JP7764789B2 - Method for manufacturing a multi-chamber container - Google Patents

Description

The present invention relates to a method for manufacturing a multi-chamber container using a specific resin and through a specific process.

In medical practice, it is common to administer a mixture of multiple pharmaceutical ingredients at the time of treatment. Various methods are used depending on the combination of pharmaceutical ingredients to be mixed, and in some cases, the ingredients are mixed just before administration to prevent denaturation.
When combining a liquid infusion with a solid drug, the liquid medicine is prepared by preparing the liquid infusion and the solid drug in separate containers such as vials, mixing and melting them in a sterile environment using a syringe or the like to make a mixed liquid, and then returning the mixture to the vial or soft bag.
However, these methods are time-consuming and involve the step of removing a portion of the infusion solution, which can lead to contact with contaminated atmospheres or equipment, posing the risk of bacterial contamination or foreign matter contamination.

In order to solve these problems, a multi-chamber container having a partition formed inside has been proposed.
A multi-chamber container is a container with a partition formed inside, and is made by making a bag from a resin film or sheet by heat sealing.
However, when attaching a drug solution discharge port and a drug solution mixing port to the bag-shaped container and when filling the formed multiple chambers with drug solution, it is necessary to peel off the film in the non-welded area to open the areas corresponding to the port attachment area and drug solution filling area. In particular, when filling a solid drug after filling it with an infusion solution and sterilizing it, blocking of the film in the non-welded area can occur, making it impossible to fill the solid drug. In the case of a multiple-chamber container such as the one described above, it is necessary to prevent film blocking from occurring during sterilization.
As a method for suppressing blocking, embossing methods are known, as disclosed in JP 2008-125836 A (Patent Document 1) and JP 6-178804 A (Patent Document 2). However, the embossing method requires an embossing step during or after film formation, and the additional steps result in a decrease in productivity.
Another method for suppressing blocking during sterilization is a method described in Japanese Patent Laid-Open No. 8-215285 (Patent Document 3), in which two bags are produced and then fused together in a post-process while creating fluid communication between the bags. However, this method requires an additional process and reduces productivity.
Furthermore, Japanese Patent Laid-Open Publication No. 2007-222292 (Patent Document 4) describes a method of suppressing blocking by using a mixture of two or more specific polyethylene resins obtained by polymerization with a single-site catalyst in a sealing layer. However, this method only claims to suppress blocking when the amount of liquid is small, and furthermore, the sterilization temperature is only a low temperature of 105°C.

Japanese Patent Application Laid-Open No. 2008-125836 Japanese Patent Application Publication No. 6-178804 Japanese Patent Application Publication No. 8-215285 Japanese Patent Application Laid-Open No. 2007-222292

Under these circumstances, an object of the present invention is to provide a method for producing a multi-chamber container, such as an infusion bag, which is sterilized at a temperature of 110°C or higher, having a heat seal layer that has an inner surface fusion strength of 0.3 N/15 mm or less even when sterilized with the films in contact with each other without placing anything inside the chambers, and that is capable of forming a strong seal of 30 N/15 mm width at a practical heat seal temperature of 160°C or less.
Another object of the present invention is to provide a multi-chamber container obtained by the above production method, and a resin composition used in the heat seal layer.

In order to solve the above problems, the inventors discovered a heat-sealing resin composition that combines a low-melting point polypropylene resin and a high-melting point polypropylene resin in a specific range as the propylene resin used in the sealant layer (heat seal layer), and further adds a specific polyethylene and a specific elastomer component to these polypropylene resins.This composition prevents inner fusion of more than 0.3 N/15 mm even when sterilized in an empty chamber with the films in contact with each other, and also enables the formation of strong seals of up to 30 N/15 mm wide at a practical heat-sealing temperature of 160°C or less, leading to the completion of the present invention.

That is, according to the first aspect of the present invention, there is provided a method for producing a multi-chamber container including a layer made of a resin composition containing 30 to 95 parts by weight of the following polypropylene-based resin (A) component, 5 to 70 parts by weight of the following polypropylene-based resin (B) component, and 5 to 60 parts by weight of the following polyethylene-based resin (C) component and 5 to 50 parts by weight of the elastomer (D) component per 100 parts by weight of the total of the polypropylene-based resin (A) component and the polypropylene-based resin (B) component, the method comprising producing the multi-chamber container via the following steps (i) to (ii):
Component (A): A polypropylene resin that satisfies the following requirements (A-1) and (A-2).
(A-1) The melt flow rate (JIS K7210, temperature 230°C, 2.16 kg load) is 0.5 g/10 min or more and 30 g/10 min or less.
(A-2) The melting peak temperature as measured by DSC is 110°C or higher and lower than 145°C.
Component (B): Polypropylene resin (B-1) that satisfies the following requirements (B-1) and (B-2): The melt flow rate (230°C, 2.16 kg load) is 0.5 g/10 min or more and 100 g/30 min or less.
(B-2) The melting peak temperature measured by DSC is 145°C or higher.
Component (C): A polyethylene resin that satisfies the following requirement (C-1): (C-1) The melt flow rate (190°C, 2.16 kg load) is 0.01 g/10 min or more and 50 g/10 min or less.
Step (i): A step of heat-sterilizing the layers in contact with each other in at least one chamber of the multi-chamber container at a temperature of 110°C or higher.
Step (ii): A step of opening the chamber that has been sterilized in a state where the layers are in contact with each other during the heat sterilization in step (i), adding a drug, and then sealing it to create a chamber again.

According to a second aspect of the present invention, there is provided a method for producing a multi-chamber container comprising a layer made of a resin composition containing 30 to 95 parts by weight of the following polypropylene-based resin (A) component, 5 to 70 parts by weight of the following polypropylene-based resin (B) component, and 5 to 50 parts by weight of the following polyethylene-based resin (C) component and 5 to 50 parts by weight of the following elastomer (D) component per 100 parts by weight of the total of the polypropylene-based resins (A) and (B), the method comprising the steps of (i) and (ii) below:
Component (A): A polypropylene resin that satisfies the following requirements (A-1) and (A-2).
(A-1) The melt flow rate (JIS K7210, temperature 230°C, 2.16 kg load) is 0.5 g/10 min or more and 30 g/10 min or less.
(A-2) The melting peak temperature as measured by DSC is 110°C or higher and lower than 145°C.
Component (B): Polypropylene resin (B-1) that satisfies the following requirements (B-1) and (B-2): The melt flow rate (230°C, 2.16 kg load) is 0.5 g/10 min or more and 100 g/10 min or less.
(B-2) The melting peak temperature measured by DSC is 145°C or higher.
Component (C): A polyethylene resin that satisfies the following requirement (C-1): (C-1) The melt flow rate (190°C, 2.16 kg load) is 0.01 g/10 min or more and 50 g/10 min or less.
Step (i): A step of heat-sterilizing the layers in contact with each other in at least one chamber of the multi-chamber container at a temperature of 110°C or higher.
Step (ii): A step of opening the chamber sterilized in the heat sterilization step (i) with the layers still in contact with each other, adding a drug, and then sealing the chamber again to create a new chamber.

The third aspect of the present invention provides a method for producing a multi-chamber container according to the first or second aspect, wherein the polypropylene resin (A) is a polypropylene resin polymerized using a metallocene catalyst.

The fourth aspect of the present invention provides a method for producing a multi-chamber container according to the first or second aspect, wherein the elastomer (D) is one or more selected from the group consisting of ethylene-α-olefin copolymers, propylene-α-olefin copolymers, and styrene-based elastomers.

Furthermore, according to the fifth aspect of the present invention, there is provided a multi-chamber container manufactured by the manufacturing method of the first or second aspect of the present invention.

Furthermore, according to a sixth aspect of the present invention, there is provided a resin composition as described in the first aspect, which is used in a multi-chamber container manufactured by the manufacturing method of the first aspect.

Furthermore, according to the seventh aspect of the present invention, there is provided a resin composition according to the second aspect, which is used in a multi-chamber container manufactured by the manufacturing method of the first or second aspect.

Furthermore, according to the eighth aspect of the present invention, there is provided a method of using the multi-chamber container described in the fifth aspect, in which the chemical placed in step (ii) of the first or second aspect is mixed with the chemical in the other chamber.

The manufacturing method of the present invention makes it possible to provide multi-chamber containers, such as infusion bags, that are sterilized at temperatures of 110°C or higher. Even when sterilized with the films in contact with each other without any contents in the chambers, the multi-chamber containers have a heat seal layer that prevents inner fusion of more than 0.3 N/15 mm width, and can form strong seals of 30 N/15 mm width at practical heat seal temperatures of 160°C or less.

[Resin composition]
The resin composition used as the heat-sealable layer of the multi-chamber container in the method for producing a multi-chamber container of the present invention contains 30 to 95 parts by weight of a polypropylene resin (A) component, 5 to 70 parts by weight of a polypropylene resin (B) component, 5 to 60 parts by weight of a polyethylene resin (C) component, and 5 to 50 parts by weight of an elastomer (D) component per 100 parts by weight of the total of the polypropylene resins (A) and (B) components (hereinafter, this resin composition will also be referred to as the "resin composition of the present invention" or the "heat-sealable resin composition of the present invention"). Details of the polypropylene resin (A), the polypropylene resin (B), the polyethylene resin (C), and the elastomer (D) component will be described later.

(1) Polypropylene Resin (A)
The polypropylene resin (A) is composed of one or more polypropylene polymers. When it is composed of two or more components, the mixture of the two or more components may satisfy the following requirements (A-1) to (A-2).

The polypropylene-based resin (A) is selected from one or more types of propylene homopolymers and copolymers of propylene and an α-olefin having 2 to 12 carbon atoms (excluding 3 carbon atoms), and is preferably a propylene-ethylene copolymer or a propylene-ethylene-1-butene copolymer.

The polypropylene resin (A) can be appropriately selected from commercially available propylene homopolymers and propylene-α-olefin copolymers. Specific examples include products manufactured by Japan Polypropylene Corporation under the trade names "Novatec PP," "Wintec," and "Wellnex."

The catalyst used to produce polypropylene-based resin (A) is not particularly limited, but polypropylene-based resin (A) polymerized using a metallocene catalyst is preferred.

It is known that the structural characteristics of ethylene polymers and propylene polymers, such as molecular weight, molecular weight distribution, and branching structure, can be controlled by selecting the catalyst, and those skilled in the art can distinguish between types of polymers based on the type of catalyst. For example, ethylene polymers and propylene polymers polymerized using a metallocene catalyst are sometimes referred to as metallocene-based ethylene polymers and metallocene-based propylene polymers, while ethylene polymers and propylene polymers polymerized using a catalyst other than a metallocene catalyst are sometimes referred to as non-metallocene-based ethylene polymers and non-metallocene-based propylene polymers.

(A-1) Melt flow rate (230°C, 2.16 kg load)
The melt flow rate (230°C, 2.16 kg load) of the polypropylene resin (A) is 0.5 g/10 min or more and 30 g/10 min or less, preferably 0.5 to 25 g/10 min, more preferably 0.5 to 15 g/10 min, and particularly preferably 1.0 to 15 g/10 min. If the melt flow rate is 0.5 g/10 min or more, the load during molding of the heat-sealable film does not increase, and molding of the laminate itself becomes easy. If it is 30 g/10 min or less, molding stability during molding of the heat-sealable film is good.

(A-2) Melting Peak Temperature by Differential Scanning Calorimetry (DSC) The melting peak temperature (by DSC) of the polypropylene resin (A) is 110°C or higher but lower than 145°C, preferably 115°C or higher but lower than 145°C, more preferably 120°C or higher but lower than 140°C, and particularly preferably 125°C or higher but lower than 140°C. The melting peak temperature is sometimes referred to as the melting point. If the melting peak temperature is 110°C or higher, the heat-sealable film obtained by combining it with the polypropylene resin (B) is less likely to undergo unintended fusion between unheat-sealed portions of the film during sterilization at a high temperature, for example, 121°C for 30 minutes. Furthermore, if the melting peak temperature is lower than 145°C, it is easier to achieve a wide heat-sealing temperature range in which the heat-sealing strength is 2.9 to 9.8 N/15 mm width by combining it with the polypropylene resin (B).

(2) Polypropylene resin (B)
The polypropylene resin (B) is composed of one or more types of propylene polymers. When the polypropylene resin (B) is composed of two or more components, the mixture of the two or more components may satisfy the following requirements (B-1) to (B-2).

The polypropylene-based resin (B) is selected from one or more types of propylene homopolymers and copolymers of propylene and α-olefins having 2 to 12 carbon atoms (excluding 3 carbon atoms), and is preferably a propylene homopolymer.
The polypropylene resin (B) can be appropriately selected from commercially available propylene homopolymers and propylene-α-olefin copolymers, specifically, those under the trade names "Novatec PP" and "Wintec" manufactured by Japan Polypropylene Corporation.

(B-1) Melt flow rate (230°C, 2.16 kg load)
The melt flow rate (230°C, 2.16 kg load) of the polypropylene resin (B) is 0.5 g/10 min or more and 100 g/10 min or less, preferably 0.5 to 20 g/10 min, more preferably 0.5 to 15 g/10 min, and particularly preferably 1.0 to 15 g/10 min. If the melt flow rate is 0.5 g/10 min or more, the load during molding of the heat-sealable film does not increase, and molding of the film itself becomes easy. If it is 100 g/10 min or less, molding stability during molding of the heat-sealable film is good.

(B-2) Melting Peak Temperature by Differential Scanning Calorimetry (DSC) The melting peak temperature (by DSC) of the polypropylene resin (B) is 145°C or higher, preferably 150°C or higher, more preferably 155°C or higher, and particularly preferably 160°C or higher. If the melting peak temperature is 145°C or higher, it is easy to widen the heat sealing temperature range in which the heat seal strength of the heat-sealable film obtained by combining it with the polypropylene resin (A) is 10 to 15 N/15 mm width. The upper limit of the melting peak temperature of the polypropylene resin (B) is not particularly limited, but is preferably 170°C or lower, for example.

In the present invention, from the viewpoint of ensuring a wide sealing temperature range, the difference between the peak melting temperature of polypropylene-based resin (A) and the peak melting temperature of polypropylene-based resin (B) is preferably 5°C or more, more preferably 10°C or more, and particularly preferably 20°C or more.

(3) Polyethylene Resin (C)
The polyethylene resin (C) is composed of one or more types of ethylene polymers. When it is composed of two or more components, it is sufficient that the mixture of two or more components satisfies the following requirement (C-1).

(C-1) Melt flow rate (190°C, 2.16 kg load)
The melt flow rate of the polyethylene resin (C) (190°C, 2.16 kg load) is 0.01 g/10 min or more and 50 g/10 min or less, preferably 0.01 to 20 g/10 min, more preferably 0.1 to 20 g/10 min, and particularly preferably 0.1 to 10 g/10 min. If the melt flow rate is 0.01 g/10 min or more, fish eyes (FE) are unlikely to occur when mixed with the polypropylene resin (A) and the polypropylene resin (B). If the melt flow rate is 50 g/10 min or less, molding stability during molding of a heat-sealable film is good.

Furthermore, the density of the polyethylene resin (C) is not particularly limited, but is desirably 0.911 g/cm ^or more. If the density is 0.911 g/cm ^or more, unintended fusion of unheat-sealed portions of the films is unlikely to occur during sterilization treatment at a high temperature, for example, 121°C for 30 minutes. In general, the density of polyethylene polymers is 0.990 g/cm ^or less. The density is a value measured by Method D (density gradient tube method) according to JIS K7112.

The polyethylene used in polyethylene-based resin (C) is not particularly limited, but low-density polyethylene, linear low-density polyethylene, high-density polyethylene, or a combination thereof can be used.

(4) Elastomer (D)
The elastomer (D) is not particularly limited as long as it can impart impact resistance, but is preferably an ethylene-α-olefin copolymer, a propylene-α-olefin copolymer, a styrene-based elastomer, or a mixture of two or more of these.

Ethylene-α-olefin copolymers are copolymers obtained by copolymerizing the main component ethylene with an α-olefin preferably having 3 to 20 carbon atoms. Preferred examples of α-olefins include those having 3 to 20 carbon atoms, such as propylene, 1-butene, 1-pentene, 1-hexene, 1-octene, and 1-heptene.

Commercially available examples of ethylene-α-olefin copolymers include the "Kernel" series, a trademark of Japan Polyethylene Co., Ltd.; the "Tafmer A" series and "Tafmer MY" series, a trademark of Mitsui Chemicals, Inc.; the "Affinity" series and "Engage" series, a trademark of Dow; and the "Exact" series, a trademark of ExxonMobil.

The density of the ethylene-α-olefin copolymer is preferably 0.860 to 0.910 g/cm ³ , and more preferably 0.870 to 0.900 g/cm ³ .
The melt index (190° C., 2.16 kg load) of the ethylene-α-olefin copolymer is preferably 0.5 to 10 g/10 min.

Propylene-α-olefin copolymers are copolymers obtained by copolymerizing the main component propylene with an α-olefin preferably having 2 to 20 carbon atoms (excluding 3). Preferred examples of α-olefins include those having 2 to 20 carbon atoms (excluding 3), such as ethylene, 1-butene, 1-pentene, 1-hexene, 1-octene, and 1-heptene. While the melting point is not particularly specified, it is often below 110°C or not observable (meaning an amorphous polymer with no melting point).

Commercially available examples of propylene-α-olefin copolymers include the Vistamaxx series, a trademark of ExxonMobil Corporation.

The styrene-based elastomer may be appropriately selected from commercially available products. For example, hydrogenated styrene-butadiene block copolymers are sold by Kraton Polymer Japan Co., Ltd. under the trade name "Kraton G" and by Asahi Kasei Chemicals Corporation under the trade name "Tuftec," hydrogenated styrene-isoprene block copolymers are sold by Kuraray Co., Ltd. under the trade name "Septon," hydrogenated styrene-vinylated polyisoprene block copolymers are sold by Kuraray Co., Ltd. under the trade name "Hybler," and hydrogenated styrene-butadiene random copolymers are sold by JSR Corporation under the trade name "Dynalon." An appropriate product may be selected from these product groups and used.

(5) Formulation of Resin Composition of the Present Invention The resin composition of the present invention contains 30 to 95 parts by weight of a polypropylene-based resin (A) component, 5 to 70 parts by weight of a polypropylene-based resin (B) component, 5 to 60 parts by weight of a polyethylene-based resin (C) component, and 5 to 50 parts by weight of an elastomer (D) component per 100 parts by weight in total of the polypropylene-based resin (A) and the polypropylene-based resin (B).

The amount of polypropylene resin (A) component blended is 30 to 95 parts by weight, preferably 40 to 95 parts by weight, more preferably 45 to 90 parts by weight, and even more preferably 50 to 85 parts by weight, per 100 parts by weight of the total of polypropylene resin (A) component and polypropylene resin (B) component. The amount of polypropylene resin (B) component blended is 5 to 70 parts by weight, preferably 5 to 60 parts by weight, more preferably 10 to 55 parts by weight, and even more preferably 15 to 50 parts by weight.
When the blending amounts of the polypropylene-based resin (A) component and the polypropylene-based resin (B) component are within the above ranges, it is easy to achieve a wide heat-sealing temperature range in which the heat-seal strength of the resulting heat-sealable layer is 10 to 15 N/15 mm width. Furthermore, it is possible to prevent the temperature at which the heat-seal strength exceeds 29.4 N/15 mm width from becoming too high. Therefore, a strong seal can be formed at a practical heat-sealing temperature of 160°C or less.

The resin composition of the present invention also contains 5 to 60 parts by weight of a polyethylene resin (C) component and 5 to 50 parts by weight of an elastomer (D) component per 100 parts by weight of the total of the polypropylene resin (A) component and the polypropylene resin (B) component.

The polyethylene resin (C) is blended for the purpose of preventing blocking of the heat seal layer made of the heat-sealable resin composition of the present invention during heat sterilization. Blocking is prevented by roughening the film surface due to the presence of the polyethylene resin (C) in the polypropylene resins (A) and (B).
The blending amount of the polyethylene resin (C) component is 5 parts by weight or more and 60 parts by weight or less, preferably 5 parts by weight or more and 50 parts by weight or less, more preferably 5 parts by weight or more and 40 parts by weight or less, even more preferably 5 parts by weight or more and 30 parts by weight or less, particularly preferably 10 parts by weight or more and 30 parts by weight or less, and most preferably 10 parts by weight or more and 20 parts by weight or less, relative to 100 parts by weight of the total of the polypropylene resin (A) component and the polypropylene resin (B) component.
When the blending amount of the polyethylene resin (C) component is 50 parts by weight or less, the obtained heat seal layer is likely to form a strong seal. When the blending amount of the polyethylene resin (C) component is 5 parts by weight or more, the film surface is roughened, and unintended fusion of the unheat-sealed portions of the films constituting the multi-chamber container is unlikely to occur during sterilization treatment at a high temperature, for example, 121°C for 30 minutes.

The blending amount of the elastomer (D) component is 5 parts by weight or more and 50 parts by weight or less, preferably 5 parts by weight or more and 40 parts by weight or less, more preferably 5 parts by weight or more and 30 parts by weight or less, even more preferably 10 parts by weight or more and 30 parts by weight or less, and particularly preferably 10 parts by weight or more and 20 parts by weight or less, relative to 100 parts by weight of the total of the polypropylene-based resin (A) component and the polypropylene-based resin (B) component.
When the blending amount of the elastomer (D) component is 50 parts by weight or less, the obtained heat-sealable film tends to form a strong seal, and when the blending amount of the elastomer (D) is 5 parts by weight or more, the film is endowed with impact resistance.

[Method of producing resin composition]
The resin composition of the present invention can be obtained by mixing the polypropylene resin (A), the polypropylene resin (B), the polyethylene resin (C), and the elastomer (D) in a Henschel mixer (trade name), a V blender, a ribbon blender, a tumbler blender, or the like, followed by kneading with a kneader such as a single-screw extruder, a multi-screw extruder, a kneader, or a Banbury mixer. Alternatively, the polypropylene resin (A), the polypropylene resin (B), the polyethylene resin (C), and the elastomer (D) can be individually mixed in a Henschel mixer (trade name), a V blender, a ribbon blender, a tumbler blender, or the like, followed by kneading and pelletizing with a kneader such as a single-screw extruder, a multi-screw extruder, a kneader, or a Banbury mixer, followed by mixing the resulting mixture in a Henschel mixer (trade name), a V blender, a ribbon blender, a tumbler blender, or the like to obtain a pellet mixture. If other additives are used as optional components, they can be added when obtaining the pellet mixture. Alternatively, the mixture prepared using the Henschel mixer (trade name) can be used as a pellet mixture as is.

Additives such as antioxidants that can be added to polypropylene resins can be appropriately blended as long as they do not impair the effects of the present invention.
Specifically, 2,6-di-t-butyl-p-cresol (BHT), tetrakis[methylene-3-(3,5-di-t-butyl-4-hydroxyphenyl)propionate]methane (manufactured by BASF Japan Ltd. under the trade name "IRGANOX 1010"), and n-octadecyl-3-(4-hydroxy-3,5-di-t-butylphenyl)propionate (manufactured by BASF Japan Ltd. under the trade name "IRGANOX"1076"), phosphite stabilizers such as bis(2,4-di-t-butylphenyl)pentaerythritol diphosphite and tris(2,4-di-t-butylphenyl)phosphite, lubricants such as higher fatty acid amides, such as oleic acid amide and erucic acid amide, higher fatty acid esters, and silicone oils, antistatic agents such as glycerin partial esters of fatty acids having 8 to 22 carbon atoms, sorbitan acid esters, and polyethylene glycol esters, sorbitol nucleating agents (for example, "Gelall MD" manufactured by New Japan Chemical Co., Ltd.), aromatic phosphate esters (for example, "ADK STAB NA-21" and "ADK STAB NA-11" manufactured by ADEKA Corporation), and other additives. Nucleating agents such as those manufactured by Milliken Corporation under the trade name "Millad" series, Milliken Corporation under the trade name "Hyperform" series, New Japan Chemical Co., Ltd. under the trade name "Njestar NU-100", talc, and high-density polyethylene, antiblocking agents such as silica, calcium carbonate, and talc, molecular weight modifiers and crosslinking aids such as organic peroxides, neutralizing agents such as higher fatty acid metal salts such as calcium stearate and hydrotalcites, light stabilizers, ultraviolet absorbers, metal deactivators, peroxides, fillers, antibacterial and antifungal agents, antibacterial agents, bacteriostatic agents, fluorescent brighteners, antifogging agents, flame retardants, colorants, pigments, natural oils, synthetic oils, waxes, and organic or inorganic flame retardants may also be added in appropriate amounts depending on the application.

[film]
The resin composition of the present invention can be suitably used for heat-sealable films containing one or more heat-sealable layers of the resin composition, and can be suitably used for heat-sealable films that can form strong seal strength at 160°C or less, have a wide temperature range for forming weak seals, and have excellent blocking resistance.
The film of the present invention is a film consisting of one or more layers including at least a heat seal layer, and is characterized in that the heat seal layer is made of the above-mentioned heat-sealable resin composition of the present invention.

The film of the present invention may be a single-layer or multi-layer film, but a multi-layer film is preferred from the standpoint of ease of handling during heat sealing.

There are no particular restrictions on the thickness of the film of the present invention, but in the case of a single-layer film, a thickness of approximately 10 to 500 μm is suitable for use as a sealant. In the case of a multilayer film, the overall thickness of the multilayer film is approximately 10 to 500 μm, and the heat seal layer made of the heat-sealable resin composition of the present invention is preferably approximately 5 to 100 μm, preferably 10 to 60 μm, and more preferably approximately 20 to 50 μm.

Examples of multilayer films include two-layer films having a heat-sealing layer made from the heat-sealing resin composition of the present invention and an outer layer adjacent to it; three-layer films having a heat-sealing layer made from the heat-sealing resin composition of the present invention, an intermediate layer adjacent to it, and an outer layer further adjacent to the intermediate layer; and five-layer films having a heat-sealing layer made from the heat-sealing resin composition of the present invention, an adhesive layer adjacent to it, a gas barrier layer adjacent to the adhesive layer, an adhesive layer adjacent to the gas barrier layer, and an outer layer further adjacent to the adhesive layer. However, the film is not limited to these and can have any configuration as long as the heat-sealing resin composition of the present invention is used as the heat-sealing layer.
Examples of methods for producing the multilayer film include coextrusion, extrusion lamination, and dry lamination, with the coextrusion being preferred from the standpoint of economy.

For example, the gas barrier layer can be made of a mixture of polyolefin resin and ethylene-vinyl alcohol copolymer, or a composition of polyolefin resin blended with layered silicates such as montmorillonite or mica.

Adhesives that can be used to form the adhesive layer include polyurethane adhesives, vinyl acetate adhesives, hot melt adhesives, or adhesive resins such as maleic anhydride-modified polyolefins and ionomer resins. When an adhesive layer is included in the layer structure, the main layers, such as the inner layer, middle layer, and outer layer, can be laminated by co-extrusion with these adhesives.

The method for producing the film of the present invention is not particularly limited, and the film can be produced by a known method using the above resin composition, for example, by a known technique such as extrusion molding using a T-die or a circular die.
Among these, the water-cooled inflation molding method using a circular die is preferred from the viewpoint of transparency.

The film of the present invention contains a heat seal layer made of the heat-sealable resin composition of the present invention described above, so it can form a weak seal strength of 10 to 15 N/15 mm width over a wide temperature range, and can even form a strong seal strength of 30 N/15 mm width without using extremely harsh conditions. Furthermore, unintended fusion of films is unlikely to occur during heat treatment processes such as pasteurization and sterilization, making it ideal for multi-chamber packaging bags for heat treatment, particularly large multi-chamber bags for infusions.

[Multi-chamber container and its manufacturing method]
The method for producing a multi-chamber container of the present invention includes a step (step (i)) of heat-treating a multi-chamber container containing the resin composition of the present invention as one or more heat-sealable layers at a temperature of 110°C or higher in a state where the heat-sealable layers are in contact with each other for at least one chamber.
The heat treatment temperature is 110° C. or higher, preferably 115° C. or higher, and more preferably 121° C. or higher. If the heat treatment temperature is 110° C. or higher, a sterilization effect is exhibited during the heat treatment.
The method for producing a multi-chamber container of the present invention further includes a step (step (ii)) of opening the chamber that has been subjected to the heat treatment step, placing a drug therein, and then sealing the chamber again to form a new chamber.
In the method for producing a multi-chamber container of the present invention, a multi-chamber container is produced through the above steps (i) and (ii), and the multi-chamber container obtained by this production method is also referred to as the multi-chamber container of the present invention.

The multi-chamber container of the present invention can be used by mixing the chemical placed in step (ii) above with chemicals in other chambers.

The multi-chamber container of the present invention has at least one chamber (storage chamber) for storing a medicinal solution, and this storage chamber is made of the film of the present invention described above.

In the multi-chamber container of the present invention, after the drug is placed in the container in step (ii), when the container is sealed again to form the chambers, the easily peelable seal portion that separates the chambers is formed by fusing the heat seal layers of the film of the present invention together.
The seal strength of the easily peelable seal portion is 10 N/15 mm width to 10 N/15 mm width.

The seal strength of the easily peelable seal portion is adjusted by the sealing temperature (heating temperature of the heat seal bar), sealing pressure, and sealing time, but usually the sealing pressure and sealing time are fixed and the sealing temperature is adjusted so as to obtain the desired seal strength. There are no particular restrictions on the sealing pressure and sealing time, but usually the sealing pressure is set in the range of 1 to 6 kg/cm ² (0.098 to 0.59 MPa), and the sealing time is set in the range of 0.5 to 8 seconds.

The peripheral edge of the multi-chamber container of the present invention can be formed using conventional methods. For example, when using a film formed using a co-extrusion multilayer T-die method, dry lamination method, extrusion lamination method, or the like, the sealant layers can be stacked facing each other, then sandwiched between a pair of heat-sealing bars and uniformly heated and pressurized to achieve heat fusion. Furthermore, when using a cylindrical film formed using a water-cooled or air-cooled co-extrusion multilayer inflation method, only both ends of the film need to be heat-sealed; it is not necessary to heat-seal the entire circumference of the container.

The seal strength of the peripheral edge of the multi-chamber container of the present invention varies depending on the shape and use of the container, but it is preferable to set it within the strength range of 20 to 60 N/15 mm.

The multi-chamber container of the present invention can be used for all types of intravenous infusion bags, including liquid/liquid mixing bags for amino acid infusions and glucose infusions, and solid (powder)/liquid mixing bags for antibiotics and their dissolving solutions.

The present invention will be explained in more detail using the following examples, but the present invention is not limited to these examples as long as they do not deviate from the spirit of the invention. The methods for measuring various physical properties and the materials used in the examples are as follows:

1. Measurement Method (1) MFR (unit: g/10 min): For polyethylene-based resins, the MFR was measured at 190°C and a load of 2.16 kg in accordance with the appendix of JIS-K6922-2, and for polypropylene-based resins, the MFR was measured at 230°C and a load of 2.16 kg in accordance with JIS K-7210.
(2) Melting peak temperature: A differential scanning calorimeter was used to measure the melting peak temperature Tm of a 5 mg sample, which was held at 200°C for 5 minutes, crystallized at a temperature drop rate of 10°C/min to -10°C, and then melted at a temperature increase rate of 10°C/min.
(3) Heat seal strength (unit: N/15 mm width): Using a 10 mm x 300 mm heat seal bar, a film cut to a length of 210 mm was sealed perpendicular to the melt extrusion direction (MD) under heat sealing conditions of 0.34 MPa for 5 seconds at 5°C increments in the range of 105°C to 160°C. 250 ml of water was then filled into the container, and the heat-sealed side and the opposite side were sealed by impulse sealing. The container was then placed in a heated autoclave and heat-treated at 121°C for 30 minutes. The impulse-sealed side was then cut off, the water removed, and the film was dried.
The heat seal strength was measured by cutting a sample into a 15 mm wide heat seal portion and pulling it apart at a tensile tester at a pulling speed of 500 mm/min. The relationship between the heat seal temperature and the heat seal strength was plotted, and the slope of the resulting curve was calculated to determine the weak seal initiation temperature (the temperature at which the heat seal strength reached 10 N/15 mm width), the weak seal end temperature (the temperature at which the heat seal strength reached 15 N/15 mm width), and the strong seal initiation temperature (the temperature at which the heat seal strength reached 30 N/15 mm width).
If the heat seal strength is 10 to 15 N/15 mm width, the resin films or sheets in the partition inside the container are unlikely to peel apart during production or transportation, but are easily peeled apart by hand or with a tool during use (mixing).It can be said that a weak seal strength can be easily achieved if the weak seal temperature range is 2°C or higher.
Furthermore, if the heat seal strength is 30 N/15 mm width or more, it can be said that the heat seal strength is sufficient to prevent peeling during production or transportation. If the strong seal initiation temperature is 160°C or less, it can be said that the film does not deform during heat sealing, and a strong seal can be formed stably.

(4) Inner surface fusion strength (unit: N/15 mm width): A container was prepared by impulse sealing without putting any contents inside, with the heat-sealed layers of the film tightly attached to each other, and then placed in a heated and pressure sterilizer and subjected to heat treatment at 121°C for 30 minutes. Thereafter, the impulse-sealed portion was cut off, and the film was dried.
The heat-sealed layers were partially peeled from each other, and a sample was cut out to a width of 15 mm. The sample was then pulled apart at a pulling speed of 500 mm/min using a tensile tester to measure the peel strength between the heat-sealed layers. If the peel strength was 0.3 N/15 mm width or less, the heat-sealed layers could be easily peeled from each other, and it can be said that blocking did not occur.

2. Material used: PP1 (propylene-α-olefin random copolymer polymerized with a Ziegler catalyst): Novatec PP FA3KM (trade name, manufactured by Japan Polypropylene Corporation) (melting peak temperature Tm: 160°C, MFR: 10 g/10 min).
PP2 (propylene-based elastomer polymerized with a metallocene catalyst): Wellnex RFG4VM (trade name) manufactured by Japan Polypropylene Corporation (melting peak temperature Tm: 130°C, MFR: 7 g/10 min).
PP3 (propylene homopolymer polymerized with a Ziegler catalyst): Novatec PP FL4 (trade name) manufactured by Japan Polypropylene Corporation (melting peak temperature Tm: 164°C, MFR: 5 g/10 min).
PP4 (propylene-α-olefin random copolymer polymerized with a metallocene catalyst): Wintec WFW4M (trade name) manufactured by Japan Polypropylene Corporation (melting peak temperature Tm: 135° C., MFR: 7 g/10 min).
PP5 (propylene-α-olefin random copolymer polymerized with a metallocene catalyst): Wintec WFX4M (trade name) manufactured by Japan Polypropylene Corporation (melting peak temperature Tm: 125° C., MFR: 7 g/10 min).
PP6 (propylene-α-olefin random copolymer polymerized with a metallocene catalyst): Wintec WSX03 (trade name, melting peak temperature Tm: 125° C., MFR: 25 g/10 min), manufactured by Japan Polypropylene Corporation.
PP7 (propylene-α-olefin random copolymer polymerized with a metallocene catalyst): Wintec WFX6 (trade name, melting peak temperature Tm: 125° C., MFR: 2 g/10 min), manufactured by Japan Polypropylene Corporation.
PE1 (polyethylene): Trade name Novatec LD LM360 (density: 0.928 g/cm ³ , melt index: 0.9 g/10 min) manufactured by Japan Polyethylene Co., Ltd.
PE2 (polyethylene): Novatec HD HM160 (trade name) manufactured by Japan Polyethylene Co., Ltd. (density: 0.953 g/cm ³ , melt index: 5.0 g/10 min).
SEBS1 (styrene-based elastomer): styrene-based elastomer manufactured by Kraton Corporation, trade name G1645MO.
SEBS2 (styrene-based elastomer): styrene-based elastomer manufactured by Kraton Corporation, trade name G1657MS.

Examples and Comparative Examples
The extruder for the outer layer of the tubular film of the three-type three-layer water-cooled inflation molding machine is charged with a mixture of the outer layer weight ratio shown in Table 1 by shaking the bag up and down and left and right by hand to thoroughly agitate the contents, and the extruder for the middle layer of the tubular film of the three-type three-layer water-cooled inflation molding machine is charged with a mixture of the middle layer weight ratio shown in Table 1 by shaking the bag up and down and left and right by hand to thoroughly agitate the contents, and the extruder for the heat-seal ... The contents were mixed by shaking the bag by hand up and down and left and right to thoroughly agitate the contents in the weight ratio of the inner layer shown in Table 1 into the extruder, and the mixture was melt-extruded from a cylindrical die at an extrusion temperature of 200°C, cooled and solidified in water adjusted to 10°C, and a tubular film having a thickness of 200 μm and a folded diameter (the width of the product when the tube is folded flat and wound using the inflation method) of 91 mm was produced at a speed of 3 m per minute, with a thickness ratio of outer layer (surface layer):middle layer:inner layer (heat seal layer) of 1:8:1. Table 1 shows the results of various evaluations of the film.
All of the films of the comparative examples had an inner surface fusion strength of more than 0.3 N/15 mm width, and can be said to be unsuitable for the multi-chamber container of the present invention.

Claims (6)

A method for producing a multi-chamber container comprising a layer made of a resin composition containing 30 to 95 parts by weight of the following polypropylene-based resin (A) component, 5 to 70 parts by weight of the following polypropylene-based resin (B) component, and 5 to 60 parts by weight of the following polyethylene-based resin (C) component and 5 to 50 parts by weight of an elastomer (D) component per 100 parts by weight of the polypropylene-based resin (A) component and the polypropylene-based resin (B) component combined, the method comprising producing the multi-chamber container through the following steps (i) and (ii):
Component (A): A polypropylene resin that satisfies the following requirements (A-1) and (A-2).
(A-1) The melt flow rate (JIS K7210, temperature 230°C, 2.16 kg load) is 0.5 g/10 min or more and 30 g/10 min or less.
(A-2) The melting peak temperature as measured by DSC is 110°C or higher and lower than 145°C.
Component (B): Polypropylene resin (B-1) that satisfies the following requirements (B-1) and (B-2): Melt flow rate (230°C, 2.16 kg load) of 0.5 g/10 min or more and 100 g/ 10 min or less.
(B-2) The melting peak temperature measured by DSC is 145°C or higher.
Component (C): A polyethylene resin that satisfies the following requirement (C-1): (C-1) The melt flow rate (190°C, 2.16 kg load) is 0.01 g/10 min or more and 50 g/10 min or less.
Step (i): A step of heat-sterilizing the layers in contact with each other in at least one chamber of the multi-chamber container at a temperature of 110°C or higher.
Step (ii): A step of opening the chamber that has been sterilized in a state where the layers are in contact with each other during the heat sterilization in step (i), adding a drug, and then sealing it to create a chamber again. A method for producing a multi-chamber container comprising a layer made of a resin composition including 30 to 95 parts by weight of the following polypropylene-based resin (A) component, 5 to 70 parts by weight of the following polypropylene-based resin (B) component, and 5 to 50 parts by weight of the following polyethylene-based resin (C) component and 5 to 50 parts by weight of an elastomer (D) component per 100 parts by weight of the total of the polypropylene-based resin (A) component and the polypropylene-based resin (B) component, the method comprising producing the multi-chamber container through the following steps (i) and (ii):
Component (A): A polypropylene resin that satisfies the following requirements (A-1) and (A-2).
(A-1) The melt flow rate (JIS K7210, temperature 230°C, 2.16 kg load) is 0.5 g/10 min or more and 30 g/10 min or less.
(A-2) The melting peak temperature as measured by DSC is 110°C or higher and lower than 145°C.
Component (B): Polypropylene resin (B-1) that satisfies the following requirements (B-1) and (B-2): Melt flow rate (230°C, 2.16 kg load) of 0.5 g/10 min or more and 100 g/ 10 min or less.
(B-2) The melting peak temperature measured by DSC is 145°C or higher.
Component (C): A polyethylene resin that satisfies the following requirement (C-1): (C-1) The melt flow rate (190°C, 2.16 kg load) is 0.01 g/10 min or more and 50 g/10 min or less.
Step (i): A step of heat-sterilizing the layers in contact with each other in at least one chamber of the multi-chamber container at a temperature of 110°C or higher.
Step (ii): A step of opening the chamber that has been sterilized in a state where the layers are in contact with each other during the heat sterilization in step (i), adding a drug, and then sealing it to create a chamber again. The manufacturing method described in claim 1 or 2, wherein the polypropylene-based resin (A) is a polypropylene-based resin polymerized using a metallocene catalyst. The manufacturing method described in claim 1 or 2, wherein the elastomer (D) is one or more selected from the group consisting of ethylene-α-olefin copolymers, propylene-α-olefin copolymers, and styrene-based elastomers. A resin composition comprising 30 to 95 parts by weight of the following polypropylene-based resin (A) component, 5 to 70 parts by weight of the following polypropylene-based resin (B) component, and 5 to 60 parts by weight of the following polyethylene-based resin (C) component and 5 to 50 parts by weight of an elastomer (D) component per 100 parts by weight of the total of the polypropylene-based resin (A) component and the polypropylene-based resin (B) component, wherein the resin composition is used for a multi-chamber container produced by the production method according to claim 1.
Component (A): A polypropylene resin that satisfies the following requirements (A-1) and (A-2).
(A-1) The melt flow rate (JIS K7210, temperature 230°C, 2.16 kg load) is 0.5 g/10 min or more and 30 g/10 min or less.
(A-2) The melting peak temperature as measured by DSC is 110°C or higher and lower than 145°C.
Component (B): Polypropylene resin (B-1) that satisfies the following requirements (B-1) and (B-2): Melt flow rate (230°C, 2.16 kg load) of 0.5 g/10 min or more and 100 g/ 10 min or less.
(B-2) The melting peak temperature measured by DSC is 145°C or higher.
Component (C): A polyethylene resin that satisfies the following requirement (C-1): (C-1) The melt flow rate (190°C, 2.16 kg load) is 0.01 g/10 min or more and 50 g/10 min or less. A resin composition containing 30 to 95 parts by weight of a polypropylene-based resin (A) component, 5 to 70 parts by weight of a polypropylene-based resin (B) component, 5 to 50 parts by weight of a polyethylene-based resin (C) component, and 5 to 50 parts by weight of an elastomer (D) component per 100 parts by weight of the total of the polypropylene-based resin (A) component and the polypropylene-based resin (B) component, said resin composition being used in a multi-chamber container manufactured by the manufacturing method described in claim 1 or 2.