Liquid-filled combination container, container set, and method of manufacturing liquid-filled container

Abstract

To provide a combination container restricting oxygen-induced deterioration of a container including liquid.SOLUTION: A combination container 10 L including liquid has a first container 30 that stores liquid L of a volume γ(mL) and is pervious to oxygen at least partially, and a second container 40 that stores the first container and has an oxygen barrier property. A sum of a value obtained by subtracting the volume γ(mL) from a maximum capacity (mL) of the first container and a value obtained by subtracting the volume occupied by the first container (mL) from a maximum capacity (mL) of the second container is equal to or greater than (2.56×10-4×(β×T / α)) times of the volume γ(mL). T is an ambient temperature (K). β is a saturation solubility (mg / L) of oxygen to the liquid in the air atmosphere under air pressure at the temperature T(K). α is oxygen concentration (%) in the second container.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a combination liquid-filled container, a container set, and a method for manufacturing a liquid-filled container. [Background technology]

[0002] Containers for storing liquids are known (for example, Patent Document 1). Depending on the type of liquid, the liquid may be decomposed by oxygen inside the container. To address this problem, it is conceivable to use a container with oxygen barrier properties. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2011-212366 Summary of the Invention [Problem to be solved by the invention]

[0004] However, oxygen can dissolve in the liquid during production. Containers with oxygen barrier properties cannot address deterioration of the liquid caused by dissolved oxygen in the liquid. In other words, conventional technologies cannot adequately suppress oxygen-induced deterioration of the liquid contained in the container. The present disclosure aims to suppress deterioration of the liquid caused by oxygen. [Means for solving the problem]

[0005] A first liquid-containing combination container according to the present disclosure comprises: a first container containing a liquid of volume γ (mL) and at least a portion of which is oxygen permeable; a second container that houses the first container and has oxygen barrier properties; The sum of the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container and the value obtained by subtracting the volume (mL) occupied by the first container from the maximum volume (mL) of the second container is (2.56 × 10 -4× (β × T / α) times or more, where T is the temperature of the environment (K), β is the saturated solubility of oxygen (mg / L) in the liquid in an air atmosphere under atmospheric pressure at temperature T (K), and α is the oxygen concentration (%) in the second container.

[0006] The second liquid-containing combination container according to the present disclosure comprises: a first container containing a liquid of volume γ (mL) and at least a portion of which is oxygen permeable; a second container that houses the first container and has oxygen barrier properties; The first container and the second container have a total volume of (2.56 × 10 -4 × β × T), where T is the temperature of the environment (K) and β is the saturated solubility of oxygen (mg / L) in the liquid in an air atmosphere at atmospheric pressure at temperature T (K).

[0007] In the combination container containing the first and second liquids according to the present disclosure, the oxygen concentration α may be less than 1%.

[0008] In the first and second liquid-containing combination containers according to the present disclosure, the sum of the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container and the value obtained by subtracting the volume (mL) occupied by the first container from the maximum volume (mL) of the second container is greater than or equal to (2.56×10 -4 ×(β×T / α)) and the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container multiplied by (21.0 / α).

[0009] In the first and second liquid-containing combination containers according to the present disclosure, the first container and the second container together make the volume γ (mL) (2.56×10 -4 × β × T) and the maximum volume (mL) of the first container minus the volume γ (mL) multiplied by 21.0.

[0010] In the first and second liquid-containing combination containers according to the present disclosure, the volume γ (mL) may be greater than half the maximum volume (mL) of the first container.

[0011] In the first and second liquid-containing combination containers according to the present disclosure, the volume γ may be 0.5 mL or more.

[0012] In the first and second liquid-containing combination containers according to the present disclosure, the volume γ may be 97.5% or more of the maximum volume (mL) of the first container.

[0013] In the first and second liquid-containing combination containers according to the present disclosure, the volume γ may be 20 mL or less.

[0014] In the combination container containing first and second liquids according to the present disclosure, the first container may be capable of containing gas while maintaining a negative pressure.

[0015] In the combination container containing the first and second liquids according to the present disclosure, the second container may be under negative pressure.

[0016] In the combination container containing the first and second liquids according to the present disclosure, the first container may be under negative pressure.

[0017] In a first and second liquid-containing combination container according to the present disclosure, the first container has a container body having an opening and a plug that closes the opening, The oxygen may be permeable through the plug.

[0018] In the combination container containing the first and second liquids according to the present disclosure, the container body may have oxygen barrier properties.

[0019] In a first and second liquid-containing combination container according to the present disclosure, the first container has a container body having an opening and a plug that closes the opening, The material constituting the stopper may have an oxygen permeability coefficient greater than that of the material constituting the container body.

[0020] In a first and second liquid-containing combination container according to the present disclosure, the first container has a container body having an opening and a plug that closes the opening, The plug may be constructed at least in part from silicone.

[0021] In the combination container containing the first and second liquids according to the present disclosure, the container body may be made of glass.

[0022] In a first and second liquid-containing combination container according to the present disclosure, the first container includes a syringe having a cylinder and a piston with a gasket disposed in the cylinder to define a space for containing the liquid; The oxygen may be permeable through the gasket.

[0023] In the combination container containing the first and second liquids according to the present disclosure, the cylinder may have oxygen barrier properties.

[0024] In a first and second liquid-containing combination container according to the present disclosure, the first container includes a syringe having a cylinder and a piston with a gasket disposed in the cylinder to define a space for containing the liquid; The oxygen permeability coefficient of the material constituting the gasket may be greater than the oxygen permeability coefficient of the material constituting the cylinder.

[0025] In a first and second liquid-containing combination container according to the present disclosure, the first container includes a syringe having a cylinder and a piston with a gasket disposed in the cylinder to define a space for containing the liquid; The gasket may be constructed at least in part from silicone.

[0026] In the combination container containing the first and second liquids according to the present disclosure, the cylinder may be made of glass.

[0027] A first container set according to the present disclosure includes: a first container containing a liquid of volume γ (mL) and at least a portion of which is oxygen permeable; a second container capable of accommodating the first container and having oxygen barrier properties; The sum of the maximum volume (mL) of the first container minus the volume γ (mL) and the maximum volume (mL) of the second container minus the volume (mL) occupied by the first container is greater than 0.663 times the volume γ (mL).

[0028] A second container set according to the present disclosure includes: a first container containing a liquid of volume γ (mL) and at least a portion of which is oxygen permeable; a second container capable of accommodating the first container and having oxygen barrier properties; The sum of the maximum volume (mL) of the first container minus the volume γ (mL) and the maximum volume (mL) of the second container minus the volume (mL) occupied by the first container is greater than 0.921 times the volume γ (mL).

[0029] A third container set according to the present disclosure comprises: a first container containing a liquid of volume γ (mL) and at least a portion of which is oxygen permeable; a second container capable of accommodating the first container and having oxygen barrier properties; In a state in which the first container is contained and the second container is closed, the first container and the second container can contain a total volume of gas that is greater than 0.663 times the volume γ (mL).

[0030] A fourth container set according to the present disclosure includes: a first container containing a liquid of volume γ (mL) and at least a portion of which is oxygen permeable; a second container capable of accommodating the first container and having oxygen barrier properties; In a state in which the first container is contained and the second container is closed, the first container and the second container can contain a total volume of gas that is greater than 0.921 times the volume γ (mL).

[0031] In the first to fourth container sets according to the present disclosure, the sum of the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container and the value obtained by subtracting the volume (mL) occupied by the first container from the maximum volume (mL) of the second container may be greater than the sum of the value obtained by multiplying the volume γ (mL) by 0.663 and the value obtained by multiplying the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container by 21.0.

[0032] In the first to fourth container sets according to the present disclosure, the sum of the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container and the value obtained by subtracting the volume (mL) occupied by the first container from the maximum volume (mL) of the second container may be greater than the sum of the value obtained by multiplying the volume γ (mL) by 0.921 and the value obtained by multiplying the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container by 21.0.

[0033] In the first to fourth container sets according to the present disclosure, when the first container is accommodated and the second container is closed, the first container and the second container may be capable of accommodating a volume of gas that is greater than the sum of 0.663 times the volume γ (mL) and 21.0 times the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container.

[0034] In the first to fourth container sets according to the present disclosure, when the first container is accommodated and the second container is closed, the first container and the second container may be capable of accommodating a volume of gas that is greater than the sum of 0.921 times the volume γ (mL) and 21.0 times the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container.

[0035] In the first to fourth container sets according to the present disclosure, the volume γ (mL) may be greater than half the maximum volume (mL) of the first container.

[0036] In the first to fourth container sets according to the present disclosure, the volume γ may be 0.5 mL or more.

[0037] In the first to fourth container sets according to the present disclosure, the volume γ may be 20 mL or less.

[0038] In the first to fourth container sets according to the present disclosure, the first container may be capable of containing a gas while maintaining a negative pressure.

[0039] In the first to fourth container sets according to the present disclosure, the oxygen concentration in the first container may be 1.5% or less.

[0040] A first method for manufacturing a liquid-filled container according to the present disclosure includes: closing a second container containing the first container and filled with an inert gas; storing the first container within the second container; the first container contains a liquid of volume γ (mL) and is at least partially oxygen permeable; the second container has oxygen barrier properties, In a state in which the first container is accommodated and the second container is closed, the first container and the second container have a total volume of (2.56 × 10 -4 × β × T), where T is the temperature of the environment (K) and β is the saturated solubility of oxygen (mg / L) in the liquid in an air atmosphere at atmospheric pressure at temperature T (K).

[0041] A second method for manufacturing a liquid-filled container according to the present disclosure includes: closing a second container containing the first container and filled with an inert gas; storing the first container within the second container; the first container contains a liquid of volume γ (mL) and is at least partially oxygen permeable; the second container has oxygen barrier properties, The sum of the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container and the value obtained by subtracting the volume (mL) occupied by the first container from the maximum volume (mL) of the second container is (2.56 × 10 -4 × (β × T / α) times or more, where T is the temperature of the environment (K), β is the saturated solubility of oxygen (mg / L) in the liquid in an air atmosphere under atmospheric pressure at temperature T (K), and α is the oxygen concentration (%) in the second container.

[0042] In the method for manufacturing first and second liquid-filled containers according to the present disclosure, the oxygen concentration in the first container before the second container is closed may be 1.5% or less.

[0043] In the method for manufacturing first and second liquid-containing containers according to the present disclosure, when the second container is closed with the first container contained therein, the first container and the second container have a total volume γ (mL) of (2.56×10 -4 ×β×T) and the maximum volume (mL) of the first container minus the volume γ (mL) multiplied by 21.0.

[0044] In the manufacturing method of the first and second liquid-containing containers according to the present disclosure, the sum of the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container and the value obtained by subtracting the volume (mL) occupied by the first container from the maximum volume (mL) of the second container is less than or equal to (2.56 × 10 -4 ×(β×T / α)) and the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container multiplied by (21.0 / α).

[0045] In the method for manufacturing first and second liquid-filled containers according to the present disclosure, the volume γ (mL) may be greater than half the maximum volume of the first container.

[0046] In the first and second methods of manufacturing a liquid-filled container according to the present disclosure, the volume γ may be 0.5 mL or more.

[0047] In the first and second methods of manufacturing a liquid-filled container according to the present disclosure, the volume γ may be 20 mL or less.

[0048] In the method for manufacturing first and second liquid-filled containers according to the present disclosure, the first container may be capable of containing gas while maintaining a negative pressure therein. [Effects of the Invention]

[0049] According to the present invention, deterioration of the liquid due to oxygen can be suppressed. [Brief explanation of the drawings]

[0050] [Figure 1] FIG. 1 is a diagram for explaining an embodiment of the present disclosure, and is a perspective view showing an example of a combination container containing liquids. [Figure 2] FIG. 2 is a longitudinal cross-sectional view showing a first container filled with liquid that can be included in the combination container filled with liquid of FIG. [Figure 3] FIG. 3 is a diagram showing an example of a method for manufacturing the combination container filled with liquid of FIG. 1 and the first container filled with liquid of FIG. [Figure 4] FIG. 4 is a diagram showing an example of a method for manufacturing the combination container filled with liquid of FIG. 1 and the first container filled with liquid of FIG. [Figure 5] FIG. 5 is a diagram showing an example of a method for manufacturing the combination container filled with liquid of FIG. 1 and the first container filled with liquid of FIG. [Figure 6] FIG. 6 is a perspective view showing how to use the first container filled with liquid shown in FIG. [Figure 7] FIG. 7 is a vertical cross-sectional view showing a modified example of the second container. [Figure 8] FIG. 8 is a vertical cross-sectional view showing a modified example of the first container. [Figure 9] FIG. 9 is a vertical cross-sectional view showing another modified example of the first container. DETAILED DESCRIPTION OF THE INVENTION

[0051] An embodiment of the present invention will now be described with reference to the accompanying drawings. In the drawings accompanying this specification, the scale and aspect ratios have been appropriately changed and exaggerated from those of the actual objects for the sake of clarity and ease of understanding.

[0052] 1 to 9 are diagrams illustrating one embodiment of the present disclosure. A container set 20 includes a first container 30L containing liquid and a second container 40. The first container 30L contains a first container 30 and a liquid L contained in the first container 30. The first container 30 includes a portion that is at least partially permeable to oxygen. The second container 40 has oxygen barrier properties. The second container 40 is capable of containing the first container 30L. A combined container 10L containing liquid includes the first container 30L containing liquid and the second container 40, and the first container 30L containing liquid is contained in the second container 40. With this combined container 10L containing liquid, by adjusting the oxygen concentration in the second container 40, it is possible to adjust not only the oxygen concentration in the first container 30 but also the amount of oxygen dissolved in the liquid L.

[0053] Each component of the liquid-containing combination container 10L will be described in more detail with reference to the illustrated specific example. First, the liquid-containing first container 30L will be described.

[0054] As described above, the liquid-filled first container 30L includes the first container 30 and the liquid L contained in the first container 30. At least a portion of the first container 30 is permeable to oxygen. On the other hand, the first container 30 can seal the liquid L. In other words, the first container 30 is permeable to oxygen but impermeable to the liquid L.

[0055] The liquid L contained in the first container 30 is not particularly limited. The liquid may be a solution containing a solvent and a solute dissolved in the solvent. The solvent is not particularly limited and may be water or alcohol. The liquid is not limited to a liquid in the strict sense and may be a suspension in which solid particles are dispersed. The liquid L as food may be tea, coffee, black tea, soup, broth, stock, or a concentrated liquid obtained by concentrating one or more of these. The liquid as medicine may be an oral medicine, an external medicine, or an injection. In addition to food and medicine, the liquid L may be blood or a bodily fluid.

[0056] The interior of the first container 30 may be sterile. That is, the liquid L may be a liquid that must be maintained in a sterile state. Examples of the liquid L that must be maintained in a sterile state include food and medicine. The liquid L as food or medicine is highly sensitive and is preferably stored in a sterile state to prevent deterioration. The liquid L as food or medicine is easily deteriorated by post-sterilization treatment performed after production. Post-sterilization (also known as terminal sterilization), such as high-pressure steam, dry heat, radiation, ethylene oxide gas, and hydrogen peroxide gas plasma, cannot be applied to highly sensitive liquids. Such highly sensitive liquid L can be produced using a production line arranged in a sterile environment. That is, it can be produced by an aseptic operation. To adjust the oxygen content of the liquid L produced by an aseptic operation, the entire space in which the liquid L production line is located can be replaced with an inert gas. However, filling the entire space in which the liquid L production line is located with an inert gas atmosphere requires a huge capital investment and may also raise safety concerns for workers. In view of the above background, the amount of oxygen in the liquid L has generally been adjusted by replacing the atmosphere in a formulation container containing the liquid L with an inert gas.

[0057] In contrast to this, according to the invention of the present inventors described below, simply storing the first container 30L containing the liquid in the second container 40 can sufficiently reduce the oxygen concentration (%) in the first container 30 and the amount of dissolved oxygen (mg / L) in the liquid L in the first container 30. The effects resulting from the invention of the present inventors are remarkable and go beyond the range predicted from the state of the art.

[0058] In addition, the "sterile state" used here includes products (liquid L) labeled as "sterilized" or "sterile" and the inside of the container that holds said products, as well as pharmaceutical products (liquid L) and the inside of the container that holds said products, for which "sterility" is a condition for commercialization. -6 The product (liquid L) that fills the container and the inside of the container that holds the product also fall under the category of "sterile state" as used herein. A product that does not grow bacteria when stored at room temperature (e.g., 20°C) or higher for four weeks and the inside of a container that holds the product, and a product that does not grow bacteria when stored in a refrigerated state (e.g., 8°C or lower) for eight weeks or more, and the inside of a container that holds the product, also fall under the category of "sterile state" as used herein. Furthermore, a drug that does not grow bacteria when stored at a temperature between 28°C and 32°C for two weeks and the inside of a container that holds the drug also fall under the category of "sterile state" as used herein.

[0059] Next, a description will be given of the first container 30 that contains the liquid L. As described above, the first container 30 can seal the liquid L. In other words, the first container 30 can hold the liquid L without leakage.

[0060] The first container 30 includes a portion that is at least partially permeable to oxygen. The entire first container 30 may be permeable to oxygen. Only a portion of the first container 30 may be permeable to oxygen. Alternatively, all gases may be permeable to the first container 30. Alternatively, only some gases containing oxygen, for example, only oxygen, may be permeable to the first container 30.

[0061] The material that makes up the oxygen permeable part is 1 × 10 -12 (cm 3 (STP)·cm / (cm 2 ·sec·Pa)) or more, more preferably 5×10 -12 (cm 3 (STP)·cm / (cm 2 ·sec·Pa)) or more, more preferably 1×10 -11 (cm 3(STP)·cm / (cm 2 The oxygen permeability coefficient of the first container 30 is 1 / 2 sq. m / s or more. When the oxygen-permeable portion has multiple layers, it is preferable that the material constituting at least one of the layers has such a permeability coefficient, and it is more preferable that the materials constituting all of the layers have the above-mentioned permeability coefficient. This promotes oxygen permeation through the first container 30, allowing the oxygen concentration inside the first container 30 to be adjusted quickly.

[0062] In order to prevent the leakage of water vapor and the like, and to prevent the influence on the liquid in the first container 30 due to the high gas permeation rate after the second container 40 is opened, an upper limit may be set on the oxygen permeability coefficient of the material constituting the oxygen-permeable portion. Specifically, the oxygen permeability coefficient may be set to 1×10 -1 (cm 3 (STP)·cm / (cm 2 ·sec·Pa) or less, preferably 1×10 -2 (cm 3 (STP)·cm / (cm 2 ·sec·Pa) or less, more preferably 1×10 -3 (cm 3 (STP)·cm / (cm 2 If the oxygen-permeable portion has multiple layers, it is preferable that the material constituting at least one of the layers has such a permeability coefficient, and it is more preferable that the materials constituting all of the layers have the above-mentioned permeability coefficient.

[0063] When the object to be measured is a resin film or resin sheet, the oxygen permeability coefficient is a value measured in accordance with JIS K7126-1. When the object to be measured is rubber, the oxygen permeability coefficient is a value measured in accordance with JIS K6275-1. The oxygen permeability coefficient can be measured using an OXTRAN (2 / 21) permeability measuring device manufactured by MOCON, USA, under an environment of a temperature of 25°C and a humidity of 60% RH.

[0064] The area of ​​the oxygen permeable portion is preferably 1 mm 2 More preferably, 10 mm 2More preferably, 30 mm 2 That's all. Similarly, the thickness of the oxygen-permeable portion is preferably 3 mm or less, more preferably 1 mm or less, and even more preferably several tenths of a mm or less. This promotes gas permeation through the first container 30, allowing the oxygen concentration inside the first container 30 to be adjusted quickly.

[0065] The amount of oxygen that permeates the entire first container 30 is preferably 1×10 -3 (mL / (day×atm)) or more, more preferably 1×10 -2 (mL / (day×atm)) or more, more preferably 1×10 -1 The oxygen permeation rate is preferably 100 mL / day×atm or less, more preferably 50 mL / day×atm or less, and even more preferably 10 mL / day×atm or less. This prevents water vapor and other vapors from leaking. Furthermore, the liquid in the first container 30 can be prevented from being adversely affected by the high gas permeation rate after the second container 40 is opened. The oxygen permeation rate can be measured, for example, as follows: First, the oxygen concentration in the first container 30 is set to approximately 0%, and the first container 30 is left in the atmosphere. The change in the oxygen concentration in the first container 30 is measured over time. The amount of oxygen permeating the first container 30 can be determined by calculating the amount of oxygen that has entered the first container 30 per day from the change in oxygen concentration over time.

[0066] For example, the configuration of the oxygen-permeable portion of the first container may be determined so that storing a first container 30 containing a liquid with an oxygen dissolution rate of 8 mg / L in the second container 40 for four weeks can reduce the oxygen concentration (%) in the first container 30 by 5% or more.

[0067] The illustrated first container 30 has a container body 32 having an opening 33, and a stopper 34 held in the opening 33 of the container body 32. The stopper 34 restricts leakage of the liquid L from the opening 33. In this example, the stopper 34 has oxygen permeability and has the above-mentioned oxygen permeability coefficient (cm 3 (STP)·cm / (cm 2 The stopper 34 may be formed of a material having a permeability (MPa) of 1 / 2·sec·Pa. The oxygen permeability coefficient of the material forming the stopper 34 may be greater than the oxygen permeability coefficient of the material forming the container body 32. Also, a portion of the stopper 34 may be oxygen permeable. A portion of the stopper 34 may be made of a material having oxygen permeability throughout its entire thickness. For example, the stopper 34 may have oxygen permeability throughout its entire thickness in a central portion spaced from the periphery, and have oxygen barrier properties in a peripheral portion surrounding the central portion.

[0068] In the illustrated example, the area of ​​the opening 33, i.e., the opening area of ​​the container body 32, is preferably 1 mm 2 More preferably, 10 mm 2 More preferably, 30 mm 2 That's all. Similarly, the thickness of the stopper 34 is preferably 3 mm or less, more preferably 1 mm or less, and even more preferably several tenths of a mm or less. This promotes oxygen permeation through the first container 30, allowing the oxygen concentration inside the first container 30 to be adjusted quickly. Furthermore, from the viewpoint of ensuring flexibility and airtightness, the thickness of the stopper, for example, the thickness of a rubber stopper, may be 20 mm or less. Furthermore, from the viewpoint of being able to be punctured by a syringe needle or a straw, the thickness of the stopper, for example, the thickness of a rubber stopper, may be 1 mm or less.

[0069] From the viewpoint of suppressing the leakage of water vapor and the like, and from the viewpoint of suppressing the influence on the liquid in the first container 30 due to the high gas permeation rate after the second container 40 is opened, an upper limit may be set on the area of ​​the opening 33. Specifically, the area of ​​the opening 33 may be set to 5000 mm 2 From the viewpoint of ensuring strength, the thickness of the stopper, for example, the thickness of a rubber stopper, may be 0.01 mm or more.

[0070] The oxygen-permeable stopper 34 is not particularly limited, and various configurations can be employed. In the illustrated example, the stopper 34 is inserted into the opening 33 of the container body 32 to close the opening 33. In addition to the stopper shown in the figure, a liquor bottle cap may be used, more specifically, a stopper having a stopper body portion inserted into the opening 33 and a flange portion extending in diameter from the stopper body portion. Also, a stopper having an outer spiral or an inner spiral and attached to the container body portion by the engagement of the spirals may be used.

[0071] The plug 34 may be made of silicone. Silicone is a substance with a siloxane bond as its main chain. The plug 34 may be made of silicone rubber. Silicone rubber refers to a rubber-like material made of silicone. Silicone rubber is a synthetic resin with silicone as its main component, and is a rubber-like substance. Silicone rubber is a rubber-like substance with a siloxane bond as its main chain. Silicone rubber may be a thermosetting compound containing a siloxane bond. Examples of silicone rubber include methyl silicone rubber, vinyl-methyl silicone rubber, phenyl-methyl silicone rubber, dimethyl silicone rubber, and fluorosilicone rubber. The oxygen permeability coefficient of silicone and the oxygen permeability coefficient of silicone rubber are 1×10 -12 (mL / (m 2 ×day×atm)) or more, even 1×10 -11 (mL / (m 2 The oxygen permeability coefficient of silicone and silicone rubber is 1×10 -9 (cm 3 (STP)·cm / (cm 2 ·sec·Pa) or less. Compared to natural rubber, silicone and silicone rubber have a hydrogen permeability coefficient that is about 10 times higher, an oxygen permeability coefficient that is about 20 times higher, and a nitrogen permeability coefficient that is about 30 times higher. Compared to butyl rubber, silicone and silicone rubber have a hydrogen permeability coefficient that is more than 70 times higher, an oxygen permeability coefficient that is more than 40 times higher, and a nitrogen permeability coefficient that is more than 650 times higher.

[0072] At least a portion of the plug 34 may be made of silicone. That is, the entirety or a portion of the plug 34 may be made of silicone or silicone rubber. For example, a portion of the plug 34 may be made of silicone or silicone rubber over its entire thickness. The portion may be the central portion of the plug 34, or a part or all of the peripheral portion surrounding the central portion.

[0073] As shown in FIG. 2, the illustrated container body 32 has a bottom 32a, a body wall 32b, a neck 32c, and a head 32d, in this order. The bottom 32a and the body wall 32b mainly form a storage space for the liquid L. The head 32d forms the tip of the container body 32. The head 32d is thicker than the other parts. The neck 32c is located between the body wall 32b and the head 32d. The neck 32c has a narrower width, particularly a narrower diameter, than the body wall 32b and the head 32d. The container body 32 may be transparent so that the stored liquid L can be observed from the outside. Here, "transparent" means that the visible light transmittance, specified as the average value of the transmittance at each wavelength when measured using a spectrophotometer ("UV-3100PC" manufactured by Shimadzu Corporation, compliant with JIS K 0115) within the measurement wavelength range of 380 nm to 780 nm, is 50% or more, and preferably 80% or more.

[0074] In the illustrated example, the container body 32 is made of a material having a smaller oxygen permeability coefficient than the material of the stopper 34. The container body 32 may have oxygen barrier properties. That is, the first container 30 may be oxygen permeable only in a portion thereof. Having oxygen barrier properties means that the oxygen permeability coefficient is 1×10 -13 (cm 3 (STP)·cm / (cm 2 The oxygen barrier property preferably means that the material is made of a material having an oxygen permeability coefficient of 1×10 -17 (cm 3 (STP)·cm / (cm 2 ·sec·Pa) or less.

[0075] Examples of the container body 32 having oxygen barrier properties include a can made of metal, a container body having a metal layer formed by vapor deposition or transfer, and a glass bottle. Oxygen barrier properties can also be imparted to a container body 32 made using a resin sheet or resin plate. In this example, the resin sheet or resin plate may include a layer having oxygen barrier properties, such as an ethylene-vinyl alcohol copolymer (EVOH) or polyvinyl alcohol (PVA). The container body 32 may also include a laminate including a metal vapor deposition film. A container body 32 using a laminate and a container body 32 using glass or resin can be imparted with transparency as well as oxygen barrier properties. Transparent first containers 30 and container bodies 32 are preferred because the liquid L contained therein can be observed from the outside of the first container 30.

[0076] The volume of the first container 30 may be, for example, 1 mL or more and 1100 mL or less, 3 mL or more and 700 mL or less, or 5 mL or more and 200 mL or less.

[0077] In the illustrated example, the container body 32 is a colorless or colored glass bottle. The container body 32 is formed of, for example, borosilicate glass. The first container 30 is a vial. The volume of the first container 30 that is a vial may be 1 mL or more, or 3 mL or more. The volume of the first container 30 that is a vial may be 500 mL or less, or 200 mL or less.

[0078] When the first container 30 is a vial, the oxygen permeability coefficient of the material that constitutes the stopper 34 may be greater than the oxygen permeability coefficient of the glass that constitutes the container body 32 .

[0079] The illustrated first container 30 further includes a fastener 36. The fastener 36 prevents the stopper 34 from being removed from the container body 32. The fastener 36 is attached to the head 32d of the container body 32. As shown in FIGS. 1 and 2, the fastener 36 covers the periphery of the stopper 34. As a result, the fastener 36 prevents the stopper 34 from being removed from the container body 32 while leaving a portion of the stopper 34 exposed. The fastener 36 may be a sheet metal fixed to the head 32d. The fastener 36 may also be a cap that is screwed onto the head 32d.

[0080] The illustrated first container 30 can maintain a negative internal pressure under atmospheric pressure. That is, the first container 30 can contain a gas while maintaining the gas at a negative pressure under atmospheric pressure. Alternatively, the first container 30 may be capable of containing a gas while maintaining the gas at a positive pressure under atmospheric pressure. In these examples, the first container 30 may have sufficient rigidity to maintain its shape. However, the first container 30 may deform somewhat under atmospheric pressure when maintaining a negative or positive internal pressure. Examples of first containers 30 capable of maintaining a negative or positive internal pressure include the specific examples illustrated above and cans made of metal.

[0081] Next, the second container 40 will be described.

[0082] The second container 40 can be airtightly sealed by welding, such as heat sealing or ultrasonic bonding, or by bonding using a bonding material, such as an adhesive or glue. The second container 40 has oxygen barrier properties. Examples of second containers 40 with oxygen barrier properties include metal cans, containers with metal layers formed by vapor deposition or transfer, and glass bottles. The second container 40 may also include a laminate with oxygen barrier properties. The laminate may include a resin layer with oxygen barrier properties, such as ethylene-vinyl alcohol copolymer (EVOH) or polyvinyl alcohol (PVA), or a metal vapor deposition film. At least a portion of the second container 40 may be transparent. A second container 40 using a laminate, or a second container 40 using glass or resin, can be imparted with transparency in addition to oxygen barrier properties. Giving the second container 40 transparency is preferable because it allows the liquid-filled first container 30L contained therein to be confirmed from the outside of the second container 40.

[0083] The second container 40 has a volume capable of accommodating the first container 30. The volume of the second container 40 may be, for example, 500 mL or more, 1 L or more, 5 L or more, 10 L or more, or 20 L or more. The volume of the second container 40 may be, for example, 50 L or less, 40 L or less, or 30 L or less. From the viewpoint of adjusting the oxygen concentration in the first container 30 and the amount of oxygen dissolved in the liquid L, the second container 40 can accommodate a predetermined volume of gas that is determined in consideration of the volume γ (mL) of the liquid L, etc. The predetermined volume will be described in detail later.

[0084] In the illustrated example, the second container 40 is made of a resin film having oxygen barrier properties. The second container 40 is formed as a so-called pouch. The second container 40 is formed as a so-called gusset bag. Specifically, the second container 40 has a first main film 41a, a second main film 41b, a first gusset film 41c, and a second gusset film 41d. The first main film 41a and the second main film 41b are arranged opposite each other. The first gusset film 41c is folded and arranged between the first main film 41a and the second main film 41b. The first gusset film 41c connects one side edge of the first main film 41a and one side edge of the second main film 41b. The second gusset film 41d is folded and arranged between the first main film 41a and the second main film 41b. The second gusset film 41d connects the other side edge of the first main film 41a and the other side edge of the second main film 41b. The first and second main films 41a, 41b and the first and second gusset films 41c, 41d are also joined to each other at their upper and lower edges. The films 41a-41d are airtightly joined, for example, by welding such as heat sealing or ultrasonic bonding, or by joining using a bonding material such as an adhesive or glue. However, instead of joining separate films, two or more of the films 41a-41d may be formed adjacent to each other by folding a single film. As shown in FIG. 1, the gusset bag can form a rectangular bottom surface in the second container 40. By placing the first container 30 on the bottom surface, the first container 30 can be stably stored in the second container 40. However, instead of a gusset bag, the second container 40 may be a pouch having a bottom film in addition to the first main film 41a and the second main film 41b. The bottom can also be formed by such a pouch, and the first container 30 can be stably stored inside the second container 40. In these examples, the film forming the second container 40 may be transparent.

[0085] As another example, as shown in FIG. 7, the second container 40 may have a container body 42 and a lid 44. The container body 42 has a storage section 42a and a flange section 42b. The storage section 42a forms a rectangular parallelepiped storage space. The first container 30 is stored in this storage space. The storage section 42a has a rectangular parallelepiped outer shape with one side open. The flange section 42b is provided on the periphery of the opening of the storage section 42a. The lid 44 is flat. The periphery of the lid 44 can be airtightly joined to the flange section 42b of the container body 42. The container body 42 and the lid 44 may be formed of a resin plate having gas barrier properties. The lid 44 and the container body 42 may be transparent. The thickness of the resin plate having gas barrier properties may be 0.05 mm to 2 mm or 0.1 mm to 1.5 mm. The second container 40 can maintain a negative internal pressure under atmospheric pressure. That is, the second container 40 can contain a gas while maintaining the gas at a negative pressure under atmospheric pressure. The second container 40 may also be capable of containing a gas while maintaining the gas at a positive pressure under atmospheric pressure. The second container 40 has sufficient rigidity to maintain its shape. However, the second container 40 may deform somewhat under atmospheric pressure when maintaining a negative or positive internal pressure.

[0086] The container set 20 is made up of the liquid-containing first container 30L and the second container 40 described above. The container set 20 having the liquid-containing first container 30L and the second container 40 is used to obtain a liquid-containing combination container 10L. The first container 30 and the container set 20 are used to obtain a combination container 10.

[0087] Next, a method for manufacturing the liquid-containing combination container 10L will be described. By manufacturing the liquid-containing combination container 10L, a liquid-containing first container 30L with an adjusted oxygen concentration is obtained.

[0088] First, a first container 30L filled with liquid and a second container 40 before closing are prepared. The first container 30L filled with liquid is manufactured by filling the first container 30 with liquid L. For example, the liquid L, such as food or medicine, is manufactured using a manufacturing line installed in a sterile environment maintained at positive pressure. The internal pressure of the first container 30L filled with liquid obtained in this manner becomes positive, similar to the manufacturing environment.

[0089] As shown in Fig. 3, the second container 40 before closing has an opening 40a for accommodating a first container 30L containing liquid. In the second container 40 shown in Fig. 1, for example, the upper edges of the films 41a to 41d are not joined to each other to form the opening 40a. In the second container 40 shown in Fig. 7, a container body 42 is prepared without a lid 44 attached. Then, as shown in Fig. 3, the first container 30L containing liquid is accommodated in the second container 40 through the opening 40a.

[0090] Thereafter, the second container 40 is filled with an inert gas, for example, nitrogen. In the example shown in FIG. 4, the inert gas is supplied from a supply pipe 55. The supply pipe 55 passes through the opening 40a and enters the second container 40. The outlet 56 of the supply pipe 55 is located inside the second container 40. By supplying the inert gas from the supply pipe 55, the inside of the second container 40 is replaced with the inert gas. In other words, the liquid-filled first container 30L is placed in an inert gas atmosphere. The inert gas is a stable gas with low reactivity. Examples of inert gases other than nitrogen include rare gases such as helium, neon, and argon.

[0091] It should be noted that either the filling of the second container 40 with the inert gas or the placement of the first container 30L containing the liquid in the second container 40 may be carried out first, or both may be carried out in parallel.

[0092] Next, as shown in Fig. 5, the second container 40 is closed while containing the liquid-containing first container 30L and filled with inert gas. In the second container 40 shown in Fig. 1, the second container 40 is closed by joining the upper edge portions of the films 41a to 41d together to close the opening 40a. In the second container 40 shown in Fig. 7, the second container 40 is closed by joining the peripheral edge portion of the lid 44 to the flange portion 42b of the container body 42. Joining may be performed using a joining material such as an adhesive or bonding material, or may be performed by welding using heat sealing, ultrasonic bonding, or the like.

[0093] It should be noted that the second container 40 containing the liquid-containing first container 30L may be closed under an inert gas atmosphere instead of supplying the inert gas from the supply pipe 55. This method also allows the liquid-containing first container 30L to be sealed in the second container 40 together with the inert gas.

[0094] Furthermore, the steps up to closing the second container 40 may be performed in a sterile environment. That is, the liquid-filled first container 30L, which has been manufactured in a sterile environment, and the second container 40, which has been sterilized or manufactured in a sterile environment, are brought into a sterile environment, such as a sterile chamber. If this chamber is separated from the atmosphere and contains an inert gas atmosphere, the supply of inert gas through the supply pipe 55 can be omitted. Then, the second container 40 containing the liquid-filled first container 30L is closed in a sterile environment. Therefore, the inside of the second container 40 containing the liquid-filled first container 30L is also kept sterile. That is, the liquid-filled first container 30L can be stored in the second container 40 in a sterile environment.

[0095] The liquid-filled first container 30L is then stored in the second container 40. As described above, the second container 40 has oxygen barrier properties. Therefore, oxygen permeation through the second container 40 is effectively suppressed. On the other hand, at least a portion of the first container 30 is permeable to oxygen. Furthermore, the second container 40 is filled with an inert gas, and the oxygen concentration within the second container 40 is very low. In this liquid-filled combination container 10L, oxygen within the first container 30 permeates the first container 30 and moves into the second container 40. As oxygen moves from the first container 30 to the second container 40, the oxygen concentration within the second container 40 increases and decreases. At a final equilibrium state where oxygen permeation through the first container 30 is balanced, the oxygen concentration within the first container 30 will be the same as the oxygen concentration within the second container 40.

[0096] In addition, when the oxygen concentration in the first container 30 decreases, the oxygen partial pressure in the first container 30 decreases. When the oxygen partial pressure in the first container 30 decreases, the saturated solubility (mg / L) of oxygen in the liquid L in the first container 30 also decreases. As a result, the amount of oxygen dissolved in the liquid L (mg / L) decreases.

[0097] In order to sufficiently reduce the oxygen concentration (%) of the liquid L and the amount of oxygen dissolved in the liquid L (mg / L), it is preferable to fill the second container 40 with a large amount of inert gas together with the liquid-containing first container 30L and then close the second container 40. Similarly, it is preferable to fill the first container 30 with a large amount of inert gas together with the liquid L and then close the first container 30. That is, when the maximum volume V of the second container 40 is 2MAX (mL) minus the volume occupied by the first container 30, 2MAX It is preferable that the volume (mL) of the first container 30 is large. Also, assuming that the inside of the first container 30 is replaced with an inert gas, the maximum volume V 1MAX (mL) minus the volume γ (mL), 1MAX The maximum usable volume EV (mL) of the second container 40 is preferably large. 2MAX(mL) is the maximum volume of gas that can be contained in the second container 40 when the second container 40 contains only the liquid-containing first container 30L and gas. 1MAX (mL) is the maximum volume of gas that can be contained in the first container 30 when the first container 30 contains only the liquid L and gas.

[0098] Specifically, the maximum usable volume EV of the first container 30 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX The total volume (mL) of the liquid L contained in the first container 30 is (2.56 × 10 -4 × (β × T / α) times or more. Here, T is the temperature (K) of the environment in which the liquid-containing combination container 10L is placed. T can also be said to be the temperature (K) of the storage space for the liquid-containing combination container 10L, i.e., the interior of the second container 40. β is the saturated solubility (mg / L) of oxygen in the liquid L in an air atmosphere under atmospheric pressure at temperature T (K). α is the oxygen concentration (%) in the second container 40. α may also be the oxygen concentration (%) in the second container 40 in an equilibrium state.

[0099] In addition, the maximum volume V 1MAX (mL) and maximum volume V 2MAX (mL) means the maximum volume when the volume of the target container 30, 40 changes due to deformation, etc. Therefore, when the volume of the target container 30, 40 is constant, the constant volume is the maximum volume V 1MAX (mL) and maximum volume V 2MAX (mL).

[0100] The maximum amount of oxygen that can be dissolved in liquid L with a volume γ (mL) placed in an air atmosphere at a temperature T (K) is expressed as follows: As an example, the amount of oxygen expressed as follows may be the maximum amount of oxygen that can be dissolved in liquid L with a volume γ (mL) that is produced in an air atmosphere at a temperature T (K) and stored in first container 30. Oxygen molecular weight: β×γ / 1000 (mg) Molar amount of oxygen: β×γ / 1000 / 32 (mmol) It is then assumed that the maximum amount of oxygen dissolved in the liquid L is completely degassed from the liquid L, the solubility of oxygen becomes 0 (mg / L), and the oxygen concentration in the first container 30 and the second container 40 becomes α (%). Under this assumption, immediately after the second container 40 containing the first container 30 is closed, no oxygen gas is contained in the first container 30 and the second container 40. At this time, the volume Vx (mL) of oxygen in the first container 30 and the second container 40 is determined as follows using the equation of state: Vx=nRT / P =(β×γ / 1000 / 32)×0.082×T / (α / 100) =2.56×10 -4 ×(β×T / α)×γ(mL) In this equation of state, the gas constant is set to 0.082 (L×atm / K / mol). If the oxygen concentration in the first container 30 and the second container 40 is α (%), the partial pressure of oxygen is “α / 100” (atm).

[0101] That is, the volume γ (mL) of the liquid L contained in the first container 30 is (2.56 × 10 -4 × (β × T / α) times is the volume of oxygen in the liquid-containing combination container 10L when all the oxygen dissolved in the liquid L has been degassed from the liquid L. Therefore, the maximum usable volume EV of the first container 30 is 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX (mL) of the liquid L, the volume γ (mL) is 2.56 x 10 -4 × (β × T / α) times or more, the maximum amount of oxygen that can be dissolved in the liquid L can be present in the first container 30 and the second container 40 as a degassed gas. This allows the amount of oxygen dissolved in the liquid L (mg / L) to be sufficiently reduced, and the amount of dissolved oxygen in the liquid L to be sufficiently reduced.

[0102] In reality, in an equilibrium state, oxygen dissolves in the liquid L at a solubility that corresponds to the oxygen concentration (%) or partial pressure of oxygen in the first container 30. For example, if the liquid L is produced in an air atmosphere where the partial pressure of oxygen is 21.0 (%), the amount of oxygen dissolved in the liquid L in an equilibrium state is "β×α / 21.0" (mg / L). Therefore, the volume of oxygen that is degassed from the liquid L and exists as a gas is "2.56×10" of the volume γ (mL) of the liquid L. -4 ×(β×T / α) times.

[0103] Based on the above considerations, the volumes of the first container 30 and the second container 40 may be determined from the target oxygen concentration in the liquid-containing combination container 10L and the target amount of oxygen dissolved (mg / L) in the liquid L. Furthermore, the total volume of gas contained in the first container 30 and the second container 40 may be determined from the target oxygen concentration in the liquid-containing combination container 10L and the target amount of oxygen dissolved (mg / L) in the liquid L.

[0104] For example, the volumes of the containers 30, 40 and the volumes of the gases contained in the containers 30, 40 may be determined so that the oxygen concentration in the first container 30 and the second container 40 can be reduced to less than 1%. In this example, the maximum usable volume EV 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX (mL) of the liquid L contained in the first container 30 is calculated by multiplying the total volume γ (mL) of the liquid L contained in the first container 30 by (2.56 × 10 -4 × β × T). More specifically, when the liquid L is an aqueous solution and the temperature T is set to 293 K, which is approximately room temperature, the oxygen saturation solubility β of the solvent water is 8.84 (mg / L). In this specific example, the maximum available volume EV of the first container 30 is 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX The total volume (mL) of the first container 30 and the second container 40 may be greater than 0.663 times the volume γ (mL) of the liquid L. In addition, the total volume (mL) of the first container 30 and the second container 40 may be greater than (2.56×10 -4× β × T). More specifically, assuming that the liquid L is an aqueous solution and the temperature T is 293 K, which is about room temperature, the first container 30 and the second container 40 may contain a total volume of gas that is greater than 0.663 times the volume γ (mL) of the liquid L contained in the first container 30.

[0105] As another example, consider refrigerated storage. If the liquid L is an aqueous solution and the temperature T is 276 K, which corresponds to a refrigerated state, the oxygen saturation solubility β of the solvent water is 13.04 (mg / L). In this specific example, the maximum available volume EV of the first container 30 is 13.04 (mg / L). 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX The total volume (mL) of the gas may be greater than 0.921 times the volume γ (mL) of the liquid L. Furthermore, the first container 30 and the second container 40 may contain a total volume of gas that is greater than 0.921 times the volume γ (mL) of the liquid L contained in the first container 30.

[0106] The volumes of the containers 30, 40 and the volumes of the gases contained in the containers 30, 40 may be determined so that the oxygen concentrations in the first container 30 and the second container 40 can be reduced to 0.5% or less. In this example, the maximum usable volume EV 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX (mL) of the liquid L contained in the first container 30 is calculated by multiplying the total volume γ (mL) of the liquid L contained in the first container 30 by (5.12 × 10 -4 More specifically, assuming that the liquid L is an aqueous solution and the temperature T is 293 K, which is approximately room temperature, the maximum effective volume EV of the first container 30 may be set to EV 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX The total volume (mL) of the first container 30 and the second container 40 may be 1.32 times or more the volume γ (mL) of the liquid L. In addition, the total volume (mL) of the first container 30 and the second container 40 may be 5.12×10 times the volume γ (mL) of the liquid L contained in the first container 30. -4× β × T) times or more of the volume of gas contained in the first container 30. More specifically, assuming that the liquid L is an aqueous solution and the temperature T is 293 K, which is approximately room temperature, the first container 30 and the second container 40 may contain a total volume of gas that is 1.32 times or more the volume γ (mL) of the liquid L contained in the first container 30.

[0107] As another example, consider refrigerated storage. If the liquid L is an aqueous solution and the temperature T is 276 K, which corresponds to a refrigerated state, the oxygen saturation solubility β of the solvent water is 13.04 (mg / L). In this specific example, the maximum available volume EV of the first container 30 is 13.04 (mg / L). 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX The total volume (mL) of the gas may be greater than 1.84 times the volume γ (mL) of the liquid L. Furthermore, the first container 30 and the second container 40 may contain a total volume of gas that is greater than 1.84 times the volume γ (mL) of the liquid L contained in the first container 30.

[0108] Furthermore, the volumes of the containers 30, 40 and the volumes of the gases contained in the containers 30, 40 may be determined so that the oxygen concentration in the first container 30 and the second container 40 can be reduced to 0.2% or less. In this example, the maximum usable volume EV 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX (mL) of the liquid L contained in the first container 30 is calculated by multiplying the total volume γ (mL) of the liquid L contained in the first container 30 by (1.28 × 10 -3 More specifically, assuming that the liquid L is an aqueous solution and the temperature T is 293 K, which is approximately room temperature, the maximum effective volume EV of the first container 30 may be set to EV 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX The total volume (mL) of the first container 30 and the second container 40 may be 3.32 times or more the volume γ (mL) of the liquid L. In addition, the total volume (mL) of the first container 30 and the second container 40 may be 1.28×10 times the volume γ (mL) of the liquid L contained in the first container 30. -3× β × T) times or more of the volume of gas contained in the first container 30. More specifically, assuming that the liquid L is an aqueous solution and the temperature T is 293 K, which is approximately room temperature, the first container 30 and the second container 40 may contain a total volume of gas that is 3.32 times or more the volume γ (mL) of the liquid L contained in the first container 30.

[0109] As another example, consider refrigerated storage. If the liquid L is an aqueous solution and the temperature T is 276 K, which corresponds to a refrigerated state, the oxygen saturation solubility β of the solvent water is 13.04 (mg / L). In this specific example, the maximum available volume EV of the first container 30 is 13.04 (mg / L). 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX The total volume (mL) of the gas may be greater than 4.61 times the volume γ (mL) of the liquid L. Furthermore, the first container 30 and the second container 40 may contain a total volume of gas that is greater than 4.61 times the volume γ (mL) of the liquid L contained in the first container 30.

[0110] It is also possible that oxygen is present in the headspace HS, the space not occupied by the liquid L in the first container 30, during the manufacturing of the liquid-filled first container 30L. For example, if the liquid L is placed in the first container 30 and the first container 30 is closed in an air atmosphere, air will be present in the headspace HS of the first container 30. That is, the oxygen concentration in the liquid-filled first container 30L will be approximately 21.0%. In other words, in the initial state, the liquid-filled first container 30L will contain oxygen dissolved in the liquid L and gaseous oxygen in the headspace HS. In this case, the amount of oxygen in the headspace HS is determined as follows: Molar amount of oxygen: 0.210 x EV 1MAX / 0.082 / T(mmol) Here, EV 1MAX is the maximum volume V of the first container 30 1MAX (mL) minus the volume γ (mL), 1MAX (mL), and is the maximum volume (mL) of the headspace HS. The volume of oxygen present in gas form in the headspace HS is (EV) at equilibrium when the oxygen concentration is α (%). 1MAX×21.0 / α) (mL).

[0111] The volume γ (mL) of the liquid L mentioned above is (2.56 × 10 -4 × (β × T / α) times is the volume of gas in the liquid-containing combination container 10L when all the oxygen dissolved in the liquid L has been removed from the liquid L. Therefore, the maximum usable volume EV of the first container 30 is 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX The total volume (mL) of the liquid L is expressed as γ (mL) (2.56 x 10 -4 × (β × T / α)) and the maximum effective volume EV of the first container 30 1MAX The oxygen concentration (mL) may be equal to or greater than the sum of the oxygen concentration (mL) multiplied by (21.0 / α). According to this design, the maximum amount of oxygen that can be dissolved in the liquid L can be present in the first container 30 and the second container 40 as a degassed gas, together with the oxygen that was present in the headspace HS. This allows the amount of oxygen dissolved in the liquid L to be sufficiently reduced, and the amount of dissolved oxygen in the liquid L to be sufficiently reduced.

[0112] From the viewpoint of suppressing deterioration of the liquid L due to oxygen, it is preferable that the oxygen concentration in the first container 30 immediately after the production of the liquid-filled first container 30L is low. The oxygen concentration in the first container 30 may be preferably set to 1.5% or less. Such an oxygen concentration in the first container 30 can be achieved by supplying an inert gas into the first container 30 containing the liquid L.

[0113] Even when taking into consideration the oxygen in the air present in the headspace HS during the production of the first liquid-containing container 30L, the volumes of the first container 30 and the second container 40 may be determined from the target oxygen concentration in the liquid-containing combination container 10L or the target amount of oxygen dissolved (mg / L) in the liquid L. Furthermore, the total volume of gas contained in the first container 30 and the second container 40 may be determined from the target oxygen concentration in the liquid-containing combination container 10L or the target amount of oxygen dissolved (mg / L) in the liquid L.

[0114] For example, the volumes of the containers 30, 40 and the volumes of the gases contained in the containers 30, 40 may be determined so that the oxygen concentration in the first container 30 and the second container 40 can be reduced to less than 1%. In this example, the maximum usable volume EV 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX (mL), the volume γ (mL) of the liquid L contained in the first container 30 is (2.56 × 10 -4 × β × T) and the maximum effective volume EV of the first container 30. 1MAX (mL) of the first container 30 may be larger than the sum of the value obtained by multiplying the maximum usable volume EV of the first container 30 by 21.0. More specifically, when the liquid L is an aqueous solution, if the temperature T is 293 K, which is approximately room temperature, the oxygen saturation solubility β of water is 8.84 (mg / L). In this specific example, 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX (mL), the total volume γ (mL) of the liquid L multiplied by 0.663, and the maximum effective volume EV of the first container 30. 1MAX The volume γ (mL) of the liquid L contained in the first container 30 may be larger than the sum of the volume γ (mL) of the liquid L contained in the first container 30 multiplied by 21.0. -4 × β × T) and the maximum effective volume EV of the first container 30. 1MAX More specifically, assuming that the liquid L is an aqueous solution and the temperature T is 293 K, which is approximately room temperature, the first container 30 and the second container 40 may accommodate a gas of a volume greater than the sum of the volume γ (mL) of the liquid L accommodated in the first container 30 multiplied by 0.663 and the maximum effective volume EV of the first container 30. 1MAX It may contain a volume of gas greater than the sum of the volume (mL) multiplied by 21.0.

[0115] As another example, consider refrigerated storage. If the liquid L is an aqueous solution and the temperature T is 276 K, which corresponds to a refrigerated state, the oxygen saturation solubility β of the solvent water is 13.04 (mg / L). In this specific example, the maximum available volume EV of the first container 30 is 13.04 (mg / L). 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX(mL), multiplied by 0.921 the volume γ (mL) of the liquid L, and the maximum usable volume EV of the first container 30. 1MAX The total volume of the first container 30 and the second container 40 may be greater than the sum of the volume γ (mL) of the liquid L contained in the first container 30 multiplied by 0.921 and the maximum usable volume EV of the first container 30 multiplied by 21.0. 1MAX It may contain a volume of gas greater than the sum of the volume (mL) multiplied by 21.0.

[0116] The volumes of the containers 30, 40 and the volumes of the gases contained in the containers 30, 40 may be determined so that the oxygen concentrations in the first container 30 and the second container 40 can be reduced to 0.5% or less. In this example, the maximum usable volume EV 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX The total volume γ (mL) of the liquid L contained in the first container 30 is calculated by multiplying the volume γ (mL) of the liquid L contained in the first container 30 by (5.12 × 10 -4 × β × T) and the maximum effective volume EV of the first container 30. 1MAX More specifically, assuming that the liquid L is an aqueous solution and the temperature T is 293 K, which is approximately room temperature, the maximum usable volume EV of the first container 30 may be equal to or greater than the sum of the values ​​obtained by multiplying the liquid L by 41.9 (mL). 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX (mL), multiply the volume γ (mL) of the liquid L by 1.32 and the maximum effective volume EV of the first container 30. 1MAX The volume γ (mL) of the liquid L contained in the first container 30 may be set to 5.12×10 or more. -4 × β × T) and the maximum effective volume EV of the first container 30. 1MAX More specifically, assuming that the liquid L is an aqueous solution and the temperature T is 293 K, which is approximately room temperature, the first container 30 and the second container 40 may accommodate a gas of a volume equal to or greater than the sum of the volume γ (mL) of the liquid L accommodated in the first container 30 multiplied by 1.32 and the maximum effective volume EV of the first container 30. 1MAXIt may contain a volume of gas equal to or greater than the total value of the volume (mL) multiplied by 41.9.

[0117] As another example, consider refrigerated storage. If the liquid L is an aqueous solution and the temperature T is 276 K, which corresponds to a refrigerated state, the oxygen saturation solubility β of the solvent water is 13.04 (mg / L). In this specific example, the maximum available volume EV of the first container 30 is 13.04 (mg / L). 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX (mL), multiplied by 1.84 the volume γ (mL) of the liquid L, and the maximum usable volume EV of the first container 30. 1MAX The total volume of the first container 30 and the second container 40 may be greater than the sum of the volume γ (mL) of the liquid L contained in the first container 30 multiplied by 1.84 and the maximum usable volume EV of the first container 30 multiplied by 41.9. 1MAX It may contain a volume of gas greater than the sum of the volume (mL) multiplied by 41.9.

[0118] Furthermore, the volumes of the containers 30, 40 and the volumes of the gases contained in the containers 30, 40 may be determined so that the oxygen concentration in the first container 30 and the second container 40 can be reduced to 0.2% or less. In this example, the maximum usable volume EV 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX (mL) of the liquid L contained in the first container 30 is calculated by multiplying the total volume γ (mL) of the liquid L contained in the first container 30 by (1.28 × 10 -3 × β × T) and the maximum effective volume EV of the first container 30. 1MAX More specifically, assuming that the liquid L is an aqueous solution and the temperature T is 293 K, which is approximately room temperature, the maximum effective volume EV of the first container 30 may be equal to or greater than the sum of the values ​​obtained by multiplying the liquid L by 105 (mL). 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX (mL), multiplied by 3.32 times the volume γ (mL) of the liquid L, and the maximum usable volume EV of the first container 30. 1MAX The volume γ (mL) of the liquid L contained in the first container 30 may be set to 1.28×10 or more. -3× β × T) and the maximum effective volume EV of the first container 30. 1MAX More specifically, assuming that the liquid L is an aqueous solution and the temperature T is 293 K, which is approximately room temperature, the first container 30 and the second container 40 may accommodate a gas of a volume equal to or greater than the sum of the volume γ (mL) of the liquid L accommodated in the first container 30 multiplied by 3.32 and the maximum effective volume EV of the first container 30. 1MAX It may contain a volume of gas equal to or greater than the total value of the volume (mL) multiplied by 105.

[0119] As another example, consider refrigerated storage. If the liquid L is an aqueous solution and the temperature T is 276 K, which corresponds to a refrigerated state, the oxygen saturation solubility β of the solvent water is 13.04 (mg / L). In this specific example, the maximum available volume EV of the first container 30 is 13.04 (mg / L). 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX (mL), multiplied by 4.61 the volume γ (mL) of the liquid L, and the maximum usable volume EV of the first container 30. 1MAX The total volume of the first container 30 and the second container 40 may be greater than the sum of the volume γ (mL) of the liquid L contained in the first container 30 multiplied by 4.61 and the maximum usable volume EV of the first container 30 multiplied by 105. 1MAX It may contain a volume of gas greater than the sum of the volume (mL) multiplied by 105.

[0120] From the above, by storing the liquid-containing first container 30L in the second container 40, the oxygen concentration of the gas contained together with the liquid in the first container 30 can be reduced. In addition, the amount of dissolved oxygen dissolved in the liquid L in the first container 30 can also be reduced. On the other hand, highly sensitive liquids L, such as food and medicines, can be decomposed by oxygen. By storing the liquid L in the first container 30 stored in the second container 40, it is possible to suppress the decomposition of the liquid L by oxygen. In other words, this embodiment, in which the oxygen concentration in the first container 30 can be adjusted after the liquid L is sealed, is suitable for highly sensitive liquids L, such as food and medicines.

[0121] It is believed that the amount of dissolved oxygen in the liquid contained in the container can be reduced by producing the liquid in an atmosphere substituted with an inert gas and storing the liquid in a container with oxygen barrier properties. However, installing the entire liquid production line in an atmosphere substituted with an inert gas requires extensive modifications to the production equipment and huge capital investment. Furthermore, in the field of expensive chemicals, the chemicals are often freeze-dried and stored in powder form to ensure stability against temperature, oxygen, moisture, light, etc. However, converting liquid chemicals into powder form for storage and then returning the powdered chemicals to liquid form for use have significant disadvantages in terms of effort, time, and cost.

[0122] In contrast, according to this embodiment, a first container containing a liquid can be manufactured in the conventional manner using existing equipment, etc. Therefore, equipment modifications and capital investments can be avoided. In particular, when applied to liquids such as chemicals, this is useful in that it eliminates the need for approval applications to public institutions regarding changes to manufacturing equipment or manufacturing processes. It also eliminates the need for the labor of freezing and drying the liquid L or reconstituting a powder into a liquid. Furthermore, there are no special restrictions on the first container 30. Therefore, materials that are widely used as containers for foods, chemicals, etc. because of their low elution amounts, such as glass and resins such as polyethylene and polypropylene, can be used as materials for the first container.

[0123] Additionally, in the above-described specific example, the first container 30 has a container body 32 and a stopper 34. This first container 30 may be a vial. However, conventionally, vials containing liquid, particularly vials containing liquid in a sterile state, are made of butyl rubber or fluororubber, which have low oxygen permeability and even oxygen barrier properties. In contrast, in the above-described specific example, oxygen can permeate through the stopper 34. That is, the oxygen permeability coefficient (cm 3 (STP)·cm / (cm 2·sec·Pa) is set to be large. Specifically, the stopper 34 is made of silicone or silicone rubber. Furthermore, the oxygen permeability coefficient of the silicone or silicone rubber that makes up the stopper 34 is larger than the oxygen permeability coefficient of the material that makes up the container body 32. According to this specific example, oxygen permeates the stopper 34 and moves out of the first container 30. Therefore, oxygen permeability can be easily imparted to existing containers such as vials that have been used conventionally.

[0124] In this specific example, the time required to reach equilibrium depends on the oxygen permeability of the stopper 34. Therefore, by adjusting the lower limit of the area of ​​the opening 33 of the container body 32 and the upper limit of the thickness of the stopper 34 as described above, it is possible to shorten the time required for oxygen permeation through the first container 30 to reach equilibrium after the first container 30 is placed inside the second container 40. This makes it possible to suppress decomposition of the liquid L due to oxygen.

[0125] In addition, the maximum volume V of the first container 30 1MAX The maximum effective volume EV of the first container 30 is calculated by subtracting the volume γ of the liquid L from 1MAX The volume of the gas contained in the first container 30 together with the liquid L may be 20 mL or less, or 5 mL or less. With such a liquid-filled combination container 10L, the time required for oxygen permeation through the first container 30 to reach equilibrium after the second container 40 containing the first container 30 is closed can be shortened. This makes it possible to suppress decomposition of the liquid L due to oxygen.

[0126] Similarly, the volume of the liquid L contained in the first container 30 may be 20 mL or less, or 5 mL or less. Such a liquid-filled combination container 10L can shorten the time it takes for oxygen permeation through the first container 30 to reach equilibrium after the second container 40 containing the first container 30 is closed. This can suppress decomposition of the liquid L due to oxygen. Furthermore, by setting an upper limit on the amount of liquid in the first container 30 in this manner, it is possible to prevent the second container 40 from becoming larger and reducing the handleability of the combination container 10. This is suitable for applications in which a highly concentrated concentrate of tea or soup stock is contained in the first container as a liquid, or for applications in which expensive and highly pharmacologically active chemicals are contained in the first container as a liquid.

[0127] Furthermore, the maximum volume V of the first container 30 1MAX The maximum effective volume EV of the first container 30 is calculated by subtracting the volume γ of the liquid L from 1MAX The maximum volume V of the second container 40 2MAX The maximum usable volume EV of the second container 40 is calculated by subtracting the volume occupied by the first container 30 from the 2MAX An upper and lower limit may be set for the ratio (%) of the oxygen content to the total oxygen content of the liquid L. This ratio may be set to 50% or less, or 20% or less. Setting such an upper limit reduces the oxygen concentration in the first container 30. Furthermore, it is possible to ensure storage space for the first container 30 within the second container 40, making it easier to store the first container 30 within the second container 40. Furthermore, it is possible to shorten the time it takes for oxygen permeation through the first container 30 to reach equilibrium after the second container 40 containing the first container 30 is closed. This reduces decomposition of the liquid L due to oxygen. Furthermore, this ratio may be set to 5% or more, or 1% or more. Setting a lower limit in this manner prevents the second container 40 from becoming too large compared to the first container 30, thereby preventing a decrease in the ease of handling of the combination container 10.

[0128] Whether oxygen permeation through the first container 30 is in equilibrium is determined based on the oxygen concentration inside the first container 30. This determination is made when the difference between the oxygen concentration value (%) inside the first container 30 at a certain point in time and the oxygen concentration value (%) inside the first container 30 24 hours before that point in time is within ±5% of the oxygen concentration value (%) inside the first container 30 at that point in time.

[0129] In this manner, a liquid-containing first container 30L and a liquid-containing combination container 10L with adjusted oxygen concentrations and dissolved oxygen amounts can be obtained. In an equilibrium state where oxygen permeation through the first container 30 is balanced, the oxygen concentrations in the first container 30 and the second container 40 may be, for example, less than 1%. In conventional techniques, simply replacing the air with an inert gas often makes it difficult to reduce the oxygen concentration (%) in the headspace HS in the first container 30 due to the presence of liquid L in the first container 30. As a result, it is difficult to reduce the dissolved oxygen present in large amounts in the liquid L. In contrast, according to one specific example of the above-described embodiment, the second container 40 contains the liquid formulation-containing container 30LF and a gas, and does not need to contain the liquid L directly. This allows the oxygen concentration in the second container 40 to be sufficiently reduced. Therefore, by adjusting the volume of the second container 40, the oxygen concentration in the first container 30 in an equilibrium state can be reduced to less than 1%, preferably 0.5% or less, and more preferably 0.2% or less. Such an effect is suitable when the liquid L is a highly sensitive drug or food.

[0130] In contrast, the maximum volume V of the first container 30 can be increased without using the second container 40. 1MAX The maximum effective volume EV of the first container 30 is calculated by subtracting the volume γ of the liquid L from 1MAXIt may be possible to secure a large volume and fill the first container 30 with an inert gas. However, in this case, the excess space inside the first container becomes large compared to the liquid volume γ (mL), making it difficult to drain the liquid from the first container. Furthermore, the liquid may spread inside the first container, accelerating oxygen degradation. Furthermore, when applied to liquids such as food, this may reduce purchasing desire and lower the product's appeal. When applied to liquids such as medicines, it becomes difficult to check the state of the liquid inside the first container and to extract the appropriate amount of liquid from the first container.

[0131] If it takes a long time for the oxygen concentration or dissolved oxygen amount to decrease, deterioration of the liquid L due to oxygen will progress. The period or time from closing the second container 40 until oxygen permeation through the first container 30 reaches equilibrium is preferably within four weeks. If equilibrium is reached within four weeks, for example, if the oxygen concentration in the second container 40 becomes less than 1%, deterioration of the liquid L as a chemical can be effectively suppressed. For more sensitive liquids L, the period until equilibrium is reached is preferably within 20 days, more preferably within one week, and even more preferably within three days. On the other hand, it takes a certain period of time for the liquid L to reach equilibrium, which reduces the dissolved oxygen amount to a certain extent. To effectively adjust the dissolved oxygen amount, the period or time from closing the second container 40 until oxygen permeation through the first container 30 reaches equilibrium may be one hour or longer.

[0132] An example of a measuring device used to determine the oxygen concentration (%) and dissolved oxygen amount (mg / L) is the Fibox3 oxygen meter from PreSens, Germany. The Fibox3 oxygen meter can measure the oxygen concentration and dissolved oxygen amount in a non-contact manner without destroying the container, for example, for a combination container containing a liquid formulation shown in FIG. 1 or a formulation container containing a liquid formulation shown in FIG. 2. The oxygen concentration (%) and dissolved oxygen amount (mg / L) may also be measured using the Microx4 oxygen meter from PreSens, Germany. The Microx4 oxygen meter is a needle-type device. The Microx4 oxygen meter can measure the oxygen concentration and dissolved oxygen amount in a container by inserting a needle into the container.

[0133] The first container 30 may be stored in the second container 40 until oxygen permeation through the first container 30 reaches equilibrium. The first container 30 may be stored in the second container 40 until the oxygen concentration in the second container 40 increases to a predetermined value. The first container 30 may be stored in the second container 40 until the oxygen concentration in the first container 30 decreases to a predetermined value. The first container 30 may be stored in the second container 40 until the amount of dissolved oxygen in the liquid L in the first container 30 decreases to a predetermined value. The first container 30 may be stored in the second container 40 until the liquid L in the combination container 10 is to be used. Furthermore, while the first container 30 is stored in the second container 40, the liquid-filled combination container 10L may be circulated.

[0134] Next, a method of using the liquid-containing combination container 10L will be described.

[0135] When using the liquid L contained in the combination container 10, first, the second container 40 is opened. Next, the first container 30L containing the liquid is removed from the opened second container 40. Thereafter, the liquid L can be removed from the first container 30L containing the liquid and used. For the illustrated first container 30, the first container 30 can be opened by removing the fastener 36 from the container body 32 and then removing the stopper 34 from the container body 32. This allows the liquid L in the first container 30 to be used.

[0136] 6, the liquid L may be a medicine to be injected into the syringe 60. That is, the liquid L may be an injection. The syringe 60 has a cylinder 62 and a piston 66. The cylinder 62 has a cylinder body 63 and a needle 64 protruding from the cylinder body 63. The cylindrical needle 64 allows access to the space in the cylinder body 63 for storing the liquid L. The piston 66 has a piston body 67 and a gasket 68 held by the piston body 67. The gasket 68 may be made of rubber or the like. The gasket 68 is inserted into the cylinder body 63 to define a storage space for the liquid L within the cylinder body 63.

[0137] It is preferable that the pressure inside the liquid-containing first container 30L be adjusted. As an example, it is preferable that the pressure inside the liquid-containing first container 30L be maintained low, particularly at a negative pressure. This example effectively prevents unintended leakage of the liquid during storage of the liquid-containing first container 30L and splashing of the liquid L when the first container 30L is opened. The problem of container leakage and splashing is more serious for toxic liquids, such as highly pharmacologically active drugs. Furthermore, in the example shown in FIG. 6, if the liquid-containing first container 30L is under positive pressure, the liquid L automatically flows into the syringe 60. In this case, it becomes difficult to precisely inject the desired amount of liquid L into the syringe 60.

[0138] On the other hand, highly sensitive liquids, such as foods and pharmaceuticals, that are susceptible to degradation by post-production sterilization processes, such as gas, heat, or gamma radiation, are manufactured and packaged in a sterile environment. In other words, liquids that cannot be sterilized are manufactured using aseptic procedures. This sterile environment is typically maintained at a predetermined positive pressure to prevent the intrusion of bacteria. Therefore, the pressure inside the container is a predetermined positive pressure corresponding to the sterile environment, making it difficult to adjust the internal pressure of the container after it is closed.

[0139] The above-described specific example can address such a problem. As described above, the first container 30L containing the liquid is stored in the second container 40. During this storage, the oxygen concentration in the second container 40 decreases due to the inert gas substitution, causing oxygen in the first container 30 to permeate the first container 30 and move into the second container 40. This allows the pressure in the first container 30 to be reduced. In other words, the pressure in the first container 30 containing the liquid L can be adjusted after the first container 30 is closed and the liquid L is sealed inside.

[0140] From the viewpoint of adjusting the internal pressure of the first container 30, a second container 40 capable of storing a gas while maintaining a negative pressure may be used. For example, the second container 40 shown in FIG. 7 may be used, and the second container 40 containing the first container 30 may be closed under an inert gas atmosphere maintained at a negative pressure. The pressure inside the closed second container 40 becomes less than atmospheric pressure. In this case, oxygen permeation from the first container 30 to the second container 40 is promoted. In particular, the pressure inside the first container 30 can be significantly adjusted by ensuring a large volume of the second container 40 or by significantly reducing the initial pressure of the second container 40. As a result, the pressure inside the first container 30, which is initially positive pressure, can be adjusted to negative pressure by storing the first container 30 inside the second container 40. This allows the production of a pressure-adjusted liquid-filled first container 30L without depending on the method for producing the liquid L or the method for sealing the liquid L into the first container 30.

[0141] By adjusting the pressure inside the liquid-containing first container 30L, it is possible to extract a desired amount of liquid L from the first container 30. From the viewpoint of enabling the desired amount of liquid L to be extracted from the first container 30 with high precision, the volume of the liquid L contained in the first container 30 may be set to 0.5 mL or more, and more preferably 1 mL or more.

[0142] Furthermore, closing the second container 40 under negative pressure promotes oxygen permeation through the first container 30. Therefore, the time required for oxygen permeation through the first container 30 to reach equilibrium after the second container 40 containing the liquid-filled first container 30L is closed can be shortened.

[0143] Negative pressure refers to pressure less than atmospheric pressure, or 1 atm. Positive pressure refers to pressure greater than atmospheric pressure, or 1 atm. Whether a container is under negative pressure can be determined using a pressure gauge if the container is equipped with one. If the container is not equipped with a pressure gauge, it can also be determined using a syringe. Specifically, when a syringe needle is inserted into a target container, it can be determined by whether the liquid or gas contained in the syringe flows into the container when only atmospheric pressure is applied to the syringe piston. If the liquid or gas contained in the syringe flows into the container, it is determined that the container is under negative pressure. Similarly, whether a container is under positive pressure can be determined using a pressure gauge, but it can also be determined using a syringe. Specifically, when a syringe needle is inserted into a target container, it can be determined by whether the liquid or gas contained in the container flows into the syringe when only atmospheric pressure is applied to the syringe piston. If the liquid or gas contained in the container flows into the syringe, it is determined that there was positive pressure inside the container.

[0144] In the embodiment described above, the container set 20 includes a first container 30 that contains a liquid L and is at least partially gas permeable, and a second container 40 that can contain the first container 30 and has gas barrier properties. The combination container 10 is obtained by containing the first container 30 in the second container 40. That is, the liquid-filled combination container 10L includes a first container 30 that contains a liquid L and is at least partially gas permeable, and a second container 40 that contains the first container 30 and has oxygen barrier properties. The method for producing the liquid-filled first container 30L includes the steps of closing the second container 40 that contains the liquid-filled first container 30L and is filled with an inert gas, and storing the first container 30 in the second container 40. During the storage step, oxygen in the first container 30 permeates through the first container 30, thereby reducing the oxygen concentration in the first container 30. By decreasing the oxygen concentration in the first container 30, the amount of oxygen dissolved in the liquid L can be reduced.

[0145] According to this embodiment, oxygen in the first container 30 can pass through the first container 30 and move into the second container 40. By replacing the atmosphere in the second container 40 with an inert gas, the oxygen concentration (%) in the first container 30 can be reduced. As the oxygen concentration (%) in the first container 30 decreases, the amount of oxygen dissolved in the liquid L (mg / L) also decreases. Therefore, the amount of oxygen dissolved in the liquid L can be reduced, and decomposition of the liquid L by oxygen can be suppressed.

[0146] In this combination container 10, the second container 40 is responsible for reducing the amount of oxygen and for providing oxygen barrier properties. Meanwhile, the liquid-filled first container 30L may be responsible for ensuring the sterility of the interior and the contained liquid L. In this way, the storage environment required for the liquid L is efficiently realized by the combination of the first container 30 and the second container 40. With the combination container 10 and container set 20, the storage environment required for the liquid L can be realized inexpensively and easily with a high degree of freedom.

[0147] In this embodiment, the maximum volume V of the first container 30 1MAX The maximum usable volume EV of the first container 30 is calculated by subtracting the volume γ (mL) from the 1MAX (mL), and the maximum volume V of the second container 40 2MAX (mL) minus the volume (mL) occupied by the first container 30, 2MAX The sum of the volume γ (mL) of the liquid L is (2.56 × 10 -4 × (β × T / α) times or more. Here, T is the temperature (K) of the environment in which the liquid-containing combination container 10L is placed. β is the saturated solubility (mg / L) of oxygen in the liquid L in an air atmosphere under atmospheric pressure at temperature T (K). α is the oxygen concentration (%) in the second container 40 in a state in which oxygen permeation through the first container 30 is in equilibrium. By using the first container 30 and the second container 40 with such volumes, the first container 30 and the second container 40 can accommodate a sufficient volume of gas. As a result, in an equilibrium state in which oxygen permeation through the first container 30 is in equilibrium, the oxygen concentration in the second container 40 can be reduced to α (%) or less.

[0148] As a specific example, the maximum usable volume EV of the first container 30 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX may be greater than 0.663 times the volume γ (mL) of the liquid L. According to this example, in an air atmosphere at a temperature of 293 K and atmospheric pressure, the oxygen concentration in the second container 40 can be reduced to less than 1%.

[0149] In this embodiment, when the first container 30 is accommodated and the second container 40 is closed, the first container 30 and the second container 40 contain a total of (2.56 × 10) of the volume γ (mL) of the liquid L. -4 ×β×T). According to this example, the oxygen concentration in the second container 40 can be reduced to less than 1%. As a specific example, when the second container 40 is closed with the first container 30 inside, the first container 30 and the second container 40 can contain a total volume of gas that is greater than 0.663 times the volume γ (mL) of the liquid L. According to this example, the oxygen concentration in the second container 40 can be reduced to less than 1% in an air atmosphere at a temperature of 293 K and atmospheric pressure.

[0150] According to the above embodiment, it is possible to reduce the amount of oxygen dissolved in the liquid L and suppress decomposition by oxygen of the liquid L. For example, in an application in which a medicine is stored in the first container as a liquid, the loss of the pharmacological component over a three-year period can be reduced to 5% or less, more preferably 3% or less, and even more preferably 1% or less.

[0151] If the volume required to store a large amount of gas were secured using only the first container without using a second container, the excess space within the first container would be larger than the liquid volume γ (mL), making it difficult to remove the liquid from the first container. Furthermore, the liquid would be stirred within the first container, potentially accelerating deterioration due to oxygen. Furthermore, when applied to liquids such as food, this would discourage consumers and reduce product appeal. When applied to liquids such as medicines, it would be difficult to check the state of the liquid within the first container and remove the appropriate amount of liquid from the first container. In contrast, according to the above-described embodiment, the liquid-filled combination container 10L includes a second container 40 in addition to the liquid-filled first container 30L. Therefore, the excess space within the first container 30 where the liquid L is not contained can be reduced. Furthermore, because the second container 40 does not directly contain the liquid L, the internal atmosphere of the second container 40 can be easily replaced with an inert gas.

[0152] As a specific example of the above-described embodiment, the volume γ (mL) of the liquid L may be larger than half the maximum volume (mL) of the first container 30. By reducing the space in the first container 30 where the liquid L is not contained, the so-called headspace HS, in this manner, it is possible to reduce the amount of oxygen gas remaining in the first container 30 when the first container 30 containing the liquid L is closed. This makes it possible to suppress decomposition of the liquid L due to oxygen. Furthermore, it is possible to reduce the size of the first container 30 that is finally removed from the second container 40, thereby improving the handleability of the first container 30. Furthermore, it is possible to facilitate removal of the liquid L from the first container 30.

[0153] More preferably, the volume γ (mL) of the liquid L contained in the first container 30 is set to the maximum volume V of the first container 30. 1MAX( (mL). In this example, the number of moles of oxygen dissolved in the liquid L in the first container 30 is greater than the number of moles of oxygen in the headspace HS of the first container 30. As described above, it is difficult to sufficiently reduce the amount of dissolved oxygen dissolved in the liquid L by inert gas substitution. Therefore, when the volume γ (mL) of the liquid L is greater than the maximum volume V of the first container 30, 1MAX(This embodiment is particularly useful for the liquid-filled first container 30L where the volume is 97.5% or more (mL).

[0154] As a specific example of the above-described embodiment, the maximum usable volume EV of the first container 30 is 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX The total volume γ (mL) is (2.56 × 10 -4 × (β × T / α)) and the maximum effective volume EV of the first container 30. 1MAX The headspace HS may be equal to or greater than the sum of the headspace HS (mL) multiplied by (21.0 / α). By using a first container 30 and a second container 40 having such volumes, the first container 30 and the second container 40 can accommodate a sufficient volume of gas. By storing the liquid-filled first container 30L, in which air is accommodated in the headspace HS, in the second container 40, the oxygen concentration in the second container 40 can be reduced to α (%) or less in an equilibrium state in which oxygen permeation through the first container 30 is balanced.

[0155] As a more specific example, the maximum usable volume EV of the first container 30 1MAX (mL) and the maximum usable volume EV of the second container 40 2MAX The sum of the volume γ (mL) of the liquid L multiplied by 0.663 and the maximum effective volume EV of the first container 30 is 1MAX (mL) multiplied by 21.0. According to this example, by storing the liquid-containing first container 30L, in which air is accommodated in the headspace HS, in the second container 40, the oxygen concentration in the second container 40 can be reduced to less than 1% in an air atmosphere at a temperature of 293 K and atmospheric pressure.

[0156] As a specific example of the above-described embodiment, when the first container 30 is accommodated and the second container 40 is closed, the first container 30 and the second container 40 together accommodate a volume γ (mL) of the liquid L of (2.56×10 -4 × β × T) and the maximum effective volume EV of the first container 30. 1MAXThe first container 30L may contain a volume of gas greater than the sum of the volume γ (mL) of the liquid L multiplied by 21.0 and the maximum usable volume EV of the first container 30L. According to this example, by storing the first container 30L containing liquid with air in the headspace HS in the second container 40, the oxygen concentration in the second container 40 can be reduced to less than 1%. As a more specific example, when the first container 30 is contained and the second container 40 is closed, the first container 30 and the second container 40 have a total volume greater than the sum of the volume γ (mL) of the liquid L multiplied by 0.663 and the maximum usable volume EV of the first container 30. 1MAX The volume of gas contained therein may be greater than the sum of the volume of the liquid in the first container 30L and the volume of the liquid in the headspace HS multiplied by 21.0 (mL). According to this example, by storing the liquid-containing first container 30L, in which air is contained in the headspace HS, in the second container 40, the oxygen concentration in the second container 40 can be reduced to less than 1% in an air atmosphere at a temperature of 293 K and atmospheric pressure.

[0157] In one specific example of the above-described embodiment, the volume γ of the liquid L may be 0.5 mL or more, more preferably 1 mL or more. By setting a lower limit on the amount of liquid in the first container 30 in this way, it is possible to extract a certain amount of liquid from the first container 30, thereby reducing errors in the amount extracted.

[0158] In a specific example of the above-described embodiment, the first container 30 has a container body 32 having an opening 33 and a plug 34 that closes the opening 33. The oxygen permeability coefficient of the material that makes up the plug 34 is 1×10 -12 (mL / (m 2 The stopper 34 may be made of silicone rubber. The oxygen permeability coefficient (mL / (m 2 × day × atm) is the oxygen permeability coefficient (mL / (m 2× day × atm). According to this specific example, oxygen permeates the stopper 34 and moves out of the first container 30. Therefore, oxygen permeability can be imparted to the area of ​​the first container 30 exposed to the liquid L, such as the so-called headspace HS. This allows oxygen to permeate smoothly through the first container 30, and shortens the time it takes for oxygen permeation through the first container 30 to reach equilibrium after the first container 30 is placed inside the second container 40.

[0159] In a specific example of the above-described embodiment, the container body 32 may have oxygen barrier properties. Oxygen that has permeated the first container 30 enters a region separated from the liquid L, such as the headspace HS, within the first container 30. Therefore, dissolution of oxygen that has permeated the first container 30 into the liquid L can be suppressed.

[0160] Although one embodiment has been described with reference to specific examples, the above-described specific examples do not limit the present invention. The above-described embodiment can be implemented with various other specific examples, and various omissions, substitutions, changes, additions, etc. can be made without departing from the spirit of the present invention.

[0161] An example of the modification will be described below with reference to the drawings. In the following description and the drawings used in the following description, parts that can be configured similarly to the above-described specific example will be designated by the same reference numerals as those used for the corresponding parts in the above-described specific example, and duplicated descriptions will be omitted.

[0162] Although the specific configuration of the first container 30 has been described in the above specific example, various containers may be used without being limited to this example. For example, as shown in Fig. 8, the plug 34 of the first container 30 may be in the form of a film or sheet that covers the opening 33. The plug 34 shown in Fig. 8 is joined to the tip surface of the container body 32 using, for example, a bonding material or by welding. The plug 34 may have oxygen permeability or oxygen barrier properties.

[0163] FIG. 9 shows another modified example of the first container 30. The first container 30 shown in FIG. 9 is a syringe 60. Similar to the syringe already described with reference to FIG. 6, the syringe 60 shown in FIG. 9 has a cylinder 62 and a piston 66. The cylinder 62 has a glass or resin cylinder body 63 and a metal needle 64. The cylinder 62 is the container body 32 of the first container 30 and forms a space for containing the liquid L. The piston 66 has a glass or resin piston body 67 and a gasket 68 disposed in the opening 33 of the cylinder 62. The gasket 68 is the stopper 34 of the first container 30 and closes the opening 33. A space for containing the liquid L is defined between the cylinder 62 and the gasket 68. The illustrated syringe 60 further has a cap 69. The cap 69 is removably attached to the needle 64. The cap 69 prevents leakage of the liquid L from the needle 64 and seals the liquid L in the syringe 60. In the example shown in Fig. 9, by using the syringe 60 as the first container 30, the syringe 60 removed from the second container 40 can be used on a patient or the like as is.

[0164] In the example shown in FIG. 9, the gasket 68 may be made oxygen permeable. A stopper made of silicone rubber may be used as the oxygen-permeable gasket 68. The cylinder 62 may be made oxygen barrier. The oxygen permeability of the gasket 68 may be set to the same as the oxygen permeability of the stopper 34 described above. The oxygen permeability of the cylinder 62 may be set to the same as the oxygen permeability of the container body 32 described above.

[0165] 9, oxygen passes through the gasket 68, and is thereby discharged from the interior of the first container 30, which is partitioned by the cylinder body 63 and the gasket 68. This reduces the oxygen concentration in the syringe 60, and the amount of oxygen dissolved in the liquid L. As a result, decomposition of the liquid L by oxygen can be effectively suppressed.

[0166] In the above-described specific example, the first container 30 has a container body 32 and a stopper 34, and the stopper 34 has gas permeability. However, at least a portion of the container body 32 may be gas permeable, and the stopper 34 may have gas barrier properties. Furthermore, the specific configuration of the second container 40 described above is merely an example, and various modifications are possible. [Explanation of symbols]

[0167] 10L: combination container containing liquid, 10: combination container, 20: container set, 30L: first container containing liquid, 30: first container, 32: container body, 33: opening, 34: stopper, 36: fastener, 40: second container, 40a: opening, 41a: first main film, 41b: second main film, 41c: first gusset film, 41d: second gusset film, 42: container body, 42a: storage section, 42b: flange section, 44: lid, 55: supply pipe, 56: discharge port, 60: syringe, 62: cylinder, 63: cylinder body, 64: needle, 66: piston, 67: piston body, 68: gasket, 69: cap, L: liquid

Claims

1. a first container containing a liquid of volume γ (mL) and at least a portion of which is oxygen permeable; a second container that houses the first container and has oxygen barrier properties; The sum of the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container and the value obtained by subtracting the volume (mL) of the first container from the maximum volume (mL) of the second container is (2.56 × 10 －４ × (β × T / α) times or more, where T is the temperature of the environment (K), β is the saturated solubility of oxygen in the liquid in an air atmosphere under atmospheric pressure at temperature T (K) (mg / L), and α is the oxygen concentration (%) in the second container; the first container is a vial bottle having a glass container body with an opening and a stopper containing silicone that closes the opening, The liquid-filled combination container, wherein the amount of oxygen permeating the entire first container is 1×10 −2 (mL / (day×atm)) or more and 100 (mL / (day×atm)) or less.

2. 2. The liquid combination container according to claim 1, wherein the oxygen concentration α is less than 1%.

3. The sum of the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container and the value obtained by subtracting the volume (mL) occupied by the first container from the maximum volume (mL) of the second container is 2.56×10 －４ 3. The combination container containing liquid according to claim 1, wherein the volume γ (mL) is greater than or equal to the sum of the value obtained by multiplying the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container by (21.0 / α).

4. a first container containing a liquid of volume γ (mL) and at least a portion of which is oxygen permeable; a second container that houses the first container and has oxygen barrier properties; The sum of the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container and the value obtained by subtracting the volume (mL) occupied by the first container from the maximum volume (mL) of the second container is (2.56 × 10 －４ × β × T) times or more, where T is the temperature of the environment (K), and β is the saturated solubility of oxygen in the liquid in an air atmosphere at temperature T (K) and atmospheric pressure (mg / L); the first container is a vial bottle having a glass container body with an opening and a stopper containing silicone that closes the opening, The liquid-filled combination container, wherein the amount of oxygen permeating the entire first container is 1×10 −2 (mL / (day×atm)) or more and 100 (mL / (day×atm)) or less.

5. The sum of the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container and the value obtained by subtracting the volume (mL) occupied by the first container from the maximum volume (mL) of the second container is 2.56×10 －４ 4. The combination container containing liquid according to claim 3, wherein the volume γ (mL) is equal to or greater than the sum of the value obtained by multiplying the value obtained by multiplying the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container by 21.0 (×β×T).

6. The liquid-containing combination container according to any one of claims 1 to 5, wherein the volume γ (mL) is greater than half the maximum volume (mL) of the first container.

7. The liquid-containing combination container according to any one of claims 1 to 6, wherein the volume γ is 0.5 mL or more.

8. The liquid-filled combination container according to any one of claims 1 to 7, wherein the volume γ is 20 mL or less.

9. The liquid-filled combination container according to any one of claims 1 to 8, wherein the first container is capable of containing gas while maintaining a negative pressure.

10. a first container containing a liquid of volume γ (mL) and at least a portion of which is oxygen permeable; a second container capable of accommodating the first container and having oxygen barrier properties; the sum of the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container and the value obtained by subtracting the volume (mL) occupied by the first container from the maximum volume (mL) of the second container is greater than 0.663 times the volume γ (mL); the first container is a vial bottle having a glass container body with an opening and a stopper containing silicone that closes the opening, The container set, wherein the amount of oxygen permeating through the entire first container is 1×10 −2 (mL / (day×atm)) or more and 100 (mL / (day×atm)) or less.

11. The container set described in claim 10, wherein the sum of the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container and the value obtained by subtracting the volume (mL) occupied by the first container from the maximum volume (mL) of the second container is greater than the sum of the value obtained by multiplying the volume γ (mL) by 0.663 and the value obtained by multiplying the value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container by 21.

0.

12. The container set according to claim 10 or 11, wherein the volume γ (mL) is greater than half the maximum volume (mL) of the first container.

13. The container set according to any one of claims 10 to 12, wherein the volume γ is 0.5 mL or more.

14. The container set according to any one of claims 10 to 13, wherein the volume γ is 20 mL or less.

15. The container set according to any one of claims 10 to 14, wherein the first container is capable of containing a gas while maintaining a negative pressure.

16. closing a second container containing the first container and filled with an inert gas; storing the first container within the second container; the first container contains a liquid of volume γ (mL) and is at least partially oxygen permeable; the second container has oxygen barrier properties, In a state in which the first container is accommodated and the second container is closed, the first container and the second container have a total volume of (2.56 × 10 －４ × β × T), where T is the temperature of the environment (K), and β is the saturated solubility of oxygen (mg / L) in the liquid in an air atmosphere at atmospheric pressure at temperature T (K); the first container is a vial bottle having a glass container body with an opening and a stopper containing silicone that closes the opening, The method for manufacturing a liquid-filled container, wherein the amount of oxygen permeating the entire first container is 1×10 −2 (mL / (day×atm)) or more and 100 (mL / (day×atm)) or less.

17. In a state in which the first container is accommodated and the second container is closed, the first container and the second container have a total volume γ (mL) of (2.56 × 10 －４ 17. The method for manufacturing a liquid-filled container according to claim 16, wherein the volume of gas contained in the first container is greater than the sum of a value obtained by multiplying the volume γ (mL) by 1.0 (×β×T) and a value obtained by subtracting the volume γ (mL) from the maximum volume (mL) of the first container.

18. The method for manufacturing a liquid-filled container according to claim 16 or 17, wherein the volume γ (mL) is greater than half the maximum volume of the first container.

19. The method for manufacturing a liquid-filled container according to any one of claims 16 to 18, wherein the volume γ is 0.5 mL or more.

20. The method for manufacturing a liquid-filled container according to any one of claims 16 to 19, wherein the volume γ is 20 mL or less.

21. The method for manufacturing a liquid-filled container according to any one of claims 16 to 20, wherein the first container is capable of containing gas while maintaining a negative pressure.

Images