Laminates and plastic containers

Abstract

To provide a laminate and a plastic container that hardly cause a decrease in transparency even after sterilization treatment and breaking under impacts such as dropping, exhibit suitable strength as a storage container, and offer superior storage stability for ingredients such as pharmaceuticals stored therein.SOLUTION: A laminate is composed of at least two layers, the layers including a first resin layer 11 that includes an amorphous cyclic-olefin-based resin configured from an olefin monomer component having a cyclic hydrocarbon skeleton, and a second resin layer 12 that has polyethylene, polypropylene or ethylene α-olefin copolymer as a main component, wherein the first resin layer 11 contains a thermoplastic elastomer in a proportion of 10 mass% or less and is an innermost layer in contact with the contents. An adhesive layer or an anchor agent layer may be interposed between each layer.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] This invention relates to laminates and containers. [Background technology]

[0002] In recent years, soft bag formulations have been developed for intravenous infusion, in which injectable drugs are pre-diluted and prepared, then filled into flexible containers (plastic containers) made of plastic or similar materials. These soft bag formulations are considered useful because, in addition to their convenience and speed of use, they reduce the risk of breakage and are easier to dispose of compared to glass bottles and ampoules. This application claims priority based on Japanese Patent Application No. 2018-018232, filed in Japan on February 5, 2018, and the contents of that application are incorporated herein by reference.

[0003] However, films molded from ordinary polyolefin resins such as polyethylene (hereinafter sometimes referred to as "PE") and polypropylene (hereinafter sometimes referred to as "PP") (hereinafter sometimes referred to as "PO resin"), as well as resins commonly used as materials for pharmaceutical containers such as polyvinyl chloride, adsorb or permeate certain chemicals, including radical scavenging agents. As a result, the active ingredients of the drug solution may be adsorbed onto the plastic container, or the drug solution may interact with additives and low-molecular-weight components contained in the resin film that makes up the plastic container, which have been challenges in developing soft bag formulations.

[0004] Therefore, it has been proposed to use cyclic olefin resins as a barrier resin that suppresses the adsorption and permeation of chemicals and other substances into plastic containers. Because cyclic olefin resins have an alicyclic hydrocarbon structure in their molecular backbone, they are bulky and the movement of molecular chains is restricted, making them less susceptible to molecular absorption and permeation. As a result, they have less interaction with the above-mentioned additives and drug components, and are known to exhibit excellent storage stability.

[0005] For example, Patent Document 1 describes that an infusion bag having a structure in which the outer layer (surface layer) is made of PP, the innermost layer is made of a cyclic olefin resin, and the intermediate layer between the two layers is made of PP is suitable as a container for "edaravone". Although a container with such a structure has sufficient storage stability for the formulation, the cyclic olefin resin is hard and brittle, so if the container is accidentally dropped or subjected to an impact, partial peeling of the seal or breakage such as pinholes may occur, leading to leakage, and thus the container has problems with impact resistance.

[0006] Cyclic olefin resins have the drawback of being prone to gel formation, fisheye formation, or defects (such as impurities) caused by oxidation or carbonization during film formation and molding processes due to the aggregation of components contained in the resin. To overcome these shortcomings, Patent Documents 2 and 3 propose a method of blending polyethylene, polypropylene, or ethylene-α-olefin copolymer (olefin resin) with cyclic olefin resins in a certain proportion.

[0007] While this technology improves processability, it presents a problem in that the transparency of the container is significantly reduced by the steam sterilization process performed after filling with drugs or other substances. This is undesirable because it hinders the visual inspection and camera-based inspection of whether the contents are of appropriate quality during the manufacturing process of pharmaceuticals, and there is a concern that it may deviate from the transparency standards stipulated in 7.02 Test Methods for Plastic Pharmaceutical Containers of the 17th Edition of the Japanese Pharmacopoeia.

[0008] Furthermore, when the weight of the contents is large, the proportion of olefin resin used in the formulation must be increased to provide a sufficient level of impact resistance. This increases the molecular mobility of the barrier layer, which may lead to a decrease in the concentration of the contents and other issues that could result in insufficient storage stability, which is essential for a container to function properly.

[0009] As mentioned above, for pharmaceuticals and other products where drug adsorption to plastics is likely to occur, a plastic container that possesses sufficient transparency and physical properties while also offering excellent storage stability for the drug components has not yet been developed, and its development is highly desired.

Prior Art Documents

Patent Documents

[0010]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0011] The present invention has been made in view of the above circumstances, and is difficult to cause a decrease in transparency even by sterilization treatment, is difficult to be damaged by impacts such as dropping, has appropriate strength as a storage container, and further has excellent storage stability of components such as pharmaceuticals as the contained substance. An object of the present invention is to provide a laminate and a plastic container.

Means for Solving the Problems

[0012] In order to solve the above problems, the present invention provides a laminate comprising at least two or more layers including a first resin layer containing an amorphous cyclic olefin resin composed of an olefin monomer component having a cyclic hydrocarbon skeleton, and a second resin layer mainly composed of polyethylene, polypropylene or an ethylene-α-olefin copolymer, wherein the first resin layer contains an elastomer at a ratio of 10% by mass or less.

[0013] The elastomer may be a thermoplastic elastomer. The thermoplastic elastomer may be selected from one or more of an olefin thermoplastic elastomer and a styrene thermoplastic elastomer. The elastomer may be contained in the first resin layer at a ratio of 0.05 to 10% by mass.

[0014] The present invention also provides a plastic container, which is characterized in that the above-described laminate is arranged to be overlapped so as to face each other, and includes a storage portion for storing the contents and a mouth portion for discharging the contents.

[0015] The contents may be pharmaceuticals. The pharmaceutical may be an aqueous solution containing edaravone, which is a pyrazolone derivative, or a pharmaceutically acceptable salt thereof. The plastic container may be an infusion bag or a blow molded container.

Advantages of the Invention

[0016] According to the present invention, it is possible to provide a laminate and a plastic container that are excellent in adhesive strength between layers and heat seal strength, are less likely to have reduced transparency even in high-temperature sterilization treatment, are less likely to be damaged by impacts such as dropping, have appropriate strength as a storage container, and are excellent in storage stability of components such as pharmaceuticals as the stored contents.

Brief Description of the Drawings

[0017] [Figure 1] It is a cross-sectional view showing the laminate of the first embodiment. [Figure 2] It is a cross-sectional view showing the laminate of the second embodiment. [Figure 3] It is a cross-sectional view showing the laminate of the third embodiment. [Figure 4] It is a cross-sectional view showing the laminate of the fourth embodiment. [Figure 5] It is a side view showing an example of the plastic container of the present invention.

Modes for Carrying Out the Invention

[0018] Hereinafter, the present invention will be described based on preferred embodiments. The laminate of this embodiment is a laminate comprising at least two layers, comprising a first resin layer containing an amorphous cyclic olefin resin composed of olefin monomer components having a cyclic hydrocarbon skeleton, and a second resin layer mainly composed of polyethylene, polypropylene, or ethylene-α-olefin copolymer, wherein the first resin layer contains elastomer in a proportion of 10% by mass or less.

[0019] The laminate 10 shown in Figure 1 has a two-layer structure with a second resin layer 12 positioned on one side of a first resin layer 11. The laminate 20 shown in Figure 2 has a three-layer structure with second resin layers 12 positioned on both sides of the first resin layer 11. In the two-layer laminate 10, the innermost layer in contact with the contents may be the first resin layer 11, and the second resin layer 12 may be positioned on the outside. In the three-layer laminate 20, the innermost layer in contact with the contents may be one of the second resin layers 12, and the outermost layer may be the other second resin layer 12.

[0020] The second resin layer 12 mainly consists of polyethylene, polypropylene, or ethylene-α-olefin copolymer. Preferably, the second resin layer 12 contains at least one of polyethylene, polypropylene, or ethylene-α-olefin copolymer, or two or more in total, for example, 50 to 100% by weight. When the second resin layer 12 is placed on both sides of the first resin layer 11, the thickness, composition, etc. of each second resin layer 12 may be the same, or at least one of the thickness, resin grade, blend ratio, etc. may differ.

[0021] When a sterilization temperature of 120°C or higher is applied, a polypropylene resin with a high melting point may be used in place of the polyethylene resin in the second resin layer 12. If the second resin layer 12 contains a polypropylene resin, it is appropriate to have a structure in which an adhesive resin layer 13 is provided between the first resin layer 11 and the second resin layer 12, which adheres well to both layers, as shown in Figures 3-4. The laminate 30 shown in Figure 3 has a three-layer structure in which a second resin layer 12 is placed on one side of a first resin layer 11 via an adhesive resin layer 13. The laminate 40 shown in Figure 4 has a five-layer structure in which a second resin layer 12 is placed on both sides of a first resin layer 11 via an adhesive resin layer 13. When adhesive resin layers 13 are placed on both sides of the first resin layer 11, the thickness, composition, etc., of each adhesive resin layer 13 may be the same, or at least one of the thickness, resin grade, blend ratio, etc., may differ. When second resin layers 12 are placed on both sides of the first resin layer 11, only one of the second resin layers 12 may contain polypropylene resin, or a four-layer structure may be provided with an adhesive resin layer 13 only between the first resin layer 11 and one of the second resin layers 12.

[0022] To impart appropriate physical properties such as flexibility and transparency to the plastic container, the second resin layer 12 and the adhesive resin layer 13 may be made by mixing two or more resins having different physical properties, or by arranging two or more layers. For example, two or more second resin layers 12 mainly composed of polyethylene, polypropylene, or ethylene-α-olefin copolymer may be placed adjacent to each other. Alternatively, two or more adhesive resin layers 13 may be placed between the first resin layer 11 and the second resin layer 12.

[0023] Linear low-density polyethylene (LLDPE) is preferred as the polyethylene-based resin (polyethylene or ethylene-α-olefin copolymer) used in the second resin layer 12. LLDPE is typically produced by copolymerizing α-olefins with 4 or more carbon atoms and introducing short-chain branching, resulting in fewer long-chain branchings and a linear molecular structure. Examples of α-olefins copolymerized with LLDPE include 1-butene, 1-hexene, 4-methyl-1-pentene, and 1-octene. LLDPE polymerized using a single-site catalyst is particularly preferred because it has a narrow molecular weight distribution and excellent mechanical properties. Examples of single-site catalysts include metallocene catalysts. Examples of metallocene catalysts include catalysts containing metallocene compounds that include a ligand having a cyclopentadienyl skeleton and in which the metal is zirconium, hafnium, etc.

[0024] The polypropylene resin layer used in the second resin layer 12 is a layer mainly containing polypropylene (PP) resin. The polypropylene resin used in the polypropylene resin layer may be a homopolymer of propylene, or a copolymer with ethylene or at least one α-olefin having 4 to 8 carbon atoms. If the polypropylene resin contained in the polypropylene resin layer is a copolymer, the copolymer may be a random copolymer or a block copolymer. The polypropylene resin layer may contain one type of polypropylene resin, or it may contain two or more types of polypropylene resin layers. To impart flexibility to the polypropylene resin layer, a grade of soft polypropylene (R-TPO) may be selected, and rubber or thermoplastic elastomer components may be added as needed.

[0025] Examples of adhesive resin layers 13 include, for example, when bonding a cyclic olefin resin layer and a polypropylene resin layer, a resin layer containing a resin component consisting of linear low-density polyethylene, styrene elastomer, and polypropylene resin, wherein the ratio of (linear low-density polyethylene):(total of styrene elastomer and polypropylene resin) is in the range of 40:60 to 95:5 by weight. Other examples include Modic®, a polyolefin-based adhesive resin from Mitsubishi Chemical Corporation and MCPP Innovation LLC, and Zelas®, an olefin-based thermoplastic elastomer.

[0026] As the first resin layer 11, a resin having a cyclic hydrocarbon skeleton (cyclic olefin skeleton) as a unit structure, which has a glass transition temperature sufficiently higher than the storage environment of the contents, can be used. The resin constituting the first resin layer 11 is a polymer composed of one or more olefin monomers or a polymer in which the double bond is hydrogenated, and at least one of the olefin monomers is a cyclic olefin monomer having a cyclic hydrocarbon skeleton. Examples of cyclic olefin monomers include norbornene compounds. Such amorphous polymers are referred to here as cyclic olefin resins. A cyclic olefin resin may be a copolymer in which at least one of two or more olefin monomers is an acyclic olefin monomer that does not have a cyclic hydrocarbon skeleton. Examples of acyclic olefin monomers that can be used in cyclic olefin resins include ethylene or α-olefins having 4 to 8 carbon atoms.

[0027] Cyclic olefin resins include polymers in which the remaining double bond is hydrogenated after ring-opening metathesis polymerization of norbornene compounds, addition polymers consisting of two or more cyclic olefin monomers, and addition polymers obtained by copolymerizing cyclic olefin monomers with acyclic olefin monomers. Methods for producing cyclic olefin resins include hydrogenating a ring-opening metathesis polymer of norbornene compounds, copolymerization of two or more cyclic olefin monomers, and copolymerization of cyclic olefin monomers with α-olefins.

[0028] A basic structure of a polymer obtained by hydrogenating a ring-opening metathesis polymer of norbornene compounds can be seen, for example, in the following formula (I). That is, formula (I) describes a polymer in which a cyclic skeleton and an ethylene skeleton are arranged alternately. The cyclic skeleton in formula (1) is a 1,3-cyclopentylene skeleton. However, the ring-opening metathesis polymer of norbornene compounds itself does not need to be a copolymer.

[0029] [ka]

[0030] In formula (I), n is an integer of 1 or more, and R 1 and R 2 represent a hydrogen atom or an alkyl group. R 1 and R 2 may be the same as or different from each other. R 1 and R 2 may be bonded to each other to form a ring.

[0031] The structure shown in formula (I) is not limited to the case where the substituents R 1 and R 2 having n 1,3-cyclopentylene skeletons are the same as each other and the ring-opening metathesis polymer of a norbornene compound is a homopolymer. The structure shown in formula (I) may be a polymer obtained by hydrogenating a ring-opening metathesis polymer of two or more norbornene compounds. An example thereof is the following formula (II).

[0032]

Chemical formula

[0033] In formula (II), m and n are integers of 1 or more, and R 1 and R 2 represent a hydrogen atom or an alkyl group. m and n may be the same as or different from each other. R 1 and R 2 may be the same as or different from each other. R 1 and R 2 may be bonded to each other to form a ring.

[0034] Specific examples of the polymer obtained by hydrogenating the ring-opening metathesis polymer of a norbornene compound include, for example, "ZEONEX (registered trademark)", "ZEONOR (registered trademark)", etc. manufactured by Nippon Zeon Co., Ltd.

[0035] Furthermore, an addition polymer obtained by copolymerizing a cyclic olefin monomer and an acyclic olefin monomer is shown in formula (III). The copolymer of formula (III) is described as a polymer in which the cyclic and ethylene skeletons are randomly arranged. The cyclic skeleton of formula (I1I) is the 2,3-norbornylene skeleton.

[0036] [ka]

[0037] In equation (III), m and n are integers greater than or equal to 1, and R 1 , R 2 and R 3 represents a hydrogen atom or an alkyl group. m and n may be the same or different from each other. 1 , R 2 and R 3 They may be the same or they may be different. 1 and R 2 These elements may be joined to each other to form a ring.

[0038] Here, R 1 , R 2 , R 3 An example of a polymer in which both atoms are hydrogen atoms is "TOPAS (registered trademark)" manufactured by Polyplastics Co., Ltd. Also, R 1 and R 2 is an alkyl group, R 3 An example of a polymer in which hydrogen atoms are present is "Apel®," manufactured by Mitsui Chemicals, Inc.

[0039] These cyclic olefin resins have excellent water vapor barrier properties and are readily available. As described above, in the laminate of this embodiment, these cyclic olefin resins can be used as the main component of the first resin layer. The first resin layer preferably contains at least one type of cyclic olefin resin, or if there are two or more types, in a total proportion of, for example, 50% by weight or more and less than 100% by weight.

[0040] The first resin layer may contain one type of cyclic olefin resin, or two or more types of cyclic olefin resins. Here, the two or more types of cyclic olefin resins may be two or more cyclic olefin resins corresponding to any one of formulas (I) to (III), or one or more cyclic olefin resins for two or more formulas (I) to (III), or it may also contain cyclic olefin resins that do not correspond to formulas (I) to (III). Furthermore, the first resin layer may be the innermost layer (sealant layer) in the laminate.

[0041] Next, we will give examples of commercially available cyclic olefin resins. Some of these will overlap with the above, but for example, we can give ZEONEX (registered trademark) (manufactured by Nippon Zeon Co., Ltd., a hydrogenated polymer of a ring-opening metathesis polymer of norbornene monomers), TOPAS (registered trademark) (manufactured by Polyplastics Co., Ltd., a copolymer of norbornene and ethylene), ZEONOR (registered trademark) (manufactured by Nippon Zeon Co., Ltd., a copolymer based on ring-opening polymerization of dicyclopentadiene and tetracyclopentadodecene), Apel (registered trademark) (manufactured by Mitsui Chemicals, Inc., a copolymer of ethylene and tetracyclododecene), and Arton (registered trademark) (manufactured by JSR Corporation, a cyclic olefin resin containing polar groups using dicyclopentadiene and methacrylate esters as raw materials).

[0042] The first resin layer contains an elastomer in addition to the cyclic olefin resin. Examples of elastomers used in the first resin layer include rubber and thermoplastic elastomers. The inclusion of an elastomer in the first resin layer reduces the risk of breakage when external forces such as drops are applied. The proportion of elastomer in the first resin layer is preferably 10% by mass or less, and is desirable to be between 0.05% and 10% by mass. If the composition ratio of the cyclic olefin resin is low, the risk of breakage when external forces such as drops are applied is reduced, but trace components and drug components with high affinity to plastics may be adsorbed, potentially resulting in insufficient storage stability of the contained drug components. The proportion of cyclic olefin resin in the first resin layer is preferably 90% by mass or more, and is desirable to be between 90% and 99.95% by mass. The first resin layer does not necessarily have to contain acyclic polyolefin resins such as PE and PP, and the polymer components contained in the first resin layer may consist only of cyclic olefin resin and elastomer.

[0043] The elastomer used in the first resin layer is preferably a styrene-based elastomer. Examples of styrene-based elastomers used in the first resin layer include copolymers of styrene and aliphatic olefins. Blocks containing styrene constitute hard blocks, and blocks containing aliphatic olefins constitute soft blocks. Specific examples of styrene-based elastomers include one or more of the following: styrene-ethylene copolymer, styrene-butadiene copolymer, styrene-isoprene copolymer, styrene-ethylene-propylene-styrene block copolymer (SEPS), styrene-ethylene-butylene-styrene block copolymer (SEBS), styrene-butadiene-styrene block copolymer (SBS), styrene-isoprene-styrene block copolymer (SIS), styrene-isoprene-butadiene-styrene block copolymer (SIBS), styrene-ethylene-butylene-olefin crystalline block copolymer (SEBC), hydrogenated styrene-butadiene rubber (HSBR), etc.

[0044] The elastomer used in the first resin layer may be an olefin-based thermoplastic elastomer. Examples of olefin-based thermoplastic elastomers (sometimes referred to as "TPO") include copolymers having an olefin-based polymer (resin component) such as polyethylene (PE) or polypropylene (PP) as a molecularly restricting component (hard segment), and an olefin-based rubber component such as ethylene-propylene-diene ternary copolymer (EPDM) or ethylene-propylene rubber (EPR) as a flexible component exhibiting rubber elasticity (soft segment).

[0045] The materials constituting each layer of the laminate in this embodiment, i.e., the first resin layer, adhesive resin layer, second resin layer, etc., may contain various additives such as antioxidants, ultraviolet absorbers, antistatic agents, lubricants, and antiblocking agents, to the extent that safety and hygiene are not compromised, in order to improve the appearance of the container, stabilize its quality, and impart other necessary performance.

[0046] The method for forming each layer (film) used in the laminate (sheet) of this embodiment is not particularly limited, but examples include T-die molding and inflation molding. After T-die molding, the film, sheet, etc. may be rapidly cooled with a cooling roll. When continuously forming long lengths of film, sheet, etc., it is preferable to wind up the long molded body of film, sheet, etc. after molding, as this provides excellent productivity.

[0047] The laminate is exemplified by a structure in which a substrate, a sealant layer, and other layers are laminated together as needed. That is, there may be an adhesive layer or an anchoring agent layer between each layer, or the layers may be laminated so that they are in direct contact with each other. Other layers may include a reinforcing layer, a gas barrier layer, a light-shielding layer, a printing layer, etc., and one or more layers can be selected as appropriate. The sealant layer is a layer used for heat sealing and is placed as the innermost layer in contact with the contents in the packaging material. Heat sealing is a method of bonding by melting the sealant layer, but there are no particular restrictions on the sealing method, and examples include hot plate sealing, ultrasonic sealing, high-frequency sealing, and impulse sealing. The substrate may be the outermost surface of the laminate opposite to the sealant layer, or it may be laminated inside the outermost surface of the other layer.

[0048] The manufacturing method for the laminate of this embodiment is not particularly limited, and each layer constituting the laminate may be appropriately laminated by extrusion lamination, dry lamination, co-extrusion, or a combination of two or more of these methods. The thickness of the sealant layer is not particularly limited, as it depends on the application of the packaging material, but is usually about 5 to 150 μm, preferably 15 to 100 μm. The thickness of the adhesive resin layer is not particularly limited, but is, for example, 10 to 100 μm. The total thickness of the laminate is preferably 150 to 300 μm, and is particularly common at 190 to 250 μm, considering the balance between the required performance (transparency, flexibility) and cost (productivity, material cost).

[0049] According to the laminate of this embodiment, the interlayer strength between the first resin layer and the second resin layer, or the interlayer strength between the first resin layer, the adhesive resin layer, and the second resin layer can be significantly improved. Furthermore, in the laminate of this embodiment, when the second resin layer contains a polypropylene resin, it has higher heat resistance compared to a laminate composed of a polyethylene resin layer and a cyclic olefin resin layer. Therefore, it has heat resistance even to high temperatures exceeding 120°C and can be sterilized by high-pressure steam. Furthermore, compared to a laminate composed of a polypropylene resin layer and a cyclic olefin resin layer, the laminate of this embodiment has high heat resistance, suppresses the decrease in peel strength even when subjected to high-pressure steam sterilization, and can improve the impact resistance of the container.

[0050] The container of this embodiment can be formed using the laminate of this embodiment. Examples of containers include packaging bags (pouches) and tube packaging. When a spout is provided in the packaging bag, the spout can be suitably used as long as it can be joined to the sealant layer of the laminate constituting the packaging bag to ensure airtightness. Preferably, it is desirable to use a spout made of a heat-sealable resin and the sealant layer of the laminate, and to join the spout and the laminate by heat sealing. When heat sealing the laminate and the spout, the spout may be inserted between stacked laminates with the sealant layer on the inside and then heat-sealed, or a flange portion or a boat-shaped fusion base may be provided at one end of the spout, and this flange portion or fusion base may be heat-sealed to the periphery of a hole in the laminate or the inner surface of the opening of the packaging bag.

[0051] The container of this embodiment can be suitably used as a container for storing pharmaceuticals, food and beverages, cosmetics, etc. The pharmaceuticals may be substances with high adsorption or permeability to general resins, such as nitroglycerin, albumin, vitamins, trace elements, and radical scavengers. Preferred pharmaceuticals include aqueous solutions containing edaravone, a pyrazolone derivative, or a pharmaceutically acceptable salt thereof. The pyrazolone derivative may have one or more substituents such as alkyl groups, aromatic groups, or halogen atoms on the carbon or nitrogen atom of pyrazolone. The pyrazolone derivative may also form salts with organic acids, inorganic acids, etc.

[0052] The packaging bag can be any type of small packaging bag (pouch) such as three-sided bags, four-sided bags, gusseted bags, self-standing bags, etc., as well as larger bags such as inner bags for bag-in-boxes or inner bags for drums, etc., without any particular limitations. As for the container, a plastic container 50 having a storage section 51 for storing contents and an opening 52 for discharging contents is preferred, as shown in Figure 5. Examples include infusion bags or blow-molded containers. The storage section 51 can be constructed by arranging the laminated bodies of this embodiment so that they face each other and overlap.

[0053] Although the present invention has been described above based on preferred embodiments, the present invention is not limited to the embodiments described above, and various modifications are possible without departing from the spirit of the invention. [Examples]

[0054] The present invention will be specifically described below with reference to examples.

[0055] (Method of manufacturing a laminate) Using a T-die multilayer film manufacturing machine, laminates were produced by co-extrusion so that the thicknesses of the surface layer, intermediate layer, and innermost layer were 180 μm, 50 μm, and 30 μm, respectively. The surface layer (second resin layer) is made of polypropylene-based thermoplastic elastomer "Zelus®" (manufactured by Mitsubishi Chemical Corporation, density 0.89 g / cm³). 3 A melting peak temperature of 162°C was used.

[0056] The intermediate layer (adhesive resin layer) used pellets made by dry-blending three components—LLDPE, polypropylene (PP), and a compatibilizer—in a predetermined ratio. As the LLDPE, gas-phase metallocene polyethylene "Harmolex®" (manufactured by Nippon Polyethylene Co., Ltd., density 0.908 g / cm³) was used. 3 (with a melting peak temperature of 120°C) was used as the PP. As the PP, metallocene polypropylene "Wintec®" (manufactured by Nippon Polypropylene Co., Ltd., density 0.90 g / cm³) was used. 3A compound with a melting peak temperature of 125°C was used. As a compatibilizer, SEBS "ToughTec®" (manufactured by Asahi Kasei Corporation) with a styrene content of 12% by weight was used. The adhesive resin layer was formulated so that the mass ratio of LLDPE:PP:SEBS was 55:35:10.

[0057] The innermost layer (first resin layer) is made of cyclic olefin resin "TOPAS (registered trademark)" (density 1.02 g / cm³). 3 Using a glass transition temperature of 138°C, various elastomer components shown in Table 1 were blended in predetermined ratios.

[0058] [Table 1]

[0059] As for the four types of SEBS (styrene-ethylene-butylene-styrene block copolymer), "ToughTec®" (manufactured by Asahi Kasei Corporation, styrene content 12-43% by weight) was used. For SEPS (styrene-ethylene-propylene-styrene block copolymer), "Septon®" (manufactured by Kuraray Co., Ltd., styrene content 18% by weight) was used. For SEBC (styrene-ethylene-butylene-olefin crystal block copolymer), HSBR (hydrogenated styrene-butadiene rubber), and CEBC (olefin crystal-ethylene-butylene-olefin crystal block copolymer), "Dynalon®" (manufactured by JSR Corporation) was used, respectively.

[0060] (Experiment 1) Using the above-described method for manufacturing laminates, laminates having the innermost layer with the composition shown in Table 2 were manufactured. Using the manufactured laminates, the innermost layers were stacked together, and the outer circumference of the laminates was heat-sealed except for the filling opening to create an infusion bag-shaped pouch container with outer dimensions of 172 mm x 115 mm. The outer circumference was trimmed to a seal width of 5 mm, 105 mL of water was filled into the pouch, and the filling opening was heat-sealed to seal the pouch.

[0061] [Table 2]

[0062] The sealed pouches were autoclaved using a steam sterilizer at 121°C for 20 minutes. After autoclaving, the pouch temperature was rapidly reduced with cooling water, and then the heat seal strength, transparency, and impact resistance of the pouches were measured using a drop test. In addition, the stability of long-term storage was evaluated using samples filled with a model formulation described later, instead of water.

[0063] The heat seal strength was measured using the following procedure. First, a test specimen with a width of 15.0 mm and an unfolded length of 100 mm or more was taken perpendicular to the heat seal portion of the pouch. The sheet portions on both sides of the heat seal portion were opened 180° with the heat seal portion in the center, and each sheet portion on both sides was attached to the grips of a tensile testing machine with a gripping distance of 50 mm. Next, the tensile load was measured at a constant tensile speed of 300 mm / min until the heat seal portion broke, and the maximum load (N / 15 mm) until breakage was defined as the heat seal strength. For evaluating heat seal strength, we considered JIS Z0238 (Test methods for heat-sealable flexible packaging bags and semi-rigid containers) and evaluated values ​​of 23N / 15mm or higher as "good" and values ​​below that as "poor," in cases where strong heat seal strength is required, such as for retort sterilization bags.

[0064] Transparency was evaluated using the following procedure. Following the transparency test method 1 described in section 7.02 of the Japanese Pharmacopoeia, 17th edition (JP17), five 0.9 cm x 4 cm samples of the laminate were cut from the pouch portion and immersed in a UV absorption spectrum measurement cell filled with water. A cell filled only with water was used as a control, and the light transmittance at a wavelength of 450 nm was measured and recorded using a UV-Vis spectrophotometer. For the evaluation of transparency, considering that the specifications for plastic aqueous injection containers in the same Pharmacopoeia require a light transmittance of 55% or more, samples with an average light transmittance of 65% or more of the five samples were classified as "good," and those below that were classified as "poor."

[0065] The impact resistance of the bags was evaluated using the following procedure: Bags filled with water and sterilized were cooled in a 5°C refrigerator for at least 12 hours. While maintaining the cold temperature, each bag was subjected to 50 consecutive free drops from a height of 2m with the pouch facing downwards. If a bag was found to have ruptured, the test was stopped at that point, the number of drops at which the bag ruptured was recorded, and a score was assigned using the following formula.

[0066] (Drop test score) = 0.2 × (Number of drops when bag breaks - 1) However, for samples that did not show bag rupture after 50 drops, the number of drops before bag rupture (number of drops at the time of rupture - 1) was considered to be 50, and the drop test score was set to 10 points.

[0067] Tests were conducted using 10 bags per level, and the sum of the drop test scores from these 10 samples was used as the total drop test score. The total drop test scores for each level were compared to determine the relative performance. Products with a total drop test score of 80 points or higher were classified as "good," while those with a score below 80 points were classified as "poor."

[0068] The storage stability of the model formulation was evaluated by the following procedure. A pouch container in the shape of an infusion bag was formed from a laminate film manufactured according to the above-described method for producing the laminate. The container was filled with 105 mL of an edaravone-containing aqueous solution prepared to pH 3.85 with the composition shown in Table 3 below (composition of the edaravone model formulation), and then sealed. The container holding the model formulation was sterilized in an autoclaver at 121°C for 20 minutes. After cooling, the outside of the container was dried to create a bag formulation. The bag formulation, after this sterilization process, was placed in a dry laminate outer bag consisting of three layers: biaxially oriented polyester, aluminum foil, and linear low-density polyethylene, along with an oxygen absorber ("Ageless®" manufactured by Mitsubishi Gas Chemical Company, Inc.). The opening of the outer bag was then heat-sealed to complete the preparation of the bag sample containing the model formulation.

[0069] [Table 3]

[0070] The prepared model formulation bag samples were stored for 15 days in an environment with a temperature of 70°C and a relative humidity of 90%. The remaining edaravone percentage after storage was measured by liquid chromatography under the following conditions.

[0071] Detector: UV absorbance spectrophotometer (measurement wavelength: 243 nm) Column: A liquid chromatography column consisting of a stainless steel tube with an inner diameter of 4.6 mm and a length of 150 mm, packed with octadecylsilylated silica gel with a particle size of 5 μm. Column temperature: Constant temperature around 40°C. Mobile phase: methanol:water:acetic acid = 49.8:49.8:0.4 Flow rate: 1.0mL / min. Injection volume: 20μL

[0072] A precise 3 mL sample, corresponding to approximately 0.9 mg of edaravone, was taken from the test sample bag. A mobile phase was added to make a total volume of 10 mL. From this solution, 1 mL was accurately measured, and a mobile phase was added to make a total volume of 100 mL, which was used as the measurement solution. 20 μL of the measurement solution was tested by liquid chromatography under the above-described test conditions. The peak area of ​​each component was measured using automated integration. The residual rate of edaravone was determined for each test condition using the following formula. The initial edaravone peak area was measured using the same procedure as for the edaravone peak area after the completion of the storage test, starting from a precise 3 mL sample taken from the model formulation immediately after preparation before filling the test sample bag.

[0073] Edaravone retention rate (%) = (Edaravone peak area after storage test completion) / (Initial edaravone peak area) × 100 (%)

[0074] A sample was judged "good" if the edaravone retention rate relative to the initial value was in the range of 95% to 105%, and any deviation from this range was judged "poor."

[0075] The results of the series of evaluations are shown in Table 4. It was shown that the inclusion of elastomer components and amorphous polymer in the innermost layer (first resin layer) did not result in a decrease in heat seal strength, and impact resistance was significantly improved. However, it was clear that when the amount of elastomer component added was excessive, the transparency after sterilization and the storage stability of the model formulation approached an insufficient level, suggesting that a composition containing a certain proportion of elastomer components is appropriate.

[0076] [Table 4]

[0077] (Experiment 2) To verify whether a similar performance improvement effect would occur when elastomer components other than those used in Experiment 1 were added, laminates with the innermost layer containing the elastomer addition amounts shown in Table 5 were manufactured. Other procedures (pouch preparation, sterilization, measurement of heat seal strength and transparency, drop test, and storage stability of the model formulation) were the same as in Experiment 1.

[0078] [Table 5]

[0079] Table 6 shows the evaluation results from Experiment 2, along with the evaluation results from Experiments 1, numbers 0 and 1-1. Significant improvement in impact resistance was achieved regardless of the type of styrene-based elastomer. As shown in number 2-7, while the modification effect was lower with the addition of olefin-based elastomer components that did not contain polystyrene blocks compared to the addition of styrene-based elastomers, it was confirmed that the required performance for a chemical solution bag container was met.

[0080] [Table 6]

[0081] (Experiment 3) To verify whether a performance improvement effect occurs when polyolefin resins, as presented in Patent Documents 2 and 3, are added instead of the elastomers added to the innermost layer in Experiments 1 and 2, and to verify the amount of polyolefin resin required to achieve this performance improvement, laminates were manufactured using the innermost layer compositions with the added resins and amounts shown in Table 7. Other procedures (pouch preparation, sterilization, measurement of heat seal strength and transparency, drop test, and storage stability of the model formulation) were the same as in Experiments 1 and 2. Among the polyolefin species in Table 7, the same brands of LLDPE and random PP were used as the resins constituting the intermediate layer (adhesive resin layer).

[0082] [Table 7]

[0083] Table 8 shows the evaluation results from Experiment 3, along with the evaluation results from Experiments 1, numbers 0 and 1-1. With polyethylene (LLDPE), the required performance could not be obtained at the same level of addition as the elastomer, and a large amount, as shown in numbers 3-4, tended to be necessary to improve impact resistance. With polypropylene (random PP), impact resistance was insufficient even at up to 20% addition. On the other hand, increasing the amount of polypropylene reduced the edaravone retention rate in the model formulation, suggesting that it could not meet the performance requirements for a pharmaceutical storage container. Furthermore, with polypropylene, it was observed that increasing its proportion gradually decreased the heat seal strength after sterilization. When polyolefin resin was added to the innermost layer, none of the additions up to 20% fell below the heat seal strength standard, but none of the laminates in Experiment 3 met all the required performance criteria, including other performance requirements.

[0084] [Table 8] [Industrial applicability]

[0085] According to the present invention, it is possible to provide laminates and plastic containers that have excellent interlayer adhesion strength and heat seal strength, are less prone to loss of transparency even during high-temperature sterilization processes, are less susceptible to damage from impacts such as dropping, have appropriate strength as storage containers, and have excellent storage stability for the contents such as pharmaceuticals. [Explanation of Symbols]

[0086] 10, 20, 30, 40… Laminate 11...First resin layer 12…Second resin layer 13...Adhesive resin layer

Claims

1. A first resin layer comprising an amorphous cyclic olefin resin composed of olefin monomer components having a cyclic hydrocarbon skeleton, A laminate comprising at least two layers, including a second resin layer mainly composed of polyethylene, polypropylene, or ethylene-α-olefin copolymer, The first resin layer contains thermoplastic elastomer in a proportion of 10% by mass or less and is the innermost layer that comes into contact with the contents. An adhesive layer or an anchoring agent layer may be interposed between each layer. A laminate characterized in that, if the second resin layer contains a polypropylene resin, an adhesive resin layer is provided between the first resin layer and the second resin layer.

2. The laminate according to claim 1, characterized in that the thermoplastic elastomer is selected from one or more types of olefin-based thermoplastic elastomers and styrene-based thermoplastic elastomers.

3. The laminate according to claim 1 or 2, characterized in that the thermoplastic elastomer is contained in the first resin layer in a proportion of 0.05 to 10% by mass.

4. A plastic container characterized by comprising a storage section for storing contents and an opening for discharging the contents, wherein the laminates described in any one of claims 1 to 3 are arranged to overlap each other.

5. The plastic container according to claim 4, characterized in that the contents are a pharmaceutical product.

6. The plastic container according to claim 5, characterized in that the pharmaceutical is an aqueous solution containing edaravone, a pyrazolone derivative, or a pharmaceutically acceptable salt thereof.

7. The plastic container according to any one of claims 4 to 6, wherein the plastic container is an infusion bag or a blow-molded container.

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