Multilayer structures for containers, containers, medical containers, and medical containers containing pharmaceuticals

Abstract

The present invention provides a container multilayered body (1, 2) that is used to form a container, the container multilayered body (1, 2) having: an innermost layer (3) consisting of a cyclic polyolefin; an intermediate layer (4) that is formed so as to be adjacent to the innermost layer (3) and that contains, as a principal component, a linear low-density polyethylene manufactured by using a single-site catalyst; and an outer layer (5) consisting of one of a random polypropylene manufactured by using the single-site catalyst and a polypropylene containing an elastomer.

Description

[Technical Field]

[0001] The present invention relates to multilayer containers, containers, medical containers, and pharmaceutical medical containers. This application claims priority under Japanese Patent Application No. 2021-026286, filed in Japan on February 22, 2021, the contents of which are incorporated herein by reference. [Background technology]

[0002] For example, resin containers for liquid pharmaceuticals used in the medical field include ampoules and syringes, as well as plastic bottles, liquid sticks made of plastic film, and infusion bags. Infusion bags are particularly widely used for infusions and injectable drugs administered directly intravenously by injection or drip. Various materials are used for the resin in these infusion bags. When the contents of the drug solution contain specific drugs, such as fat-soluble vitamins, it is known that a cyclic polyolefin layer made of thermoplastic saturated norbornene polymer is used as the wetted layer (innermost layer) to prevent drug adsorption to the resin. Patent Document 1 discloses a multilayer body for use in containers, having an outermost layer made of high-density polyethylene, an intermediate layer made of linear low-density polyethylene, and an innermost layer made of cyclic polyethylene. [Prior art documents] [Patent Documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 2008-18063 [Overview of the project] [Problems that the invention aims to solve]

[0004] Generally, liquid pharmaceuticals, especially intravenous solutions and injectable drugs, undergo sterilization such as high-pressure steam sterilization after the contents are filled into the container. However, if there is a wide temperature distribution within the sterilization chamber, the chamber temperature must be set high to ensure that sterilization conditions are met even in the relatively lower temperature areas and to guarantee sterilization of all products. In such cases, conventional containers like those described in Patent Document 1 may have insufficient heat resistance for the aforementioned high-temperature sterilization treatment. As a result, problems may occur such as a decrease in interlayer strength and delamination in high-temperature areas within the chamber, containers sticking to the sterilization tray resulting in poor appearance and the hassle of removing them, or whitening occurring on the surface of the container when it is removed from the sterilization tray, impairing transparency. In addition, shrinkage due to heat during sterilization may cause wrinkles and deformation in the container, potentially worsening its appearance and impairing transparency.

[0005] The present invention aims to provide a multilayer container with excellent heat resistance and the ability to suppress problems during sterilization, as well as containers, medical containers, and drug-containing medical containers using the said multilayer container. [Means for solving the problem]

[0006] The present invention has the following aspects. A first aspect of the present invention is a multilayer container used for forming a container, comprising: an innermost layer made of a cyclic polyolefin; an intermediate layer formed adjacent to the innermost layer and mainly composed of linear low-density polyethylene produced using a single-site catalyst; and an outer layer made of either random polypropylene or polypropylene containing an elastomer, both produced using a single-site catalyst. A second aspect of the present invention is a multilayer container according to the first aspect, wherein the outermost layer is made of polypropylene and is located outside the outer layer. A third aspect of the present invention is a multilayer container according to the first or second aspect, wherein the cyclic polyolefin is a hydrogenated product of a ring-opening polymer of a cyclic olefin monomer. A fourth aspect of the present invention is a multilayer container according to any one of the first to third aspects, wherein the elastomer is an olefin-based elastomer and / or a styrene-based elastomer. A fifth aspect of the present invention is a container having a storage section for storing contents, wherein at least the storage section is made of a multilayer container described in any one of the first to fourth aspects. A sixth aspect of the present invention is a medical container having a storage section for storing a drug solution, wherein at least the storage section is made of a multilayer container described in any one of the first to fourth aspects. A seventh aspect of the present invention is a drug-containing medical container in which a drug is contained in the medical container described in the sixth aspect above. In this application, the term "container" includes not only rigid containers but also packaging made of film or the like. [Effects of the Invention]

[0007] According to the present invention, it is possible to provide a multilayer container with excellent heat resistance and the ability to suppress problems during sterilization, and a container using the said multilayer container, particularly a medical container and a medical container for pharmaceuticals. The following description will mainly focus on the multilayer container for medical use. [Brief explanation of the drawing]

[0008] [Figure 1] This is a cross-sectional view showing a multilayer container according to an embodiment. [Figure 2] This is a cross-sectional view showing a multilayer container for another embodiment. [Figure 3] This figure shows a medical container according to an embodiment, where Figure 3(A) is a plan view and Figure 3(B) is a cross-sectional view taken along line I-I' in Figure 3(A). [Figure 4] Figure 4(A) shows a plan view of a medical container in another embodiment, and Figure 4(B) shows a plan view of another aspect of the port portion. [Figure 5] Figure 4 shows a film molded product used in the manufacture of medical containers, with Figure 5(A) being a front view and Figure 5(B) being a side view. [Figure 6] It is a plan view showing a medical container of another embodiment. [Figure 7] It is a plan view showing a multi-chamber medical container which is an example of a medical container of another embodiment.

Embodiments for Carrying out the Invention

[0009] [Multi-layer body for container] The multi-layer body for a container of the present invention (hereinafter, also simply referred to as "multi-layer body") is a multi-layer body used for forming a container. The multi-layer body of the present invention is particularly preferably used for forming a storage portion for storing a chemical solution in a medical container. The multi-layer body of the present invention has at least an innermost layer, an intermediate layer formed adjacent to the innermost layer, and an outer layer.

[0010] Hereinafter, an example of the multi-layer body of the present invention will be shown and described. Note that the dimensions and the like of the figures illustrated in the following description are merely examples. The present invention is not necessarily limited thereto, and can be appropriately modified and implemented without changing the gist thereof.

[0011] Examples of the multi-layer body of the present invention include, for example, the multi-layer body 1 for a container (hereinafter, also referred to as "multi-layer body 1") shown in FIG. 1 and the multi-layer body 2 for a container (hereinafter, also referred to as "multi-layer body 2") shown in FIG. 2. As shown in FIG. 1, the multi-layer body 1 is a multi-layer body having a three-layer structure including an innermost layer 3, an intermediate layer 4, and an outer layer 5. In the multi-layer body 1, the innermost layer 3, the intermediate layer 4, and the outer layer 5 are laminated in this order. As shown in FIG. 2, the multi-layer body 2 is a multi-layer body having a four-layer structure including an innermost layer 3, an intermediate layer 4, an outer layer 5, and an outermost layer 6. In the multi-layer body 2, the innermost layer 3, the intermediate layer 4, the outer layer 5, and the outermost layer 6 are laminated in this order.

[0012] (Innermost layer) The innermost layer 6 is the innermost layer (wetted layer) when forming the container and is in contact with the contents. It is made of cyclic polyolefin. Because cyclic polyolefin has low adsorption and absorption of drugs, it can suppress the reduction in the potency of drugs if the contents are pharmaceuticals. Furthermore, because cyclic polyolefin has excellent heat resistance and transparency, it is suitable for medical containers where high-temperature sterilization is necessary and it is desirable to be able to visually inspect the contents from the outside.

[0013] Examples of cyclic polyolefins include ring-opened polymers of cyclic olefin monomers, hydrogenated ring-opened polymers of cyclic olefin monomers, addition polymers of cyclic olefin monomers, and addition copolymers of cyclic olefin monomers with other monomers copolymerizable with cyclic olefin monomers. Among the cyclic polyolefins, hydrogenated ring-opened polymers of cyclic olefin monomers are preferred due to their excellent heat resistance. The cyclic polyolefin forming the innermost layer may be one type or two or more types.

[0014] The cyclic olefin monomers are not particularly limited, and examples include norbornene monomers and monocyclic cyclic olefin monomers. Norbornene monomers are monomers that have units derived from a norbornene structure in their monomer structure, and examples include bicyclo[2.2.1]hepto-2-ene, tricyclo[4.3.0.12,5]deca-3,7-diene, 7,8-benzotricyclo[4.3.0.12,5]deca-3-ene, and tetracyclo[4.4.0.12,5.17,10]dodeca-3-ene. Examples of monocyclic cyclic olefin monomers include cyclohexene, cycloheptene, and cyclooctene. The cyclic olefin monomers may be used individually or in combination of two or more.

[0015] Examples of other monomers that can be addition copolymerized with cyclic olefin monomers include α-olefins with 2 to 20 carbon atoms, such as ethylene, propylene, 1-butene, and 1-hexene. These other monomers may be used individually or in combination of two or more.

[0016] Ring-opening polymers of cyclic olefin monomers are obtained by polymerizing the cyclic olefin monomers by metathesis in the presence of a ring-opening polymerization catalyst. Hydrogenated ring-opening polymers of cyclic olefin monomers are obtained by hydrogenating the ring-opening polymers with known hydrogenation catalysts. Addition polymers and addition copolymers of cyclic olefin monomers can be obtained by polymerization using catalysts consisting of known titanium, zirconium compounds and organoaluminum compounds.

[0017] Examples of commercially available addition polymers and addition copolymers of cyclic olefin monomers include Apel® manufactured by Mitsui Chemicals, Inc. and TOPAS® manufactured by Polyplastics Co., Ltd. Examples of hydrogenated ring-opening polymers of cyclic olefin monomers include Zeonor® and Zeonex® manufactured by Nippon Zeon Corporation.

[0018] The glass transition temperature (hereinafter also referred to as "Tg") of cyclic polyolefins is preferably 70 to 180°C, and more preferably 100 to 140°C. If Tg is above the lower limit of the above range, the container has excellent heat resistance. If Tg is below the upper limit of the above range, the multilayer body has excellent moldability and heat sealability. Note that Tg is a value measured by differential scanning calorimeter (DSC) in accordance with JIS K 7121. As the cyclic polyolefin, two or more types with different Tg values ​​may be mixed. This is because mixing allows for setting an appropriate molding temperature when co-extruding multilayer 1 and 2, thereby improving molding stability. For example, if a cyclic polyolefin with a Tg of 100°C and a cyclic polyolefin with a Tg of 136°C are mixed in a 1:1 ratio, the Tg will be in the range of 113 to 118°C, making extrusion molding possible at a molding temperature of around 250°C. At this temperature, molding stability is maintained without deviating significantly from the optimal molding temperatures of the adjacent intermediate layer 4, outer layer 5, and outermost layer 6. If the Tg of the mixture is lowered too much, the inner cyclic polyolefin layer may become flexible during autoclaving, potentially causing the bag to rupture during sterilization. Therefore, it is preferable to set the Tg of the mixture considering both cyclic polyolefins with different Tg values. Furthermore, if the Tg of the inner cyclic polyolefin layer is higher than the Tg or melting point of the resin used in the outer layer 5 or outermost layer 6, a high heat seal temperature is set during the bag-making process to allow the cyclic polyolefin to melt or soften, enabling bag formation. This results in excessive heat being applied to the outer layer 5 or outermost layer 6, leading to a defective appearance of the container. Therefore, it is undesirable for the Tg of the inner cyclic polyolefin layer to be higher than the Tg or melting point of the resin used in the outer layer 5 or outermost layer 6.

[0019] The innermost layer 3 may contain various additives commonly used in the field of resins, such as antistatic agents, antioxidants, lubricants, antifogging agents, ultraviolet absorbers, and neutralizing agents, as long as they do not impair the effects of the present invention.

[0020] (Middle class) The intermediate layer 4 is formed adjacent to the innermost layer 3 and is a layer mainly composed of linear low-density polyethylene (hereinafter also referred to as "single-site LLDPE") manufactured using a single-site catalyst. However, "mainly composed of single-site LLDPE" means that the content of single-site LLDPE in the intermediate layer 4 is 50% by mass or more of the total mass of the intermediate layer 4.

[0021] Single-site LLDPE exhibits excellent adhesion to cyclic polyolefins, and its adhesive properties do not deteriorate significantly even after autoclaving. Therefore, by using the intermediate layer 4, the innermost layer 3, which is made of cyclic polyolefin, can be stably bonded to the outer layer. The single-site catalyst is not particularly limited; for example, metallocene catalysts can be cited.

[0022] The density of single-site LLDPE is preferably 0.860 g / cm³. 3 More than 0.940g / cm 3 Less than 0.890 to 0.924 g / cm³ 3If the density of the single-site LLDPE is above the lower limit, it exhibits excellent heat resistance and makes it easier to suppress the decrease in peel strength between the intermediate layer 4 and the innermost layer 3. If the density of the single-site LLDPE is below the upper limit, it makes it easier to suppress the decrease in transparency and impact resistance of the container. For single-site LLDPE systems, two or more types with different densities may be used in combination.

[0023] The intermediate layer 4 may contain other resins besides single-site LLDPE, as long as they do not impede adhesion to the innermost layer 3. Examples of other resins include polyethylene and cyclic polyolefins, with high-density polyethylene (hereinafter also referred to as "HDPE") being preferred.

[0024] The content of single-site LLDPE in the intermediate layer 4 is 50% by mass or more relative to the total mass of the intermediate layer 4, preferably 65% ​​by mass or more, and more preferably 80% by mass or more, from the standpoint of excellent flexibility. In terms of improved heat resistance, further suppression of the decrease in adhesion of the intermediate layer 4 due to high-pressure steam sterilization, and reduced shrinkage of the intermediate layer 4, it is preferable that the intermediate layer 4 further contains HPDE with a higher density than single-site LLDPE in a range of 30% by mass or less, more preferably 25% by mass or less, relative to the total mass of the intermediate layer 4. This has the effect of improving molding stability and reducing the likelihood of thermal deformation and wrinkling when used in containers.

[0025] The intermediate layer 4 may contain various additives commonly used in the field of resins, such as antistatic agents, antioxidants, lubricants, antifogging agents, ultraviolet absorbers, and neutralizing agents, as long as they do not impair the effects of the present invention.

[0026] (outer layer) The outer layer 5 is formed to be the outermost layer in the container if the outermost layer 6 described later is not provided, and is formed adjacent to the inside of the outermost layer if the outermost layer is provided. The outer layer 5 consists of either random polypropylene manufactured using a single-site catalyst (hereinafter also referred to as "single-site random PP") or polypropylene containing an elastomer (hereinafter also referred to as "flexible PP").

[0027] Single-site random PP is obtained by randomly copolymerizing polypropylene and ethylene using a single-site catalyst, and has constituent units based on polypropylene (hereinafter also referred to as "polypropylene units") and constituent units based on ethylene (hereinafter also referred to as "ethylene units"). Because single-site random PP is a polymer with a high molecular weight and a narrow molecular weight distribution, it has excellent adhesion to the intermediate layer 4.

[0028] The ethylene unit content in single-site random PP is preferably 0.3 to 7% by mass, and more preferably 1.7 to 5.5% by mass, relative to the total constituent units. If the ethylene unit content is above the lower limit of the above range, it has sufficient flexibility and excellent thermal adhesion between the outer layer 5 and the intermediate layer 4. If the ethylene unit content is below the upper limit of the above range, it has excellent heat resistance.

[0029] Because the flexible PP contains an elastomer, it exhibits excellent thermal adhesion to the intermediate layer 4. Examples of elastomers include olefin-based elastomers, styrene-based elastomers, and polybutadiene-based elastomers. Among these, olefin-based elastomers, styrene-based elastomers, and mixtures of olefin-based and styrene-based elastomers are preferred as elastomers that have relatively high compatibility with the matrix PP and also adhere to LLDPE. More specifically, ethylene-propylene copolymers, ethylene-butene copolymers, styrene-butadiene copolymers, hydrogenated styrene-butadiene copolymers, etc., are preferred. The elastomer contained in the flexible PP may be one type or two or more types.

[0030] The elastomer content in the flexible PP is preferably 20 to 60% by mass, and more preferably 20 to 40% by mass, relative to the total mass of the flexible PP. If the elastomer content is above the lower limit of the above range, it exhibits excellent thermal adhesion to the intermediate layer 4. If the elastomer content is below the upper limit of the above range, it exhibits excellent heat resistance.

[0031] The outer layer 5 may contain various additives commonly used in the field of resins, such as antistatic agents, antioxidants, lubricants, antifogging agents, ultraviolet absorbers, and neutralizing agents, as long as they do not impair the effects of the present invention.

[0032] (outermost layer) The outermost layer 6 is made of polypropylene (PP). The outermost layer 6 of PP may be PP produced using a single-site catalyst, or PP produced using a catalyst other than a single-site catalyst. For example, PP produced using a Ziegler-type catalyst. A propylene homopolymer is preferred as the outermost layer 6 of PP, but a copolymer containing ethylene units, etc., is also acceptable as long as it does not affect the heat resistance, for example, to an amount of 5% by mass or less. Furthermore, the outermost layer of PP may contain a styrene-based elastomer such as a styrene-butadiene copolymer or a hydrogenated styrene-butadiene copolymer.

[0033] The outermost layer may contain various additives commonly used in the field of resins, such as antistatic agents, antioxidants, lubricants, antifogging agents, ultraviolet absorbers, and neutralizing agents, as long as they do not impair the effects of the present invention.

[0034] (Thickness) The total thickness of the multilayer bodies 1 and 2 of the present invention is not particularly limited and can be, for example, 60 to 1000 μm. In terms of flexibility and strength of the multilayer bodies 1 and 2, 100 to 600 μm is preferred, and 100 to 400 μm is more preferred.

[0035] The thickness of each layer is not particularly limited. The thickness of the innermost layer 3 is preferably 5 to 100 μm. If the thickness of the innermost layer 3 is greater than or equal to the lower limit, the contents such as the contained drug will be less likely to be adsorbed. If the thickness of the innermost layer 3 is less than or equal to the upper limit, the flexibility of the multilayer bodies 1 and 2 is excellent, and the heat sealability when forming a container from the multilayer bodies 1 and 2 is excellent. The thickness of the intermediate layer 4 can be set so that the total thickness falls within the aforementioned range, depending on the thicknesses of the innermost layer 3, the outermost layer 5, and the outermost layer 6. For example, it can be set to 50 to 300 μm.

[0036] The thickness of the outer layer 5 is preferably 5 to 100 μm. If the thickness of the outer layer 5 is greater than or equal to the lower limit, it has excellent heat resistance. If the thickness of the outer layer 5 is less than or equal to the upper limit, the flexibility of the entire infusion bag is excellent. The thickness of the outermost layer 6 is preferably 5 to 100 μm. If the thickness of the outermost layer 6 is greater than or equal to the lower limit, it has excellent heat resistance. If the thickness of the outermost layer 6 is less than or equal to the upper limit, the flexibility of the entire infusion bag is excellent.

[0037] In a three-layer structure like multilayer 1, for example, a ratio of the thicknesses of the innermost layer 3, intermediate layer 4, and outer layer 5 of 10-20:210-220:20 provides a particularly good balance of flexibility, heat resistance, and other properties. In a four-layer structure like multilayer 2, for example, a particularly good balance of flexibility and heat resistance is achieved when the thickness ratio of the innermost layer 3, intermediate layer 4, outermost layer 5, and outermost layer 6 is 10-20:190-200:20:20.

[0038] Furthermore, the multilayer structure of the present invention is not limited to a three-layer structure like multilayer structure 1 or a four-layer structure like multilayer structure 2. For example, one or more other layers may be provided between the intermediate layer 4 and the outer layer 5, as long as the effects of the present invention are not impaired. Examples of other layers include a gas barrier resin layer such as ethylene-vinyl alcohol copolymer, an adhesive resin layer such as ethylene-vinyl acetate copolymer, an ultraviolet shielding layer such as an iron oxide-containing polyolefin resin, and an oxygen absorption layer made of a polyamide resin such as MXD nylon and a cobalt salt.

[0039] The method for manufacturing the multilayer body of the present invention is not particularly limited, and known multilayer extrusion methods can be employed. Specifically, examples include multilayer T-die extrusion, multilayer inflation, and multilayer blow molding.

[0040] (Effects and Benefits) As described above, the multilayer structures 1 and 2 of the present invention comprise an innermost layer 3 made of cyclic polyolefin, an intermediate layer 4 mainly composed of single-site LLDPE, and an outer layer 5 made of either single-site random PP or flexible PP. Single-site LLDPE exhibits excellent adhesion to cyclic polyolefins and also to single-site random PP and flexible PP. Therefore, in the multilayer structures 1 and 2 of the present invention, the interlayer strength of the innermost layer 3, the intermediate layer 4, and the outer layer 5 is high, and the decrease in interlayer strength during sterilization is suppressed. This is thought to be because LLDPE and PP produced using single-site catalysts have reduced low molecular weight components that inhibit interlayer adhesion.

[0041] Furthermore, by using single-site random PP or flexible PP for the outer layer 5, the melting point of the outer layer 5 can be increased while maintaining high interlayer strength, thereby improving heat resistance. As a result, even in sterilization processes with high oven temperatures, the container is less likely to stick to the sterilization tray, reducing the effort required to remove the container from the sterilization tray and preventing problems such as whitening of the container surface. In addition, the multilayer structures 1 and 2 are less likely to shrink due to heat during sterilization, reducing the likelihood of wrinkles, thus preventing deterioration of the container's appearance.

[0042] Furthermore, by providing an outermost layer 6 made of PP on the outside of the outer layer 5, the heat resistance of the outer surface of the multilayer body 2 can be further enhanced. This further suppresses the adhesion of the container to the sterilization tray during sterilization and the deterioration of the container's appearance due to wrinkle formation. In particular, when the outer layer 5 contains flexible PP, providing an outermost layer 6 made of PP can stably suppress the adhesion of the elastomer to the heat seal bar and the resulting stickiness during the heat-seal bag-making process. As a result, the multilayer body 2 is less likely to get caught on the heat seal bar during heat sealing, thus improving the bag-making speed.

[0043] [container] The container of the present invention is a container equipped with storage sections 11, 21, 31, and 41 for containing contents, wherein at least the storage sections 11, 21, 31, and 41 are made of the multilayer bodies 1 and 2 of the present invention. In the container, the multilayer bodies 1 and 2 are arranged such that the innermost layer 3 is inside the storage sections 11, 21, 31, and 41, and the outer layer 5 and outermost layer 6 are outside. The container of the present invention is not particularly limited to other embodiments, as long as at least the storage sections 11, 21, 31, and 41 are made of the multilayer bodies 1 and 2 of the present invention. For example, in addition to the storage sections 11, 21, 31, and 41, the container may be provided with rigid port sections 12, 22, and 32 that function as inlets and outlets for dispensing the contents. The inlets and outlets of the port sections 12, 22, and 32 are filling ports for filling the contents during manufacturing and dispensing outlets for dispensing the contents during use. These port sections 12, 22, and 32 are made using the same type of COP as the inner layer by injection molding or the like. Alternatively, tubes may be used as inlets and outlets. The tube is a multilayer tube, and at least the outer layer of the tube, which is heat-sealed to the inner layer of the bag, is made of PP containing a large amount of the same COP as the inner layer of the bag, or an elastomer that adheres to COP.

[0044] The container of the present invention is particularly useful as a medical container equipped with a compartment for containing a drug solution. By filling medical containers 10, 20, and 30 using the multilayer structures 1 and 2 of the present invention with drugs, a medical body can be created. The drug solution is not particularly limited, and examples include intravenous solutions such as physiological saline, glucose infusion, and amino acid infusion, as well as drug solutions used as injections, such as cardiovascular drugs, neuroprotective agents, antibacterial agents, antiemetics, and plasma-derived products. It is particularly suitable when the drug solution contains lipid-soluble drugs, such as lipid-soluble vitamins or drugs that are easily adsorbed onto polyethylene or polypropylene, in order to prevent drug adsorption to the resin. The contents contained in the container of the present invention are not limited to drug solutions, and may also consist of drugs in the form of powders, such as antibiotics.

[0045] Hereinafter, embodiments of medical containers 10, 20, and 30 will be shown and described as examples of containers of the present invention. As shown in Figure 3, the medical container (container) 10 of the embodiment includes a storage section 11 for containing contents such as liquid medicine, and a port section 12 which serves as an inlet and outlet for dispensing the contents.

[0046] Above the storage section 11 of the medical container 10, a suspension section 13 with a hanging hole is provided. The port section 12 is located below the storage section 11. In this example, the port section 12 is sealed by attaching a rubber stopper 12a, which is made of a cylindrical rubber material through which an injection needle can be inserted, to the outer circumference of its side surface, with a synthetic resin that can be welded to the innermost layer 3 of the multilayer bodies 1 and 3, formed by injection molding.

[0047] The medical container 10 can be manufactured by a conventional multilayer blow molding method using a multilayer blow molding machine. That is, a multilayer parison is extruded, the multilayer parison is sandwiched in a mold, and then clean air is blown into the multilayer parison. By using a mold that can integrally mold the housing section 11 and the port section 12, a medical container 10 consisting of a hollow blow-molded body can be formed. Furthermore, when sandwiching the multilayer parison in the mold, it is pre-blown with clean air beforehand, and after closing the mold, negative pressure is created inside the mold through a vacuum hole formed in the mold. This improves the transfer accuracy of the mold.

[0048] As for the method of forming the port portion 12, for example, it can be integrally formed together with the housing portion 41 by multilayer blow molding, or a separate cylindrical member can be heat-sealed to the housing portion 41, or a cylindrical member can be inserted and integrated simultaneously with molding by insert blow molding. When using these cylindrical members, in addition to the form in which the rubber stopper body 22a is attached to the cylindrical member and sealed, the rubber stopper can be loaded into the cylindrical member, and then the peripheral edge of the rubber stopper can be held down with a ring-shaped lid member, and the lid member and the cylindrical member can be welded together by ultrasonic waves or the like to seal it.

[0049] The container of the present invention may be the medical container 20 illustrated in Figure 4. As shown in Figure 4(A), the medical container 20 comprises a housing portion 21 formed by hot plate molding (vacuum forming, pressure forming, etc.) and a port portion 22 made of a cylindrical member that can be sealed by heat sealing a rubber stopper 22a.

[0050] The housing portion 21 of the medical container 20 is formed by overlapping two film molded products 24, which have recesses obtained by hot plate molding of the multilayer bodies 1 and 2 of the present invention as shown in Figure 5, so that the recesses face each other, and then heat sealing the peripheral portion 23 while arranging a cylindrical member in a predetermined position. The formation of the housing portion 21 and the formation of the port portion 22 may be carried out in separate processes.

[0051] The material of the cylindrical member forming the port portion 22 can be any material that can be heat-sealed liquid-tight with the housing portion 21. A cyclic polyolefin, the same as the innermost layer 3 of the multilayer bodies 1 and 2, is preferred because it has good heat-sealing properties with the housing portion 21. A multilayer body in which a heat-sealable resin is used on the heat-sealing surface of the cylindrical member may also be used.

[0052] In the medical container 20, instead of forming the port portion 22 from the cylindrical member and the rubber stopper 22a, as shown in Figure 4(B), the rubber stopper 22b may be loaded into the cylindrical member, and then the lid member 22c and the cylindrical member may be welded together by ultrasonic waves or the like, with the ring-shaped lid member 22c pressing down on the peripheral edge of the rubber stopper 22b.

[0053] The container of the present invention may be the medical container 30 illustrated in Figure 6. The medical container 30 is a film bag type container comprising a storage section 31 formed in the shape of a bag from film-like multilayer bodies 1 and 2, and a port section 32 made of a cylindrical member. In this example, the port section 32 is closed by a cylindrical member, a rubber stopper 32a through which an injection needle can be inserted, and a ring-shaped lid member 32b that holds down the periphery of the rubber stopper 32a.

[0054] The medical container 30 can be manufactured by using multilayer bodies 1 and 2 formed into a cylindrical shape by a multilayer inflation method or the like, heat-sealing both ends to form a housing section 31, and heat-sealing a cylindrical member at a predetermined position on one end to form a port section 32, and forming a suspension section at the other end as needed. The heat sealing of both ends and the heat sealing of the cylindrical member may be performed simultaneously or in separate processes. Instead of using cylindrical multilayer bodies 1 and 2, two multilayer bodies 1 and 2 manufactured by a multilayer T-die extrusion molding method or the like may be used, stacked together, and then the peripheral edges may be heat-sealed to form the housing section 31. In the case of a film bag type container, a tube may be used instead of the port portion 32, resulting in a container with a tube.

[0055] The container's form is not limited to one having a single storage compartment 11, 21, or 31. For example, it may be a multi-chamber container in which the storage compartment is divided into multiple sections by a connecting partition seal, allowing multiple types of contents to be stored separately. Specifically, as shown in Figure 7, it may be a multi-chamber medical container 40 in which the storage compartment 41 is divided into multiple sections by a connecting partition seal 42, allowing multiple types of drug solutions to be stored separately.

[0056] In the multi-chamber medical container 40, a partition seal portion 42 is provided along the width direction of the bag-shaped storage portion 41, and the storage portion 41 is divided into a first storage portion 41a and a second storage portion 41b. When using the multi-chamber medical container 40, the partition seal portion 42 is detached when the user presses the first storage portion 41a or the second storage portion 41b from the outside, and the drug solution in the first storage portion 41a and the drug solution in the second storage portion 41b are mixed.

[0057] The method for forming the partition seal portion 42 is not particularly limited. For example, the partition seal portion 42 can be formed by a known sealing method such as heat sealing or impulse sealing, or by providing a mechanism for forming the partition seal portion 42 in the mold used during blow molding.

Example

[0058] Hereinafter, the present invention will be specifically described by way of examples, but the present invention is not limited to the following description.

[0059] [Abbreviations of materials] The abbreviations of the materials used in this example are shown below. In the following description, "MFR" is the melt flow rate measured under a load of 21.18 N. COP1: Cyclic polyolefin (product name "ZEONEX 690R", manufactured by Zeon Corporation, Japan, MFR (280 ° C): 17 g / 10 min, Tg: 136 ° C, density: 1.010 g / cm 3 ) COP2: Cyclic polyolefin (product name "ZEONOR 1020R", manufactured by Zeon Corporation, Japan, MFR (280 ° C): 20 g / 10 min, Tg: 102 ° C, density: 1.010 g / cm 3 ) S-LL-1: Single-site LLDPE (product name "Harmolex NM325N", manufactured by Japan Polyethylene Corporation, MFR (190 ° C): 0.9 g / 10 min, density: 0.908 g / cm 3 ) S-LL-2: Single-site LLDPE (product name "Yumelite 125FN", manufactured by Ube Maruzen Polyethylene Co., Ltd., MFR (190 ° C): 2.2 g / 10 min, density: 0.924 g / cm 3 ) S-LL-3: Single-site LLDPE (product name "Yumelite 0520F", manufactured by Ube Maruzen Polyethylene Co., Ltd., MFR (190 ° C): 2.0 g / 10 min, density: 0.904 g / cm 3 ) HD-1: HDPE (product name "Novatec HM4503", manufactured by Japan Polyethylene Corporation, MFR (190 ° C): 1.9 g / 10 min, density: 0.962 g / cm 3 ) Z-LL-1: LLDPE manufactured using a Ziegler catalyst (product name "Novatec UF332", manufactured by Nippon Polyethylene Co., Ltd., MFR (190℃): 1.0g / 10min, density: 0.923g / cm³) 3 ) Z-LL-2: LLDPE manufactured using a Ziegler catalyst (product name "Moretec 3500Z", manufactured by Prime Polymer Co., Ltd., MFR (190℃): 2.0g / 10min, density: 0.923g / cm³) 3 ) S-PP: Single-site random PP (product name "Wintec WF4TA", manufactured by Nippon Polypropylene Co., Ltd., MFR (230℃): 7.0g / 10min, density: 0.900g / cm³) 3 ) F-PP: Flexible PP (product name "Zelus MC617", manufactured by Mitsubishi Chemical Corporation, MFR (230℃): 1.5g / 10min, density: 0.890g / cm³) 3 (It is a blend of olefin-based elastomer and styrene-based elastomer.) n-PP: PP produced using a Ziegler catalyst (product name "Excellen FH3471M", manufactured by Sumitomo Chemical Co., Ltd., MFR (230℃): 2.5g / 10min, density: 0.898g / cm³) 3 ) LD-1:LDPE (Product name "Novatec LM360", manufactured by Nippon Polyethylene Co., Ltd., MFR (190℃): 0.9g / 10min, Density: 0.928g / cm³) 3 )

[0060] [Example 1] A container filled with 100 mL of water was manufactured as follows: First, using a multilayer blow molding method with a multilayer blow molding machine, the housing sections 11, 21, and 31 and the port sections 12, 22, and 32 were integrally molded from a three-layer blow molded body (multilayer body 1) consisting of a 30 μm thick innermost layer 3, a 250 μm thick intermediate layer 4, and a 20 μm thick outer layer 5, which were sequentially laminated. For the innermost layer 3, a mixture of cyclic polyolefins, a blend of COP1 and COP2 in a 1:1 mass ratio, was used. Only one Tg was observed for this mixed cyclic polyolefin, which was 119°C. For the intermediate layer 4, a blend of S-LL-1 and HD-1 in an 8:2 mass ratio was used. For the outer layer 5, S-PP was used.

[0061] Next, 100 mL of water was filled into the storage sections 11, 21, and 31 from the port sections 12, 22, and 32, and then the rubber stopper was ultrasonically welded to the port section to seal the container. As the rubber stopper, an assembled rubber stopper was used, in which a chlorinated butyl rubber stopper was inserted into the outer circumference of an annular shape formed by injection molding using COP1. The sealed containers were sterilized using an autoclaver at 123°C for 15 minutes.

[0062] [Example 2] A container was obtained in the same manner as in Example 1, except that F-PP was used for the outer layer 5.

[0063] [Example 3] A container was obtained in the same manner as in Example 2, except that only COP1 was used for the innermost layer 3.

[0064] [Example 4] A container was obtained in the same manner as in Example 2, except that only S-LL-2 was used for the intermediate layer 4, and the outer circumference of the rubber stopper was made by injection molding using the same S-LL-2 used in the intermediate layer 4.

[0065] [Example 5] A container was obtained in the same manner as in Example 1, except that the intermediate layer 4 used a blend of S-LL-3 and HD-1 in a mass ratio of 8:2, and the outer circumference of the rubber stopper was injection-molded using COP1.

[0066] [Example 6] A container filled with 100 mL of water was manufactured as follows: First, an inflation film (multilayer 1) consisting of three layers was manufactured by sequentially laminating an innermost layer 3 with a thickness of 20 μm, an intermediate layer 4 with a thickness of 220 μm, and an outer layer 5 with a thickness of 20 μm using a water-cooled multilayer inflation film molding machine. The composition of each layer was the same as in Example 1. Next, both ends of the inflation film were heat-sealed to form a bag, and a cylindrical member, which was an injection-molded product of COP1, was heat-sealed to one end to form port portions 12, 22, and 32 in the film bag-shaped container. Then, 100 mL of water was filled into the container through the port portions 12, 22, and 32, and the container was sealed by ultrasonic welding a rubber stopper to the port portions 12, 22, and 32. As the rubber stopper, an assembled rubber stopper was used, in which a chlorinated butyl rubber stopper was inserted into the outer circumference of an annular shape molded by injection molding using COP1. The sealed containers were sterilized using an autoclaver at 123°C for 15 minutes.

[0067] [Example 7] A container was obtained in the same manner as in Example 6, except that F-PP was used for the outer layer 5.

[0068] [Example 8] A container was obtained in the same manner as in Example 7, except that only COP1 was used for the innermost layer 3.

[0069] [Example 9] A container was obtained in the same manner as in Example 7, except that only S-LL-2 was used for the intermediate layer 4.

[0070] [Example 10] A container was obtained in the same manner as in Example 6, except that the intermediate layer 4 used a blend of S-LL-3 and HD-1 in a mass ratio of 8:2.

[0071] [Example 11] A container filled with 100 mL of water was manufactured as follows: First, an inflation film (multilayer 2) consisting of four layers was manufactured by sequentially laminating an innermost layer 3 with a thickness of 10 μm, an intermediate layer 4 with a thickness of 200 μm, an outer layer 5 with a thickness of 20 μm, and an outermost layer 6 with a thickness of 20 μm using a water-cooled multilayer inflation film molding machine. For the innermost layer 3, a mixture of cyclic polyolefins, a blend of COP1 and COP2 in a 1:1 mass ratio, was used. Only one Tg was observed for this mixed cyclic polyolefin, which was 119°C. For the intermediate layer 4, a blend of S-LL-1 and HD-1 in an 8:2 mass ratio was used. For the outer layer 5, S-PP was used. For the outermost layer 6, n-PP was used. Next, using this inflation film, a container was obtained in the same manner as in Example 6. The sealed container was subjected to autoclaving at 123°C for 15 minutes.

[0072] [Example 12] A container was obtained in the same manner as in Example 11, except that F-PP was used for the outer layer 5.

[0073] [Comparative Example 1] A container was obtained in the same manner as in Example 1, except that only Z-LL-1 was used for the intermediate layer 4.

[0074] [Comparative Example 2] A container was obtained in the same manner as in Example 1, except that only Z-LL-2 was used for the intermediate layer 4.

[0075] [Comparative Example 3] A container was obtained in the same manner as in Example 2, except that only Z-LL-2 was used for the intermediate layer 4.

[0076] [Comparative Example 4] A container was obtained in the same manner as in Example 1, except that HD-1 was used for the outer layer 5.

[0077] [Comparative Example 5] A container was obtained in the same manner as in Example 1, except that the outer layer 5 used a blend of HD-1 and LD-1 in a mass ratio of 3:7.

[0078] [Comparative Example 6] A container was obtained in the same manner as in Example 6, except that only Z-LL-1 was used for the intermediate layer 4.

[0079] [Comparative Example 7] A container was obtained in the same manner as in Example 6, except that only Z-LL-2 was used for the intermediate layer 4.

[0080] [Comparative Example 8] A container was obtained in the same manner as in Example 7, except that only Z-LL-2 was used for the intermediate layer 4.

[0081] [Comparative Example 9] A container was obtained in the same manner as in Example 6, except that HD-1 was used for the outer layer 5.

[0082] [Comparative Example 10] A container was obtained in the same manner as in Example 6, except that the outer layer 5 used a blend of HD-1 and LD-1 in a mass ratio of 3:7.

[0083] [Comparative Example 11] A container was obtained in the same manner as in Example 9, except that n-PP was used for the outer layer 5.

[0084] Tables 1 and 2 show the composition (mass ratio) of each layer, rubber stopper, and port portion of Multilayer 1 in Examples 1-10 and Comparative Examples 1-11. Table 3 shows the composition (mass ratio) of each layer, rubber stopper, and port portion of Multilayer 2 in Examples 11 and 12. In Tables 1-3, "10" indicating a composition (mass ratio) means that only that component is used in each layer, rubber stopper, or port portion of Multilayer 1 and 2. In other words, "10" indicating a composition (mass ratio) means that only the component corresponding to the location where the composition (mass ratio) "10" is listed is used in each layer, rubber stopper, or port portion of Multilayer 1 and 2. In the examples and comparative examples, the evaluation of blocking resistance was performed only in the cases where the housing portions 11, 21, 31, and 41 were formed by molding from a film, and not in the cases where the housing portions 11, 21, 31, and 41 were formed by multilayer blow molding, as in Example 1.

[0085] [Table 1]

[0086] [Table 2]

[0087] [Table 3]

[0088] [Evaluation Method] The containers obtained in each example were evaluated as follows.

[0089] (1) Molding stability In blow molding, the shape stability of the parison during molding and the thickness variation after molding were evaluated according to the following criteria. A: The parison shape is stable. No areas of extreme thinness are observed in the blow-molded container. B: The parison shape is mostly stable. Some areas of the blow-molded container are slightly thinner. C: The parison shape is unstable and draws down. Extremely thin areas are observed in the blow-molded container.

[0090] In water-cooled inflation film molding, the shape stability of the tubular film (bubble) during molding and the occurrence of wrinkles in the molded film were evaluated according to the following criteria. A: The tube shape is constant and stable. The tube diameter is constant. B: The tube shape is mostly stable. The tube diameter is almost constant. Wrinkles are partially observed in the film. C: The tube shape is unstable. There is variation in tube diameter. Wrinkles are observed in the film.

[0091] (2) Blocking resistance Two test pieces, each measuring 10cm x 10cm, cut from the container in each example, were placed on top of each other so that their outer layers were in contact, and then subjected to a 98N / 100cm² test. 2 The specimens were subjected to a load and held at 60°C for 24 hours. After cooling to room temperature and removing the load, the two specimens were separated. The state of separation was evaluated in the following two stages. A: It peels off easily. C: I'm hesitant to peel it off.

[0092] (3) Adhesion to the sterilization tray For each example, a steam sterilizer was used to sterilize the containers at a temperature of 123°C for 15 minutes. The containers were placed on a perforated metal tray (sterilization tray) with circular holes and sterilized by high-pressure steam. The containers after high-pressure steam sterilization were evaluated to see if they were adhered to the perforated metal tray of the sterilizer according to the following criteria. The perforated metal tray was made of stainless steel. A: They are not glued together at all. B: It's slightly adhesive, but it peels off easily. C: It's glued on and difficult to peel off.

[0093] (4) Heat resistance The appearance of the containers after high-pressure steam sterilization was visually inspected and evaluated according to the following criteria. A: No deformation or shrinkage after sterilization. B: Fine roughness and wrinkles are observed locally on the surface, and there is some shrinkage. C: Significant deformation and shrinkage are observed, and clear circular tray marks are visible.

[0094] (5) Peel strength Strip-shaped samples, 15 mm wide, were cut from the containers before and after the aforementioned autoclaving process. The T-shaped peel strength between the intermediate and outer layers was measured at a tensile speed of 300 mm / min, in accordance with JIS K6854-3. The test was performed using a tensile testing machine.

[0095] (6) Transparency The haze after the aforementioned autoclaving was measured in accordance with JIS K 7136.

[0096] The evaluation results for each case are shown in Table 4.

[0097] [Table 4]

[0098] As shown in Table 4, Examples 1 to 12, which used multilayer bodies 1 and 2 comprising an innermost layer 3 made of cyclic polyolefin, an intermediate layer 4 mainly composed of single-site LLDPE, and an outer layer 5 made of either single-site random PP or flexible PP, exhibited excellent heat resistance, and problems such as a decrease in peel strength, sticking to sterilization trays, and the occurrence of wrinkles and deformation were suppressed even after sterilization. Furthermore, Examples 1 to 12 also exhibited excellent molding stability and blocking resistance, and sufficient transparency was ensured even after sterilization.

[0099] On the other hand, in Comparative Examples 1-3 and 6-8, where single-site LLDPE was not used in the intermediate layer 4, the peel strength between the intermediate layer 4 and the outer layer 5 was low, and the peel strength further decreased after sterilization. In Comparative Examples 4, 5, 9, and 10, where HDPE or LDPE was used instead of single-site random PP or flexible PP in the outer layer 5, adhesion to the sterilization tray was not sufficiently suppressed. Furthermore, in Comparative Example 11, where PP manufactured using a Ziegler catalyst was used instead of single-site random PP or flexible PP in the outer layer 5, the peel strength between the intermediate layer 4 and the outer layer 5 was low, and the peel strength further decreased after sterilization.

[0100] Comparing Example 1 with Comparative Examples 1 and 2, it was confirmed that using single-site LLDPE for the intermediate layer 4 increased the adhesion strength (peel strength) between the intermediate layer 4 and the outer layer 5 compared to using LLDPE produced with a Ziegler catalyst for the intermediate layer 4. This improvement was such that sufficient peel strength was maintained even after sterilization. Similar results were confirmed when comparing Examples 2 and 4 with Comparative Example 3. Comparing Examples 1-3 with Comparative Examples 4 and 5, it was confirmed that using single-site random PP or flexible PP for the outer layer 5 significantly reduced adhesion to the sterilization tray compared to using HDPE or LDPE for the outer layer 5. The same was confirmed when comparing Examples 6-10 with Comparative Examples 6-10. [Industrial applicability]

[0101] According to the present invention, it is possible to provide a multilayer container with excellent heat resistance and the ability to suppress problems during sterilization, and a container using the multilayer container, particularly a medical container and a medical container containing pharmaceuticals. [Explanation of symbols]

[0102] 1, 2 Multilayer body for containers 3. Innermost layer 4. Middle Class 5 Outer layer 6 outermost layer 10, 20, 30 medical containers 11, 21, 31 containment units Ports 12, 22, and 32 40 Multi-chamber medical containers 41 Storage Unit 42 Partition seal section

Claims

1. A multilayer container used for forming containers, The innermost layer is made of cyclic polyolefin, An intermediate layer formed adjacent to the innermost layer, mainly composed of linear low-density polyethylene produced using a single-site catalyst, An outer layer consisting of either random polypropylene manufactured using a single-site catalyst, or polypropylene containing an elastomer, It has, The intermediate layer consists only of the linear low-density polyethylene and high-density polyethylene, which is denser than the linear low-density polyethylene and is contained in an amount of 30% by mass or less relative to the total mass of the intermediate layer, for use as a multilayer container.

2. The outermost layer, made of polypropylene, is located outside the aforementioned outer layer. A multilayer container according to claim 1.

3. The cyclic polyolefin is a hydrogenated product of a ring-opening polymer of a cyclic olefin monomer. A multilayer container according to claim 1 or 2.

4. The elastomer is an olefin-based elastomer and / or a styrene-based elastomer. A multilayer container according to any one of claims 1 to 3.

5. A container having a compartment for holding contents, At least the housing portion is made of a multilayer container according to any one of claims 1 to 4. container.

6. A medical container equipped with a compartment for containing a liquid medicine, At least the housing portion is made of a multilayer container according to any one of claims 1 to 4. Medical container.

7. A drug-containing medical container in which a drug is contained in the medical container according to claim 6.

Images