WO2023068158A1

WO2023068158A1 - Perfusion bag and perfusion apparatus

Info

Publication number: WO2023068158A1
Application number: PCT/JP2022/038220
Authority: WO
Inventors: 弘道小原; 直徒松野
Original assignee: 東京都公立大学法人
Priority date: 2021-10-18
Filing date: 2022-10-13
Publication date: 2023-04-27
Also published as: JPWO2023068158A1

Abstract

The perfusion bag according to the present invention is provided with: a bag body of which the inside is partitioned into at least a storage part and a positive-displacement pump part, in which the storage part is arranged in an organ excised from a living body or cultured cell and the positive-displacement pump is so configured that a liquid can be stored or filled in the inside of a volume-variable closed space; a first check valve which regulates the direction of the flow of a liquid to a direction from the positive-displacement pump part toward the storage part; and a second check valve which regulates the direction of the flow of a liquid to a direction from the storage part toward the positive-displacement pump part.

Description

Perfusion bag and perfusion device

The present invention relates to perfusion bags and perfusion devices. This application claims priority based on Japanese Patent Application No. 2021-170279 filed in Japan on October 18, 2021, and the contents thereof are incorporated herein.

　In transplant surgery such as organ transplantation, the organ is temporarily preserved after being removed from the body. Various preservation methods and perfusion methods have been developed in order to preserve the excised organ in a transplantable state. In recent years, in fields such as pharmaceutical production, gene therapy, regenerative medicine, and immunotherapy, development and research on culturing and inducing differentiation of cells (including tissues, microorganisms, viruses, etc.) in an artificial environment has been active. be. The organ perfusion apparatus described in Patent Document 1 is widely known as a method for perfusion of organs.

Japanese Patent Application Laid-Open No. 2012-92114

However, while the perfusion device described in Patent Document 1 can provide a perfusion device capable of maintaining, restoring, preserving, and transporting organs, the device configuration is complicated, and multiple units each use expensive parts. Consists of A sterilized and clean environment is indispensable for medical instruments, and in order to prevent infectious diseases caused by reuse of used medical instruments, basically many parts are disposable from the viewpoint of hygiene. Therefore, in case of emergencies or in developing countries with insufficient medical facilities, the use of expensive components of existing perfusion devices still poses a cost problem. Furthermore, no perfusion device that can be used regardless of the type of organ or cultured cell has been put into practical use. As described above, from the standpoint of manufacturing costs and from the standpoint of environmental conditions such as emergency disasters and developing countries, there is a demand for simpler and less expensive devices for rapidly preparing medical devices, medical solutions, and the like.

The present invention has been made in consideration of such circumstances, and aims to perfuse organs and cultured cells using a perfusion device with a simple structure that uses an inexpensive and disposable perfusion bag.

In order to solve the above problems, the present invention proposes the following means.
A perfusion bag according to a first aspect of the present invention comprises a storage section in which at least an organ extracted from a living body or cultured cells is placed, a volumetric pump section for storing or filling a volume-variable closed space with a liquid, a first non-return valve that regulates the direction in which the liquid flows from the volume pump section to the storage section; and the liquid flows from the storage section to the volume pump section. and a second non-return valve that regulates the direction of the flow.

According to the second aspect of the present invention, in the perfusion bag according to the first aspect, the bag body is made of a flexible plastic film.

According to a third aspect of the present invention, the perfusion bag according to the first or second aspect is provided with a first end connected to the organ, a first end connecting the storage portion and the volumetric pump portion, and the a supply pipe formed in the first check valve; a first end that communicates with the container and is connected to the organ; and a volumetric pump unit. and a reflux pipe formed in the second check valve, having a second end communicating with the closed space.

According to a fourth aspect of the present invention, in the perfusion bag according to any one of the first to third aspects, the storage section is provided vertically above the volumetric pump section.

According to a fifth aspect of the present invention, a perfusion device comprising the perfusion bag according to any one of the first to fourth aspects applies external pressure to the volumetric pump section from outside the bag body to change the volume. and an external pressure generating section for generating a flow of said liquid from said volumetric pump section toward said receiving section to form a pump.

According to the perfusion apparatus of the present invention, organs and cultured cells can be perfused using a simple structure, inexpensive and disposable perfusion bag.

1 is a side view of a perfusion bag of the perfusion device according to the first embodiment of the invention; FIG. FIG. 4 is a diagram explaining the action of the perfusion device according to the first embodiment of the present invention; Fig. 2 is a perspective view of a perfusion device according to a second embodiment of the present invention; Fig. 2 is a side view of a perfusion device according to a second embodiment of the invention; FIG. 10 is a diagram illustrating the action of the perfusion device according to the second embodiment of the present invention; Fig. 10 is a perspective view of a perfusion device according to a third embodiment of the invention; FIG. 11 is a perspective view of a perfusion device according to a fourth embodiment of the invention; FIG. 10 is a diagram illustrating a modified example of the perfusion bag of the present invention; FIG. 10 is a diagram illustrating a modified example of the perfusion bag of the present invention;

(First embodiment)
A first embodiment of the present invention will be described with reference to FIGS. 1 and 2. FIG.

A perfusion device 100 (see FIG. 2) according to the first embodiment of the present invention is a device that perfuses organs or cultured cells. Below, the case of perfusing an organ will be described. As an organ, kidney K is used as an example. This perfusion device 100 comprises a perfusion bag 1 .

The perfusion bag 1 includes a bag body 10, a supply pipe 40 having a first check valve 20, and a reflux pipe 50 having a second check valve 30, as shown in FIG.

As an example, the bag body 10 may be a polypropylene housing bag or the like that is water-resistant and flexible, and whose upper portion can be opened and closed by means of a zipper 10a. By using this bag body 10, it is possible to easily obtain the kidney K, and by opening and closing the opening 61 using the chuck 10a provided on the upper part, the kidney K can be taken in and out of a container 60, which will be described later. Alternatively, the perfusate E can be prevented from leaking by closing the opening 61 with the chuck 10a to seal the container 60. As shown in FIG. As the zipper 10a, for example, a sliding zipper known as Ziplock (registered trademark) can be preferably provided. Moreover, as shown in FIG. 1, the bag body 10 has, in the vicinity of the center of the interior S, a partition wall 11, a first installation hole 12 through which a supply pipe 40 described later passes, and a second installation hole 12 through which a second check valve 30 passes. and an installation hole 13 .

The partition wall 11 is heat-sealed or the like from the first side portion 14 to the second side portion 15 of the bag body 10 horizontally with respect to the bag body 10 in a range excluding the first installation hole 12 and the second installation hole 13. It is formed by thermocompression bonding by The partition wall 11 partitions the interior S of the bag body 10 into at least two parts, namely, an upper storage part 60 and a lower volume pump part 70 . The first installation hole 12 and the second installation hole 13 are formed in the partition wall 11 of the interior S of the bag body 10 so as to allow the accommodation portion 60 and the volumetric pump portion 70 to communicate with each other. Note that the partition wall 11 may be formed by a method other than thermocompression bonding such as heat sealing, and the partition wall 11 may be formed by bonding the inside S of the bag body 10 with an adhesive or the like and applying the adhesive. The width of the partition wall 11 is preferably set so as not to exceed the longitudinal length of the second check valve 30, which will be described later.

The accommodating part 60 is provided in the upper part of the partition wall 11 formed in the bag body 10, has a size capable of accommodating organs or cultured cells, and has an opening in the upper part of the bag body 10 through which organs or cultured cells can be taken in and out. A portion 61 is provided. In the present embodiment, the kidney K is arranged in the internal space of the storage section 60, and liquid such as the perfusate E is further stored.

The volumetric pump section 70 is provided below the partition wall 11 formed in the bag body 10, and stores or fills the perfusate E into a volume-variable closed space. The volumetric pump section 70 forms a pump function when pressure is applied from the outside. Here, the pump function means that an external pressure is applied to the volumetric pump section 70 to compress the volumetric pump section 70 to send the perfusate E in the volumetric pump section 70 to the storage section 60, or to expand the volumetric pump section 70. It means that the perfusate E is pumped by repeating the operation of returning the perfusate E in the storage section 60 to the volumetric pump section 70 . The perfusate E discharged from the volumetric pump section 70 is sent to the kidney K housed in the housing section 60 into which the tip 41 of the supply pipe 40 is inserted.

The supply pipe 40 is fitted into the first installation hole 12 of the bag body 10 without a gap, and communicates the storage section 60 of the bag body 10 and the volumetric pump section 70 . Further, the space between the supply pipe 40 and the diameter of the first installation hole 12 is configured so that the perfusate E does not leak. A distal end 41 of the supply pipe 40 is inserted into a blood vessel or the like of the kidney K housed in the housing section 60 . The proximal end 42 of the supply pipe 40 is submerged in the perfusate E of the volumetric pump section 70 . Also, the supply pipe 40 is provided with the first check valve 20 in the central portion. The first check valve 20 allows unidirectional flow of the perfusate E from the volumetric pump section 70 to the housing section 60, and regulates the direction of flow of the perfusate E. As shown in FIG.

The reflux pipe 50 is fitted into the second installation hole 13 of the bag body 10 without any gap, and communicates the storage portion 60 of the bag body 10 and the volumetric pump portion 70 . Also, the perfusate E is prevented from leaking between the reflux pipe 50 and the hole diameter of the second installation hole 13 . Moreover, the reflux pipe 50 is equipped with the second check valve 30 in the central part. A proximal end 51 of the reflux pipe 50 is provided on the side of the container 60 and is submerged in the perfusate E discharged by the kidney K and accumulated in the container 60 . Note that the proximal end 51 may be inserted into a blood vessel or the like of the kidney K, for example. A distal end 52 of the return line 50 is disposed within the volumetric pump section 70 . The second check valve 30 allows unidirectional flow of the irrigating fluid E from the storage unit 60 to the volumetric pump unit 70, and regulates the direction in which the irrigating fluid E flows.

Note that the number of the first check valve 20 and the second check valve 30 may be one (one system) or a plurality depending on the type of organ to be perfused and the perfusion conditions. (Multiple systems) may be used. In addition, the supply pipe 40, the reflux pipe 50, the first check valve 20, and the second check valve 30 are made of a material such as synthetic resin, so that the perfusion apparatus 100 can be manufactured at low cost.

The perfusate E (liquid) is provided inside the storage section 60 and the volumetric pump section 70 . This perfusate E can be flowed through the opening 61 of the container 60 . The perfusate E may be filled in the perfusion bag 1 completely, or may be filled with air. A UW solution is used as the perfusate E in this embodiment. As the perfusate E, other types of liquid such as HTK solution, ETK solution, physiological saline, lactec, etc., which are used when perfusing an organ or the like may be used. Furthermore, in the present embodiment, the type of perfusate used in the perfusion of the organ is described. Liquid media may be applied as perfusate. Also, the perfusate E injected into the storage section 60 and the volumetric pump section 70 may be the same or different types of liquids. The volumetric pump section 70 can inject a perfusate E different from that of the housing section 60 by further providing an injection port through which the perfusate E can be injected from the outside.

The perfusion device 100 should be as simple as possible. Therefore, as shown in FIG. 2, the perfusion device 100 can further use the user's hand H (external pressure generator) as the external pressure generator. The external pressure generating section is a mechanism for applying pressure from the outside to the volumetric pump section.

A user (not shown) such as a doctor or nurse compresses or expands the volumetric pump section 70 by holding the volumetric pump section 70 between the hands H and applying or releasing pressure to the volumetric pump section 70 . In this embodiment, the user places the perfusion bag 1 on the palm and holds the perfusion bag 1 with the thumb and fingers other than the thumb. The perfusion device 100 can be realized by external pressure from the perfusion bag 1 and the user's hand H described above. Therefore, in this embodiment, the simplest perfusion apparatus 100 can be constructed in a severe environment such as an emergency or a medical site in a developing country.

Next, the action of the perfusion device 100 according to this embodiment will be described with reference to FIG.

FIG. 2(a) is a diagram showing a state before the user pressurizes the volume pump section 70 of the perfusion bag 1 with the hand H. FIG. The user holds the perfusion bag 1 in hands H and clamps it. It should be noted that how the user holds the perfusion bag 1 is appropriately adjusted. It is preferable for the user to hold the volumetric pump section 70 formed in the lower portion of the bag body 10 of the perfusion bag 1 with the hand H so as to wrap it. Moreover, as shown in FIG. 2, the user may hold the perfusion bag 1 with both hands or with one hand. The user places the kidney K in the internal space of the housing portion 60 of the perfusion bag 1 . Furthermore, the user cuts the blood vessel of the kidney K and connects the tip 41 of the supply pipe 40 .

Next, FIG. 2(b) is a diagram showing a state in which the user pressurizes the volume pump section 70 of the perfusion bag 1 with the hand H. The user presses the volumetric pump portion 70 of the perfusion bag 1 with the hand H. Then, the volumetric pump section 70 is compressed and the perfusate E is pushed out. At this time, the first check valve 20 of the supply pipe 40 regulates the direction of the perfusate E inside the volumetric pump unit 70 to flow into the supply pipe 40 by the amount of the compressed volume. Therefore, the perfusate E is sent to the kidney K into which the tip 41 of the supply pipe 40 is inserted. On the other hand, the second check valve 30 of the reflux pipe 50 tries to flow the perfusate E from the storage unit 60 to the volumetric pump unit 70 in the opposite direction, so that the perfusate E is stored from the volumetric pump unit 70 . It is regulated so that it does not flow back to the part 60 . The volume inside the volumetric pump portion 70 decreases as the perfusate E decreases.

Next, FIG. 2(c) is a diagram showing a state after the user pressurizes the volumetric pump section 70 of the perfusion bag 1 with the hand H. The user stops pressing the volumetric pump portion 70 of the perfusion bag 1 with the hand H. Then, the volume of the volumetric pump section 70 that was compressed expands to return to its original volume, and the perfusate E accumulated in the storage section 60 forms a flow path to the reflux pipe 50 connected to the volumetric pump section 70, The liquid is sent to the volumetric pump section 70 . At this time, the first check valve 20 of the supply pipe 40 regulates the direction so that the perfusate E does not flow back, because the perfusate E tries to flow in the direction opposite to the direction in which it flows from the volumetric pump section 70 to the supply pipe 40. . On the other hand, the second check valve 30 of the reflux pipe 50 regulates the direction of the perfusate E from the container 60 to the volumetric pump 70 . When the perfusate E in the storage section 60 runs out, or when the volume of the volumetric pump section 70 reaches its maximum, the perfusate E from the storage section 60 to the volumetric pump section 70 is stopped.

In this embodiment, by repeating the action of (a) to (c) in FIG. 2 a predetermined number of times, the volumetric pump section 70 of the perfusion bag 1 can have a pumping function.

In this embodiment, since the volumetric pump section 70 of the perfusion bag 1 has a simple structure having a pump function, the perfusion device 100 can be realized by external pressure using the user's hand H as a driving source. Therefore, the perfusion apparatus 100 of the present embodiment can be used quickly in urgent situations without requiring a drive source for generating external pressure accompanied by electricity or the like in the event of a disaster or emergency. Moreover, it can be effectively used even in an environment where there is a shortage of medical equipment in areas such as developing countries.

In addition, in the present embodiment, the perfusion bag 1 has a plurality of compartments and has a pump function, so that the device configuration is simplified and the perfusion device 100 can be realized without preparing expensive parts for each unit. .

In addition, in the present embodiment, the perfusion bag 1 can be used as a disposable one using inexpensive materials, so cleaning and sterilization can be omitted.

In addition, since this embodiment has a simple structure and a compact design, it can be installed near the surgical field during a transplant surgery or the like. Therefore, surgery such as transplant surgery can be performed while perfusion by the perfusion device 100 is continued. As a result, the organ ischemia time can be shortened, and the success rate of transplant surgery can be improved.

(Second embodiment)
Next, a perfusion device 100A according to a second embodiment of the present invention will be described with reference to FIGS. 3 to 5. FIG. 3 and 4 are a perspective view and a side view of a perfusion device 100A according to this embodiment. FIG. 5 is a diagram illustrating the action of the perfusion device 100A according to this embodiment.

A case where the perfusion apparatus 100A according to the present embodiment perfuses an organ as in the first embodiment will be described. As an organ, kidney K is used as an example. The perfusion apparatus 100A includes a perfusion bag 1, a casing section 200, and an external pressure generating section 90, as shown in FIGS.

The perfusion bag 1 has substantially the same configuration as that of the perfusion bag 1 according to the first embodiment described above. Holes 16 are provided near both corners of the upper portion.

The casing section 200 includes a casing main body 210 and a hanging support section 220 . The casing main body 210 is a housing that accommodates the perfusion bag 1 and has side walls 230 and a bottom surface 240 . Sidewall 230 includes a first sidewall 231 and a second sidewall 232 facing first sidewall 231 , and a drive sidewall 233 and a perfusion bag sidewall 234 facing drive sidewall 233 . The drive side wall 233 has a side wall hole 235 that allows an actuator 91, which will be described later, to slide in a direction in which the drive side wall 233 and the perfusion bag side wall 234 face each other. Side wall hole 235 may be a notch. The side wall hole or notch may have any shape, but it is preferable to have a shape that matches the shape of the actuator 91 and allows the actuator 91 to slide smoothly. Note that the casing main body 210 may have a size in which the external pressure generating section 90 and the like are installed.

The hanging support 220 extends vertically from the upper ends 232j of the first side wall 231 and the second side wall 232 of the casing body 210 to a position where the perfusion bag 1 can be placed adjacent to the perfusion bag side wall 234 of the casing body 210. Extend upwards. The suspending support 220 has a hook 221 at its upper end. The height from the upper end to the tip of the first side wall 231 and the second side wall 232 of the casing main body 210 of the hanging support part 220 is the same as the lower end of the bag when the hook 221 is hooked on the hook 221 to hang the bag. is preferably set to a height such that it contacts the bottom of the casing body 210 .

The external pressure generating section 90 deforms the volumetric pump section 70 by applying pressure to the volumetric pump section 70 . The external pressure generating section 90 includes an actuator 91 , a pressing section 92 and a driving section 93 .

The actuator 91 is fitted into the side wall hole 235 of the driving side wall 233, and the tip 911 of the actuator 91 is attached with the pressing portion 92, which pushes the pressing portion 92 toward the perfusion bag 1 side, pulls the pressing portion 92, and pulls the driving side wall. 233. The proximal end 912 side is positioned on the driving side wall 233 side of the casing section 200 and is connected to the driving section 93 . The actuator 91 slides in the side wall hole 235 and is configured to reciprocate in the direction in which the drive side wall 233 and the perfusion bag side wall 234 face each other as shown in FIGS.

The pressing part 92 is attached to the tip of the actuator 91 , is a plate-like member, and presses the volumetric pump part 70 of the perfusion bag 1 . The pressing portion 92 is installed inside the casing body 210 so that the lower surface thereof abuts on the bottom surface 240 of the casing body 210 . In addition, the lower surface of the pressing portion 92 is arranged along the bottom surface 240 of the casing body 210 so that the driving side wall 233 and the perfusion bag side wall 234 can reciprocally slide in the facing direction in conjunction with the actuator 91 . The height of the pressing-side side surface 921 of the pressing portion 92 is equal to or lower than that of the volumetric pump portion 70 . With the above configuration, the pressing part 92 operates without coming into contact with the accommodating part 60 provided above the volume part. Therefore, the volumetric pump section 70 can be pressed without damaging the kidney K housed in the housing section 60 . Also, the width of the pressing-side side surface 921 of the pressing portion 92 is preferably set smaller than the width of the casing main body 210 .

The driving portion 93 is attached to the proximal end 912 of the actuator 91 and applies a pressing force, and the actuator 91 and the pressing portion 92 are moved forward toward the perfusion bag side wall 234 and backward toward the drive side wall 233 . , so that the driving side wall 233 and the perfusion bag side wall 234 can move forward and backward in opposite directions. As this reciprocating mechanism, for example, a solenoid coil (not shown) is used to advance or retreat the actuator 91 (moving member) toward the pressing portion 92, or an air cylinder or the like is used to move the piston rod toward the actuator 91. You can move forward or backward. Here, the drive unit 93 uses a battery (not shown) as a drive source. This eliminates the need to connect the perfusion device 100A to a separate power source, further facilitating transport of the perfusion device 100A. Also, the use of batteries allows the perfusion device 100A to be further miniaturized. Therefore, the perfusion apparatus 100A of the present embodiment can be used quickly in emergency situations such as disasters and emergencies. The drive source may be supplied from the outside with a power cord (not shown) or the like interposed therebetween. Alternatively, the drive unit 93 of the perfusion device 100A may be operated as a rechargeable device by providing a rechargeable battery in the casing body 210, for example.

In addition, the external pressure generating section 90 further includes a control section 94 for controlling the driving section 93 .

The control unit 94 is a device for transmitting a signal for reciprocating the actuator 91 and the pressing unit 92 forward and backward to the driving unit 93 and controlling the operation of the external pressure generating unit 90 . The number of round trips, the time required for round trips, and the like are not particularly limited, and may be appropriately changed according to the situation. Note that the control unit 94 does not have to be provided in the external pressure generating unit 90 assuming that the driving unit 93 is provided with the function for controlling the forward and backward reciprocating movements of the actuator 91 and the pressing unit 92 .

Next, the action of the perfusion device 100A according to this embodiment will be described with reference to FIG.

FIG. 5(A) is a diagram showing a state in which the pressing part 92 pressurizes the volumetric pump part 70 of the perfusion bag 1 of the perfusion device 100A. The control section 94 of the external pressure generating section 90 sends a forward movement signal to the driving section 93 to move the actuator 91 and the pressing section 92 . The pressing part 92 presses the volumetric pump part 70 of the perfusion bag 1 to apply an external pressure to the volumetric pump part 70 . Then, the volumetric pump section 70 is compressed, and the perfusate E inside is pushed out. At this time, the first check valve 20 of the supply pipe 40 regulates the direction of the perfusate E inside the volumetric pump unit 70 to flow into the supply pipe 40 by the amount of the compressed volume. Therefore, the perfusate E is sent to the kidney K into which the tip 41 of the supply pipe 40 is inserted. On the other hand, the second check valve 30 of the reflux pipe 50 tries to flow the perfusate E from the storage unit 60 to the volumetric pump unit 70 in the opposite direction, so that the perfusate E is stored from the volumetric pump unit 70 . It is regulated so that it does not flow back to the part 60 . The internal volume of the volumetric pump portion 70 decreases as the perfusate E therein decreases.

FIG. 5(B) is a diagram showing a state in which the pressing portion 92 is separated from the volumetric pump portion 70 of the perfusion bag 1 of the perfusion device 100A. The control section 94 of the external pressure generating section 90 sends a backward movement signal to the driving section 93 to move the actuator 91 and the pressing section 92 . Since the pressing portion 92 moves backward and leaves the volumetric pump portion 70, the pressure applied to the volumetric pump portion 70 disappears. Then, since the volumetric pump unit 70 expands to return to its original volume, the perfusate E accumulated in the storage unit 60 forms a flow path to the reflux pipe 50 connected to the volumetric pump unit 70, and the volumetric pump unit 70 The liquid is sent to At this time, the first check valve 20 of the supply pipe 40 regulates the direction so that the perfusate E does not flow back, because the perfusate E tries to flow in the direction opposite to the direction in which it flows from the volumetric pump section 70 to the supply pipe 40. . On the other hand, the second check valve 30 of the reflux pipe 50 regulates the direction of the perfusate E from the container 60 to the volumetric pump 70 . When the perfusate E in the storage section 60 runs out, or when the volume of the volumetric pump section 70 reaches its maximum, the perfusate E from the storage section 60 to the volumetric pump section 70 is stopped.

Also in this case, in this embodiment, the volumetric pump section 70 of the perfusion bag 1 can have a pump function by repeating the actions of FIGS.

(Third embodiment)
Next, a perfusion device 100B according to a third embodiment of the invention will be described with reference to FIG. FIG. 6 is a perspective view of a perfusion device 100B according to this embodiment.

A case where the perfusion apparatus 100B of the present invention perfuses an organ in substantially the same manner as in the first embodiment will be described. As an organ, kidney K is used as an example. The perfusion device 100B includes a perfusion bag 1, a casing section 300, and an external pressure generating section 90, as shown in FIG.

The perfusion bag 1 has substantially the same configuration as the perfusion bag 1 according to the first embodiment described above, so a description of the configuration will be omitted.

The casing section 300 includes a casing main body 310 and a housing section mounting section 320 . The casing main body 310 is a housing that accommodates the perfusion bag 1 and has side walls 330 and a bottom surface 340 . Sidewall 330 includes a first sidewall 331 and a second sidewall 332 facing first sidewall 331 , and a drive sidewall 333 and a perfusion bag sidewall 334 facing drive sidewall 333 . The drive sidewall 333 includes a sidewall aperture 335 to the extent that the actuator 91 can slide in opposite directions between the drive sidewall 333 and the perfusion bag sidewall 334 . Side wall hole 335 may be a notch. The side hole or cutout may have any shape, but it is preferable to have a shape that matches the shape of the actuator 91 and allows the actuator 91 to slide smoothly. It should be noted that an external pressure generator 90 and the like may be installed inside the casing main body 310 .

The housing section mounting section 320 is a box-shaped mounting table for mounting the housing section 60 of the perfusion bag 1 , and is provided adjacent to the perfusion bag side wall 334 inside the casing body 310 . The upper surface 321 of the accommodation part mounting part 320 has a size that allows the accommodation part 60 to be placed thereon. The upper surface has a slight gradient from the side wall 334 of the perfusion bag toward the side wall 333 of the perfusion bag so that the perfusate E accumulated in the storage section 60 can be easily sent to the volumetric pump section 70 of the perfusion bag 1 by gravity. . Moreover, in order to fix the organ in the housing part 60, a concave portion may be provided so that the organ falls slightly from the upper surface. The height of the container mounting portion 320 is such that when the container 60 of the perfusion bag 1 is placed on the upper surface and the volumetric pump portion 70 is woven downward near one end of the upper surface on the drive side wall 333 side, the height of the container mounting portion 320 is the same as that of the perfusion bag. It is preferable to set the height to such an extent that the lower end of 1 contacts the bottom of the casing main body 310 . Correctly, the angle at which the perfusion bag 1 is woven is set to such an extent that the channels in the supply pipe 40 and the reflux pipe 50 are not closed. Further, the shape of the housing portion 60 is not limited to a box-shaped installation table, and may be a mounting plate or the like formed so as to protrude from the perfusion bag side wall 334 of the casing main body 310 .

The external pressure generating section 90 has substantially the same configuration as the external pressure generating section 90 according to the above-described second embodiment, so description of the configuration is omitted.

Also in this case, in this embodiment, substantially the same action as in the above-described second embodiment can be employed. In FIG. 6, the control section 94 of the external pressure generating section 90 sends a signal to move forward to the driving section 93 to move the actuator 91 and the pressing section 92 . The pressing part 92 is pressed against the volume pump part 70 of the perfusion bag 1 and applies an external pressure to the volume pump part 70 by pressing. Then, the volumetric pump section 70 is compressed, and the perfusate E inside is pushed out. At this time, as in the above embodiment, the first check valve 20 of the supply pipe 40 regulates the direction so that the perfusate E inside the volumetric pump unit 70 flows into the supply pipe 40 by the amount of the compressed volume. do. Therefore, the perfusate E is sent to the kidney K into which the tip 41 of the supply pipe 40 is inserted. On the other hand, the second check valve 30 of the reflux pipe 50 tries to flow the perfusate E from the storage unit 60 to the volumetric pump unit 70 in the opposite direction, so that the perfusate E is stored from the volumetric pump unit 70 . It is regulated so that it does not flow back to the part 60 . The internal volume of the volumetric pump portion 70 decreases as the perfusate E therein decreases.

Subsequently, the control section 94 of the external pressure generating section 90 sends a backward movement signal to the driving section 93 to move the actuator 91 and the pressing section 92 . Since the pressing portion 92 pressed against the volumetric pump portion 70 moves backward and leaves the volumetric pump portion 70, the pressure applied to the volumetric pump portion 70 disappears. Then, since the volumetric pump unit 70 expands to return to its original volume, the perfusate E accumulated in the storage unit 60 forms a flow path to the reflux pipe 50 connected to the volumetric pump unit 70, and the volumetric pump unit 70 The liquid is sent to At this time, the first check valve 20 of the supply pipe 40 regulates the direction so that the perfusate E does not flow back, because the perfusate E tries to flow in the direction opposite to the direction in which it flows from the volumetric pump section 70 to the supply pipe 40. . On the other hand, the second check valve 30 of the reflux pipe 50 regulates the direction of the perfusate E from the container 60 to the volumetric pump 70 . When the perfusate E in the storage section 60 runs out, or when the volume of the volumetric pump section 70 reaches its maximum, the perfusate E from the storage section 60 to the volumetric pump section 70 is stopped.

By repeating this action a predetermined number of times, the volumetric pump section 70 of the perfusion bag 1 can have a pumping function also in this embodiment.

(Fourth embodiment)
Next, a perfusion device 100C according to a fourth embodiment of the invention will be described with reference to FIG. FIG. 7 is a perspective view of a perfusion device 100C according to this embodiment.

A case where the perfusion apparatus 100C of the present invention perfuses an organ in substantially the same manner as in the first embodiment will be described. As an organ, kidney K is used as an example. The perfusion apparatus 100C includes a perfusion bag 1, a casing section 200, and an external pressure generating section 400, as shown in FIG.

The perfusion bag 1 and the casing part 200 have substantially the same configurations as the perfusion bag 1 and the casing part 200 according to the above-described second embodiment, so description of the configuration will be omitted.

The external pressure generating section 400 compresses the volumetric pump section 70 by applying pressure to the volumetric pump section 70 . The external pressure generator 400 includes an airbag 410 , an air pipe 420 and a compressor 430 .

The airbags 410 are provided on both sides of the perfusion bag 1 inside the casing body 210, and are flexible bag-like members capable of expanding and compressing the volume of the interior S. The airbag 410 is formed so that the height of the maximum inflated airbag 410 is substantially the same as the height of the upper portion of the volumetric pump section 70 of the perfusion bag 1 suspended therefrom. Further, the position or shape of airbag 410 is set so that the pressure to volumetric pump portion 70 when inflated to the maximum is greater than the internal pressure of volumetric pump portion 70 . It should be noted that the airbag 410 does not have to be flexible as long as the volume of the interior S can be inflated/compressed. Also, the airbag 410 may be provided only on one side, or may be provided in plurality.

The air pipe 420 is provided between the airbag 410 and the compressor 430, and the air blown or sucked from the compressor 430 forms a flow path inside. The tip of the air pipe 420 is communicated with the airbag 410 to supply air. The air pipe 420 may be installed at a position such that it will not be caught between the perfusion bag 1 and the casing body 210 when the airbag 410 is inflated by being injected with air from the compressor 430. It may be installed inside or outside.

The compressor 430 expands or compresses air, and blows or sucks the air into the airbag 410 through the air pipe 420 . The compressor 430 is provided on the proximal end side of the air pipe 420, as shown in FIG. Here, the power source of the compressor 430 is not particularly limited, and may be supplied from the outside via a power cord (not shown) or the like, or may be operated by providing a battery or rechargeable battery.

In addition, the external pressure generating section 400 further includes a control section 440 for controlling the compressor 430 .

The control unit 440 is a device for transmitting signals for inflating and deflating the airbag 410 to the compressor 430 and controlling the operation of the external pressure generating unit 400 . The number of times of expansion/contraction, the time required for expansion/contraction, and the like are not particularly limited, and can be appropriately changed according to the situation. Note that the control unit 440 does not have to be provided in the external pressure generating unit 400 assuming that the compressor 430 is provided with the function for controlling the inflation and deflation of the airbag 410 .

Next, the action of the perfusion device 100C according to this embodiment will be described with reference to FIG. FIG. 7 is a perspective view showing a state.

In FIG. 7, the control section 440 of the external pressure generating section 400 transmits to the compressor 430 a signal for inflating the airbag 410 to the compressor 430 . Then, the inflated airbag 410 presses the volumetric pump section 70, the volumetric pump section 70 is compressed, and the perfusate E inside is pushed out. At this time, as in the above embodiment, the first check valve 20 of the supply pipe 40 regulates the direction so that the perfusate E inside the volumetric pump unit 70 flows into the supply pipe 40 by the amount of the compressed volume. do. Therefore, the perfusate E is sent to the kidney K into which the tip 41 of the supply pipe 40 is inserted. On the other hand, the second check valve 30 of the reflux pipe 50 tries to flow the perfusate E from the storage unit 60 to the volumetric pump unit 70 in the opposite direction, so that the perfusate E is stored from the volumetric pump unit 70 . It is regulated so that it does not flow back to the part 60 . The internal volume of the volumetric pump portion 70 decreases as the perfusate E therein decreases.

Subsequently, the controller 440 of the external pressure generator 400 transmits to the compressor 430 a signal for compressing the airbag 410 to the compressor 430 . Airbag 410 compresses and moves away from volumetric pump section 70 . Then, since the volumetric pump unit 70 expands to return to its original volume, the perfusate accumulated in the storage unit 60 forms a flow path to the reflux pipe 50 connected to the volumetric pump unit 70, and the volumetric pump unit 70 The liquid is sent to At this time, the first check valve 20 of the supply pipe 40 regulates the direction so that the perfusate E does not flow back, because the perfusate E tries to flow in the direction opposite to the direction in which it flows from the volumetric pump section 70 to the supply pipe 40. . On the other hand, the second check valve 30 of the reflux pipe 50 regulates the direction of the perfusate E from the container 60 to the volumetric pump 70 . When the perfusate E in the storage section 60 runs out, or when the volume of the volumetric pump section 70 reaches its maximum, the perfusate E from the storage section 60 to the volumetric pump section 70 is stopped.

Even in this case, in this embodiment, the volumetric pump section 70 of the perfusion bag 1 can have a pumping function by repeating the above action a predetermined number of times.

It should be noted that the present invention is not limited to the above embodiments, and various modifications can be made without departing from the scope of the invention.

(Modification)
In the above embodiment, the perfusion apparatus 100 accommodates the kidney K in the accommodation section 60 of the perfusion bag 1, but the present invention is not limited to the kidney K. The organ preserved by the perfusion device of the present invention may be other organs such as liver and pancreas. Furthermore, as shown in FIG. 8, a perfusion bag 1A, which is a modification of the perfusion bag 1, may contain cultured cells C instead of organs. Note that the size of the storage section 60 can be appropriately changed according to the size of the organ or the cultured cells C. FIG.

Also, in the above embodiment, the perfusion bag 1 has one housing portion 60, but the number of housing portions 60 is not limited. For example, when it is desired to culture a plurality of cultured cells at once, a large number of storage sections may be provided by dividing the storage section into a plurality of sections.

In addition, in the above embodiment, the number of volumetric pumps of the perfusion bag is not limited, and a plurality of volumetric pumps may be provided.

Further, in the above-described embodiment, the volumetric pump section 70 is arranged below the housing section 60. However, as shown in FIG. It may be arranged on the upper side instead of the lower side. In this case, perfusion by natural fall is possible, and by separately attaching an external pump unit P that pumps water from the storage unit 60 to the volumetric pump unit 70 and appropriately setting the length, inner diameter, etc. of the supply pipe 40, natural It can be used for organs that require perfusion by dropping.

In addition, the return pipe in the above embodiment can appropriately set the length, inner diameter, etc., and can control the flow of the perfusate by giving pressure loss to the perfusate flowing inside.

In addition, the perfusion bag in the above embodiment may further include a port or the like that penetrates the interior S from the outside of the bag body and allows liquid to be injected and extracted and the contents of the interior S to be taken in and out. For example, the port can be used to add chemicals or suck out samples.

Further, in the above-described embodiment, the supply pipe 40 and the reflux pipe 50 are provided, and the first check valve 20 is provided inside the supply pipe 40, and the second check valve 30 is provided inside the return pipe 50. , the supply line 40 and the return line 50 may be eliminated by providing the first check valve 20 and the second check valve 30 directly to the perfusion bag 1 .

The type of liquid is not limited to the perfusate E described in this embodiment. In the above embodiments, the type of perfusate used in the perfusion of organs is described, but a liquid medium such as a basal medium for mammalian cells or a commercially available culture medium for maintaining stem cells that can be applied to cultured cells is applied as the perfusate. You may

In addition, in the above-described embodiment, a polypropylene storage bag or the like whose upper opening 61 can be opened and closed with a chuck 10a is used as the bag body of the perfusion bag, but the present invention is not limited to this. For example, a general-purpose medical bag may be used, or a bag body formed by pasting two plastic films together by a method such as heat sealing may be used.

Also, in the above embodiment, the same liquid is injected into the inside of the storage section and the pump section, but the liquid may not be the same.

Further, an operation button for adjusting the pressing force of the pressing portion of the driving portion may be provided on the outer surface of the casing main body 210 in the above embodiment.

Further, the casing main body 210 in the above embodiment may be further provided with a temperature control function. By setting the perfusion bag to normal body temperature (approximately 37 degrees) or hypothermia (approximately 4 degrees) by temperature control function, cell metabolism is suppressed, and organ transportation and organ preservation and can prevent ischemic injury in preparation for organ transplantation.

Further, in the above embodiment, the perfusion bag 1 may be further provided with fixing pins or the like in the casing part 200, and the perfusion bag 1 may be held down by the fixing pins or the like so as to be more pressed.

In the above-described embodiment, the perfusion bag 1 is divided into only the storage section and the volumetric pump section, but the interior S of the perfusion bag 1 is further divided into a heat exchange section, an oxygen exchange section, an oxygen addition section, or the like. good too. Optional functions may be added as needed.

Also, the external pressure generating portion according to the present invention may be other than the above embodiments. For example, the perfusion device 100 may be configured by arranging a magnetic material near the volumetric pump portion of the perfusion bag and applying external pressure to the volumetric pump portion 70 by generating a magnetic field.

Although each embodiment of the present invention has been described above, the technical scope of the present invention is not limited to the above-described embodiments, and the combination of components in each embodiment may be changed without departing from the scope of the present invention. , it is possible to add or remove various changes to each element. The invention is not limited by the preceding description.

In any of the above embodiments, according to the perfusion bag and perfusion device of the present invention, an organ/cultured cell can be perfused using a simple, inexpensive, and disposable perfusion bag.

(Example)
A kidney perfusion experiment using the perfusion bag 1 described above will be described below as an example.

In this example, an experiment was conducted using the kidney (hereinafter referred to as kidney K) of a pig (body weight 20 kg) in which the warm ischemic time was controlled to reflect the condition of the organ requiring mechanical perfusion. Mechanical perfusion, in this example, means performing perfusion using the perfusion apparatus shown in the above-described first to fourth embodiments. The excised kidney K is placed under low-temperature control to remove blood, and the tip 41 of the supply pipe 40 (connector for connection) of the perfusion bag 1 is attached to the renal artery (pulse of the kidney K). The kidney K is accommodated in the accommodation section 60 of the perfusion bag 1 and placed in a cold-controlled (4-8° C.) storage cabinet. The user then performed mechanical perfusion in cold conditions. As the perfusate E, UW-MP (Bridge of Life, USA) for renal mechanical perfusion, which is widely used clinically, was used in this example. The perfusion time was set at 4 hours as a basic evaluation. The long-term perfusion experiment will be left as a future topic.

After perfusion for about 4 hours, the user performs perfusion with an experimental device for ischemia-reperfusion evaluation using blood at a body temperature that allows evaluation of organ function, and the production of urine, the dynamics of deviant enzymes, and various fluids. sex factors were assessed. Based on these results, the user confirmed the equivalence between this embodiment and the existing method using a general pump.

According to the perfusion bag and perfusion device according to the present invention, an inexpensive and disposable perfusion bag with a simple structure can be used for perfusion of organs and cultured cells, making it industrially applicable.

100, 100A, 100B, 100C Perfusion device 1 Perfusion bag 10 Bag body 10a Chuck 11 Partition wall 20 First check valve 30 Second check valve 40 Supply pipe 50 Return pipe 60 Storage unit 70

Volume pump unit

90, 400 External

pressure generation Parts

200, 300 Casing part S Inside H User's hand (external pressure generating part)
K kidney (organ)
E perfusate (liquid)
C cultured cells

Claims

a storage unit in which at least an organ extracted from a living body or cultured cells is placed;
a volumetric pump that stores or fills a volume-variable closed space with a liquid;
A bag body that is divided into two of
a first non-return valve that regulates the direction of the liquid flowing from the volumetric pump unit to the storage unit;
a second non-return valve that regulates the direction of the liquid flowing from the storage portion to the volumetric pump portion;
A perfusion bag comprising:
The perfusion bag according to claim 1, wherein the bag is made of a flexible plastic film.
The bag is
A supply formed in the first non-return valve that communicates with the containing portion and the volumetric pump portion, has a first end that is connected to the organ, and a second end that is submerged in the liquid. piping;
a reflux pipe formed in the second check valve, having a first end communicating with the housing portion and a second end communicating with the sealed space of the positive displacement pump portion;
3. The perfusion bag of claim 1 or claim 2, wherein the interior comprises a .
The perfusion bag according to claim 1 or claim 2, wherein the storage section is provided vertically above the volumetric pump section.
A chuck is provided at the opening of the accommodation unit,
The perfusion bag according to claim 1 or 2, wherein the chuck allows the opening to be opened and closed.
The volumetric pump section is provided vertically above the housing section,
3. The perfusion bag of claim 1 or claim 2, further comprising an external pump section for pumping water from said housing section to said volumetric pump section.
A perfusion device comprising the perfusion bag according to claim 1 or claim 2,
A perfusion device comprising an external pressure generating section that applies an external pressure to the volumetric pump section from the outside of the bag body to change the volume of the volumetric pump section, thereby generating a flow of the liquid from the volumetric pump section toward the storage section, thereby forming a pump. .
The external pressure generating part is
an actuator capable of reciprocating movement;
a drive unit that provides a motion to reciprocate the actuator;
a pressing portion that is attached to the tip of the actuator and reciprocates together with the actuator to press the volumetric pump portion;
with
8. The perfusion device of claim 7, further comprising a controller that controls the driver.
The external pressure generating part is
an airbag that expands and presses the volumetric pump unit;
a compressor for ejecting or sucking air into the airbag;
with
8. The perfusion device of Claim 7, further comprising a controller that controls the compressor.
8. The perfusion apparatus according to claim 7, wherein the external pressure generating section includes a magnetic body arranged near the volumetric pump section and applying external pressure to the volumetric pump section by generating a magnetic field.