Liquid agent containing combination medical container, medical container set, manufacturing method of liquid agent containing container, and manufacturing method of liquid agent containing combination medical container

Abstract

To provide a liquid agent containing combination medical container capable of stably suppressing quality deterioration of a liquid agent.SOLUTION: A liquid agent containing combination medical container includes: a first container in which a liquid agent is stored; a second container which has an oxygen barrier property and stores the first container; and an oxygen absorbent which absorbs oxygen in the second container. The first container includes a container body which has an opening, and a plug which closes the opening. A first oxygen permeation performance of a material constituting the plug is 0.00010 (cc×mm / (mm2×day)) or more at a temperature of 23°C and a humidity of 50% RH. A first water vapor permeability of the material constituting the plug is 1.0 (mg×mm / (mm2×day)) or less at a temperature of 40°C and a humidity of 90% RH.SELECTED DRAWING: Figure 1A

Description

[Technical field]

[0001] The present disclosure relates to a combined medical container containing a liquid agent, a medical container set, a method for manufacturing a container containing a liquid agent, and a method for manufacturing a medical container containing a liquid agent. [Background technology]

[0002] A liquid medicine is a liquid drug. The liquid medicine contains a medicinal ingredient and a vehicle liquid. The liquid medicine may be distributed in a vial or a syringe. Vials and syringes are common in medical settings because they are easy to use.

[0003] Pharmaceutical ingredients are susceptible to deterioration due to oxygen-induced deterioration. Pharmaceutical ingredients contained in liquid preparations are affected not only by gaseous oxygen in the container, but also by oxygen dissolved in the liquid medium. Pharmaceutical ingredients that are susceptible to deterioration may be handled in powder form by freeze-drying. Powdered pharmaceutical ingredients are less likely to deteriorate. However, powdered pharmaceutical ingredients must be mixed with a liquid medium to form a liquid preparation of a predetermined concentration before administration to a patient. Therefore, it is preferable that pharmaceutical ingredients are handled as liquid preparations contained in vials, syringes, etc.

[0004] As disclosed in Patent Documents 1 to 3, a combination container including a first container having gas permeability and a second container having gas non-permeability is known. In this combination container, the first container is accommodated in the second container together with an oxygen scavenger. Oxygen in the first container permeates the first container and moves to the second container. The oxygen scavenger absorbs the oxygen in the second container. Therefore, the amount of oxygen in the first container decreases. With this combination container, oxygen deterioration of the contents in the first container can be suppressed.

[0005] Patent document 1: JPH05-319459A Patent document 2: JP2005-6737A Patent document 3: JPH04-200465A DISCLOSURE OF THEINVENTION

[0006] It is considered that the deterioration of the quality of the liquid medicine caused by oxygen can be dealt with by storing the liquid medicine in a combination container. However, when the liquid medicine is handled using the combination container, the quality deterioration occurs in the liquid medicine, which is not a problem with other stored items such as food. The present disclosure aims to stably suppress the deterioration of the quality of the liquid medicine.

[0007] A first liquid combination medical container according to an embodiment of the present disclosure includes: A first container containing a liquid agent; a second container that houses the first container and has oxygen barrier properties; an oxygen absorbent that absorbs oxygen in the second container; The first container includes a container body having an opening and a plug that closes the opening, The first oxygen permeability of the material constituting the plug is 0.00010(cc×mm / (mm 2 ×day) or more, The first water vapor permeability of the material constituting the plug is 1.0 (mg×mm / (mm 2 ×day) or less.

[0008] The second liquid combination medical container according to one embodiment of the present disclosure includes: A first container containing a liquid agent; a second container that houses the first container and has oxygen barrier properties; an oxygen absorbent that absorbs oxygen in the second container; The second oxygen permeability of the first container is 0.010 (cc / day) or more at a temperature of 23° C. and a humidity of 50% RH; The second water vapor permeability of the first container is 20 (mg / day) or less at a temperature of 40° C. and a humidity of 90% RH.

[0009] A first medical container set according to one embodiment of the present disclosure includes: A first container for containing a liquid agent; a second container that accommodates the first container; an oxygen absorbent that absorbs oxygen in the second container; The second container has an oxygen barrier property, The first container includes a container body having an opening and a plug that closes the opening, The first oxygen permeability of the material constituting the plug is 0.00010(cc×mm / (mm 2 ×day) or more, The first water vapor permeability of the material constituting the plug is 1.0 (mg×mm / (mm 2 ×day) or less.

[0010] A second medical container set according to an embodiment of the present disclosure includes: A first container for containing a liquid agent; a second container that accommodates the first container; An oxygen absorbent that absorbs oxygen in the second container, The second container has an oxygen barrier property, The second oxygen permeability of the first container in the first state is 0.010 (cc / day) or more at a temperature of 23° C. and a humidity of 50% RH; The second water vapor permeability of the first container in the first state is 20 (mg / day) or less at a temperature of 40° C. and a humidity of 90% RH.

[0011] A third medical container set according to an embodiment of the present disclosure includes: A first container for containing a liquid agent; a second container that accommodates the first container; An oxygen absorbent that absorbs oxygen in the second container, The second container has an oxygen barrier property, The second oxygen permeability of the first container is 0.010 (cc / day) or more at a temperature of 23° C. and a humidity of 50% RH; The second water vapor permeability of the first container is 20 (mg / day) or less at a temperature of 40° C. and a humidity of 90% RH.

[0012] A method for producing a first liquid-containing combination medical container according to an embodiment of the present disclosure includes the steps of: A method for producing a combination medical container containing a liquid agent according to one embodiment of the present disclosure, comprising the steps of: a step of closing an opening of a container body of the first container containing the liquid agent with a plug to prepare a first container containing the liquid agent; and placing the first container containing the liquid agent in the second container.

[0013] A method for producing a second liquid-containing combination medical container according to an embodiment of the present disclosure includes the steps of: A method for producing a combination medical container containing a liquid agent according to one embodiment of the present disclosure, comprising the steps of: placing the first container in the second container; and closing the second container.

[0014] A method for manufacturing a liquid-filled container according to an embodiment of the present disclosure includes the steps of: A method for manufacturing a liquid-containing container using a liquid-containing combined medical container according to one embodiment of the present disclosure, comprising the steps of: closing the second container containing the first container; adjusting the oxygen concentration by absorbing oxygen in the second container with the oxygen absorbent; covering the plug of the first container with a second plug, or closing the opening with a second plug having oxygen barrier properties instead of the plug of the first container; In the step of adjusting the oxygen concentration, oxygen in the first container permeates the first container, moves to the outside of the first container, and is absorbed by the oxygen absorbent in the second container.

[0015] According to the present disclosure, deterioration of the quality of a liquid formulation can be stably suppressed. [Brief description of the drawings]

[0016] [Figure 1A] FIG. 1A is a view for explaining an embodiment according to the present disclosure, and is a front view showing an example of a combined medical container containing a liquid agent. [Figure 1B] FIG. 1B is a vertical cross-sectional view showing the liquid combination medical container shown in FIG. 1A. [Figure 1C] FIG. 1C is a vertical cross-sectional view showing an example of a first container containing a liquid agent that can be included in the combined medical container containing a liquid agent shown in FIG. 1A. [Figure 1D] FIG. 1D is a diagram showing a modified example of the arrangement of the first container in the combined medical container containing the liquid agent shown in FIG. 1A. [Figure 1E] FIG. 1E is a diagram showing a modified example of the sealing portion of the combined medical container containing the liquid agent shown in FIG. 1A. [Figure 2A] FIG. 2A is a diagram illustrating a first method for measuring oxygen permeability. [Figure 2B] FIG. 2B is a diagram illustrating a method for measuring the first water vapor permeability. [Figure 2C] FIG. 2C is a chemical formula showing a siloxane bond having a chain structure. [Figure 2D] FIG. 2D is a chemical formula showing a siloxane bond having a ring-like structure. [Figure 2E] FIG. 2E is a graph showing an example of an IR spectrum obtained by ATR-IR. [Figure 2F] FIG. 2F is a diagram illustrating a method for measuring the oxygen permeability of a stopper. [Figure 3A] FIG. 3A is a diagram showing an example of a syringe as a first container that can be included in a combination medical container containing a liquid medicine. [Figure 3B] FIG. 3B is a diagram showing another example of a syringe as a first container that can be included in the liquid combination medical container. [Figure 3C] FIG. 3C is a diagram showing yet another example of a syringe as a first container that can be included in the liquid combination medical container. [Figure 3D] FIG. 3D is a partial cross-sectional view of one embodiment of the syringe shown in FIG. 3C. [Figure 4A] FIG. 4A is a front view showing an example of the second container. [Figure 4B] FIG. 4B is a front view showing another example of the second container. [Figure 4C] FIG. 4C is a perspective view showing still another example of the second container. [Figure 4D] FIG. 4D is a perspective view showing still another example of the second container. [Figure 4E] FIG. 4E is a perspective view showing still another example of the second container. [Figure 4F] FIG. 4F is a perspective view showing still another example of the second container. [Figure 5A] FIG. 5A is a cross-sectional view showing an example of an oxygen absorbing member containing an oxygen absorbent. [Figure 5B] FIG. 5B is a cross-sectional view showing an example of an oxygen absorbing film containing an oxygen absorbent. [Figure 5C] FIG. 5C is a cross-sectional view showing another example of an oxygen absorbing member including an oxygen absorbent. [Figure 6A] FIG. 6A is a diagram showing an example of a method for producing the combined medical container containing the liquid agent and the first container containing the liquid agent shown in FIGS. 1A to 1C. [Figure 6B] FIG. 6B is a diagram showing an example of a method for producing the combined medical container containing the liquid agent and the first container containing the liquid agent shown in FIGS. 1A to 1C. [Figure 6C] FIG. 6C is a diagram showing an example of a method for producing the combined medical container containing a liquid agent and the first container containing a liquid agent shown in FIGS. 1A to 1C. [Figure 7A] FIG. 7A is a diagram illustrating a modified example of a method for producing a combined medical container containing a liquid agent and a first container containing a liquid agent. [Figure 7B] FIG. 7B is a diagram illustrating another modified example of the method for producing the combined medical container containing a liquid agent and the first container containing a liquid agent. [Figure 8A] FIG. 8A is a diagram illustrating yet another modified example of the method for producing a combined medical container containing a liquid agent and a first container containing a liquid agent. [Figure 8B] FIG. 8B is a diagram illustrating yet another modified example of the method for producing the combined medical container containing a liquid agent and the first container containing a liquid agent. [Figure 9] FIG. 9 is a diagram showing a method of using the first container containing the liquid agent of FIG. 1C. [Figure 10A]FIG. 10A is a diagram illustrating a second method for measuring oxygen permeability of a stopper. [Figure 10B] FIG. 10B is a diagram illustrating a method for measuring the second oxygen permeability of the container body. [Figure 10C] FIG. 10C is a diagram illustrating a method for measuring the second water vapor permeability performance of the stopper. [Figure 10D] FIG. 10D is a diagram illustrating a method for measuring the second water vapor permeability performance of the container body. [Figure 10E] FIG. 10E is a diagram illustrating a method for measuring the second water vapor permeability performance of the container body. [Figure 11A] FIG. 11A is a vertical cross-sectional view showing an example of a first container in the second embodiment. [Figure 11B] FIG. 11B is a vertical cross-sectional view showing another example of the first container in the second embodiment. [Figure 12A] FIG. 12A is a diagram showing an example of a layer structure of a laminate that can be used for the second container. [Figure 12B] FIG. 12B is a diagram showing another example of a layer structure of a laminate that can be used for the second container. [Figure 12C] FIG. 12C is a diagram showing yet another example of a layer structure of a laminate that can be used for the second container. [Figure 12D] FIG. 12D is a diagram showing still another example of a layer structure of a laminate that can be used for the second container. [Figure 12E] FIG. 12E is a diagram showing still another example of a layer structure of a laminate that can be used for the second container. [Figure 12F] FIG. 12F is a diagram showing yet another example of a layer structure of a laminate that can be used for the second container. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] The embodiments of the present disclosure relate to the following [1] to

[36] .

[0018] [1] A first container containing a liquid agent; a second container that houses the first container and has oxygen barrier properties; an oxygen absorbent that absorbs oxygen in the second container; The first container includes a container body having an opening and a plug that closes the opening, The first oxygen permeability of the material constituting the plug is 0.00010(cc×mm / (mm 2 ×day) or more, The first water vapor permeability of the material constituting the plug is 1.0 (mg×mm / (mm 2 × day) or less.

[0019] [2] The liquid-containing combination medical container of [1], wherein the type A durometer hardness of the stopper is 25 or more and 60 or less.

[0020] [3] The liquid-containing combination medical container of [1] or [2], wherein the type A durometer hardness of the stopper is 25 or more and 45 or less.

[0021] [4] The liquid-containing combination medical container according to any one of [1] to [4], wherein the average thickness of the portion of the plug facing the opening is 0.5 mm or more and 10 mm or less.

[0022] [5] The area of ​​the opening is 25 mm 2 More than 1000mm 2 A combination medical container containing any one of the following liquids: [1] to [3].

[0023] [6] The liquid-containing combined medical container according to any one of [1] to [5], wherein the stopper contains a compound having a main skeleton formed by a siloxane bond.

[0024] [7] The first container includes a vial; The container body includes a glass bottle.

[0025] [8] the first container includes a syringe; The syringe is a liquid-containing combined medical container according to any one of [1] to [7], which includes a cylinder that contains the liquid and constitutes the container body, and a piston that is inserted into the cylinder.

[0026] [9] The liquid-containing combination medical container of [8], wherein the piston includes a gasket that is inserted into the cylinder to form the stopper.

[0027]

[10] The cylinder includes a cylinder body into which the piston is inserted, and a needle connected to the cylinder body and including the opening, The stopper is pierced by the needle to close the opening of the needle.

[0028]

[11] The cylinder includes a cylinder body having the opening into which the piston is inserted, and a needle that can be fixed to the cylinder body so as to cover the opening, The stopper is fixably attached to the cylinder body to close the opening.

[0029]

[12] The second oxygen permeability of the first container in the first state is 0.010 (cc / day) or more at a temperature of 23°C and a humidity of 50% RH; The liquid-containing combined medical container according to any one of [1] to

[11] , wherein the second water vapor permeability of the first container in a first state is 20 (mg / day) or less at a temperature of 40° C. and a humidity of 90% RH.

[0030]

[13] The second oxygen permeability of the first container is 0.010 (cc / day) or more at a temperature of 23°C and a humidity of 50% RH; The liquid-containing combined medical container according to any one of [1] to

[12] , wherein the second water vapor permeability of the first container is 20 (mg / day) or less at a temperature of 40° C. and a humidity of 90% RH.

[0031]

[14] A first container containing a liquid agent; a second container that houses the first container and has oxygen barrier properties; an oxygen absorbent that absorbs oxygen in the second container; The second oxygen permeability of the first container in the first state is 0.010 (cc / day) or more at a temperature of 23° C. and a humidity of 50% RH; The first container has a second water vapor permeability of 20 (mg / day) or less in a first state at a temperature of 40° C. and a humidity of 90% RH.

[0032]

[15] A first container containing a liquid agent; a second container that houses the first container and has oxygen barrier properties; an oxygen absorbent that absorbs oxygen in the second container; The second oxygen permeability of the first container is 0.010 (cc / day) or more at a temperature of 23° C. and a humidity of 50% RH; The second water vapor permeability of the first container is 20 (mg / day) or less at a temperature of 40° C. and a humidity of 90% RH.

[0033]

[16] The liquid-containing combination medical container of

[14] or

[15] , wherein the first container includes a container body having an opening, a stopper at least partially covering the opening, and a cover covering the stopper.

[0034]

[17] The liquid-containing combination medical container according to

[16] , wherein the stopper comprises butyl rubber.

[0035]

[18] The first oxygen permeability of the material constituting the cover is 0.00010(cc×mm / (mm 2 ×day) or more, The first water vapor permeability of the material constituting the cover is 1.0 (mg×mm / (mm 2 2. A combination medical container containing a liquid formulation according to claim 16 or 17, wherein the maximum length of said container is less than or equal to 1 × day.

[0036]

[19] The first container includes a container body having an opening and a plug that closes the opening, The first oxygen permeability of the material constituting the container body is 0.00010(cc×mm / (mm 2 ×day) or more, The first water vapor permeability of the material constituting the container body is 1.0 (mg×mm / (mm 2 A combination medical container containing any of the liquids listed in

[14] to

[18] , wherein the liquid-containing capacity is less than or equal to 100 mg / kg / day.

[0037]

[20] A first container that contains a liquid and is oxygen permeable; A second container that houses the first container and has an oxygen barrier property, the second container includes a laminate; The laminate includes an inner surface facing the storage space of the second container and an outer surface opposite to the inner surface, The laminate comprises, in order from the inner surface to the outer surface, a sealant layer, a first barrier layer, a resin layer, and a second barrier layer.

[0038]

[21] A first container that contains a liquid and is oxygen permeable; a second container that houses the first container and has oxygen barrier properties; an oxygen absorbing member housed in the second container; The oxygen absorbing member includes an oxygen absorbent that absorbs oxygen in the second container, The second container includes a first film and a second film that houses the first container between the first film, The first film and the second film are joined at a seal portion, The sealing portion includes a first sealing portion positioned facing the first container, the first seal portion is bent so as to protrude away from the first container in a direction in which the first seal portion and the first container face each other, A liquid-containing combined medical container, wherein the first container is positioned between the first sealed portion and the oxygen absorbing member in a direction in which the first sealed portion and the first container face each other.

[0039]

[22] The second container is bent with the second film on the inside, so that a first portion of the second container that accommodates the first container and a second portion of the second container overlap with each other, the second portion is located on one side of the first portion in a direction in which the first seal portion and the first container face each other when the second container is in an unfolded state before being bent; The liquid-containing combined medical container according to any of

[21] , wherein the oxygen absorbing member is bent together with the second container so that the intermediate portion of the oxygen absorbing member is positioned on the bent apex of the second film.

[0040]

[23] The second container is bent with the second film on the inside, so that the first portion and the third portion of the second container overlap each other. the third portion is located on the other side of the first portion in a direction in which the first seal portion and the first container face each other when the second container is in an unfolded state before being bent, The liquid-containing combination medical container of

[22] , wherein the first portion, the third portion, and the second portion are stacked in this order.

[0041]

[24] Further comprising an outer box for housing the second container, the second container accommodates the first container and the oxygen absorbing member such that one of the stopper and the container body is adjacent to the first seal portion and the other of the stopper and the container body is adjacent to the oxygen absorbing member; The second container is bent with the second film on the inside, so that a first portion of the second container accommodating the first container and a second portion of the second container overlap each other, The second container is bent with the second film on the inside, so that the first portion and the third portion of the second container overlap each other, In an unfolded state of the second container before being bent, the first portion is located between the second portion and the third portion, The outer box includes a bottom portion, a top portion facing the bottom portion, and a side wall portion located between the bottom portion and the top portion, A liquid-containing combined medical container according to any one of

[21] to

[23] , wherein a second container is contained in the outer box, the second container being folded so that the first portion, the second portion, and the third portion overlap, with the container body of the first container facing the bottom portion of the outer box and the stopper of the first container facing the top portion of the outer box.

[0042]

[25] A first container for containing a liquid agent; a second container that accommodates the first container; an oxygen absorbent that absorbs oxygen in the second container; The second container has an oxygen barrier property, The first container includes a container body having an opening and a plug that closes the opening, The first oxygen permeability of the material constituting the plug is 0.00010(cc×mm / (mm 2 ×day) or more, The first water vapor permeability of the material constituting the plug is 1.0 (mg×mm / (mm 2 ×day)) or less, medical container set.

[0043]

[26] A first container for containing a liquid agent; a second container that accommodates the first container; An oxygen absorbent that absorbs oxygen in the second container, The second container has an oxygen barrier property, The second oxygen permeability of the first container in the first state is 0.010 (cc / day) or more at a temperature of 23° C. and a humidity of 50% RH; The medical container set, wherein the first container in the first state has a second water vapor permeability of 20 (mg / day) or less at a temperature of 40° C. and a humidity of 90% RH.

[0044]

[27] A first container for containing a liquid agent; a second container that accommodates the first container; An oxygen absorbent that absorbs oxygen in the second container, The second container has an oxygen barrier property, The second oxygen permeability of the first container is 0.010 (cc / day) or more at a temperature of 23° C. and a humidity of 50% RH; The medical container set, wherein the second water vapor permeability of the first container is 20 (mg / day) or less at a temperature of 40° C. and a humidity of 90% RH.

[0045]

[28] A first container for containing a liquid; A second container that accommodates the first container, the first container is oxygen permeable; The second container has an oxygen barrier property, the second container includes a laminate; The laminate includes an inner surface facing the storage space of the second container and an outer surface opposite to the inner surface, The medical container set, wherein the laminate includes, in order from the inner surface to the outer surface, a sealant layer, a first barrier layer, a resin layer, and a second barrier layer.

[0046]

[29] A first container for containing a liquid; a second container that accommodates the first container; an oxygen absorbing member housed in the second container; the first container is oxygen permeable; The second container has an oxygen barrier property, The oxygen absorbing member includes an oxygen absorbent that absorbs oxygen in the second container, The second container includes a first film and a second film that houses the first container between the first film, The first film and the second film are joined at a seal portion, The sealing portion includes a first sealing portion positioned facing the first container, the first seal portion is bent so as to protrude away from the first container in a direction in which the first seal portion and the first container face each other, a medical container set, wherein the first container is positioned between the first seal portion and the oxygen absorbing member in a direction in which the first seal portion and the first container face each other.

[0047]

[30] A first container for containing a liquid; A second container that accommodates the first container, the first container is oxygen permeable; The second container has an oxygen barrier property, The second container includes a first film and a second film that houses the first container between the first film, The first film and the second film are joined at a seal portion, The sealing portion includes a first sealing portion positioned facing the first container, the first seal portion is bent so as to protrude away from the first container in a direction in which the first seal portion and the first container face each other, the sealing portion further includes a first side seal portion connected to one end of the first seal portion, a second side seal portion connected to the other end of the first seal portion, and an additional seal portion positioned between at least one of the first side seal portion and the second side seal portion and the first container.

[0048]

[31] A method for producing a liquid-containing combination medical container according to any one of [1] to

[24] , a step of closing an opening of a container body of the first container containing the liquid agent with a plug to prepare a first container containing the liquid agent; and placing the first container containing the liquid in the second container.

[0049]

[32] A method for producing a liquid-containing combination medical container according to any one of [1] to

[24] , placing the first container in the second container; and closing the second container.

[0050]

[33] A method for producing a liquid-containing container using a liquid-containing combined medical container according to any one of [1] to

[24] , comprising the steps of: closing the second container containing the first container; and adjusting the oxygen concentration by absorbing the oxygen in the second container with an oxygen absorbent. A method for manufacturing a container containing a liquid agent, wherein, in the step of adjusting the oxygen concentration, oxygen in the first container permeates the first container, moves to the outside of the first container, and is absorbed by the oxygen absorber in the second container.

[0051]

[34] A method for producing a liquid-containing container using any one of the liquid-containing combined medical containers according to [1] to

[24] , comprising the steps of: closing the second container containing the first container; adjusting the oxygen concentration by absorbing oxygen in the second container with the oxygen absorbent; a step of covering the plug of the first container with a second plug, or a step of closing an opening of the container body with a second plug having oxygen barrier properties instead of the plug of the first container, A method for manufacturing a container containing a liquid agent, wherein, in the step of adjusting the oxygen concentration, oxygen in the first container permeates the first container, moves to the outside of the first container, and is absorbed by the oxygen absorber in the second container.

[0052]

[35] A laminate comprising: The container, wherein the laminate includes, in order from the inner surface to the outer surface, a sealant layer, a first barrier layer, a resin layer, and a second barrier layer.

[0053]

[36] A laminate for use in a container, comprising: A laminate comprising, in order from the inner surface to the outer surface, a sealant layer, a first barrier layer, a resin layer, and a second barrier layer.

[0054] Hereinafter, an embodiment of the present disclosure will be described with reference to the drawings. In the drawings attached to this specification, the scale and aspect ratios are appropriately changed and exaggerated from those of the actual objects for the convenience of illustration and understanding. Configurations shown in some drawings may be omitted in other drawings. In the following description and the drawings used in the following description, the same reference numerals are used for parts that may be configured in common between the illustrated examples, and duplicated descriptions are omitted.

[0055] In this specification, terms that specify shapes or geometric conditions and their degrees, such as "parallel," "orthogonal," and "same," as well as values ​​of lengths and angles, are not limited to their strict meanings, but are interpreted to include a range within which similar functions can be expected.

[0056] In this specification, when multiple upper limit candidates and multiple lower limit candidates are given for a certain parameter, the numerical range of the parameter may be formed by combining any one of the upper limit candidates and any one of the lower limit candidates. As an example, consider the description "Parameter B may be A1 or more, A2 or more, or A3 or more. Parameter B may be A4 or less, A5 or less, or A6 or less." In this example, the numerical range of parameter B may be A1 or more and A4 or less, A1 or more and A5 or less, A1 or more and A6 or less, A2 or more and A4 or less, A2 or more and A5 or less, A2 or more and A6 or less, A3 or more and A4 or less, A3 or more and A5 or less, or A3 or more and A6 or less.

[0057] "Restrain" means to hold back the realization or occurrence, etc., or to hinder the realization or occurrence, etc. "Restrain" means not only to completely prevent the realization or occurrence, etc., but also to reduce the possibility of the realization or occurrence, etc., or to make the realization or occurrence, etc., less likely to occur.

[0058] 1A to 12F are diagrams for explaining an embodiment of the present disclosure. The medical container set includes a first container, a second container, and an oxygen absorber. The first container containing a liquid agent includes the first container and a liquid agent L contained in the first container. The first container containing a liquid agent is also called a container containing a liquid agent or a medical container containing a liquid agent. The first container has oxygen permeability. Oxygen can pass through the first container. The first container includes at least a portion that is at least partially oxygen permeable. The second container has oxygen barrier properties. The second container has a storage space S capable of storing the first container containing a liquid agent. The combined medical container containing a liquid agent includes the first container containing a liquid agent and the second container, and the first container containing a liquid agent is stored in the second container.

[0059] In the combined medical container containing the liquid agent, the oxygen absorber absorbs oxygen in the second container. The oxygen absorber reduces the oxygen concentration (%) in the second container 40. When the oxygen concentration in the second container reduces, oxygen in the first container passes through the first container and moves from the first container to the second container. The movement of oxygen from the first container to the second container reduces the amount of oxygen in the first container. The oxygen absorber maintains the oxygen concentration (%) in the second container 40 in a reduced state. The amount of oxygen in the first container is maintained in a reduced state. As a result, the combined medical container containing the liquid agent can suppress deterioration of the liquid agent in the first container due to oxygen.

[0060] A liquid is a liquid medicine. A medicine is an object intended to be used for the diagnosis, treatment, or prevention of a disease in humans or animals, and is not a machine, device, or the like. A medicine may be one that can affect the structure or function of the body of a human or animal. A medicine includes pharmaceuticals defined in the Pharmaceutical Affairs Act of Japan or laws and systems of countries other than Japan. A liquid may include a medium liquid. A liquid may include a medicinal ingredient and a medium liquid. The medium liquid may be a medicinal ingredient. The medicinal ingredient may be an ingredient, compound, item, or the like that can affect the structure or function of the body of a human or animal. The medium liquid is a medium that disperses the medicinal ingredient. The medicinal ingredient may be dissolved in the medium liquid. The medicinal ingredient may not be dissolved in the medium liquid. The medium liquid may be a liquid. The medium liquid may be a dispersion medium. The dispersion medium may be a liquid containing a dispersoid that is a dispersed particle. The dispersion medium may include one or more of a sol, a gel, a suspension, and an emulsion.

[0061] The medium liquid may be water. The medium liquid may be physiological saline. The liquid preparation L may contain two or more types of medium liquids. The medium liquid may be an aqueous medium liquid. The aqueous medium liquid refers to a medium liquid whose main component with the largest volumetric ratio is water. The medium liquid may contain a non-aqueous medium liquid. The non-aqueous medium liquid refers to a medium liquid whose main component with the largest volumetric ratio is other than water. By using a non-aqueous medium liquid, hydrolysis of the medicinal ingredient can be suppressed. By using a non-aqueous medium liquid, stability can be imparted to the medicinal ingredient. Examples of medium liquids other than water include alcohols such as ethanol, polyethylene glycol, propylene glycol, glycerin, benzyl alcohol, N,N-dimethylacetamide, and the like. The medium liquid may contain water and polyethylene glycol, and the like.

[0062] The liquid L may contain one or more of a pH adjuster, a solubilizer, a stabilizer, a surfactant, an antifoaming agent, a dissolving agent, a solubilizing agent, a dispersing agent, a preservative, and the like.

[0063] The liquid L may be an RTU (Ready To Use) formulation or an RTD (Ready To Dilute) formulation. The liquid L as an RTU or RTD can omit preparation before application to a patient, and is easy to use. The liquid L may be an injectable administered to a patient by injection. Injectables include liquids used for drip infusion. The injection to which the liquid L is applied may be any of intravenous injection, intramuscular injection, and subcutaneous injection. The liquid L may be administered by injection into a blood vessel, intraperitoneum, submeningeal space, intraventricular space, urethra, sternum, intracranial space, etc.

[0064] A liquid medicine can be usually distributed in a state where it is contained in a vial or a syringe. Vials and syringes are widely used in medical fields because they are easy to use. Vials and syringes containing a small amount of liquid medicine are particularly excellent in terms of handling the liquid medicine. For example, a liquid medicine contained in a syringe can be used by a patient or the like as it is without requiring any special preparation. The liquid medicine in the vial is transferred into the syringe by piercing the rubber stopper of the vial with the needle of the syringe, and is then used by a patient or the like.

[0065] Pharmaceutical ingredients are susceptible to deterioration due to deterioration caused by oxygen. For liquids contained in small amounts in vials, syringes, etc., even slight deterioration can have a significant effect on the quality of the liquid. Pharmaceutical ingredients contained in liquids are affected not only by gaseous oxygen in the container, but also by oxygen dissolved in the medium liquid. Pharmaceutical ingredients that are susceptible to deterioration may be handled in powder form by freeze-drying. Powdered pharmaceutical ingredients are less likely to deteriorate. However, powdered pharmaceutical ingredients must be mixed with a medium liquid to make a liquid of a predetermined concentration before application to a patient. This operation also lengthens the preparation time until the drug is administered to a patient. In other words, pharmaceutical ingredients are preferably handled as liquids contained in vials or syringes.

[0066] In this context, from the viewpoint of suppressing oxygen deterioration of the liquid L, application of a medical container set including a first container, a second container, and an oxygen absorber to the liquid was considered. In other words, handling of the liquid L using a combined medical container containing the liquid was considered.

[0067] Compared with foods, etc., medicinal ingredients are more susceptible to oxygen degradation. In addition, the range of permissible deterioration of medicinal ingredients due to oxygen, etc. is significantly narrower than that of foods, etc. From these points of view, the first container should be given very high oxygen permeability. However, as oxygen passes through the first container and moves to the second container, the liquid medium may evaporate. When oxygen can pass through the first container, other gases including the vapor of the liquid medium, such as water vapor, can also pass through the first container. That is, water vapor generated by the evaporation of the liquid medium can also pass through the first container and move to the second container.

[0068] When the amount of the medium in the liquid formulation decreases in the first container, the concentration of the medicinal ingredient in the liquid formulation and the hydrogen ion concentration (pH) of the liquid formulation change, which may lead to a deterioration in the quality of the medicinal ingredient contained in the liquid formulation.

[0069] Usually, the concentration of a pharmaceutical ingredient in a liquid is strictly controlled. A change in the concentration of a pharmaceutical ingredient in a liquid can cause the pharmaceutical ingredient to deteriorate. If the hydrogen ion concentration of a liquid changes, the decomposition and solubility of the pharmaceutical ingredient may change, and the structure of the pharmaceutical ingredient may also change. In other words, it may be possible that the expected efficacy of the pharmaceutical ingredient is not obtained. In addition, the administration conditions of a liquid are determined based on a predetermined controlled concentration. Therefore, for a liquid whose concentration has changed, it is necessary to measure the concentration and review the administration conditions.

[0070] Furthermore, when the liquid preparation contains a non-aqueous medium, water vapor in the second container may migrate into the first container, and in this case, the medicinal ingredient dispersed in the non-aqueous solvent may be hydrolyzed by the water that has migrated into the first container.

[0071] The deterioration of the liquid due to water vapor permeation is remarkable when only a small amount of the liquid is contained in the first container. Therefore, when a vial or a syringe is used as the first container, the small amount of the liquid contained in the first container is easily deteriorated in quality. That is, for a liquid contained in a small amount in a vial or a syringe, even a slight deterioration can have a significant effect on the quality of the liquid.

[0072] The inventors' study above has revealed that there are problems specific to liquid medicines that are not a problem with food products, etc., when using a combination container including a first container, a second container, and an oxygen absorber. In particular, when attempting to more effectively suppress oxygen degradation of a liquid medicine by imparting high oxygen permeability to the first container that contains a liquid medicine that is prone to oxygen degradation and promoting oxygen permeation, the quality deterioration of the liquid medicine due to water vapor permeation becomes more pronounced. Therefore, in order to handle a liquid medicine as a liquid-containing combination medical container by applying a combination container to the liquid medicine, it is necessary to address two problems, namely, suppression of deterioration caused by oxygen and suppression of deterioration caused by water vapor, which are conflicting solutions. In other words, in a combination medical container that is applied to a liquid medicine, it is necessary to impart to the first container that contains the liquid medicine the normally conflicting properties of promoting oxygen permeation and suppressing water vapor permeation.

[0073] Through repeated intensive research aimed at solving such problems, it has been found that it is possible to impart a permeability characteristic capable of sufficiently promoting the permeation of oxygen and sufficiently suppressing the permeation of water vapor to the stopper included in the first container, and further, that the quality deterioration of the liquid medicine can be suppressed by using the stopper provided with such permeability. The first embodiment is based on such findings.

[0074] More specifically, in the first embodiment, the first container includes a container body having an opening and a plug for closing the opening. The first oxygen permeability of the material constituting the plug is 0.00010(cc×mm / (mm 2 The first water vapor permeability of the material constituting the stopper is 1.0 (mg×mm / (mm 2 ×day) or less.

[0075] According to the medical container set and the combined medical container containing the liquid according to the first embodiment, the first oxygen permeability promotes oxygen permeation of the first container. That is, the transfer of oxygen from the first container to the second container maintained in a hypoxic state by the oxygen absorbent is promoted. This reduces the oxygen concentration (%) in the first container, and the amount of oxygen dissolved in the liquid (mg / L) decreases. Therefore, deterioration of the liquid L due to oxygen can be suppressed. In addition, the first water vapor permeability suppresses water vapor permeation of the first container. This suppresses changes in the concentration and hydrogen ion concentration of the medicinal ingredient in the liquid L using the aqueous medium. Hydrolysis of the medicinal ingredient dispersed in the non-aqueous medium can be suppressed. That is, according to the first embodiment, both oxygen deterioration of the liquid L and quality deterioration of the liquid L caused by water vapor permeation can be stably suppressed.

[0076] In the first embodiment, the stopper is provided with a first oxygen permeability and a first water vapor permeability within a predetermined range, and therefore, by observing the state of the stopper when handling the first container, for example by making the stopper observable from the transparent second container, the quality of the liquid-containing combination medical container can be stably managed.

[0077] Furthermore, as a result of extensive investigations, it has been found that it is possible to impart a first oxygen permeability and a first water vapor permeability within a predetermined range to a stopper, and at the same time, to impart properties suitable for use as a medical container to the stopper. As an example, stoppers used for medical containers are required to have a high level of sealing, suitability for puncture with an injection needle, and temperature resistance in consideration of heat sterilization of the stopper and refrigerated storage of liquid medicine. It has been found that it is possible to impart these properties required for a stopper for a medical container, as well as a first oxygen permeability and a first water vapor permeability within a predetermined range to the stopper.

[0078] In the first embodiment, since the stopper has a predetermined permeability, it is not necessary to adjust the permeability of the container body of the first container. Therefore, as the container body 32, a container body that has been widely used as a medical container and has a high reliability can be used. This allows the quality of the combined medical container containing the liquid agent to be more stably managed.

[0079] On the other hand, it has been found that the deterioration of the quality of the liquid formulation can be suppressed by the first container having a second oxygen permeability within a predetermined range and a second water vapor permeability within a predetermined range as a whole. The second embodiment is based on such a finding.

[0080] More specifically, in the second embodiment, the first container has the following permeability: The second oxygen permeability of the first container is 0.010 (cc / day) or more at a temperature of 23° C. and a humidity of 50% RH. The second water vapor permeability of the first container is 20 (mg / day) or less at a temperature of 40° C. and a humidity of 90% RH.

[0081] According to the medical container set and the combined medical container containing the liquid according to the second embodiment, the second oxygen permeability promotes oxygen permeation of the first container. That is, the transfer of oxygen from the first container to the second container maintained in a hypoxic state by the oxygen absorbent is promoted. This reduces the oxygen concentration (%) in the first container, and the amount of oxygen dissolved in the liquid (mg / L) decreases. Therefore, deterioration of the liquid L due to oxygen can be suppressed. In addition, the second water vapor permeability suppresses water vapor permeation of the first container. This suppresses changes in concentration of the medicinal ingredient and changes in hydrogen ion concentration in the liquid using an aqueous medium. Hydrolysis of the medicinal ingredient dispersed in the non-aqueous medium can be suppressed. That is, the second embodiment also suppresses both oxygen deterioration of the liquid L and quality deterioration of the liquid L caused by water vapor permeation.

[0082] In the first embodiment, the material constituting the stopper may have a first oxygen permeability and a first water vapor permeability, and the first container including the stopper may have a second oxygen permeability. In the first embodiment, the material constituting the stopper may have a first oxygen permeability and a first water vapor permeability, and the first container including the stopper may have a second water vapor permeability. In the first embodiment, the material constituting the stopper may have a first oxygen permeability and a first water vapor permeability, and the first container including the stopper may have a second oxygen permeability and a second water vapor permeability.

[0083] Hereinafter, the first and second embodiments will be described in detail with reference to a specific example shown in Figures 1A and 1B. Figure 1A is a front view showing a specific example of a combined medical container 10L containing a liquid agent. Figure 1B is a vertical cross-sectional view showing the combined medical container 10L containing a liquid agent shown in Figure 1A.

[0084] As described above, the first container 30L containing the liquid agent includes the first container 30 and the liquid agent L contained in the first container 30. The first container 30 has oxygen permeability. The first container 30 can seal the liquid agent L. The first container 30 is permeable to oxygen but not permeable to the liquid agent L.

[0085] The first container 30 may further be an airtight container. Airtight means a container from which no gas leakage is detected by the liquid immersion method specified in JIS Z2330:2012. More specifically, a container that can prevent air bubbles from leaking when the container containing gas is immersed in water is judged to be an airtight container. Also, an airtight container is judged to be in an airtight state when no air bubbles are confirmed to leak from the container when the container containing gas is immersed in water. In the liquid immersion test, the container to be tested is immersed to a depth of 10 cm to 30 cm below the water surface. The presence or absence of air bubbles is judged by visual observation for 10 minutes.

[0086] The inside of the first container 30 may be in a sterile state. The liquid L may be a liquid that should be maintained in a sterile state. The liquid L that should be maintained in a sterile state may be highly sensitive. A highly sensitive liquid L is easily deteriorated by post-sterilization (also called final sterilization) performed after production. Post-sterilization cannot be applied to a highly sensitive liquid. Examples of post-sterilization include high-pressure steam, dry heat, radiation, ethylene oxide gas, and hydrogen peroxide gas plasma. A highly sensitive liquid L means a liquid in which 5% or more of the total pharmaceutical ingredients contained in the liquid L are decomposed by post-sterilization of the liquid L, and one or more active ingredients contained in the liquid L are decomposed by 1% or more by weight by post-sterilization of the liquid L. A highly sensitive liquid L to which post-sterilization cannot be applied may be manufactured using a manufacturing line arranged in a sterile environment. That is, a highly sensitive liquid L may be manufactured by an aseptic operation method. Examples of highly sensitive liquid agents L include anticancer agents, antiviral agents, vaccines, and antipsychotics.

[0087] In order to adjust the amount of oxygen in the liquid L produced by a sterile operation method, the entire space in which the production line for the liquid L is arranged may be replaced with an inert gas. However, filling the entire space in which the production line for the liquid L is arranged with an inert gas atmosphere requires a huge investment in equipment and may cause safety concerns for workers. In view of the above, the adjustment of the amount of oxygen in the liquid L has generally been entrusted to replacing the atmosphere in the first container containing the liquid L with an inert gas or bubbling the liquid L with an inert gas. In contrast, according to the liquid-containing combination medical container 10L, the amount of oxygen in the liquid-containing first container 30L can be reduced by housing the liquid-containing first container 30L in the second container 40.

[0088] The term "sterile state" used in this specification includes products (liquid L) labeled as "sterile" or "aseptic" and the inside of containers that contain such products, as well as pharmaceutical products (liquid L) and the inside of containers that contain such products, for which "aseptic" is a condition for commercialization.-6 A product (liquid L) that satisfies the above conditions and the inside of a container that contains the product also fall under the "sterile state" used in this specification. A product in which bacteria do not grow when stored for four weeks at a temperature above room temperature (e.g., 20°C) and the inside of a container that contains the product also fall under the "sterile state" used in this specification. A product in which bacteria do not grow when stored for eight weeks or more in a refrigerated state (e.g., below 8°C) and the inside of a container that contains the product also fall under the "sterile state" used in this specification. A drug in which bacteria do not grow when stored for two weeks at a temperature between 28°C and 32°C and the inside of a container that contains the drug also fall under the "sterile state" used in this specification.

[0089] 1C , the first container 30 may include a container body 32 and a stopper 34. The container body 32 includes an opening 33. The stopper 34 may be held in the opening 33. The stopper 34 closes the opening 33. The stopper 34 regulates leakage of the liquid agent L from the opening 33. The stopper 34 may close the opening 33 in an airtight manner.

[0090] The plug 34 is not particularly limited and may have various configurations. In the example shown in FIG. 1C, the plug 34 is inserted into the opening 33 of the container body 32 to close the opening 33. The plug 34 shown in FIG. 1C includes a plate-shaped plate portion 34a and an insertion protrusion 34b extending from the plate portion 34a. The insertion protrusion 34b may be tubular. The insertion protrusion 34b is, for example, cylindrical. A plurality of insertion protrusions 34b may be provided on a circumference. The insertion protrusion 34b is inserted into the opening 33. The plate portion 34a includes a flange portion extending radially outward from the insertion protrusion 34b. The flange portion of the plate portion 34a is placed on the head 32d of the container body 32. The plug 34 may include an outer spiral or an inner spiral. The plug 34 may be attached to the container body 32 by the meshing of the spirals.

[0091] The inventors of the present invention have discovered that the plug 34 having the function of closing the opening can be imparted with a specified first oxygen permeability and a specified first water vapor permeability by, for example, modifying the material or manufacturing conditions.

[0092] The first oxygen permeability of the material constituting the plug 34 is 0.00010(cc×mm / (mm 2 ×day)) or more, and 2 × day)) or more, and 0.00075 (cc × mm / (mm 2 × day)) or more, and 0.0010(cc×mm / (mm 2 × day)) or more, and 0.0020 (cc × mm / (mm 2 × day)) or more, and 0.0050 (cc × mm / (mm 2 × day)) or more, and 0.010(cc×mm / (mm 2 ×day)) or more, and 0.025(cc×mm / (mm 2 × day)) or more, and 0.027(cc×mm / (mm 2 × day)) or more, and 0.050 (cc × mm / (mm 2 × day)) or more, and 0.057(cc×mm / (mm 2 × day)) or more, and 0.076 (cc × mm / (mm 2 × day)) or more, and 0.082 (cc × mm / (mm 2 ×day)) or more. The first oxygen permeability is a characteristic at a temperature of 23°C and a humidity of 50% RH. By setting the lower limit of the first oxygen permeability of the material constituting the stopper 34 in this manner, oxygen permeation through the first container 30 can be sufficiently promoted and oxygen deterioration of the liquid agent L can be suppressed. The first oxygen permeability is 10(cc×mm / (mm 2 × day)) or less, and 5.0 (cc × mm / (mm 2 × day)) or less, and 1.0 (cc × mm / (mm 2 ×day) or less is also acceptable.

[0093] In the case where the plug 34 is composed of multiple layers of different materials, the permeability of the material that substantially determines the permeability of the entire plug means the permeability of the material that constitutes the plug 34. In the case where there is no material that substantially determines the permeability of the entire plug, the permeability of the material that constitutes the plug 34 means the permeability of the material that constitutes the layer with the largest volume ratio among the multiple layers.

[0094] The first oxygen permeability of the material constituting the plug 34 is 0.00010(cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day)) or less, and 0.00010(cc×mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day)) or less, and 0.00010(cc×mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2 The first oxygen permeability of the material constituting the plug 34 may be 0.00050 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day)) or less, and 0.00050 (cc × mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day)) or less, and 0.00050 (cc × mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2 The first oxygen permeability of the material constituting the plug 34 may be 0.00075 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day) or less, and 0.00075 (cc × mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day) or less, and 0.00075 (cc × mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2 The first oxygen permeability of the material constituting the plug 34 may be 0.0010 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day) or less, and 0.0010(cc×mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day) or less, and 0.0010(cc×mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2The first oxygen permeability of the material constituting the plug 34 may be 0.0020 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day) or less, and 0.0020 (cc × mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day) or less, and 0.0020 (cc × mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2 The first oxygen permeability of the material constituting the plug 34 may be 0.0020 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day) or less, and 0.0020 (cc × mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day) or less, and 0.0020 (cc × mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2 The first oxygen permeability of the material constituting the plug 34 may be 0.0050 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day) or less, and 0.0050(cc×mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day) or less, and 0.0050(cc×mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2 The first oxygen permeability of the material constituting the plug 34 may be 0.010 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day) or less, and 0.010(cc×mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day) or less, and 0.010(cc×mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2The first oxygen permeability of the material constituting the plug 34 may be 0.025 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day) or less, and 0.025(cc×mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day) or less, and 0.025(cc×mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2 The first oxygen permeability of the material constituting the plug 34 may be 0.027 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day) or less, and 0.027(cc×mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day) or less, and 0.027(cc×mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2 The first oxygen permeability of the material constituting the plug 34 may be 0.050 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day)) or less, and 0.050(cc×mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day)) or less, and 0.050(cc×mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2 The first oxygen permeability of the material constituting the plug 34 may be 0.057 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day)) or less, and 0.057 (cc × mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day)) or less, and 0.057 (cc × mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2The first oxygen permeability of the material constituting the plug 34 may be 0.076 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day) or less, and 0.076(cc×mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day) or less, and 0.076(cc×mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2 The first oxygen permeability of the material constituting the plug 34 may be 0.082 (cc×mm / (mm 2 ×day)) or more 10(cc×mm / (mm 2 × day)) or less, and 0.082 (cc × mm / (mm 2 ×day)) or more 5.0(cc×mm / (mm 2 × day)) or less, and 0.082 (cc × mm / (mm 2 ×day)) or more 1.0(cc×mm / (mm 2 ×day) or less is also acceptable.

[0095] The first oxygen permeability is a characteristic related to oxygen permeation depending on the material. The first oxygen permeability represents the volume of oxygen that permeates a measurement object of unit thickness and unit area per unit time, which divides an area where oxygen is substantially absent from an area where oxygen-containing air is present. The unit length is 1 mm. The unit area is 1 mm. 2 The unit of time is 1 day = 24 hours. The unit of oxygen volume is "cc."

[0096] As shown in FIG. 2A, the first oxygen permeability is measured using a test container 70 including a test sheet 30X. The test sheet 30X is made of a material to be measured. The test sheet 30X is produced by cutting the thickness of the plug 34 to be measured so that the region facing the through hole 72A described below has a certain thickness. The thickness of the region facing the through hole 72A of the test sheet 30X is set to 1.0 mm. For a measurement target in which a thickness of 1.0 mm cannot be secured in the region facing the through hole 72A, the test sheet 30X is produced so that the maximum thickness is obtained in that region.

[0097] The test container 70 includes a partition wall 71. The test container 70 includes an internal space partitioned by the partition wall 71 and the test sheet 30X. The partition wall 71 includes a main wall 72 having oxygen barrier properties. The main wall 72 has a through hole 72A. The test sheet 30X faces the through hole 72A. The through hole 72A is closed by the test sheet 30X. The peripheral portion of the test sheet 30X is airtightly joined to the peripheral portion of the through hole 72A of the main wall 72 via a barrier bonding material 73 having oxygen barrier properties.

[0098] The oxygen concentration in the test container 70 is adjusted to 0.05% or less. That is, there is substantially no oxygen in the test container 70. The test container 70 is connected to a first flow path 71A and a second flow path 71B. The second flow path 71B is connected to an oxygen measuring device 74 that measures the amount of oxygen. The oxygen measuring device 74 can measure the amount of oxygen (cc) flowing through the second flow path 71B. The oxygen measuring device 74 is an oxygen amount measuring device built into OXTRAN (2 / 61) manufactured by MOCON, USA. The first flow path 71A supplies a gas that does not contain oxygen into the test container 70. The first flow path 71A supplies nitrogen. The second flow path 71B exhausts the gas in the test container 70. The first flow path 71A and the second flow path 71B have oxygen barrier properties. The first flow path 71A and the second flow path 71B maintain the test container 70 in a state where there is substantially no oxygen.

[0099] The test container 70 is placed in a test atmosphere at a temperature of 23°C and a humidity of 50% RH. The test atmosphere is an air atmosphere under atmospheric pressure. The oxygen concentration of the test atmosphere is 20.95%. When the test container 70 is placed in the test atmosphere, oxygen moves from the test atmosphere into the test container 70 through the test sheet 30X. The gas in the test container 70 is discharged from the second flow path 71B. By measuring the amount of oxygen flowing through the second flow path 71B with the oxygen measuring device 74, the daily oxygen transmission amount (cc / day) through the test sheet 30X in an atmosphere at a temperature of 23°C and a humidity of 50% RH can be measured. The measured daily oxygen transmission amount is calculated based on the opening area (mm 2 ) and then multiplying it by the thickness (mm) of the test sheet 30X to obtain the first oxygen permeability (cc×mm / (mm 2 The thickness (mm) of the test sheet 30X is determined as the average value of the thicknesses of the test sheet 30X measured at five measurement points in the portion facing the through hole 72A.

[0100] As shown in FIG. 2A, the test container 70 is placed in a test chamber 75. The atmosphere in the test chamber 75 is adjusted to a temperature of 23° C. and a humidity of 50% RH. The atmosphere in the test chamber 75 is an air atmosphere under atmospheric pressure. Air is supplied into the test chamber 75 from a supply path 75A. Gas in the test chamber 75 is exhausted from an exhaust path 75B. Air is circulated by the supply path 75A and the exhaust path 75B, and the oxygen concentration in the test chamber 75 is maintained at 20.95%.

[0101] In the example shown in Fig. 2A, a pump for circulating air may be provided in one of the supply path 75A and the exhaust path 75B. If the oxygen concentration in the test chamber 75 can be maintained the same as in the air atmosphere, the supply path 75A and the exhaust path 75B shown in Fig. 2A may be open to the air atmosphere under atmospheric pressure.

[0102] The first water vapor permeability of the material constituting the plug 34 is 1.0 (mg×mm / (mm 2 × day)) or less, and 2× day)) or less, and 0.60 (mg × mm / (mm 2 × day)) or less, and 0.45 (mg × mm / (mm 2 × day)) or less, and 0.41 (mg × mm / (mm 2 × day)) or less, and 0.25 (mg × mm / (mm 2 × day) or less, and 0.15 (mg × mm / (mm 2 × day) or less, and 0.11 (mg × mm / (mm 2 × day) or less, and 0.10 (mg × mm / (mm 2 ×day) or less. The first water vapor permeability is a characteristic at a temperature of 40°C and a humidity of 90% RH. By setting the upper limit of the first water vapor permeability of the material constituting the stopper 34 in this manner, water vapor permeation of the first container 30 can be sufficiently suppressed, and deterioration of the quality of the liquid agent L due to water vapor permeation can be suppressed. The first water vapor permeability is 0.0010(mg×mm / (mm 2 × day)) or more, and 0.0050 (mg × mm / (mm 2 × day)) or more, and 0.010 (mg × mm / (mm 2 ×day) or more is acceptable.

[0103] The first water vapor permeability of the material constituting the plug 34 is 0.0010 (mg×mm / (mm 2 ×day)) or more 1.0(mg×mm / (mm 2 × day) or less, and may be 0.0010 (mg × mm / (mm 2 ×day)) or more 0.80(mg×mm / (mm) 2 × day) or less, and may be 0.0010 (mg × mm / (mm 2 ×day)) or more 0.60(mg×mm / (mm 2 × day) or less, and may be 0.0010 (mg × mm / (mm 2 ×day)) or more 0.45(mg×mm / (mm) 2 × day) or less, and may be 0.0010 (mg × mm / (mm 2 ×day)) or more 0.41(mg×mm / (mm) 2× day) or less, and may be 0.0010 (mg × mm / (mm 2 ×day)) or more 0.25(mg×mm / (mm) 2 × day) or less, and may be 0.0010 (mg × mm / (mm 2 ×day)) or more 0.15(mg×mm / (mm) 2 × day) or less, and may be 0.0010 (mg × mm / (mm 2 ×day)) or more 0.11(mg×mm / (mm 2 × day) or less, and may be 0.0010 (mg × mm / (mm 2 ×day)) or more 0.10(mg×mm / (mm 2 The first water vapor permeability of the material constituting the plug 34 may be 0.0050 (mg×mm / (mm 2 ×day)) or more 1.0(mg×mm / (mm 2 × day) or less, and may be 0.0050 (mg × mm / (mm 2 ×day)) or more 0.80(mg×mm / (mm) 2 × day) or less, and may be 0.0050 (mg × mm / (mm 2 ×day)) or more 0.60(mg×mm / (mm 2 × day) or less, and may be 0.0050 (mg × mm / (mm 2 ×day)) or more 0.45(mg×mm / (mm) 2 × day) or less, and may be 0.0050 (mg × mm / (mm 2 ×day)) or more 0.41(mg×mm / (mm) 2 × day) or less, and may be 0.0050 (mg × mm / (mm 2 ×day)) or more 0.25(mg×mm / (mm) 2 × day) or less, and may be 0.0050 (mg × mm / (mm 2 ×day)) or more 0.15(mg×mm / (mm) 2 × day) or less, and may be 0.0050 (mg × mm / (mm 2 ×day)) or more 0.11(mg×mm / (mm 2 × day) or less, and may be 0.0050 (mg × mm / (mm 2×day)) or more 0.10(mg×mm / (mm 2 The first water vapor permeability of the material constituting the plug 34 may be 0.010 (mg×mm / (mm 2 ×day)) or more 1.0(mg×mm / (mm 2 × day) or less, and may be 0.010 (mg × mm / (mm 2 ×day)) or more 0.80(mg×mm / (mm) 2 × day) or less, and may be 0.010 (mg × mm / (mm 2 ×day)) or more 0.60(mg×mm / (mm 2 × day) or less, and may be 0.010 (mg × mm / (mm 2 ×day)) or more 0.45(mg×mm / (mm) 2 × day) or less, and may be 0.010 (mg × mm / (mm 2 ×day)) or more 0.41(mg×mm / (mm) 2 × day) or less, and may be 0.010 (mg × mm / (mm 2 ×day)) or more 0.25(mg×mm / (mm) 2 × day) or less, and may be 0.010 (mg × mm / (mm 2 ×day)) or more 0.15(mg×mm / (mm) 2 × day) or less, and may be 0.010 (mg × mm / (mm 2 ×day)) or more 0.11(mg×mm / (mm 2 × day) or less, and may be 0.010 (mg × mm / (mm 2 ×day)) or more 0.10(mg×mm / (mm 2 ×day) or less is also acceptable.

[0104] The first water vapor permeability is a characteristic related to water vapor permeation depending on the material. The first water vapor permeability represents the volume of water vapor that permeates a measurement object of unit thickness and unit area per unit time, which divides an area where water vapor is substantially absent from an area where air containing water vapor is present. The unit length is 1 mm. The unit area is 1 mm. 2 The unit of time is 1 day = 24 hours. The volume of water vapor is expressed in mg.

[0105] As shown in FIG. 2B, the first water vapor permeability is measured using a test container 77 including a test sheet 30Y. The test sheet 30Y is made of a material to be measured. The test sheet 30Y is prepared by shaving the thickness of the plug 34 to be measured so that the area facing the opening 78A described below has a certain thickness. The thickness of the area facing the opening 78A of the test sheet 30Y is set to 1.0 mm. For a measurement object in which a thickness of 1.0 mm cannot be secured in the area facing the opening 78A, the test sheet 30Y is prepared so that the maximum thickness is obtained in that area.

[0106] The test container 77 includes a test container 78. The test container 78 is a container having an opening 78A. The test sheet 30Y faces the opening 78A. The opening 78A is closed by the test sheet 30Y. The peripheral portion of the test sheet 30Y is airtightly joined to the peripheral portion of the opening 78A of the test container 78 via a barrier bonding material 73 having water vapor barrier properties. With reference to the provisions of JIS Z0208-1976, the mass of calcium chloride 79 is determined so that the test is completed before calcium chloride 79 absorbs moisture of 10% of its mass. When the volume of the test container 77 is 1 mL or more and 50 mL or less, about 10 g of calcium chloride is usually accommodated in the test container 77. By setting the mass of calcium chloride in this manner, water vapor that has permeated the test sheet 30Y is absorbed, and the test container 77 can be maintained in a state where water vapor is substantially absent.

[0107] The test container 77 is placed in a test atmosphere adjusted to a temperature of 40° C. and a humidity of 90% RH. The test atmosphere is an air atmosphere under atmospheric pressure. When the test container 77 is placed in the test atmosphere, water vapor moves from the test atmosphere into the test container 77 through the test sheet 30Y. In the test container 77, the water vapor is absorbed as moisture by calcium chloride 79. By measuring the weight increase of the test container 77, the amount of water vapor permeated (mg) through the test sheet 30Y in an atmosphere of a temperature of 40° C. and a humidity of 90% RH can be measured. Water vapor may be present in the test container 77 immediately after the test container 77 is closed by blocking the opening 78A of the test storage section 78 with the test sheet 30Y. In order to eliminate the influence of water vapor, the weight of the test container 77 after one day has elapsed since the test container 77 was closed and the weight of the test container 77 after 11 days have elapsed since the test container 77 was closed are divided by 10 (days) to measure the amount of water vapor permeating through the test sheet 30Y in one day (mg / day). The measured amount of water vapor permeating per day was multiplied by the opening area (mm 2 ) and then multiplied by the thickness (mm) of the test sheet 30Y to obtain the first oxygen permeability (cc×mm / (mm 2 The thickness (mm) of the test sheet 30Y is determined as the average value of the thicknesses of the test sheet 30Y measured at five measurement points in the region facing the through hole 72A.

[0108] As shown in FIG. 2B, the test container 77 is placed in the test chamber 75. The atmosphere in the test chamber 75 is adjusted to a temperature of 40° C. and a humidity of 90% RH. The atmosphere in the test chamber 75 is an air atmosphere under atmospheric pressure. Air is supplied into the test chamber 75 from a supply path 75A. The gas in the test chamber 75 is exhausted from an exhaust path 75B. The test chamber 75 is maintained at a test atmosphere by the supply path 75A and the exhaust path 75B.

[0109] The average thickness of the portion of plug 34 having the above-mentioned first oxygen permeability and first water vapor permeability facing opening 33 may be 0.50 mm or more, 0.70 mm or more, 1.0 mm or more, 1.5 mm or more, or 2.0 mm or more. The average thickness of the portion of plug 34 facing opening 33 may be 10 mm or less, 8.0 mm or less, 6.0 mm or less, or 5.0 mm or less.

[0110] The average thickness of the portion of the plug 34 facing the opening 33 may be 0.50 mm or more and 10 mm or less, 0.50 mm or more and 8.0 mm or less, 0.50 mm or more and 6.0 mm or less, or 0.50 mm or more and 5.0 mm or less. The average thickness of the portion of the plug 34 facing the opening 33 may be 0.70 mm or more and 10 mm or less, 0.70 mm or more and 8.0 mm or less, 0.70 mm or more and 6.0 mm or less, or 0.70 mm or more and 5.0 mm or less. The average thickness of the portion of the plug 34 facing the opening 33 may be 1.0 mm or more and 10 mm or less, 1.0 mm or more and 8.0 mm or less, 1.0 mm or more and 6.0 mm or less, or 1.0 mm or more and 5.0 mm or less. The average thickness of the portion of plug 34 facing opening 33 may be 1.50 mm or more and 10 mm or less, 1.50 mm or more and 8.0 mm or less, 1.50 mm or more and 6.0 mm or less, or 1.50 mm or more and 5.0 mm or less. The average thickness of the portion of plug 34 facing opening 33 may be 2.0 mm or more and 10 mm or less, 2.0 mm or more and 8.0 mm or less, 2.0 mm or more and 6.0 mm or less, or 2.0 mm or more and 5.0 mm or less.

[0111] The average thickness of the portion of the plug 34 facing the opening 33 refers to the average thickness, along the direction DA, of the portion of the plug that overlaps with the opening 33 along the direction DA in which the plug 34 is inserted into the opening 33, as shown in FIG. 1C. Therefore, the portion of the plug 34 facing the opening 33 includes the portion of the plug 34 facing the opening 33 along the direction DA and the portion of the plug 34 located within the opening 33. When the plug 34 having the above-mentioned first oxygen permeability and first water vapor permeability has an average thickness in such a range in the portion facing the opening 33, the oxygen permeation of the first container 30 can be sufficiently promoted and the water vapor permeation of the first container 30 can be sufficiently suppressed. This makes it possible to sufficiently suppress both the quality deterioration of the liquid agent L caused by oxygen permeation and the quality deterioration of the liquid agent L caused by water vapor permeation.

[0112] When the average thickness of the portion of plug 34 overlapping opening 33 is not constant, the average thickness of the portion of plug 34 facing opening 33 is determined by the following method. (1) The density of the plug (g / mm 3 ) is measured. (2) Cut out the part facing the opening of the stopper and measure the weight (g) of the part facing the opening of the stopper. (3) The weight (g) of the part facing the opening of the plug is multiplied by the density (g / mm 3 ) to obtain the volume (mm 3 ) is calculated. (4) Area of ​​the opening of the container body (mm 2 ) and the volume (mm 3 ) to the area of ​​the opening (mm 2 ) to obtain the average thickness (mm) of the part facing the plug opening.

[0113] When the first container 30 is a vial, the opening area of ​​the opening 33 of the container body 32 is 25 mm 2 More than 50mm is fine. 2 More than 100mm is fine. 2 More than 150mm is fine. 2When the first container 30 is a vial, the opening area of ​​the opening 33 of the container body 32 is 1000 mm 2 Less than 800mm is also acceptable. 2 Less than 500mm is also acceptable. 2 Less than 400mm is also acceptable. 2 Less than 300mm is also acceptable. 2 Less than 200mm is fine. 2 The following is also fine.

[0114] When the first container 30 is a vial, the opening area of ​​the opening 33 of the container body 32 may be set as follows: 2 More than 1000mm 2 Less than 25mm is fine. 2 More than 800mm 2 Less than 25mm is fine. 2 More than 500mm 2 Less than 25mm is fine. 2 More than 400mm 2 Less than 25mm is fine. 2 More than 300mm 2 Less than 25mm is fine. 2 More than 200mm 2 The opening area of ​​the opening 33 may be 50 mm 2 More than 1000mm 2 Less than 50mm is fine. 2 More than 800mm 2 Less than 50mm is fine. 2 More than 500mm 2 Less than 50mm is fine. 2 More than 400mm 2 Less than 50mm is fine. 2 More than 300mm 2 Less than 50mm is fine. 2 More than 200mm 2 The opening area of ​​the opening 33 may be 100 mm 2 More than 1000mm 2 Less than 100mm is fine. 2 More than 800mm 2 Less than 100mm is fine. 2 More than 500mm 2 Less than 100mm is fine.2 More than 400mm 2 Less than 100mm is fine. 2 More than 300mm 2 Less than 100mm is fine. 2 More than 200mm 2 The opening area of ​​the opening 33 may be 150 mm 2 More than 1000mm 2 Less than 150mm is fine. 2 More than 800mm 2 Less than 150mm is fine. 2 More than 500mm 2 Less than 150mm is fine. 2 More than 400mm 2 Less than 150mm is fine. 2 More than 300mm 2 Less than 150mm is fine. 2 More than 200mm 2 The following is also fine.

[0115] When the first container 30 is a syringe, the opening area of ​​the opening 33 of the container body 32 is 0.50 mm 2 More than 1.0mm is acceptable. 2 More than 5.0mm is acceptable. 2 More than 25mm is fine. 2 More than 50mm is fine. 2 More than 100mm is fine. 2 When the first container 30 is a syringe, the opening area of ​​the opening 33 of the container body 32 is 800 mm 2 Less than 500mm is also acceptable. 2 Less than 400mm is also acceptable. 2 Less than 300mm is also acceptable. 2 Less than 200mm is fine. 2 The following is also fine.

[0116] When the first container 30 is a syringe, the opening area of ​​the opening 33 of the container body 32 may be set as follows: 2 More than 800mm 2 Less than 0.50mm is acceptable. 2 More than 500mm 2 Less than 0.50mm is acceptable.2 More than 400mm 2 Less than 0.50mm is acceptable. 2 More than 300mm 2 Less than 0.50mm is acceptable. 2 More than 200mm 2 The opening area of ​​the opening 33 may be 1.0 mm 2 More than 800mm 2 Less than 1.0mm is acceptable. 2 More than 500mm 2 Less than 1.0mm is acceptable. 2 More than 400mm 2 Less than 1.0mm is acceptable. 2 More than 300mm 2 Less than 1.0mm is acceptable. 2 More than 200mm 2 The opening area of ​​the opening 33 may be 5.0 mm 2 More than 800mm 2 Less than 5.0mm is acceptable. 2 More than 500mm 2 Less than 5.0mm is acceptable. 2 More than 400mm 2 Less than 5.0mm is acceptable. 2 More than 300mm 2 Less than 5.0mm is acceptable. 2 More than 200mm 2 The opening area of ​​the opening 33 may be 25 mm 2 More than 800mm 2 Less than 25mm is fine. 2 More than 500mm 2 Less than 25mm is fine. 2 More than 400mm 2 Less than 25mm is fine. 2 More than 300mm 2 Less than 25mm is fine. 2 More than 200mm 2 The opening area of ​​the opening 33 may be 50 mm 2 More than 800mm 2 Less than 50mm is fine. 2 More than 500mm 2 Less than 50mm is fine. 2 More than 400mm 2 Less than 50mm is fine. 2More than 300mm 2 Less than 50mm is fine. 2 More than 200mm 2 The opening area of ​​the opening 33 may be 100 mm 2 More than 800mm 2 Less than 100mm is fine. 2 More than 500mm 2 Less than 100mm is fine. 2 More than 400mm 2 Less than 100mm is fine. 2 More than 300mm 2 Less than 100mm is fine. 2 More than 200mm 2 The following is also fine.

[0117] By having the opening 33 closed by the plug 34 having the above-mentioned first oxygen permeability and first water vapor permeability in such an area range, oxygen permeation of the first container 30 can be sufficiently promoted and water vapor permeation of the first container 30 can be sufficiently suppressed. This makes it possible to sufficiently suppress both quality deterioration of the liquid agent L caused by oxygen permeation and quality deterioration of the liquid agent L caused by water vapor permeation.

[0118] The material of the plug 34 having the above-mentioned first oxygen permeability and first water vapor permeability may be a compound having a main skeleton based on a siloxane bond. That is, the plug 34 may include a compound having a main skeleton based on a siloxane bond (-R-Si-). The entire plug 34 may be made of a compound having a main skeleton based on a siloxane bond. Only a part of the plug 34 may be made of a compound having a main skeleton based on a siloxane bond.

[0119] A compound having a main skeleton based on siloxane bonds is also called silicone. The silicone contained in the plug 34 is solid in the environment in which the first container 30 is planned to be used. The silicone contained in the plug 34 does not need to contain silicone that becomes liquid in a room temperature environment, such as silicone oil. The plug 34 may contain a silicone elastomer. The plug 34 may contain silicone rubber. Silicone rubber refers to a rubber-like material made of silicone. Silicone rubber is a synthetic resin whose main component is silicone, and is a rubber-like material. Silicone rubber is a rubber-like material whose main chain is a siloxane bond. Silicone rubber may be a thermosetting compound containing a siloxane bond. Examples of silicone rubber include methyl silicone rubber, methyl vinyl silicone rubber, phenyl methyl silicone rubber, dimethyl silicone rubber, phenyl vinyl methyl silicone rubber, and fluoro silicone rubber.

[0120] The first container 30 containing the liquid agent may be placed in an environment with a temperature range of 5°C to 40°C. It is also assumed that the first container 30L containing the liquid agent may be refrigerated for a long period of time in an environment with a temperature drop close to 5°C. The plug 34 is expected to maintain its function as a plug over a temperature range of 5°C to 40°C. The plug 34 is expected to keep the first container 30 airtight over a temperature range of 5°C to 40°C. It is preferable that the dimensions of the plug 34 do not change significantly with temperature changes within a range of 5°C to 40°C. It is preferable that the hardness of the plug 34 does not change significantly with temperature changes within a range of 5°C to 40°C. From this perspective, the compound having a main skeleton formed by a siloxane bond may include one or more of dimethyl silicone, methyl vinyl silicone, dimethyl silicone rubber, and methyl vinyl silicone rubber.

[0121] At least a portion of the plug 34 may be made of silicone. That is, the entire plug 34 may be made of silicone or silicone rubber. 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 a central portion of the plug 34, or the entire or a portion of a peripheral portion surrounding the central portion.

[0122] The rubber stopper of the vial is usually made of butyl rubber. Silicone and silicone rubber generally have an oxygen permeability coefficient about 20 times that of natural rubber and a hydrogen permeability coefficient about 10 times that of natural rubber. Silicone and silicone rubber generally have an oxygen permeability coefficient 40 times or more that of butyl rubber and a hydrogen permeability coefficient 70 times or more that of natural rubber.

[0123] When the object to be measured does not contain rubber and is not a molded container, the oxygen permeability coefficient is a value measured using an OXTRAN (2 / 21) permeability measuring device manufactured by MOCON, USA, in an environment of 23°C and 50%RH in accordance with JIS K7126-2:2006. When the object to be measured corresponds to at least one of the following: containing rubber or being a molded container, the oxygen permeability coefficient is a value measured in accordance with ASTM D3985. In this case, the oxygen permeability coefficient is a value measured using an OXTRAN (2 / 61) permeability measuring device manufactured by MOCON, USA, in an environment of 23°C and 50%RH.

[0124] The measurement sample is prepared by cutting the plug 34 to be measured so that it has a certain thickness. The thickness of the measurement sample is 1.0 mm. For measurement objects where a thickness of 1.0 mm cannot be ensured, the measurement sample is prepared so that the maximum thickness is obtained.

[0125] For the stopper 34 containing a compound having a main skeleton formed by siloxane bonds, the structure, hardness, density, etc. can be adjusted to maintain the first water vapor permeability of the material constituting the stopper 34 stably low against changes in environmental conditions while maintaining its suitability as the stopper 34. When the first water vapor permeability of the material constituting the stopper 34 can be stably maintained low, the second water vapor permeability of the stopper 34 containing that material can also be stably maintained low, and further the second water vapor permeability of the first container 30 containing the stopper 34 containing that material can also be stably maintained low.

[0126] Compounds having a main skeleton based on siloxane bonds include siloxane bonds forming a chain structure as shown in FIG. 2C and siloxane bonds forming a ring structure as shown in FIG. 2D. Hexamethylcyclotrisiloxane (CH 18 O3Si3), Octamethylcyclotetrasiloxane (C8H 24 O4Si4), decamethylcyclopentasiloxane (C 10 H 30 O5Si5) are examples. The siloxane bonds forming a chain structure make the plug soft and easy to stretch. By using siloxane bonds forming a chain structure, the function as a plug is enhanced. The proportion of the chain structure can be adjusted, for example, by adjusting the polymerization conditions or the vulcanization conditions. The siloxane bonds used as rubber plugs usually contain a large number of siloxane bonds forming a chain structure.

[0127] As a method for evaluating compounds, Fourier transform infrared spectroscopy, also known as FT-IR (Fourier Transform Infrared Spectroscopy), is known. As one method of Fourier transform infrared spectroscopy, attenuated total reflection infrared spectroscopy, also known as ATR-IR (Attenuated Total Reflection - Infrared Spectroscopy), is known. By using ATR-IR, the amount of compounds containing siloxane bonds that form a chain structure and the amount of compounds containing siloxane bonds that form a cyclic structure can be quantitatively evaluated.

[0128] By using ATR-IR, the amount of compounds containing siloxane bonds that form a chain structure can be quantitatively evaluated. The intensity of absorbance due to the Si-O-Si stretching vibration of the siloxane bonds in the chain structure is measured at a wave number of 1000 cm in the IR spectrum. -1 More than 1020cm -1 On the other hand, the intensity of the absorbance due to the Si-O-Si stretching vibration of the siloxane bond of the cyclic structure is specified as the maximum value of absorbance occurring in the range of 1060 cm wavenumber in the IR spectrum. -1 More than 1100cm -1 It is specified as the maximum value of absorbance occurring in the following range: 1060 cm wavenumber -1 More than 1100cm -1 The absorbance occurring in the following range includes not only the absorbance intensity due to the Si-O-Si stretching vibration of the siloxane bond of the cyclic structure, but also the absorbance intensity due to the Si-O-Si stretching vibration contained in the silica particle SiO2.

[0129] When the plug 34 is analyzed by ATR-IR, the flat portion of the surface of the plug 34 is the target. For a coated plug 34, the flat portion of the surface of the plug 34 that is not coated is the target of the analysis. If there is no flat portion or no flat surface that is not coated, the coating is removed and the exposed flat surface is the target of the analysis.

[0130] The inventors of the present invention have investigated and confirmed the following regarding the "ratio of cyclic and silica particles to chain-like particles" calculated based on the infrared spectrum of the stopper obtained by ATR-IR. Here, the "ratio of cyclic and silica particles to chain-like particles" refers to the ratio of the wave number of 1060 cm in the infrared spectrum of the stopper obtained by infrared spectroscopy using the attenuated total reflection method. -1 More than 1100cm -1 The maximum value occurs in the following range: wavenumber 1000 cm -1 More than 1020cm -1It is a ratio value with respect to the maximum value occurring in the following range. In other words, the "cyclic and silica particle / chain ratio" is the ratio of the absorbance intensity originating from the Si-O-Si stretching vibration of the siloxane bond of the cyclic structure and the Si-O-Si stretching vibration contained in the silica particle SiO2 to the absorbance intensity originating from the Si-O-Si stretching vibration of the siloxane bond of the chain structure. The Si-O-Si stretching vibration of the siloxane bond of the chain structure is an antisymmetric stretching vibration that is seen in silicone resins and not seen in silica particles.

[0131] It was confirmed that the first water vapor permeability of the material constituting the plug and the second water vapor permeability of the plug can be reduced by increasing the ratio of the cyclic and silica particles / chain compared to the range normally adopted. In addition, as the ratio of the cyclic and silica particles / chain increases, the first water vapor permeability of the material constituting the plug and the second water vapor permeability of the plug decrease. In other words, as the ratio of the cyclic and silica particles / chain increases, water vapor becomes less likely to permeate the plug 34. Furthermore, when the ratio of the cyclic and silica particles / chain is increased compared to the range normally adopted, the fluctuation of the first water vapor permeability of the material constituting the plug and the second water vapor permeability of the plug in the above-mentioned temperature range of 5°C to 40°C can be suppressed. It is presumed that by setting an upper limit to the ratio of the cyclic and silica particles / chain, the ratio of the siloxane bond constituting the cyclic structure and the ratio of the silica particles, which are inorganic particles, increase, and the water vapor permeability can be stably maintained at a low level.

[0132] The ratio of cyclic and silica particles / chain may be 0.63 or more, 0.64 or more, 0.65 or more, or 0.66 or more. In this way, by setting a lower limit for the ratio of cyclic and silica particles / chain, the first water vapor permeability of the material constituting the plug and the second water vapor permeability of the plug can be reduced. In addition, by setting a lower limit for the ratio of cyclic and silica particles / chain, the fluctuation of the first water vapor permeability of the material constituting the plug and the second water vapor permeability of the plug in the temperature range of 5°C to 40°C can be suppressed.

[0133] The ratio of cyclic and silica particles to chain-like particles may be 0.85 or less, 0.80 or less, or 0.75 or less. When a stopper having an upper limit for the ratio of cyclic and silica particles to chain-like particles set in this manner is applied to a vial having a volume of 1 mL to 200 mL including a glass container body, the airtightness of the vial can be sufficiently ensured in the temperature range of 5°C to 40°C.

[0134] The ratio of cyclic and silica particles / chain may be 0.63 to 0.85, 0.63 to 0.80, or 0.63 to 0.75. The ratio of cyclic and silica particles / chain may be 0.64 to 0.85, 0.64 to 0.80, or 0.64 to 0.75. The ratio of cyclic and silica particles / chain may be 0.65 to 0.85, 0.65 to 0.80, or 0.65 to 0.75. The ratio of cyclic and silica particles / chain may be 0.66 to 0.85, 0.66 to 0.80, or 0.66 to 0.75.

[0135] That is, the wave number of 1060 cm in the infrared spectrum of the stopper obtained by infrared spectroscopy using the attenuated total reflection method -1 More than 1100cm -1 The wavenumber of the maximum value occurring in the range below 1000 cm -1 More than 1020cm -1 The ratio value (the ratio of cyclic and silica particles / chain-like particles) to the maximum value occurring in the following range may be 0.64 or more, 0.65 or more, or 0.66 or more. -1 More than 1100cm -1 The wavenumber of the maximum value occurring in the range below 1000 cm -1 More than 1020cm -1 The ratio for the maximum value occurring in the following range may be 0.85 or less, 0.80 or less, or 0.75 or less.

[0136] It has been found that the hardness of a plug containing a compound having a main skeleton formed by a siloxane bond affects the first water vapor permeability of the material constituting the plug and the second water vapor permeability of the plug.

[0137] When the influence of the hardness of the stopper was confirmed, the following technical matter was found. When the type A durometer hardness of the stopper containing a compound having a main skeleton based on siloxane bonds was increased, the first water vapor permeability of the material constituting the stopper and the second water vapor permeability of the stopper decreased. In addition, as the type A durometer hardness of the stopper containing a compound having a main skeleton based on siloxane bonds increased, the first water vapor permeability of the material constituting the stopper and the second water vapor permeability of the stopper decreased. From the viewpoint of reducing the first water vapor permeability of the material constituting the stopper and the second water vapor permeability of the first container, a lower limit may be set for the type A durometer hardness of the stopper containing a compound having a main skeleton based on siloxane bonds. The type A durometer hardness of the stopper may be 25 or more, 30 or more, 35 or more, or 40 or more. By setting the type A durometer hardness of the stopper containing a compound having a main skeleton formed by a siloxane bond to 25 or more, the first water vapor permeability of the material constituting the stopper can be set to 1.0 (mg×mm / (mm 2 By setting the type A durometer hardness of the stopper containing a compound having a main skeleton formed by siloxane bonds to 25 or more, the second water vapor permeability of the first container can be set to 20 (mg / day) or less at a temperature of 40°C and a humidity of 90% RH.

[0138] Furthermore, by increasing the Type A durometer hardness of a stopper containing a compound having a main skeleton based on siloxane bonds, it was possible to suppress fluctuations in the first water vapor permeability of the material constituting the stopper and the second water vapor permeability of the stopper in the temperature range of 5° C. to 40° C. described above. From this point of view, the Type A durometer hardness of a stopper containing a compound having a main skeleton based on siloxane bonds may be 40 or more, 45 or more, 48 or more, or 50 or more.

[0139] The Type A durometer hardness of a stopper containing a compound having a main skeleton formed by a siloxane bond may be equal to or less than 60, equal to or less than 58, or equal to or less than 55. When a stopper with an upper limit for Type A durometer hardness set in this manner is applied to a vial having a volume of 1 mL to 200 mL and including a glass container body, the airtightness of the vial can be ensured in a temperature range of 5°C to 40°C.

[0140] From the above viewpoints, the type A durometer hardness of the plug containing a compound having a main skeleton formed by a siloxane bond may be set as follows. The type A durometer hardness of the plug may be 25 or more and 60 or less, 25 or more and 58 or less, or 25 or more and 55 or less. The type A durometer hardness of the plug may be 30 or more and 60 or less, 30 or more and 58 or less, or 30 or more and 55 or less. The type A durometer hardness of the plug may be 35 or more and 60 or less, 35 or more and 58 or less, or 35 or more and 55 or less. The type A durometer hardness of the plug may be 40 or more and 60 or less, 40 or more and 58 or less, or 40 or more and 55 or less. The type A durometer hardness of the plug may be 45 or more and 60 or less, 45 or more and 58 or less, or 45 or more and 55 or less. The plug's Type A durometer hardness may be 48 or more and 60 or less, 48 ​​or more and 58 or less, or 48 or more and 55 or less. The plug's Type A durometer hardness may be 50 or more and 60 or less, 50 or more and 58 or less, or 50 or more and 55 or less.

[0141] The Type A durometer hardness of the stopper means the Type A durometer hardness of the portion of the stopper facing the opening of the container body as the measurement area. The Type A durometer hardness of the stopper is measured as follows.

[0142] A measurement sample is prepared by cutting and removing the protrusions of the plug so that the thickness in the measurement area is constant. For example, for the plug 34 shown in FIG. 1C, the insertion protrusion 34b is removed to prepare a measurement sample. The measurement sample is placed on a smooth table and the hardness is measured. The measurement sample includes an inner surface that faces the storage space of the first container when attached to the container body as a plug, and an outer surface that becomes the outside side of the first container when attached to the container body as a plug. The measurement sample is placed on the smooth table with the inner surface facing the smooth table, and the hardness is measured on the outer surface.

[0143] When the thickness of the measurement sample is less than 6 mm, multiple measurement samples are stacked on the smooth table so that the total thickness is 6 mm or more and less than 9 mm. When cutting the plug to prepare the measurement sample, the plug is not cut too much so that the number of stacked sheets is minimized. All multiple measurement samples are arranged in the same direction with the inner surface close to the smooth table. When the thickness changes outside the measurement area of ​​the measurement sample, for example, when a chamfer is present on the peripheral part of the plug, gaps may occur between the stacked measurement samples during hardness measurement. When such gaps occur, the outside of the measurement area of ​​the measurement sample is cut off to make the thickness of the measurement sample constant.

[0144] Set the equipment and conditions in consideration of the provisions of JISK6253-3:2012. The pressing speed should be 3.2 mm / sec or less. Measure at any 10 points, and the average of the 10 measurements should be the Type A durometer hardness.

[0145] It was found that the density of the stopper containing a compound having a main skeleton based on siloxane bonds affects the first water vapor permeability of the material constituting the stopper and the second water vapor permeability of the stopper. In general, when the density of the stopper is low, the stopper becomes soft and easy to stretch. In order to enhance the function as a stopper, a stopper with a low density has been used. When the effect of the density of the stopper was confirmed for such conventional technology, the following technical matters were found. When the density of the stopper containing a compound having a main skeleton based on siloxane bonds was increased, the first water vapor permeability of the material constituting the stopper and the second water vapor permeability of the stopper decreased. In addition, as the density of the stopper containing a compound having a main skeleton based on siloxane bonds increased, the first water vapor permeability of the material constituting the stopper and the second water vapor permeability of the stopper decreased. Furthermore, when the density of the stopper containing a compound having a main skeleton based on siloxane bonds was increased, the fluctuation of the first water vapor permeability of the material constituting the stopper and the second water vapor permeability of the stopper in the temperature range of 5°C to 40°C described above could be suppressed. From this point of view, the density of the plug containing a compound with a main skeleton of siloxane bonds is 1.02 g / mm 3 More than 1.04g / mm 3 More than 1.06g / mm 3 More than 1.08g / mm 3 More than 1.10g / mm 3 More than 1.12g / mm 3 More than 1.14g / mm 3 More than 1.16g / mm 3 The density of the plug is measured in accordance with the A method specified in JIS K6268.

[0146] The density of the plug containing a compound with a main skeleton formed by siloxane bonds is 1.24 g / mm 3 Less than 1.20g / mm 3 When a stopper with an upper limit on density set in this manner is applied to a vial having a volume of 1 mL to 200 mL including a glass container body, the airtightness of the vial can be ensured in a temperature range of 5° C. to 40° C.

[0147] From the above viewpoint, the density of the plug containing the compound having a main skeleton formed by siloxane bonds may be set as follows. The density of the plug is 1.02 g / mm 3 More than 1.24g / mm 3 Less than 1.02g / mm 3 More than 1.20g / mm 3 The density of the plug may be 1.04 g / mm 3 More than 1.24g / mm 3 Less than 1.04g / mm 3 More than 1.20g / mm 3 The density of the plug may be 1.06 g / mm 3 More than 1.24g / mm 3 Less than 1.06g / mm 3 More than 1.20g / mm 3 The density of the plug may be 1.08 g / mm 3 More than 1.24g / mm 3 Less than 1.08g / mm 3 More than 1.20g / mm 3 The density of the plug may be 1.10 g / mm 3 More than 1.24g / mm 3 Less than 1.10g / mm 3 More than 1.20g / mm 3 The density of the plug may be 1.12 g / mm 3 More than 1.24g / mm 3 Less than 1.12g / mm 3 More than 1.20g / mm 3 The density of the plug may be 1.14 g / mm 3 More than 1.24g / mm 3 Less than 1.14g / mm 3 More than 1.20g / mm 3 The density of the plug may be 1.16 g / mm 3 More than 1.24g / mm 3 Less than 1.16g / mm 3 More than 1.20g / mm 3 The following is also fine.

[0148] The Type A durometer hardness and density of the plug containing a compound having a main skeleton based on siloxane bonds can be adjusted by selecting the material, adjusting the polymerization conditions, vulcanization conditions, and the like.

[0149] Here, the results of investigating the variation in permeability due to temperature conditions for Samples 1 and 2 of stoppers containing a compound having a main skeleton formed by siloxane bonds will be described.

[0150] Samples 1 and 2 of stoppers made of a compound having a main skeleton formed by a siloxane bond were prepared. The stoppers were not sterilized. The stoppers had the outer shape shown in FIG. 1C. The plate-shaped portion of the stopper was a disk shape having a diameter of 13 mm. The thickness of the portion to be pierced by a needle 34g located in the portion facing the opening of the stopper was 2.7 mm.

[0151] The planned needle piercing portion 34g is a portion that is planned to be pierced by the needle of a syringe. The planned needle piercing portion 34g is a portion that is planned to be pierced by a needle. The planned needle piercing portion 34g is located in a portion of the stopper 34 that faces the opening 33. The planned needle piercing portion 34g may be exposed from the fixing device 36. That is, the planned needle piercing portion 34g may not be covered by the fixing device 36. As shown in FIG. 1C, the planned needle piercing portion 34g may be a portion of the stopper 34 that faces the opening 33 and has the smallest thickness. The planned needle piercing portion 34g may be a portion located at the center of the stopper 34 that faces the opening 33. As shown in FIG. 1C, the planned needle piercing portion 34g may be visible by a convex portion 34ga or a concave portion. The planned needle piercing portion 34g may be a portion surrounded by a plurality of convex portions 34ga or concave portions. The intended needle piercing portion 34g may be a portion surrounded by linear convex portions 34ga or concave portions. The linear convex portions 34ga or concave portions may extend circumferentially. The linear convex portions 34ga or concave portions may extend circumferentially. The intended needle piercing portion 34g may be located on an extension line of the linear convex portions 34ga or concave portions. The intended needle piercing portion 34g may be located on an extension line of the linear convex portions 34ga or concave portions.

[0152] In this specification, the "portion of the plug facing the opening" used in relation to thickness includes not only the portion of the plug facing the opening along the direction DA (see FIG. 1C) in which the plug is attached to the container body to close the opening, but also the portion of the plug located within the opening when the plug closes the opening of the container body. Unless otherwise specified, the thickness of the plug is the thickness when the plug is not compressed.

[0153] The thickness of the plug at the intended needle insertion portion 34g is a value measured using a measuring tool. However, if it is difficult to measure directly using the measuring tool, the value is measured from an observation image of the cross section.

[0154] The ratio of cyclic and silica particle / chain structure for samples 1 and 2 was investigated. First, infrared spectra for samples 1 and 2 were obtained by infrared spectroscopy using attenuated total reflection. The infrared spectrum is shown in FIG. 2E. In the IR spectrum shown in FIG. 2E, the ratio of the absorbance intensity originating from the Si-O-Si stretching vibration of the siloxane bond of the cyclic structure and the Si-O-Si stretching vibration contained in the silica particles to the absorbance intensity originating from the Si-O-Si stretching vibration of the siloxane bond of the chain structure (antisymmetric stretching vibration seen in silicone resins and not seen in silica particles) is the cyclic and silica particle / chain structure ratio to be specified. The absorbance intensity originating from the Si-O-Si stretching vibration of the siloxane bond of the cyclic structure and the Si-O-Si stretching vibration contained in the silica particles is expressed as the ratio of cyclic and silica particle / chain structure ... -1 More than 1100cm -1 The maximum absorbance value occurring in the following range was determined. The absorbance intensity due to the Si-O-Si stretching vibration of the siloxane bond in the chain structure was determined in the IR spectrum at a wave number of 1000 cm. -1 More than 1020cm -1 The maximum absorbance value that occurred in the following range was set as the wave number 1060 cm -1 More than 1100cm -1 The maximum absorbance occurs in the following range: 1000 cm wavenumber -1 More than 1020cm -1The ratio of cyclic and silica particles / chain particles for each sample was determined as the ratio to the maximum absorbance value occurring in the following range. The cyclic and silica particles / chain particle ratio for each sample is shown in the "Ratio of cyclic and silica particles / chain particles" column in Table 1.

[0155] The conditions for the infrared spectroscopic analysis by attenuated total reflection method were as follows: (Device configuration) Equipment: Thermo Scientific Nicolet 6700 Fourier transform infrared spectrometer (FT-IR) - Accessory: Single reflection ATR measurement accessory (iS50 ATR) Diamond ATR crystal Measurement method: Attenuated total reflection (ATR) (Measurement conditions) Detector: DTGS detector ·Resolution: 4cm -1 Number of times: 32 ·Incidence angle: 45° (Measurement sample) A silicone rubber block was pressed against a diamond crystal using the dedicated indenter of the iS50 ATR module to measure.

[0156] The type A durometer hardness of Sample 1 and Sample 2 was measured by the above-mentioned method. Two measurement samples with a thickness of about 3 mm were prepared, and the durometer hardness was measured with the two measurement samples stacked on top of each other. The durometer hardness was measured using an Asker rubber hardness tester Type A manufactured by Kobunshi Keiki Co., Ltd. The type A durometer hardness of each sample is shown in the "Hardness" column in Table 1.

[0157] The density (g / mm 3 ) was measured. The density was measured using an electronic specific gravity meter MD-300S manufactured by Alpha Mirage Co., Ltd. The type A durometer hardness of each sample is shown in the "Density" column in Table 1.

[0158] For each sample, the second water vapor permeability (mg / day) of the stopper under environmental condition 1 and the second water vapor permeability (mg / day) of the stopper under environmental condition 2 were measured. Environmental condition 1 was set to a temperature of 40°C and a humidity of 90% RH. Environmental condition 2 was set to a temperature of 5°C and a humidity of 90% RH. The method for measuring the second water vapor permeability of the stopper will be described in detail later with reference to FIG. 10C. The second water vapor permeability of the first container is an index indicating the amount of water vapor that permeates the entire first container per day. The second water vapor permeability of the stopper is an index indicating the amount of water vapor that permeates the stopper assembled in the first container per day. Therefore, the second water vapor permeability (mg / day) of the stopper can also be said to be the water vapor permeability (mg / day) of the stopper.

[0159] As shown in FIG. 10C, the test container 77 used to measure the second water vapor permeability of the stopper is different from the test container 77 shown in FIG. 2B in that the stopper 34 is used instead of the test sheet 30Y. Except for this, the device for measuring the second water vapor permeability of the stopper 34 has the same configuration as the device for measuring the first water vapor permeability shown in FIG. 2B. In the test container 77 shown in FIG. 10C, the test container 78 of the test container 77 is a container having an opening 78A. The test container 78 has water vapor barrier properties. The stopper 34 faces the opening 78A. The opening 78A is closed by the stopper 34. The stopper 34 is airtightly joined to the surrounding portion of the opening 78A of the test container 78 using a barrier bonding material 73 having water vapor barrier properties. In the test container 77, the portion facing the opening 78A of the stopper 34 is the portion facing the opening 33 of the stopper 34 in normal use of the first container 30. The portion of the stopper 34 that comes into contact with the barrier bonding material 73 is the portion that comes into contact with the container body 32 of the stopper 34 during normal use of the first container 30. The test container 77 contains calcium chloride 79. The second water vapor permeability is evaluated as the weight increase of the test container 77. From the weight change of the test container 77, the amount of water vapor permeating through the stopper 34 per day (mg / day) becomes the second water vapor permeability of the stopper.

[0160] The second water vapor permeability of the stopper of each sample is shown in the "Water vapor permeability" column in Table 1. The "Water vapor permeability" column shows the second water vapor permeability (mg / day) of the stopper under environmental condition 1 and environmental condition 2. The "Water vapor permeability" column also shows the rate of change of the second water vapor permeability of the stopper under environmental condition 1 relative to the second water vapor permeability of the stopper under environmental condition 2 as a ratio (= "Water vapor permeability of the stopper under environmental condition 1" / "Water vapor permeability of the stopper under environmental condition 2").

[0161] For each sample, the oxygen permeability of the stopper under environmental condition 1 (third oxygen permeability) (cc / day) and the oxygen permeability of the stopper under environmental condition 2 (third oxygen permeability) (cc / day) were measured. Environmental condition 1 was a temperature of 40°C and a humidity of 90% RH. Environmental condition 2 was a temperature of 5°C and a humidity of 90% RH. The oxygen permeability (cc / day) of the stopper measured here is an index showing the amount of oxygen that permeates the stopper incorporated in the first container per day. Therefore, the oxygen permeability (cc / day) of the stopper can also be said to be the oxygen permeation amount (cc / day) of the stopper.

[0162] The oxygen permeability of the stopper was measured using a test container 76 including the stopper, as shown in FIG. 2F. The test container 76 includes a test storage section 76X. The test storage section 76X is a container having an opening 76XA. The test storage section 76X has oxygen barrier properties. The stopper 34 faces the opening 76XA. The opening 76XA is closed by the stopper 34. The stopper 34 is airtightly joined to the periphery of the opening 76XA of the test storage section 76X using a barrier bonding material 73 having oxygen barrier properties. In the test container 76, the part of the stopper 34 facing the opening 76XA is the part facing the opening 33 of the stopper 34 in normal use of the first container 30. The part of the stopper 34 in contact with the barrier bonding material 73 is the part in contact with the container body 32 of the stopper 34 in normal use of the first container 30.

[0163] The volume of the test vessel 76 is 9.2 mm 3The test container 76 was filled with air. The oxygen concentration in the test container 76 at the start of the experiment was 20.95%. The test container 76 was placed in the test atmosphere immediately after the test container 76X filled with air was closed with the plug 34. The test atmosphere was environmental condition 1 and environmental condition 2. The test atmosphere was an inert gas atmosphere in which oxygen was substantially absent. As shown in FIG. 2F, the test container 76 was placed in the test chamber 75. The test chamber 75 was maintained in the test atmosphere. An inert gas was supplied from the supply path 75A into the test chamber 75. The gas in the test chamber 75 is discharged from the discharge path 75B. After the start of the experiment, the oxygen in the test container 76 placed in the test atmosphere in the test chamber 75 permeated the plug 34 and moved outside the test container 76. The oxygen that moved outside the test container 76 is discharged from the discharge path 75B. The atmosphere within test chamber 75 was maintained as an inert gas atmosphere substantially free of oxygen using supply line 75A and exhaust line 75B.

[0164] The oxygen concentration in the test container 76 was measured immediately after placing the test container 76 in the test atmosphere and one day (24 hours) later. 3 ) and the oxygen concentration (%), the amount of oxygen transmitted through the stopper 34 per day (cc / day) was determined. This amount of oxygen transmitted was taken as the oxygen permeability (third oxygen permeability) (cc / day) for the stopper. The oxygen permeability (cc / day) for each sample stopper is shown in the "Oxygen Permeability" column in Table 1. The "Oxygen Permeability" column shows the oxygen permeability (cc / day) for the stopper under environmental condition 1 and environmental condition 2. The "Oxygen Permeability" column also shows the rate of change of the oxygen permeability for the stopper under environmental condition 1 relative to the oxygen permeability for the stopper under environmental condition 2 (= "Oxygen permeability for the stopper under environmental condition 1" / "Oxygen permeability for the stopper under environmental condition 2").

[0165] The oxygen concentration in the test container 76 was measured using a non-destructive, non-contact, highly sensitive oxygen meter OXY-1 SMA trace manufactured by PreSens of Germany. This oxygen meter is a fluorescent non-contact type oxygen meter. An oxygen sensor was placed in advance inside the container to be measured. The oxygen sensor emits light when it receives light in a specific wavelength range. The amount of light emitted by the oxygen sensor increases with the amount of oxygen around the sensor. The oxygen meter OXY-1 SMA trace can emit light of a specific wavelength that the oxygen sensor emits itself, and can measure the oxygen concentration (%) by measuring the amount of light emitted by the oxygen sensor.

[0166] As a preliminary test, the oxygen permeability of the stopper was measured under standard environmental conditions. The standard environmental conditions were a temperature of 23°C and a humidity of 50% RH. As the oxygen permeability of the stopper under the standard environmental conditions, two performances were measured: a third oxygen permeability measured by a measurement method using a test container 76 described with reference to FIG. 2F, and a second oxygen permeability measured by a measurement method using a test container 70 described with reference to FIG. 10A. The third oxygen permeability (cc / day) measured by the measurement method using the test container 76 described with reference to FIG. 2F and the second oxygen permeability (cc / day) measured by a measurement method using the test container 70 shown in FIG. 10A, described below, were roughly similar values, with no significant difference.

[0167] [Table 1]

[0168] According to the evaluation results shown in Table 1, both the water vapor permeability and the oxygen permeability increased with increasing temperature. As the environmental temperature increased, oxygen and water vapor were more likely to permeate the stopper. For the stopper made of a compound having a main skeleton formed by a siloxane bond, the variation in water vapor permeability with the environmental conditions was greater than the variation in oxygen permeability with the environmental conditions. Therefore, the quality of the liquid L can be stabilized by reducing the variation in water vapor permeability at temperatures of 5°C or higher and 40°C or lower, at which the first container 30L containing the liquid is expected to be stored.

[0169] The ratio of the second water vapor permeability (mg / day) of the stopper at a temperature of 40°C and a humidity of 90%RH to the second water vapor permeability (mg / day) of the stopper at a temperature of 5°C and a humidity of 90%RH, i.e., the above-mentioned rate of change, may be 4.4 or less, 4.2 or less, 4.0 or less, 3.7 or less, 3.5 or less, 3.3 or less, or 3.1 or less. This rate of change may be 1.0 or more. That is, this rate of change may be 1.0 or more and 4.4 or less, 1.0 or more and 4.2 or less, 1.0 or more and 4.0 or less, 1.0 or more and 3.7 or less, 1.0 or more and 3.5 or less, 1.0 or more and 3.3 or less, or 1.0 or more and 3.1 or less.

[0170] The ratio of the third oxygen permeability (cc / day) for the stopper at a temperature of 40°C and a humidity of 90% RH to the third oxygen permeability (cc / day) for the stopper at a temperature of 5°C and a humidity of 90% RH, i.e., the above-mentioned rate of change, may be 2.0 or less, 1.8 or less, 1.7 or less, 1.6 or less, or 1.5 or less. This rate of change may be 1.0 or more. That is, this rate of change may be 1.0 or more and 2.0 or less, 1.0 or more and 1.8 or less, 1.0 or more and 1.7 or less, 1.0 or more and 1.6 or less, or 1.0 or more and 1.5 or less.

[0171] The first container 30L containing the liquid agent is refrigerated and stored for a long period of time in an environment where the temperature has dropped to about 5°C. Therefore, the water vapor transmission performance (mg / day) of the stopper at a temperature of 5°C or higher and a humidity of 90% RH is sufficiently low, so that deterioration of the quality of the liquid agent L can be effectively suppressed. In this respect, the second water vapor transmission performance of the stopper may be 1.45 mg / day or less, 1.42 mg / day or less, 1.39 (mg / day) or less, 1.35 (mg / day) or less, 1.30 (mg / day) or less, 1.25 (mg / day) or less, or 1.21 (mg / day) or less at a temperature of 5°C and a humidity of 90% RH. The water vapor transmission performance of the stopper may be 0 (mg / day) or more at a temperature of 5°C and a humidity of 90% RH. That is, the water vapor permeability of the stopper may be, at a temperature of 5°C and a humidity of 90% RH, 0 mg / day or more and 1.45 mg / day or less, 0 mg / day or more and 1.42 mg / day or less, 0 mg / day or more and 1.39 mg / day or less, 0 mg / day or more and 1.35 mg / day or less, 0 mg / day or more and 1.30 mg / day or less, 0 mg / day or more and 1.25 mg / day or less, or 0 mg / day or more and 1.21 mg / day or less.

[0172] The stopper 34 is given specific oxygen permeability and water vapor permeability required for application to the first container 30L containing the liquid. The stopper 34 closing the opening 33 of the container body 32 of the first container 30 containing the liquid is required to have this specific permeability as well as performance specific to the liquid, which is different from the stopper of a container containing food or the like. As will be described later with reference to FIG. 9, when the liquid L is taken out from the syringe 60, it is possible that the needle 64 of the syringe 60 will pierce the stopper 34. When the needle 64 pierces the stopper 34, there is a possibility that a part of the stopper 34 will separate from the other parts as a stopper piece. The stopper 34 of the first container 30 containing the liquid L is required to have performance capable of suppressing the generation of stopper pieces. When a plug 34 made of silicone rubber having a main skeleton formed by siloxane bonds was examined for the generation of rubber fragments (plug fragments) when the needle 64 was inserted, it was found that the generation of rubber fragments could be suppressed by the hardness of the plug 34 and the thickness of the plug 34 at the intended needle insertion portion 34g.

[0173] As described above, the intended needle piercing portion 34g is a portion that is intended to be pierced with a needle. The intended needle piercing portion 34g is included in a portion of the plug 34 that faces the opening 33. The intended needle piercing portion 34g may be exposed from the fixing device 36. As shown in FIG. 1C, the intended needle piercing portion 34g may be a portion of the plug 34 that faces the opening 33 and has the smallest thickness.

[0174] In this experiment, a number of samples of the first container, A1 to A5, B1 to B4, C1 to C4, and D1 to D4, were prepared. As shown in FIG. 1C, each sample of the first container included a container body and a stopper. The stopper closed the opening of the container body. The stopper was a silicone rubber stopper having a main skeleton formed by siloxane bonds. The hardness of the stopper and the thickness of the stopper at the intended needle insertion portion 34g were different among the multiple samples. The rubber stopper of each sample was pierced with an injection needle 1 (made of stainless steel, 23G, regular bevel) and an injection needle 2 (made of stainless steel, 18G, regular bevel). The injection needle 2 was a thick needle used for blood transfusion. The injection needle was pierced at the intended needle insertion portion 34g along the direction DA (see FIG. 1C) in which the stopper is inserted into the opening. The injection needle was pierced into the stopper from above in the vertical direction. When the injection needle was pierced into the stopper, it was confirmed whether or not rubber pieces were generated. Each sample was punctured 20 times with each injection needle, and samples that produced rubber fragments more than twice were deemed to have failed, while samples that produced rubber fragments once or less (5% or less) were deemed to have passed. The results of evaluation based on the following criteria are shown in the "Evaluation" column of Table 2. The "Hardness" column of Table 2 shows the Type A durometer hardness of the stoppers used in each sample. The "Thickness" column of Table 2 shows the thickness (mm) of the silicone rubber stopper at the intended needle puncture portion 34g of each sample. Grade AA: Passed both tests using needle 1 and needle 2 Grade A: Passed only the experiment using needle 1 Grade B: Failed the experiment using needle 1

[0175] [Table 2]

[0176] The hardness of the plug was the type A durometer hardness measured by the above-mentioned measuring method. The thickness of the plug means the thickness in the intended needle piercing portion 34g along the direction DA in which the plug is inserted into the opening, and was the arithmetic average value at five measurement points in the intended needle piercing portion 34g. The thickness of the plug in the intended needle piercing portion 34g was the thickness when the plug was not compressed. The thickness of the plug in the intended needle piercing portion 34g was measured using a measuring tool.

[0177] As can be seen from the results shown in Table 2, the higher the Type A durometer hardness of the stopper containing a compound having a main skeleton based on siloxane bonds, the more likely rubber fragments tended to be generated. From this point of view, in order to suppress the generation of rubber fragments, it is effective to set an upper limit on the Type A durometer hardness of the stopper containing a compound having a main skeleton based on siloxane bonds. By setting the Type A durometer hardness of the stopper 34 to 60 or less, the generation of rubber fragments can be sufficiently suppressed. From the viewpoint of more effectively suppressing the generation of rubber fragments, the Type A durometer hardness of the stopper 34 may be 25 or more and 45 or less, 25 or more and 42 or less, 25 or more and 40 or less, 25 or more and 35 or less, or 25 or more and 30 or less.

[0178] When the thickness of the stopper containing a compound having a main skeleton based on siloxane bonds at the intended needle piercing portion 34g becomes large, rubber fragments tend to be generated easily. From this point of view, in order to suppress the generation of rubber fragments, it is effective to set an upper limit on the thickness of the silicone rubber stopper containing a compound having a main skeleton based on siloxane bonds at the intended needle piercing portion 34g. From the viewpoint of suppressing the generation of rubber fragments, the thickness of the rubber stopper containing a compound having a main skeleton based on siloxane bonds at the intended needle piercing portion 34g may be 4.0 mm or less, 3.9 mm or less, 3.0 mm or less, 2.8 mm or less, 1.5 mm or less, 1.2 mm or less, or 1.0 mm or less. For example, the thickness at the needle puncture portion 34g may be 0.50 mm or more and 4.0 mm or less, 0.50 mm or more and 3.9 mm or less, 0.50 mm or more and 3.0 mm or less, 0.50 mm or more and 2.8 mm or less, 0.50 mm or more and 1.5 mm or less, 0.50 mm or more and 1.2 mm or less, or 0.50 mm or more and 1.0 mm or less.

[0179] The United States Pharmacopeia USP381 specifies a coring test to check for the generation of rubber fragments due to puncture with an injection needle. The conditions for the coring test described in USP381 are more severe than the conditions for the test whose results are shown in Table 2 above. Samples E1 to E4 of the first container were prepared and the coring test based on USP381 was carried out as follows.

[0180] The first container samples E1 to E4 were vials with a capacity of 4 ml. As shown in FIG. 1C, the first container samples E1 to E4 included a container body, a stopper, and a fixing device. The stopper was a silicone rubber stopper having a main skeleton formed by siloxane bonds. The rubber stopper had a thickness of (2.7) mm. Rubber stoppers with different hardness were used among the samples E1 to E4.

[0181] For each of samples E1 to E4, 12 rubber stoppers manufactured under the same conditions were prepared. For example, 12 rubber stoppers manufactured under the same conditions were prepared for sample E1. Therefore, 12 vials were evaluated for each of samples E1 to E4.

[0182] A rubber stopper was attached to the container body, and then the fixing device was wound around the container body. The first container of each sample was left for 16 hours after the fixing device was wound around the container. Then, a syringe needle was pierced into the rubber stopper of the first container of each sample, and 1 ml of water was injected into the first container through the syringe needle. The rubber stopper of each first container was pierced with the syringe needle four times, and a total of 4 ml of water was injected.

[0183] The injection needle was inserted into the intended needle insertion portion 34g along the direction DA (see FIG. 1C) in which the stopper was inserted into the opening. The injection needle was inserted into the stopper from above in the vertical direction. The four puncture positions for one rubber stopper were four positions as far apart as possible within the intended needle insertion portion. The injection needle was replaced every four punctures. The same injection needle was used to puncture the rubber stopper of the same first container.

[0184] USP381 specifies that a 21G needle should be used as the injection needle. Therefore, injection needle 3 (stainless steel, 21G, regular bevel) was used as the 21G injection needle for the coring test. Although it is outside the scope of USP381, injection needle 1 (stainless steel, 23G, regular bevel) and injection needle 2 (stainless steel, 18G, regular bevel) were also used to carry out the coring test. The tests using injection needles 1 to 3 were carried out on different rubber stoppers.

[0185] After four punctures, the presence or absence of rubber fragments in the first container was confirmed. More specifically, the water in the first container after the test was filtered through a membrane filter, and rubber fragments were collected on the membrane filter. The hole size of the membrane filter was 0.45 μm. If rubber fragments with a maximum length of 50 μm or more were collected, it was determined that rubber fragments had occurred in the first container.

[0186] Table 3 shows the results of the coring tests on each of the samples E1 to E4 using the injection needles 1 to 3. Table 3 also shows the number of rubber pieces generated in the 12 first containers in the coring tests using each of the injection needles 1 to 3.

[0187] The type A durometer hardness of the silicone rubber stoppers having a main skeleton based on siloxane bonds constituting samples E1 to E4 was measured by the method described above. The type A durometer hardness of the rubber stopper of sample E1 was 27. The type A durometer hardness of the rubber stopper of sample E2 was 31. The type A durometer hardness of the rubber stopper of sample E3 was 41. The type A durometer hardness of the rubber stopper of sample E4 was 54.

[0188] Further, infrared spectra were obtained for samples E1 to E4 by infrared spectroscopy using attenuated total reflection. The conditions used in the infrared spectroscopy using attenuated total reflection for samples E1 to E4 were the same as those used in the infrared spectroscopy using attenuated total reflection for samples 1 and 2. Based on the obtained infrared spectra, the peak intensity ratios for samples E1 to E4 were calculated. The peak intensity ratios were calculated based on the peak intensity ratios at a wavenumber of 1060 cm in the infrared spectrum of the stopper obtained by infrared spectroscopy using attenuated reflection. -1 More than 1100cm -1 The maximum value occurs in the following range: wavenumber 1240 cm -1 More than 1280cm -1 This is the ratio value for the maximum value occurring in the following range. The peak intensity ratio has a value between 0 and 1.

[0189] As mentioned above, the wave number is 1060 cm -1 More than 1100cm -1 The maximum values ​​occurring in the following ranges include the absorbance intensity due to the Si-O-Si stretching vibration of the siloxane bond of the cyclic structure and the absorbance intensity due to the Si-O-Si stretching vibration contained in the silica particles SiO2. -1 More than 1280cm -1 The maximum values ​​occurring in the following ranges include peak intensities derived from the vibration of Si-CH3 constituting the chain structure of siloxane bonds. The peak intensity ratio can be an index showing the ratio of "peak intensity derived from silica" / "peak intensity derived from Si-CH3", in other words, the magnitude of the silica particle ratio.

[0190] For each of samples E1 to E4, the peak intensity due to silica particles in the infrared spectrum, i.e., the wave number 1060 cm -1 More than 1100cm -1 The maximum values ​​occurring in the following ranges were measured. The obtained maximum values ​​(peak intensities) were entered in the "first intensity" column in Table 3.

[0191] For each of samples E1 to E4, the peak intensity due to Si-CH3 in the infrared spectrum, i.e., the wave number 1240 cm -1More than 1280cm -1 The maximum values ​​occurring in the following ranges were measured. The obtained maximum values ​​(peak intensities) were entered in the "second intensity" column in Table 3.

[0192] For each of the samples E1 to E4, a peak intensity ratio was calculated as the ratio of the “first intensity” to the “second intensity.” The calculated peak intensity ratios are shown in the “Intensity ratio” column of Table 3.

[0193] For the rubber stopper of sample E1, the first intensity including the peak intensity derived from silica was 0.483, the second intensity which was the peak intensity derived from Si-CH3 was 0.568, and the peak intensity ratio was 0,850. For the rubber stopper of sample E2, the first intensity was 0.433, the second intensity was 0.650, and the peak intensity ratio was 0.666. For the rubber stopper of sample E3, the first intensity was 0.417, the second intensity was 0.641, and the peak intensity ratio was 0.651. For the rubber stopper of sample E4, the first intensity was 0.416, the second intensity was 0.680, and the peak intensity ratio was 0.612.

[0194] [Table 3]

[0195] According to USP381, if five or fewer rubber pieces are generated in the twelve first containers using a 21G injection needle 3, the container is deemed to pass.

[0196] The results shown in Table 3 also showed that as the Type A durometer hardness of a rubber stopper having a main skeleton based on siloxane bonds increases, rubber fragments tend to be more easily generated. From this point of view, in order to suppress the generation of rubber fragments, it is effective to set an upper limit on the Type A durometer hardness of the rubber stopper. By setting the Type A durometer hardness of the stopper to 60 or less, the generation of rubber fragments can be sufficiently suppressed. However, from the viewpoint of more effectively suppressing the generation of rubber fragments, the Type A durometer hardness of the stopper may be 45 or less, 41 or less, 40 or less, 35 or less, 31 or less, or 30 or less.

[0197] By setting the type A durometer hardness of a rubber stopper having a main skeleton based on siloxane bonds to 25 or more, the first water vapor permeability of the material constituting the stopper is set to 1.0 (mg×mm / (mm 2 By making the Type A durometer hardness of a rubber stopper having a main skeleton based on siloxane bonds 25 or more, the second water vapor permeability of the material constituting the stopper can be made 20 (mg / day) or less at a temperature of 40°C and a humidity of 90% RH.

[0198] From these viewpoints, the Type A durometer hardness of the plug having a main skeleton based on siloxane bonds may be set as follows: The Type A durometer hardness of the plug may be 25 or more and 45 or less, 25 or more and 41 or less, 25 or more and 40 or less, 25 or more and 35 or less, 25 or more and 31 or less, or 25 or more and 30 or less.

[0199] Furthermore, from the results of the peak intensity ratio as the "intensity ratio" shown in Table 3, it was possible to suppress the generation of rubber fragments by increasing the proportion of silica particles (by increasing the peak intensity ratio). From this point of view, in order to suppress the generation of rubber fragments, the peak intensity ratio calculated by "first intensity" / "second intensity" determined by ATR-IR for the rubber stopper may be set as follows. The peak intensity ratio for the stopper may be 0.620 or more, 0.630 or more, 0.640 or more, 0.645 or more, 0.651 or more, 0.655 or more, or 0.666 or more.

[0200] Furthermore, by making the first intensity, which includes "silica-derived intensity", smaller than the second intensity, which is "Si-CH3-derived intensity", it was possible to suppress the generation of rubber fragments. In other words, by making the peak intensity ratio less than 1, it was possible to suppress the generation of rubber fragments. Although the details of why this phenomenon occurs are unclear, one possible factor is that when the first intensity, which includes "silica-derived intensity", is larger than the second intensity, which is "Si-CH3-derived intensity", the rubber stopper becomes brittle.

[0201] From the above, the wave number of the infrared spectrum of the stopper obtained by infrared spectroscopy using the attenuated total reflection method is 1060 cm -1 More than 1100cm -1 The maximum value occurs in the following range: wavenumber 1240 cm -1 More than 1280cm -1 The peak intensity ratio, which is the ratio value to the maximum value occurring in the following range, may be set as follows: The peak intensity ratio may be 0.620 or more and less than 1.0, 0.630 or more and less than 1.0, 0.640 or more and less than 1.0, 0.645 or more and less than 1.0, 0.651 or more and less than 1.0, 0.655 or more and less than 1.0, or 0.666 or more and less than 1.0.

[0202] In addition, compounds having a main skeleton based on siloxane bonds are usually produced by various vulcanization reactions. For example, they are produced by addition reactions using peroxides or platinum catalysts. Among such production methods, production using peroxides is particularly convenient because reaction control using heat is easy, and is excellent in stability when producing low hardness rubber. Therefore, according to the production method using a reaction using peroxides, it is possible to more stably obtain compounds having low hardness that is unlikely to generate rubber fragments and high peak intensity ratio that is unlikely to generate rubber fragments.

[0203] Furthermore, the plug 34 closing the opening 33 of the container body 32 of the first container 30 containing the liquid agent is required to have the performance of suppressing liquid leakage and gas leakage when pierced with the needle 64 of the syringe 60. That is, even in a state where the needle 64 is pierced into the plug 34, it is preferable that the first container 30 is liquid-tight, and furthermore, airtight. When the plug 34 using silicone rubber having a main skeleton based on siloxane bonds was examined for the occurrence of liquid leakage and gas leakage when pierced with the needle 64, it was found that the occurrence of leakage can be suppressed by the hardness of the plug 34 and the thickness of the plug 34 at the intended needle piercing portion 34g.

[0204] In this experiment, a plurality of samples of the first container A1-A4, B1-B4, C1-C4, and D1-D4 were prepared. The samples A1-A4, B1-B4, C1-C4, and D1-D4 used in the leakage confirmation experiment were the same as the samples A1-A4, B1-B4, C1-C4, and D1-D4 used in the rubber piece confirmation experiment. In this experiment, water was placed in the first container.

[0205] In the first experiment, the presence or absence of liquid leakage and gas leakage was confirmed when the injection needle 1 (stainless steel, 23G, regular bevel) was pierced into the rubber stopper of each sample. With the needle pierced into the stopper, the piston of the syringe was moved relative to the cylinder, and the presence or absence of liquid leakage and gas leakage was confirmed from the feel of operating the piston. Regarding liquid leakage, it was also confirmed whether or not liquid was leaking at the needle piercing position of the stopper in the position shown in FIG. 9, that is, in the position where the needle was pierced into the stopper and the syringe was positioned vertically below the first container. Regarding gas leakage, it was also confirmed whether or not gas that had passed through the stopper appeared in the form of bubbles in the water in the position shown in FIG. In the first experiment, no gas leakage or liquid leakage occurred for all samples.

[0206] In the second experiment, the rubber stopper of the sample after the first experiment was punctured again with the injection needle 1, and the presence or absence of liquid leakage and gas leakage was confirmed. In the second experiment, the injection needle 1 was punctured at a position inside the rubber stopper different from the position where the injection needle 1 had punctured in the first experiment. In all samples, no gas leakage or liquid leakage occurred at the needle puncture position in the second experiment. However, in some samples, gas leakage occurred at the needle puncture position in the first experiment during the second experiment.

[0207] The results of the leak confirmation test are shown in the "Evaluation" column of Table 4. Table 4 shows the evaluation results based on the following criteria. The "Hardness" column of Table 4 shows the Type A durometer hardness of the stopper used in each sample. The "Thickness" column of Table 4 shows the thickness (mm) of the silicone rubber stopper at the intended needle puncture portion 34g in each sample. AA: No leaks occurred in both the first and second experiments. A: No leakage occurred in the first experiment, but gas leakage occurred from the needle puncture position in the second experiment. B: A leak occurred in the first experiment.

[0208] [Table 4]

[0209] There was a tendency that the risk of leakage increased as the type A durometer hardness of the plug containing a compound having a main skeleton based on siloxane bonds increased. From this point of view, in order to suppress leakage, it is effective to set an upper limit on the type A durometer hardness of the plug containing a compound having a main skeleton based on siloxane bonds. From the viewpoint of suppressing leakage, leakage can be sufficiently suppressed by setting the type A durometer hardness of the plug to 60 or less. From the viewpoint of suppressing leakage more effectively, the type A durometer hardness of the plug may be 25 or more and 45 or less, 25 or more and 42 or less, 25 or more and 40 or less, 25 or more and 35 or less, or 25 or more and 30 or less.

[0210] When the thickness of the stopper containing a compound having a main skeleton based on a siloxane bond at the intended needle piercing portion 34g becomes smaller, the risk of leakage tends to increase. From this point of view, it is effective to set a lower limit for the thickness of the stopper containing a compound having a main skeleton based on a siloxane bond at the intended needle piercing portion 34g in order to suppress leakage. From the viewpoint of suppressing leakage, the minimum thickness of the stopper containing a compound having a main skeleton based on a siloxane bond at the intended needle piercing portion 34g may be 0.70 mm or more, 0.90 mm or more, 1.0 mm or more, or 1.2 mm or more. The minimum thickness of the stopper containing a compound having a main skeleton based on a siloxane bond at the intended needle piercing portion 34g may be 3.0 mm or less, or 2.8 mm or less. The minimum thickness of the intended needle piercing portion 34g may be 0.70 mm or more and 3.0 mm or less, 0.90 mm or more and 3.0 mm or less, 1.0 mm or more and 3.0 mm or less, or 1.2 mm or more and 3.0 mm or less. The minimum thickness of the intended needle piercing portion 34g may be 0.70 mm or more and 2.8 mm or less, 0.90 mm or more and 2.8 mm or less, 1.0 mm or more and 2.8 mm or less, or 1.2 mm or more and 2.8 mm or less.

[0211] Since the stopper 34 has oxygen permeability, the container body 32 may have oxygen barrier properties. As shown in FIG. 1C, the container body 32 may include a bottom 32a, a body 32b, a neck 32c, and a head 32d in this order. As shown in FIG. 1C, a storage space S for the liquid agent L is formed mainly by the bottom 32a and the body 32b. 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 32b and the head 32d. The neck 32c is narrower in width, particularly narrower in diameter, than the body 32b and the head 32d.

[0212] The container body 32 may include a transparent portion. The transparent portion of the container body 32 allows the contained liquid L to be observed from the outside of the container body 32. Transparent means that the transmission haze of the target portion is 80.0 or less so that the inside of the target portion can be observed from the outside. The transmission haze of at least a part of the container body 32 may be 58.0% or less, 29.0% or less, 14.5% or less, 7.0% or less, 3.5% or less, or 1.0% or less so that the target portion can be more clearly observed from the outside.

[0213] A light source that mimics the spectrum of D65 standard light (hereafter referred to as D65 standard light source) is used to measure transmission haze. Before measuring transmission haze, turn on the D65 standard light source for 15 minutes to stabilize the output of the D65 standard light source. The angle of incidence on the sample when measuring transmission haze is 0°. The test environment when measuring transmission haze is a temperature of 23°C ± 2°C and a relative humidity of 50% ± 5%. The sample is placed in the test environment for 16 hours before starting the test. Other measurement conditions when measuring transmission haze are in accordance with JIS K7136:2000. Transmission haze is the arithmetic average of five measured values. The five measured values ​​are measured at five measurement positions on the measurement sample to be evaluated.

[0214] The first container 30 shown in FIG. 1C further includes a fixing device 36. The fixing device 36 prevents the plug 34 from coming off the container body 32. The fixing device 36 is attached to the head 32d of the container body 32. As shown in FIG. 1C, the fixing device 36 covers the periphery of the plate-shaped portion 34a of the plug 34. The fixing device 36 presses the flange portion of the plate-shaped portion 34a toward the head 32d. As a result, the fixing device 36 prevents the plug 34 from coming off the container body 32 while exposing a portion of the plug 34. In addition, the fixing device 36 can make the gap between the plug 34 and the container body 32 liquid-tight and airtight. The fixing device 36 puts the first container 30 in an airtight state. The fixing device 36 may be a sheet-shaped metal fixed to the head 32d. The fixing device 36 may be a cap screwed to the head 32d. The metal fixing device 36 may have oxygen barrier properties.

[0215] The volume of the first container 30 may be 1.0 mL or more, 3.0 mL or more, or 5.0 mL or more. The volume of the first container 30 may be 200 mL or less, 100 mL or less, 50 mL or less, 30 mL or less, or 20 mL or less.

[0216] Incidentally, the first container 30 shown in FIG. 1C is a vial. The container body 32 of this first container 30 may be a glass bottle. The glass bottle is a container made of glass. The glass bottle may be colorless or colored. The container body 32 is formed of, for example, borosilicate glass. The container body 32, which is a glass bottle, may have oxygen barrier properties and water vapor barrier properties. A vial is a container that includes a container body, a stopper inserted into the opening of the container body, and a seal as a fixing device 36 for fixing the stopper, and the seal is crimped to the head of the container body together with the stopper using a hand gripper or the like.

[0217] The volume of the first container 30 which is a vial may be 1.0 mL or more, or 3.0 mL or more. The volume of the first container 30 which is a vial may be 200 mL or less, 100 mL or less, 50 mL or less, 30 mL or less, or 20 mL or less.

[0218] The volume of the first container 30, which is a vial, may be 1.0 mL or more and 200 mL or less, 1.0 mL or more and 100 mL or less, 1.0 mL or more and 50 mL or less, 1.0 mL or more and 30 mL or less, or 1.0 mL or more and 20 mL or less. The volume of the first container 30, which is a vial, may be 200 mL or less, 3.0 mL or more and 100 mL or less, 3.0 mL or more and 50 mL or less, 3.0 mL or more and 30 mL or less, or 3.0 mL or more and 20 mL or less.

[0219] In addition, the oxygen permeable portion of the first container 30 can promote oxygen permeation in a state where it is in contact with a gas such as the head space HS, rather than in contact with the liquid L. The oxygen permeable and water vapor permeable portion of the first container 30 can suppress water vapor permeation in a state where it is in contact with the liquid L, rather than in contact with a gas such as the head space HS. From the viewpoint of promoting oxygen permeation of the first container 30, it is preferable that the oxygen permeable portion of the first container 30 is not in contact with the liquid L. In the normal position of the first container 30 including the container body 32 and the stopper 34, when the liquid L does not contact the stopper 34, the stopper 34 is made a part through which oxygen can pass, and the stopper 34 is given the first oxygen permeability in the above-mentioned predetermined range and the second oxygen permeability in the above-mentioned predetermined range, so that deterioration of the quality of the liquid L can be stably suppressed. In this regard, the first container 30, which is a vial bottle, can be stably placed on the mounting surface by bringing the bottom 32a of the container body 32 into contact with the mounting surface. At this time, the stopper 34 is separated from the liquid L. The plug 34 does not come into contact with the liquid agent L. Therefore, when the first container 30 is in a normal storage state, permeation of oxygen within the first container 30 through the first container 30 can be promoted.

[0220] The first container 30 shown in FIG. 1C can maintain a negative internal pressure under atmospheric pressure. The first container 30 can contain a gas while maintaining the gas at a negative pressure under atmospheric pressure. 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 the internal pressure at a negative pressure or positive pressure. Examples of the first container 30 capable of maintaining a negative or positive internal pressure include the above-mentioned vial bottle and a can made of metal.

[0221] Capable of storing gas while maintaining a negative pressure under atmospheric pressure means that the gas can be stored without being damaged while maintaining the internal pressure at a negative pressure of 0.80 atm or more. The container capable of storing gas while maintaining a negative pressure under atmospheric pressure may be airtight when the internal pressure is 0.80 atm. The container capable of storing gas while maintaining a negative pressure under atmospheric pressure may be capable of maintaining a volume at 95% or more of the volume at 1.0 atm when the internal pressure is 0.80 atm. The container capable of storing gas while maintaining a positive pressure in the atmosphere means that the gas can be stored without being damaged while maintaining a positive internal pressure of 1.2 atm or less. The container capable of storing gas while maintaining a positive pressure under atmospheric pressure may be airtight when the internal pressure is 1.20 atm. The container capable of storing gas while maintaining a positive pressure under atmospheric pressure may be capable of maintaining a volume at 1.2 atm or less of the volume at 1.0 atm when the internal pressure is 105% or less of the volume at 1.0 atm when the internal pressure is 1.0 atm.

[0222] The first container 30 is intended to be housed in the second container 40. The first container 30 housed in the second container 40 may be able to house gas without breaking when the difference between the internal pressure of the first container 30 and the internal pressure of the second container 40 is 0.2 atm or less. The first container 30 housed in the second container 40 may be airtight when the difference between the internal pressure of the first container 30 and the internal pressure of the second container 40 is 0.2 atm or less. The first container 30 housed in the second container 40 may have a volume of 95% to 105% of the volume of the first container 30 when the internal pressure of the first container 30 is the same as the internal pressure of the second container 40 when the difference between the internal pressure of the first container 30 and the internal pressure of the second container 40 is 0.2 atm or less. In these states in which the first container 30 is housed in the second container 40, the internal pressure of the first container 30 may be lower than the internal pressure of the second container 40, or the internal pressure of the first container 30 may be higher than the internal pressure of the second container 40.

[0223] It should be noted that the first container 30 is not limited to a vial bottle. As an example, the first container 30 may include a syringe 60. As shown in Figs. 3A to 3C, the syringe 60 constituting the first container 30 may include a cylinder 62 and a piston 66. The cylinder 62 contains the liquid agent L. The cylinder 62 constitutes the container body 32. The piston 66 is partially inserted into the cylinder 62.

[0224] 3A , the cylinder 62 may include a cylinder body 63 made of glass or resin and a metal needle 64. The cylinder 62 is the container body 32 of the first container 30, and forms a storage space S for the liquid agent L. The piston 66 may include a piston body 67 made of glass or resin, and a gasket 68 disposed in the opening 33 of the cylinder 62.

[0225] The gasket 68 may constitute the plug 34 of the first container 30. The gasket 68 may close the opening 33 of the cylinder 62 constituting the container body 32. The opening 33 of the cylinder 62 opens on the side opposite to the needle 64. A piston 66 is inserted into the cylinder 62 from the opening 33. A storage space S for the liquid agent L is defined between the cylinder 62 and the gasket 68. The syringe 60 may further include a cap 69. The cap 69 is removably attached to the needle 64. The cap 69 seals the liquid agent L in the syringe 60 and regulates leakage of the liquid agent L from the needle 64. In the example shown in FIG. 3A, by using the syringe 60 as the first container 30, the syringe 60 taken out of the second container 40 can be used as it is for a patient or the like.

[0226] 3A, the first oxygen permeability and the first water vapor permeability of the material constituting the gasket 68, which is the plug 34, may be set to the above-mentioned ranges. The material of the gasket 68 may be the same as the material of the plug 34 described above. The gasket 68 may contain silicone or silicone rubber. The cylinder 62 may have oxygen barrier properties and water vapor barrier properties.

[0227] 3B, the cylinder 62 may include a cylinder body 63 into which a piston 66 is inserted, and a needle 64 connected to the cylinder body 63 and including an opening 33. The needle 64 constitutes the opening 33. The syringe 60 as the first container 30 may further include a plug 34 that closes the opening 33 provided in the cylinder 62. In this example, the needle 64 may be pierced into the plug 34 having the above-mentioned predetermined first oxygen permeability and first water vapor permeability, and the plug 34 may close the opening 33 opened at the tip of the needle 64.

[0228] As shown in the example of FIG. 3C, the cylinder 62 may include a cylinder body 63 including an opening 33 and into which a piston 66 is inserted, and a needle 64 that can be attached to the cylinder body 63 so as to cover the opening 33. The syringe 60 constituting the first container 30 may be housed in the second container 40 with the needle 64 removed. As shown in FIG. 3C, the cylinder body 63 may include a tip protruding portion 63a. The opening 33 is formed in the tip protruding portion 63a. The cylinder body 63 including the tip protruding portion 63a may be made of glass or resin. The cylinder body 63 including the tip protruding portion 63a may have oxygen barrier properties. The cylinder body 63 including the tip protruding portion 63a may have water vapor barrier properties.

[0229] The needle 64 can be attached to the tip protruding portion 63a so as to cover the opening 33. The needle 64 can be fixed to the cylinder body 63 so as to cover the opening 33. The syringe 60 may include a stopper 34 that can be fixed to the cylinder body 63. The stopper 34 may be attachable to the tip protruding portion 63a. The stopper 34 having the above-mentioned predetermined first oxygen permeability and first water vapor permeability may close the opening 33 when fixed to the cylinder body 63.

[0230] FIG. 3D is a partial cross-sectional view showing a specific example of the syringe 60 shown in FIG. 3C. In the specific example shown in FIG. 3D, the cylinder 62 may further include a cylindrical holder 63b located around the tip protrusion 63a of the cylinder body 63. The cylindrical holder 63b may include an internal thread 63c. The cylindrical holder 63b may be an integral part with the cylinder body 63 without any seams. The cylindrical holder 63b may be configured as a separate part from the cylinder body 63. The cylinder body 63 is made of, for example, glass. The cylinder body 63 may have oxygen barrier properties. The cylinder body 63 may have water vapor barrier properties. The cylindrical holder 63b may have a resin material. The cylindrical holder 63b may have oxygen permeability.

[0231] The plug 34 may be treated as a plug member 39 together with the plug holder 38. The plug holder 38 is cylindrical. The plug holder 38 holds the plug 34 inside. The plug holder 38 may be formed of a resin material. The plug holder 38 may be oxygen permeable. The plug holder 38 is removably attached to the cylinder 62. When the plug holder 38 is attached to the cylinder body 63, the plug 34 held by the plug holder 38 closes the opening 33 of the tip protruding portion 63a. The plug holder 38 holds the plug 34 so that it cannot move relatively in the axial direction. The plug holder 38 may include an external thread 38a that meshes with the internal thread 63c of the cylindrical holding portion 63b. The plug 34 includes a cylindrical portion 34c that contacts the periphery of the tip protruding portion 63a and an insertion closing portion 34d that is inserted into the opening 33 of the tip protruding portion 63a. The opening 33 can be airtightly closed by pressing the tubular portion 34c and the insertion closing portion 34d against the tip protruding portion 63a. In this example, the cylindrical holding portion 63b presses the plug member 39 toward the tip protruding portion 63a due to the elasticity of the cylindrical holding portion 63b. This stably maintains the airtightness of the opening 33. In addition, from the viewpoint of promoting oxygen permeation of the plug 34, as shown in FIG. 3D, the plug 34 does not have to be at least partially covered by the plug holder 38. In other words, the plug 34 may be at least partially exposed from the plug holder 38.

[0232] 3C, needle 64 may include a cylindrical needle portion 64a and a holder portion 64b that holds needle portion 64a. Holder portion 64b may include an external thread that mates with internal thread 63c of cylindrical holder portion 63b.

[0233] 3B to 3D, the first oxygen permeability and the first water vapor permeability of the material constituting the plug 34 may be set within the above-mentioned ranges. The material of the plug 34 may be the same as the material of the plug 34 described above. The plug 34 may contain silicone or silicone rubber. The cylinder 62 may have oxygen barrier properties and water vapor barrier properties.

[0234] 3B to 3D, the first oxygen permeability and the first water vapor permeability of the material constituting the gasket 68 may be set within the above-mentioned ranges. The material constituting the gasket 68 may be the same as the material of the plug 34 described above. The gasket 68 may include silicone or silicone rubber.

[0235] In the example shown in FIG. 3A to FIG. 3D, oxygen in the storage space partitioned by the syringe 60, the gasket 68, the stopper 34, etc. can permeate through the stopper 34 and the gasket 68. The oxygen that has moved outside the syringe 60 can be absorbed by the oxygen absorbent 22 in the second container 40. This reduces the amount of oxygen in the syringe 60, which is the first container 30, and oxygen deterioration of the liquid L can be suppressed. In addition, water vapor permeation through the stopper 34 and the gasket 68 is suppressed. This prevents a concentration change caused by a reduction in water from the medium liquid of the liquid L, and prevents water vapor in the second container 40 from moving into the syringe 60 to hydrolyze the medicinal ingredient of the liquid L. In other words, the quality deterioration of the liquid L caused by water vapor permeation can be suppressed.

[0236] The second container 40 has a volume capable of accommodating the first container 30. The second container 40 can be sealed by welding such as heat sealing or ultrasonic bonding, or by bonding using a bonding material such as an adhesive or bonding material. The second container 40 may be an airtight container. The volume of the second container 40 may be, for example, 5 mL or more and 1200 mL or less. When the first container 30 is a small container such as a vial, for example, a container with a volume of 1 mL or more and 20 mL or less, the volume of the second container may be 1.5 mL or more and 500 mL or less.

[0237] The second container 40 has oxygen barrier properties. When an object has oxygen barrier properties, the oxygen permeability (mL / (m 2 × day × atm) is 10,000 or less. 2×day×atm) may be 10 or less, 5.0 or less, 1.0 or less, 0.50 or less, or 0.10 or less. The oxygen permeability is measured using an OXTRAN (2 / 61) permeability measuring device manufactured by MOCON, USA, in an environment of 23°C temperature and 50% RH. The oxygen permeability (mL / (m 2 There is no particular lower limit for the oxygen permeability (mL / (m 2 × day × atm) may be 0.010 or more.

[0238] When the measurement object does not contain rubber and is not a molded container, the oxygen permeability is measured in accordance with JIS K7126-2:2006 under an environment of 23°C temperature and 50% RH using an OXTRAN (2 / 21) permeability measuring device manufactured by MOCON, USA.

[0239] When the measurement object is at least one of the objects containing rubber and the molded container, the oxygen permeability is a value measured in accordance with ASTM D3985. In this case, the oxygen permeability is a value measured using an OXTRAN (2 / 61) permeability measuring device manufactured by MOCON, USA, in an environment of a temperature of 23°C and a humidity of 50% RH.

[0240] The second container 40 having oxygen barrier properties can usually sufficiently suppress water vapor permeation. The second container 40 may have water vapor barrier properties. When an object has water vapor barrier properties, the water vapor permeability (g / (m 2 This means that the water vapor permeability (g / (m × day)) of the material that constitutes the object having water vapor barrier properties, such as a container, is 1000 or less. 2×day)) may be 10 or less, 5.0 or less, 1.0 or less, 0.50 or less, or 0.20 or less. The water vapor excess is measured in accordance with JIS K7129-2:2019. The water vapor permeability is measured using a PERMATRAN (3 / 33), a permeability measuring device manufactured by MOCON, USA, in an environment with a temperature of 40°C and a humidity of 90% RH. For an object having water vapor barrier properties, the water vapor permeability (g / (m 2 There is no particular lower limit for the water vapor permeability (g / (m 2 ×day)) may be 0.0010 or more.

[0241] Examples of the second container 40 having oxygen barrier properties include a can made of metal, a container having a metal layer formed by deposition or transfer, and a glass bottle. As shown in the example of FIG. 1A and FIG. 1B, the second container 40 may be a film container. The film container is a container made of film. The film constituting the film container may be a laminate including a layer having oxygen barrier properties. The laminate may include a resin layer having oxygen barrier properties such as ethylene-vinyl alcohol copolymer (EVOH) or polyvinyl alcohol (PVA), or a metal vapor deposition film. The second container 40 may include a transparent portion. A part of the second container 40 may be transparent. The entire second container 40 may be transparent. The second container 40 using a laminate and the second container 40 using glass or resin can be given transparency as well as oxygen barrier properties. By giving transparency to the second container 40, the first container 30L containing the liquid agent contained therein can be confirmed from the outside of the second container 40.

[0242] In the example shown in FIG. 1A and FIG. 1B, the second container 40 is a film container. The second container includes a first film (first main film) 41a and a second film (second main film) 41b. The first film 41a and the second film 41b are arranged facing each other. The first film 41a and the second film 41b may be different films from each other. The first film 41a and the second film 41b may be a single film folded back as described later with reference to FIG. 4B and FIG. 4C. The first film 41a and the second film 41b are joined to each other at a linear seal portion 49. The joining at the seal portion 49 may be, for example, welding such as heat sealing or ultrasonic joining, or joining using an adhesive or bonding material. A storage space S for accommodating the first container 30 is formed between the first film 41a and the second film 41b.

[0243] The first film 41a and the second film 41b are peelable at the sealed portion 49. When a user applies force to peel the first film 41a and the second film 41b, the first film 41a and the second film 41b separate from each other at the sealed portion 49. The sealed portion 49 becomes peelable by adjusting the processing conditions during bonding and the material and thickness of the bonding material (sealant layer). The sealed portion 49 may be linear.

[0244] By "peelable" it is meant that a user of the liquid-containing combination medical container 10L can grasp the second container 40 by hand and peel the first film 41a and the second film 41b from each other without using any device or aid. The heat seal strength of the peelably joined seal portion measured in accordance with JIS Z 0238 may be 3N / 15mm or more and 15N / 15mm or less, or 3N / 15mm or more and 6N / 15mm or less. The heat seal strength is the arithmetic mean value of five measured values.

[0245] The seal portion 49 includes a curved first seal portion 49a. The first seal portion 49a may be linear. The first container 30 accommodated in the second container 40 faces the first seal portion 49a. The first container 30 faces the linear first seal portion 49a in the first direction D1. The first seal portion 49a is curved so as to protrude toward a side away from the first container 30 in the first direction D1. The first seal portion 49a is curved so as to protrude toward the outside of the accommodation space S of the second container 40. The first seal portion 49a is curved so as to protrude toward a side that widens the accommodation space S of the second container 40.

[0246] In the illustrated example, the seal portion 49 includes a first side seal portion 49b connected to one end of the first seal portion 49a and a second side seal portion 49c connected to the other end of the first seal portion 49a. Between the first side seal portion 49b and the second side seal portion 49c, an accommodation space S for the second container 40 that accommodates the first container 30 is formed. The minimum distance DXa between the first side seal portion 49b and the second side seal portion 49c along the first film 41a may be shorter than the length L30 of the first container 30 along the direction in which the plug 34 is inserted into the opening 33. The minimum distance DXb between the first side seal portion 49b and the second side seal portion 49c along the second film 41b may be shorter than the length L30 of the first container 30 along the direction in which the plug 34 is inserted into the opening 33. In the illustrated example, the direction in which the plug 34 is inserted into the opening 33 is the same as the first direction D1 in which the first container 30 and the first seal portion 49a face each other.

[0247] The minimum distance DXa along the first film 41a between the first side seal portion 49b and the second side seal portion 49c is the minimum length of the first film 41a between the first side seal portion 49b and the second side seal portion 49c. The minimum distance DXb along the second film 41b between the first side seal portion 49b and the second side seal portion 49c is the minimum length of the second film 41b between the first side seal portion 49b and the second side seal portion 49c. The length L30 of the first container 30 is the axial length of the first container 30, and is usually the longitudinal length of the first container 30.

[0248] By making the minimum distances DXa, DXb along the films 41a, 41b between the side seal portions 49b, 49c shorter than the length L30 of the first container 30, it is possible to prevent the orientation of the first container 30 from changing significantly within the second container 40. In other words, the orientation of the first container 30 within the second container 40 is stabilized. This allows the stopper 34 of the first container 30 and the oxygen absorbing member 20 including the oxygen absorbent 22 to be stably maintained in a facing state as described below, and promotes the discharge of oxygen from the first container 30.

[0249] The seal portion 49 further includes a second seal portion 49d facing the first seal portion 49a in the first direction D1. In the illustrated example, the seal portion 49 includes the first seal portion 49a and the second seal portion 49d facing the first direction D1, and the first side seal portion 49b and the second side seal portion 49c facing the second direction D2. The seal portion 49 is formed in a circumferential shape by the first seal portion 49a, the second seal portion 49d, the first side seal portion 49b, and the second side seal portion 49c. The circumferential seal portion 49 defines the storage space S of the second container 40. Instead of the second seal portion 49d, a folded portion 41x formed by folding back a sheet of film as shown in FIG. 7C described later may be provided.

[0250] As shown in FIG. 1A and FIG. 1B, the first film 41a and the second film 41b each include a main portion 50a forming the storage space S and an extension portion 50b connected to the main portion 50a. The main portion 50a includes a first seal portion 49a, a second seal portion 49d, a first side seal portion 49b, and a second side seal portion 49c, and a portion surrounded by these seal portions 49a, 49d, 49b, and 49c. The extension portion 50b is connected to the main portion 50a at the first seal portion 49a. The extension portion 50b may be connected to at least the curved top portion of the first seal portion 49a. The extension portion 50b may be connected to at least the portion of the first seal portion 49a that protrudes most from the first container 30 in the first direction D1 in which the first container 30 and the first seal portion 49a face each other. In the extension portion 50b, the space between the first film 41a and the second film 41b is open to the outside. In the extension portion 50b, the space between the first film 41a and the second film 41b is not sealed by a seal portion.

[0251] A user can easily apply a peeling force to the first film 41a and the second film 41b by grasping the extension portion 50b. At this time, the peeling force is concentrated at the top of the bend of the first sealed portion 49a. In the illustrated example, the peeling force is concentrated at the bent portion of the bent first sealed portion 49a. This allows the first film 41a and the second film 41b to be easily and smoothly peeled off starting from the bent first sealed portion 49a. In this second container 40, the first sealed portion 49a is the portion to be opened. The portion to be opened is a portion intended to be opened when the second container 40 is opened.

[0252] In the illustrated example, the second direction D2 is perpendicular to the first direction D1. The third direction D3 is perpendicular to both the first direction D1 and the second direction D2. The first film 41a and the second film 41b face each other in the third direction D3. The first film 41a and the second film 41b are rectangular in shape when laid out flat. The first film 41a and the second film 41b include a pair of edges extending in the first direction D1. The first film 41a and the second film 41b include a pair of edges extending in the second direction D2. The edges extending in the first direction D1 form the long sides of the rectangular shape. The edges extending in the second direction D2 form the short sides of the rectangular shape.

[0253] In order to clarify the relationship between directions between the drawings, common directions are indicated in several drawings by arrows with common symbols. The tip of the arrow is the first side of each direction. The opposite side of the arrow is the second side of each direction. An arrow pointing into the paper in a direction perpendicular to the paper surface of the drawing is indicated by a symbol of a cross in a circle, as shown in FIG. 1A, for example. An arrow pointing out of the paper in a direction perpendicular to the paper surface of the drawing is indicated by a symbol of a dot in a circle, as shown in FIG. 1B, for example.

[0254] The second container 40 is not limited to the example shown in Figures 1A and 1B. As shown in Figure 4A, a seal portion 49 may be joined at the periphery of the films 41a and 41b.

[0255] Instead of joining separate films, the films 41a and 41b may be formed from a single folded film. The two films 41a and 41b may be formed from a single seamless film.

[0256] The second container 40 shown in FIG. 4B includes a film 41 folded at a fold portion 41x. The second container 40 can be produced by joining the facing portions of the folded film 41 at a seal portion 49. In the second container 40 shown in FIG. 4B, a storage space S is formed in a portion surrounded by the fold portion 41x and the three-sided seal portion 49. In the example shown in FIG. 4B, the first film 41a and the second film 41b forming the storage space S between the first film 41a and the second film 41b are formed by a single film. There is no seam between the first film 41a and the second film 41b.

[0257] The second container 40 shown in Fig. 4C is also called a pillow type. The two ends of a single film 41 are joined together as a seal portion 49 to form a cylindrical film, and the two ends of the cylindrical film are further joined as a seal portion 49 to obtain the second container 40. In the example shown in Fig. 7D, the first film 41a and the second film 41b that forms the storage space S between the first film 41a and the second film 41b are made of a single film material. There is no seam between the first film 41a and the second film 41b.

[0258] As shown in Fig. 4D, the second container 40 may be a gusset bag. In the example shown in Fig. 4D, the second container 40 includes a first film 41 (first main film) a, a second film (second main film) 41b, a first gusset film 41c, and a second gusset film 41d. The gusset bag can form a rectangular bottom surface. Therefore, the posture of the first container 30 in the second container 40 is stable.

[0259] As shown in Fig. 4E, the second container 40 may be a standing pouch. The second container 40 shown in Fig. 4D includes a first film 41a, a second film 41b, and a bottom film 41e. The standing pouch includes a bottom surface formed by the bottom film 41e. Therefore, the posture of the first container 30 in the second container 40 is stable.

[0260] The film constituting the second container 40 may be transparent. The first container 30 in the storage space S can be observed through the transparent second container 40.

[0261] The second container 40 does not have to be a film container made of a film. As shown in FIG. 3A to FIG. 3C and FIG. 4F, the second container 40 may include a container body 42 and a lid 44. The container body 42 includes a storage section 42a and a flange section 42b. The storage section 42a may form a rectangular storage space S. The first container 30 is stored in this storage space S. The storage section 42a may have 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 oxygen barrier properties. The lid 44 and the container body 42 may be transparent. The thickness of the resin plate having oxygen barrier properties may be 0.05 mm or more and 2 mm or less, or 0.1 mm or more and 1.5 mm or less.

[0262] The second container 40 shown in FIG. 4F can maintain a negative internal pressure under atmospheric pressure. The second container 40 can contain a gas while maintaining the gas at a negative pressure under atmospheric pressure. The second container 40 may be capable of containing a gas while maintaining the gas at a positive pressure under atmospheric pressure. In these examples, the second container 40 may have 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. An example of the second container 40 capable of maintaining a negative or positive internal pressure is a can made of metal.

[0263] The oxygen permeable portion of the first container 30 may be at least partially separated from the second container 40 having oxygen barrier properties. According to this example, it is possible to promote the transfer of oxygen from inside the first container 30 to inside the second container 40. In the illustrated example, a gap G (see FIG. 4D) is formed between the stopper 34 of the first container 30 housed in the second container 40 and the second container 40.

[0264] The oxygen absorbent 22 absorbs oxygen in the second container 40. By absorbing oxygen, the oxygen concentration in the second container 40 decreases, and the oxygen in the first container 30 moves to the second container 40. The amount of the oxygen absorbent 22 is set to an amount that can absorb the total amount of oxygen present in the first container 30 and the second container 40. The oxygen absorbent 22 is not particularly limited as long as it is a composition that can absorb oxygen. The oxygen absorbent 22 may be an iron-based oxygen absorbent or a non-iron-based oxygen absorbent. The oxygen absorbent 22 may be an oxygen scavenger composition in which a metal powder such as iron powder, a reducing inorganic substance such as an iron compound, a reducing organic substance such as polyhydric phenols, polyhydric alcohols, ascorbic acid or a salt thereof, or a metal complex is used as the main agent for the oxygen absorption reaction.

[0265] As shown in FIG. 1A and FIG. 1B, the combined medical container 10L containing the liquid agent may include an oxygen absorbing member 20 housed in a second container 40 together with a first container 30L containing the liquid agent. As shown in FIG. 5A, the oxygen absorbing member 20 may include an oxygen permeable packaging body 23 and an oxygen absorbent 22 housed in the packaging body 23. The oxygen absorbing member 20 containing the oxygen absorbent 22 may be an iron-based moisture-dependent FX type, an iron-based self-reacting S type, an SPE type, a ZP type, a ZI-PT type, a ZJ-PK type, or an E type among oxygen absorbers available from Mitsubishi Gas Chemical Company, Inc. The oxygen absorbing member 20 containing the oxygen absorbent 22 may be an organic self-reacting GLS type, a GL-M type, or a GE type, among oxygen absorbers available from Mitsubishi Gas Chemical Company, Inc. The oxygen absorbing member 20 containing the oxygen absorbent 22 may be an oxygen absorber available from Mitsubishi Gas Chemical Company, Inc., such as ZH type, Z-PKya, Z-PR, Z-PKR, or ZM type for pharmaceutical use.

[0266] In order to promote oxygen absorption by the oxygen absorbent 22, the oxygen absorbing member 20 may include a water retention agent 24 that retains moisture, as shown in Fig. 5C. The water retention agent 24 may be one or more selected from the group consisting of diatomaceous earth, silica, and activated carbon. The water retention agent 24 may be used as a support that supports the oxygen absorbent 22. In an example in which the liquid agent L contains a non-aqueous solvent such as alcohol or oil, the water retention agent 24 that retains moisture is effective in ensuring the oxygen absorption function of the oxygen absorbent 22.

[0267] The oxygen absorbent 22 may be included in the oxygen absorbing film 21. FIG. 5B shows an example of a laminate 46 including the oxygen absorbing film 21. The laminate 46 including the oxygen absorbing film 21 may constitute the films 41a to 41e of the second container 40 shown in FIG. 1A, FIG. 1B, and FIG. 4A to FIG. 4E. The laminate 46 including the oxygen absorbing film 21 may constitute the container body 42 or the lid 44 of the second container 40 shown in FIG. 4F. The laminate 46 shown in FIG. 5B includes a first layer 46a, a second layer 46b, and a third layer 46c. The first layer 46a may be an outermost layer made of polyethylene terephthalate, polyamide, or the like. The second layer 46b may be an oxygen barrier layer made of aluminum foil, a metal oxide vapor deposition film, a metal vapor deposition film, or the like. The third layer 46c may be an innermost layer forming a heat seal layer. The illustrated third layer 46c includes a base material 25 made of a thermoplastic resin and an oxygen absorbent 22 dispersed in the base material 25. The oxygen absorbent 22 is not limited to being included in the heat seal layer or the innermost layer 46c, and may be included in an intermediate layer of the laminate, such as an adhesive layer.

[0268] As another example, the first container 30 may include an oxygen absorbing film 21 containing an oxygen absorbent 22 .

[0269] The medical container set 15 and the combined medical container 10 may include an oxygen detector 28 that detects the oxygen state in the second container 40. The oxygen detector 28 may display information related to the detected oxygen state. The oxygen detector 28 may include a display unit 28a that displays information related to the oxygen state. The oxygen detector 28 may detect the oxygen concentration. The oxygen detector 28 may display the detected oxygen concentration value. The oxygen detector 28 may display the detected oxygen concentration value by color. The oxygen detector 28 may display the oxygen concentration range to which the detected oxygen concentration value belongs by color.

[0270] The oxygen detector 28 may include a variable organic dye that reversibly changes color due to oxidation and reduction. For example, the oxygen reducer may include an organic dye such as a thiazine dye, an azine dye, or an oxazine dye, and a reducing agent, and may be in a solid form. The oxygen reducer may include an oxygen indicator ink composition. The oxygen indicator ink composition may include a resin solution, a thiazine dye, etc., a reducing sugar, and an alkaline substance. The thiazine dye, etc., the reducing sugar, and the alkaline substance may be dissolved or dispersed in the resin solution. The substance included in the oxygen detector 28 may reversibly change due to oxidation and reduction. By using an oxygen detector 28 that includes a reversible substance, the oxygen detector 28 that is contained in the container before deoxidation is completed changes its display color as the oxygen in the container is deoxidized. By observing the display of the oxygen detector 28, the oxygen-related condition in the container can be understood. In addition, the oxygen detector 28 contained in the container can change its display color to indicate an increase in oxygen concentration after deoxygenation is complete, for example, if a pinhole or the like has formed in the container during the distribution process and oxygen has flowed into the container.

[0271] The oxygen detector 28 may be a commercially available tablet-type oxygen detector. The oxygen detector 28 may be an oxygen detector available from Mitsubishi Gas Chemical Co., Ltd. under the product name "Ageless Eye". The oxygen detector 28 may be an oxygen detector coated with an ink composition having an oxygen detection function, for example, an oxygen detector available from Mitsubishi Gas Chemical Co., Ltd. under the product name "Paper Eye". "Ageless Eye" and "Paper Eye" are functional products that can easily indicate, by a color change, that an oxygen-free state in which the oxygen concentration in a transparent container is less than 0.1% by volume. As the oxygen detector 28, a material that can be used for maintaining the freshness of food and maintaining the quality of medical drugs, etc., together with an oxygen scavenger, for example, an oxygen scavenger available from Mitsubishi Gas Chemical Co., Ltd. under the product name "Ageless", may be used.

[0272] As shown in FIG. 1A, the oxygen detector 28 may be arranged so that the display unit 28a can be observed from the outside of the transparent second container 40. In the example shown in FIG. 1A, the oxygen detector 28 is accommodated in the second container 40, similar to the oxygen absorbent 22 and the oxygen absorbing member 20. The oxygen detector 28 may be welded to the inner surface of the second container 40 or the outer surface of the first container 30, or may be joined via a bonding material. The oxygen detector 28 may be arranged so that the display unit 28a is not obscured by the oxygen absorbing member 20 or the water retention agent 24. In addition, when a label is attached to the first container 30, the oxygen absorbing member 20 and the oxygen detector 28 may be arranged so as not to cover the label.

[0273] Furthermore, the oxygen detector 28 may detect the oxygen state in the first container 30. That is, the medical container set 15 and the combined medical container 10 may include an oxygen detector 28 that detects the oxygen state in the first container 30. The oxygen detector 28 may be housed in the first container 30. The oxygen detector 28 may display information about the detected oxygen state in the first container 30. The oxygen detector 28 may include a display unit 28a that displays information about the oxygen state in the first container 30. The oxygen detector 28 may detect the oxygen concentration in the first container 30. The oxygen detector 28 may display the detected oxygen concentration value in the first container 30. The oxygen detector 28 may display the detected oxygen concentration value in the first container 30 by color. The oxygen detector 28 may display the oxygen concentration range to which the detected oxygen concentration value in the first container 30 belongs by color.

[0274] A method for manufacturing the combined medical container 10L containing a liquid agent will be described below. By manufacturing the combined medical container 10L containing a liquid agent, a first container 30L containing a liquid agent with an adjusted oxygen concentration can be obtained.

[0275] Next, a method for producing the liquid-containing combination medical container 10L shown in FIGS. 1A to 1C will be described with reference to FIGS. 6A to 6C.

[0276] First, as shown in FIG. 6A, a first container 30L containing a liquid agent, an oxygen absorbing member 20, an oxygen detector 28, and a second container 40 are prepared. The second container 40 is not yet closed. In the example shown in FIG. 6A, the first film 41a and the second film 41b are joined at a first seal portion 49a, a first side seal portion 49b, and a second side seal portion 49c. A space S for accommodating the first container 30, the oxygen absorbing member 20, and the oxygen detector 28 is generally formed by this three-sided seal. On the other hand, the first film 41a and the second film 41b are not joined at a second seal portion 49d. That is, the second container 40 has an opening 40a that communicates with the storage space S. In the second container 40 shown in FIG. 6A to FIG. 6C, the lid 44 is not joined to the container body 42, and the opening 40a may be formed.

[0277] The first container 30L containing the liquid agent is manufactured by filling the first container 30 with the liquid agent L. For example, the liquid agent L is manufactured using a manufacturing line installed in a sterile environment maintained at a positive pressure. The sterile environment is maintained at a positive pressure from the viewpoint of suppressing the intrusion of foreign matter such as bacteria. As a result, the internal pressure of the obtained first container 30L containing the liquid agent becomes a positive pressure, similar to the manufacturing environment.

[0278] 6B, the first container 30 is accommodated in the accommodation space S of the second container 40. In the illustrated example, the first container 30 is accommodated in the accommodation space S of the second container 40 such that the container body 32 of the first container 30 faces the first seal portion 49a. The bottom portion 32a of the container body 32 faces the first seal portion 49a in the first direction D1.

[0279] Next, as shown in FIG. 6C, the oxygen absorbing member 20 and the oxygen detector 28 are accommodated in the accommodation space S of the second container 40. The oxygen absorbing member 20 is sheet-shaped. The oxygen absorbing member 20 is accommodated in the accommodation space S of the second container 40 so that one side edge of the sheet-shaped oxygen absorbing member 20 faces the stopper 34 of the first container 30. The oxygen detector 28 is sheet-shaped. The sheet-shaped oxygen detector 28 is overlapped with the oxygen absorbing member 20 in the third direction D3. The amount of the oxygen absorbent 22 is set to an amount capable of absorbing the total amount of oxygen present in the first container 30 and the second container 40.

[0280] Thereafter, the first film 41a and the second film 41b are joined at the second seal portion 49d to close the second container 40. The first film 41a and the second film 41b may be joined using a joining material such as an adhesive or a bonding material, or may be welded by heat sealing, ultrasonic bonding, or the like. The second container 40 is made airtight. As a result, the liquid-containing combined medical container 10L is obtained. Prior to closing the second container 40, the storage space S of the second container 40 may be replaced with an inert gas. The second container 40 may be closed under an inert gas atmosphere. The second seal portion 49d may be formed in a linear shape, unlike the first seal portion 49a. The second seal portion 49d may be joined in a non-peeling manner, unlike the first seal portion 49a. Therefore, even in a state in which the first container 30, the oxygen absorbing member 20, and the oxygen detector 28 are housed therein, the first film 41a and the second film 41b can be easily and stably joined at the second seal portion 49d.

[0281] The steps up to closing the second container 40 may be performed in a sterile environment. That is, the first container 30L containing the liquid agent, which has been manufactured in a sterile condition, and the second container 40 and the oxygen absorbing member 20, which have been sterilized or manufactured in a sterile condition, are brought into a sterile environment, such as a sterile chamber. In the sterile environment, the second container 40 containing the first container 30L containing the liquid agent is closed. The inside of the second container 40 containing the first container 30L containing the liquid agent is also in a sterile state. That is, the first container 30L containing the liquid agent can be stored in the second container 40 in a sterile condition.

[0282] In the above manner, a combined medical container 10L containing a liquid agent as shown in Figs. 1A and 1B is obtained. In the obtained combined medical container 10L containing a liquid agent, a first container 30L containing a liquid agent is stored in a second container 40. The oxygen absorbent 22 of the oxygen absorbing member 20 absorbs oxygen in the second container 40. The second container 40 has oxygen barrier properties. This reduces the oxygen concentration (%) in the second container 40. As the oxygen concentration in the second container 40 decreases, oxygen passes through the stopper 34, which has oxygen permeability, and moves from inside the first container 30 to inside the second container 40. This reduces the oxygen concentration (%) in the head space HS of the first container 30, and reduces the amount of oxygen dissolved (mg / L) in the liquid agent L contained in the first container 30. The first oxygen permeability of the material constituting the stopper 34 is 0.00010(cc x mm / (mm 2 The first oxygen permeability of the material constituting the plug 34 is 0.00050 (cc×mm / (mm 2 × day)) or more, and 0.00075 (cc × mm / (mm 2 × day)) or more, and 0.0010(cc×mm / (mm 2 × day)) or more, and 0.0020 (cc × mm / (mm 2 ×day) or more. Therefore, oxygen permeation through the first container 30 is promoted, and oxygen transfer from the first container 30 to the second container 40 proceeds quickly. This makes it possible to effectively suppress oxygen deterioration of the liquid agent L.

[0283] The oxygen concentration (%) in the head space HS of the first container 30 is also simply referred to as the oxygen concentration (%) in the first container 30.

[0284] 3A to 3D, oxygen permeation through the stopper 34 of the syringe 60 and the gasket 68 constituting the first container 30 is promoted, thereby suppressing oxygen deterioration of the liquid agent L. Water vapor permeation through the stopper 34 of the syringe 60 and the gasket 68 is suppressed, thereby suppressing quality deterioration of the liquid agent L.

[0285] By using a sufficient amount of oxygen absorbent 22, the oxygen concentration in the second container 40 and the oxygen concentration in the first container 30 can be maintained sufficiently low, for example, less than 0.3%, 0.1% or less, 0.05% or less, less than 0.03%, or even 0%. By using a sufficient amount of oxygen absorbent 22, the amount of oxygen dissolved in the liquid L can be significantly reduced, for example, less than 0.15 mg / L, 0.04 mg / L or less, 0.03 mg / L or less, 0.02 mg / L or less, less than 0.015 mg / L, or even preferably 0 mg / L.

[0286] 1A and 1B, the stopper 34 faces the oxygen absorbing member 20. Therefore, it is possible to effectively prevent the movement path of oxygen passing through the stopper 34 from inside the first container 30 toward the oxygen absorbing member 20 from being unintentionally blocked, for example, the pair of films 41a, 41b from sticking to each other. This allows the amount of oxygen in the first container 30 to be steadily and rapidly reduced.

[0287] On the other hand, water vapor can also pass through the plug 34 that has oxygen permeability. However, the first water vapor permeability of the material that constitutes the plug 34 is 1.0 (mg×mm / (mm 2 The first water vapor permeability of the material constituting the plug 34 is 0.80 (mg×mm / (mm 2 × day)) or less, and 0.50 (mg × mm / (mm 2 × day)) or less, and 0.25 (mg × mm / (mm 2 × day) or less, and 0.15 (mg × mm / (mm 2 ×day) or less. In this way, the water vapor permeation of the first container 30 is suppressed, thereby suppressing deterioration in the quality of the liquid L. For example, when the liquid L contains a non-aqueous medium, it is possible to suppress a large amount of water vapor from passing through the stopper 34 and moving from the second container 40 into the first container 30. This suppresses hydrolysis of the medicinal ingredient of the liquid L. When the liquid L contains an aqueous medium, evaporation of the aqueous medium and water vapor permeation of the first container 30 are suppressed. This suppresses changes in the concentration of the medicinal ingredient in the liquid L and changes in the hydrogen ion concentration of the liquid L.

[0288] In contrast, the conventional technology could not sufficiently reduce the amount of oxygen in a container containing a liquid. For this reason, the liquid was sometimes freeze-dried and powdered before storage. By powdering, oxygen deterioration can be suppressed. However, powdering a drug used as a liquid and returning the powdered drug to a liquid L when used is a major disadvantage in terms of effort, time, and cost. The first container 30L containing a liquid used in the liquid-containing combination medical container 10L can be manufactured as usual using existing equipment, etc. While eliminating the need for equipment renovation or capital investment, the quality deterioration of the liquid L in the first container 30 can be suppressed. In addition, the effort of freeze-drying the liquid L and returning the powder to a liquid can be eliminated.

[0289] In addition to sufficiently reducing the oxygen concentration in the first container 30, the decomposition of the liquid L by oxygen can also be suppressed by quickly reducing the oxygen concentration in the first container 30. Therefore, the oxygen in the space not occupied by the liquid L in the first container 30, that is, the oxygen in the so-called head space HS, may be replaced with an inert gas before closing the first container 30. The oxygen dissolved in the liquid may be removed by bubbling an inert gas in the liquid L. By inert gas replacement or bubbling, the oxygen concentration in the first container 30 in the equilibrium state can be about 1.0%, for example, about 0.50% or more and 1.0% or less. This allows the amount of oxygen in the first container 30 to be quickly reduced. The inert gas is a stable gas with low reactivity. Examples of the inert gas include rare gases such as nitrogen, helium, neon, and argon.

[0290] The adjustment of the amount of oxygen in the first container 30 in the second container 40 may be performed until the permeation of oxygen through the first container 30 reaches equilibrium. The adjustment of the amount of oxygen in the first container 30 in the second container 40 may be performed until the oxygen concentration in the second container 40 falls to a predetermined value. The adjustment of the amount of oxygen in the first container 30 in the second container 40 may be performed until the oxygen concentration in the first container 30 falls to a predetermined value. The adjustment of the amount of oxygen in the first container 30 in the second container 40 may be performed until the amount of oxygen dissolved in the liquid agent L in the first container 30 falls to a predetermined value. The adjustment of the amount of oxygen in the first container 30 in the second container 40 may be performed until the liquid agent L in the liquid agent-containing combined medical container 10L is used. In addition, while the first container 30 is contained in the second container 40 and the amount of oxygen is adjusted, the liquid agent-containing combined medical container 10L may be circulated.

[0291] Furthermore, as already explained, the use of a combination container including a first container, a second container, and an oxygen absorber for the liquid L has not been sufficiently considered in the past. On the other hand, when the present inventors considered the application of the combination container to the liquid L, they found that there were problems specific to the liquid that were not a problem with food and the like. In particular, if the first container that contains a liquid that is easily deteriorated by oxygen is given high oxygen permeability and oxygen permeation is promoted to more effectively suppress oxygen deterioration of the liquid, the quality deterioration of the liquid due to water vapor permeation becomes more noticeable. Therefore, in order to apply the combination container to the liquid and handle the liquid as a liquid-containing combination medical container, it is necessary to deal with two problems, namely, suppression of deterioration caused by oxygen and suppression of deterioration caused by water vapor, which are conflicting solutions. In other words, in a combination medical container applied to a liquid, it is necessary to impart normally conflicting properties, such as promoting oxygen permeation and suppressing water vapor permeation, to the first container that contains the liquid. Through repeated intensive studies aimed at solving such problems, it has been found that a stopper included in the first container can be given permeability properties that can sufficiently promote oxygen permeation and sufficiently suppress water vapor permeation, and further, that the quality deterioration of the liquid agent can be suppressed by using a stopper given such permeability. That is, the first container 30 having the above-mentioned first oxygen permeability in the predetermined range and the first water vapor permeability in the predetermined range can suppress the deterioration of the liquid agent L caused by oxygen while suppressing the deterioration of the liquid agent caused by water vapor, which did not exist in the past. In this respect, the action and effect of this embodiment is remarkable and far beyond the range predicted from the state of the art at the time of filing the present application.

[0292] As shown in FIG. 7A, the manufacturing method of the liquid-containing combination medical container 10L may include a step of attaching the second plug 35 to the plug 34 or the container body 32 and covering the plug 34 with the second plug 35. This step may be performed after the adjustment of the oxygen amount of the first container 30 in the second container 40 is completed. This step may be performed after the oxygen concentration has sufficiently decreased or after a certain period of time has passed. According to this step, the opening 33 can be closed using both the plug 34 and the second plug 35. By attaching the second plug 35, oxygen permeation of the first container 30 can be suppressed. That is, by using the second plug 35, the state in which the oxygen amount in the first container 30 is reduced can be stably maintained. In addition, by attaching the second plug 35, water vapor permeation of the first container 30 can be suppressed. That is, by using the second plug 35, quality deterioration of the liquid L caused by water vapor can be sufficiently suppressed.

[0293] The material constituting the second plug 35 may have a first oxygen permeability in the above-mentioned predetermined range and a first water vapor permeability in the above-mentioned predetermined range. The material constituting the second plug 35 may have a lower first oxygen permeability and a lower first water vapor permeability than the material constituting the plug 34. The second plug 35 may have a lower second oxygen permeability and a lower second water vapor permeability than the plug 34. The second plug 35 may have oxygen barrier properties. The second plug 35 may have water vapor barrier properties.

[0294] As shown in FIG. 7B, the manufacturing method of the liquid-containing combination medical container 10L may include a step of closing the opening 33 with a second plug 35 instead of the plug 34. In this step, the plug 34 is removed from the container body 32, and the opening 33 of the container body is closed with the second plug 35. This step may be performed after the adjustment of the oxygen amount of the first container 30 in the second container 40 is completed. This step may be performed after the oxygen concentration has sufficiently decreased or after a certain period of time has passed. By using the second plug 35 having a first oxygen permeability lower than the first oxygen permeability of the plug 34, oxygen permeation of the first container 30 can be suppressed. By using the second plug 35 having a second oxygen permeability lower than the second oxygen permeability of the plug 34, oxygen permeation of the first container 30 can be suppressed. As a result, by using the second plug 35, the state in which the oxygen amount in the first container 30 is reduced can be stably maintained. By using the second plug 35 having a first water vapor permeability lower than the first water vapor permeability of the plug 34, it is possible to suppress water vapor permeation of the first container 30. By using the second plug 35 having a second water vapor permeability lower than the second water vapor permeability of the plug 34, it is possible to suppress water vapor permeation of the first container 30. As a result, by using the second plug 35, it is possible to sufficiently suppress quality deterioration of the liquid agent L caused by water vapor.

[0295] These second plugs 35 may be attached to the plug 34 or the container body 32 by screwing, fitting, or the like. These second plugs 35 may be attached to the plug 34 or the container body 32 using a bonding material such as an adhesive or a pressure sensitive adhesive. These additional steps may be performed in an inert gas atmosphere with the second container 40 open. These additional steps may be performed without opening the second container 40, for example, by manipulating the second plugs 35 through a film constituting the second container 40.

[0296] When the combined medical container 10L containing the liquid is stored, shipped, or distributed, the combined medical container 10L containing the liquid may be further folded as shown in FIG. 8A. In the example shown in FIG. 8A, the second container 40 is bent with the second film 41b on the inside. FIG. 1A shows a first folding axis BA1 along which the second container 40 is folded. By bending the second container 40, the second portion 40P2, which was located on one side (first side) in the first direction D1 from the first portion 40P1 in the unfolded state of the second container 40, faces the first portion 40P1 containing the first container 30 of the second container 40 from the third direction D3. That is, the first portion 40P1 and the second portion 40P2 overlap in the third direction D3. The first portion 40P1 and the second portion 40P2 may be in contact with each other or may be separated from each other. The first portion 40P1 and the second portion 40P2 may be joined together.

[0297] The oxygen absorbing member 20 containing the oxygen absorbent 22 is in a sheet shape. The sheet-shaped oxygen absorbing member 20 is bent together with the second container 40. The middle part of the bent oxygen absorbing member 20 is located on a bent apex (folded-back apex) 41bx of the second film 41b. As shown in FIG. 8A, the bent apex 41bx is the position of the folded second film 41b that protrudes most toward the first side in the first direction D1. The bent apex 41bx is the position farthest from the first container in the direction in which the plug 34 is inserted into the container body 32.

[0298] 8A, by folding the sheet-like oxygen absorbing member 20 together with the second film 41b, it becomes easy to secure an oxygen transfer path connecting the first container 30 and the oxygen absorbing member 20. More specifically, a gap is easily formed between the oxygen absorbing member 20, the stopper 34 of the first container 30, and the second film 41b. Since oxygen can stably transfer from the stopper 34 to the oxygen absorbing member 20 through this gap, the oxygen concentration in the first container 30 and the amount of oxygen dissolved in the liquid agent L contained in the first container 30 can be stably reduced.

[0299] 8A, the oxygen detector 28 is positioned between the oxygen absorbing member 20 and the first film 41a. The display portion 28a of the oxygen detector 28 arranged in this manner can be easily observed through the transparent first film 41a. Therefore, by observing the display portion 28a of the oxygen detector 28, information regarding the oxygen concentration in the second container 40 can be stably obtained.

[0300] In the example shown in FIG. 8A, the second container 40 is folded twice with the second film 41b on the inside. In addition to the first folding axis BA1, FIG. 1A shows a second folding axis BA2 along which the second container 40 is folded. By folding along the second folding axis BA2, the third portion 40P3, which was located on the other side (second side) in the first direction D1 from the first portion 40P1 in the unfolded state of the second container 40, faces the third direction D3 with respect to the first portion 40P1 containing the first container 30 of the second container 40. That is, the first portion 40P1 and the third portion 40P3 overlap in the third direction D3. The first portion 40P1 and the third portion 40P3 may be in contact with each other or may be separated from each other. The first portion 40P1 and the third portion 40P3 may be joined together. The second container 40 is folded about the second folding axis BA2 so that the second film 41b faces inward. By folding the second container 40 twice, the combined medical container 10L containing the liquid agent can be made compact.

[0301] By folding twice, the second portion 40P2 and the third portion 40P3 are located on the same side with respect to the first portion 40P1. The first film 41a in the first portion 40P1 is not covered by the second portion 40P2 and the third portion 40P3. Therefore, the first container 30 can be clearly observed through the first film 41a of the second container 40. This makes it easy to observe the state of the first container 30 and the state of the liquid agent L contained in the first container 30. In addition, the label attached to the first container 30 can also be easily observed. Information regarding the liquid agent L may be written on this label.

[0302] In the illustrated example, the first portion 40P1, the third portion 40P3, and the second portion 40P2 are overlapped in this order. The second portion P2 and the third portion 40P3 may be in contact with each other or may be separated from each other. The second portion P1 and the third portion 40P3 may be joined together. According to this example, the radius of curvature of the bend of the second portion 40P2 relative to the first portion 40P1 can be increased. Therefore, the oxygen transfer path connecting the first container 30 and the oxygen absorbing member 20 can be more stably secured. As a result, oxygen can stably transfer from the stopper 34 to the oxygen absorbing member 20, so that the oxygen concentration in the first container 30 and the amount of oxygen dissolved in the liquid agent L contained in the first container 30 can be stably reduced.

[0303] As shown in FIG. 8B, the combined medical container 10L containing the liquid may further include an outer box 55 that contains the second container 40. The outer box 55 includes a bottom 56, a top 57 facing the bottom 56, and a side wall 58 located between the bottom 56 and the top 57. As shown in FIG. 8A, the second container 40 is folded so that the first portion 40P1, the second portion 40P2, and the third portion 40P3 overlap. As shown by the two-dot chain line in FIG. 8A, the second container containing the first container 30 may be contained in the outer box 55 such that the bottom 32a of the container body 32 of the first container 30 faces the bottom 56 of the outer box 55 and the stopper 34 of the first container 30 faces the top 57 of the outer box 55. According to this example, the combined medical container 10L containing the liquid can be stored with the bottom 56 positioned on the placement surface of a desk, shelf, or the like. At this time, the oxygen-permeable plug 34 separates from the liquid agent L and comes into contact with the gas in the head space HS in the first container 30. By storing the liquid agent-containing combined medical container 10L in this state, oxygen permeation through the plug 34 is promoted, and the oxygen concentration in the first container 30 and the amount of oxygen dissolved in the liquid agent L can be quickly reduced after the first container 30 is placed in the second container 40.

[0304] Next, a method of using the combined medical container 10L containing the liquid agent will be described.

[0305] When using the liquid agent L contained in the combination medical container 10, first, the second container 40 is opened. Next, the first container 30L containing the liquid agent is removed from the opened second container 40. Thereafter, the liquid agent L is removed from the first container 30L containing the liquid agent, and the liquid agent L can be used. For the first container 30L containing the liquid agent shown in FIG. 1C, the first container 30 can be opened by removing the fixing device 36 from the container body 32 and further removing the stopper 34 from the container body 32. This allows the liquid agent L in the first container 30 to be used.

[0306] In the liquid-containing combined medical container 10L shown in FIG. 1A and FIG. 1B, the second container 40 includes a first film 41a and a second film 41b that accommodates the first container 30 between the first film 41a. The first film 41a and the second film 41b are joined at a seal portion 49 so as to be peelable. The seal portion 49 includes a first seal portion 49a that faces the first container 30. The first seal portion 49a is linear. The first seal portion 49a is curved. The first seal portion 49a is curved so as to protrude toward the side away from the first container 30 in the first direction D1 in which the first seal portion 49a and the first container 30 face each other. Therefore, the second container 40 can be easily opened by peeling off the first film 41a and the second film 41b at the first seal portion 49a starting from the curved first seal portion 49a.

[0307] Moreover, when the second container 40 is opened, the first container 30 is located at the open portion of the second container 40. In particular, the first container 30 can be positioned in the second container 40 by the first seal portion 49a protruding toward the side away from the first container 30. Therefore, when the second container 40 is opened, the first container 30 can be stably held. This allows the first container 30 to be removed from the second container 40. That is, when the liquid agent L contained in the first container 30 is to be used, the first container 30 can be easily removed from the second container 40.

[0308] In the example shown in FIG. 1A and FIG. 1B, the first container 30 was placed in the second container 40 so that the container body 32 faced the first seal portion 49a and the stopper 34 faced the oxygen absorbing member 20. As shown in FIG. 1D, the first container 30 may be placed in the second container 40 so that the stopper 34 faces the first seal portion 49a and the bottom portion 32a of the container body 32 faces the oxygen absorbing member 20. The combined medical container 10L containing a liquid agent shown in FIG. 1D can also be expected to have the following effects as the combined medical container 10L containing a liquid agent shown in FIG. 1A and 1B. That is, the first film 41a and the second film 41b can be easily peeled off at the first seal portion 49a starting from the bent first seal portion 49a, and the second container 40 can be easily opened. Furthermore, when the second container 40 is opened, the first container 30 is located at the open portion of the second container 40. In particular, the first container 30 is positioned in the second container 40 by the first seal portion 49a protruding toward the side away from the first container 30. Therefore, when the second container 40 is opened, the first container 30 can be stably held. This allows the first container 30 to be easily removed from the second container 40 when the liquid agent L contained in the first container 30 is used. In particular, in the example shown in FIG. 1D, when the second container 40 is opened, the fastener 36 of the first container 30 and the head portion 32d and neck portion 32c of the container body 32 can be held, and the first container 30 can be more stably removed from the second container 40.

[0309] 1A and 1D, furthermore, no waste such as scraps is generated when the second container 40 is opened. The oxygen absorbing member 20 and the oxygen detector 28 are contained in the second container 40 even after the first container 30 is removed from the second container 40. Therefore, it is easy to handle the second container 40, the oxygen absorbing member 20, and the oxygen detector 28 that are discarded after the second container 40 is opened.

[0310] As shown in FIG. 1A, the seal portion 49 may include a main seal portion 49X that defines a space S that accommodates the first container 30, and an auxiliary seal portion 49Y that joins the first film 41a and the second film 41b at the extension portion 50b. In the illustrated example, the main seal portion 49X includes the above-mentioned first seal portion 49a, the first side seal portion 49b, the second side seal portion 49c, and the second seal portion 49d. By providing the auxiliary seal portion 49Y, it is possible to prevent the first film 41a and the second film 41b from curling at the extension portion 50b. Therefore, by providing the auxiliary seal portion 49Y, it is possible to make it easier to grip the extension portion 50b of the first film 41a and the second film 41b. This makes it easier to handle the liquid-containing combined medical container 10L. In addition, the rigidity of the second container 40 is improved at the extension portion 50b, and the first container 30 can be protected by the second container 40.

[0311] In the example shown in FIG. 1A, the auxiliary seal portion 49Y includes a first auxiliary seal portion 49Ya connected to the first side seal portion 49b and a second auxiliary seal portion 49Yb connected to the second side seal portion 49c. The first auxiliary seal portion 49Ya may extend linearly on an extension line of the first side seal portion 49b. The second auxiliary seal portion 49Yb may extend linearly on an extension line of the second side seal portion 49c. According to these examples, it is possible to more effectively prevent the first film 41a and the second film 41b from curling at the extension portion 50b. According to these examples, the rigidity of the second container 40 is more effectively improved at the extension portion 50b.

[0312] The configuration of the auxiliary seal portion 49Y is not limited to the configuration shown in FIG. 1A and the like. As shown in FIG. 1E, the auxiliary seal portion 49Y may be separated from the main seal portion 49X. In the example shown in FIG. 1E, the auxiliary seal portion 49Y includes a first auxiliary seal portion 49Ya located on an extension line of the first side seal portion 49b and a second auxiliary seal portion 49Yb located on an extension line of the second side seal portion 49c. The first auxiliary seal portion 49Ya and the second auxiliary seal portion 49Yb may be linear, may be on a broken line, or may be dot-shaped as shown in FIG. 1E. These examples also prevent the first film 41a and the second film 41b from curling at the extension portion 50b. These examples also improve the rigidity of the second container 40 at the extension portion 50b.

[0313] As shown in FIG. 9, the liquid L may be an injection. Examples of the injection include an anticancer drug, an antiviral drug, a vaccine, and an antipsychotic. The liquid L may be taken out from the first container 30 using a syringe 60. The syringe 60 may include a cylinder 62 and a piston 66, similar to the syringe constituting the first container 30 described above. The cylinder 62 may include 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 may include 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 partition a storage space for the liquid L within the cylinder body 63. The liquid L injected into the syringe 60 may be transferred from the syringe 60 to another syringe, container, or the like before being administered to a patient or the like. In this example, it may be administered to the patient from a separate syringe, container, etc.

[0314] In the example shown in FIGS. 3A to 3D in which the syringe 60 constitutes the first container 30, the second container 40 can be opened, and the syringe 60 taken out from the second container 40 can be used on a patient as is.

[0315] The pressure in the first container 30L containing the liquid may be adjusted. As an example, the pressure in the first container 30L containing the liquid may be maintained low or may be maintained at a negative pressure. According to this example, it is possible to suppress unintended leakage of the liquid L during storage of the first container 30L containing the liquid, scattering of the liquid L when the first container 30 is opened, and the like. The problem of leakage and scattering is more serious in a toxic liquid, for example, a highly pharmacologically active drug. In addition, in the example shown in FIG. 9, when the first container 30L containing the liquid is at a positive pressure, the liquid L automatically enters the syringe 60. In this case, it becomes difficult to inject the desired amount of the liquid L into the syringe 60 with high accuracy.

[0316] On the other hand, liquid agents L that deteriorate due to post-sterilization treatment carried out after production using, for example, gas, heat, gamma rays, etc., such as anticancer drugs, antiviral drugs, vaccines, antipsychotics, etc., are produced in a sterile environment and sealed in a container. That is, liquid agents L to which terminal sterilization cannot be applied are produced by an aseptic operation method. This sterile environment is usually maintained at a predetermined positive pressure to suppress the intrusion of bacteria. Therefore, the pressure inside the container becomes a predetermined positive pressure corresponding to the sterile environment, and it is difficult to adjust the internal pressure of the container after the container is closed.

[0317] The combined medical container 10L containing the liquid agent can address such problems. As described above, the first container 30L containing the liquid agent is stored in the second container 40. During this storage, oxygen in the first container 30 passes through the first container 30 and moves into the second container 40. This causes the pressure in the first container 30 to decrease. That is, the pressure of the first container 30 containing the liquid agent L can be adjusted after the first container 30 is closed and the liquid agent L is sealed in.

[0318] 3A to 3C, the syringe 60 may further include a fixing part 61 that restricts the relative movement of the piston 66 with respect to the cylinder 62. The fixing part 61 is removably attached to one or more of the cylinder 62 and the piston 66. The fixing part 61 makes it possible to maintain the storage space S partitioned by the cylinder 62 and the piston 66 at a negative or positive pressure. In other words, the pressure in the storage space S of the syringe 60 can be maintained lower or higher than the pressure in the second container 40 and the pressure of the environment in which the syringe 60 is placed.

[0319] 3A to 3C, the pressure inside the syringe 60 can be adjusted by gas permeating through the stopper 34 and the gasket 68. Specifically, the storage space S of the first container 30 partitioned by the cylinder body 63 and the gasket 68 can be depressurized, particularly to a negative pressure. By reducing the internal pressure of the syringe 60, splashing of the liquid L when the fixing part 61 is removed can be suppressed.

[0320] From the viewpoint of adjusting the internal pressure of the first container 30, the second container 40 capable of storing gas under atmospheric pressure while maintaining it at a negative pressure may be used. For example, the second container 40 shown in FIG. 3A to FIG. 3 and FIG. 4F may be used, and the second container 40 storing the first container 30 may be closed under an inert gas atmosphere maintained at a negative pressure. The pressure in the closed second container 40 becomes lower than atmospheric pressure. In this case, oxygen transmission from the first container 30 to the second container 40 is promoted. In particular, the pressure in the first container 30 can be significantly adjusted by ensuring a large volume of the second container 40 or by significantly lowering the initial pressure of the second container 40. As a result, the pressure in the first container 30, which was initially positive, can be adjusted to atmospheric pressure (1 atm) or lower, and further adjusted to negative pressure, by storing the first container 30 in the second container 40. As a result, the first container 30L containing the liquid agent with the adjusted pressure can be manufactured without depending on the manufacturing method of the liquid agent L or the method of sealing the liquid agent L in the first container 30.

[0321] 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 agent-containing first container 30L is closed can be shortened.

[0322] Negative pressure means pressure below atmospheric pressure, i.e., pressure below 1 atm. Positive pressure means pressure above atmospheric pressure, 1 atm. Whether or not the inside of a container is under negative pressure is determined using a pressure gauge if the container is provided with one. If the container is not provided with one, it is determined using a syringe. Specifically, when the needle of the syringe is inserted into the target container, it is determined whether or not the liquid or gas contained in the syringe flows into the container when only atmospheric pressure is applied to the piston of the syringe. If the liquid or gas contained in the syringe flows into the container, it is determined that the inside of the container was under negative pressure. Similarly, whether or not the inside of a container is under positive pressure is determined using a pressure gauge. If the pressure gauge is not provided in the container, it is determined using a syringe. Specifically, when the needle of the syringe is inserted into the target container, it is determined whether or not the liquid or gas contained in the container flows into the syringe when only atmospheric pressure is applied to the piston of the syringe. When the liquid or gas contained in the container flows into the syringe, it is determined that there was a positive pressure inside the container.

[0323] In the first embodiment described above, the first container 30L containing a liquid agent includes the first container 30 and the liquid agent L contained in the first container 30. The combined medical container 10L containing a liquid agent includes the first container 30L containing a liquid agent, a second container 40, and an oxygen absorber 22. The second container 40 contains the first container 30L containing a liquid agent. The second container 40 has oxygen barrier properties. The oxygen absorber 22 absorbs oxygen in the second container 40.

[0324] In the first embodiment, the first container 30 includes a container body 32 having an opening 33, and a plug 34 that closes the opening 33. The first oxygen permeability of the material constituting the plug 34 is 0.00010(cc×mm / (mm 2 × day) or more. Therefore, oxygen permeation through the stopper 34 of the first container 30 is promoted, and oxygen transfer from the first container 30 to the second container 40 proceeds quickly. This makes it possible to effectively suppress oxygen deterioration of the liquid agent L.

[0325] In the first embodiment, the first water vapor permeability of the material constituting the plug 34 is 1 (mg×mm / (mm 2 ×day) or less. In this way, the water vapor permeation through the stopper 34 of the first container 30 is suppressed, thereby suppressing the deterioration of the quality of the liquid L. For example, when the liquid L contains a non-aqueous medium, the movement of a large amount of water vapor from the second container 40 to the first container 30 through the stopper 34 can be suppressed. This suppresses hydrolysis of the medicinal component of the liquid L. When the liquid L contains an aqueous medium, the evaporation of the aqueous medium and the water vapor permeation through the first container 30 are suppressed. This suppresses the change in concentration of the medicinal component in the liquid L and the change in the hydrogen ion concentration of the liquid L. That is, according to the first embodiment, it is possible to deal with the problem of quality deterioration of the liquid L newly caused by applying the combination container to the liquid L. Since this problem is specific to the combination of the combination container and the liquid L and is a problem that has not been known in the past, it can be said that the action and effect obtained by the first embodiment is remarkable and far beyond the range predicted from the state of the art.

[0326] In the first embodiment described above, the quality deterioration of the liquid L is suppressed by promoting oxygen permeation through the stopper 34 and suppressing water vapor permeation through the stopper 34. As a second embodiment, the quality deterioration of the liquid L may be suppressed by adjusting the permeability of the first container as a whole. That is, the oxygen permeability of the first container 30 may be promoted and the water vapor permeability of the first container 30 may be suppressed. Even with the second embodiment, both the oxygen deterioration of the liquid L and the quality deterioration of the liquid L caused by water vapor can be sufficiently suppressed. Hereinafter, a second oxygen permeability of a predetermined range and a second water vapor permeability of a predetermined range given to the first container will be described. Note that the first container 30 used in the first embodiment may have a second oxygen permeability of a predetermined range and a second water vapor permeability of a predetermined range described below in addition to the first oxygen permeability of a predetermined range and the first water vapor permeability of a predetermined range described above.

[0327] In the second embodiment, the first container 30 has a second oxygen permeability in a predetermined range and a second water vapor permeability in a predetermined range. In other respects, the second embodiment may include the same configuration as the first embodiment described above. For example, the second embodiment may include a first container 30L containing a liquid agent, a medical container set 15, and a combined medical container 10L containing a liquid agent, as shown in Figs. 1A to 9. In the following description of the second embodiment and in the drawings used in the following description of the second embodiment, the same reference numerals are used for parts that can be configured similarly to the parts described in the first embodiment described above, and duplicated descriptions are omitted.

[0328] The second oxygen permeability of the first container 30 is 0.010 (cc / day) or more, may be 0.050 (cc / day) or more, may be 0.10 (cc / day) or more, may be 0.20 (cc / day) or more, may be 0.48 (cc / day) or more, may be 0.50 (cc / day) or more, may be 0.72 (cc / day) or more, may be 1.0 (cc / day) or more, may be 1.5 (cc / day) or more, or may be 1.68 (cc / day) or more. The second oxygen permeability is a characteristic at a temperature of 23°C and a humidity of 50% RH. By setting the lower limit of the second oxygen permeability of the first container 30 in this way, the oxygen permeability of the first container 30 can be sufficiently promoted, and oxygen deterioration of the liquid agent L can be suppressed. The second oxygen permeability may be 10 (cc / day) or less, may be 5.0 (cc / day) or less, or may be 1.0 (cc / day) or less.

[0329] The second oxygen permeability of the first container 30 may be 0.010 (cc / day) or more and 10 (cc / day) or less, 0.050 (cc / day) or more and 10 (cc / day) or less, 0.10 (cc / day) or more and 10 (cc / day) or less, 0.20 (cc / day) or more and 10 (cc / day) or less, 0.48 (cc / day) or more and 10 (cc / day) or less, 0.50 (cc / day) or more and 10 (cc / day) or less, 0.72 (cc / day) or more and 10 (cc / day) or less, 1.0 (cc / day) or more and 10 (cc / day) or less, 1.5 (cc / day) or more and 10 (cc / day) or less, or 1.68 (cc / day) or more and 10 (cc / day) or less. The second oxygen permeability of the first container 30 may be 0.010 (cc / day) or more and 5.0 (cc / day) or less, 0.050 (cc / day) or more and 5.0 (cc / day) or less, 0.10 (cc / day) or more and 5.0 (cc / day) or less, 0.20 (cc / day) or more and 5.0 (cc / day) or less, 0.48 (cc / day) or more and 5.0 (cc / day) or less, 0.50 (cc / day) or more and 5.0 (cc / day) or less, 0.72 (cc / day) or more and 5.0 (cc / day) or less, 1.0 (cc / day) or more and 5.0 (cc / day) or less, 1.5 (cc / day) or more and 5.0 (cc / day) or less, or 1.68 (cc / day) or more and 5.0 (cc / day) or less.The second oxygen permeability of the first container 30 may be 0.010 (cc / day) or more and 1.0 (cc / day) or less, 0.050 (cc / day) or more and 1.0 (cc / day) or less, 0.10 (cc / day) or more and 1.0 (cc / day) or less, 0.20 (cc / day) or more and 1.0 (cc / day) or less, 0.48 (cc / day) or more and 1.0 (cc / day) or less, 0.50 (cc / day) or more and 1.0 (cc / day) or less, 0.72 (cc / day) or more and 1.0 (cc / day) or less, 1.0 (cc / day) or more and 1.0 (cc / day) or less, 1.5 (cc / day) or more and 1.0 (cc / day) or less, or 1.68 (cc / day) or more and 1.0 (cc / day) or less.

[0330] The second oxygen permeability is a characteristic related to oxygen permeation of components such as parts that make up a container and the entire container. The second oxygen permeability represents the volume of oxygen that permeates the container per unit time when the container to be measured is placed in an air atmosphere and the inside of the container is maintained in a state where oxygen is substantially absent. The unit time is 1 day = 24 hours. The unit of oxygen volume is "cc".

[0331] The second oxygen permeability of the components constituting the first container 30 is set to the same numerical range as the second oxygen permeability of the first container 30. The second oxygen permeability of the first container 30 in the first state (disassembled state) will be described later, and the second oxygen permeability of the first container 30 in the first state (disassembled state) is set to the same numerical range as the second oxygen permeability of the first container 30.

[0332] The second oxygen permeability of components such as parts constituting a container is measured using a test container 70 including components to be measured, as shown in Figures 10A and 10B. The test container 70 for measuring the above-mentioned first oxygen permeability includes a test sheet 30X, as shown in Figure 2A. The test container 70 for measuring the second oxygen permeability uses each component that can be an oxygen permeation path of the first container 30 instead of the test sheet 30X. Except for this point, the device for measuring the second oxygen permeability shown in Figures 10A and 10B has the same configuration as the device for measuring the first oxygen permeability shown in Figure 2A described above.

[0333] In the test container 70 shown in Fig. 10A, the partition wall 71 of the test container 70 includes a main wall 72 and a plug 34. The plug 34 faces the through hole 72A. The through hole 72A is closed by the plug 34. The plug 34 is airtightly joined to the surrounding portion of the through hole 72A of the main wall 72 using a barrier bonding material 73 having oxygen barrier properties. The portion of the plug 34 that comes into contact with the barrier bonding material 73 is the portion that comes into contact with the container body 32 during normal use of the first container 30.

[0334] In the test container 70 shown in Fig. 10B, the partition wall 71 of the test container 70 includes a main wall 72 and a container body 32. The container body 32 faces a through hole 72A. The through hole 72A is closed by the container body 32. The container body 32 is airtightly joined to the surrounding portion of the through hole 72A of the main wall 72 using a barrier bonding material 73 having oxygen barrier properties. The portion of the container body 32 in contact with the barrier bonding material 73 is the portion that is in airtight contact with the stopper 34 during normal use of the first container 30.

[0335] The oxygen concentration in the test container 70 is maintained at 0.05% or less. That is, there is substantially no oxygen in the test container 70. The test container 70 is connected to a first flow path 71A and a second flow path 71B. The second flow path 71B is connected to an oxygen measuring device 74 that measures the amount of oxygen. The oxygen measuring device 74 can measure the amount of oxygen (cc) flowing through the second flow path 71B. The oxygen measuring device 74 is an oxygen amount measuring device built into OXTRAN (2 / 61) manufactured by MOCON, USA. The first flow path 71A supplies a gas that does not contain oxygen into the test container 70. The first flow path 71A supplies nitrogen. The second flow path 71B exhausts the gas in the test container 70. The first flow path 71A and the second flow path 71B have oxygen barrier properties. The first flow path 71A and the second flow path 71B maintain the test container 70 in a state where there is substantially no oxygen.

[0336] The test container 70 is placed in a test atmosphere with a temperature of 23° C. and a humidity of 50% RH. The test atmosphere is an air atmosphere under atmospheric pressure. The oxygen concentration of the test atmosphere is 20.95%. When the test container 70 is placed in the test atmosphere, oxygen moves from the test atmosphere into the test container 70 by passing through the parts 32 and 34 to be measured. The gas in the test container 70 is discharged from the second flow path 71B. By measuring the amount of oxygen flowing through the second flow path 71B with the oxygen measuring device 74, the oxygen transmission amount (cc / day) of the parts 32 and 34 to be measured in one day in an atmosphere with a temperature of 23° C. and a humidity of 50% RH can be measured. The oxygen transmission amount (cc / day) measured for the container body 32 is the second oxygen transmission performance of the container body 32. The oxygen transmission amount (cc / day) measured for the stopper 34 is the second oxygen transmission performance of the stopper 34.

[0337] The second oxygen permeability (cc / day) of the first container 30 is evaluated in a state in which it is housed in the second container 40. The second oxygen permeability (cc / day) of the first container 30 is an index showing the permeability of the first container in an assembled state. For example, for the first container 30 in which the stopper is attached to the container body 32 in a compressed state, this state is reproduced to measure the second oxygen permeability (cc / day). In this case, too, the first container 30 is divided into a plurality of parts, the second oxygen permeability (cc / day) is evaluated for each of the divided parts, and the second oxygen permeability (cc / day) of the first container 30 is determined by adding up the second oxygen permeability (cc / day) for each of the divided parts. The position at which the first container 30 is divided is a position that is not subjected to the action of pressure or the like from other parts of one component.

[0338] For example, the first container 30 shown in Fig. 1C includes a fastener 36 for fastening the stopper 34 to the container body 32. The fastener 36 pressurizes the stopper 34 toward the container body 32. For this first container 30, the second oxygen permeability (cc / day) is measured for a portion 30Z of the first container 30 including the stopper 34 and the fastener 36 and for the remaining portion of the first container 30 in a test container 70 shown in Fig. 10E, and the measured values ​​are added together to specify the second oxygen permeability (cc / day) of the first container 30.

[0339] In the example shown in Fig. 10E, the portion 30Z includes the plug 34, the fastener 36, and a portion of the container body 32 to which the plug 34 and the fastener 36 are attached. The portion of the container body 32 is airtightly joined to a peripheral portion of the through-hole 72A of the main wall portion 72 via a flash-resistant joining material 73 having oxygen barrier properties. In the example shown in Fig. 10E, the portion 30Z is obtained by cutting the container body 32 of the first container 30 shown in Fig. 1C near the plug 34.

[0340] The second oxygen permeability (cc / day) for the portion 30Z is determined by using the test container 70 shown in Fig. 10E. The test container 70 is formed using the other portion of the first container other than the portion 30Z, and the second oxygen permeability (cc / day) for the other portion is determined by using the test container. The second oxygen permeability (cc / day) for the portion 30Z and the second oxygen permeability (cc / day) for the other portion are added together, and the total value is the daily oxygen permeability (cc / day) measured for the portion 30Z and the other portion, thereby determining the second oxygen permeability (cc / day) of the first container 30 consisting of the portion 30Z and the other portion.

[0341] As an index separate from the second oxygen permeability (cc / day) in the assembled state (or in use state) of the first container measured by the method described with reference to Fig. 10E, the sum of the daily oxygen permeability (cc / day) measured for each part 32, 34 of the container also serves as an index indicating the oxygen permeability of the first container 30. The total oxygen permeability (cc / day) obtained by adding up the second oxygen permeability performance (cc / day) of each of the above-mentioned parts (components) measured by the method described with reference to Fig. 10A and Fig. 10B is defined as the second oxygen permeability (cc / day) of the first container 30 in the first state (or disassembled state).

[0342] When the first container 30 is obtained in a state disassembled into parts, the second oxygen permeability performance (cc / day) of the first container 30 in the first state is calculated by adding up the second oxygen permeability performance (cc / day) measured for each part. When the first container 30 is obtained in an assembled state (used state), the first container 30 is disassembled into parts (components) and the second oxygen permeability performance (cc / day) of the first container 30 in the first state is calculated by adding up the second oxygen permeability performance (cc / day) measured for each part.

[0343] The second oxygen permeability of the first container 30 in the first state (decomposed state) is set to the same numerical range as the numerical range of the second oxygen permeability of the first container 30.

[0344] In the example shown in Figures 10A, 10B, and 10E, the test container 70 is placed in a test chamber 75. The atmosphere in the test chamber 75 is maintained at a temperature of 23°C and a humidity of 50% RH. Air is supplied into the test chamber 75 from a supply path 75A. Gas in the test chamber 75 is exhausted from an exhaust path 75B. Air is circulated by the supply path 75A and the exhaust path 75B, and the oxygen concentration in the test chamber 75 is maintained at 20.95%.

[0345] In the examples shown in Figures 10A, 10B, and 10E, a pump for circulating air may be provided in one of the supply path 75A and the discharge path 75B. If the oxygen concentration in the test chamber 75 can be maintained the same as in the air atmosphere, the supply path 75A and the discharge path 75B shown in Figures 10A, 10B, and 10E may be open to the air atmosphere under atmospheric pressure.

[0346] The second water vapor permeability of the first container 30 is 20 (mg / day) or less, may be 18 (mg / day) or less, may be 15 (mg / day) or less, may be 10 (mg / day) or less, may be 6.0 (mg / day) or less, may be 4.6 (mg / day) or less, may be 3.9 (mg / day) or less. The first water vapor permeability is a characteristic at a temperature of 40°C and a humidity of 90% RH. By setting the upper limit of the second water vapor permeability of the first container 30 in this manner, water vapor permeation of the first container 30 can be sufficiently suppressed, and deterioration of the quality of the liquid agent L caused by water vapor permeation can be suppressed. The second water vapor permeability may be 0.050 (mg / day) or more, may be 0.10 (mg / day) or more, or may be 0.50 (mg / day) or more.

[0347] The second water vapor permeability of the first container 30 may be 0.050 (mg / day) or more and 20 (mg / day) or less, or 0.050 (mg / day) or more and 18 (mg / day) or less, or 0.050 (mg / day) or more and 15 (mg / day) or less, or 0.050 (mg / day) or more and 10 (mg / day) or less, or 0.050 (mg / day) or more and 6.0 (mg / day) or less, or 0.050 (mg / day) or more and 4.6 (mg / day) or less, or 0.050 (mg / day) or more and 3.9 (mg / day) or less. The second water vapor permeability of the first container 30 may be 0.10 (mg / day) or more and 20 (mg / day) or less, or 0.10 (mg / day) or more and 18 (mg / day) or less, or 0.10 (mg / day) or more and 15 (mg / day) or less, or 0.10 (mg / day) or more and 10 (mg / day) or less, or 0.10 (mg / day) or more and 6.0 (mg / day) or less, or 0.10 (mg / day) or more and 4.6 (mg / day) or less, or 0.10 (mg / day) or more and 3.9 (mg / day) or less. The second water vapor permeability of the first container 30 may be 0.50 (mg / day) or more and 20 (mg / day) or less, 0.50 (mg / day) or more and 18 (mg / day) or less, 0.50 (mg / day) or more and 15 (mg / day) or less, 0.50 (mg / day) or more and 10 (mg / day) or less, 0.50 (mg / day) or more and 6.0 (mg / day) or less, 0.50 (mg / day) or more and 4.6 (mg / day) or less, or 0.50 (mg / day) or more and 3.9 (mg / day) or less.

[0348] The second water vapor permeability is a characteristic related to the water vapor permeability of the components such as parts that make up a container and the entire container. The second water vapor permeability represents the volume of water vapor that permeates the container per unit time when the container to be measured is placed in an air atmosphere and the inside of the container is maintained in a state where water vapor is substantially absent. The unit time is 1 day = 24 hours. The unit of water vapor volume is "mg".

[0349] The second water vapor permeability of the components constituting the first container 30 is set to the same numerical range as the second water vapor permeability of the first container 30. The second water vapor permeability of the first container 30 in the first state (disassembled state) will be described later, and the second water vapor permeability of the first container 30 in the first state (disassembled state) is set to the same numerical range as the second water vapor permeability of the first container 30.

[0350] The second water vapor permeability of the components such as parts constituting the container is measured using a test container 77 including the components to be measured, as shown in Figures 10C and 10D. The test container 77 for measuring the above-mentioned first water vapor permeability includes a test sheet 30Y, as shown in Figure 2B. The test container 77 for measuring the second water vapor permeability uses each part that can be a water vapor permeation path of the first container 30 instead of the test sheet 30Y. Except for this point, the device for measuring the second water vapor permeability shown in Figures 10C and 10D has the same configuration as the device for measuring the first water vapor permeability shown in Figure 2B described above.

[0351] In the test container 77 shown in FIG. 10C, the test container 77 has a test storage section 78 having an opening 78A. The test storage section 78 has water vapor barrier properties. The plug 34 faces the opening 78A. The opening 78A is closed by the plug 34. The plug 34 is airtightly joined to the periphery of the opening 78A of the test storage section 78 using a barrier bonding material 73 having water vapor barrier properties. In the test container 77, the portion of the plug 34 facing the opening 78A is the portion facing the opening 33 of the plug 34 in normal use of the first container 30. The portion of the plug 34 in contact with the barrier bonding material 73 is the portion in contact with the container body 32 of the plug 34 in normal use of the first container 30.

[0352] In the test container 77 shown in Fig. 10D, the container body 32 faces the opening 78A. The opening 78A is closed by the container body 32. The container body 32 is airtightly joined to the surrounding portion of the opening 78A of the test storage section 78, which has water vapor barrier properties, by using a barrier bonding material 73 having water vapor barrier properties. The portion of the container body 32 that comes into contact with the barrier bonding material 73 is the portion that comes into contact with the stopper 34 during normal use of the first container 30.

[0353] With reference to the provisions of JIS Z0208-1976, the mass of calcium chloride 79 is determined so that the test ends before calcium chloride 79 absorbs moisture of a mass that is 10% of its mass. When the volume of test container 77 is 1 mL or more and 50 mL or less, usually, about 10 g of calcium chloride is placed in test container 77. By setting the mass of calcium chloride in this manner, the inside of test container 77 can be maintained in a state where water vapor is substantially absent.

[0354] The test container 70 is placed in a test atmosphere maintained at a temperature of 40° C. and a humidity of 90% RH. The test atmosphere is an air atmosphere under atmospheric pressure. When the test container 77 is placed in the test atmosphere, water vapor moves from the test atmosphere into the test container 77 through each of the components 32, 34 of the container to be measured. In the test container 77, the water vapor is absorbed as moisture by calcium chloride 79. By measuring the weight increase of the test container 77, the amount of water vapor permeated (mg) through each of the components 32, 34 of the container to be measured in an atmosphere of a temperature of 40° C. and a humidity of 90% RH can be measured. Water vapor may be present in the test container 77 immediately after the test container 77 is closed by blocking the opening 78A of the test storage section 78 with each of the components 32, 34 of the container to be measured. In order to eliminate the influence of this water vapor, the weight change of the test container 77 one day after the test container 77 is closed and the weight of the test container 77 11 days after the test container 77 is closed are divided by 10 (days) to measure the amount of water vapor permeating (mg / day) through each part 32, 34 of the container being measured in one day.

[0355] The second water vapor permeability (mg / day) of the first container 30 is evaluated in a state in which it is housed in the second container 40, similar to the second oxygen permeability of the first container 30. The second water vapor permeability (mg / day) of the first container 30 is an index showing the permeability of the first container in an assembled state. Except for using the first container 30 in an assembled state (usage state) containing calcium chloride as the test container 77, the second water vapor permeability (mg / day) of the first container 30 is determined by the same measurement method as the measurement method described above with reference to Figs. 10C and 10D.

[0356] As shown in Figures 10C and 10D, the test container 77 is placed in a test chamber 75. The atmosphere in the test chamber 75 is maintained at a temperature of 40°C and a humidity of 90% RH. The atmosphere in the test chamber 75 is an air atmosphere under atmospheric pressure. Air is supplied into the test chamber 75 from a supply path 75A. The gas in the test chamber 75 is exhausted from an exhaust path 75B. The test chamber 75 is maintained at a test atmosphere by the supply path 75A and the exhaust path 75B.

[0357] The total water vapor permeation amount (mg / day) obtained by adding up the second water vapor permeation performance (mg / day) of each of the above-mentioned parts (components) measured by the method described with reference to Figures 10C and 10D is defined as the first water vapor permeation performance (mg / day) in the first state (or disassembled state) of the first container 30. The first water vapor permeation performance of the first container 30 in the first state (or disassembled state) is also an index indicating the water vapor permeation performance of the first container 30, similar to the above-mentioned second water vapor-oxygen permeation performance (mg / day) of the first container measured using the first container 30 in an assembled state.

[0358] When the first container 30 is obtained in a state disassembled into parts, the second water vapor permeability performance (mg / day) of the first container 30 in the first state is calculated by adding up the second water vapor permeability performance (mg / day) measured for each part. When the first container 30 is obtained in an assembled state (used state), the first container 30 is disassembled into parts (components), and the second water vapor permeability performance (mg / day) of the first container 30 in the first state is calculated by adding up the second water vapor permeability performance (mg / day) measured for each part.

[0359] The second water vapor permeability of the first container 30 in the first state (decomposed state) is set to the same numerical range as the numerical range of the second water vapor permeability of the first container 30.

[0360] In the second embodiment, the first container 30L containing a liquid agent includes a first container 30 and a liquid agent L contained in the first container 30. The combined medical container 10L containing a liquid agent includes a first container 30L containing a liquid agent, a second container 40, and an oxygen absorber 22. The second container 40 contains the first container 30L containing a liquid agent. The second container 40 has oxygen barrier properties. The oxygen absorber 22 absorbs oxygen in the second container 40.

[0361] In the second embodiment, the second oxygen permeability of the first container 30 is 0.010 (cc / day) or more at a temperature of 23° C. and a humidity of 50% RH. Therefore, oxygen permeation through the stopper 34 of the first container 30 is promoted, and oxygen transfer from the first container 30 to the second container 40 proceeds quickly. This makes it possible to effectively suppress oxygen deterioration of the liquid agent L.

[0362] In the second embodiment, the second water vapor permeability of the first container 30 is 20 (mg / day) or less at a temperature of 40° C. and a humidity of 90% RH. In this way, the water vapor permeation through the stopper 34 of the first container 30 is suppressed, thereby suppressing deterioration in the quality of the liquid L. For example, when the liquid L contains a non-aqueous medium, it is possible to suppress a large amount of water vapor from passing through the stopper 34 and moving from the second container 40 to the first container 30. This suppresses hydrolysis of the medicinal ingredient of the liquid L. When the liquid L contains an aqueous medium, evaporation of the aqueous medium and water vapor permeation through the first container 30 are suppressed. This suppresses changes in the concentration of the medicinal ingredient in the liquid L and changes in the hydrogen ion concentration of the liquid L. That is, according to the second embodiment, it is possible to address the problem of quality deterioration of the liquid L that arises newly when the combination container is applied to the liquid L. Since this problem is specific to the combination of the combination container and liquid agent L and was not previously known, it can be said that the effect obtained by the second embodiment is remarkable and far exceeds the range predicted from the state of the art.

[0363] In the second embodiment, the second oxygen permeability and the second water vapor permeability of the first container 30 are within the above-mentioned predetermined ranges, respectively, and the deterioration of the quality of the liquid agent L is suppressed. In the second embodiment, the first oxygen permeability of the material constituting the stopper 34 may be within the predetermined range described in the first embodiment, or may be outside the predetermined range described in the first embodiment. Similarly, the first water vapor permeability of the material constituting the stopper 34 may be within the predetermined range described in the first embodiment, or may be outside the predetermined range described in the first embodiment. In the second embodiment, the stopper 34 may have oxygen barrier properties. For example, the material of the stopper 34 may be butyl rubber.

[0364] In the example shown in FIG. 11A, the first container 30 includes a container body 32, a plug 34, and a fastener 36. The plug 34 may be made of a material that is difficult to transmit oxygen and water vapor. The first oxygen permeability of the material constituting the plug 34 is 0.00010(cc×mm / (mm 2×day)). The material of the stopper 34 may be butyl rubber or natural rubber. This can suppress water vapor permeation of the stopper 34. The thickness of the stopper 34 may be very thin, such as several tens of μm to several hundreds of μm. In the example shown in FIG. 11A, the thickness of the stopper 34 is thin, so that oxygen permeation of the stopper 34 can be promoted. As a result, the first container 30 shown in FIG. 11A has the second oxygen permeability and the second water vapor permeability in the above-mentioned predetermined range, and can suppress quality deterioration of the liquid agent L. In the example shown in FIG. 11A, the container body 32 may or may not have oxygen barrier properties.

[0365] As shown in FIG. 11B, the first container 30 may include a container body 32, a stopper 34, and a cover 29. The stopper 34 at least partially covers the opening 33 of the container body 32. The cover 29 covers the stopper 34. In this example, the combination of the stopper 34 and the cover 29 promotes oxygen permeation and suppresses water vapor permeation. As another example, the combination of the stopper 34 and the fastener 36 that fixes the stopper 34 to the container body 32 may promote oxygen permeation and suppress water vapor permeation. As a result, the first container 30 has the above-mentioned second oxygen permeability in the predetermined range and the second water vapor permeability in the predetermined range, and the quality deterioration of the liquid agent L can be suppressed. In the example shown in FIG. 11B, the container body 32 may or may not have oxygen barrier properties.

[0366] A second oxygen permeability performance for the combination of the plug 34 and the cover 29 is measured using a test vessel 70 that includes the combination of the plug 34 and the cover 29. A second oxygen permeability performance for the combination of the plug 34 and the fastener 36 is measured using a test vessel 70 that includes the combination of the plug 34 and the fastener 36.

[0367] In the example shown in FIG. 11B, a through hole 34e or a recess 34f may be formed in the plug 34. Oxygen permeation through the plug 34 is promoted in the through hole 34e or the recess 34f. The material constituting the plug 34 may or may not have oxygen barrier properties. The material constituting the plug 34 may be butyl rubber or natural rubber. The first oxygen permeability of the material constituting the plug 34 is 0.00010(cc×mm / (mm 2 × days)).

[0368] In the example shown in FIG. 11B, the cover 29 may be a resin cap. The cover 29 may be a resin film. The first oxygen permeability and the first water vapor permeability of the material constituting the cover 29 may each be within the predetermined ranges described in the first embodiment. That is, the first oxygen permeability of the material constituting the cover 29 may be 0.00010(cc×mm / (mm 2 The first water vapor permeability of the material constituting the cover 29 may be 1.0 (mg×mm / (mm 2 ×day) or less is also acceptable.

[0369] In the second embodiment, the container body 32 may have oxygen permeability. The first oxygen permeability and the first water vapor permeability of the material constituting the container body 32 may each be within the predetermined range described in the first embodiment. That is, the first oxygen permeability of the material constituting the container body 32 may be 0.00010(cc×mm / (mm 2 The first water vapor permeability of the material constituting the container body 32 may be 1.0 (mg×mm / (mm 2 ×day) or less is also acceptable.

[0370] In these examples relating to the second embodiment, the first container 30 has the second oxygen permeability and the second water vapor permeability within a predetermined range, so that deterioration of the quality of the liquid agent L can be suppressed.

[0371] Next, a further description will be given of a specific example of the laminate 47 that can be used in the second container 40. In the following description and the drawings used in the following description, the same reference numerals as those used for the corresponding parts in the above-mentioned specific example are used for parts that can be configured similarly to the above-mentioned specific example or corresponding configurations, and duplicated descriptions will be omitted.

[0372] By improving the oxygen barrier property of the second container 40, the oxygen concentration (%) in the second container 40, the oxygen concentration (%) in the first container 30, and the amount of oxygen dissolved (mg / L) in the liquid agent L in the first container 30 can be sufficiently reduced and stably maintained at a reduced state. Furthermore, by improving the water vapor barrier property of the second container 40, when the liquid agent L in the first container 30 contains a non-aqueous medium, an increase in the amount of water vapor in the first container 30 can be suppressed. In addition, when the liquid agent L in the first container 30 contains an aqueous medium, the concentration of the liquid agent L can be stably maintained.

[0373] The laminate such as the films 41a-41d included in the second container 40 may include a barrier layer having an oxygen barrier function or a water vapor barrier function. By increasing the thickness of the barrier layer included in the laminate, the barrier function of the laminate can be strengthened. However, when the thickness of the barrier layer formed as a vapor deposition film is increased, the adhesive strength between the barrier layer and the adjacent layer is usually reduced. Furthermore, when the thickness of the barrier layer formed as a vapor deposition film is increased, the barrier layer is easily cracked. For these reasons, there is a limit to the oxygen barrier property and water vapor barrier property of the laminate used in the conventional container. As a result of the intensive research conducted by the present inventors on this point, they have created a laminate with excellent barrier property. The laminate created by the present inventors will be described below.

[0374] The laminate described below can be applied to the second container 40 included in the combined medical container 10 and the medical container set 15. More specifically, the laminate 47 described below may constitute the films 41a to 41e of the second container 40 shown in Figures 1A, 1B, 1D, 1E, and 4A to 4EC. The laminate 47 described below may constitute the container body 42 and the lid 44 of the second container 40 shown in Figures 3A to 3C and 4F.

[0375] The laminate 47 includes an inner surface 47a facing the storage space S of the container and an outer surface 47b opposite to the inner surface 47a. As shown in FIG. 12A, the laminate 47 may include, in the order from the inner surface 47a toward the outer surface 47b, a sealant layer 48a, a first barrier layer 48c, a resin layer 48f, and a second barrier layer 48h. The laminate 47 includes two barrier layers 48c and 48h having a barrier function. Therefore, the laminate 47 has high barrier properties even without increasing the thickness of each of the barrier layers 48c and 48h included in the laminate 47. That is, the laminate 47 can exhibit high barrier function while suppressing a decrease in adhesion and cracking of the barrier layers 48c and 48h.

[0376] Even if defects such as pinholes or cracks occur in one of the barrier layers 48c, 48h, the laminate 47 can maintain a certain level of barrier properties due to the other barrier layer 48c, 48h. In particular, the resin layer 48f is disposed between the first barrier layer 48c and the second barrier layer 48h. The resin layer 48f, which functions as the base material of the laminate 47, can prevent defects such as pinholes or cracks from occurring in both the first barrier layer 48c and the second barrier layer 48h.

[0377] When the laminate 47 is applied to the second container 40 of the combined medical container 10 and the medical container set 15, the laminate 47 can exhibit high oxygen barrier function and high water vapor barrier function. By improving the oxygen barrier property of the second container 40, the oxygen concentration (%) in the second container 40, the oxygen concentration (%) in the first container 30, and the amount of oxygen dissolved in the liquid L (mg / L) can be sufficiently reduced and stably maintained in a reduced state. By improving the water vapor barrier property of the second container 40, when the liquid L in the first container 30 contains a non-aqueous solvent, an increase or decrease in the amount of water vapor in the first container 30 and the second container 40 can be suppressed. When the liquid L in the first container 30 contains an aqueous solvent, the concentration of the liquid L in the first container 30 can be stably maintained.

[0378] By disposing the resin layer 48f between the two barrier layers 48c, 48h, it is possible to suppress the generation of air bubbles in the laminate 47. As a result, when the laminate 47 is applied to the second container 40 of the medical container set 15 and the combined medical container 10, the state of the first container 30 can be observed from the outside of the second container 40. In addition, the oxygen concentration in the second container 40 can be measured using a non-contact oxygen amount measuring device without opening the second container 40. Furthermore, if the container body 32 of the first container 30 is also transparent, the liquid agent L in the first container 30 can be observed from the outside of the second container 40. In this case, the oxygen concentration in the first container 30 can be measured using a non-contact oxygen amount measuring device without opening the first container 30 and the second container 40. Similarly, the amount of oxygen dissolved in the liquid agent L in the first container 30 can be measured using a non-contact oxygen amount measuring device without opening the first container 30 and the second container 40.

[0379] The laminate 47 may be transparent. The laminate 47 may include a transparent portion. As described above, transparency means that the transmission haze in the target portion is 80.0% or less so that the inside of the target portion can be observed from the outside. The transmission haze in at least a portion of the laminate 47 may be 58.0% or less, 29.0% or less, 14.5% or less, 7.0% or less, 3.5% or less, or 1.0% or less so that the target portion can be more clearly observed from the outside.

[0380] If the laminate 47 is transparent, the state of the first container 30 can be observed from the outside of the second container 40 to which the laminate 47 is applied. In addition, the oxygen concentration in the second container 40 can be measured using a non-contact oxygen amount measuring device without opening the second container 40. Furthermore, if the container body 32 of the first container 30 is also transparent, the liquid L in the first container 30 can be observed from the outside of the second container 40. In this case, the oxygen concentration in the first container 30 can be measured using a non-contact oxygen amount measuring device without opening the first container 30 and the second container 40. Similarly, the amount of oxygen dissolved in the liquid L in the first container 30 can be measured using a non-contact oxygen amount measuring device without opening the first container 30 and the second container 40.

[0381] There is no particular lower limit set for the transmission haze in at least a portion of the laminate 47. The transmission haze in at least a portion of the laminate 47 may be 0% or more, or may be greater than 0%.

[0382] The total light transmittance of a part or the whole of the laminate 47 may be 50% or more, 70% or more, 80% or more, or 90% or more. By setting a lower limit for the total light transmittance of the laminate 47, the state of the first container 30 can be clearly observed from the outside of the second container 40 to which the laminate 47 is applied. No particular lower limit is set for the total light transmittance of the laminate 47. The total light transmittance of the laminate 47 may be 0% or more, or may be greater than 0%.

[0383] The laminate 47 may have a transmission haze in the above-mentioned predetermined range and a total light transmittance in the above-mentioned predetermined range.

[0384] A D65 standard light source is used to measure total light transmittance. Before measuring total light transmittance, turn on the D65 standard light source for 15 minutes to stabilize the output of the D65 standard light source. The angle of incidence on the sample when measuring total light transmittance is 0°. The test environment when measuring total light transmittance is a temperature of 23°C ± 2°C and a relative humidity of 50% ± 5%. The sample is placed in the test environment for 16 hours before starting the test. Other measurement conditions when measuring total light transmittance are in accordance with JIS K7361-1:1997. The total light transmittance is the arithmetic average of five measured values. The five measured values ​​are measured at five measurement positions on the measurement sample to be evaluated.

[0385] The yellowness index (YI value) of the laminate 47 in part or in its entirety may be 20 or less, 15 or less, 13 or less, or 10 or less. When the YI value is 20 or less, the color of the inside of the package becomes easier to confirm, and the degree of identification of an indicator that distinguishes by color, such as Ageless Eye, is improved. The yellowness index is an index showing the degree of yellow coloring of the laminate 47. The laminate 47 exhibits high barrier properties due to the two barrier layers. Compared to using one thick barrier layer, the yellowness index of the laminate 47 can be reduced to the above upper limit or less by using two barrier layers.

[0386] Setting the above upper limit for the yellowness index (YI value) makes it possible to limit the yellowish coloring of the laminate 47. Setting the above upper limit for the yellowness index (YI value) makes it possible to clearly observe the state of the first container 30 from the outside of the second container 40 to which the laminate 47 is applied.

[0387] There is no particular lower limit for the yellowness index (YI value) of the laminate 47. The yellowness index (YI value) of the laminate 47 may be 0 or more, or may be greater than 0.

[0388] Yellowness is measured by transmitted light. Using a spectrophotometric method, auxiliary illuminant C and a 2-degree visual field, the transmittance is measured at 0.5 nm intervals in the range from 300 nm to 780 nm, and the tristimulus values ​​X, Y, and Z in the XYZ color system are calculated based on the transmittance. The yellowness (YI value) is determined from the calculated X, Y, and Z values ​​using the following formula. YI=100(1.2769X-1.0592Z) / Y The geometrical optical condition e of JIS Z 8722:2009 is adopted as the geometrical optical condition when measuring the yellowness. In order to eliminate the influence of scattered light from the end of the test piece, the diameter of the light beam incident on the test piece is made smaller than the diameter of the opening. Before measuring the yellowness, the light source of the measuring device is turned on for 15 minutes to stabilize the output of the D65 general light source. The incident surface when measuring the yellowness is the inner surface 47a of the laminate 47. The test environment when measuring the yellowness is a temperature of 23°C ± 2°C and a relative humidity of 50% ± 5%. The sample is placed in the test environment for 16 hours before starting the test.

[0389] The yellowness index (YI value) is the arithmetic average of five measured values. The five measured values ​​are measured at five measurement positions on the optical sheet to be evaluated. The five measurement positions are located at least 10 mm apart from each other. Other measurement conditions for measuring the yellowness index (YI value) are in accordance with JIS K7373-1:2006.

[0390] The laminate 47 may have one or more of the transmission haze in the above-mentioned predetermined range and the total light transmittance in the above-mentioned predetermined range, and may also have the yellowness index in the above-mentioned predetermined range.

[0391] The oxygen permeability of the laminate 47 is 0.20 (mL / (m 2 × day × atm), and may be less than 0.15 (mL / (m 2 × day × atm) or less, and 0.14 (mL / (m 2×day×atm) or less. With an oxygen permeability having such an upper limit, an extremely high oxygen barrier property is imparted to the second container 40, and the oxygen concentration (%) in the first container 30 and the amount of oxygen dissolved (mg / L) in the liquid L can be sufficiently reduced and stably maintained in a reduced state. No lower limit is particularly set for the oxygen permeability of the laminate 47. The oxygen permeability of the laminate 47 is preferably 0 (mL / (m 2 × day × atm)) or more, and 0(mL / (m 2 ×day×atm).

[0392] The oxygen permeability of the laminate 47 is 0 (mL / (m 2 ×day×atm)) or more but less than 0.20 (mL / (m 2 × day × atm)) or less, and 0(mL / (m 2 ×day×atm)) or more 0.15(mL / (m) 2 × day × atm)) or less, and 0(mL / (m 2 ×day×atm)) or more 0.14(mL / (m) 2 ×day×atm) or less. The oxygen permeability of the laminate 47 may be 0 (mL / (m 2 ×day×atm)) but less than 0.20 (mL / (m 2 × day × atm)) or less, and 0(mL / (m 2 ×day×atm)) or greater than 0.15(mL / (m 2 × day × atm)) or less, and 0(mL / (m 2 ×day×atm)) or greater than 0.14(mL / (m 2 ×day×atm) or less is also acceptable.

[0393] The water vapor permeability of the laminate 47 is 0.50 (g / (m 2 × day)) or less, and 0.30 (g / (m 2 × day)) or less, and 0.20 (g / (m 2×day) or less. With a water vapor permeability having such an upper limit, it is possible to impart extremely high water vapor barrier properties to the second container 40. By suppressing the permeation of water vapor within the second container 40 to the outside, it is possible to suppress the amount of evaporation of the liquid agent L and thereby suppress changes in concentration. There is no particular lower limit set for the water vapor permeability of the laminate 47. The water vapor permeability of the laminate 47 is preferably 0 (mL / (m 2 × day × atm)) or more, and 0(mL / (m 2 ×day×atm).

[0394] The water vapor permeability of the laminate 47 is 0 (mL / (m 2 ×day×atm)) or more 0.50(g / (m) 2 × day) or less, and 0(mL / (m 2 ×day×atm)) or more 0.30(g / (m) 2 × day) or less, and 0(mL / (m 2 ×day×atm)) or more 0.20(g / (m) 2 The water vapor permeability of the laminate 47 may be 0 (mL / (m 2 ×day×atm)) or greater than 0.50(g / (m 2 × day) or less, and 0(mL / (m 2 ×day×atm)) or greater than 0.30(g / (m 2 × day) or less, and 0(mL / (m 2 ×day×atm)) or greater than 0.20(g / (m 2 ×day) or less is also acceptable.

[0395] The water vapor permeability is measured in accordance with JIS K 7129-2:2019. The water vapor permeability is measured using a PERMATRAN (3 / 33), a permeability measuring device manufactured by MOCON, USA, in an environment of a temperature of 40°C and a humidity of 90% RH.

[0396] The resin layer 48f functions as a resin base material for the entire laminate 47. The resin layer 48f may be a stretched film. The resin layer 48f may contain a thermoplastic resin as a main component. The main component means a component having the largest mass ratio. A lower limit may be set for the thickness of the resin layer 48f. The thickness of the resin layers 48f, 48j may be 5 μm or more and 60 μm or less, or 7 μm or more and 30 μm or less. These resin layers 48f can function as a resin base material for the entire laminate 47.

[0397] The resin layer 48f may be a substrate that supports at least one of the first barrier layer 48c and the first barrier substrate layer 48d.

[0398] The resin layer 48f functioning as a resin substrate imparts mechanical properties, such as strength, hardness, Young's modulus, bending rigidity, etc., required for the laminate 47. The material of the resin layer 48f functioning as a resin substrate may be polyamide, polypropylene, or polyethylene terephthalate.

[0399] As a specific example, the resin layer 48f may be oriented polyamide or oriented polyester. The oriented polyamide may be uniaxially oriented polyamide or biaxially oriented polyamide. The oriented polyamide may be uniaxially oriented nylon or biaxially oriented nylon. The oriented polyester may be uniaxially oriented polyester or biaxially oriented polyester, or uniaxially oriented polyethylene terephthalate or biaxially oriented polyethylene terephthalate.

[0400] Stretched polyamide and stretched nylon are excellent in puncture resistance, abrasion resistance, and bending resistance. Therefore, by using stretched polyamide or stretched nylon for the resin layer 48f, defects such as pinholes and cracks in the laminate 47 can be made less likely to occur. By using stretched polyamide or stretched nylon for the resin layer 48f, the thickness of the laminate 47 can be reduced while maintaining the strength of the laminate 47. Furthermore, the resin layer 48f containing stretched polyamide or stretched nylon can suppress the occurrence of defects in the other barrier layer 48c, 48h even if defects such as pinholes and cracks occur in one of the barrier layers 48c, 48h. In this respect, stretched polyamide and stretched nylon are extremely suitable for the resin layer 48f disposed between the two barrier layers 48c, 48h.

[0401] As shown in Fig. 12B, the laminate 47 may include an inner adhesive layer 48b located between the sealant layer 48a and the first barrier layer 48c. The inner adhesive layer 48b may be adjacent to the sealant layer 48a and the first barrier layer 48c. The inner adhesive layer 48b may be bonded to the sealant layer 48a and the first barrier layer 48c. Alternatively, only a layer that does not transmit water vapor, for example a polyethylene terephthalate layer (PET layer) having a thickness of 9 µm or more and 16 µm or less, may be located between the inner adhesive layer 48b and the first barrier layer 48c. According to this example, fluctuations in the water vapor concentration in the container can be sufficiently suppressed.

[0402] As shown in FIG. 12C and FIG. 12D, the laminate 47 may further include a first adhesive layer 48e located between the first barrier layer 48c and the resin layer 48f, and a second adhesive layer 48g located between the resin layer 48f and the second barrier layer 48h. The first adhesive layer 48e may include a cured product of a curable resin composition. The second adhesive layer 48g may include a cured product of a curable resin composition. FIG. 12C shows a laminate in which adhesive layers 48e and 48g are added to the laminate shown in FIG. 12A. FIG. 12D shows a laminate in which adhesive layers 48e and 48g are added to the laminate shown in FIG. 12B.

[0403] During the curing process of the curable resin composition, air bubbles may be generated, although only slightly. The air bubbles may contain, for example, carbon dioxide or water vapor. The generated air bubbles cannot permeate the barrier layers 48c and 48h.

[0404] On the other hand, the resin layer 48f is made of, for example, polyamide such as nylon, polypropylene, or polyethylene terephthalate, and has gas permeability. The bubbles generated from the first adhesive layer 48e pass through one main surface (the main surface on the inner surface 47a side) of the resin layer 48f, proceed through the resin layer 48f, and can be further discharged from the side end surface of the resin layer 48f to the outside of the container. The bubbles generated from the second adhesive layer 48g pass through the other main surface (the main surface on the outer surface 47b side) of the resin layer 48f, proceed through the resin layer 48f, and can further be discharged from the side end surface of the resin layer 48f to the outside of the container. That is, the resin layer 48f constitutes a permeation path for discharging the bubbles generated during the curing process of the adhesive layers 48e and 48g.

[0405] Also, the resin layer 48f is located between the first barrier layer 48c and the second barrier layer 48h. Therefore, one of the first barrier layer 48c and the second barrier layer 48h and the resin layer 48f can be bonded by an adhesive layer, and then the other of the first barrier layer 48c and the second barrier layer 48h and the resin layer 48f can be bonded by an adhesive layer. The resin layer 48f bonded to one barrier layer on one side by the adhesive layer can expose the other side. Therefore, air bubbles generated in the adhesive layer can be quickly removed by penetrating the resin layer 48f. At this time, aging under appropriate conditions can further promote the discharge of air bubbles.

[0406] These features prevent air bubbles from remaining in the high-barrier laminate 47 including two barrier layers. They also prevent the high-barrier laminate 47 including two barrier layers from becoming cloudy. In addition, the visible light transmittance of the laminate 47 is maintained high, allowing the first container 30 and the liquid L to be clearly observed from outside the second container 40. In addition, the oxygen concentration in the second container 40, the oxygen concentration in the first container 30, and the amount of oxygen dissolved in the liquid L in the first container 30 can be measured with high accuracy from outside the second container 40.

[0407] From the viewpoint of suppressing the generation of air bubbles in the laminate 47, the resin layer 48f may contain a polyester such as polyethylene terephthalate. The resin layer 48f may contain a polyester such as polyethylene terephthalate as a main component. The main component means a component having the largest mass ratio. The resin layer 48f may contain a polyester film such as polyethylene terephthalate. The polyester film may be a uniaxially stretched polyester film, a biaxially stretched polyester film, or a stretched polyester film. It may be a uniaxially stretched nylon film or a biaxially stretched nylon film.

[0408] Furthermore, from the viewpoint of increasing the puncture resistance of the laminate 47, the resin layer 48f may contain a polyamide such as nylon. The resin layer 48f may contain a polyamide such as nylon as a main component. The main component means a component having the largest mass ratio. The resin layer 48f may contain a polyamide film such as nylon. The polyamide film may be a uniaxially stretched polyamide film, a biaxially stretched polyamide film, or a stretched polyamide film. It may be a uniaxially stretched nylon film or a biaxially stretched nylon film.

[0409] 12E, the laminate 47 may include a first barrier substrate layer 48d adjacent to the first barrier layer 48c. The laminate 47 may include a second barrier substrate layer 48i adjacent to the second barrier layer 48h. The first barrier substrate layer 48d may be a resin substrate that supports the first barrier layer 48c. The second barrier substrate layer 48i may be a resin substrate that supports the second barrier layer 48h.

[0410] In the illustrated example, the first barrier substrate layer 48d is located between the first barrier layer 48c and the inner adhesive layer 48b. With this arrangement, the first barrier 48c does not come into direct contact with the sealant layer 48a, which is prone to dimensional changes and deformation. The presence of the first barrier substrate layer 48d reduces the effects of dimensional changes and deformation of the sealant layer 48a on the first barrier layer 48c. This makes it possible to suppress the occurrence of defects such as cracks and pinholes in the first barrier layer 48c.

[0411] In the illustrated example, the second barrier layer 48h is located between the resin layer 48f and the second barrier substrate layer 48i. The second barrier layer 48h is located between the second adhesive layer 48g and the second barrier substrate layer 48i. That is, the second barrier substrate layer 48i may be closer to the outer surface 47b than the second barrier layer 48h, or may constitute the outer surface 47b. With this arrangement, the second barrier substrate layer 48i receives an external force due to contact with the outside or an impact from the outside before the second barrier layer 48h. The external force or impact received by the second barrier layer 48h is weakened by the second barrier substrate layer 48i. This can suppress the occurrence of defects such as cracks and pinholes in the twelfth barrier layer 48h.

[0412] As shown in FIG. 12F, the laminate 47 may include three or more barrier layers. In the example shown in FIG. 12F, the laminate 47 further includes a second resin layer 48j and a third barrier layer 48k. A laminate including three or more barrier layers can further improve the oxygen barrier property and water vapor barrier property of the laminate 47. FIG. 12F adds a second resin layer 48j and a third barrier layer 48k to the laminate shown in FIG. 12E. Furthermore, the laminate 47 shown in FIG. 12F includes a third barrier substrate layer 48l. The third barrier substrate layer 48l constitutes the outer surface 47b. The third barrier substrate layer 48l may be a resin substrate that supports the third barrier layer 48k.

[0413] A third adhesive layer may be provided between the second resin layer 48j and the second barrier substrate layer 48i. A fourth adhesive layer may be provided between the second resin layer 48j and the third barrier layer 48k. These third and fourth adhesive layers may be configured similarly to the adhesive layers 48e and 48g.

[0414] 12F, the first barrier substrate layer 48d may be located between the first barrier layer 48c and the inner adhesive layer 48b for the reasons described above. Also in the example shown in Fig. 12F, the second barrier layer 48h may be located between the resin layer 48f and the second barrier substrate layer 48i, or between the second adhesive layer 48g and the second barrier substrate layer 48i for the reasons described above.

[0415] In the example shown in FIG. 12F, the third barrier layer 48k may be located between the second resin layer 48j and the third barrier substrate layer 48l. The third barrier layer 48k may be located between the fourth adhesive layer and the third barrier substrate layer 48l. That is, the third barrier substrate layer 48l may be closer to the outer surface 47b than the third barrier layer 48k, or may constitute the outer surface 47b. According to this arrangement, the third barrier substrate layer 48l receives an external force or impact due to contact with the outside before the third barrier layer 48k. Therefore, the external force or impact received by the third barrier layer 48k is weakened by the third barrier substrate layer 48l. This can suppress the occurrence of defects such as cracks and pinholes in the third barrier layer 48k.

[0416] Each layer that may be included in stack 47 will now be described in further detail.

[0417] The barrier layers 48c, 48h, and 48k may include a metal or an inorganic oxide. The barrier layer may be formed by chemical vapor deposition (CVD) or physical vapor deposition (PVD). The barrier layer may be a vapor deposition film. The barrier layer may include a vapor deposition film. The vapor deposition film is a layer produced by vapor deposition. The vapor deposition film may include a metal or an inorganic oxide. The vapor deposition film provides a thin barrier layer with excellent barrier properties. The barrier layer may be a transparent vapor deposition film. The barrier layer may include a transparent vapor deposition film. The transparent vapor deposition film is a transparent layer produced by vapor deposition. The barrier layers 48c, 48h, and 48k as transparent vapor deposition films can provide a laminate 47 including a thin barrier layer with high barrier properties, together with other layers, with transparency. By using the transparent laminate 47 for the second container 40, the first container 30 can be observed from the outside of the second container 40.

[0418] The metal contained in the barrier layers 48c, 48h, and 48k is not particularly limited. Examples of the metal include aluminum, tin, chromium, zinc, gold, silver, platinum, and nickel. Each of the barrier layers 48c, 48h, and 48k may contain two or more of these metals.

[0419] The inorganic oxide contained in the barrier layers 48c, 48h, and 48k is not particularly limited. Examples of inorganic oxides include oxides of silicon, aluminum, magnesium, calcium, potassium, tin, sodium, boron, titanium, lead, zirconium, and yttrium. Each of the barrier layers 48c, 48h, and 48k may contain two or more of these inorganic oxides. As a specific example, the inorganic oxide contained in the barrier layers 48c, 48h, and 48k may be aluminum oxide or silicon oxide. The inorganic oxide is represented by MOX, such as AlOX and SiOX. In the above formula, "M" represents an inorganic element. From the viewpoint of transparency and gas barrier property, when M is aluminum (Al), the value of X may be 0.5 or more and 2.0 or less. When M is silicon (Si), the value of X may be 1 or more and 2 or less.

[0420] The thickness of the barrier layers 48c, 48h, 48k may be 1 nm or more and 1.0 μm or less, 3 nm or more and 100 nm or less, 5 nm or more and 80 nm or less, or 8 nm or more and 50 nm or less.

[0421] The barrier layers 48c, 48h, 48k may include multiple layers. The multiple layers may include a base barrier layer formed by chemical vapor deposition (CVD) or physical vapor deposition (PVD). The base barrier layer may include a metal or an inorganic oxide. The base barrier layer may be a vapor-deposited film. The base barrier layer may be a transparent vapor-deposited film, i.e., a transparent vapor-deposited film. The vapor-deposited film is a layer produced by vapor deposition. The vapor-deposited film may include a metal or an inorganic oxide.

[0422] The barrier layers 48c, 48h, 48k may include, in order from the barrier substr...

Claims

[Claim 1] A first container containing a liquid agent; a second container that houses the first container and has oxygen barrier properties; an oxygen absorbent that absorbs oxygen in the second container; The first container includes a container body having an opening and a plug that closes the opening, The first oxygen permeability of the material constituting the plug is 0.00010 (cc×mm / (mm ２ × day) or more, The first water vapor permeability of the material constituting the plug is 1.0 (mg×mm / (mm ２ A combined medical container containing a liquid, the combined medical container having a shelf life of 10 days or less.

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