A filling method and apparatus for filling contents into a bag-shaped container, a method for manufacturing a product in a bag-shaped container, and a cell culture method using a bag-shaped container.

Abstract

The present invention provides a filling method and apparatus that enables the filling of a bag-shaped container, which comprises a container body made of a flexible material and an outlet for injecting contents, without including unintended air bubbles in the container body; a method for manufacturing a product in a bag-shaped container that enables the manufacturing of a product without including unintended air bubbles in the container body; and a cell culture method that is less likely to be affected by air bubbles unintentionally mixed into the container body when the bag-shaped container is used as a cell culture bag. [Solution] The contents are injected into the container body of a bag-shaped container through an injection port. After injecting a predetermined amount of contents, the container body is compressed from the outside to exhaust any gas that has accumulated inside the container body through the injection port.

Description

Technical Field

[0001] The present invention relates to a filling method and a filling device for filling a bag-shaped container with contents, a method for manufacturing a product contained in a bag-shaped container, and a cell culture method using a bag-shaped container.

Background Art

[0002] Conventionally, bag-shaped containers having a container body made of a flexible material formed by overlapping plastic films and heat-sealing the peripheral portions are used in a wide range of fields. For example, as a pouch container containing jelly drinks or foods as contents, as a pouch container containing refillable cosmetics or the like as contents, as a sampling bag used for sample collection, as a drip bag containing therapeutic drugs or infusions as contents, and in recent years, it is known to be used as a container used in the manufacturing process of biopharmaceuticals and as a cell culture bag used in cell culture. For example, Patent Document 1 discloses a bag-shaped culture container in which two multilayer sheets are overlapped and the periphery is sealed.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] When filling a bag-shaped container with contents containing a liquid, there is a risk that a gas such as air will be mixed in and get caught in the uneven shape of the flexible container body, resulting in bubbles remaining in the container body. When using a bag-shaped container, in many usage purposes, it is preferable that when the contents are filled into the container body, no gas other than the target contents is contained inside. For example, if air remains in the container, it may lead to deterioration of the contents. However, especially with bag-shaped containers that have a flexible body, it is difficult to manually remove the various sizes of air bubbles remaining inside. Furthermore, manually removing such gases would be a complicated process and it would be difficult to ensure reproducibility. Emptying the contents from the container once they have been filled in order to completely remove the bubbles is also undesirable as it would waste the contents. Therefore, when filling a bag-shaped container with its contents, it is required that the filling process be carried out in a way that prevents air bubbles from being contained inside the container itself.

[0005] The present invention aims to provide a filling method and apparatus that enable the filling of a bag-shaped container, which comprises a container body made of a flexible material and an outlet for injecting contents, without unintended air bubbles being included inside the container body; a method for manufacturing a product in a bag-shaped container that enables the manufacturing of a product without unintended air bubbles being included inside the container body; and a cell culture method that is less likely to be affected by air bubbles unintentionally mixed into the container body when the bag-shaped container is used as a cell culture bag. [Means for solving the problem]

[0006] One embodiment of the present invention is a filling method for filling a bag-shaped container, which comprises a container body made of a flexible material and a content injection outlet, the method comprising: injecting the content into the container body from the injection outlet; and, after injecting a predetermined amount of the content, compressing the container body from the outside to exhaust any gases remaining inside the container body from the injection outlet while the internal pressure of the container body does not fall below the ambient pressure.

[0007] Furthermore, one embodiment of the present invention is a filling device for filling a bag-shaped container, which has a container body made of a flexible material and an outlet for injecting contents, the filling device comprising: a pressurizing means for compressing the container body from the outside; a pressurizing gas supply element for pumping pressurizing gas into the inside of the container body; a contents supply container containing the contents to be injected into the inside of the container body; an injection channel connecting the pressurizing gas supply element and the contents supply container to the injection outlet; and a gas discharge channel for opening the inside of the container body to the atmosphere from the injection outlet.

[0008] Furthermore, one embodiment of the present invention is a method for manufacturing a product in a bag-shaped container, in which contents are contained in a bag-shaped container having a container body made of a flexible material and an outlet for injecting contents, the method comprising: increasing the internal pressure inside the container body by pressurizing gas through the outlet; injecting the contents into the container body under increased internal pressure through the outlet; and, after injecting a predetermined amount of contents, exhausting the stagnant gas inside the container body through the outlet while ensuring that the internal pressure inside the container body does not fall below the ambient pressure.

[0009] Furthermore, one embodiment of the present invention is a cell culture method for culturing cells using a cell culture bag comprising a container body made of a flexible material and an inlet for injecting contents, the method comprising: increasing the internal pressure inside the container body by pressurizing gas through the inlet; injecting a culture medium and cells as contents into the container body under increased internal pressure through the inlet; after injecting a predetermined amount of the culture medium, exhausting the stagnant gas inside the container body from the inlet while ensuring that the internal pressure inside the container body does not fall below the ambient pressure; and culturing the cells after the stagnant gas inside the container body has been exhausted. [Effects of the Invention]

[0010] According to the present invention, it is possible to provide a filling method and apparatus that enables filling a bag-shaped container, which has a container body made of a flexible material and an outlet for injecting contents, in a way that prevents unintended air bubbles from being included inside the container body; a method for manufacturing a product in a bag-shaped container that enables the manufacturing of a product that prevents unintended air bubbles from being included inside the container body; and a cell culture method that is less likely to be affected by air bubbles unintentionally mixed into the container body when the bag-shaped container is used as a cell culture bag. [Brief explanation of the drawing]

[0011] [Figure 1] This is a schematic diagram showing an example of a bag-shaped container used in embodiments of the present invention. [Figure 2] This is an explanatory diagram illustrating a schematic filling method according to one embodiment of the present invention. [Figure 3] This is an explanatory diagram illustrating a schematic filling method according to another example of an embodiment of the present invention. [Figure 4] This is an explanatory diagram illustrating a schematic filling method according to yet another embodiment of the present invention. [Figure 5] This is an explanatory diagram illustrating one step of a filling method according to yet another embodiment of the present invention. [Figure 6] This is an explanatory diagram illustrating a schematic filling method according to yet another example of an embodiment of the present invention. [Figure 7] This is an explanatory diagram showing a schematic representation of a filling apparatus according to one embodiment of the present invention. [Figure 8] This is a schematic diagram illustrating an example of a cell culture bag that can be used in one embodiment of the present invention. [Figure 9] This diagram illustrates the time course of cell sedimentation when air bubbles are introduced during cell culture using a cell culture bag. [Figure 10] This graph shows the results of the example. [Modes for carrying out the invention]

[0012] Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings.

[0013] [Bag-shaped container] Prior to the description of the preferred embodiments of the filling method, filling device, manufacturing method of a product in a bag-shaped container, and cell culture method of the present invention, an example of a bag-shaped container 10 that can be preferably used in these embodiments will be briefly described with reference to FIG. 1. FIG. 1 is a perspective view of the bag-shaped container 10.

[0014] The bag-shaped container 10 used in this embodiment includes a container body 11 made of a flexible material for accommodating the content, and at least one injection port 12 attached to the container body 11 for injecting and discharging the content. In the illustrated example, the planar shape of the container body 11 of the bag-shaped container 10 is a substantially rectangular shape. The size of the container body 11 is not particularly limited, but for example, it can be 50 to 500 mm in length and 50 to 500 mm in width.

[0015] The container body 11 can be formed by overlapping plastic films and heat-sealing the peripheral portions, and includes an upper surface 11a and a lower surface 11b. In the illustrated example, the upper surface 11a has a bulging shape bulging in a terraced shape composed of a substantially flat top surface portion and a side wall portion formed around the top surface portion. However, the bag-shaped container 10 used in this embodiment is not limited to the illustrated mode.

[0016] Examples of the material used for the plastic film forming the container body 11 include thermoplastic resins such as polyethylene, polypropylene, ethylene-vinyl acetate copolymer, polyester, silicone-based elastomer, polystyrene-based elastomer, and tetrafluoroethylene-hexafluoropropylene copolymer (FEP). These may be used alone or by laminating the same or different materials. However, considering the heat fusion property during heat-sealing of the peripheral portion, it is preferable to have a layer that functions as a sealant layer.

[0017] The injection outlet 12 is composed of a tubular member through which a gas or the content accommodated in the container body can flow, and a tube can be connected thereto. The injection outlet 12 can be formed of a thermoplastic resin such as polyethylene, polypropylene, vinyl chloride, polystyrene-based elastomer, FEP, etc.

[0018] [Filling method] Regarding the filling method of the present invention, a preferred embodiment will be described. The filling method of the embodiment described below is a method for filling the bag-shaped container 10 with the content so as not to contain air bubbles inside the bag-shaped container 10, that is, inside the container body 11. Here, in the present invention, the "air bubble" is not limited to only a relatively small round "bubble" that confines a gas, but refers to a gas such as air or an inert gas existing inside the container body 11 that is confined regardless of its size or shape.

[0019] 1. First Embodiment The filling method according to the first embodiment of the present invention will be described. The filling method of this embodiment includes injecting the content from the injection outlet 12 into the container body 11, and after injecting a predetermined amount of the content, compressing the container body 11 to exhaust the gas (hereinafter also referred to as "remaining gas") staying inside the container body 11 from the injection outlet 12 in a state where the internal pressure of the container body 11 does not fall below the external atmospheric pressure.

[0020] FIG. 2 is an explanatory diagram showing an outline of the filling method according to a preferred example of this embodiment. FIG. 2 shows a state where the bag-shaped container 10 is arranged such that the upper surface 11a and the lower surface 11b of the container body 11 are substantially parallel in the vertical direction and the injection outlet 12 is located above the container body 11. In this embodiment, for example, as shown in Figure 2, it is preferable to hold the container body 11 of the bag-shaped container 10 between a pair of pressing members 2 and 3 arranged at a predetermined interval, and to inject the contents into the container body 11 with the injection outlet 12 positioned vertically above the container body 11. It is also preferable to exhaust stagnant gas from the container body 11 while holding the container body 11 between a pair of pressing members 2 and 3 arranged at a predetermined interval and to position the injection outlet 12 vertically above the container body 11.

[0021] The preferred filling method of this embodiment will be described in more detail below with reference to Figure 2. In the illustrated example, the pair of pressing members 2 and 3 are flat plate-shaped first member 2 and second member 3. In the illustrated example, in order to show the relationship between the first member 2, the second member 3, and the bag-shaped container 10, the bag-shaped container 10 is shown as seen through the first member 2 and the second member 3.

[0022] In the filling method described as a preferred example of this embodiment, first, the container body 11 is held between a pair of pressing members (first member 2 and second member 3) arranged at a predetermined interval, and with the injection outlet 12 positioned above the container body 11, a predetermined amount of contents is injected into the inside of the container body 11 using a peristaltic pump or the like (Figure 2(a)). The bag-shaped container 10 is held between a pair of pressing members 2 and 3 arranged at a predetermined interval, and the pouring outlet 12 is positioned above the container body 11. When contents are poured into the container body 11, the contents gradually accumulate from the bottom inside the container body 11. As the contents accumulate, the upper surface 11a and lower surface 11b of the container body 11 come into contact with the contact surface 2a of the first member 2 and the contact surface 3a of the second member 3, and are gradually pressed down by them from below. This is preferable because it gradually smooths out any wrinkles or other irregularities on the upper surface 11a and lower surface 11b of the container body 11 from below. Furthermore, before the contents are poured in beyond the specified capacity of the container body 11, the upper surface 11a and lower surface 11b of the container body 11 come into contact with the contact surface 2a of the first member 2 and the contact surface 3a of the second member 3, and are pressed down by them. Therefore, it is preferable that the contents can be distributed to every corner of the container body 11 without injecting more contents than the predetermined capacity into the container body 11, and that the container body 11 can be expanded in such a way that folded shapes do not form at the edges of the container body 11. Furthermore, it is preferable that the contents leak from the injection outlet 12 is effectively avoided by injecting a predetermined amount of contents into the container body 11 with the injection outlet 12 positioned above the container body 11.

[0023] The amount of contents injected into the container body 11 in this process may be any desired amount. In order to obtain the effects described above, such as pressing down on the container body 11 and ensuring that the contents reach every corner of the container body 11, the distance between the pair of pressing members 2 and 3 that clamp the container body 11 should be appropriately set, taking into account the amount of contents and the shape of the bag-shaped container 10.

[0024] If the contents to be injected are liquid or contain a sol, by injecting the contents into the container body 11 with the injection port 12 positioned vertically above the container body 11, any gas originally present inside the container body 11 will move above the contents and easily gather near the injection port 12. This makes it less likely for stagnant gas to accumulate in specific parts of the container body 11, allowing the contents to reach every corner of the container body 11. As the contents reach every corner of the container body 11, stagnant gas is less likely to accumulate inside the container body 11. Furthermore, as mentioned above, when the contents are injected while the container body 11 is held between a pair of pressing members 2 and 3 arranged at predetermined intervals in the previous process, the inside of the container body 11 is in a state where gaps into which gas can enter are unlikely to form. It is assumed that gas that gets caught in gaps such as the uneven shape of the container body 11 and cannot move towards the injection outlet 12, thus remaining inside the container body 11 as air bubbles, is unlikely to exist.

[0025] Once a predetermined amount of contents has been injected into the container body 11, the injection of contents through the injection port 12 is stopped, and the inside of the container body 11 is opened to the atmosphere through the injection port 12. Next, the arrangement of the first member 2 and the second member 3 is displaced so that the distance between them is narrowed. In this embodiment, when exhausting the stagnant gas inside the container body 11 through the injection port 12 in this manner, the container body 11 is compressed from the outside while maintaining the posture of the bag-shaped container 10 so that the injection port 12 is positioned vertically above the container body 11 (Figure 2(b)).

[0026] Since the bag-shaped container 10 is installed so that the injection outlet 12 is located above the container body 11, the gas inside the container body 11 is concentrated towards the injection outlet 12. In this state, the gap between the first member 2 and the second member 3 is narrowed, and the container body 11 is clamped between these members and compressed from the outside, thereby reducing the volume of the container body 11, and any stagnant gas inside the container body 11 is pushed out into the atmosphere through the injection outlet 12. In other words, in this embodiment, when exhausting the stagnant gas inside the container body 11 from the injection port 12, the stagnant gas inside the container body 11 is not sucked out using a pump or the like, and the internal pressure of the container body 11 does not fall below the ambient pressure.

[0027] In this way, by compressing the container body 11 from the outside to reduce its volume, and especially by compressing the container body 11 from the outside using a pair of pressing members 2 and 3 as described in this embodiment, when stagnant gas is exhausted, there is no risk that the opposing films forming the container body 11 (the upper surface 11a and the lower surface 11b in the illustrated example) will come into contact with each other as the stagnant gas is discharged. For example, if stagnant gas is discharged from the container body 11 by suction using a pump or the like, there is a risk that the opposing films forming the container body 11 of the bag-shaped container 10 will come into contact with each other before the stagnant gas has been sufficiently discharged. If the films forming the container body 11 come into contact with each other, it is undesirable because the stagnant gas cannot be effectively discharged.

[0028] Furthermore, when discharging stagnant gas, compressing the container body 11 from the outside reduces its volume, which creates movement in the container body 11 and its contents. This can induce stagnant gas (bubbles) that get caught in the uneven surface of the container body 11 and fail to collect at the top to be released vertically upward. In this way, it becomes possible to discharge stagnant gas from the container body 11 more effectively than by using a pump or the like to suck the gas out of the container body 11.

[0029] If the contents foam up and small bubbles are mixed in when the contents are injected and filled into the container body 11, especially if the contents are viscous and the bubbles tend to remain inside, when releasing the retained gas to the outside of the container body 11, it is possible to allow an appropriate amount of time to pass until the bubbles present in the contents gather on the vertically upward side of the container body 11.

[0030] In the illustrated example, the bag-shaped container 10 is positioned such that the inlet 12 is located above the container body 11, with the upper surface 11a and lower surface 11b of the container body 11 being substantially parallel to the vertical direction. However, the arrangement of the bag-shaped container 10 is not limited to this configuration. When discharging the gas from inside the container body 11, it is sufficient to maintain the posture of the bag-shaped container 10 such that the inlet 12 is positioned vertically above the container body 11, so that the gas inside the container body 11 collects near the connection point between the container body 11 and the inlet 12. For example, the container body 11 may be tilted so that the angle of inclination with respect to the ground surface is 15° to 90°, by lifting one end of the bag-shaped container 10 where the inlet 12 is located, starting from a state where the bag-shaped container 10 is placed on a horizontal surface with the upper surface 11a or lower surface 11b of the container body 11 facing downwards, so that the inlet 12 is positioned vertically above the container body 11.

[0031] In this way, the filling method of this embodiment makes it possible to fill the bag-shaped container 10 with contents in a way that does not include unintended air bubbles in the container body of the bag-shaped container 10.

[0032] 2. Second Embodiment A filling method according to a second embodiment of the present invention will be described. The filling method of this embodiment includes injecting contents into the container body 11 from the injection port 12, leveling the surface of the container body 11 after injecting a predetermined amount of contents, and, after leveling the surface of the container body 11, exhausting the stagnant gas inside the container body 11 from the injection port 12 by compressing the container body 11 while the internal pressure of the container body 11 does not fall below the ambient pressure. The filling method of this embodiment differs from the first embodiment in that it includes leveling the surface of the container body 11 prior to exhausting the stagnant gas inside the container body 11 from the injection port 12.

[0033] A preferred filling method of this embodiment will be described in more detail below with reference to Figure 3. Figure 3 is an explanatory diagram showing a schematic of a preferred filling method according to this embodiment. Figure 3 shows a state in which a bag-shaped container 10 is arranged such that the upper surface 11a and the lower surface 11b of the container body 11 are substantially parallel in the vertical direction, and the pouring outlet 12 is located above the container body 11. Note that components identical to those in the embodiments described above are denoted by the same reference numerals, and their detailed descriptions are omitted.

[0034] In the filling method described as a preferred example of this embodiment, for example as shown in Figure 3, it is preferable to hold the container body 11 of the bag-shaped container 10 between a pair of pressing members (first member 2 and second member 3) arranged at a predetermined interval, and to position the injection outlet 12 vertically above the container body 11, while injecting the contents into the container body 11, leveling the surface of the container body 11, and exhausting any stagnant gas from the container body 11.

[0035] In the filling method described as a preferred example of this embodiment, first, a predetermined amount of contents is injected into the container body 11 of the bag-shaped container 10 using a peristaltic pump or the like, in the same manner as described as a preferred example of the first embodiment (Figure 3(a)).

[0036] Once a predetermined amount of contents has been injected into the container body 11, the injection of contents through the injection outlet 12 is stopped, and the surface of the container body 11 is smoothed by scraping it with the scraping plate 8 (Figure 3(b)). In the filling method described as a preferred example of this embodiment, the container body 11 is held between a pair of pressing members (first member 2 and second member 3) arranged at a predetermined interval. In this case, the scraping plate 8 can be inserted between the first member 2 or the second member 3 and the container body 11, and the surface can be scraped. Even when the container body 11 is in close contact with the first member 2 or the second member 3, since the container body 11 is made of a flexible film, the container body 11 will flex when the scraping plate 8 is inserted between the first member 2 or the second member 3 and the container body 11, allowing the scraping plate 8 to move somewhat freely. Before exhausting the gas accumulating inside the container body 11 from the injection port 12, the surface of the container body 11 is smoothed. This allows gas bubbles to be released upwards from the container body 11, even if they get caught in wrinkles or uneven surfaces on the upper surface 11a or lower surface 11b of the container body 11 when the contents are injected into the container body 11. In particular, by scraping the area near the edges of the surface of the container body 11 with the scraping plate 8, the contents can be distributed to every corner of the container body 11, even if there are folded shapes at the edges of the container body 11, preventing gas from accumulating in those folded areas. Furthermore, leveling the surface of the container body 11 may be done by temporarily stopping the injection of a predetermined amount of contents into the container body 11, or it may be done simultaneously with the injection of a predetermined amount of contents into the container body 11, as long as the gas accumulating inside the container body 11 is not exhausted from the injection port 12.

[0037] As shown in the figure, by positioning the inlet 12 above the container body 11 and leveling the surface of the container body 11, the stagnant gas easily gathers near the inlet 12. This is preferable because it makes it less likely for the stagnant gas to accumulate in a specific part inside the container body 11.

[0038] After leveling the surface of the container body 11, the scraping plate 8 is removed from between the first member 2 or the second member 3 and the container body 11, and the container body 11 is compressed from the outside in the same manner as described in the preferred example of the first embodiment, thereby exhausting the gas accumulated inside the container body 11 from the injection port 12 (Figure 3(c)).

[0039] In this embodiment, when filling the contents into the bag-shaped container 10 in this manner, it is possible to fill the container without unintended air bubbles being included in the container body of the bag-shaped container 10.

[0040] This embodiment differs from the first embodiment in the points described above, but other configurations are the same as those of the first embodiment, so redundant explanations will be omitted.

[0041] 3. Third Embodiment A filling method according to a third embodiment of the present invention will be described. The filling method of this embodiment includes increasing the internal pressure of the container body 11 by pumping pressurizing gas from the injection port 12 into the container body 11, injecting the contents into the container body 11 under increased internal pressure from the injection port 12, and, after injecting a predetermined amount of contents, exhausting any stagnant gas inside the container body 11 from the injection port 12 by compressing the container body 11 while ensuring that the internal pressure of the container body 11 does not fall below the ambient pressure. The filling method of this embodiment differs from the first embodiment in that it includes increasing the internal pressure of the container body 11 by pumping pressurizing gas from the injection port 12 into the container body 11 prior to injecting the contents from the injection port 12.

[0042] The preferred filling method of this embodiment will be described in more detail below with reference to Figure 4. Figure 4 is an explanatory diagram showing a schematic of a preferred filling method according to this embodiment. Figure 4 shows a state in which a bag-shaped container 10 is arranged such that the upper surface 11a and the lower surface 11b of the container body 11 are substantially parallel in the vertical direction, and the pouring outlet 12 is located above the container body 11. Note that components identical to those in the embodiments described above are denoted by the same reference numerals, and their detailed descriptions are omitted.

[0043] In the filling method described as a preferred example of this embodiment, for example as shown in Figure 4, it is preferable to hold the container body 11 of the bag-shaped container 10 between a pair of pressing members (first member 2 and second member 3) arranged at a predetermined interval, and to position the injection outlet 12 vertically above the container body 11, while injecting pressurizing gas into the container body 11, injecting contents into the container body 11, and exhausting retained gas from the container body 11.

[0044] In the filling method described as a preferred example of this embodiment, first, before injecting the contents into the container body 11, a predetermined amount of pressurizing gas is pumped into the container body 11 from the injection port 12 using a pump or the like (Figure 4(a)). This increases the internal pressure of the container body 11. That is, the internal pressure inside the container body 11 is made higher than the external air pressure outside the container body 11. By increasing the internal pressure of the container body 11, as shown in Figure 5, it is possible to inflate the container body 11 so that wrinkles do not form on the upper surface 11a or lower surface 11b of the container body 11, and gas reaches every corner of the container body 11, preventing the formation of folded shapes at the ends of the container body 11, etc. Figure 5 is a diagram illustrating the process of increasing the internal pressure of the container body 11. It schematically shows the side view of the container body 11, with the view from the top surface 11a of the container body 11 being considered a front view. Figure 5(a) shows the state before increasing the internal pressure of the container body 11, and (b) shows the state after increasing the internal pressure by supplying pressurizing gas to the container body 11, with the container body 11 positioned between the first member 2 and the second member 3.

[0045] As described above, in this embodiment, when pressurizing gas is pumped into the container body 11 to increase the internal pressure, the container body 11 is held between a pair of pressing members (first member 2 and second member 3) arranged at a predetermined interval while the pressurizing gas is pumped. This is preferable because it allows the internal pressure of the container body 11 to be easily increased without injecting more gas than the original capacity of the bag-shaped container 10 to expand the container body 11. In other words, by arranging the first member 2 and the second member 3 at a predetermined interval from each other and injecting gas into the container body 11 while holding the container body 11 between them, the upper surface 11a and lower surface 11b of the container body 11 come into contact with the contact surface 2a of the first member 2 and the contact surface 3a of the second member 3 and are pressed against them before the amount of gas injected exceeds the predetermined capacity of the container body 11. Therefore, even if the amount of gas injected is less than the predetermined capacity of the container body 11, the gas can reach every corner of the container body 11. This is preferable because it not only reduces the amount of pressurizing gas injected, but also eliminates the need to vent the gas injected in this step simultaneously with the injection of the contents when the contents are injected into the container body 11 in subsequent steps. Furthermore, it is preferable because it avoids the container body 11 becoming excessively swollen and deformed due to the injection of an excessive amount of gas, which could cause wrinkles to form in the container body 11. However, increasing the internal pressure of the container body 11 is not limited to this configuration. For example, even without using such a pair of pressing members 2 and 3, the internal pressure of the container body 11 can be increased by injecting an appropriate amount of gas into the container body 11 while visually observing the bulge of the container body 11.

[0046] The amount of pressurizing gas injected into the container body 11 in this process can be appropriately set, taking into consideration the shape of the bag-shaped container 10 and the spacing between the pair of pressing members 2 and 3, so that wrinkles are not formed in the flexible material forming the container body 11 and the gas reaches every corner of the container body 11. For example, if a bag-shaped container 10 with a usable capacity of 400 ml is used and the spacing between the pair of pressing members 2 and 3 is set to 1 to 5 mm, injecting 150 to 600 ml of pressurizing gas is preferable because it prevents wrinkles from forming in the flexible material forming the container body 11 and allows the gas to reach every corner of the container body 11, thus preventing the formation of folded shapes at the inner edges of the container body 11.

[0047] Next, with the internal pressure inside the container body 11 still increased, a predetermined amount of contents is injected and filled into the container body 11 from the injection port 12 using, for example, a peristaltic pump (Figure 4(b)). Pressurizing gas was injected into the container body 11 in the previous step, causing it to expand to prevent wrinkles. In this step, the contents are injected while the internal pressure inside the container body 11 remains high, that is, while the container body 11 is expanded without actively releasing the gas from inside the container body 11. When injecting and filling the contents into the container body 11, the arrangement of the first member 2 and the second member 3 may be changed as needed, such as by widening the gap between them.

[0048] If the contents being injected are liquid or contain a sol, the gas injected in the previous step, or any gas originally present inside the container body 11, will easily accumulate above the contents. Furthermore, as mentioned above, since pressurizing gas was injected into the container body 11 in the previous step, the inside of the container body 11 is free of wrinkles or gaps into which gas can enter. Therefore, it is assumed that there will be almost no gas remaining inside the container body 11 as bubbles that cannot move towards the injection outlet 12.

[0049] By injecting the contents into the container body 11 in this manner, it is possible to avoid gas entering the gaps in the unevenness on the inner surface of the container body 11 and becoming difficult to remove. Furthermore, by injecting the contents into the container body 11, which is made of a flexible material that is free of wrinkles, it is possible to avoid the uneven shape caused by wrinkles on the inner surface of the container body 11 hindering the flow of the contents and making the contents prone to foaming. In this way, when filling the contents into the bag-shaped container 10, it is possible to effectively avoid the incorporation of air bubbles into the container body 11.

[0050] Once a predetermined amount of contents has been injected into the container body 11, the injection of contents through the injection port 12 is stopped, and the container body 11 is compressed from the outside in the same manner as described in the preferred example of the first embodiment, thereby exhausting the gas accumulated inside the container body 11 through the injection port 12 (Figure 4(c)).

[0051] In this embodiment, when filling the contents into the bag-shaped container 10 in this manner, it is possible to fill the container without unintended air bubbles being included in the container body of the bag-shaped container 10.

[0052] This embodiment differs from the first embodiment in the points described above, but other configurations are the same as those of the first embodiment, so redundant explanations will be omitted.

[0053] 4. Fourth Embodiment A filling method according to the fourth embodiment of the present invention will be described. The filling method of this embodiment includes injecting contents into the container body 11 from the injection port 12, injecting pressurizing gas into the container body 11 from the injection port 12 after injecting a predetermined amount of contents or simultaneously with injecting the contents to increase the internal pressure of the container body 11, and then, after increasing the internal pressure of the container body 11, compressing the container body 11 while the internal pressure of the container body 11 does not fall below the outside air pressure to exhaust any stagnant gas from inside the container body 11 from the injection port 12. The filling method of this embodiment differs from the first embodiment in that it includes increasing the internal pressure of the container body 11 prior to compressing the container body from the outside.

[0054] The preferred filling method of this embodiment will be described in more detail below with reference to Figure 6. Figure 6 is an explanatory diagram showing a schematic of a preferred filling method according to this embodiment. Figure 6 shows a state in which the bag-shaped container 10 is arranged such that the upper surface 11a and the lower surface 11b of the container body 11 are substantially parallel in the vertical direction, and the pouring outlet 12 is located above the container body 11. Note that components identical to those in the embodiments described above are denoted by the same reference numerals, and their detailed descriptions are omitted.

[0055] In the filling method described as a preferred example of this embodiment, for example as shown in Figure 6, it is preferable to hold the container body 11 of the bag-shaped container 10 between a pair of pressing members (first member 2 and second member 3) arranged at a predetermined interval, and to position the injection outlet 12 vertically above the container body 11, while injecting the contents into the container body 11, injecting pressurizing gas into the container body 11, and exhausting stagnant gas from the container body 11.

[0056] In the filling method described as a preferred example of this embodiment, first, a predetermined amount of contents is injected into the container body 11 of the bag-shaped container 10 using a peristaltic pump or the like, in the same manner as described as a preferred example of the first embodiment (Figure 6(a)).

[0057] Once a predetermined amount of contents has been injected into the container body 11, the injection of contents through the injection port 12 is stopped, and a predetermined amount of pressurizing gas is pumped into the container body 11 from the injection port 12 using a pump or the like (Figure 6(b)). This increases the internal pressure of the container body 11. In other words, the internal pressure inside the container body 11 is made higher than the external air pressure outside the container body 11.

[0058] Alternatively, in this embodiment, to increase the internal pressure of the container body 11, although not shown in the figures, a predetermined amount of pressurizing gas may be pumped in at the same time as the contents are injected into the container body 11. In this case, for example, a single injection outlet 12 may be provided with multiple branched connecting pipes so that the contents and gas are sent into the container body 11 simultaneously.

[0059] By increasing the internal pressure of the container body 11, wrinkles are not formed on the upper surface 11a or lower surface 11b of the container body 11. Furthermore, the contents and gas can be distributed to every corner of the container body 11, preventing the formation of folded shapes at the edges of the container body 11. In this way, it is possible to avoid gas getting trapped in gaps and irregularities on the inner surface of the container body 11, making it difficult to remove.

[0060] As described above, in this embodiment, when injecting contents into the container body 11 and pressurizing gas is pumped to increase the internal pressure, the container body 11 is held between a pair of pressing members 2 and 3 arranged at a predetermined interval while the contents and pressurizing gas are pumped in. This is preferable because it allows the internal pressure of the container body 11 to be easily increased without having to pump a large amount of gas into the container body 11 in addition to the contents to expand the container body 11. However, increasing the internal pressure of the container body 11 is not limited to this configuration. For example, even without using such a pair of pressing members 2 and 3, the internal pressure of the container body 11 can be increased by injecting an appropriate amount of gas into the container body 11 while visually observing the bulge of the container body 11.

[0061] The amount of pressurizing gas injected into the container body 11 can be appropriately set, taking into consideration the shape of the bag-shaped container 10 and the spacing between the pair of pressing members 2 and 3, so that wrinkles are not formed in the flexible material forming the container body 11 and the gas reaches every corner of the container body 11.

[0062] Once a predetermined amount of contents and gas has been injected into the container body 11, the injection of contents and gas through the injection port 12 is stopped, and the container body 11 is compressed from the outside in the same manner as described in the preferred example of the first embodiment, thereby exhausting the gas remaining inside the container body 11 through the injection port 12 (Figure 6(c)).

[0063] In this embodiment, when filling the contents into the bag-shaped container 10 in this manner, it is possible to fill the container without unintended air bubbles being included in the container body of the bag-shaped container 10.

[0064] This embodiment differs from the embodiment described above in the points mentioned above, but other configurations are the same as those of the embodiment described above, so redundant explanations will be omitted.

[0065] As described above, the filling method of the embodiment of the present invention makes it possible to fill the bag-shaped container 10 with contents without including unintended air bubbles in the container body of the bag-shaped container 10. In particular, the filling method of this embodiment can be preferably applied when the contents include a liquid or sol when the contents are injected into the bag-shaped container 10. By eliminating unintended gases, it is possible to slow down the deterioration of the contents during storage, reduce the risk of contamination, and improve efficiency by reducing the volume during transport.

[0066] [Filling device] Next, a filling apparatus 1 suitable for use in the filling method described above, particularly the embodiment described as a preferred example of the third embodiment, will be described. The filling device 1 is a device for filling a bag-shaped container 10 having a container body 11 made of a flexible material and a content injection outlet 12. In order to carry out the filling method described above, the filling device 1 is equipped with means for increasing the internal pressure inside the container body 11 by pressurizing gas through the injection outlet 12, injecting the contents into the container body 11, and after injecting a predetermined amount of contents, for exhausting the stagnant gas inside the container body 11 through the injection outlet 12 by compressing the container body 11 from the outside, so that the internal pressure of the container body 11 does not fall below the ambient pressure.

[0067] A preferred filling apparatus 1 of this embodiment will be described in detail below with reference to Figure 7. Figure 7 is an explanatory diagram showing a schematic representation of a filling apparatus 1 according to an example of this embodiment. A filling device 1 described as a preferred example of this embodiment includes a pair of pressing members 2 and 3 arranged at a variable distance from each other as pressurizing means for compressing the container body from the outside, a pressurizing gas supply element 4 for pumping pressurizing gas into the container body 11, a contents supply container 5 containing the contents to be injected into the container body 11, an injection channel 6 connecting the pressurizing gas supply element 4 and the contents supply container 5 to an injection outlet 12, and a gas discharge channel 7 for releasing the inside of the container body 11 to the atmosphere from the injection outlet 12.

[0068] In the illustrated example, the pair of pressing members 2 and 3 are flat plate-shaped first member 2 and second member 3 having a substantially rectangular planar shape larger than the area of ​​the upper surface 11a or lower surface 11b of the container body 11 of the bag-shaped container 10. The first member 2 and the second member 3 each have planar contact surfaces 2a and 3a that contact the upper surface 11a or lower surface 11b of the container body 11 of the bag-shaped container 10. The first member 2 and / or the second member 3 may be partially or entirely transparent so that the internal condition of the bag-shaped container 10 can be observed. In that case, the relevant parts can be made of, for example, highly transparent synthetic resin or glass. Figure 7 shows the first member 2 and the second member 3 arranged such that their respective contact surfaces 2a and 3a are approximately parallel to the vertical. In addition, in Figure 7, the bag-shaped container 10 is shown as a transparent view from the first member 2 and the second member 3 to illustrate the relationship between the first member 2, the second member 3, and the bag-shaped container 10.

[0069] The first member 2 and the second member 3 are positioned facing each other with their contact surfaces 2a and 3a facing each other, fixed at a predetermined distance from each other, and supported by each other in such a way that the distance between them can be displaced. Such a support structure could, for example, be provided with multiple screws passing through the first member 2 and the second member 3, with the distance between them being narrowed by tightening the screws and widened by loosening the screws. Alternatively, an actuator, such as an air cylinder, robot cylinder, or linear motor, may be used as a mechanism to move the first member 2 and the second member 3. In Figure 7, other components such as the support structure are omitted as appropriate in order to show the relationship between the pair of pressing members (first member 2, second member 3) and the bag-shaped container 10.

[0070] The first member 2 and / or the second member 3 preferably include holding means (not shown) for holding the bag-shaped container 10 held between them such that the pouring outlet 12 is positioned vertically upward relative to the container body 11. The specific form of the holding means is not particularly limited. For example, the first member 2 and / or the second member 3 may be equipped with a nozzle holder as a holding means for fixing the injection outlet 12 to the upper side of the first member 2 and / or the second member 3. Alternatively, for example, the first member 2 and / or the second member 3 may be equipped with a fastener such as a clip for fixing the container body 11 to the first member 2 and / or the second member 3 as a holding means. Furthermore, for example, when using a bag-shaped container 10 having a hole drilled in the container body 11, the first member 2 and / or the second member 3 may be equipped with a fastener for engaging the hole in the bag-shaped container 10, provided at corresponding positions on the first member 2 and / or the second member 3 as a holding means.

[0071] In the illustrated example, the first member and the second member 3 are arranged such that their respective contact surfaces 2a and 3a are substantially parallel to the vertical direction. In this case, the first member 2 and the second member 3 may be mounted on the surface by support devices (not shown) that support their respective contact surfaces 2a and 3a so that they are substantially parallel to the vertical direction. However, the arrangement of the first member and the second member 3 is not limited to the illustrated example. As mentioned above, the first member and the second member 3 should be arranged such that the bag-shaped container 10 held inside the first member and the second member 3 is maintained in a position where the pouring outlet 12 is located vertically above the container body 11. For example, as mentioned above, the first member and the second member 3 may be arranged so that the upper surface 11a and lower surface 11b of the container body 11 are inclined at an angle of 15° to 90° with respect to the ground surface, and the bag-shaped container 10 is held in such a position where the pouring outlet 12 is located vertically above the container body 11. In this case, the first member 2 and the second member 3 may be installed on the mounting surface by a support such as an inclined plate that supports the first member and the second member 3 in an inclined state at a predetermined inclination angle.

[0072] In the illustrated example, the pressurizing gas supply element 4 is a container for storing pressurizing gas to be injected into the container body 11 of the bag-shaped container 10, and is equipped with at least one port 4a for injecting and discharging the pressurizing gas. In this case, the pressurizing gas supply element 4 may consist of multiple containers for injecting different pressurizing gases into the container body 11 of the bag-shaped container 10. The pressurizing gas supply element 4 is connected via port 4a to an injection channel 6, which will be described in detail later, and is fluidly connected to the container body 11 via an injection outlet 12. The stored pressurizing gas is not particularly limited as long as it can be temporarily injected into the container body 11 and will not likely affect the contents injected into the container body 11, for example, nitrogen gas. Alternatively, if the pressurizing gas supply element 4 does not affect the contents injected into the container body 11 in a later process, it may be a filter that opens one end of the injection channel 6 to the atmosphere in order to release the inside of the container body 11 to the atmosphere through the injection outlet 12 via the injection channel 6. In this case, the air that has passed through the filter can be pressurized and sent into the container body 11 by a pump or the like provided in the injection channel 6.

[0073] The contents supply container 5 is a container that stores the contents to be injected into the container body 11 of the bag-shaped container 10. This contents supply container 5 may consist of multiple containers to inject different contents into the container body 11 of the bag-shaped container 10. The contents supply container 5 is equipped with at least one port 5a for injecting and discharging contents. The port 5a is connected to the injection channel 6, which will be described in detail below, and is fluidly connected to the container body 11 via the injection outlet 12.

[0074] In the illustrated example, the injection channel 6 includes a first tube T1, one end of which is connected to the injection outlet 12 of the bag-shaped container 10 and the other end of which is connected to a first connecting pipe C1 that branches into three; a second tube T2, one end of which is connected to the first connecting pipe C1 and the other end of which is connected to a second connecting pipe C2 that branches into four; a third tube T3, one end of which is connected to the second connecting pipe C2 and the other end of which is connected to the pressurizing gas supply element 4; and a fourth tube T4, one end of which is connected to the second connecting pipe C2 and the other end of which is connected to the port 5a of the contents supply container 5. These tubes T1, T2, T3, and T4 enable the transfer of pressurized gas from the pressurized gas supply element 4 to the container body 11, and the transfer of contents from the contents supply container 5 to the container body 11.

[0075] A pressure gauge PG may be connected to the other end of the second connecting pipe C2, which is not connected to the first tube T1, the second tube T2, and the third tube T3, as shown in the figure. This allows the internal pressure of the container body 11 to be measured. However, the pressure gauge PG may be installed in a location other than the one shown in the figure, as long as it can measure the internal pressure of the container body 11.

[0076] In the illustrated example, the gas discharge channel 7 includes a first tube T1 and a fifth tube T5, one end of which is connected to the first connecting pipe C1 and the other end of which is open to the atmosphere. These tubes T1 and T5 enable the transfer of stagnant gas so that the gas inside the container body 11 is discharged into the atmosphere.

[0077] In the illustrated example, the second tube T2 is provided with the first flow path opening / closing means V1, the third tube T3 with the second flow path opening / closing means V2, the fourth tube T4 with the third flow path opening / closing means V3, and the fifth tube T5 with the fourth flow path opening / closing means V4. The flow path opening / closing means V1, V2, V3, and V4 control the flow rate of the fluid flowing through the tubes T1, T2, T3, T4, and T5, as well as the opening and closing of the flow paths. The flow path opening and closing means V1, V2, V3, and V4 can be, for example, pinch valves, but are not particularly limited. For example, three-way stopcocks or four-way stopcocks may be used as the first connecting pipe C1 and the second connecting pipe C2 to connect the tubes and control the fluid flow rate and the opening and closing of the flow path.

[0078] In the illustrated example, a pump P is provided in the second tube T2 for supplying the contents and pressurizing gas to the container body 11. A peristaltic pump, for example, can be used as the pump P, but is not limited to this.

[0079] A flow meter F may be provided in the second tube T2 to check the flow rate of the fluid flowing through the injection channel 6.

[0080] As an operating method for filling the container body 11 of the bag-shaped container 10 with the filling device 1 according to this embodiment in a way that does not include unintended air bubbles inside, the operating method of the filling device 1 will be described below, with the method described above as a preferred example of the third embodiment as an example.

[0081] The bag-shaped container 10 is held such that, as shown in the figure, the injection port 12 is positioned vertically above the container body 11, and the container body 11 is positioned between the first member 2 and the second member 3. The first tube T1, which will be the end of the injection channel 6 and the gas discharge channel 7 connected to the bag-shaped container 10, is attached to the injection port 12 of the bag-shaped container 10.

[0082] First, with the flow path opening / closing means V1, V2, V3, and V4 all closed, the first flow path opening / closing means V1 and the second flow path opening / closing means V2 are opened, and pressurizing gas is injected into the container body 11 from the injection outlet 12 using the pump P.

[0083] When pressurizing gas is injected, the upper surface 11a and lower surface 11b of the container body 11 come into contact with the contact surface 2a of the first member 2 and the contact surface 3a of the second member 3, and the internal pressure of the container body 11 is increased. When the internal pressure inside the container body 11 is thus higher than the external air pressure outside the container body 11, the first flow path opening / closing means V1 remains open and the second flow path opening / closing means V2 is closed.

[0084] Next, the third flow path opening / closing means V3 is opened, and the contents contained in the contents supply container 5 are injected into the container body 11 from the injection outlet 12 using the pump P.

[0085] Once the contents have been filled into the container body 11, the first flow path opening / closing means V1 and the third flow path opening / closing means V3 are closed.

[0086] Next, after a predetermined time has elapsed, allowing the gas inside the container body 11 to gather near the injection port 12 as needed, the fourth flow path opening / closing means V4 is opened to release the inside of the container body 11 to the atmosphere through the injection port 12. As a result, the stagnant gas inside the container body 11 begins to be discharged from the injection port 12 located above the container body 11.

[0087] Next, with the fourth flow path opening / closing means V4 remaining open, the gap between the first member 2 and the second member 3 is reduced, compressing the container body 11 from the outside. As a result, the volume of the container body 11 sandwiched between the first member 2 and the second member 3 decreases, and the stagnant gas remaining inside the container body 11 is discharged from the injection outlet 12. According to this embodiment, when discharging the stagnant gas inside the container body 11, the stagnant gas is not sucked in by a pump or the like, and the internal pressure of the container body 11 does not fall below the ambient pressure.

[0088] According to the filling device 1 of this embodiment, with this configuration, pressurizing gas is pumped into the container body 11 from the injection port 12 to increase the internal pressure, the contents are injected into the container body 11 while the internal pressure is increased, and after a predetermined amount of contents has been injected, the contents are vented from the injection port 12 while ensuring that the internal pressure of the container body 11 does not fall below the ambient pressure, thereby filling the bag-shaped container 10 with the contents, and making it possible to fill the bag-shaped container 10 without unintended air bubbles being included inside the container body 11.

[0089] [Manufacturing method for products in bag-shaped containers] Next, a method for manufacturing a bag-shaped container product according to this embodiment will be described. The method for manufacturing a bag-shaped container product according to this embodiment is an example of a specific use of the filling method described above, and a bag-shaped container product can be suitably manufactured by this method.

[0090] The method for manufacturing a bag-shaped container product according to this embodiment involves manufacturing a bag-shaped container product in which contents are contained in a bag-shaped container 10 having a container body 11 made of a flexible material and a contents injection outlet 12, and includes increasing the internal pressure of the container body 11 by pressurizing gas through the injection outlet 12, injecting the contents into the container body 11 under increased internal pressure through the injection outlet 12, and after injecting a predetermined amount of contents, exhausting the stagnant gas inside the container body 11 through the injection outlet 12 while ensuring that the internal pressure of the container body 11 does not fall below the ambient air pressure. This makes it possible to manufacture products in bag-shaped containers without unintended air bubbles being contained inside the container body 11.

[0091] In the manufacturing method of the bag-shaped container product of this embodiment, pressurizing gas is injected into the container body 11 to increase the internal pressure of the container body 11, similar to the filling method described as a preferred example of the third embodiment above. Then, the contents are injected into the container body 11. Subsequently, while ensuring that the internal pressure of the container body 11 does not fall below the ambient pressure, the stagnant gas inside the container body 11 can be exhausted from the injection outlet 12. Since the details of these steps can be carried out in the same manner as the filling method described above, redundant explanations will be omitted. Furthermore, in the manufacturing method of the bag-shaped container product of this embodiment, the aforementioned filling apparatus 1 can be suitably used.

[0092] The method for manufacturing a bag-shaped container product according to this embodiment can be suitably used to manufacture a bag-shaped container product containing a pharmaceutical product.

[0093] Furthermore, the method for manufacturing a bag-shaped container product according to this embodiment can be suitably used to manufacture a bag-shaped container product containing a gel-like substance. A more specific example of a product is, for instance, a jelly drink. It is known that jelly drinks are made by filling a bag-shaped container 10 with a sol-like contents containing a gelling agent for forming a gel-like contents from liquid contents, and then cooling the contents after filling the bag-shaped container 10 to gel them. According to this embodiment, even with the contents of such a gel-like product, if the contents are in a sol-like state at the time of filling, the product can be manufactured suitably without including unintended air bubbles during filling.

[0094] Furthermore, the method for manufacturing a bag-shaped container product according to this embodiment can be suitably used to manufacture a bag-shaped container product containing a culture medium for cell culture.

[0095] Thus, the manufacturing method of the bag-shaped container product of this embodiment can be particularly suitably used for liquid contents that include a liquid or sol when injected into the bag-shaped container 10.

[0096] The manufacturing method for the bag-shaped container product of this embodiment is preferable because it eliminates unintended air bubbles as much as possible during product distribution, thereby minimizing the risk of deterioration and contamination of the contents. Furthermore, since the volume of the bag-shaped container product containing the contents is not unnecessarily increased, it is preferable because it improves efficiency during product transport.

[0097] [Cell culture method] Next, a cell culture method according to this embodiment will be described. The cell culture method according to this embodiment is an example of a specific use of the aforementioned packing method, and cell culture can be suitably carried out by this method.

[0098] [Cell culture bag] In the cell culture method according to this embodiment, the aforementioned bag-shaped container 10 can be used as a cell culture bag for culturing cells. An example of another cell culture bag 20 that can be preferably used will be briefly described with reference to Figure 8. Figure 8(a) is a plan view of the cell culture bag 20, (b) is an enlarged view of (a) along line AA', and (c) is an enlarged cross-sectional view of (b) along line BB', which is a schematic explanatory diagram showing the cross-section. Note that the wall thickness of the container body 11 shown in the cross-section of Figure 8(c) is exaggerated.

[0099] The cell culture bag 20 that can be preferably used in this embodiment, like the bag-shaped container 10 described above, comprises a container body 21 made of a flexible material and at least one injection outlet 22 attached to the container body 21 for injecting and discharging the contents.

[0100] The cell culture bag 20 differs from the aforementioned bag-shaped container 10 in that the lower surface 21b of the cell culture bag 20 has multiple recesses 21c, each of which serves as a cell culture area. By providing multiple recesses 21c on the bottom surface of the container body 21, cells settling in the culture medium are collected at the bottom of each recess 21c, and the cells are cultured at a predetermined cell density with cell movement suppressed within the cell culture bag 20, allowing the formation of cell aggregates (also called cell aggregates or spheroids). In the cell culture bag 20, the recesses 21c have a spherical shape, as shown in Figure 8(c), to facilitate the collection of cells at the bottom of the recesses 21c. The recess 21c preferably has an opening diameter (diameter) D of 0.3 to 10 mm and a depth d of 0.1 mm or more, in order to suppress the movement of cells within the container body 21 and to ensure that the cultured cells remain in one recess 21c.

[0101] Furthermore, as shown in Figure 8(c), the upper surface 21a of the cell culture bag 20 has a plateau-like bulge shape, consisting of a substantially flat top surface portion 21d that covers the entire upper part of the multiple recesses 21c, and a side wall portion 21e formed around the top surface portion 21d. As a result, compared to a flat pouch-type container made by simply overlapping two plastic films and sealing the edges, deformation of the periphery of the bottom surface 21b is suppressed when the container body 21 is filled with culture medium while, for example, the bottom surface 21b is placed in contact with the ground surface.

[0102] The material used for the plastic film forming the container body 21 of the cell culture bag 20 can be the same as that used for the bag-shaped container 10 described above, but it is preferable that the container body 21 of the cell culture bag 20 be formed from a gas-permeable plastic film. The gas permeability of the plastic film is determined by the gas permeability test method of JIS K 7126, and the oxygen permeability measured at a test temperature of 37°C is 5000 mL / (m³). 2 It is preferable that it is at least (day·atm). The cell culture bag 20, which can be preferably used in this embodiment, differs from the bag-shaped container 10 in the points mentioned above, but its other configurations are the same as those of the bag-shaped container 10, so redundant explanations will be omitted.

[0103] When culturing cells using such a flexible cell culture bag 20, when placing the culture medium and cells to be cultured inside the container body 21, the culture medium is first injected into the container body 21, and then the cells are seeded, or a cell suspension containing the culture medium and cells is injected into the container body 11. If the cells to be cultured are, for example, suspension cells, when the culture medium and cells are injected into the container body 11, the cells are cultured while suspended in the culture medium. If the cells to be cultured are, for example, adherent cells, the container body 11 is placed so that the side of the inner surface of the container body 11 that becomes the culture surface, for example, in the case of a cell culture bag 20 with the recess 21c described above, the bottom surface 21b is facing downwards, and the cells are cultured by settling them on the culture surface. However, as shown in Figure 9, if air bubbles B are present inside the container body 11, when the cells are injected into the container body 11 and diffuse into the culture medium inside, the air bubbles B may hinder the cell movement and inhibit diffusion (Figure 9(a)). Therefore, there is a risk that areas with different cell concentrations may form inside the container body 11. Furthermore, if cell diffusion is inhibited inside the container body 11, when cells settle on the culture surface, the same number of cells will not be present above the culture surface, meaning that the number of settling cells C will differ depending on the region of the culture surface, and there is a risk that areas on the culture surface of the container body 21 will have areas with and without cells C (Figure 9(b)). In particular, when using a cell culture bag 20 provided with recesses 21c, the intention is to collect cells C in each recess 21c to achieve a predetermined cell density and perform culture to form cell aggregates S, but there is a risk that this cannot be achieved (Figure 9(c)). Figure 9 is an explanatory diagram showing the diffusion and sedimentation of cells C over time, from (a) to (c), when cells C are seeded in a culture medium containing air bubbles B using a cell culture bag.

[0104] Furthermore, if air bubbles remain inside the container body 11, there is a concern that the culture medium components may be easily depleted in some of the cells or cell aggregates that are in contact with those air bubbles, thus reducing the overall culture efficiency of the cells or cell aggregates.

[0105] Therefore, in the cell culture method of this embodiment, when culturing cells using a cell culture bag 20 equipped with a container body 21 made of a flexible material and an inlet 22 for injecting contents, the method includes increasing the internal pressure of the container body 21 by pumping pressurizing gas from the inlet 22 into the container body 21, injecting culture medium as contents into the container body 21 while the internal pressure is increased, and after injecting a predetermined amount of culture medium, exhausting the stagnant gas inside the container body 21 from the inlet 22 while ensuring that the internal pressure of the container body 21 does not fall below the ambient air pressure. This allows cells to be cultured in a state where as many air bubbles as possible that may have been unintentionally introduced into the container body 11 have been eliminated.

[0106] In the cell culture method of this embodiment, except that the bag-shaped container 10 is replaced with a cell culture bag 20 and the contents are culture medium and cells for cell culture, the filling method is the same as the filling method described as a preferred example in the third embodiment above. Before injecting the culture medium and cells into the container body 21, pressurizing gas is injected into the container body 21 to increase the internal pressure of the container body 21. Then the culture medium is injected into the container body 21. Then, while ensuring that the internal pressure of the container body 21 does not fall below the ambient pressure, the stagnant gas inside the container body 21 can be exhausted from the injection outlet 22. Since the details of these steps can be carried out in the same manner as the filling method described above, redundant explanations are omitted.

[0107] In the cell culture method of this embodiment, the aforementioned filling device 1 can be suitably used as the device for filling the culture medium.

[0108] To culture cells by settling them on the culture surface, the cell culture bag 20, from which the stagnant gas inside the container body 21 has been evacuated, can be placed with the culture surface facing the bottom, and cell culture can be carried out. The timing for injecting cells into the container body 21 can be at any time before proceeding with cell culture. Cells can be injected when the culture medium is injected into the container body 21, that is, as a cell suspension containing the medium and cells, or cells can be injected into the container body 21 immediately before placing the cell culture bag 20 with the culture surface facing the bottom. When placing the cell culture bag 20 with the culture surface facing the bottom and allowing cells to settle on the culture surface to proceed with the culture, the inside of the container body 11 is designed to remove as many unintentionally introduced air bubbles as possible. This effectively prevents air bubbles from obstructing the cell settling path, allowing cells to settle in the desired area and the culture to proceed.

[0109] According to the cell culture method of this embodiment, unintended air bubbles inside the container body 21 are eliminated as much as possible, making it possible to culture cells in a state where there is little risk of being affected by air bubbles unintentionally mixed inside the container body 21. [Examples]

[0110] The present invention will be described in more detail below with reference to specific examples.

[0111] [Example 1] A bag-shaped container was prepared, consisting of a container body made of flexible polyethylene plastic film, as shown in Figure 1. The dimensions of the bag-shaped container body were 420 mm in length, 297 mm in width, and 4 mm in thickness. The prepared bag-shaped container was held between a pair of pressing members, consisting of a first and second flat plate-shaped member, with the pouring outlet positioned above the container body. The distance between the first and second members was 2.5 mm. While the bag-shaped container was held between the pair of pressing members in this manner, 200 ml of the contents were poured into the container body through the pouring outlet. Next, the inside of the container body was opened to the atmosphere through the pouring outlet. Then, the pair of pressing members were displaced so that the distance between them was 2.0 mm. Subsequently, the container body of the bag-shaped container was placed on a horizontal surface, and the area ratio (%) of the gas remaining inside the container body was calculated as "area where gas exists ÷ area of ​​the container body × 100" in a plan view. The results are shown in Figure 10.

[0112] [Example 2] A bag-shaped container identical to that in Example 1 was prepared. The container body was held between a pair of pressing members, consisting of a flat first member and a flat second member, such that the pouring outlet was located above the container body. The distance between the first and second members was 2.5 mm. While the bag-shaped container was held between the pair of pressing members in this manner, 200 ml of the contents were poured into the container body through the pouring outlet. Next, a scraping plate was inserted between the pressing members and the container body, and the surface of the container body was scraped up with the scraping plate to smooth the surface of the container body. Next, the scraping plate was removed from between the pressing members and the container body, and the inside of the container body was opened to the atmosphere through the pouring outlet. Next, the pair of pressing members were displaced so that the distance between them was 2.0 mm. Subsequently, the area ratio (%) of the gas remaining inside the container body was determined in the same manner as in Example 1. The results are shown in Figure 10.

[0113] [Example 3] A bag-shaped container identical to that in Example 1 was prepared. The prepared bag-shaped container was held between a pair of pressing members, consisting of a first and second flat plate-shaped member, such that the injection port was positioned above the container body. The distance between the first and second members was 2.5 mm. While the bag-shaped container was held between the pair of pressing members in this manner, 300 ml of pressurizing gas was injected through the injection port. Next, 200 ml of contents were injected into the container body through the injection port. Then, the inside of the container body was opened to the atmosphere through the injection port. Next, the pair of pressing members were displaced so that the distance between them was 2.0 mm. Subsequently, the area ratio (%) of the gas remaining inside the container body was determined in the same manner as in Example 1. The results are shown in Figure 10.

[0114] [Example 4] A bag-shaped container identical to that in Example 1 was prepared. The prepared bag-shaped container was held between a pair of pressing members, consisting of a flat first member and a second member, such that the injection port was positioned above the container body. The distance between the first and second members was 2.5 mm. While the bag-shaped container was held between the pair of pressing members in this manner, 200 ml of contents were injected into the container body through the injection port. Next, 300 ml of pressurizing gas was injected through the injection port. Then, the inside of the container body was opened to the atmosphere through the injection port. Next, the pair of pressing members were displaced so that the distance between them was 2.0 mm. Subsequently, the area ratio (%) of the gas remaining inside the container body was determined in the same manner as in Example 1. The results are shown in Figure 10.

[0115] [Comparative Example 1] A bag-shaped container identical to that in Example 1 was prepared. 200 ml of the contents were poured into the container body through the inlet of the prepared bag-shaped container. Next, the inside of the container body was opened to the atmosphere through the inlet. Then, using a pump, the gas was aspirated until no gas could be visually detected inside the container body. Subsequently, the area ratio (%) of the gas remaining inside the container body was determined in the same manner as in Example 1. The results are shown in Figure 10.

[0116] In Examples 1-5, it was confirmed that the stagnant gas could be effectively removed compared to Comparative Example 1, in which the stagnant gas accumulated in the container body of the bag-shaped container was exhausted by a pump. In particular, in Comparative Example 1, it was confirmed that the films forming the container body came into contact with each other before the gas accumulated inside the container body could be exhausted, causing the gas to get stuck in that area and preventing the stagnant gas from being properly exhausted. On the other hand, in Examples 1-5, exhaust was carried out without using a pump, while the internal pressure of the container body did not fall below the ambient pressure, which suppressed contact between the films forming the container body and allowed for the effective exhaust of the stagnant gas.

[0117] Although the present invention has been described above with reference to preferred embodiments, it goes without saying that the present invention is not limited to the embodiments described above, and various modifications can be made within the scope of the present invention.

[0118] For example, the planar shape of the container bodies 11 and 21 of the bag-shaped container 10 and the cell culture bag 20 is approximately rectangular, but the planar shape of the container bodies 11 and 21 of the bag-shaped container 10 and the cell culture bag 20 is not limited to this, and can be various shapes such as square, hexagonal, elliptical, or circular. The at least one injection port 12 and 22 provided in the container bodies 11 and 21 for discharging the contents is preferably positioned at the top vertically when the container bodies 11 and 21 are tilted so that the injection port 12 and 22 is positioned vertically upward, but it goes without saying that the position of the injection port 12 and 22 can be appropriately designed depending on the planar shape of the container bodies 11 and 21. Furthermore, although the above-described embodiment used a bag-shaped container 10 and a cell culture bag 20, each provided with one injection port 12, 22, as examples, the number of injection ports 12, 22 is not limited to one, as long as the filling method of the present invention can be implemented.

[0119] Furthermore, in the above-described embodiment, the injection channel 6 for injecting pressurizing gas and contents into the container body 11 is exemplified as a first tube T1, a second tube T2, a third tube T3, and a fourth tube T4, and a configuration in which the first tube T1 and the second tube T2 are used together for transferring pressurizing gas and contents to the container body 11 is exemplified, but the tube path can be appropriately designed according to the contents to be transferred and is not limited to the above-described configuration. The pressurizing gas supply element 4 and the contents supply container 5 may also be configured as an injection channel 6 consisting only of dedicated tubes, without using a tube that is used in common. In that case, the respective tubes may be switched to the injection outlet 12 of the bag-shaped container 10 according to the process, and dedicated tubes for the pressurizing gas supply element 4 and the contents supply container 5 may be directly connected, or a connecting pipe branching into multiple parts may be provided at the injection outlet 12 and dedicated tubes may be connected. Similarly, in the above-described embodiment, the first tube T1 and the fifth tube T5 were exemplified as gas discharge channels 7 that open the inside of the container body 11 to the atmosphere, but the gas discharge channels 7 are not limited to those described above.

[0120] Furthermore, in the above-described embodiment, a pair of pressing members (a flat plate-shaped first member 2 and a second member 3) arranged at a variable distance from each other was described as an example of a pressurizing means for compressing the container body from the outside. However, the embodiment is not limited to this configuration as long as the container body can be compressed from the outside. The pair of pressing members described in the above-described embodiment is preferable because it makes it easy to compress the container body from the outside and to hold the bag-shaped container held between them so that the injection outlet is positioned vertically upward relative to the container body. However, compressing the container body from the outside and holding the bag-shaped container in a desired position may be carried out by other members. For example, to compress the container body from the outside, a rod-shaped member that sandwiches the container body may be used as the pressing member. Alternatively, for example, a chamber large enough to hold a bag-shaped container inside may be used as the pressing member. When a chamber is used as the pressing member, the container body can be compressed from the outside by putting gas or liquid into the chamber. [Explanation of Symbols]

[0121] 1 Filling device 2. Pressing member (first member) 3. Pressing member (second member) 4. Pressurizing gas supply element 5 Content supply container 6 Injection channel 7. Gas discharge channel 8. Scrubbing board 10 Bag-shaped containers 11 Container body 12 Inlet 20 cell culture bags 21 Container body 22 Inlet

Claims

1. A filling method for filling a bag-shaped container, which has a container body made of a flexible material and a content injection outlet, The contents are poured into the container body through the injection port, After injecting a predetermined amount of the contents, the container body is compressed from the outside, thereby exhausting any gas trapped inside the container body through the injection port while the internal pressure of the container body does not fall below the ambient pressure. A filling method characterized by including the following.

2. The filling method according to claim 1, further comprising leveling the surface of the container body prior to exhausting the gas accumulated inside the container body from the injection outlet.

3. The filling method according to claim 1, wherein pressurizing gas is injected into the container body from the injection port to increase the internal pressure of the container body, and then the contents are injected into the container body, which is under increased internal pressure, from the injection port.

4. The filling method according to claim 1, wherein after or simultaneously with the injection of the contents, pressurizing gas is injected into the container body from the injection port to increase the internal pressure of the container body, and then the gas remaining inside the container body is exhausted from the injection port.

5. The filling method according to any one of claims 1 to 4, wherein when injecting the contents into the container body from the injection outlet, the container body is held between a pair of pressing members arranged at a predetermined interval while the contents are injected.

6. The filling method according to any one of claims 1 to 4, wherein when exhausting the stagnant gas inside the container body from the injection outlet, the container body is compressed from the outside while maintaining the posture of the bag-shaped container such that the injection outlet is positioned vertically upward relative to the container body.

7. The filling method according to claim 3 or 4, wherein when pressurizing gas is pumped into the container body to increase the internal pressure, the container body is held between a pair of pressing members arranged at a predetermined interval while the pressurizing gas is pumped.

8. A filling device for filling a bag-shaped container, which has a container body made of a flexible material and a content injection outlet, A pressurizing means for compressing the container body from the outside, A pressurizing gas supply element for supplying pressurizing gas into the interior of the container body, A contents supply container containing the contents to be injected into the container body, An injection channel is provided to connect the pressurizing gas supply element and the contents supply container to the injection outlet, A gas discharge channel for releasing the inside of the container body to the atmosphere from the aforementioned injection outlet, A filling apparatus characterized by being equipped with the following features.

9. The filling apparatus according to claim 8, wherein the pressurizing means is a pair of pressing members arranged at a variable distance from each other.

10. The filling apparatus according to claim 9, wherein the pair of pressing members are provided with holding means for holding the bag-shaped container such that the injection outlet is positioned vertically upward with respect to the container body.

11. A method for manufacturing a product in a bag-shaped container, wherein the contents are contained in a bag-shaped container having a container body made of a flexible material and an outlet for injecting the contents, The internal pressure of the container body is increased by pumping pressurizing gas from the injection outlet, The contents are injected into the container body, which is under increased internal pressure, through the injection port. After injecting a predetermined amount of the contents, the internal pressure of the container body is kept from falling below the ambient pressure, and any stagnant gas inside the container body is exhausted from the injection outlet. A method for producing a product in a bag-shaped container, characterized by including the following:

12. A method for manufacturing a product in a bag-shaped container containing a pharmaceutical product, according to claim 11.

13. A method for manufacturing a product in a bag-shaped container containing a gel-like substance, according to claim 11.

14. A method for producing a product in a bag-shaped container containing a culture medium for cell culture, according to claim 11.

15. A cell culture method for culturing cells using a cell culture bag that comprises a container body made of a flexible material and an outlet for injecting contents, The internal pressure of the container body is increased by pumping pressurizing gas from the injection outlet, The process involves injecting the culture medium and cells as the contents into the container body, which is under increased internal pressure, through the injection port. After injecting a predetermined amount of the culture medium, the internal pressure of the container body is kept from falling below the ambient pressure, and any stagnant gas inside the container body is exhausted from the injection outlet. After the stagnant gas inside the container body is exhausted, the cells are cultured. A cell culture method characterized by including the following.

16. The cell culture method according to claim 15, wherein culturing the cells includes allowing the cells to settle on the culture surface inside the container body and culturing them.

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