JP4696773B2 - Multi-layer medical container and multi-layer medical multi-chamber container - Google Patents

Description

  The present invention relates to a medical multi-layer container and a medical multi-layer multi-chamber container for containing a medicine, and more particularly to a medical multi-layer container and a medical multi-layer multi-chamber container that suppresses components eluted from the container and an adhesive layer. .

Conventionally, as a container for containing a drug, a container using a linear polyolefin single-layer film or a multilayer film of a linear polyolefin and a polymer having moisture or gas barrier properties has been widely used. In recent years, due to the revision of the Japanese Pharmacopoeia, the use of multi-layer films in which these films are bonded with adhesives has been recognized, and medical containers with many performances have been developed. It can be accommodated.
However, by improving the performance of the container and accommodating various drugs, impurities such as low molecular weight components eluted from linear polyolefins and components eluted from the adhesive layer and drugs that are active ingredients Problems such as a decrease in drug content due to interaction, an increase in drug related substances, an increase in turbidity of drug solutions, or an increase in insoluble fine particles have occurred.

Under these circumstances, various plastic products have been proposed as medical materials that do not deform containers due to sterilization, do not alter drugs due to elution of impurities or adsorption of active ingredients, and do not deteriorate transparency due to steam sterilization. Has been.
Among these products, a thermoplastic norbornene resin, which is a kind of cyclic polyolefin, is used as a medical material (Patent Document 1, Patent Document 2, Patent Document 3, Patent Document 4, and Patent Document 5).
JP-A-4-276253 Japanese Patent Laid-Open No. 6-255053 Japanese Unexamined Patent Publication No. 7-266517 Japanese Patent Laid-Open No. 10-59345 JP 2002-301796 A

  As these medical containers, although sterilized at a high temperature such as high-pressure sterilization and hot water sterilization are described, γ-ray irradiation is possible, and after sterilizing a plurality of containers, solid drugs A multi-chamber container that contains liquid medicine and liquid medicine in a separate container and is mixed at the time of use has not yet been studied. In particular, in multi-chamber containers, when a long-term stored solid drug is formulated into the target drug in liquid form, examine changes in the drug, changes in turbidity in the prepared drug, changes in the appearance of the container due to γ-ray sterilization, etc. It is important.

  An object of the present invention is to sterilize γ-rays in a medical multi-layer container and a medical multi-layer multi-chamber container mainly using a cyclic polyolefin, and a low molecular weight component and an adhesive that are eluted from these multi-layer containers. By reducing the layer components, problems such as a decrease in drug content due to the interaction between these components and the drug, an increase in related substances, an increase in turbidity in the drug, and an increase in insoluble fine particles are eliminated, and drug stability is further improved. An object of the present invention is to provide a medical multilayer container and a medical multilayered multi-chamber container.

  The present invention is a container having a main body for containing a drug and a port provided in the main body, wherein the main body is made of a cyclic polyolefin or a polymer blend containing the cyclic polyolefin, and a line adjacent to the layer. It is the medical multilayer container shape | molded from the multilayer film containing the 2nd layer which consists of glassy polyolefin or polyamide.

  According to the present invention, a liquid medicine compartment containing a liquid medicine and a medicine compartment containing a medicine are fluid-tightly separated by a peelable seal portion, and the medicine compartment is a bag-like material composed of a front seat and a rear seat. A multi-chamber container having a lead-out port, wherein a front sheet and / or a rear sheet of a drug compartment has a layer made of a cyclic polyolefin or a polymer blend containing a cyclic polyolefin and a layer made of a linear polyolefin or a polyamide adjacent to the layer. A multi-layer medical multi-chamber container formed from a multi-layer film.

  In the present invention, a liquid medicine compartment containing a liquid medicine and a medicine compartment containing a medicine are fluid-tightly separated by a peelable seal portion, and the medicine compartment is a bag-like material composed of a front seat and a rear seat. In a multi-chamber container, the front sheet of the drug compartment comprises (i) a layer made of cyclic polyolefin or a polymer blend containing cyclic polyolefin, and (ii) a layer made of linear polyolefin or polyamide adjacent to the layer, iii) A medical multilayered multi-chamber container composed of a multilayer film formed by sequentially laminating a polyester layer or a polyester layer having an inorganic vapor-deposited thin film and (iv) a linear polyolefin layer.

  Further, in the present invention, the liquid medicine compartment containing the liquid medicine and the medicine compartment containing the medicine are fluid-tightly separated by a peelable seal portion, and the medicine compartment is a bag-like shape composed of a front seat and a rear seat. A multi-compartment container, wherein the rear sheet of the drug compartment is (i) a layer made of cyclic polyolefin or a polymer blend containing cyclic polyolefin and (ii) a layer made of linear polyolefin or polyamide adjacent to the layer, (V) A medical multi-layered multi-chamber container composed of a multilayer film formed by sequentially laminating a metal foil, a metal vapor-deposited layer or an inorganic vapor-deposited layer, and (vi) a polyester layer.

  Further, in the present invention, the liquid medicine compartment containing the liquid medicine and the medicine compartment containing the medicine are fluid-tightly separated by a peelable seal part, and the medicine compartment is a bag-like shape composed of a front seat and a rear seat. A front chamber compartment sheet comprising: (i) a layer made of cyclic polyolefin or a polymer blend containing cyclic polyolefin, and (ii) a layer made of linear polyolefin or polyamide adjacent to the layer (Iii) a polyester layer or a polyester layer having an inorganic vapor-deposited thin film and (iv) a multilayer film obtained by sequentially laminating a linear polyolefin layer, and the rear sheet of the drug compartment is composed of (i) a cyclic polyolefin or A layer comprising a polymer blend comprising a cyclic polyolefin and (ii) a linear polyolefin adjacent to the layer Or a layer of polyamide, a (v) a metal foil, a metal deposited layer or an inorganic vapor deposited layer and (vi) a polyester layer sequentially medical multilayer multi-chamber container made of a multilayer film formed by laminating.

In the present invention, a multilayer film including a layer made of cyclic polyolefin or a polymer blend containing cyclic polyolefin and a layer made of linear polyolefin or polyamide adjacent to the layer is used as a container material, and the layer containing cyclic polyolefin is the innermost layer. By reducing the low molecular weight components and adhesive layer components eluted from these multilayer containers, the drug content decreases due to the interaction between these components and the drug, the related substances increase, and the turbidity in the drug increases. In addition, it is possible to provide a multi-layer medical container having drug stability by solving problems such as an increase in insoluble fine particles. Further, in the present invention, it has an effect that γ-ray sterilization can be performed instead of steam sterilization. Further, in a multi-chamber container, when a solid medicine stored for a long time is formulated as a target medicine in a liquid form, changes in the medicine, It is possible to minimize changes in turbidity in the drug and changes in the appearance of the container due to γ-ray sterilization.
Furthermore, in the present invention, by making the layer containing the cyclic polyolefin the innermost layer, the drug compartment and the liquid agent compartment are welded to form a weak seal portion, and the weak seal portion is peeled off during use. And the liquid agent are mixed, and the target drug can be prepared and discharged.

In the present invention, the medical multi-layer container is a multi-layer container having a plurality of films or sheets (hereinafter referred to as a film including a sheet), such as a bag, a bottle, a tube, a cell, and a prefilled syringe. It means a container having various shapes and containing one or more kinds of drugs. Of the plurality of films, at least one layer is made of a cyclic polyolefin or a polymer blend of the cyclic polyolefin.
Further, in the present invention, the medical multi-layered multi-chamber container has one or more kinds of compartments for containing a liquid agent and one or more kinds of compartments for containing a medicine. It is a container. The multi-layered multi-chamber container is a container formed with one or more films, like the above-described medical multi-layer container, and has various shapes such as bags, bottles, prefilled syringes, etc. Of the film or sheet, at least one layer is based on a cyclic polyolefin or a polymer blend of the cyclic polyolefin.
The multilayer container may be provided with a discharge port such as a drug outlet part according to the purpose of use.

In the present invention, the gas barrier layer is a layer having the performance of blocking the passage of moisture or gas. In the present invention, the printable layer means a layer capable of printing a medium such as printing ink when displaying characters or designs on the surface of the container.
In the present invention, the easy peel function means a function that can be easily peeled at the time of drug preparation after the films forming the container are bonded to each other.
In the present invention, the adhesive layer means an adhesive resin or adhesive layer that enables adhesion between a layer containing a cyclic polyolefin and another layer, or adhesion between two other layers.

  The cyclic polyolefin used in the present invention is a thermoplastic saturated norbornene polymer and is already known (Japanese Patent Laid-Open No. 4-276253, Japanese Patent Laid-Open No. 5-317411, Japanese Patent Laid-Open No. 8-155007, etc.). Specific examples thereof include a polymer having a structural unit represented by Chemical Formula 1 and / or Chemical Formula 2.

(Wherein R ₁ and R ₂ are hydrogen or a hydrocarbon residue having 1 to 10 carbon atoms and may be the same or different, and R ₁ and R ₂ may form a ring with each other) Good, n is a positive integer.

Wherein R ₃ and R ₄ are hydrogen or a hydrocarbon residue having 1 to 5 carbon atoms, and may be the same or different, and R ₃ and R ₄ may form a ring with each other L and m are positive integers, and p is 0 or a positive integer.)

  A polymer having a structural unit represented by Chemical formula 1 is, for example, 2-norbornene and its alkyl and / or alkylidene-substituted products such as 5-methyl-2-norbornene, 5,5-dimethyl as monomers. 2-norbornene, 5-ethyl-2-norbornene, 5-butyl-2-norbornene, 5-ethylidene-2-norbornene, etc .; dicyclopentadiene, 2,3-dihydrodicyclopentadiene, and their methyl, ethyl, Alkyl substituents such as propyl and butyl; dimethanooctahydronaphthalene, and alkyl and / or alkylidene substituents thereof such as 6-methyl-1,4: 5,8-dimethano-1,4,4a, 5,6 , 7,8,8a-octahydronaphthalene, 6-ethyl-1,4: 5,8-dimethano-1,4,4 5,6,7,8,8a-octahydronaphthalene, 6-ethylidene-1,4: 5,8-dimethano-1,4,4a, 5,6,7,8,8a-octahydronaphthalene, etc .; Cyclopentadiene tri- and tetramers such as 4,9: 5,8-dimethano-3a, 4,4a, 5,8,8a, 9,9a-octahydro-1H-benzoindene, 5,8-methano- 3a, 4,4a, 5,8,8a, 9,9a-octahydro-1H-benzoindene, 5,8-methano-1,4,4a, 4b, 5,8,8a, 9b-octahydro-1H-fluorene 4, 11: 5, 10: 6, 9-trimethano-3a, 4, 4a, 5, 5a, 6, 9, 9a, 10, 10a, 11, 11a-dodecahydro-1H-cyclopentanthracene, etc. Polymerized by a known ring-opening polymerization method The ring-opening polymer obtained Te, a saturated polymer produced by hydrogenation by conventional hydrogenation methods.

The polymer having the structural unit represented by Chemical Formula 2 is a polymer obtained by copolymerizing a norbornene-based monomer as described above with ethylene by a known method and / or a hydrogenated product thereof. And both are saturated polymers.
The cyclic polyolefin used in the present invention is a hydrogenated product of a ring-opening polymer in which a thermoplastic saturated norbornene-based polymer is a polar monomer, a copolymer of the norbornene-based monomer and ethylene, and a hydrogenated product of the copolymer. May be.

  In the present invention, a thermoplastic saturated norbornene-based polymer composed only of a monomer not containing the polar group is preferable from the viewpoint of moisture impermeability, but a part of the polar monomer is copolymerized within a range not impairing the object of the present invention. It may be a polymer.

Polymers that may be blended with the cyclic polyolefin include other materials such as low density polyethylene, linear low density polyethylene, medium density polyethylene, high density polyethylene, polypropylene, ethylene / propylene copolymer, ethylene / vinyl acetate copolymer, etc. Polymers. The blend ratio is usually cyclic polyolefin: other polymer = 50 to 99:50 to 1 (weight ratio).
The layer formed from the cyclic polyolefin or polymer blend thereof has a thickness of usually 3 to 5000 μm, preferably 5 to 2000 μm. When used as a medical multi-chamber container, the thickness is usually 10 to 10 μm. It is 500 μm, preferably 20 to 300 μm.

  Examples of the linear polyolefin layer adjacent to the cyclic polyolefin layer include linear polyolefins such as low density polyethylene, linear low density polyethylene, medium density polyethylene, high density polyethylene, polypropylene, ethylene / propylene copolymer, and styrene elastomers. And other polymer layers. Examples of the polyamide layer include layers such as nylon 6, nylon 66, nylon 12, nylon 612, and a blend of these polymers.

In the present invention, a layer made of linear polyolefin or polyamide is adjacent to a layer made of cyclic polyolefin or a polymer blend containing cyclic polyolefin. Specifically, it can be produced by dry lamination, extrusion coating, coextrusion lamination (T-die method, inflation method), heat lamination, etc., or a lamination method combining these methods. It is preferable to do. The coextrusion lamination is performed by employing a T-die, a multilayer air-cooled inflation method or a multilayer water-cooled inflation method.
The thickness of the linear polyolefin or polyamide layer is usually 10 to 500 μm, preferably 20 to 300 μm.

In the present invention, a gas barrier layer and / or a printable layer is further provided on the layer made of the linear polyolefin or polyamide.
In the present invention, the gas barrier layer is specifically a metal foil, a metal vapor deposition layer or an inorganic vapor deposition layer, and examples of the metal foil include an aluminum foil. As a metal vapor deposition layer, an alumina vapor deposition polyester film, a nylon film, etc. are mentioned. A silica vapor deposition polyester film etc. are mentioned as an inorganic vapor deposition layer. The thickness of the gas barrier layer is usually 5 to 50 μm.
Examples of the printable layer include a polyester layer such as polyethylene terephthalate or a polyester layer deposited with an inorganic material such as silica. The thickness of the printable layer is usually 5 to 50 μm.

  As one embodiment of the multilayer film of the present invention, (i) a layer made of cyclic polyolefin or a polymer blend containing cyclic polyolefin, (ii) a layer made of linear polyolefin or polyamide adjacent to the layer, and (iii) a polyester layer Or there exists what laminated | stacked the polyester layer which has an inorganic vapor deposition thin film, and (iv) linear polyolefin layer one by one. The (ii) layer made of linear polyolefin or polyamide, (iii) the polyester layer or the polyester layer having an inorganic vapor-deposited thin film, and (iv) the linear polyolefin layer are preferably laminated via an adhesive layer.

  Other embodiments of the multilayer film of the present invention include (i) a layer made of cyclic polyolefin or a polymer blend containing cyclic polyolefin, (ii) a layer made of linear polyolefin or polyamide adjacent to the layer, and (v) a metal. There is one in which a foil, a metal vapor deposition layer or an inorganic vapor deposition layer, and (vi) a polyester layer are sequentially laminated. The (ii) layer made of linear polyolefin or polyamide, (v) the metal foil, the metal vapor-deposited layer or the inorganic vapor-deposited layer, and (vi) the polyester layer are preferably laminated via an adhesive layer.

  As a method for producing a multilayer film, there is a method of laminating each layer by dry lamination, extrusion coating, coextrusion lamination (T-die method, inflation method), heat lamination, or a lamination method combining these methods. In addition, thermoplastic saturated norbornene polymers are good solvents such as alicyclic hydrocarbon solvents (cyclopentene, cyclohexane, methylcyclohexanedecalin, etc.), aromatic hydrocarbon solvents (toluene, xylene, ethylbenzene, etc.), chlorinated carbonization. A method of applying and drying as a solution dissolved in a hydrogen-based solvent (chloroform, chlorobenzene, etc.), a mixed solvent thereof, or a mixed solvent with another solvent can also be employed.

Moreover, you may laminate | stack using an adhesive agent or adhesive resin between layers. Examples of adhesives include polyurethane adhesives, and adhesive resins include vinyl acetate copolymer emulsions, synthetic rubber (chloropreman, SBR, butyl rubber, etc.) solution types, polyolefins modified with chlorinated or maleic anhydride Examples include a solution type.
The thickness of the adhesive layer is appropriately selected depending on the type and thickness of the film to be adhered.

As a method for producing a multilayer container, a sheet molding method (thermoforming method) such as vacuum molding or pressure forming, a blow molding method such as multilayer coextrusion blow molding, or a peripheral portion between multilayer films cut into a predetermined shape is heated. Various methods such as a method of producing a bag-like material by fusing or bonding with an adhesive can be employed.
The medical multilayer container of the present invention is characterized in that the multilayer film is adhered to each other so that the innermost layer is a layer made of cyclic polyolefin or a polymer blend containing cyclic polyolefin.
By making the innermost layer a layer of cyclic polyolefin or a polymer blend containing the same, it is possible to reduce the low molecular weight component and the adhesive layer component eluted from the multilayer container. Since the cyclic polyolefin has a density higher than that of polyethylene and has a three-dimensional structure, the molecular motion of the polymer is suppressed as compared with the linear polyolefin. Further, in the present invention, the cyclic polyolefin and the linear polyolefin are bonded to form a layer, which reduces the hardness of the film, which is a characteristic of the cyclic polyolefin itself, and has an effect that can be finished into a smooth film. is there.
Furthermore, the multilayer container of the present invention can have bag rigidity due to the polyester layer, and can be printed, and also provides water vapor and gas barrier properties due to the metal foil, metal vapor deposition layer, or inorganic vapor deposition layer. Drugs that are unstable with respect to gas such as moisture and oxygen can also be accommodated.

  As one embodiment of the multi-layer medical multi-chamber container of the present invention, the liquid medicine compartment containing the liquid medicine and the medicine compartment containing the medicine are separated fluid-tightly by a peelable seal portion, There is a bag-like material composed of a front sheet and a rear sheet, and the liquid agent compartment is a bag-like material molded from a tubular film. One embodiment of the multi-chamber container of the present invention is shown in FIGS. In the figure, 1 is a multi-chamber container, 2 is a liquid agent compartment, 3 is a medicine compartment, 4 is a front seat, 5 is a rear seat, 6 is a weak seal, and 7 is a medicine outlet. One embodiment of the multilayer film constituting the container of the present invention is shown in FIGS. In FIG. 3, a is a layer made of cyclic polyolefin or a polymer blend containing cyclic polyolefin (innermost layer), b is a layer made of linear polyolefin or polyamide (intermediate layer), and c is a polyester layer or a polyester having an inorganic deposited thin film. Layer (intermediate layer), d represents a linear polyolefin layer (outermost layer). In FIG. 4, o is a layer made of cyclic polyolefin or a polymer blend containing cyclic polyolefin (innermost layer), p is a layer made of linear polyolefin or polyamide (intermediate layer), q is a metal foil, metal vapor deposition layer or inorganic vapor deposition Layer (intermediate layer), r represents a polyester layer (outermost layer).

  The front sheet of the drug compartment is composed of (i) a layer made of cyclic polyolefin or a polymer blend containing cyclic polyolefin (innermost layer) and (ii) a layer made of linear polyolefin or polyamide (intermediate layer) adjacent to the layer ( iii) A polyester layer or a polyester layer (intermediate layer) having an inorganic vapor-deposited thin film and (iv) a multilayer film formed by sequentially laminating a linear polyolefin layer (outermost layer) (FIG. 3). Further, the rear sheet of the drug compartment is composed of (i) a layer made of cyclic polyolefin or a polymer blend containing cyclic polyolefin (innermost layer) and (ii) a layer made of linear polyolefin or polyamide (intermediate layer) adjacent to the layer, (V) It is comprised from the multilayer film formed by laminating | stacking a metal foil, a metal vapor deposition layer, or an inorganic substance vapor deposition layer (intermediate layer), and (vi) polyester layer (outermost layer) one by one (FIG. 4).

  In another embodiment of the present invention, the front sheet of the drug compartment comprises (i) a layer (innermost layer) comprising a cyclic polyolefin or a polymer blend comprising a cyclic polyolefin and (ii) a linear polyolefin or polyamide adjacent to the layer. Layer (intermediate layer), (iii) a polyester layer or a polyester layer (intermediate layer) having an inorganic vapor-deposited thin film, and (iv) a multilayer film formed by sequentially laminating a linear polyolefin layer (outermost layer) ( 3), and the rear sheet of the drug compartment has a linear polyolefin layer (innermost layer), a metal foil, a metal vapor-deposited layer or an inorganic vapor-deposited layer (intermediate layer), and a polyester layer (outermost layer) in sequence on the substrate. You may be comprised from the multilayer film (not shown) formed by laminating | stacking.

  In yet another embodiment of the present invention, the rear sheet of the drug compartment is composed of (i) a layer (innermost layer) comprising a cyclic polyolefin or a polymer blend containing the cyclic polyolefin and (ii) a linear polyolefin or polyamide adjacent to the layer. Layer (intermediate layer), (v) metal foil, metal vapor-deposited layer or inorganic vapor-deposited layer (intermediate layer) and (vi) a polyester film (outermost layer) are sequentially laminated to form a multilayer film (FIG. 4). A multilayer film in which the front sheet of the medicine compartment is formed by sequentially laminating a linear polyolefin layer (innermost layer), a polyester layer or a polyester layer (intermediate layer) having an inorganic deposited thin film and a linear polyolefin layer (outermost layer). (Not shown).

  The liquid compartment is preferably composed of a single layer or a multilayer film made of a polyolefin resin, and is preferably a bag or a tubular film made of two films. Examples of the polyolefin resin include low density polyethylene, linear low density polyethylene, medium density polyethylene, high density polyethylene, polypropylene, ethylene / propylene copolymer, and blends thereof.

The liquid medicine compartment containing the liquid medicine and the medicine compartment containing the medicine are fluid-tightly separated by a peelable seal portion.
The peelable seal portion is a member having an easy peel function, and is a portion in which innermost layers forming a drug compartment and / or a liquid agent compartment are welded to each other, or a linear polyolefin film and / or a cyclic polyolefin This is a portion where a film and another member formed from a resin having a low welding strength and the innermost layer forming the drug compartment and / or the liquid agent compartment are welded. As such another member, a blend polymer containing polyethylene and polypropylene, an ethylene / propylene copolymer, or a propylene / α-olefin copolymer (A), the copolymer (A), and an α-olefin content rate Examples thereof include blends of different propylene / α-olefin copolymers (B) and / or propylene homopolymers (C) (Japanese Patent Laid-Open No. 2001-226499).

  Examples of the liquid preparation of the present invention include water for injection, physiological saline, glucose liquid, amino acid liquid, high calorie infusion, fat emulsion, vitamin preparation, or metal element preparation, and the drug is a solid or liquid drug. Yes, antibiotics, antibacterial agents, anticancer agents, or hormonal agents, herbal medicines and the like. In particular, it is desirable to accommodate a solid drug that is more unstable in storage than a liquid drug, for example, a powdered solid drug.

Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples.
In the examples and comparative examples, each measurement item was measured by the following method.
Turbidity: Using a turbidimeter (HACH, 2100N), the transmitted light attenuated by the turbid substance (parallel light from the LED light source) and the amount of scattered light generated by the turbid substance (90 ° to the light source) (Measured at the light receiving portion arranged in the) at the same time to determine the respective ratios. Fordazine turbidity (NTU) is adopted as a unit of turbidity measurement.

Example 1
A cyclic polyolefin (manufactured by ZEON, trade name ZEONOR) was extruded together with medium density polyethylene (density 0.938) using a co-extrusion machine at 250 ° C. to form a two-layer film (the former 30 μm, the latter 20 μm). . A polyethylene terephthalate film (Mitsubishi Chemical, thickness 12 μm) and a medium density polyethylene film (density 0.938, thickness 40 μm) are passed through a polyolefin adhesive resin (LLDPE) on the medium density polyethylene layer of this two-layer film. Were sequentially laminated to obtain a multilayer film (front sheet A). The thickness of the adhesive layer was 20 μm.
Next, a cyclic polyolefin (manufactured by ZEON, trade name ZEONOR) was extruded at 250 ° C. together with a medium density polyethylene (density 0.938) using a co-extruder to produce a two-layer film (the former 30 μm, the latter 20 μm). Filmed. Separately, an aluminum foil (manufactured by Sun Aluminum, thickness 20 μm) and a polyethylene terephthalate film (manufactured by Toyobo, thickness 16 μm) are laminated using a polyurethane adhesive (manufactured by Takeda Pharmaceutical) to form a two-layer laminate. Obtained. A multilayer film (rear sheet B) was manufactured by laminating an aluminum foil of a two-layer laminate on a medium-density polyethylene layer of the two-layer film via a polyolefin-based adhesive resin (LLDPE). The thickness of the adhesive layer was 20 μm.
The three-side periphery of the multilayer film (A) and the multilayer film (B) is strongly sealed with a heat sealer at 170 ° C. and a pressure of 0.3 MPa using a cyclic polyolefin layer as the innermost layer, and a bag-like container (140 mm × 115 mm).
The powdered antibiotic (a) (1.0 g) was placed in the bag and sealed with heat to prepare a sample. After the sample was stored at 50 ° C. for 1 month, 10 g of powdered solid antibiotic was taken out, dissolved in 50 ml of water, and turbidity (NTU) was measured with a turbidimeter (HACH, 2100N). . The results are shown in Table 1.

Comparative Example 1
A container was manufactured using the innermost cyclic polyolefin layer of the multilayer films (A) and (B) in Example 1 as a linear low-density polyethylene layer. That is, a cyclic polyolefin (manufactured by ZEON, trade name ZEONOR) is extruded with a linear low density polyethylene (density 0.930) at 250 ° C. using a co-extruder to form a two-layer film (the former 30 μm, the latter 20 μm). ) Was formed. A polyethylene terephthalate film (Mitsubishi Chemical, thickness 12 μm) and a linear low-density polyethylene film (density 0.930, thickness) via a polyolefin-based adhesive resin (LLDPE) on the cyclic polyolefin layer of the two-layer film. 40 μm) were sequentially laminated to obtain a multilayer film (front sheet C). The thickness of the adhesive layer was 20 μm.
Next, a cyclic polyolefin (manufactured by ZEON, trade name ZEONOR) was extruded with a linear low density polyethylene (density 0.930) at 250 ° C. using a co-extruder to form a two-layer film (the former 30 μm, the latter 20 μm). ) Was formed. Aluminum foil (manufactured by Sun Aluminum, thickness 20 μm) and polyethylene terephthalate film (manufactured by Toyobo, thickness 16 μm) were laminated using a polyurethane adhesive (manufactured by Takeda Pharmaceutical) to obtain a two-layer laminate. . A multilayer film (rear sheet D) was manufactured by laminating a two-layer laminate aluminum foil on the cyclic polyolefin layer of the two-layer film via a polyolefin-based adhesive resin (LLDPE). The thickness of the adhesive layer was 20 μm.
The three-side periphery of the multilayer film (C) and the multilayer film (D) has a linear low density polyethylene layer as the innermost layer and is strongly sealed with a heat sealer at 165 ° C. and a pressure of 0.3 MPa. A container (140 mm × 115 mm) was prepared.
In the same manner as in Example 1, the sample was stored in a bag-like container at 50 ° C. for 1 month, and turbidity (NTU) was measured. The results are shown in Table 1.

Comparative Example 2
High-density polyethylene film (density 0.957, thickness 60 μm), silica-deposited polyethylene terephthalate film layer (Mitsubishi Chemical, thickness 12 μm), polyethylene terephthalate film layer (Mitsubishi Chemical, thickness 12 μm) and high-density polyethylene film ( A multilayer film (front sheet E) was manufactured by sequentially laminating a density of 0.957 and a thickness of 40 μm via a polyurethane adhesive. On the other hand, a high-density polyethylene film (density 0.957, thickness 40 μm), aluminum foil (San-aluminum, thickness 20 μm) and polyethylene terephthalate film (Toyobo, thickness 16 μm) are polyurethane adhesives (Takeda Pharmaceutical) ) Was used to obtain a multilayer film (rear sheet F). The three-side periphery of the multilayer film (front sheet E) and the multilayer film (rear sheet F) has a high density polyethylene layer as the innermost layer and is strongly sealed with a heat sealer at 170 ° C. and a pressure of 0.3 MPa to form a bag. A container (140 mm × 115 mm) was prepared.
In the same manner as in Example 1, the sample was stored in a bag-like container at 50 ° C. for 1 month, and turbidity (NTU) was measured. The results are shown in Table 1.

Comparative Example 3
A multilayer film (front sheet G, rear sheet H) excluding the cyclic polyolefin layer (manufactured by ZEON, trade name ZEONOR) layer in Comparative Example 1 was produced, and a bag-like container was produced in the same manner as Comparative Example 1.
In the same manner as in Example 1, the sample was stored in a bag-like container at 50 ° C. for 1 month, and turbidity (NTU) was measured. The results are shown in Table 1.

Comparative Example 4
A multilayer film (front sheet I, rear sheet J) was produced using a linear low-density polyethylene film (density 0.930, thickness 60 μm) instead of the high-density polyethylene film in Comparative Example 2, and Comparative Example 2 A bag-like container was produced in the same manner as described above.
In the same manner as in Example 1, the sample was stored in a bag-like container at 50 ° C. for 1 month, and turbidity (NTU) was measured. The results are shown in Table 1. In the table, abbreviations indicate the following compounds.
COP: Cyclic polyolefin MDPE: Medium density polyethylene LLDPE: Linear low density polyethylene PET: Polyester HDPE: High density polyethylene Al: Aluminum SiPET: Silica vapor deposited polyester

Example 2
A linear low-density polyethylene (0.923, 250 μm thick) tubular product (100 mm x 150 mm) is manufactured, a drug outlet is attached to one end, and it is strongly welded at 145 ° C for 3.0 seconds. A small piece made of a blend polymer containing polyethylene and polypropylene was sandwiched between the ends to form a liquid agent compartment weakly welded at 150 ° C. for 3.5 seconds. After forming the liquid agent compartment, the solution was stored and steam sterilized. In addition, the drug compartment prepared in Example 1 was sterilized by γ-rays in the form of a bag (140 mm × 115 mm), and the solid preparation was aseptically accommodated in the drug compartment. Next, the innermost layer of the remaining one end of the bag-like material strongly welded at the three sides and the outermost layer of the liquid medicine compartment are strongly welded at 150 ° C. for 4.0 seconds through the small piece, and the medicine compartment A multi-layer medical multi-chamber container composed of a liquid agent compartment was manufactured (FIG. 1).

Example 3 and Comparative Examples 5-8
Various powdered antibiotics (b) to (f) (1.0 g) were accommodated in the same bag as in Example 1 to prepare samples. After the sample was stored at 50 ° C. for 1 month, 10 g of powdered solid antibiotic was taken out, dissolved in 50 ml of water, and turbidity (NTU) was measured with a turbidimeter (HACH, 2100N). . For comparison, various powdered antibiotics (b) to (f) were similarly accommodated in the bag-like materials described in Comparative Examples 1 to 4, and used as samples. These results are shown in Table 2. In the table, 0T indicates the turbidity (NTU) measured after taking out powdered solid antibiotics immediately after storage and dissolving in water. 1M indicates one month later.

  As is apparent from Table 2, the change in turbidity (NTU) of various antibiotics is small even after storage at 50 ° C. for one month by using the bag-like product of the present invention.

It is sectional drawing which shows one embodiment of the multilayered medical multi-chamber container of this invention. It is a front view which shows one embodiment of the medical multilayered multi-chamber container of this invention. It is sectional drawing which shows the multilayer film (front sheet) which comprises the medical multilayer container of this invention. It is sectional drawing which shows the multilayer film (rear sheet) which comprises the medical multilayer container of this invention.

Claims (6)

A liquid medicine compartment containing a liquid medicine and a medicine compartment containing a medicine are partitioned fluid-tightly by a peelable seal part, and the medicine compartment has a bag-like material composed of a front seat and a rear seat. A container,
The front sheet of the medicine compartment is (i) a layer (innermost layer) made of cyclic polyolefin or a polymer blend containing cyclic polyolefin, and (ii) a layer made of linear polyolefin or polyamide (intermediate layer) adjacent to the layer, (Iii) a polyester layer or a polyester layer (intermediate layer) having an inorganic vapor-deposited thin film and (iv) a multilayer film formed by sequentially laminating a linear polyolefin layer (outermost layer),
(I) a layer (innermost layer) made of cyclic polyolefin or a polymer blend containing cyclic polyolefin, and (ii) a layer (intermediate layer) made of linear polyolefin or polyamide adjacent to the layer, v) A multi-layer medical multi-chamber container composed of a multilayer film in which a metal foil, a metal deposition layer or an inorganic deposition layer (intermediate layer) and (vi) a polyester layer (outermost layer) are sequentially laminated . The medical multi-layered multi-chamber container according to claim 1, wherein the liquid agent compartment is a tubular material composed of a single layer or a multi-layer film of linear polyolefin. The peelable seal portion is a portion where the innermost layers forming the drug compartment or liquid agent compartment are welded to each other, or is formed of a linear polyolefin film and / or a cyclic polyolefin film and a resin having low welding strength. The multi-layer medical multi-chamber container according to claim 1, which is a portion in which an innermost layer that forms another member and a drug compartment and / or a liquid compartment is welded. The medical multilayered multi-chamber container according to claim 1 , wherein the drug is a solid drug. The medical multi-layered multi-chamber container according to claim 1 , wherein the drug is a solid drug selected from the group consisting of antibiotics, antibacterial agents, anticancer agents, or hormone agents. The medical multilayered multi-chamber container according to claim 1, wherein the solution is water for injection, physiological saline, glucose solution, amino acid solution, high-calorie infusion solution, fat emulsion, vitamin preparation, or metal element preparation.

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