Multilayer film, roll body, container and method for producing same, and method for culturing cells
Patent Information
- Application Number
- PCT/JP2026/004611
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2025-02-20
- Filing Date
- 2026-02-09
- Publication Date
- 2026-08-27
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Figure JP2026004611_27082026_PF_FP_ABST
Abstract
Description
Multilayer film, roll body, container and method for manufacturing the same, and method for culturing cells
[0001] The present invention relates to multilayer films, rolls, containers, methods for producing the same, and methods for culturing cells.
[0002] Cell containers are known for propagating, growing, storing, and transporting cells, in which an oxygen-permeable film is heat-sealed to create an airtight state, and a port member attached to a part of the film connects the inside and outside of the container (for example, Patent Document 1). Patent Document 1 states that linear low-density polyethylene (LLDPE) and polypropylene can be suitably used as the oxygen-permeable film.
[0003] International Publication No. 2022 / 014436
[0004] Film is stored and transported as a roll wound around a core material. When the manufactured film is wound around the core material, wrinkles can occur. Heat-sealable films, such as those described in Patent Document 1, have high adhesiveness, making them prone to wrinkles when wound onto a roll.
[0005] The present invention has been made in view of the problems of the prior art described above, and aims to provide a multilayer film that is heat-sealable and less prone to wrinkles when wound onto a roll, a roll having the multilayer film, a container formed from the multilayer film, a method for manufacturing the container, and a method for culturing cells using the cell container.
[0006] One aspect of the present invention for solving the above problems relates to the following multilayer films, containers, methods for manufacturing the same, and methods for culturing cells: [1] A multilayer film having a heat-seal layer containing copolymer A, which is a 4-methyl-1-pentene copolymer, and an outer layer containing copolymer D, which is a 4-methyl-1-pentene copolymer, wherein the static friction coefficient between the heat-seal layer and the outer layer, as measured by ASTM D 1894, is 0.1 or more and 4.0 or less. [2] The multilayer film according to [1], wherein copolymer D is a copolymer with a different melting point from copolymer A. [3] The multilayer film according to [1] or [2], wherein copolymer A is a copolymer with a melting point of 100°C or more and 180°C or less, and copolymer D is a copolymer with a melting point of 180°C or more and 250°C or less. [4] The multilayer film according to any one of [1] to [3], wherein both copolymer A and copolymer D have constituent units derived from 4-methyl-1-pentene and constituent units derived from α-olefins (excluding 4-methyl-1-pentene) having 2 to 20 carbon atoms, wherein copolymer A has a ratio of 1 mol% to 55 mol% of constituent units derived from the α-olefin to the total constituent units, and copolymer D has a ratio of 1 mol% to 20 mol% of constituent units derived from the α-olefin to the total constituent units. [5] The multilayer film according to any one of [1] to [4], wherein copolymer A has constituent units derived from 4-methyl-1-pentene and constituent units derived from ethylene or propylene. [6] The multilayer film according to any one of [1] to [5], wherein copolymer D has constituent units derived from 4-methyl-1-pentene and constituent units derived from α-olefins (excluding 4-methyl-1-pentene) having 6 to 20 carbon atoms. [7] The oxygen permeability at 23°C is 3.0 L / (m³). 2 ・day・atm) or more 100.0L / (m 2[1] to [6] A multilayer film according to any one of the following, wherein the temperature is less than or equal to 100 MPa at 23°C as measured in accordance with JIS K7127:1999. [8] A multilayer film according to any one of the following, wherein the Young's modulus at 23°C is 100 MPa or more and 400 MPa or less as measured in accordance with JIS K7127:1999. [9] A multilayer film according to any one of the following, wherein the tensile elongation at 23°C is 300% or more and 1000% or less as measured in accordance with JIS K7127:1999.
[10] A multilayer film according to any one of the following, wherein the heat seal strength when the heat seal layers are heat sealed together at 150°C is 5 N / 15 mm or more and 300 N / 15 mm or less as measured.
[11] A multilayer film according to any one of the following, wherein the thickness is 50 μm or more and 1 mm or less as measured.
[12] A roll body having a core material and a multilayer film according to any one of [1] to
[11] wound around the core material.
[13] A container formed by heat-sealing the heat-seal layer of one or more multilayer films according to any one of [1] to
[11] .
[14] The container according to
[13] , wherein one or more of the multilayer films are formed into a bag shape by heat-sealing the heat-seal layer.
[15] The container according to
[14] , having a port member that connects the inside and outside of the container, wherein the port member is adhered to the multilayer film at the heat-seal portion of the heat-seal layer.
[16] The container according to
[13] , wherein one or more of the multilayer films are heat-sealed to a frame having a port portion.
[17] A medical device with a sterilization assurance level (SAL) of 10 as measured in accordance with BS EN556-1:2001. -3 A container according to any one of
[13] to
[16] below.
[18] A method for manufacturing a container, comprising the step of heat-sealing one or more multilayer films according to any one of [1] to
[11] .
[19] A method for culturing cells, comprising the steps of introducing cells into a cell container containing a multilayer film according to any one of [1] to
[11] , and culturing the cells in the cell container.
[0007] The present invention provides a multilayer film that is heat-sealable and less prone to wrinkles when wound onto a roll, a roll having the multilayer film, a container formed from the multilayer film, a method for manufacturing the container, and a method for culturing cells using the cell container.
[0008] Figure 1 is a perspective view showing the structure of a roll body formed by winding a multilayer film around a core material. Figure 2A is a plan view showing the appearance of a cell vessel manufactured from a multilayer film according to one embodiment of the present invention, and Figure 2B is a partial cross-sectional view of the cell vessel shown in Figure 2A along the dashed line 2B-2B. Figure 3A is a perspective view showing the appearance of another cell vessel manufactured from a multilayer film according to one embodiment of the present invention, and Figure 3B is an exploded perspective view of the cell vessel shown in Figure 3A.
[0009] 1. Multilayer Film The first embodiment of the present invention relates to a multilayer film. The multilayer film has a heat-seal layer and an outer layer. The heat-seal layer and the outer layer are layers that form one surface and the other surface of the multilayer film. The multilayer film may have other layers different from the heat-seal layer and the outer layer. For example, the multilayer film may have a core layer or the like disposed between them.
[0010] 1-1. Heat-seal layer: A heat-seal layer is a layer that can be fused together by overlapping different parts of the same heat-seal layer, or by overlapping it with another heat-seal layer, and then heating and pressurizing it.
[0011] The heat seal layer contains copolymer A, which is a copolymer containing structural units derived from 4-methyl-1-pentene. Copolymer A enables heat sealing by the heat seal layer and also enhances the oxygen permeability of the multilayer film. The heat seal layer may contain only one type of 4-methyl-1-pentene copolymer as copolymer A, or it may contain two or more types.
[0012] The copolymer A is preferably a copolymer of 4-methyl-1-pentene and an olefin other than 4-methyl-1-pentene. The other olefin is preferably an α-olefin having 2 to 20 carbon atoms (excluding 4-methyl-1-pentene).
[0013] The proportion of the structural unit derived from 4-methyl-1-pentene in all the structural units of the copolymer A is preferably 45 mol% or more and 99 mol% or less, more preferably 70 mol% or more and 99 mol% or less, still more preferably 75 mol% or more and 99 mol% or less, and particularly preferably 80 mol% or more and 99 mol% or less. The proportion of the structural unit derived from the other α-olefin (for example, an α-olefin having 2 to 20 carbon atoms) in all the structural units of the copolymer A is preferably 1 mol% or more and 55 mol% or less, more preferably 1 mol% or more and 30 mol% or less, still more preferably 1 mol% or more and 25 mol% or less, and further preferably 1 mol% or more and 20 mol% or less. From the viewpoint of enhancing the oxygen permeability of the multilayer film, it is preferable that the copolymer A has a high proportion of the structural unit derived from 4-methyl-1-pentene.
[0014] The other α-olefin may be linear, may have a branch, or may be a cyclic olefin.
[0015] The other linear α-olefin is preferably an α-olefin having 2 to 20 carbon atoms, more preferably an α-olefin having 2 to 10 carbon atoms, and still more preferably an α-olefin having 2 to 3 carbon atoms. Examples of the other linear α-olefin include ethylene, propylene, 1-butene, 1-pentene, 1-hexene, 1-octene, 1-decene, 1-undecene, 1-dodecene, 1-tetradecene, 1-hexadecene, 1-octadecene, and 1-eicosene. Among these, ethylene, propylene, 1-butene, 1-pentene, 1-hexene, 1-octene, and 1-decene are preferable, ethylene and propylene are more preferable, and propylene is still more preferable.
[0016] The other olefins having a branch are preferably α-olefins having 5 to 20 carbon atoms (excluding 4-methyl-1-pentene), and more preferably α-olefins having 5 to 15 carbon atoms. Examples of the other α-olefins having a branch include 3-methyl-1-butene, 3-methyl-1-pentene, 3-ethyl-1-pentene, 4,4-dimethyl-1-pentene, 4-methyl-1-hexene, 4,4-dimethyl-1-hexene, 4-ethyl-1-hexene, 3-ethyl-1-hexene, and the like.
[0017] The other olefins which are cyclic olefins are preferably α-olefins having 5 to 20 carbon atoms, and more preferably α-olefins having 5 to 15 carbon atoms. Examples of the other α-olefins which are cyclic olefins include cyclopentene, cyclohexene, cycloheptene, norbornene, 5-methyl-2-norbornene, tetracyclododecene, and vinylcyclohexane, and the like.
[0018] The copolymer A may be a copolymer with monomers other than olefins. Examples of the monomers other than the olefins include aromatic vinyl compounds, conjugated dienes, functionalized vinyl compounds, and non-conjugated polyenes, and the like.
[0019] Examples of the aromatic vinyl compounds include styrene, and monoalkylstyrenes or polyalkylstyrenes such as α-methylstyrene, o-methylstyrene, m-methylstyrene, p-methylstyrene, o,p-dimethylstyrene, o-ethylstyrene, m-ethylstyrene, and p-ethylstyrene, and the like.
[0020] The conjugated diene is preferably a compound having 4 to 20 carbon atoms, and more preferably a compound having 4 to 10 carbon atoms. Examples of the conjugated diene include 1,3-butadiene, isoprene, chloroprene, 1,3-pentadiene, 2,3-dimethylbutadiene, 4-methyl-1,3-pentadiene, 1,3-hexadiene, and 1,3-octadiene, and the like.
[0021] Examples of the functionalized vinyl compounds mentioned above include hydroxyl group-containing olefins, halogenated olefins, unsaturated carboxylic acids such as (meth)acrylic acid, propionic acid, 3-butenoic acid, 4-pentenoic acid, 5-hexenoic acid, 6-heptenoic acid, 7-octenoic acid, 8-nonenic acid, 9-decenoic acid, and 10-undecenoic acid, as well as their acid anhydrides or acid halides, unsaturated amines such as allylamine, 5-hexenamine, and 6-heptenamine, (2,7-octadienyl) succinic anhydride, pentapropenyl succinic anhydride, unsaturated epoxy compounds, and ethylenically unsaturated silane compounds. The hydroxyl group-containing olefins can be linear or branched α-olefins having 2 to 20 carbon atoms, preferably linear or branched α-olefins having 2 to 15 carbon atoms, with terminally hydroxyl groups formed. The above-mentioned halogenated olefin can be a halogenated product of a linear or branched α-olefin having 2 to 20 carbon atoms, preferably a linear or branched α-olefin having 2 to 15 carbon atoms.
[0022] Examples of the non-conjugated polyenes mentioned above include linear, branched, or cyclic polyenes, norbornene, and norbornanediene, which have 5 to 20 carbon atoms, preferably 5 to 10 carbon atoms. The non-conjugated polyene is preferably 5-vinylidene-2-norbornene or 5-ethylidene-2-norbornene.
[0023] The copolymer A preferably has a melting point of 80°C to 180°C as measured by DSC, more preferably 85°C to 160°C, and even more preferably 90°C to 160°C. Lowering the melting point of the polyolefin makes the heat seal layer less likely to tear when subjected to impact at low temperatures, effectively improving the impact resistance of the container at low temperatures. When the heat seal layer contains multiple types of copolymer A, it is preferable that the melting point of at least one of them (for example, copolymer A in an amount of 50% by mass or more of the total mass of copolymer A contained in the heat seal layer) be within the above range.
[0024] The heat seal layer may contain resins other than copolymer A. Examples of these other resins include ethylene (co)polymers, propylene (co)polymers, and block copolymers of ethylene and silicone. The heat seal layer may contain only one of these other resins, or two or more.
[0025] According to the inventors' findings, containers molded from multilayer films often have weak impact resistance in the heat-sealed portion of the heat-seal layer (the adhesive portion 116 in Figures 2A and 2B, described later), making them prone to tearing at the heat-sealed portion. In contrast, ethylene (co)polymers and propylene (co)polymers can improve the impact resistance of the heat-seal layer, making it less likely to tear even when subjected to impact, and thus efficiently enhance the impact resistance of the container. Furthermore, ethylene (co)polymers and propylene (co)polymers can also increase the flexibility of the multilayer film and improve the heat-seal strength of the heat-seal layer.
[0026] The ethylene (co)polymer may be a homopolymer of ethylene, or a copolymer of ethylene, another monomer, and an α-olefin other than ethylene (for example, an α-olefin having 3 to 20 carbon atoms) (hereinafter referred to as copolymer B). However, from the viewpoint of efficiently obtaining the above effects, it is preferable that it is a copolymer of ethylene and an α-olefin other than ethylene. The propylene (co)polymer may be a homopolymer of propylene, or a copolymer of propylene and an α-olefin other than propylene (for example, an α-olefin having 2 to 20 carbon atoms (excluding propylene)) (hereinafter referred to as copolymer C). However, from the viewpoint of efficiently obtaining the above effects, it is preferable that it is a copolymer of propylene and an α-olefin other than propylene.
[0027] The copolymer B is a copolymer of ethylene and an α-olefin having 3 to 20 carbon atoms. Examples of the α-olefin other than ethylene include propylene, 1-butene, 1-pentene, 1-hexene, 3-methyl-1-butene, 3,3-dimethyl-1-butene, 4-methyl-1-pentene, 1-octene, 1-decene, and 1-dodecene. Among these, from the viewpoint of being able to form a container that is less likely to break even when subjected to impacts such as dropping, propylene, 1-butene, 1-pentene, 1-hexene, 4-methyl-1-pentene, and 1-octene are preferable, and 1-butene, 1-pentene, 1-hexene, 4-methyl-1-pentene, and 1-octene are more preferable. The copolymer B may have only structural units derived from one of these α-olefins, or may have only structural units derived from a plurality of types.
[0028] The proportion of the structural unit derived from ethylene in all the structural units of the copolymer B is preferably 70 mol% or more and 95 mol% or less, more preferably 75 mol% or more and 92 mol% or less, and even more preferably 80 mol% or more and 90 mol% or less. The proportion of the structural unit derived from an α-olefin having 3 to 20 carbon atoms in all the structural units of the copolymer B is preferably 5 mol% or more and 30 mol% or less, more preferably 8 mol% or more and 25 mol% or less, and even more preferably 10 mol% or more and 20 mol% or less.
[0029] The density (ASTM D 1505) of the copolymer B is preferably 850 kg / m 3 or more and 910 kg / m 3 or less, more preferably 855 kg / m 3 or more and 905 kg / m 3 or less, and even more preferably 860 kg / m 3 or more and 890 kg / m 3 or less.
[0030] The copolymer B may be a random copolymer or a block copolymer. From the viewpoint of further enhancing the flexibility of the heat seal layer and being able to form a container that is less likely to break even when subjected to impacts such as dropping, a random copolymer is preferable.
[0031] Copolymer C is a copolymer of propylene and an α-olefin (excluding propylene) having 2 to 20 carbon atoms. Examples of α-olefins other than propylene include ethylene, 1-butene, 1-pentene, 1-hexene, 4-methyl-1-pentene, 1-octene, 1-decene, 1-dodecene, 1-tetradecene, 1-hexadecene, 1-octadecene, and 1-eicosene. Of these, ethylene, 1-butene, 1-pentene, 1-hexene, 4-methyl-1-pentene, and 1-octene are preferred, and ethylene and 1-butene are more preferred, from the viewpoint of forming a container that is more resistant to tearing even when subjected to impact such as dropping. Copolymer C may have only structural units derived from one type of these α-olefins, or it may have structural units derived from multiple types.
[0032] The proportion of structural units derived from propylene to the total structural units of copolymer C is preferably 51 mol% to 90 mol%, and more preferably 65 mol% to 80 mol%. The proportion of structural units derived from α-olefins (excluding propylene) having 2 to 20 carbon atoms to the total structural units of copolymer C is preferably 10 mol% to 49 mol%, and more preferably 11 mol% to 35 mol%.
[0033] The density of copolymer C (ASTM D 1505) is 860 kg / m³. 3 More than 899kg / m 3 Preferably, it is 860 kg / m 3 More than 895kg / m 3 It is more preferable that the following conditions are met: 865 kg / m 3 More than 890kg / m 3 The following is even more preferable: Higher density tends to improve surface properties such as slipperiness and blocking properties. Also, lower density improves oxygen permeability and carbon dioxide permeability.
[0034] Copolymer C may be a random copolymer or a block copolymer. From the viewpoint of further increasing the flexibility of the heat seal layer and enabling the formation of a container that is more resistant to tearing even when subjected to impacts such as dropping, a random copolymer is preferred.
[0035] The heat seal layer may contain either copolymer B or copolymer C, or both. From the viewpoint of improving tensile properties and reducing haze, it is preferable that the heat seal layer contains copolymer C.
[0036] Polyolefins containing copolymers A, B, and C can be produced by polymerizing monomers using known polymerization methods such as gas-phase, bulk, or slurry methods in the presence of known catalysts such as Ziegler-Natta catalysts and metallocene catalysts. The monomers may be derived from biomass or fossil fuels. Alternatively, both biomass-derived and fossil fuel-derived monomers may be used.
[0037] The heat seal layer preferably contains copolymer B and copolymer C in an amount of 3% to 30% by mass relative to the total mass of copolymer A, copolymer B, and copolymer C. The higher the total content of copolymer B and copolymer C, the greater the flexibility of the heat seal layer, and the more resistant to tearing even when subjected to impacts such as dropping, the more durable the container can be. The lower the total content of copolymer B and copolymer C, the greater the transparency of the heat seal layer, and the greater the transparency of the resin film and the container formed therefrom. The total content of copolymer B and copolymer C relative to the total mass of copolymer A, copolymer B, and copolymer C is more preferably 5% to 25% by mass, and even more preferably 7% to 23% by mass. The content of copolymer A relative to the total mass of copolymer A, copolymer B, and copolymer C is preferably 70% to 97% by mass, more preferably 75% to 95% by mass, and even more preferably 77% to 93% by mass.
[0038] Block copolymers of ethylene and silicone can enhance the antiblocking properties of heat-seal layers. Furthermore, these block copolymers suppress the formation of winding wrinkles when winding multilayer films onto rolls.
[0039] The block copolymer of ethylene and silicone can be a (polyethylene)-(silicone) binary block copolymer or a (polyethylene)-(silicone)-(polyethylene) ternary block copolymer. The polyethylene may be a homopolymer of ethylene or a copolymer of ethylene and an α-olefin having 3 to 20 carbon atoms, but it is preferably a homopolymer of ethylene. Furthermore, the molar ratio of ethylene to the other α-olefin (ethylene:other α-olefin) in the copolymer is preferably 81:19 to 99:1, and more preferably 90:10 to 99:1.
[0040] For example, the block copolymer used may have the following structure: A-CH 2 -CH 2 -Si(CH 3 ) 2 -O-(Si(CH) 3 ) 2 -O) i -Si(CH 3 ) 2 -CH 2 -CH 2 -A
[0041] Here, the two A's independently represent polyethylene, and i represents an integer of 1 or more. The polyethylene represented by each of the above A's preferably has a number-average molecular weight (Mn) of 100 to 500,000, more preferably 500 to 50,000, and even more preferably 700 to 10,000. i is preferably 1 to 1000, more preferably 1 to 300, and even more preferably 1 to 50.
[0042] The content of the above-mentioned ethylene-silicone block copolymer is preferably more than 0% by mass and 8% by mass or less, more preferably 0.5% by mass or more and 6% by mass or less, and even more preferably 1% by mass or more and 3% by mass or less, based on the total mass of the heat seal layer.
[0043] 1-2. Outer Layer The outer layer is a layer containing a 4-methyl-1-pentene copolymer. The outer layer is the layer that constitutes the surface of the multilayer film opposite to the heat seal layer.
[0044] The outer layer contains copolymer D, which is a copolymer containing structural units derived from 4-methyl-1-pentene. Copolymer D enhances the oxygen permeability of the multilayer film. The outer layer may contain only one type of 4-methyl-1-pentene copolymer as copolymer D, or it may contain two or more types. Copolymer D may be a resin consisting of the same structural units as copolymer A, but from the viewpoint of reducing the occurrence of winding wrinkles when winding it onto a roll, it is preferable that it is a resin containing different structural units.
[0045] Copolymer D is preferably a copolymer of 4-methyl-1-pentene and an α-olefin having 3 to 20 carbon atoms other than 4-methyl-1-pentene, and more preferably a copolymer of 4-methyl-1-pentene and a linear α-olefin having 3 to 20 carbon atoms. Examples of linear α-olefins having 3 to 20 carbon atoms include propylene, 1-butene, 1-pentene, 1-hexene, 1-octene, 1-decene, 1-dodecene, 1-tetradecene, 1-hexadecene, 1-octadecene, and 1-eicosene. Of these, a copolymer of 4-methyl-1-pentene and 1-hexadecene or 1-octadecene is preferred.
[0046] The proportion of structural units derived from 4-methyl-1-pentene to the total structural units of copolymer D is preferably 80 mol% to 99 mol%. The proportion of structural units derived from ethylene or α-olefins other than 4-methyl-1-pentene to the total structural units of copolymer D is preferably 1 mol% to 20 mol%. From the viewpoint of improving the oxygen permeability of the multilayer film, it is preferable that copolymer D has a high proportion of structural units derived from 4-methyl-1-pentene.
[0047] From the viewpoint of reducing the occurrence of winding wrinkles when winding onto a roll, it is preferable that copolymer D is a copolymer whose melting point, as measured by DSC, is different from that of copolymer A, and more preferably a copolymer with a higher melting point than copolymer A. Copolymer D is preferably 180°C to 250°C, and more preferably 190°C to 240°C. The lower the melting point of copolymer D, the less likely the outer layer is to tear when subjected to impact at low temperatures, and the impact resistance of the container at low temperatures can be effectively improved. When the outer layer contains multiple types of copolymer D, it is preferable that the melting point of at least one of them (for example, copolymer D in an amount of 50% by mass or more of the total mass of copolymer D contained in the outer layer) is within the above range.
[0048] The outer layer may contain other resins different from copolymer D. Examples of these other resins include ethylene (co)polymers and propylene (co)polymers. The outer layer may contain only one of these other resins, or two or more.
[0049] The ethylene (co)polymer may be a homopolymer of ethylene, or it may be ethylene, another monomer, and an α-olefin other than ethylene (for example, copolymer B described for the heat seal layer), but copolymer B is preferred. The propylene (co)polymer may be a homopolymer of propylene, or it may be propylene and an α-olefin other than propylene (for example, copolymer C described for the heat seal layer), but copolymer C is preferred. The outer layer may contain only copolymer B and copolymer C, or both.
[0050] The outer layer preferably contains copolymer B and copolymer C in an amount of 3% to 30% by mass relative to the total mass of copolymer D, copolymer B, and copolymer C. The higher the total content of copolymer B and copolymer C, the greater the flexibility of the outer layer, and the more resistant the container is to tear even when subjected to impacts such as dropping. The lower the total content of copolymer B and copolymer C, the greater the transparency of the outer layer, and the greater the transparency of the resin film and the container formed therefrom. The total content of copolymer B and copolymer C relative to the total mass of copolymer D, copolymer B, and copolymer C is more preferably 5% to 25% by mass, and even more preferably 7% to 23% by mass. The content of copolymer A relative to the total mass of copolymer A, copolymer B, and copolymer C is preferably 70% to 97% by mass, more preferably 75% to 95% by mass, and even more preferably 77% to 93% by mass.
[0051] 1-3. Other multilayer films may have other layers (e.g., a core layer) sandwiched between the heat-seal layer and the outer layer.
[0052] The type of resin constituting the core layer is not limited. From the viewpoint of improving the oxygen permeability of the multilayer film, the core layer preferably contains a 4-methyl-1-pentene copolymer. Furthermore, from the viewpoint of improving the oxygen permeability of the multilayer film, the core layer preferably contains a thermoplastic elastomer such as a polyolefin-based elastomer or a styrene-based elastomer. In this specification, a thermoplastic elastomer means a polymer that exhibits fluidity when heated above its melting point if crystalline, or above its glass transition point if amorphous, while exhibiting rubber elasticity at room temperature.
[0053] The 4-methyl-1-pentene copolymer that may be contained in the core layer preferably has a melting point of 60°C to 180°C or no melting point observed by DSC, and more preferably 65°C to 150°C or no melting point observed by DSC. The lower the melting point of the polyolefin, the less likely the core layer is to break when subjected to impact at low temperatures, and the impact resistance of the container at low temperatures can be effectively improved. When the core layer contains multiple types of 4-methyl-1-pentene copolymers, it is preferable that the melting point of at least one of them (for example, a 4-methyl-1-pentene copolymer in an amount of 50% by mass or more of the total mass of 4-methyl-1-pentene copolymers contained in the core layer) is within the above range.
[0054] The 4-methyl-1-pentene copolymer contained in the core layer may also contain other resins different from the 4-methyl-1-pentene copolymer contained in the core layer. Examples of the above other resins include ethylene (co)polymers and propylene (co)polymers. The core layer may contain only one of these other resins or two or more.
[0055] The ethylene (co)polymer may be a homopolymer of ethylene, or it may be ethylene, another monomer, and an α-olefin other than ethylene (for example, copolymer B described for the heat seal layer), but copolymer B is preferred. The propylene (co)polymer may be a homopolymer of propylene, or it may be propylene and an α-olefin other than propylene (for example, copolymer C described for the heat seal layer), but copolymer C is preferred. The core layer may contain only copolymer B and copolymer C, or both.
[0056] The core layer preferably contains copolymer B and copolymer C in amounts of 3% to 30% by mass relative to the total mass of the 4-methyl-1-pentene copolymer, copolymer B, and copolymer C. The higher the total content of copolymer B and copolymer C, the greater the flexibility of the core layer, allowing for the formation of a container that is more resistant to tearing even when subjected to impacts such as dropping. The lower the total content of copolymer B and copolymer C, the greater the transparency of the core layer, and the greater the transparency of the resin film and the container formed therefrom. The total content of copolymer B and copolymer C relative to the total mass of the 4-methyl-1-pentene copolymer, copolymer B, and copolymer C is more preferably 5% to 25% by mass, and even more preferably 7% to 23% by mass. The content of copolymer A relative to the total mass of copolymer A, copolymer B, and copolymer C is preferably 70% to 97% by mass, more preferably 75% to 95% by mass, and even more preferably 77% to 93% by mass.
[0057] The styrene-based elastomer that the core layer may contain is any elastomer that contains styrene as a constituent unit. Preferably, the styrene-based elastomer is a hydrogenated product in which some or all of the unsaturated bonds derived from the raw material monomer, such as alkadiene (usually excluding the unsaturated bonds of the benzene ring derived from styrene), have been converted to saturated bonds by hydrogenation.
[0058] Examples of the above-mentioned styrene-based elastomers include block copolymers having a polystyrene block and a polyolefin block consisting of structural units derived from an alkadiene having 4 to 10 carbon atoms, and hydrogenated versions thereof. The polyolefin block preferably contains structural units derived from isoprene or butadiene. The block copolymer may be a diblock type copolymer consisting of a polystyrene block and a polyolefin block bonded thereto, or a triblock type copolymer consisting of polystyrene blocks positioned at both ends and a polyolefin block positioned between them.
[0059] Specific examples of the styrene-based elastomers that are block copolymers mentioned above include block copolymers (SBC) having a polystyrene block as the hard part (crystalline part) and a conjugated diene monomer block such as isoprene or butadiene as the soft part, hydrogenated styrene-butadiene-styrene block copolymer (HSBR), styrene-ethylene-propylene-styrene block copolymer (SEPS), styrene-ethylene-ethylene-propylene-styrene block copolymer (SEEPS), and styrene-ethylene-butene-styrene block copolymer (SEBS). Of these, styrene-ethylene-butene-styrene block copolymer (SEBS), styrene-ethylene-propylene-styrene block copolymer (SEPS), and styrene-ethylene-ethylene-propylene-styrene block copolymer (SEEPS) are preferred, and styrene-ethylene-ethylene-propylene-styrene block copolymer (SEEPS) is more preferred because it has high compatibility with polyolefins and can increase heat seal strength. These styrene-based elastomers may be used individually or in combination of two or more types.
[0060] The styrene-based elastomer can have a styrene-derived constituent unit content of 5% to 30% by mass relative to its total mass, preferably 5% to 25% by mass, and more preferably 10% to 25% by mass. The lower the styrene-derived constituent unit content, the higher the oxygen permeability of the multilayer film. Furthermore, having a styrene-derived constituent unit content within this appropriate range can improve the heat sealability of the multilayer film.
[0061] The content of 4-methyl-1-pentene copolymer or thermoplastic elastomer is preferably 60% to 97% by mass, more preferably 70% to 95% by mass, and even more preferably 75% to 93% by mass, based on the total mass of the core layer.
[0062] 1-4. Characteristics of the Multilayer Film The multilayer film according to this embodiment has a static friction coefficient between the heat seal layer and the outer layer, as measured by ASTM D 1894, which is between 0.1 and 4.0. When the static friction coefficient is 0.1 or higher, the adhesion between the multilayer films is improved, making it easier to tightly wind them onto a roll. When the static friction coefficient is 4.0 or lower, it becomes less likely to cause winding wrinkles when winding onto a roll. Preferably, the static friction coefficient is between 0.1 and 3.0, and more preferably between 0.1 and 2.0. The static friction coefficient can be adjusted by the combination of copolymer A contained in the heat seal layer and copolymer D contained in the surface layer. For example, by using a copolymer D that has constituent units derived from α-olefins with a larger number of carbon atoms than copolymer A, a polymer that has a larger proportion of constituent units derived from α-olefins other than 4-methyl-1-pentene than copolymer A, or a polymer with a higher melting point than copolymer A, the static friction coefficient between the heat seal layer and the outer layer can be adjusted to the above range.
[0063] For example, the melting point of copolymer D is preferably 40°C or more higher than the melting point of copolymer A, more preferably 50°C or more higher, and even more preferably 60°C or more higher. There is no particular upper limit to the difference between the melting points of copolymer D and copolymer A, but it can be 300°C or less.
[0064] Furthermore, the multilayer film has an oxygen permeability of 3.0 L / (m²) at 23°C. 2 ・day・atm) or more 100.0L / (m 2 It is less than or equal to 4.0 L / (m³) (day atm). 2 ・day・atm) or more 50.0L / (m 2 Preferably, the flow rate is 5.0 L / (m³) or less (day·atm). 2 ・day・atm) or more 30.0L / (m 2 It is more preferable that the oxygen permeability is less than or equal to (day·atm). By increasing the oxygen permeability of the multilayer film, the efficiency of cell culture using cell containers can be improved.
[0065] Furthermore, the multilayer film has a carbon dioxide transmission rate of 10 L / (m²) at 23°C. 2 ・day・atm) or more 400L / (m 2 Preferably, the flow rate is 10 L / (m³) or less, and 10 L / (m³) or less. 2 ・day・atm) or more 300L / (m 2 It is more preferable that the carbon dioxide permeability is below (day·atm). The higher the carbon dioxide permeability, the more efficient the cell culture using the cell vessel can be.
[0066] Oxygen and carbon dioxide permeability were measured in accordance with JIS K 7126-1:2006 using a differential pressure gas permeability measuring device (manufactured by Toyo Seiki Seisakusho) under test conditions of a test temperature of 23°C and test relative humidity of 0% R.H., with a measurement area of 5 cm² of multilayer film. 2 The measurement is performed as follows: When high oxygen or carbon dioxide permeability is expected, an aluminum mask is applied to the sample beforehand, and the actual permeable area is 5.0 cm². 2 It is preferable to do so.
[0067] The multilayer film preferably has a Young's modulus of 100 MPa to 500 MPa at 23°C, measured in accordance with JIS K7127:1999, more preferably 150 MPa to 450 MPa, and even more preferably 200 MPa to 400 MPa. The lower the Young's modulus, the easier the multilayer film is to stretch and absorb energy from impact. There is no particular lower limit to the Young's modulus, but from the viewpoint of improving the transportability of the film, it is preferable to set it to 100 MPa or higher.
[0068] The multilayer film preferably has a tensile breaking strength at 23°C measured in accordance with JIS K7127:1999 of 6 MPa to 100 MPa, more preferably 8 MPa to 100 MPa, and even more preferably 10 MPa to 100 MPa. The higher the tensile breaking strength, the less likely the multilayer film is to break and the better it is able to absorb energy from impact. There is no particular upper limit to the tensile breaking strength, but from the viewpoint of improving the cuttability of the film, it is preferable to set it to 100 MPa or less.
[0069] The multilayer film preferably has a tensile elongation at 23°C measured in accordance with JIS K7127:1999 of 300% to 1000%, more preferably 320% to 1000%, and even more preferably 330% to 1000%. The greater the tensile elongation at 23°C, the easier the multilayer film is to stretch and absorb energy from impact. There is no particular upper limit to the tensile elongation at 23°C, but from the viewpoint of improving the cutability of the film, it is preferable to keep it at 1000% or less.
[0070] The Young's modulus, tensile strength, and tensile elongation at break are calculated as the arithmetic mean of values obtained by measuring the multilayer film in the MD direction and TD direction (specifically, the long side direction and the short side direction).
[0071] The multilayer film has a film impact strength measured from the outer layer side in accordance with ASTM-D 3420:2021, which is 7 kJ / m or more and 40 kJ / m or less, preferably 8 kJ / m or more, and more preferably 9 kJ / m or more. The higher the film impact strength, the more resistant the container is to tearing even when subjected to impacts such as dropping. There is no particular upper limit to the film impact strength, but it can be, for example, 40 kJ / m or less.
[0072] It is preferable that the multilayer film has high welding strength when heat-sealed. Specifically, it is preferable that the welding strength when the multilayer film is heat-sealed at 150°C is 5 N / 15 mm width or more and 300 N / 15 mm width or less, more preferably 10 N / 15 mm width or more and 200 N / 15 mm width or less, and even more preferably 20 N / 15 mm width or more and 200 N / 15 mm width or less.
[0073] When measuring the heat-sealing strength of a multilayer film, two rectangular heat-sealing test pieces measuring 150 mm wide x 50 mm high are cut from the resin film so that the vertical direction coincides with the MD (Machine Direction) direction of the resin film. Next, these two heat-sealing test pieces are placed on top of each other so that the heat-sealing layers of the multilayer films face each other. Then, using a heat-sealing test machine (Tester Industries Co., Ltd., thermal gradient heat-sealing tester, model TP-701-G), the upper and lower temperatures (heat-sealing temperature) of the heat-sealing bar are set to 150°C, and the seal width is 5 mm, the seal pressure is 0.2 MPa, and the seal time is 2 seconds. After that, the two welded multilayer films are removed from the test machine, and strip-shaped test pieces with a width of 15 mm are cut out as surface-to-surface heat-sealing test pieces of the multilayer film, in directions perpendicular and parallel to the weld line. Using a tensile testing machine (Orientec Co., Ltd., Tensilon Universal Material Testing Machine, Model RTG-1250), strip-shaped test pieces were peeled at a test temperature of 23°C, with a chuck distance of 50 mm and a tensile speed of 300 mm / min. The maximum peel strength was measured and defined as the heat seal strength (unit: N / 15 mm). The heat seal strength was measured for five test pieces, and the average value was calculated.
[0074] From the viewpoint of improving the efficiency of cell observation, the multilayer film is preferably highly transparent to visible light and has low haze. Specifically, the total light transmittance measured in accordance with ASTM D-1003:2021 is preferably 50% to 100%, more preferably 70% to 100%, and even more preferably 90% to 100%. In addition, the haze measured in accordance with ASTM D-1003:2021 is preferably 0% to 20%, and more preferably 0% to 10%.
[0075] The multilayer film is preferably 50 μm or more and 1 mm or less in thickness, more preferably 50 μm or more and 500 μm or less, and even more preferably 50 μm or more and 300 μm or less. The thicker the multilayer film, the stronger the container and the stronger the heat-sealed bond. The thinner the multilayer film, the higher the permeability of oxygen and carbon dioxide gases.
[0076] Furthermore, the multilayer film has a moisture permeability of 10 g / m² at 40°C and 90% relative humidity. 2 ・day) or more 100g / (m 2 It is preferable that the amount is less than or equal to 12 g / (m²) per day. 2 ・day) or more 80g / (m 2 It is more preferable that the amount is less than or equal to 14 g / (m²) per day. 2 ・day) or more 60g / (m 2 It is even more preferable that the moisture permeability is less than or equal to (day). By keeping the moisture permeability within this range, the moisture lost from the contents is less likely to occur.
[0077] The moisture permeability is calculated according to the isobaric method (cup type - gravimetric method) described in JIS Z 0208:2021, under condition B (test temperature 40°C, test relative humidity 90% R.H.).
[0078] The thickness of the heat seal layer is preferably 5 μm to 300 μm, more preferably 5 μm to 200 μm, and even more preferably 5 μm to 150 μm. The thicker the heat seal layer, the better the heat sealability of the multilayer film. The thinner the heat seal layer, the better the oxygen permeability of the multilayer film.
[0079] The ratio of the thickness of the heat seal layer to the total thickness of the multilayer film (heat seal layer / multilayer film) is preferably 1 / 100 or more and 70 / 100 or less, more preferably 5 / 100 or more and 60 / 100 or less, and even more preferably 8 / 100 or more and 50 / 100 or less.
[0080] The thickness of the core layer is preferably 10 μm to 500 μm, more preferably 15 μm to 300 μm, and even more preferably 20 μm to 100 μm. The thicker the core layer, the more the flatness of the multilayer film can be improved. By making the core layer appropriately thin, the oxygen permeability of the multilayer film can be improved.
[0081] The ratio of the thickness of the core layer to the total thickness of the multilayer film (core layer / multilayer film) is preferably 10 / 100 or more and 90 / 100 or less, more preferably 15 / 100 or more and 80 / 100 or less, and even more preferably 20 / 100 or more and 70 / 100 or less.
[0082] The thickness of the outer layer is preferably 5 μm to 300 μm, more preferably 10 μm to 200 μm, and even more preferably 20 μm to 150 μm. The thicker the outer layer, the higher the antiblocking properties of the multilayer film. Conversely, the thinner the outer layer, the higher the oxygen permeability of the multilayer film.
[0083] The ratio of the thickness of the heat seal layer to the thickness of the core layer (heat seal layer / core layer) is preferably 1 / 90 or more and 9 / 1 or less, more preferably 1 / 20 or more and 4 / 1 or less, and even more preferably 1 / 10 or more and 3 / 1 or less. Increasing the ratio of the heat seal layer thickness can improve the heat seal strength and tensile properties. Increasing the ratio of the core layer thickness can improve oxygen permeability.
[0084] Furthermore, it is preferable that the multilayer film has an indicator portion indicating that the surface is a heat-seal layer, or an indicator portion indicating that the surface is an outer layer that is on the outside of the cell container. The indicator portion may be formed by attaching a sticker to one or both surfaces of the multilayer film indicating which surface it is. Alternatively, the indicator portion may be formed by writing which surface it is with ink or the like on the protective layer described above.
[0085] 1-5. Method for manufacturing multilayer film and roll The multilayer film described above can be manufactured by the steps of preparing the materials for each layer and melting the prepared materials and co-extruding them to obtain a multilayer film.
[0086] In the preparation process, a heat-seal layer material containing polyolefin, a core layer material containing styrene-based elastomer, and an outer layer material containing 4-methyl-1-pentene copolymer are prepared. The materials for each of these layers can be any of the materials described above, and it is preferable to select them so that they satisfy the above-described properties after molding.
[0087] In the process of obtaining a multilayer film, the materials for each layer are melted and kneaded, and then co-extruded using a T-die extrusion machine or an extrusion lamination machine. The co-extruded material may be molded by an inflation method or a casting method.
[0088] The manufactured multilayer film can be wound around a core material to form a roll. Figure 1 is a perspective view showing the configuration of a roll 30 formed by winding a multilayer film 10 around a core material 20. In the roll 30 shown in Figure 1, the multilayer film 10 is wound around the core material 20 such that the heat-seal layer is in contact with the outer layer. When the coefficient of static friction between the heat-seal layer and the outer layer is within the above range, wrinkles are less likely to occur in the multilayer film 10 during winding.
[0089] 2. The container multilayer film can be used to produce cell containers by stacking two or more multilayer films, or by folding a single multilayer film, overlapping the edges, and then heat-sealing the edges to form a bag. When stacking the films as described above, the heat-sealed layers should be positioned facing each other.
[0090] Figure 2A is a plan view showing the appearance of a cell vessel manufactured from the multilayer film described above, and Figure 2B is a partial cross-sectional view of the cell vessel shown in Figure 2A along the dashed line 2B-2B.
[0091] The cell container 100 includes containers that are shaped like bags and are used to culture cells by introducing a culture medium and cells into them. In this specification, cell culture means increasing, growing, or maintaining the cells in a living state.
[0092] The cell container 100 shown in Figures 2A and 2B is formed by overlapping two multilayer films 112 and 114, and creating a sealed portion 116 by heat-sealing these multilayer films around the entire circumference of the edges, thereby forming a substantially sealed bag portion 110. In a portion of the heat-sealed sealed portion 116, one or more port members 200 (three in this embodiment) are sandwiched between the multilayer films 112 and 114. The port members 200 are cylindrical members that connect the inside and outside of the bag portion 110, and are welded in contact with the heat-seal layer to adhere to these multilayer films. Alternatively, the port members 200 may be welded between the heat-seal layer of the multilayer films 112 and 114 via another welding sheet.
[0093] The heat sealing in this case should be performed at a temperature of, for example, 120°C to 200°C, preferably 140°C to 180°C, and at a pressure of 0.1 MPa to 0.5 MPa, preferably 0.1 MPa to 0.2 MPa, for 1 second to 10 seconds, preferably 1 second to 5 seconds.
[0094] The heat sealing described above joins the heat-sealed layers of the stacked multilayer films together.
[0095] Furthermore, when stacking and arranging multilayer films, the multilayer films may be shaped into a predetermined form by methods such as vacuum forming, pressure forming, and vacuum pressure forming. In this case as well, it is sufficient that the edges of the multilayer films are stacked and arranged. As for the joining method of multilayer films, in addition to the method of heat sealing by sandwiching the stacked multilayer films between two hot plates, high-frequency welding and laser welding can also be applied. For example, in the case of laser welding, as described in the method of Japanese Patent No. 4279674, a method can be used in which laser light with a wavelength in the range of 1.8 to 2 μm emitted from a Ho-YAG laser or Tm fiber laser, or laser light with a wavelength of 10.6 μm emitted from a carbon dioxide laser is irradiated onto the parts to be joined of the stacked multilayer films, causing the multilayer films to directly absorb the energy of the laser light and melt the parts to be joined, thereby welding them together.
[0096] Furthermore, the number of multilayer films used to prepare the cell container 100 is not limited to two. One multilayer film may be folded, its edges may be overlapped and the edges may be heat-sealed to form a bag, or a cell container may be formed using three or more multilayer films.
[0097] Figure 3A is a perspective view showing the appearance of another cell vessel manufactured from the multilayer film described above, and Figure 3B is an exploded perspective view of the cell vessel shown in Figure 3A.
[0098] The cell container 300 shown in Figures 3A and 3B is formed by heat-sealing multilayer films 312 and 314 to both sides of a frame 320 having a port portion 322, thereby creating a substantially sealed container portion 310. The frame 320 is a frame having a predetermined shape (a rectangle in plan view in Figures 3A and 3B) and a predetermined thickness. A port portion 322 is formed in a part of the frame 320, connecting the inside and outside of the frame. By contacting the heat-sealed layers of the multilayer films 312 and 314 to both sides of the frame 320 and heat-sealing them to form an adhesive portion 316, the opening of the frame can be sealed and the container portion 310 can be formed.
[0099] From the viewpoint of improving the weldability of the frame 320 with the multilayer film 312 and the multilayer film 314, it is preferable that the frame 320 contains a 4-methyl-1-pentene copolymer in at least the portion that forms the adhesion portion 316 (the side portion in the thickness direction of the frame in Figures 3A and 3B).
[0100] The frame 320 is preferably 5 mm to 500 mm thick, and more preferably 10 mm to 400 mm thick. The thicker the frame, the wider the gap between opposing multilayer films, making it less likely for the opposing multilayer films to fuse together when subjected to heat treatment such as retort sterilization. There is no particular upper limit to the frame thickness, but from the viewpoint of improving applicability to general-purpose heat sealing equipment, it is preferably 500 mm or less, and more preferably 400 mm or less.
[0101] The heat sealing in this case should be performed at a temperature of, for example, 200°C to 260°C, preferably 210°C to 250°C, and at a pressure of 0.1 MPa to 0.5 MPa, preferably 0.1 MPa to 0.2 MPa, for 1 second to 10 seconds, preferably 1 second to 5 seconds.
[0102] In this case as well, the multilayer film may be pre-formed into a predetermined shape by methods such as vacuum forming, pressure forming, and vacuum pressure forming. Furthermore, the heat sealing can be performed using the methods described above, such as hot plates, high-frequency welding, and laser welding.
[0103] Furthermore, cell containers can be sterilized after preparation before use. As for the sterilization method, gamma ray sterilization is preferred because the film material is resistant to gamma ray irradiation. The gamma ray irradiation dose is preferably in the range of 10 to 50 kGy. Also, from the viewpoint of preventing contamination and maintaining sterility, it is preferable to use the cell containers as single-use items. Alternatively, retort sterilization by heating and pressurizing may be performed. The temperature, pressure, and processing time during retort sterilization are not particularly limited, but for example, processing at 121°C and 0.2 MPa for about 30 minutes is sufficient. Retort sterilization is preferably performed on cell containers having a frame (Figures 3A and 3B) in which fusion of opposing films is less likely to occur.
[0104] The container has a sterilization assurance level (SAL) of 10, as measured in accordance with BS EN556-1:2001. -3 Preferably, the following: 10 -6 The following is more preferable. Here, SAL represents the degree of sterility of the sterilized product after the sterilization process, and is expressed as the probability of microorganisms being present per unit number of sterilized products after sterilization. SAL is 10 -n This is expressed as, and the number of viable bacteria per sterilized item is 10 -n This means that n is preferably 3 or greater, and more preferably 6 or greater.
[0105] 3. Method for culturing cells The cell vessels described above can be used for culturing various types of cells.
[0106] Specifically, an injection port for injecting drugs or other substances, and a tube for connecting to a Luer port are attached to each port component 200. Then, a culture medium containing cells (cell suspension) is introduced into the cell container 100 through the Luer port connected to the tube. Alternatively, a culture medium without cells may be introduced into the cell container 100 first, and then the cell suspension may be introduced afterward.
[0107] Subsequently, the cell container 100 is placed in the incubator and the cells are cultured. The conditions for culturing the cells are not particularly limited and can be selected according to the type of cells being cultured.
[0108] During culture, drugs may be injected through the injection port, or a portion of the cells may be taken to check the culture status. In addition, some or all of the cells may be transferred to another cell container 100 via a tube attached to the port component.
[0109] Finally, the cultured cells are collected through the tube attached to the port component.
[0110] The cells targeted by the cell container 100 are not particularly limited and may be differentiated somatic cells or undifferentiated stem cells. The cells may be living cells or dead cells.
[0111] 4. Other Embodiments It should be noted that the embodiments described above are merely examples of the present invention, and the present invention is not limited to the embodiments described above. It goes without saying that a wide variety of other embodiments are possible within the scope of the concept of the present invention.
[0112] For example, the multilayer film mentioned above can be used not only for cell containers but also for cell cryopreservation containers, and so on.
[0113] The present invention will be described in detail based on examples, but the present invention is not limited to these examples. 1. Preparation of multilayer films and single-layer films 1-1. Materials The following materials were prepared. ・4-methyl-1-pentene copolymer 1 (4MP1-1) A 4-methyl-1-pentene copolymer (melting point: 224°C) in which the proportion of constituent units derived from 4-methyl-1-pentene is 97.6 mol%, the proportion of constituent units derived from 1-hexadecene is 1.44 mol%, and the proportion of constituent units derived from 1-octadecene is 0.96 mol% was designated as 4MP1-1 (copolymer D). ・4-methyl-1-pentene copolymer 2 (4MP1-2) A 4-methyl-1-pentene copolymer (melting point: 130°C) in which the proportion of constituent units derived from 4-methyl-1-pentene is 85 mol%, and the proportion of constituent units derived from propylene is 15 mol% was designated as 4MP1-2 (copolymer A). 4-methyl-1-pentene copolymer 3 (4MP1-3): A 4-methyl-1-pentene copolymer was defined as 4MP1-3, in which 72 mol% of the constituent units originated from 4-methyl-1-pentene and 28 mol% of the constituent units originated from propylene. The melting point of 4MP1-3 was not observed by DSC. - Propylene-α-olefin copolymer (PP) Prepared according to the method described in the Examples section of <Third Invention> in International Publication No. 2006 / 57361, having an ethylene content of 16 mol%, a propylene content of 78 mol%, a 1-butene content of 6 mol%, and an MFR (according to ASTM D1238, temperature 230°C, load 2.16 kg) of 90% by mass of propylene-ethylene-1-butene copolymer (Copolymer C), and 10% by mass of propylene homopolymer (MFR (according to ASTM D1238, temperature 230°C, load 2.16 kg) 7.0 g / 10 min, melting point 160°C) Melted and kneaded together to obtain a propylene-based resin composition (MFR (according to ASTM D1238, temperature 230°C, load 2.16 kg) 6.0 g / 10 min, density 868 kg / m³) 3) was used as a propylene copolymer (PP). ・Copolymer of 1-butene and α-olefin (PB) Mitsui Chemicals, Inc., Tuffmer BL3450M (melting point: 100°C, MFR (according to ASTM D1238, temperature 190°C, load 2.16 kg): 4.0 g / 10 min, density 910 kg / m³ 3 ) was designated as PB. ・Linear low-density polyethylene (PE-1) Manufactured by Prime Polymer Co., Ltd., Evolu SP2040 (melting point: 116℃, density 918 kg / m³) 3 ) was designated as PE-1. ・Ethylene and α-olefin copolymer (PE-2) An ethylene-based copolymer (MFR (according to ASTM D1238, temperature 230°C, load 2.16 kg): 6.7 g / 10 min, density 885 kg / m³, melting point 66°C) in which the proportion of constituent units derived from ethylene is 89 mol% and the proportion of constituent units derived from 1-butene is 11 mol%, was designated as PE-2 (Copolymer B). ・SEBS Kraton Polymer Japan Co., Ltd. Kraton G1657VS (styrene content: 13 mass%, MFR (according to ASTM D1238, temperature 230°C, load 2.16 kg): 9.0 g / 10 min, density 900 kg / m³ 3 ) was used as SEBS. ・Ethylene-silicone block copolymer Polyethylene having a vinyl group at one end, synthesized according to the method described in Synthesis Example 2 of International Publication No. 2012 / 098865, was used as the ethylene / silicone block copolymer.
[0114] 1-2. Preparation of multilayer and single-layer films Using a tumbler blender, the materials were mixed (dry blended) in the proportions shown in Table 1 to prepare resin compositions for each layer.
[0115] Each layer's resin composition was supplied to its respective extruder, and using a cast molding die (die width 350 mmφ, lip gap 1 mm), the extrusion rate of each extruder was set so that the resin temperature reached 270°C and the thickness ratio of the outer layer, core layer, and heat seal layer was 1:1:1 or 1:2:1 in that order. Multilayer films 1 to 12 with a thickness of 100 μm were obtained by co-extrusion molding. The molding speed was 4 m / min.
[0116] PE-1 was supplied to an extruder, and a single-layer film 13 with a thickness of 100 μm was obtained by single-layer extrusion molding using a cast molding die (die width 350 mmφ, lip gap 1 mm) at a resin temperature of 230°C. The molding speed was 4 m / min.
[0117] Tables 1 and 2 show the film thickness, thickness ratio, and the materials and their amounts used in each layer of the fabricated multilayer films 1 to 12 and single-layer film 13. In Tables 1 and 2, the "thickness ratio" column indicates the ratio of the thickness of the outer layer / core layer / heat seal layer, and the "materials for each layer" column indicates the amount (in parts by mass) of each material used in the fabrication of each layer.
[0118]
[0119]
[0120] 2. Measurement of Multilayer Films and Single-Layer Films 2-1. Static and Dynamic Friction Coefficients Test specimens of each multilayer film and single-layer film, cut into strips measuring 63.5 mm wide x 100 mm long, were measured in accordance with ASTM D 1894, under the conditions of a test speed of 200 mm / min, a load of 200 g, and a temperature of 23°C, in the MD direction of the test specimen. For multilayer films 11 and 12, the friction coefficient was high, and the test specimen did not slide, so the dynamic friction coefficient could not be measured.
[0121] 2-2. Oxygen Permeability Oxygen permeability was measured in accordance with JIS K 7126-1:2006 using a differential pressure gas permeability measuring device (manufactured by Toyo Seiki Seisakusho) under test conditions of a test temperature of 23°C and test humidity of 0%RH, with a measurement area of 5 cm² of film. 2 The measurement was performed as follows: The measurement area of the film was adjusted by preparing two adhesive aluminum masks manufactured by Modern Control, each with a 25 mm diameter hole in the center, and stacking the film to be measured between these two masks. Specifically, the film was positioned so that the central holes of the two masks overlapped.
[0122] 2-3. Tensile Tests Each multilayer and single-layer film was cut into strips measuring 15 mm wide x 100 mm long. In accordance with JIS K7127:1999, a tensile testing machine (Instron, universal tensile testing machine 3380) was used to measure Young's modulus (YM) (in MPa), tensile breaking strength (TS) (in MPa), and tensile breaking elongation (EL) (in %) in the MD and TD directions of the test specimens under the following conditions: chuck distance of 50 mm, tensile speed of 300 mm / min, and temperature of 23°C. Measurements were performed in both the MD and TD directions, and the average values were used as the measured values for the film in question.
[0123] 2-4. Film Impact Strength Using a film impact tester manufactured by Toyo Seiki Seisakusho Co., Ltd. (compliant with ASTM-D 3420:2021), the impact strength of each film was measured from the outer layer side, with a film size of 100 mm x 100 mm, an impact head spherical shape of 0.5 inches in diameter, and a measurement temperature of 23°C.
[0124] 2-5. Heat Seal Strength Two strips measuring 150 mm wide x 50 mm long were prepared from each of the multilayer and single-layer films to form test specimens. Next, the two prepared test specimens were placed on top of each other with the heat seal layers facing each other, and then heat-sealed using a heat seal tester (Tester Industries Co., Ltd., thermal gradient heat seal tester TP-701-G) under the following conditions: upper temperature 150°C, lower temperature 150°C, seal width 5 mm, seal pressure 0.2 MPa, and seal time 2 seconds.
[0125] Next, the heat-sealed test specimens were removed from the heat-seal testing machine and cut into 15 mm wide strips. These 15 mm wide heat-sealed test specimens were then subjected to a test at a speed of 300 mm / min and an ambient temperature of 23°C. The specimens were pulled at a 180° angle to the heat-sealed surfaces of the specimens to separate them, and the maximum peel strength was measured. This maximum value was defined as the heat-seal strength (unit: N / 15 mm). If the specimens stretched to their limit without separation, the maximum observed tensile strength was defined as the heat-seal strength. The heat-seal strength was measured for five specimens, and the average value was calculated.
[0126] 2-6. Haze and Total Light Transmittance Multilayer and single-layer films were cut into 50 mm squares to serve as test specimens. The haze value (in %) and total transmitted light amount in air were measured using a fully automatic haze meter (Tokyo Denshoku Co., Ltd., TC-HIII DPK, light source: 12V 50W halogen lamp C) in accordance with ASTM D 1003:2021. This measurement was performed at three arbitrary points on each test specimen, and the average of the data from these three points was taken as the measured value. The total light transmittance was then calculated using the following formula: Total light transmittance (%) = 100 × (total transmitted light amount) / (incident light amount)
[0127] 2-7. Moisture Permeability The moisture permeability was calculated under condition B (test temperature 40°C, test humidity 90% R.H.) in accordance with the isobaric method (cup type - gravimetric method) described in JIS Z 0208:2021.
[0128] 2-8. The wrinkles in each multilayer film and single-layer film were visually observed when they were fabricated and wound into rolls.
[0129] The measurement results for multilayer films 1 to 12 and single-layer film 13 are shown in Tables 3 and 4.
[0130]
[0131]
[0132] 3. Preparation and Evaluation of Cell Culture Vessels 3-1. Preparation of Cell Culture Bags (Cell Culture Bag 1) Two films measuring 120 mm in length and 120 mm in width were cut from multilayer film 2. They were placed facing each other, and the three sides were heat-sealed with a 10 mm width seal at a sealing temperature of 150°C and a sealing pressure of 0.1 MPa to obtain a bag component.
[0133] A port component made from 4MP1-1 was placed at the opening of the bag component, and a cell culture bag 1 with a port was obtained by heat sealing with a welding line width (joint width) of 10 mm under the conditions of a sealing temperature of 240°C, a sealing pressure of 0.1 MPa, and a sealing time of 4 seconds. The culture space area of the cell culture bag 1 with a port is 100 cm². 2 That was the case.
[0134] (Cell culture bag 2) Two pieces of film measuring 120 mm in length and 120 mm in width were cut from a single-layer film 13. They were placed facing each other, and the three sides were heat-sealed with a 10 mm width seal at a sealing temperature of 150°C and a sealing pressure of 0.1 MPa to obtain a bag component.
[0135] A port component made of high-density polyethylene was placed at the opening of the bag component, and a cell culture bag 2 with a port was obtained by heat sealing it with a welding line width (joint width) of 10 mm under the conditions of a sealing temperature of 220°C, a sealing pressure of 0.1 MPa, and a sealing time of 4 seconds. The culture space area of the cell culture bag 2 with a port is 100 cm². 2 That was the case.
[0136] Cell culture bags with ports were sterilized by irradiating them with gamma rays at a dose of 25 kGy. The Sterility Assurance Level (SAL) of medical devices, measured according to BS EN556-1:2001, for cell culture bags manufactured under the same conditions and sterilized with gamma rays at a dose of 25 kGy was 10 in all cases. -6 That was the case.
[0137] (Cell culture bag 3) A frame 1 consisting of 4MP1-1 was fabricated by injection molding, with a frame size of 400 mm on the long side, 300 mm on the short side, 25 mm in height, and 15 mm in frame width, each having a port with an inner diameter of 6 mm on the short side.
[0138] Two pieces of film measuring 400 mm in length and 300 mm in width were prepared by cutting out a multilayer film 6. The heat-seal layer was placed in contact with the frame 1, and the multilayer films were positioned opposite each other, sandwiching the frame 1. Then, the four sides were heat-sealed with a width of 10 mm under the conditions of a sealing temperature of 240°C, a sealing pressure of 0.1 MPa, and a sealing time of 4 seconds to obtain a cell culture bag 3 with a port.
[0139] 3-2. Cell culture test 2 x 10 7 One human chronic myeloid leukemia cell line K562 (RIKEN BRC, RCB0027) was suspended in 100 ml of RPMI1640 medium (Fujifilm Wako Pure Chemical Industries) containing 10% FBS (BioWest), 1% GlutaMAX™-I supplement (Thermo Fisher Scientific), and 1% penicillin / streptomycin (Fujifilm Wako Pure Chemical Industries). The cells were introduced into the sterile ported cell culture bags 1 and 2 and cultured at 37°C under 5% CO2. 2 CO2 maintained 2 The cells were cultured in an incubator. Cell suspensions were collected from the port using a syringe three and seven days after the start of culture.
[0140] Cell density and cell viability were calculated for cell suspensions 3 and 7 days after the start of culture using the trypan blue excretion method. Specifically, the cell suspension was mixed with a 0.4 w / v% trypan blue solution (Fujifilm Wako Pure Chemical Industries, Ltd.), injected into a cell counter (Funakoshi Co., Ltd.), and observed using a phase-contrast microscope (OLYMPUS Co., Ltd.) to count the cell density. Cell viability was classified as follows: cells that did not stain due to trypan blue excretion were classified as live cells, and cells stained blue with the dye were classified as dead cells. Cell viability was calculated using the formula: live cell density ÷ total cell (live cells + dead cells) density. The results are shown in Tables 5 and 6.
[0141]
[0142]
[0143] The results shown in Tables 5 and 6 indicate that cell culture bag 1 has a higher cell culture efficiency than cell culture bag 2.
[0144] 3-3. Retort sterilization: Cell culture bags 2 and 3 were subjected to retort sterilization in a retort apparatus under a pressure of 0.2 MPa at 121°C for 30 minutes. Afterwards, the presence or absence of fusion between opposing multilayer films in cell culture bags 2 and 3 was visually confirmed.
[0145] In cell culture bag 2, fusion of opposing multilayer films was observed. On the other hand, in cell culture bag 3, no practically problematic fusion of opposing multilayer films was observed.
[0146] This application claims priority to Japanese Patent Application No. 2025-025926, filed on 20 February 2025. The matters described in the original specification, claims and drawings of said application are incorporated herein by reference.
[0147] The multilayer film according to the present invention and the cell container having the same can be applied to the culture of various cells.
[0148] 10 Multilayer film 20 Core material 30 Roll body 100, 300 Cell container 110 Bag part 112, 114, 312, 314 Multilayer film 116, 316 Adhesion part 200 Port member 320 Frame 322 Port part
Claims
1. A multilayer film comprising a heat-seal layer containing copolymer A, which is a 4-methyl-1-pentene copolymer, and an outer layer containing copolymer D, which is a 4-methyl-1-pentene copolymer, wherein the static friction coefficient between the heat-seal layer and the outer layer, as measured by ASTM D 1894, is 0.1 or more and 4.0 or less.
2. The multilayer film according to claim 1, wherein copolymer D is a copolymer with a different melting point from copolymer A.
3. The multilayer film according to claim 1, wherein copolymer A is a copolymer having a melting point of 100°C or more and 180°C or less, and copolymer D is a copolymer having a melting point of 180°C or more and 250°C or less.
4. Both copolymer A and copolymer D have constituent units derived from 4-methyl-1-pentene and constituent units derived from α-olefins (excluding 4-methyl-1-pentene) having 2 to 20 carbon atoms, wherein copolymer A has a ratio of constituent units derived from α-olefins to the total constituent units of 1 mol% to 55 mol%, and copolymer D has a ratio of constituent units derived from α-olefins to the total constituent units of 1 mol% to 20 mol%, the multilayer film according to claim 1.
5. The multilayer film according to claim 1, wherein the copolymer A comprises a structural unit derived from 4-methyl-1-pentene and a structural unit derived from ethylene or propylene.
6. The multilayer film according to claim 1, wherein the copolymer D comprises a structural unit derived from 4-methyl-1-pentene and a structural unit derived from an α-olefin (excluding 4-methyl-1-pentene) having 6 to 20 carbon atoms.
7. The oxygen permeability at 23°C is 3.0 L / (m³). 2 ・day・atm) or more 100.0L / (m 2 The multilayer film according to claim 1, wherein the temperature is less than or equal to (day atm).
8. The multilayer film according to claim 1, wherein the Young's modulus at 23°C, as measured in accordance with JIS K7127:1999, is 100 MPa or more and 400 MPa or less.
9. The multilayer film according to claim 1, wherein the tensile elongation at 23°C, measured in accordance with JIS K7127:1999, is 300% or more and 1000% or less.
10. The multilayer film according to claim 1, wherein the heat seal strength when the heat seal layers are heat sealed together at 150°C is 5 N / 15 mm or more and 300 N / 15 mm or less.
11. The multilayer film according to claim 1, wherein the thickness is 50 μm or more and 1 mm or less.
12. A roll body comprising a core material and a multilayer film according to any one of claims 1 to 11 wound around the core material.
13. A container formed by heat-sealing the heat-seal layers of one or more multilayer films according to any one of claims 1 to 11.
14. The container according to claim 13, wherein one or more of the multilayer films are formed into a bag shape by heat-sealing the heat-seal layer.
15. The container according to claim 14, wherein the container has a port member that connects the inside and outside of the container, and the port member is bonded to the multilayer film in the heat-seal portion of the heat-seal layer.
16. The container according to claim 13, wherein one or more of the multilayer films are heat-sealed to a frame having a port portion.
17. The sterility assurance level (SAL) of the medical device, as measured in accordance with BS EN556-1:2001, is 10. -3 The container according to claim 13, which is as follows:
18. A method for manufacturing a container, comprising the step of heat-sealing one or more multilayer films according to any one of claims 1 to 11.
19. A method for culturing cells, comprising the steps of: introducing cells into a cell container containing a multilayer film according to any one of claims 1 to 11; and culturing the cells in the cell container.