Multilayer films and liquid containers

Abstract

To provide a liquid agent container that is formed from a multilayer film using polybutylene terephthalate in an outer layer, which inhibits or prevents a component derived from the polybutylene terephthalate from permeating through the multilayer film and eluting in a content liquid, and a multilayer film for forming the liquid agent container.SOLUTION: A multilayer film is obtained by laminating at least (1) a layer containing polybutylene terephthalate, (2) a layer containing a cyclic olefin-based polymer, (3) a flexible layer containing an ethylene-based resin, and (4) a layer containing polyolefin. The layer (1), the layer (2), and the layer (4) forming one surface of the multilayer film are laminated in this order. A liquid agent container is formed from the multilayer film so that the layer (4) is used as an innermost layer.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a multilayer film and a liquid medication container formed from the multilayer film. [Background technology]

[0002] In recent years, drug solution bags made of flexible plastic film have become mainstream as containers for holding drug solutions such as infusions. This type of drug solution bag has the advantage of being easy to handle and dispose of. Furthermore, because this type of drug solution bag comes into direct contact with the drug solution, those made of polyolefins such as polyethylene and polypropylene, whose safety has been established, are widely used.

[0003] BACKGROUND ART Films forming liquid containers such as drug solution bags have been improved from various viewpoints. For example, containers for holding liquid medicines such as infusions are required to be heat-resistant because they are sterilized by high-pressure steam at high temperatures. For this reason, a medical laminate film using polybutylene terephthalate as the outer layer has been proposed (Patent Document 1).

[0004] Furthermore, a multilayer film using a cyclic polyolefin as an intermediate layer has also been proposed for the purpose of preventing air from penetrating the film into the film container from the outside and preventing moisture from leaking out of the film from the inside of the container during long-term storage of the film container containing a liquid agent such as an infusion solution, i.e., for the purpose of improving gas barrier properties and moisture barrier properties (Patent Document 2).

[0005] Furthermore, in order to provide heat-resistant medical containers that are excellent in heat resistance, transparency, and flexibility, medical containers or multi-layer medical containers made of ethylene-based resin compositions with a specified residual crystallinity at sterilization temperatures have also been proposed (Patent Documents 3 and 4). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 2012 / 8007 [Patent Document 2] Japanese Patent Application Laid-Open No. 2002-301796 [Patent Document 3] Japanese Patent Application Laid-Open No. 2008-253478 [Patent Document 4] Japanese Patent Application Laid-Open No. 2013-81494 Summary of the Invention [Problem to be solved by the invention]

[0007] As a result of intensive research, the present inventors have found that when polybutylene terephthalate is used as the outer layer of a multilayer film forming a liquid drug container, there is a problem in that components derived from this polybutylene terephthalate permeate the multilayer film and leach into the liquid content.

[0008] In view of the problems in the prior art, a first object of the present invention is to provide a liquid container formed from a multilayer film using polybutylene terephthalate in one layer (e.g., an outer layer), in which components derived from this polybutylene terephthalate are inhibited or prevented from permeating the multilayer film and leaching into the liquid contained therein, and a multilayer film for forming such a liquid container.

[0009] A second object of the present invention is to provide a liquid agent container having excellent heat resistance, transparency and impact resistance, and a multilayer film for forming such a liquid agent container. [Means for solving the problem]

[0010] The present invention relates to, for example, the following [1] to [9]. [1] A multilayer film, at least, (1) a layer containing polybutylene terephthalate; (2) a layer containing a cyclic olefin polymer; (3) a flexible layer comprising an ethylene-based resin; and (4) Polyolefin-containing layer are stacked, A multilayer film in which the layer (1), the layer (2), and the layer (4) forming one surface of the multilayer film are laminated in this order.

[0011] [2] The multilayer film according to [1] above, wherein the cyclic olefin polymer has a glass transition temperature of 80 to 145°C.

[0012] [3] The multilayer film of [1] or [2] above, wherein the cyclic olefin polymer has a structural unit represented by the following general formula (2):

[0013] [ka] [In formula (2), R 3 and R 4 are each independently a hydrogen atom or a hydrocarbon group having 1 to 5 carbon atoms, and may be bonded to each other to form a ring, x is an integer of 1 or greater, y is 0 or an integer of 1 or greater, and z is an integer of 1 or greater.

[0014] [4] The multilayer film of any one of [1] to [3] above, wherein the endothermic curve obtained by differential scanning calorimetry of the ethylene-based resin satisfies the following requirements [a], [b], and [c]: [a]: When t = 107°C, Ht = 55 to 75%. [b]: When t = 121°C, Ht = 65 to 80%. [c]: When t = 127°C, Ht = 70 to 95%. (In the above [a], [b], and [c], Ht is the amount of molten component calculated by the formula: Ht = ht / ΔHm, using a differential scanning calorimeter to measure the ethylene-based resin in a nitrogen atmosphere, heating it from -20°C to 230°C at a heating rate of 10°C / min, holding it at that temperature for 10 minutes, then cooling it to 30°C at a heating rate of 10°C / min, holding it at that temperature for 1 minute, and then heating it to 230°C at a heating rate of 10°C / min, and determining the total heat of fusion (ΔHm) and the heat of fusion (ht) observed from the melting onset temperature to t°C from the endothermic curve observed during the second heating.)

[0015] [5] The multilayer film of any one of [1] to [4] above, wherein the ethylene resin has a melt flow rate (190°C, 2.16 kg load) of 0.01 to 10 g / 10 min.

[0016] [6] The multilayer film according to any one of [1] to [5] above, wherein the polyolefin satisfies the following requirements [d] and [e]: Requirement [d]: Density is 0.900 to 0.960 kg / cm 3 is. Requirement [e]: The melt flow rate (190°C, 2.16 kg load) is 0.1 to 10 g / 10 min.

[0017] [7] The multilayer film according to any one of [1] to [6] above, wherein the polyolefin is a mixture of polyethylene and polypropylene.

[0018] [8] The multilayer film according to any one of [1] to [7] above, wherein the layer (1), the layer (3), the layer (2), the layer (3), and the layer (4) are laminated in this order.

[0019] [9] A liquid agent container formed from any one of the multilayer films [1] to [8] above, with the layer (4) being the innermost layer. [Effects of the Invention]

[0020] By using the multilayer film of the present invention, it is possible to manufacture a liquid container in which polybutylene terephthalate is used in one layer (e.g., the outer layer) of the multilayer film, but in which components derived from polybutylene terephthalate are suppressed or prevented from permeating the multilayer film and leaching into the liquid content. Furthermore, the liquid container formed from the multilayer film of [4] above is particularly excellent in heat resistance, transparency and impact resistance. DETAILED DESCRIPTION OF THE INVENTION

[0021] The present invention will now be described in further detail. [Multi-layer film] The multilayer film according to the present invention comprises: at least, (1) a layer containing polybutylene terephthalate; (2) a layer containing a cyclic olefin polymer; (3) a flexible layer comprising an ethylene-based resin; and (4) Polyolefin-containing layer are stacked, The layer (1), the layer (2), and the layer (4) forming one surface of the multilayer film are laminated in this order. It is characterized by the following.

[0022] (1) A layer containing polybutylene terephthalate: The layer (1) is a layer comprising polybutylene terephthalate. As the polybutylene terephthalate, any conventionally known polybutylene terephthalate can be used, and a specific example of such a commercially available product is "NovaDuran (registered trademark)" manufactured by Mitsubishi Engineering Plastics Corporation.

[0023] The melt volume flow rate of the polybutylene terephthalate (according to ISO 1133, 250°C, 2.16 kg load) is preferably 1 to 30 cm from the viewpoint of film formability. 3 / 10 minutes.

[0024] The flexural modulus (according to ISO 178) of the polybutylene terephthalate is preferably low from the viewpoint of flexibility of the film, and is 200 to 3000 MPa, preferably 500 to 2000 MPa, and more preferably 500 to 1000 MPa.

[0025] The layer (1) contains a component derived from polybutylene terephthalate or a component derived from 1,4-butanediol or the like used in the production of polybutylene terephthalate (for example, a compound represented by the following formula:

[0026] [ka] In the multilayer film of the present invention, even if the layer (1) contains such a component, the penetration of such a component to the surface that comes into contact with the liquid agent is suppressed or prevented.

[0027] The thickness of the layer (1) is preferably 1 μm or more from the viewpoint of stably forming the multilayer film, and is preferably 50 μm or less from the viewpoint of not reducing the strength of the liquid agent container formed from the multilayer film.

[0028] (2) Layer containing cyclic olefin polymer: The layer (2) is a layer containing a cyclic olefin polymer. The cyclic olefin polymer may be a conventionally known cyclic olefin polymer, specific examples of which include polymers having structural units represented by the following general formula (1) and / or the following general formula (2):

[0029] [ka] [In formula (1), R 1 and R 2 are each independently a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms, and may be bonded to each other to form a ring. m is an integer of 1 or more, and n is 0 or an integer of 1 or more.

[0030] [ka] [In formula (2), R 3 and R 4 are each independently a hydrogen atom or a hydrocarbon group having 1 to 5 carbon atoms, and may be bonded to each other to form a ring. x is an integer of 1 or more, y is 0 or an integer of 1 or more, and z is an integer of 1 or more.

[0031] The general formula (2) indicates that the polymer contains x structural units derived from a cyclic olefin and z structural units derived from ethylene, but does not necessarily represent a block copolymer consisting of a block consisting of x structural units derived from a cyclic olefin and a block consisting of z structural units derived from ethylene.

[0032] The polymer having the structural unit represented by the general formula (1) may contain, as a monomer, for example: Norbornene and its alkyl and / or alkylidene substituted derivatives (e.g., 5-methyl-2-norbornene, 5,6-dimethyl-2-norbornene, 5-ethyl-2-norbornene, 5-butyl-2-norbornene, 5-ethylidene-2-norbornene) (hereinafter also referred to as "norbornene-based monomers"); Cyclopentadiene, 2,3-dihydrodicyclopentadiene, and their alkyl-substituted derivatives such as methyl, ethyl, propyl, and butyl; Methanooctahydronaphthalene and its alkyl and / or alkylidene substituted derivatives (e.g., 6-methyl-1,4:5,8-dimethano-1,4,4a,5,6,7,8,8a-octahydronaphthalene, 6-ethyl-1,4:5,8-dimethano-1,4,4a,5,6,7,8,8a-octahydronaphthalene, 6-ethylidene-1,4:5,8-dimethano-1,4,4a,5,6,7,8,8a-octahydronaphthalene); Trimers and tetramers of cyclopentadiene (e.g., 4,9:5,8-dimethano-3a,4,4a,5,8,8a,9,9a-octahydro-1H-benzoindene, 5,8-methano-3a,4,4a,5,8,8a,9,9a-octahydro-1H-benzoindene, 5,8-methano-1,4,4a,4b,5,8,8a,9b-octahydro-1H-fluorene, 4,11:5,10:6,9-trimethano-3a,4,4a,5,5a,6,9,9a,10,10a,11,11a-dodecahydro-1H-cyclopentaanthracene) The ring-opening polymer is a saturated polymer produced by polymerizing a monomer selected from the above by a known ring-opening polymerization method, and then hydrogenating the resulting polymer by a conventional hydrogenation method.

[0033] The polymer having the structural unit represented by the general formula (2) is a polymer obtained by copolymerizing the norbornene-based monomer and ethylene by a known method and / or a hydrogenated product thereof, and both are saturated polymers.

[0034] As a commercially available product, ZEONOR (registered trademark) manufactured by Zeon Corporation may be mentioned as an example of a cyclic olefin polymer having a structural unit represented by the general formula (1). Commercially available cyclic olefin polymers having a structural unit represented by the general formula (2) include "APEL (registered trademark)" manufactured by Mitsui Chemicals, Inc. and "TOPAS (registered trademark)" manufactured by TOPAS ADVANCED POLYMERS GmbH.

[0035] From the viewpoint of preventing permeation of eluates derived from the polybutylene terephthalate constituting the layer (1), a cyclic olefin polymer having a structural unit represented by the general formula (2) is particularly preferred.

[0036] The glass transition temperature (Tg) of the cyclic olefin polymer, measured by the following method, is preferably 80°C or higher, more preferably 100°C or higher, from the viewpoint of preventing permeation of eluates derived from the polybutylene terephthalate constituting the layer (1), and is preferably 145°C or lower, more preferably 135°C or lower, from the viewpoint of not reducing the flexibility of a liquid agent container formed from the multilayer film.

[0037] <Method for measuring glass transition temperature> Using a differential scanning calorimeter, approximately 10 mg of sample was heated in a nitrogen atmosphere from 30°C to 200°C at a heating rate of 50°C / min and held at that temperature for 10 minutes. The sample was then cooled to -100°C at a rate of 10°C / min, held at that temperature for 5 minutes, and then heated to 200°C at a heating rate of 10°C / min. During the second heating, the DSC curve bends due to a change in specific heat, and this is detected as a parallel shift of the baseline. The glass transition temperature (Tg) is determined as the temperature at the intersection of the tangent to the baseline below this bend and the tangent to the point where the slope of the bend is greatest.

[0038] The molecular weight of the cyclic olefin polymer measured by gel permeation analysis using toluene as a solvent is preferably 10,000 to 100,000, more preferably 10,000 to 80,000. The thickness of the layer (2) is preferably 5 μm or more from the viewpoint of stable formation of the multilayer film, and is preferably 20 μm or less from the viewpoint of the transparency of the multilayer film.

[0039] The layer (2) may contain a resin other than a cyclic polyolefin to improve adhesion to the adjacent layer. Examples of such a resin include the polyolefin used in the polyolefin-containing layer (4) described below.

[0040] (3) Flexible layer containing ethylene-based resin: The flexible layer (3) is a layer containing an ethylene-based resin. Examples of the ethylene-based resin include low-density polyethylene, linear low-density polyethylene, medium-density polyethylene, and high-density polyethylene, which may be used alone or in combination of two or more.

[0041] From the viewpoints of heat resistance, transparency, and impact resistance, the ethylene-based resin is preferably a mixture of high-density polyethylene and linear low-density polyethylene. In this mixture, the ratio (mass of high-density polyethylene) / (mass of linear low-density polyethylene) is, for example, 95 / 5 to 5 / 95, preferably 10 / 90 to 50 / 50. Furthermore, the high-density polyethylene in this mixture is preferably an ethylene homopolymer.

[0042] Examples of methods for producing these ethylene-based resins include a slurry method, a solution method, a gas phase method, etc. When producing ethylene-based resins by these methods, examples of olefin polymerization catalysts that can be used include magnesium chloride-supported titanium catalysts, Phillips catalysts, and metallocene catalysts.

[0043] The density of the ethylene resin is preferably 955 to 900 kg / m 3 , more preferably 930 to 905 kg / m 3 is. The melt flow rate of the ethylene resin (based on ASTM D1238, 190° C., 2.16 kg load) is preferably 0.01 to 10 g / 10 min, more preferably 0.1 to 2 g / 10 min.

[0044] In the endothermic curve obtained by differential scanning calorimetry of the ethylene-based resin, the following requirements [a], [b] and [c] are preferably satisfied. [a]: When t = 107°C, Ht = 55 to 75%. [b]: When t = 121°C, Ht = 65 to 80%. [c]: When t = 127°C, Ht = 70 to 95%. (In the above [a], [b], and [c], Ht is the amount of molten component calculated by the formula: Ht = ht / ΔHm, using a differential scanning calorimeter to measure the ethylene-based resin in a nitrogen atmosphere, heating it from -20°C to 230°C at a heating rate of 10°C / min, holding it at that temperature for 10 minutes, then cooling it to 30°C at a heating rate of 10°C / min, holding it at that temperature for 1 minute, and then heating it to 230°C at a heating rate of 10°C / min, and determining the total heat of fusion (ΔHm) and the heat of fusion (ht) observed from the melting onset temperature to t°C from the endothermic curve observed during the second heating.)

[0045] When the ethylene-based resin satisfies the requirements [a], [b], and [c], a liquid container formed from the multilayer film of the present invention will not develop large wrinkles or other deformations even when sterilized under high-temperature conditions at 121°C, and will have sufficient heat resistance. After sterilization, the liquid container will have a high transmittance of 55% or more at a wavelength of 450 nm as measured by the ultraviolet-visible absorbance measurement method described in Transparency Test Method 1 of the Japanese Pharmacopoeia (17th Edition). Furthermore, leakage of the solution inside due to dropping the bag or the like will be prevented, and the liquid container will have excellent impact resistance.

[0046] An ethylene-based resin satisfying the requirements [a], [b], and [c] can be produced, for example, when producing the above-mentioned mixture of high-density polyethylene and linear low-density polyethylene, by appropriately adjusting the ratio between the high-density polyethylene and the linear low-density polyethylene, the density or melting point of the linear low-density polyethylene, etc.

[0047] The thickness of the flexible layer (3) is preferably 5 μm or more from the viewpoint of stable formation of the multilayer film, and is preferably 200 μm or less from the viewpoint of transparency of the multilayer film.

[0048] (4) Polyolefin-containing layer: The layer (4) is a layer containing a polyolefin, although the layer (4) usually does not contain either polybutylene terephthalate or a cyclic olefin polymer.

[0049] As this polyolefin, polyolefins that have conventionally been used for the innermost layer of liquid medicine containers formed from multilayer films can be used. Examples of the polyolefin include ethylene-based polymers and propylene-based polymers.

[0050] The polyolefin may be a mixture of various polyolefins, for example, the ethylene-based polymer and the propylene-based polymer. The density of the polyolefin (based on ASTM D1505, 23°C) is, for example, 900 to 960 kg / m 3 , preferably 920 to 950 kg / m 3 (Requirement [d]).

[0051] The melt flow rate of the polyolefin (based on ASTM D1238, 190°C, 2.16 kg load) is, for example, 0.1 to 10 g / 10 min, preferably 1 to 10 g / 10 min (requirement [e]).

[0052] Examples of the ethylene polymer include commercially available products such as Hi-Zex (registered trademark) 65150B and Ult-Zex (registered trademark) 4020B (both manufactured by Prime Polymer Co., Ltd.).

[0053] Examples of the propylene polymer include commercially available products such as Prime Polypro (registered trademark) J102WA (manufactured by Prime Polymer Co., Ltd.). The ethylene polymer is a polymer whose main structural unit is a structural unit derived from ethylene (hereinafter referred to as "ethylene unit"). Examples of the ethylene polymer include an ethylene homopolymer and an ethylene-α-olefin random copolymer containing a small amount of structural units derived from an α-olefin having 3 to 20 carbon atoms, for example, 10 mol % or less, preferably 5 mol % or less.

[0054] The melt flow rate of the ethylene polymer (based on ASTM D1238, 190° C., 2.16 kg load) is, for example, 0.1 to 20 g / 10 min, and preferably 1 to 10 g / 10 min.

[0055] The density of the ethylene polymer (according to ASTM D1505, 23°C) is, for example, 900 to 960 kg / m 3 , preferably 920 to 950 kg / m 3 is. The propylene-based polymer is a polymer whose main structural unit is a structural unit derived from propylene (hereinafter referred to as "propylene unit"). Examples of the propylene-based polymer include a propylene homopolymer and a propylene-α-olefin random copolymer containing a small amount of structural units derived from an α-olefin having 2 or 4 to 20 carbon atoms, for example, 10 mol % or less, preferably 5 mol % or less.

[0056] The melt flow rate of the propylene polymer (according to ASTM D1238, 230° C., 2.16 kg load) is, for example, 0.1 to 20 g / 10 min, and preferably 1 to 10 g / 10 min. The thickness of the layer (4) is preferably 5 μm or more from the viewpoint of stable formation of the multilayer film, and is preferably 50 μm or less from the viewpoint of transparency of the multilayer film.

[0057] (multilayer film) The multilayer film according to the present invention is formed by laminating at least the layer (1), the layer (2), the flexible layer (3), and the layer (4), and the layer (1), the layer (2), and the layer (4) forming one surface of the multilayer film are laminated in this order.

[0058] By using the multilayer film of the present invention, it is possible to produce a liquid container in which polybutylene terephthalate is used in one layer (e.g., the outer layer) of the multilayer film, but in which components derived from polybutylene terephthalate are inhibited or prevented from permeating the multilayer film and leaching into the liquid contained therein. Furthermore, when the flexible layer (3) satisfies the requirements [a], [b], and [c], the multilayer film of the present invention is also excellent in heat resistance, transparency, and impact resistance, among others.

[0059] Examples of layer configurations of the multilayer film of the present invention include a configuration in which layer (1), layer (2), flexible layer (3), and layer (4) are laminated in this order, and a configuration in which layer (1), flexible layer (3), layer (2), flexible layer (3), and layer (4) are laminated in this order. Among these, from the viewpoint of improving the strength of a liquid agent container formed from the multilayer film of the present invention, a configuration in which layer (1), flexible layer (3), layer (2), flexible layer (3), and layer (4) are laminated in this order is preferred.

[0060] The multilayer film according to the present invention may have laminated on the surface opposite to the layer (4) that forms one surface of the multilayer film a resin film such as polyethylene terephthalate, polyethylene naphthalate, polyamide, polypropylene, polyethylene, or an ethylene-vinyl alcohol copolymer, or a film in which an inorganic oxide or the like is vapor-deposited on such a resin film, or a metal foil such as aluminum.

[0061] An adhesive layer may be provided between adjacent layers to enhance adhesion between the layers. For example, the layer (1) and the flexible layer (3) may be adjacent to each other via the adhesive layer. The adhesive layer may be a layer containing an adhesive resin.

[0062] The thickness of the multilayer film according to the present invention is appropriately set depending on the application. For example, when a liquid container is formed from the multilayer film according to the present invention, the thickness is set depending on the strength, flexibility, etc. required for the liquid container, and is usually 100 to 300 μm, preferably 100 to 200 μm.

[0063] (Manufacturing method of multilayer film) The multilayer film of the present invention can be produced by a conventional method, such as a water-cooled or air-cooled coextrusion inflation method, a coextrusion T-die method, a dry lamination method, or an extrusion lamination method, except that the above-mentioned materials are used as the materials for each layer. Among these methods, the water-cooled coextrusion inflation method and the coextrusion T-die method are particularly preferred from the viewpoints of transparency, hygiene, etc.

[0064] [Liquid container] The liquid container of the present invention is characterized in that it is formed from the above-mentioned multilayer film of the present invention so that the layer (4) is the innermost layer, i.e., the surface that comes into contact with the contents.

[0065] According to the liquid drug container of the present invention, polybutylene terephthalate is used in one layer (e.g., the outer layer) of the multilayer film that forms the liquid drug container, and yet components derived from polybutylene terephthalate are inhibited or prevented from permeating the multilayer film and leaching into the liquid content. Furthermore, when the flexible layer (3) satisfies the requirements [a], [b], and [c], the liquid drug container of the present invention is also excellent in heat resistance, transparency, and impact resistance, among others.

[0066] The liquid container of the present invention can be produced by overlapping two sheets of the multilayer film of the present invention with the layer (4) facing each other and heat-pressing the periphery thereof. Alternatively, for example, the multilayer film of the present invention can be formed into a bag shape by an inflation method so that the layer (4) is the surface that comes into contact with the contents, and then the peripheral edge of the bag-shaped multilayer film of the present invention thus obtained is heat-pressed to form the multilayer film.

[0067] The conditions for thermocompression bonding are, for example, a temperature of preferably 130 to 200°C, more preferably 150 to 180°C, a pressure of preferably 0.1 to 0.8 MPa, more preferably 0.15 to 0.5 MPa, and a pressurization time of preferably 1 to 5 seconds, more preferably 1.5 to 3 seconds.

[0068] The liquid container of the present invention may be provided with a cylindrical member as a component for allowing a liquid, such as a medicinal solution, contained inside the liquid container to flow out of the liquid container or for allowing a medicinal solution to flow from the outside of the liquid container into the liquid container.

[0069] Furthermore, the liquid container of the present invention may be a multi-chamber container in which an easily peelable seal is formed inside the container, and the seal can be peeled off at the time of use to mix the contents. When the liquid drug container of the present invention is sterilized, a conventional method can be applied, for example, a method in which a drug solution and other contents are placed inside the liquid drug container, the container is sealed, and then the liquid drug container is sterilized.

[0070] Examples of the sterilization method include known heat sterilization methods such as high-pressure steam sterilization and hot water shower sterilization. The sterilization temperature in heat sterilization is generally about 105 to 110°C, but the sterilization temperature may be set to 118 to 121°C depending on the type of drug solution, its usage, the environment of use, etc. When the flexible layer (3) satisfies the requirements [a], [b], and [c], the liquid container of the present invention has particularly excellent heat resistance, and does not develop significant deformation such as wrinkles even when sterilized at 121°C. [Example]

[0071] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. <Method for measuring resin physical properties> The physical properties of the resins used in the examples were measured by the following methods.

[0072] Melt Flow Rate (MFR) The melt flow rate was measured under a load of 2.16 kg in accordance with ASTM D1238E at a temperature of 190°C or 230°C.

[0073] [density] Density was measured at 23°C according to ASTM D1505.

[0074] [Melting point (Tm), amount of melting component (Ht)] Using a differential scanning calorimeter (PerkinElmer DSC-7), approximately 5 mg of sample was placed in an aluminum pan and heated from -20°C to 230°C at a rate of 10°C / min under a nitrogen atmosphere, and held at that temperature for 10 minutes.The temperature was then lowered to 30°C at a rate of 10°C / min, held at that temperature for 1 minute, and then raised to 230°C at a rate of 10°C / min.

[0075] Furthermore, in the endothermic curve observed during the second heating described above, the total heat of fusion (ΔHm) and the heat of fusion (ht) observed from the melting initiation temperature to t°C were measured, and the amount of melted component (Ht) was calculated using the following formula. Ht=ht / ΔHm

[0076] <Resin used> In the examples, the following resins (1) to (4-5) were used as raw materials for each layer of the multilayer film. Representative physical properties and trade names are shown below. (1) Polybutylene terephthalate Resin (1-1): Novaduran (registered trademark) 5505S (manufactured by Mitsubishi Chemical Corporation) (2) Cyclic olefin polymer Resin (2-1): APEL (registered trademark) 6011T (manufactured by Mitsui Chemicals, Inc., glass transition temperature: 105°C) Resin (2-2): TOPAS (registered trademark) 5013S-4 (manufactured by TOPAS ADVANCED POLYMERS GmbH, glass transition temperature: 134°C) (3) Ethylene-based resin composition Resin (3-1): 20 parts by mass of high-density polyethylene (ethylene homopolymer) and 80 parts by mass of ethylene-α-olefin copolymer (linear low-density polyethylene) are mixed together, Density is 912 kg / m 3 , Melt flow rate (190°C, 2.16 kg load) is 0.5 g / 10 min, and The amount of melting component (Ht) is 71% when t = 107°C, 79% when t = 121°C, and 95% when t = 127°C. The ethylene-based resin composition prepared as follows: (4) Polyolefins, etc. Resin (4-1): Polyethylene (density: 937 kg / m 3 , MFR (190℃, 2.16kg load): 2g / 10min) Resin (4-2): Polyethylene (density: 957 kg / m 3 , MFR (190℃, 2.16 kg load): 1 g / 10 min) Resin (4-3): Polyethylene (density: 959 kg / m 3 MFR (190°C, 2.16 kg load): 15 g / 10 min Resin (4-4): Polypropylene (MFR (230°C, 2.16 kg load): 4 g / 10 min) Resin (4-5): Polyethylene (density: 900 kg / m 3 MFR (190°C, 2.16 kg load): 0.4 g / 10 min

[0077] <Manufacturing of multilayer films and liquid containers> [Examples 1 to 3] (1. Manufacturing of multilayer films) A multilayer film having a structure in which the first, second, third, fourth, and fifth layers shown in Table 1 below were laminated in this order was produced by five-layer coextrusion water-cooled inflation molding.

[0078] [Table 1]

[0079] (2. Manufacturing of liquid containers) The resulting multilayer film was cut into a size of 15 cm x 14 cm, and two pieces were stacked together with the fifth layer on the inside, and the periphery was heat-sealed to a width of 5 mm to produce a liquid container.

[0080] <Evaluation of liquid containers> (1. Amount of eluted components) A 150 mL solution containing 15 g / L soybean oil, 70 g / L glucose, amino acids, electrolytes, and vitamins was sealed in a solution container manufactured in each Example, and sterilized by high-pressure steam at 121°C. The container was then stored for two weeks at 60°C and 75% RH. After storage, the eluates from the polybutylene terephthalate (shown in Table 3) were analyzed by liquid chromatography (under the following conditions).

[0081] Liquid chromatography measurement conditions: To exactly 10 mL of the extract, add 1 g of sodium chloride, 10 mL of acetonitrile, and 4 g of magnesium sulfate. Shake vigorously for 1 minute, then centrifuge at 2000 rpm for 5 minutes. Transfer the upper layer to a recovery flask. Add 10 mL of acetonitrile to the remaining lower layer, shake vigorously for 1 minute, then centrifuge at 2000 rpm for 5 minutes. Combine the upper layer with the previous one and evaporate under reduced pressure at 40°C ± 10°C. Add a 1:1 water / acetonitrile mixture to the residue to make exactly 10 mL, and use this as the sample solution. Separately, accurately measure 10 mg of PBT-CD (see Tables 3 and 4) and dissolve in acetone to make exactly 100 mL. Add 10 mL of this solution to exactly 100 mL with acetonitrile to make exactly 100 mL, and use this as the standard stock solution. Measure exactly 5 mL of each standard stock solution and add acetonitrile to make exactly 50 mL. Take exactly 4 mL of this solution, add 5 mM ammonium acetate buffer (pH 3.0) to make exactly 50 mL, and use this as the standard solution. Take exactly 100 μL each of the standard solution and sample solution, and test them by liquid chromatography under the following conditions. t and A s Calculate the concentration of PBT-CD in the liquid (μg / L) using the following formula:

[0082] PBT-CD concentration in the liquid (μg / L) =(M / 10)×(A t / A s )×0.08×C×1000 M: Amount of PBT-CD (mg) As: Peak area of ​​PBT-CD in the standard solution At: Peak area of ​​PBT-CD in the sample solution C: Correction coefficient: 10 / 7

[0083] Test conditions: Detector: ultraviolet absorption photometer (measurement wavelength: 260 nm) Column: A stainless steel tube with an inner diameter of 4.6 mm and a length of 15 cm is packed with 5 μm octadecylsilanized silica gel for liquid chromatography (ZORBAX SB-C18, 4.6 mm ID x 150 mm, 5 μm, manufactured by Agilent). Column temperature: constant temperature around 40°C Mobile phase A: 5 mM ammonium acetate buffer (pH 3.0) Mobile phase B: acetonitrile Mobile phase delivery: The concentration gradient is controlled by changing the mixing ratio of mobile phase A and mobile phase B as follows:

[0084] [Table 2]

[0085] [Table 3]

[0086] [Table 4]

[0087] The results are shown in Table 5.

[0088] [Table 5] In all of Examples 1 to 3, the elution of eluates derived from polybutylene terephthalate into the liquid preparation was prevented.

[0089] (2. Heat resistance, transparency and impact resistance) Heat resistance: The multilayer film obtained in the examples was cut into a size of 20 cm x 28 cm, two sheets were overlapped with the fifth layer on the inside, and the periphery was heat-sealed to a width of 5 mm to produce a liquid container. 1000 mL of distilled water was sealed into the obtained liquid container, and after processing by high-pressure steam sterilization at 121°C for 15 minutes, the presence and degree of wrinkles were visually observed at the four corners of the liquid container, and heat resistance was evaluated based on the observation results according to the following criteria. ◎: No wrinkles observed ○: No noticeable wrinkles (slight wrinkles) ×: Obvious wrinkles observed

[0090] Transparency: 1000 mL of distilled water was sealed in a liquid container prepared in the same manner as in the heat resistance test, and the container was subjected to high-pressure steam sterilization at 121°C for 15 minutes. After that, the portion of the multilayer film that had been in contact with the solvent was cut out from the liquid container to prepare a sample piece. The underwater light transmittance (%) of this sample piece at 450 nm was measured using an ultraviolet-visible spectrophotometer, and the transparency was evaluated based on the measurement results according to the following criteria. ◎: Underwater light transmittance is 70% or more ○: Underwater light transmittance is 65% or more and less than 70% ×: Underwater light transmittance is less than 65%

[0091] Shock resistance: 1000 mL of distilled water was sealed in a liquid container prepared in the same manner as in the heat resistance test, and after 15 minutes of high-pressure steam sterilization at 121°C, the container was stored for 48 hours or more at a temperature of 0°C. After that, the liquid container was placed on a flat workbench, and a 6.4 kg iron plate (30 cm wide, 32 cm long) was dropped horizontally from a height of 50 cm above the container, and impact resistance was evaluated according to the following criteria. ○: No bag breakage occurred. ×: The bag was broken.

[0092] The results are shown in Table 6. [Table 6]

[0093] <Manufacturing of multilayer films and liquid containers> [Example 4, Comparative Example 1] (1. Manufacturing of multilayer films) A multilayer film having a configuration in which the first, second, third, fourth, and fifth layers shown in Table 7 below were laminated in this order was produced by five-layer coextrusion water-cooling inflation molding (Example 4). Also, a multilayer film having a configuration in which the first, second, and fifth layers were laminated in this order was produced by three-layer coextrusion water-cooling inflation molding (Comparative Example 1).

[0094] [Table 7]

[0095] (2. Manufacturing of liquid containers) The resulting multilayer film was cut into a size of 15 cm x 14 cm, and two pieces were stacked together with the sixth layer on the inside, and the periphery was heat-sealed to a width of 5 mm to produce a liquid container.

[0096] <Evaluation of liquid containers> (Amount of eluted components) The containers manufactured in each example were filled with 150 mL of either (1) water, (2) 1.33 g of ammonium chloride dissolved in 1,000 mL of water and adjusted to pH 8.5 by adding 28% aqueous ammonia dropwise (pH 8.5 buffer solution), or (3) 1.58 g of ammonium formate dissolved in 1,000 mL of water and adjusted to pH 3.5 by adding formic acid (pH 3.5 buffer solution). These containers were then autoclaved at 121°C and stored at 60°C and 75% RH for two weeks. After storage, the eluates from the polybutylene terephthalate (shown in Table 8) were analyzed by liquid chromatography (under the same conditions as in Examples 1 to 3).

[0097] [Table 8]

[0098] The results are shown in Table 9.

[0099] [Table 9]

[0100] In comparison with Comparative Example 1, in Example 4, the elution of eluates derived from polybutylene terephthalate into the liquid preparation was prevented.

Claims

1. A multilayer film, at least, (1) a layer containing polybutylene terephthalate; (2) a layer containing a cyclic olefin polymer; (3) a flexible layer comprising an ethylene-based resin; and (4) Polyolefin-containing layer are stacked, The layer (1), the layer (2), and the layer (4) forming one surface of the multilayer film are laminated in this order; Satisfy one or more of the following requirements [α], [β], and [γ]: Satisfy one or more of the following requirements [α], [δ], and [ε]: Multilayer film. [α]: In an endothermic curve obtained by differential scanning calorimetry of the ethylene-based resin, the following requirements [a], [b], and [c] are satisfied. [a]: When t = 107°C, Ht = 55 to 75%. [b]: When t = 121°C, Ht = 65 to 80%. [c]: When t = 127°C, Ht = 70 to 95%. [In the above [a], [b], and [c], Ht is the amount of molten component calculated by the formula: Ht = ht / ΔHm, using a differential scanning calorimeter to measure the ethylene-based resin in a nitrogen atmosphere by heating it from -20°C to 230°C at a heating rate of 10°C / min, holding it at that temperature for 10 minutes, then cooling it to 30°C at a heating rate of 10°C / min, holding it at that temperature for 1 minute, and then heating it to 230°C at a heating rate of 10°C / min, and determining the total heat of fusion (ΔHm) and the heat of fusion (ht) observed from the melting onset temperature to t°C from the endothermic curve observed during the second heating.] [β]: The melt flow rate of the ethylene resin (190° C., 2.16 kg load) is 0.01 to 10 g / 10 min. [γ]: The polyolefin satisfies the following requirements [d] and [e]. [d]: The density is 0.900 to 0.960 kg / cm 3 . [e]: The melt flow rate (190°C, 2.16 kg load) is 0.1 to 10 g / 10 min. [δ]: The layer (1) containing polybutylene terephthalate contains a compound represented by the following formula: 【Chemical 1】 [ε]: The layer (1) containing polybutylene terephthalate is the outer layer.

2. 2. The multilayer film according to claim 1, wherein the cyclic olefin polymer has a glass transition temperature of 80 to 145°C.

3. 3. The multilayer film according to claim 1, wherein the cyclic olefin polymer has a structural unit represented by the following general formula (2): 【Chemistry 2】 [In formula (2), R 3 and R 4 are each independently a hydrogen atom or a hydrocarbon group having 1 to 5 carbon atoms, and may be bonded to each other to form a ring, x is an integer of 1 or more, y is 0 or an integer of 1 or more, and z is an integer of 1 or more.

4. A multilayer film described in any one of claims 1 to 3, which satisfies the requirement [α].

5. A multilayer film described in any one of claims 1 to 4, which satisfies the requirement [β].

6. A multilayer film described in any one of claims 1 to 5, which satisfies the requirement [γ].

7. The multilayer film according to any one of claims 1 to 6, wherein the polyolefin is a mixture of polyethylene and polypropylene.

8. A multilayer film described in any one of claims 1 to 7, which satisfies the requirement [δ].

9. A multilayer film described in any one of claims 1 to 8, which satisfies the requirement [ε].

10. The multilayer film according to any one of claims 1 to 9, wherein the layer (1), the layer (3), the layer (2), the layer (3), and the layer (4) are laminated in this order.

11. A liquid agent container formed from the multilayer film according to any one of claims 1 to 10, with the layer (4) being the innermost layer.

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