Multilayer body for containers, container, medical container and medical container filled with a medicament

Abstract

The present invention provides a multilayer body for a container (1, 2) which is a multilayer body for a container (1, 2) for forming a container, the multilayer body for a container (1, 2) having: an innermost layer (3) formed of a cyclic polyolefin; an intermediate layer (4) formed in abutment with the innermost layer (3) and having a linear low-density polyolefin produced using a single-site catalyst as a main component; and an outer layer (5) formed of one of a random polypropylene produced using a single-site catalyst or a polypropylene containing an elastomer.

Description

Technical Field

[0001] This invention relates to a multilayer body for containers, containers, medical containers, and medical containers containing pharmaceutical agents. This application claims priority based on Japanese Patent Application No. 2021-026286, filed on February 22, 2021, the contents of which are incorporated herein by reference. Background Technology

[0002] For example, resin containers for liquid medicines used in the medical field include ampoules or syringes, as well as plastic bottles or liquid rods or infusion bags formed from plastic films. In particular, infusion bags are widely used for infusions or injections administered directly intravenously via injection or transfusion. Various materials can be used for the resin used in these infusion bags. It is known that when the liquid medicine containing a specific drug, such as a fat-soluble vitamin, is present, a cyclic polyolefin layer formed from a thermoplastic saturated norbornene polymer is used as the liquid contact layer (innermost layer) to prevent the resin from adsorbing the drug. Patent Document 1 discloses a multilayer body as a container, which has: an outermost layer formed from high-density polyethylene, an intermediate layer formed from linear low-density polyethylene, and an innermost layer formed from cyclic polyethylene.

[0003] Existing technical documents

[0004] Patent documents

[0005] Patent Document 1: Japanese Patent Application Publication No. 2008-18063 Summary of the Invention

[0006] The problem that the invention aims to solve

[0007] Typically, liquid pharmaceuticals, especially infusions or injections, are sterilized by autoclaving or similar methods after the contents are filled into the container. However, in cases where the temperature distribution within the sterilizer is wide, the sterilizer temperature must be set high to ensure sterilization even in lower-temperature areas, guaranteeing the sterilization of all products. In such cases, conventional containers, as described in Patent Document 1, exhibit insufficient heat resistance when subjected to the aforementioned high-temperature sterilization. Consequently, in areas with higher temperatures within the sterilizer, the following adverse effects may occur: reduced interlayer strength leading to easy delamination; containers adhering to the sterilization tray, resulting in poor appearance or difficulty in removal; or whitening of the container surface upon removal from the sterilization tray, impairing its transparency. Furthermore, shrinkage caused by heat during sterilization may lead to wrinkling or deformation of the container, resulting in poor appearance or impaired transparency.

[0008] The purpose of this invention is to provide a multilayer body for containers with excellent heat resistance and the ability to suppress adverse conditions during sterilization, as well as a container using the above-mentioned multilayer body, a medical container, and a medical container containing a drug.

[0009] Technical means for solving problems

[0010] The present invention has the following solutions.

[0011] The first aspect of the present invention is a multilayer body for forming a container, characterized in that it comprises: an innermost layer formed of a cyclic polyolefin; an intermediate layer formed adjacent to the innermost layer and mainly composed of linear low-density polyethylene manufactured using a single-active-center catalyst; and an outer layer formed of atactic polypropylene manufactured using a single-active-center catalyst or polypropylene containing an elastomer.

[0012] The second aspect of the present invention is the multilayer body for container described in the first aspect above, wherein an outermost layer formed of polypropylene is provided on the outside of the outer layer.

[0013] The third aspect of the present invention is the multilayer body for containers described in the first or second aspect above, wherein the cyclic polyolefin is a hydride of a ring-opening polymer of a cyclic olefin monomer.

[0014] The fourth aspect of the present invention is a multilayer body for a container as described in any one of the first to third aspects above, wherein the elastomer is an olefin-based elastomer and / or a styrene-based elastomer.

[0015] The fifth aspect of the present invention is a container having a holding portion for holding contents, characterized in that at least the holding portion is composed of a multi-layer container body as described in any one of the first to fourth aspects.

[0016] The sixth aspect of the present invention is a medical container having a receiving portion for holding liquid medicine, characterized in that at least the receiving portion is composed of a multi-layer container body as described in any one of the first to fourth aspects.

[0017] The seventh aspect of the present invention is a medical container containing a drug, characterized in that the drug is contained in the medical container described in the sixth aspect above.

[0018] It should be noted that, in this application, the concept of a container includes not only rigid containers, but also packaging made of films, etc.

[0019] Invention Effects

[0020] According to the present invention, a multilayer body for containers with excellent heat resistance and the ability to suppress adverse conditions during sterilization can be provided, as well as containers using the above-mentioned multilayer body for containers, particularly medical containers and medical containers containing pharmaceuticals. Hereinafter, the multilayer body for medical containers will be described in detail. Attached Figure Description

[0021] Figure 1 This is a cross-sectional view of a multi-layered container used in an embodiment.

[0022] Figure 2 This is a cross-sectional view showing a multi-layered container body according to another embodiment.

[0023] Figure 3 This is a diagram illustrating a medical container used in an implementation method. Figure 3 (A) is a floor plan. Figure 3 (B) is Figure 3 (A) Sectional view along line I-I'.

[0024] Figure 4 This is a diagram illustrating a medical container according to another embodiment. Figure 4 (A) is a floor plan. Figure 4 (B) is a plan view representing the port section in another way.

[0025] Figure 5 It means in manufacturing Figure 4 The image shows a membrane-molded product used in medical containers. Figure 5 (A) is the front view. Figure 5 (B) is a side view.

[0026] Figure 6 This is a plan view of a medical container according to another embodiment.

[0027] Figure 7 This is a plan view of a multi-chamber medical container, which is an example of a medical container as another embodiment. Detailed Implementation

[0028] [Multi-layered container]

[0029] The multilayer body for containers of the present invention (hereinafter also simply referred to as "multilayer body") is a multilayer body used to form containers. The multilayer body of the present invention is particularly suitable for forming a receiving portion for holding liquid medicine in a medical container. The multilayer body of the present invention has at least an innermost layer, an intermediate layer formed adjacent to the innermost layer, and an outer layer, as described later.

[0030] The following description illustrates an example of a multilayer body according to the present invention. It should be noted that the dimensions and other dimensions illustrated in the following description are merely examples. The present invention is not limited to these examples, and appropriate modifications can be made without altering its spirit.

[0031] As a multilayer body of the present invention, examples can be given as follows: Figure 1 The container shown is made of multi-layer body 1 (hereinafter also referred to as "multi-layer body 1"). Figure 2 The container shown is made of multi-layer body 2 (hereinafter also referred to as "multi-layer body 2").

[0032] like Figure 1 As shown, multilayer body 1 is a three-layer structure consisting of an innermost layer 3, a middle layer 4, and an outermost layer 5. In multilayer body 1, the innermost layer 3, the middle layer 4, and the outermost layer 5 are stacked sequentially. Figure 2 As shown, multilayer body 2 is a four-layer structure consisting of innermost layer 3, middle layer 4, outermost layer 5, and outermost layer 6. In multilayer body 2, innermost layer 3, middle layer 4, outermost layer 5, and outermost layer 6 are stacked sequentially.

[0033] (Innermost layer)

[0034] The innermost layer 6 is the innermost layer (liquid contact layer) placed in contact with the contents during container formation, and is formed of cyclic polyolefin. Because cyclic polyolefin has low adsorption or absorption of pharmaceuticals, it can inhibit the reduction of the drug's efficacy if the contents are pharmaceuticals. Furthermore, due to the excellent heat resistance and transparency of cyclic polyolefin, it is suitable for medical containers requiring high-temperature sterilization where it is desirable to have the contents visible from the outside.

[0035] Examples of cyclic polyolefins include: ring-opening polymers of cyclic olefin monomers, hydrides of ring-opening polymers of cyclic olefin monomers, addition polymers of cyclic olefin monomers, and addition copolymers with other monomers that can copolymerize with cyclic olefin monomers. From the viewpoint of excellent heat resistance, hydrides of ring-opening polymers of cyclic olefin monomers are preferred as cyclic polyolefins. The innermost cyclic polyolefin can be one type or two or more types.

[0036] As cyclic olefin monomers, there are no particular limitations, but examples include norbornene monomers and monocyclic cyclic olefin monomers. Norbornene monomers are monomers whose structure contains structural units derived from norbornene, and examples include bicyclic [2.2.1]hept-2-ene, tricyclic [4.3.0.12,5]dec-3,7-diene, 7,8-benzotricyclic [4.3.0.12,5]dec-3-ene, and tetracyclic [4.4.0.12,5.17,10]dodec-3-ene. Monocyclic olefin monomers include cyclohexene, cycloheptene, and cyclooctene. Cyclic olefin monomers can be used alone or in combination of two or more types.

[0037] Other monomers that can undergo addition copolymerization with cyclic olefin monomers include, for example, α-olefins with 2 to 20 carbon atoms such as ethylene, propylene, 1-butene, and 1-hexene. Other monomers can be used alone or in combination of two or more.

[0038] Ring-opening polymers of cyclic olefin monomers can be obtained by polymerizing the cyclic olefin monomers using a metathesis reaction in the presence of a ring-opening polymerization catalyst. Hydrates of ring-opening polymers of cyclic olefin monomers can be obtained by hydrogenating the ring-opening polymers using a known hydrogenation catalyst. Addition polymers and addition copolymers of cyclic olefin monomers can be obtained by polymerization using a catalyst composed of known titanium, zirconium compounds, and organoaluminum compounds.

[0039] Commercially available products that are addition polymers and addition copolymers of cyclic olefin monomers include, for example, APEL (registered trademark) manufactured by Mitsui Chemicals Co., Ltd., and TOPAS (registered trademark) manufactured by Polyplastics Co., Ltd. Examples of hydrides of ring-opening polymers of cyclic olefin monomers include Zeonor (registered trademark) and Zeonex (registered trademark) manufactured by Nippon Zeon Co., Ltd.

[0040] The glass transition temperature (hereinafter also referred to as "Tg") of cyclic polyolefins is preferably 70°C to 180°C, more preferably 100°C to 140°C. If Tg is above the lower limit of the above range, the container exhibits excellent heat resistance. If Tg is below the upper limit of the above range, the multilayer exhibits excellent formability and heat-sealing properties. It should be noted that Tg is a value measured using a differential scanning calorimeter (DSC) based on JIS K 7121.

[0041] As cyclic polyolefins, two or more with different Tg values ​​can be mixed. This is because mixing allows for setting an appropriate molding temperature during co-extrusion molding of multilayers 1 and 2, thus 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 becomes a range of 113°C to 118°C, allowing extrusion molding at a molding temperature of approximately 250°C. At this temperature, molding stability can be maintained without significantly deviating from the optimal molding temperatures of the adjacent intermediate layer 4, outer layer 5, and outermost layer 6. If the Tg of the mixture decreases too much, the inner cyclic polyolefin layer may soften during autoclaving, leading to bag breakage during sterilization. Therefore, it is preferable to consider two cyclic polyolefins with different Tg values ​​when setting the Tg of the mixture.

[0042] Furthermore, if the heat resistance (Tg) of the inner cyclic polyolefin layer is higher than that of the resin used in the outer layer 5 or the outermost layer 6, a higher heat-sealing temperature is set during the bag-making process to allow the cyclic polyolefin to melt or soften and for bag making. This results in excessive heat being applied to the outer layer 5 or the outermost layer 6, leading to a poor appearance of the container. Therefore, it is not preferable for the Tg of the inner cyclic polyolefin layer to be higher than that of the resin used in the outer layer 5 or the outermost layer 6.

[0043] As long as it does not impair the effects of the present invention, the innermost layer 3 may also contain various additives commonly used in the resin field, such as antistatic agents, antioxidants, lubricants, antifogging agents, ultraviolet absorbers, and neutralizers.

[0044] (Middle layer)

[0045] The intermediate layer 4 is formed adjacent to the innermost layer 3 and is primarily composed of linear low-density polyethylene (hereinafter also referred to as "single-active-center LLDPE") manufactured using a single-active-center catalyst. "Single-active-center LLDPE as the main component" means that the content of single-active-center LLDPE in the intermediate layer 4 is 50% by mass or more relative to the total mass of the intermediate layer 4.

[0046] The single-active-center LLDPE exhibits excellent adhesion to cyclic polyolefins, with minimal reduction in adhesion even after autoclaving. Therefore, by using the intermediate layer 4, the innermost layer 3, formed from cyclic polyolefins, can be stably bonded to the outermost layers.

[0047] As a single-active-center catalyst, there are no particular limitations; examples include metallocene catalysts.

[0048] The preferred density of a single-active-center LLDPE is 0.860 g / cm³. 3 Above and below 0.940 g / cm 3 More preferably, it is 0.890 g / cm³. 3 Up to 0.924 g / cm 3 If the density of the single-active-center LLDPE is above the lower limit mentioned above, it exhibits excellent heat resistance and easily suppresses the decrease in peel strength between the intermediate layer 4 and the innermost layer 3. If the density of the single-active-center LLDPE is below the upper limit mentioned above, it easily suppresses the decrease in the transparency or impact resistance of the container.

[0049] As a single-active-center LLDPE, two or more types with different densities can be used together.

[0050] The intermediate layer 4 may contain resins other than mono-active-center LLDPE, provided that it does not impede adhesion to the innermost layer 3. Examples of other resins include polyethylene, cyclic polyolefins, and preferably high-density polyethylene (hereinafter also referred to as "HDPE").

[0051] The content of single active center LLDPE in the intermediate layer 4 is 50% by mass or more relative to the total mass of the intermediate layer 4, and from the viewpoint of excellent softness, it is preferably 65% ​​by mass or more, and more preferably 80% by mass or more.

[0052] From the viewpoint of improving heat resistance, further suppressing the decrease in adhesion of the intermediate layer 4 caused by high-pressure steam sterilization, and reducing the shrinkage of the intermediate layer 4, it is preferable that the intermediate layer 4 further contains HPDE with a higher density than that of single-active-center LLDPE, in a range of 30% by mass or less relative to the total mass of the intermediate layer 4, and more preferably in a range of 25% by mass or less. This results in improved molding stability and also makes it less prone to heat deformation or wrinkling when used in containers.

[0053] As long as it does not impair the effects of the present invention, the intermediate layer 4 may also contain various additives commonly used in the resin field, such as antistatic agents, antioxidants, lubricants, antifogging agents, ultraviolet absorbers, and neutralizers.

[0054] (Outer layer)

[0055] Without the outermost layer 6 described later, the outer layer 5 is formed in a manner that it is located at the outermost edge of the container. With the outermost layer, the outer layer 5 is formed in a manner that it is adjacent to the inner edge of the outermost layer. The outer layer 5 is formed of one of random polypropylene (hereinafter also referred to as "single active center random PP") manufactured using a single active center catalyst, or polypropylene containing an elastomer (hereinafter also referred to as "flexible PP").

[0056] Monocentric random PP can be obtained by random copolymerization of polypropylene and ethylene using a monocentric catalyst. It has polypropylene-based structural units (hereinafter also referred to as "polypropylene units") and ethylene-based structural units (hereinafter also referred to as "ethylene units"). Since monocentric random PP is a polymer with high molecular weight and narrow molecular weight distribution, it has excellent adhesion to the intermediate layer 4.

[0057] The content of ethylene units in the single-active-center random PP is preferably 0.3% to 7% by mass, more preferably 1.7% to 5.5% by mass, relative to all structural units. If the content of ethylene units is above the lower limit of the above range, it possesses sufficient flexibility and excellent thermal adhesion between the outer layer 5 and the intermediate layer 4. If the content of ethylene units is below the upper limit of the above range, it exhibits excellent heat resistance.

[0058] Because soft PP contains elastomers, it has excellent thermal adhesion to the intermediate layer 4.

[0059] 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 high compatibility with PP as the matrix and adhesive properties with LLDPE. More specifically, ethylene-propylene copolymers, ethylene-butene copolymers, styrene-butadiene copolymers, and hydrogenated styrene-butadiene copolymers are preferred. The flexible PP may contain one or more types of elastomers.

[0060] The elastomer content in the flexible PP is preferably 20% to 60% by mass, 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, the thermal adhesion to the intermediate layer 4 is excellent. If the elastomer content is below the upper limit of the above range, the heat resistance is excellent.

[0061] As long as it does not impair the effects of the present invention, the outer layer 5 may also contain various additives commonly used in the resin field, such as antistatic agents, antioxidants, lubricants, antifogging agents, ultraviolet absorbers, and neutralizers.

[0062] (outermost layer)

[0063] The outermost layer 6 is made of polypropylene (PP).

[0064] The outermost PP layer 6 can be PP manufactured using a single-active-center catalyst, or PP manufactured using a catalyst other than a single-active-center catalyst. For example, PP using a Ziegler catalyst. The PP for the outermost PP layer 6 is preferably a homopolymer of propylene, but it can also be a copolymer containing ethylene units, etc., as long as it does not affect the heat resistance to a degree such as 5% by mass or less. Furthermore, the outermost PP layer may also contain styrene-based elastomers such as styrene-butadiene copolymers or hydrogenated styrene-butadiene copolymers.

[0065] As long as it does not impair the effects of the present invention, the outermost layer may also contain various additives commonly used in the resin field, such as antistatic agents, antioxidants, lubricants, antifogging agents, ultraviolet absorbers, and neutralizers.

[0066] (thickness)

[0067] The total thickness of the multilayer bodies 1 and 2 of the present invention is not particularly limited, for example, it can be set to 60 μm to 1000 μm. From the viewpoint of the flexibility or strength of the multilayer bodies 1 and 2, it is preferably 100 μm to 600 μm, more preferably 100 μm to 400 μm.

[0068] There are no specific limitations on the thickness of each layer.

[0069] The thickness of the innermost layer 3 is preferably 5 μm to 100 μm. If the thickness of the innermost layer 3 is above the lower limit mentioned above, it is less likely to adsorb the contents such as medicines contained therein. If the thickness of the innermost layer 3 is below the upper limit mentioned above, the multilayer bodies 1 and 2 have excellent flexibility, and the heat-sealing performance of the container formed by the multilayer bodies 1 and 2 is excellent.

[0070] The thickness of the intermediate layer 4 can be set according to the thicknesses of the innermost layer 3, the outermost layer 5, and the outermost layer 6, so that the total thickness is within the above range. For example, it can be set to 50μm to 300μm.

[0071] The thickness of the outer layer 5 is preferably between 5 μm and 100 μm. If the thickness of the outer layer 5 is above the lower limit mentioned above, the heat resistance is excellent. If the thickness of the outer layer 5 is below the upper limit mentioned above, the overall flexibility of the infusion bag is excellent.

[0072] The thickness of the outermost layer 6 is preferably between 5 μm and 100 μm. If the thickness of the outermost layer 6 is above the lower limit mentioned above, the heat resistance is excellent. If the thickness of the outermost layer 6 is below the upper limit mentioned above, the overall flexibility of the infusion bag is excellent.

[0073] In multilayer structures with a three-layer structure, such as multilayer 1, for example, when the thickness ratio of the innermost layer 3, the middle layer 4, and the outer layer 5 is set to 10-20:210-220:20, the balance of flexibility, heat resistance, etc. is particularly good.

[0074] In multilayer structures with four layers, such as multilayer 2, for example, when the thickness ratio of the innermost layer 3, the middle layer 4, the outermost layer 5, and the outermost layer 6 is set to 10-20:190-200:20:20, the balance of flexibility, heat resistance, etc. is particularly good.

[0075] It should be noted that 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, without impairing the effect of the present invention, one or more other layers may be provided between the intermediate layer 4 and the outer layer 5. 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 a polyolefin resin containing iron oxide, and an oxygen-absorbing layer formed from a polyamide resin such as MXD nylon and a cobalt salt.

[0076] The manufacturing method of the multilayer body of the present invention is not particularly limited, and well-known multilayer extrusion methods can be used. Specifically, examples include: multilayer T-die extrusion molding, multilayer blow molding, and multilayer blow molding.

[0077] (Effects)

[0078] As described above, the multilayers 1 and 2 of the present invention comprise: an innermost layer 3 formed of a cyclic polyolefin, an intermediate layer 4 mainly composed of mono-active-center LLDPE, and an outer layer 5 formed of either mono-active-center random PP or flexible PP. Mono-active-center LLDPE exhibits excellent adhesion to cyclic polyolefins, and also excellent adhesion to mono-active-center random PP or flexible PP. Therefore, in the multilayers 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 treatment can be suppressed. This can be attributed to the fact that the LLDPE or PP manufactured using a mono-active-center catalyst reduces the amount of low-molecular-weight components that hinder interlayer adhesion.

[0079] Furthermore, by using mono-active-center 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, thus improving heat resistance. Therefore, even during high-temperature sterilization processes, the container is less likely to adhere to the sterilization tray, suppressing problems such as difficulty in peeling the container from the tray and the appearance of whitening on the container surface. In addition, the multilayers 1 and 2 are less prone to shrinkage due to heat during sterilization, and wrinkles are less likely to form, thus also suppressing the deterioration of the container's appearance.

[0080] Furthermore, by further providing an outermost layer 6 made of PP on the outside of the outer layer 5, the heat resistance of the outer side of the multilayer 2 can be further improved. Therefore, it is possible to further suppress the adhesion of the container to the sterilization tray during sterilization and the deterioration of the container's appearance due to wrinkles. In particular, when the outer layer 5 is formed containing flexible PP, by providing the outermost layer 6 made of PP, the adhesion of the elastomer to the heat-sealing rod during the bag-making process via heat sealing can be stably suppressed. Therefore, since the multilayer 2 is less likely to be rolled up by the heat-sealing rod during heat sealing, the bag-making speed is increased.

[0081] [container]

[0082] The container of the present invention is a container having storage portions 11, 21, 31, and 41 for storing contents, wherein at least the storage portions 11, 21, 31, and 41 are constituted by the multilayer bodies 1 and 2 of the present invention. The multilayer bodies 1 and 2 in the container are arranged such that the innermost layer 3 is the inner side of the storage portions 11, 21, 31, and 41, and the outermost layers 5 and 6 are the outer sides. Other configurations of the container of the present invention are not particularly limited, as long as at least the storage portions 11, 21, 31, and 41 are constituted by the multilayer bodies 1 and 2 of the present invention. For example, in addition to the storage portions 11, 21, 31, and 41, the container may also be provided with rigid port portions 12, 22, and 32 serving as inlets and outlets for the contents. The inlets and outlets of the port portions 12, 22, and 32 are filling ports for filling the contents during manufacturing and outlets for removing the contents during use. These port portions 12, 22, and 32 are manufactured using COP of the same type as the inner layers through injection molding or the like. Alternatively, a tube can be used as the injection / dispensing inlet / outlet. The tube is a multi-layered tube, with at least the outer layer of the tube, which is heat-sealed to the inner layer of the bag, being formed of the same COP as the inner layer of the bag, or PP containing a large amount of elastomer that has adhesive properties to COP.

[0083] The container of the present invention is particularly useful as a medical container having a storage section for holding liquid medicine. By storing the medicine in the medical container 10, 20, 30 using the multilayer bodies 1 and 2 of the present invention, a medical body can be manufactured.

[0084] The pharmaceutical solution is not particularly limited, and examples include infusions such as physiological saline or glucose infusions, amino acid infusions, or circulatory drugs, neuroprotective agents, antibacterial agents, antiemetics, and plasma fractionation preparations used as injectable solutions. It is particularly suitable for preventing the adsorption of the drug onto the resin when the solution contains fat-soluble agents, such as fat-soluble vitamins or agents easily adsorbed by polyethylene or polypropylene. It should be noted that the contents contained in the container of this invention are not limited to pharmaceutical solutions, and can also be drugs formed from powders such as antibiotics.

[0085] Hereinafter, embodiments of medical containers 10, 20, and 30 will be described as examples of containers of the present invention.

[0086] like Figure 3 As shown, the medical container (container) 10 of the embodiment includes a storage section 11 for storing contents such as liquid medicine and a port section 12 for dispensing or dispensing contents.

[0087] A suspension portion 13 with a hanging hole is provided on the upper part of the housing portion 11 of the medical container 10. A port portion 12 is provided on the lower part of the housing portion 11. In this example, the port portion 12 can be sealed by installing a rubber plug 12a, which is formed by injection molding a synthetic resin that can be fused to the innermost layer 3 of the multilayer body 1 and 3 on the outer periphery of a cylindrical rubber material that can be pierced by an injection needle.

[0088] The medical container 10 can be manufactured using a multi-layer blow molding machine and a conventional multi-layer blow molding method. That is, simply extrude a multi-layer preform, clamp the preform in a mold, and then blow clean air into the preform. By using a mold capable of integrally molding the housing part 11 and the port part 12, a medical container 10 formed from a hollow blow-molded body can be formed. Furthermore, when clamping the multi-layer preform in the mold, clean air is pre-circulated while the mold is closed, and then negative pressure is generated inside the mold through vacuum holes formed on the mold. This improves the transfer accuracy of the mold.

[0089] As for the method of forming the port portion 12, in addition to the method of integrally forming it together with the housing portion 41 using a multi-layer blow molding method, other examples include: heat-sealing a separately prepared cylindrical component onto the housing portion 41, or inserting a cylindrical component and integrally forming it with the housing portion by insert blow molding. It should be noted that when using these cylindrical components, in addition to the form of sealing by installing a rubber plug 22a on the cylindrical component, the following form can also be adopted: after the rubber plug is filled into the cylindrical component, the edge of the rubber plug is pressed with an annular cap component, and the cap component and the cylindrical component are welded together by ultrasonic welding or the like to achieve a seal.

[0090] The container of the present invention can be Figure 4 Example of a medical container 20. (e.g.) Figure 4 As shown in (A), the medical container 20 has a housing portion 21 formed by hot plate forming (vacuum forming, air forming, etc.) and a port portion 22 formed by a cylindrical component that can be sealed by a heat-sealing rubber plug 22a.

[0091] The housing section 21 of the medical container 20 is formed in the following manner: Figure 5 As shown, the multilayer bodies 1 and 2 of the present invention are hot-plate molded to obtain a film-molded article 24 with recesses. Two of these film-molded articles 24 are overlapped with their recesses facing each other. While the cylindrical component is placed at a predetermined position, the edge portion 23 is heat-sealed. The formation of the housing portion 21 and the port portion 22 can also be performed in other processes.

[0092] As for the material of the cylindrical component forming the port portion 22, it is acceptable as long as it can be heat-sealed with the housing portion 21 to seal the liquid. From the viewpoint of good heat-sealing performance with the housing portion 21, a cyclic polyolefin that is the same as the innermost layer 3 of the multilayer bodies 1 and 2 is preferred. Alternatively, a multilayer material in which a heat-sealable resin is used as the heat-sealing surface of the cylindrical component may also be used.

[0093] In the medical container 20, instead of the cylindrical component and the rubber plug 22a forming the port portion 22, as shown in the example... Figure 4 As shown in (B), after the rubber plug 22b is filled into the cylindrical component, the edge of the rubber plug 22b is pressed by the annular cover component 22c, and the cover component 22c and the cylindrical component are welded together by ultrasonic welding, etc.

[0094] The container of the present invention can be Figure 6 The medical container 30 is an example. The medical container 30 is a membrane bag type container having a bag-shaped storage portion 31 formed by membrane-like multilayer bodies 1 and 2, and a port portion 32 formed by a cylindrical member. In this example, the port portion 32 is closed by the cylindrical member, a rubber plug 32a that can be punctured by an injection needle, and an annular cap member 32b that presses against the edge of the rubber plug 32a.

[0095] The medical container 30 can be manufactured by the following method: using a multi-layered body 1, 2 formed into a cylindrical shape by a multi-layered blow molding method, heat-sealing both ends to form a housing portion 31, and simultaneously heat-sealing a cylindrical component at a predetermined position at one end to serve as a port portion 32, and forming a hanging portion at the other end as needed. The heat sealing of both ends and the heat sealing of the cylindrical component can be performed simultaneously or in other processes. Alternatively, instead of using the cylindrical multi-layered body 1, 2, two multi-layered bodies 1, 2 manufactured by a multi-layered T-die extrusion molding method can be used, overlapped, and the edges heat-sealed to form the housing portion 31.

[0096] It should be noted that, in the case of membrane bag type containers, a tube can be used instead of port 32 to make a container with a tube.

[0097] The container is not limited to having a single holding section 11, 21, or 31. For example, it can also be a multi-chamber container where the holding section is divided into multiple compartments using a connectable diaphragm sealing section, each capable of holding various contents. Specifically, such as... Figure 7 As shown, a multi-chamber medical container 40 can be constructed by dividing the housing 41 into multiple compartments using a connectable diaphragm sealing section 42, each compartment capable of holding a variety of different medications.

[0098] In the multi-chamber medical container 40, a diaphragm sealing portion 42 is provided along the width direction of the bag-shaped storage portion 41, which is divided into a first storage portion 41a and a second storage portion 41b. When using the multi-chamber medical container 40, the user peels off the diaphragm sealing portion 42 by pressing the first storage portion 41a or the second storage portion 41b from the outside, mixing the medication in the first storage portion 41a and the medication in the second storage portion 41b.

[0099] There is no particular limitation on the method of forming the diaphragm seal 42. For example, the diaphragm seal 42 can be formed by known sealing methods such as heat sealing or pulse sealing, or by providing a structure for forming the diaphragm seal 42 in the mold used in blow molding.

[0100] Example

[0101] The present invention will be specifically described below through examples, but the present invention is not limited to the following description.

[0102] [Abbreviation for materials]

[0103] The abbreviations for the materials used in this embodiment are shown below. It should be noted that "MFR" in the following description refers to the melt flow rate measured under a load of 21.18 N.

[0104] COP1: Cyclic polyolefin (product name "Zeonex 690R", manufactured by Nippon Zeon Co., Ltd., MFR (280℃): 17g / 10min, Tg: 136℃, density: 1.010g / cm³) 3 )

[0105] COP2: Cyclic polyolefin (product name "Zeonor 1020R", manufactured by Nippon Zeon Co., Ltd., MFR (280℃): 20g / 10min, Tg: 102℃, density: 1.010g / cm³) 3 )

[0106] S-LL-1: Single-active-center LLDPE (product name "Harmorex NM325N", manufactured by Japan Polyethylene Corporation, MFR (190℃): 0.9 g / 10 min, density: 0.908 g / cm³) 3 )

[0107] S-LL-2: Single-active-center LLDPE (product name "Umerit 125FN", manufactured by Ube-Maruzen Polyethylene Co., Ltd., MFR (190℃): 2.2 g / 10 min, density: 0.924 g / cm³) 3 )

[0108] S-LL-3: Single-active-center LLDPE (product name "Umerit 0520F", manufactured by Ube-Maruzen Polyethylene Co., Ltd., MFR (190℃): 2.0 g / 10 min, density: 0.904 g / cm³) 3 )

[0109] HD-1: HDPE (product name "Novatec HM4503", manufactured by Japan Polyethylene Corporation, MFR (190℃): 1.9g / 10min, density: 0.962g / cm³) 3 )

[0110] Z-LL-1: LLDPE manufactured using a Ziegler-based catalyst (product name "Novatec UF332", manufactured by Japan Polyethylene Corporation, MFR (190℃): 1.0 g / 10 min, density: 0.923 g / cm³). 3 )

[0111] Z-LL-2: LLDPE manufactured using a Ziegler-based catalyst (product name "Moretech 3500Z", manufactured by PrimePolymer Co., Ltd., MFR (190℃): 2.0 g / 10 min, density: 0.923 g / cm³). 3 )

[0112] S-PP: Single-active-center random PP (product name "Wintec WF4TA", manufactured by Japan Polypropylene Corporation, MFR (230℃): 7.0g / 10min, density: 0.900g / cm³). 3 )

[0113] F-PP: Soft PP (product name "Zelas MC617", manufactured by Mitsubishi Chemical Corporation, MFR (230℃): 1.5g / 10 minutes, density: 0.890g / cm³) 3 (Contains blends of olefin-based elastomers and styrene-based elastomers)

[0114] n-PP: PP produced using a Ziegler-based catalyst (product name "Excellen FH3471M", manufactured by Sumitomo Chemical Co., Ltd., MFR (230℃): 2.5 g / 10 min, density: 0.898 g / cm³). 3 )

[0115] LD-1: LDPE (product name "Novatec LM360", manufactured by Japan Polyethylene Corporation, MFR (190℃): 0.9g / 10min, density: 0.928g / cm³) 3 )

[0116] [Example 1]

[0117] Make a container filled with 100 mL of water as follows.

[0118] First, using a multi-layer blow molding machine, the housing parts 11, 21, 31 and the port parts 12, 22, 32 are integrally molded. These housing parts are formed from a three-layer blow-molded body (multi-layer body 1) consisting of an innermost layer 3 (30 μm thick), an intermediate layer 4 (250 μm thick), and an outer layer 5 (20 μm thick), stacked sequentially. The innermost layer 3 uses a mixture of cyclic polyolefins, formed by blending COP1 and COP2 in a 1:1 mass ratio. Only one Tg was observed for this mixed cyclic polyolefin, at 119°C. The intermediate layer 4 uses a mixture of S-LL-1 and HD-1 in an 8:2 mass ratio. The outer layer 5 uses S-PP.

[0119] Next, 100 mL of water is filled into the receiving parts 11, 21, and 31 through the port portions 12, 22, and 32. Then, the rubber plug body is ultrasonically welded to the port portion to seal the container. As the rubber plug body, an assembled rubber plug body is formed by inserting a rubber plug made of chlorinated butyl rubber into the annular outer peripheral part molded using COP1 by injection molding.

[0120] For sealed containers, autoclave them at 123°C for 15 minutes.

[0121] [Example 2]

[0122] The outer layer 5 uses F-PP, and otherwise the container is obtained by operating in the same manner as in Example 1.

[0123] [Example 3]

[0124] The innermost layer 3 uses only COP1, otherwise the container is obtained by operating in the same manner as in Example 2.

[0125] [Example 4]

[0126] The intermediate layer 4 uses only S-LL-2 and serves as the outer periphery of the rubber plug. The part is obtained by injection molding using S-LL-2 used in the intermediate layer 4. Otherwise, the container is obtained by the same operation as in Example 2.

[0127] [Example 5]

[0128] The intermediate layer 4 uses a mixture of S-LL-3 and HD-1 blended in a mass ratio of 8:2, and as the outer periphery of the rubber plug, it uses a component obtained by injection molding with COP1. Otherwise, the container is obtained in the same manner as in Example 1.

[0129] [Example 6]

[0130] Make a container filled with 100 mL of water as follows.

[0131] First, a blown film (multilayer body 1) consisting of three layers—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—was manufactured by using a water-cooled multilayer blown film forming machine. The composition of each layer was set to be the same as in Example 1.

[0132] Next, the two ends of the inflated film are heat-sealed to form a bag shape, and one end is heat-sealed as a cylindrical component of the injection-molded COP1. Port portions 12, 22, and 32 are formed on the bag-shaped receiving portion. Then, 100 mL of water is filled into the receiving portion through port portions 12, 22, and 32, and the rubber plug is ultrasonically welded to port portions 12, 22, and 32 to seal the container. As the rubber plug, an assembled rubber plug is formed by inserting a rubber plug made of chlorinated butyl rubber into the annular outer periphery molded using the injection molding method of COP1.

[0133] For sealed containers, autoclave them at 123°C for 15 minutes.

[0134] [Example 7]

[0135] The outer layer 5 uses F-PP, otherwise the container is obtained in the same manner as in Example 6.

[0136] [Example 8]

[0137] The innermost layer 3 uses only COP1, otherwise the container is obtained by operating in the same manner as in Example 7.

[0138] [Example 9]

[0139] The intermediate layer 4 uses only S-LL-2, and otherwise operates in the same manner as in Example 7 to obtain the container.

[0140] [Example 10]

[0141] The intermediate layer 4 uses a mixture of S-LL-3 and HD-1 blended at a mass ratio of 8:2. Otherwise, the container is obtained in the same manner as in Example 6.

[0142] [Example 11]

[0143] Make a container filled with 100 mL of water as follows.

[0144] First, a blown film (multilayer 2) consisting of four layers—an innermost layer 3 with a thickness of 10 μm, an intermediate layer 4 with a thickness of 220 μm, an outermost layer 5 with a thickness of 20 μm, and an outermost layer 6 with a thickness of 20 μm—was manufactured using a multilayer blown film forming machine. The innermost layer 3 used a mixture of cyclic polyolefins, namely COP1 and COP2, in a 1:1 mass ratio. Only one Tg was observed for this mixed cyclic polyolefin, at 119 °C. The intermediate layer 4 used a mixture of S-LL-1 and HD-1 in an 8:2 mass ratio. The outermost layer 5 used S-PP. The outermost layer 6 used n-PP.

[0145] Next, using the inflated membrane, a container was obtained by the same procedure as in Example 6. For the sealed container, it was autoclaved at 123°C for 15 minutes.

[0146] [Example 12]

[0147] The outer layer 5 uses F-PP, and otherwise the container is obtained by operating in the same manner as in Example 11.

[0148] [Comparative Example 1]

[0149] The intermediate layer 4 uses only Z-LL-1, and otherwise operates in the same manner as in Example 1 to obtain the container.

[0150] [Comparative Example 2]

[0151] The intermediate layer 4 uses only Z-LL-2, and otherwise operates in the same manner as in Example 1 to obtain the container.

[0152] [Comparative Example 3]

[0153] The intermediate layer 4 uses only Z-LL-2, and otherwise operates in the same manner as in Example 2 to obtain the container.

[0154] [Comparative Example 4]

[0155] The outer layer 5 uses HD-1, and otherwise the container is obtained by operating in the same manner as in Example 1.

[0156] [Comparative Example 5]

[0157] The outer layer 5 uses a mixture of HD-1 and LD-1 blended in a mass ratio of 3:7. Otherwise, the container is obtained by operating in the same manner as in Example 1.

[0158] [Comparative Example 6]

[0159] The intermediate layer 4 uses only Z-LL-1, and otherwise operates in the same manner as in Example 6 to obtain the container.

[0160] [Comparative Example 7]

[0161] The intermediate layer 4 uses only Z-LL-2, and otherwise operates in the same manner as in Example 6 to obtain the container.

[0162] [Comparative Example 8]

[0163] The intermediate layer 4 uses only Z-LL-2, and otherwise operates in the same manner as in Example 7 to obtain the container.

[0164] [Comparative Example 9]

[0165] The outer layer 5 uses HD-1, and otherwise the container is obtained by operating in the same manner as in Example 6.

[0166] [Comparative Example 10]

[0167] The outer layer 5 uses a mixture of HD-1 and LD-1 blended at a mass ratio of 3:7. Otherwise, the container is obtained by operating in the same manner as in Example 6.

[0168] [Comparative Example 11]

[0169] The outer layer 5 uses n-PP, and otherwise the container is obtained by operating in the same manner as in Example 9.

[0170] The composition (mass ratio) of each layer, rubber plug, and port portion of multilayer body 1 in Examples 1 to 10 and Comparative Examples 1 to 11 is shown in Tables 1 and 2. The composition (mass ratio) of each layer, rubber plug, and port portion of multilayer body 2 in Examples 11 and 12 is shown in Table 3. It should be noted that in Tables 1 to 3, "10" indicating composition (mass ratio) means that only this component is used in each layer, rubber plug, or port portion of multilayer body 1 and 2. That is, "10" indicating composition (mass ratio) means that only the component corresponding to the position of composition (mass ratio) recorded as "10" in each layer, rubber plug, or port portion of multilayer body 1 and 2 is used.

[0171] It should be noted that in the examples and comparative examples, the evaluation of adhesion resistance was only carried out in the cases where the housing parts 11, 21, 31, and 41 were formed by film molding, and no evaluation was carried out in the cases where the housing parts 11, 21, 31, and 41 were formed by multilayer blow molding in the same manner as in Example 1.

[0172] [Table 1]

[0173]

[0174] [Table 2]

[0175]

[0176] [Table 3]

[0177]

[0178] [Evaluation Method]

[0179] The containers obtained in each example were evaluated as follows.

[0180] (1) Molding stability

[0181] In blow molding, the shape stability of the preform during molding and the thickness unevenness after molding were evaluated according to the following criteria.

[0182] A: The preform shape is stable. No extremely thin areas were observed in the blow-molded containers.

[0183] B: The shape of the preform is generally stable. Areas with slightly thinner thickness can be observed in containers produced by blow molding.

[0184] C: The preform shape is unstable and pull-down occurs. Extremely thin areas can be observed in blow-molded containers.

[0185] In water-cooled blown film forming, the shape stability of the tubular film (bubble) during forming and the formation of wrinkles in the formed film were evaluated according to the following criteria.

[0186] A: The pipe shape is fixed and stable. The pipe diameter is fixed.

[0187] B: The tube shape is roughly stable. The tube diameter is roughly fixed. Some wrinkles can be observed on the membrane.

[0188] C: The tube shape is unstable. The tube diameter is uneven. Wrinkles can be observed on the membrane.

[0189] (2) Resistance to adhesion

[0190] Two test pieces, each 10cm x 10cm, cut from the containers in each example, are overlapped with their outer layers in contact with each other, and a 98N / 100cm pressure is applied to them. 2 The load was applied and maintained at 60°C for 24 hours. Afterwards, the samples were allowed to cool naturally to room temperature and the load was removed, then two test pieces were peeled off. The peeling condition at this point was evaluated according to the following two levels.

[0191] A: Easy to peel off.

[0192] C: There is resistance during peeling.

[0193] (3) Adhesion to sterilization trays

[0194] For each container, an autoclave was used, with the temperature inside the sterilization chamber set to 123°C and the sterilization time set to 15 minutes. The containers were placed on a perforated metal tray (sterilization tray) with round holes for autoclaving. The following criteria were used to evaluate whether the autoclaved containers adhered to the perforated metal tray of the sterilizer. It should be noted that the perforated metal tray was made of stainless steel.

[0195] A: There is absolutely no adhesive.

[0196] B: Slightly adhesive, but easy to peel off.

[0197] C: Adhesion occurs, and there is resistance when peeling.

[0198] (4) Heat resistance

[0199] The appearance of the containers after high-pressure steam sterilization was confirmed by visual inspection, and the following criteria were used for evaluation.

[0200] A: It did not deform or shrink after sterilization.

[0201] B: Fine cracks or wrinkles can be observed on the surface in some areas, and there is some shrinkage.

[0202] C: Significant deformation or shrinkage, with clearly visible round, perforated tray marks.

[0203] (5) Peel strength

[0204] Strips with a width of 15 mm were cut from the containers before and after autoclaving. The T-peel strength between the middle and outer layers, based on JIS K6854-3, was determined at a tensile speed of 300 mm / min. The test was conducted using a tensile testing machine.

[0205] (6) Transparency

[0206] Based on JIS K 7136, the turbidity after the above-mentioned high-pressure steam sterilization was measured.

[0207] The evaluation results for each case are shown in Table 4.

[0208] [Table 4]

[0209]

[0210] As shown in Table 4, Examples 1 to 12, which use multilayer bodies 1 and 2 comprising an innermost layer 3 formed of cyclic polyolefin, an intermediate layer 4 mainly composed of mono-active-center LLDPE, and an outer layer 5 formed of either mono-active-center random PP or flexible PP, exhibit excellent heat resistance. Even after sterilization, adverse conditions such as reduced peel strength, adhesion to sterilization trays, wrinkling, or deformation are suppressed. Furthermore, Examples 1 to 12 also demonstrate excellent molding stability and anti-blocking properties, ensuring sufficient transparency even after sterilization.

[0211] On the other hand, in Comparative Examples 1 to 3, 6 to 8, where the intermediate layer 4 did not use LLDPE with a single active center system, the peel strength between the intermediate layer 4 and the outer layer 5 was low, and the peel strength further decreased after sterilization treatment. In Comparative Examples 4, 5, 9 and 10, where the outer layer 5 did not use random PP or flexible PP with a single active center system, but instead used HDPE or LDPE, adhesion to the sterilization tray was not sufficiently suppressed. In Comparative Example 11, where the outer layer 5 did not use random PP or flexible PP with a single active center system, but instead used PP manufactured using a Ziegler-based catalyst, the peel strength between the intermediate layer 4 and the outer layer 5 was low, and the peel strength further decreased after sterilization treatment.

[0212] Comparing Example 1 with Comparative Examples 1 and 2, it was confirmed that when the intermediate layer 4 used LLDPE manufactured using a Ziegler-based catalyst, the adhesion strength (peel strength) between the intermediate layer 4 and the outer layer 5 was increased, and improved to the point that sufficient peel strength was maintained even after sterilization. The same situation was confirmed in the comparison between Examples 2 and 4 and Comparative Example 3.

[0213] Comparing Examples 1 to 3 with Comparative Examples 4 and 5, it was confirmed that adhesion to the sterilization tray was significantly reduced when the outer layer 5 was made of single-active-center random PP or flexible PP, compared to cases where HDPE or LDPE was used. The same finding was confirmed in comparisons between Examples 6 to 10 and Comparative Examples 6 to 10.

[0214] Industrial availability

[0215] According to the present invention, a multilayer body for containers with excellent heat resistance and the ability to suppress adverse conditions during sterilization can be provided, as well as containers using the above-mentioned multilayer body for containers, particularly medical containers and medical containers containing pharmaceuticals.

[0216] Symbol Explanation

[0217] 1, 2 Containers use multi-layer bodies

[0218] 3 Innermost layer

[0219] 4. Intermediate layer

[0220] 5 Outer layer

[0221] 6 Outermost layer

[0222] 10, 20, 30 medical containers

[0223] 11, 21, 31 Packing Section

[0224] Ports 12, 22, and 32

[0225] 40+ chamber medical containers

[0226] 41. Storage Section

[0227] 42 Diaphragm Seal

Claims

1. A multilayer body for a container, characterized in that, Includes only: The innermost layer formed of cyclic polyolefins; An intermediate layer formed in a manner adjacent to the innermost layer, primarily composed of linear low-density polyethylene manufactured using a single-active-center catalyst. and The outer layer is formed from either atactic polypropylene manufactured using a single-active-center catalyst or polypropylene containing an elastomer. The intermediate layer comprises only the linear low-density polyethylene and high-density polyethylene, which contains less than 30% by mass relative to the total mass of the intermediate layer and has a higher density than the linear low-density polyethylene.

2. The multilayer body for a container according to claim 1, wherein, The outermost layer is formed of polypropylene.

3. The multilayer body for a container according to claim 1 or 2, wherein, The cyclic polyolefin is a hydride of a ring-opening polymer of a cyclic olefin monomer.

4. The multilayer body for a container according to claim 1 or 2, wherein, The elastomer is an olefin-based elastomer and / or a styrene-based elastomer.

5. The multilayer body for a container according to claim 3, wherein, The elastomer is an olefin-based elastomer and / or a styrene-based elastomer.

6. A container having a holding portion for holding contents, characterized in that, At least the loading section is composed of a multi-layered container body according to any one of claims 1 to 5.

7. A medical container, comprising a receiving portion for receiving liquid medicine, characterized in that, At least the loading section is composed of a multi-layered container body according to any one of claims 1 to 5.

8. A medical container for containing pharmaceutical agents, characterized in that, The medical container of claim 7 contains a pharmaceutical agent.

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