maximum volume of liquid.
And eighthly, the sex of the luer connector and the matching of the pipeline are optional, and the sex of the luer connector is not distinguished. As shown in fig. 2, in the inactivated state of the present invention, the third luer connector 6 and the fourth luer connector 7 should be respectively closed by using the first luer plug 26 and the second luer plug 14, and the first luer connector 4 and the second luer connector 5 are butted to form a luer connector butting body 13 for closing; as shown in fig. 3, the first luer connector 4 and the fourth luer connector 5 are loosened during use, and then the second luer connector 5 is connected with the third luer connector 6 without the first luer plug 26 to complete the connection.
In the present invention, the manufacturing method of the donor bottle cap and the recipient bottle cap is not limited, and there is no special requirement for the material, but the donor bottle cap and the recipient bottle cap are preferably manufactured by integral molding, and the material is preferably plastic, and other materials in the art may be used, for example: and (3) rubber material.
In the present invention, the first filter 16 and the second filter 27 are 0.22 micron filters to provide an effective bacterial barrier environment.
In the present invention, the donor bottle gas introduction line 2, the donor bottle liquid discharge line 3, the acceptor bottle liquid introduction line 10, the acceptor bottle gas discharge line 8, and the acceptor bottle liquid discharge line 9 are made of a silica gel material or a rubber material.
The invention also provides a use method of the auxiliary device for online culture solution supplementation of the antibacterial drug in-vitro PK/PD model, which comprises the following steps:
s1, covering the donor bottle cap 1 on a donor bottle 11 with a culture solution prepared therein, connecting the first luer 4 and the second luer 5, and performing an overall sterilization process;
s2, plugging the third luer connector 6 and the fourth luer connector 7 with the first luer plug 26 and the second luer plug 14, respectively, sterilizing the recipient bottle cap 24, covering the sterilized recipient bottle 12 after the sterilization, and connecting the liquid outlet line 9 to the central chamber 19 in the PK/PD model;
s3 connecting the second luer fitting 5 to the third luer fitting 6, connecting the first filter 16 and the second filter 27 to the first luer fitting 4 and the fourth luer fitting 7, respectively, and connecting the first filter 16 to the syringe 15 after removing the first luer fitting 26 and the second luer fitting 14, respectively;
s4 air was injected rapidly into the donor vial in the PK/PD model using the syringe 15.
In one embodiment of the invention, intravenous administration of an in vitro PK/PD model fluid supplement is shown:
as shown in fig. 4, when the fresh culture solution in the recipient bottle 12 is nearly consumed, after the connection is completed according to the method for using the auxiliary device for online supplementing the culture solution of the anti-bacterial drug in vitro PK/PD model, the large-volume syringe 15 is used to pump air, air is rapidly injected into the donor bottle 11, so that the culture solution in the donor bottle 11 flows into the recipient bottle 12, then the donor bottle and the recipient bottle are in a communicated state, under the action of gravity and the peristaltic pump 18, the culture solution flows into the central chamber 19 through the recipient bottle liquid lead-out pipeline 9 which is hermetically communicated with the central chamber 19 in the PK/PD model, the central chamber 19 is arranged on the stirrer 20, the stirrer 21 is arranged in the central chamber 19, the stirrer 20 drives the stirrer 21 to uniformly mix the culture solution in the central chamber 19, the bottle cap of the central chamber 19 is further provided with the sampling hole channel 23 and the waste liquid lead-out pipeline 25, the antibacterial drug is added into the central chamber 19 through the sampling hole channel 23, one end of the waste liquid guiding pipeline 25 is communicated with the central chamber 19, the other end is connected with the waste liquid bottle 22, and the waste liquid generated in the central chamber 19 is brought into the waste liquid bottle 22 through the waste liquid guiding pipeline 25.
In one embodiment of the invention, a protocol for intravenous infusion administration of an in vitro PK/PD model fluid supplementation is shown:
as shown in fig. 5, when the fresh culture solution in the recipient bottle 12 is nearly consumed, after the connection is completed according to the method for using the auxiliary device for online supplementing the culture solution of the anti-bacterial drug in vitro PK/PD model, the large-volume syringe 15 is used to pump air, air is rapidly injected into the donor bottle 11, so that the culture solution in the donor bottle 11 flows into the recipient bottle 12, then the donor bottle and the recipient bottle are in a communicated state, under the action of gravity and the action of the peristaltic pump 18, the culture solution flows into the central chamber 19 through the recipient bottle liquid lead-out pipeline 9 which is hermetically communicated with the central chamber 19 in the PK/PD model, the central chamber 19 is arranged on the stirrer 20, the stirrer 21 is arranged in the central chamber 19, the stirrer 20 drives the stirrer 21 to uniformly mix the culture solution in the central chamber 19, the anti-bacterial drug is injected into the drug administration bottle 17 which is communicated with the recipient bottle liquid lead-out pipeline 9 through a pipeline, the cap of the administration bottle 17 is also hermetically connected to a gas introduction line with a filter, and the gas introduction line is connected to a syringe so that the antibacterial drug is injected into the recipient bottle liquid discharge line 9 and pumped into the central chamber 19 by the peristaltic pump 18. The bottle cap of the central chamber 19 is also provided with a sampling hole channel 23 and a waste liquid guiding pipeline 25, one end of the waste liquid guiding pipeline 25 is communicated with the central chamber 19, the other end of the waste liquid guiding pipeline 25 is connected with a waste liquid bottle 22, and waste liquid generated in the central chamber 19 is brought into the waste liquid bottle 22 through the waste liquid guiding pipeline 25.
In the above two embodiments, the lower end of the waste liquid outlet pipe 25 is preferably close to the bottom end of the central chamber 19, and both the waste liquid outlet pipe 25 and the sampling hole passage 23 are made of silica gel or rubber.
It is further noted that the donor vial, the recipient vial, the donor vial cap and the recipient vial cap described in the present invention may be common reagent vials and reagent caps, or may be assembled by using non-standard or special containers and corresponding container caps and tubing to achieve the same purpose.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (5)
1. An auxiliary device for online culture solution supplementation of an antibacterial drug in-vitro PK/PD model is characterized by comprising a donor bottle cap for covering a donor bottle in the PK/PD model and a receptor bottle cap for covering a receptor bottle in the PK/PD model;
a donor bottle gas introduction pipeline and a donor bottle liquid discharge pipeline are hermetically penetrated through the donor bottle cap, a first luer connector and a second luer connector are respectively arranged at one ends of the gas introduction pipeline and the donor bottle liquid discharge pipeline, which extend out of the donor bottle, and a first filter is arranged on the first luer connector;
a receptor bottle liquid leading-in pipeline, a receptor bottle gas leading-out pipeline and a receptor bottle liquid leading-out pipeline are hermetically penetrated through the receptor bottle cap, a third luer connector and a fourth luer connector are respectively arranged at one ends of the receptor bottle liquid leading-in pipeline and the receptor bottle gas leading-out pipeline, which extend out of the receptor bottle, and a second filter is arranged on the fourth luer connector.
2. The auxiliary device for online culture solution supplementation of an antibacterial in-vitro PK/PD model as claimed in claim 1, wherein the donor bottle cap and the receiver bottle cap are integrally formed.
3. The auxiliary device for the online culture solution supplementation of an antibacterial drug in-vitro PK/PD model as claimed in claim 1, wherein the first filter and the second filter are 0.22 micron filters.
4. The auxiliary device for online supplementing of a culture solution to an antibacterial drug in-vitro PK/PD model according to claim 1, wherein the donor bottle gas inlet line, the donor bottle liquid outlet line, the recipient bottle liquid inlet line, the recipient bottle gas outlet line and the recipient bottle liquid outlet line are made of silica gel or rubber.
5. The use method of the auxiliary device for the online culture solution supplementation of the antibacterial in vitro PK/PD model according to any one of claims 1 to 4, is characterized by comprising the following steps:
s1, covering the bottle cap of the donor bottle on the donor bottle with culture solution prepared inside, connecting the first luer connector and the second luer connector, and then carrying out overall disinfection treatment;
s2, plugging the third luer connector and the fourth luer connector by using a first luer plug and a second luer plug respectively, disinfecting the bottle cap of the receptor bottle, covering the sterilized receptor bottle after the disinfection, and connecting the liquid lead-out pipeline to a central chamber in the PK/PD model;
s3, respectively removing the first and second luer plugs, connecting the second and third luer plugs, respectively connecting the first and second filters at the first and fourth luer plugs, and connecting the first filter to a syringe;
s4 Rapid injection of air into a donor vial in a PK/PD model using the syringe.
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