JPH04297265A - Container with medicinal liquid - Google Patents

Abstract

PURPOSE:To provide a container holding medicinal liquid sterilizable by a high pressure steam, having a form sealed up with an internal and an external wrapping materials, where the external wrapping material has a better sealing property as well as a blocking resistance. CONSTITUTION:This is a container which comprises a resin container (A) sealed to hold a medicinal liquid and a film or a sheet (B) sealed capable of wrapping the (A). The container (A) is composed of polyethylene or an ethylene-vinyl acetate copolymer and at least the internal wall of (B) is formed from polyvinyl chloride and the ethylene-vinyl acetate copolymer or a graft copolymer of the polyvinyl chloride and polyurethane.

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to containers containing medicinal liquids. Specifically, the present invention relates to a container containing a medical liquid that can be subjected to high-pressure steam sterilization and is suitable for preserving the outer surface of the plastic container containing the medical liquid in a sterile state and for preventing the stored medical liquid from deteriorating due to air.

0002

[Prior Art] In order to keep the outer surface of a plastic container (inner packaging material) containing blood, infusion fluids, etc. It is common practice to further wrap and seal the container with another packaging material, particularly a plastic film or sheet (outer packaging material). As the inner packaging material, flexible materials are usually used, and flexible polyvinyl chloride, polyethylene, and ethylene-vinyl acetate copolymers are typical examples, but these flexible materials have low softening points (low melting points), Because it has a low glass transition point, when wrapped in an outer packaging material and subjected to high-pressure steam sterilization, the inner packaging material softens and the surface becomes tackier, resulting in fusion at the contact surface between the inner packaging material and the outer packaging material, and after cooling. The player remains stuck and blocked,
There are problems such as that it is difficult or impossible to operate when opening the package (when using the medicinal solution). In most cases, a polymer with a low softening point is used to improve the heat sealability of the inner wall of the outer packaging material, which further exacerbates the sticking phenomenon.

[0003] In order to avoid this, measures have been considered such as (1) using polymers with a high softening point as the inner and outer packaging materials, and (2) sterilizing under relatively mild conditions. , as well as a decrease in heat sealability.
Since high softening point polymers tend to lead to high rigidity polymers, flexibility, which is an advantage of plastic containers (inner packaging materials), is lost. In addition, as an outer packaging material, polyethylene terephthalate, which has a relatively high melting point (melting point 250 to 2
Even if a polymer film with a temperature of 60° C.) is used and (1) is combined, it is difficult to sufficiently suppress blocking when the inner packaging material is made of a low softening point polymer as described above. A further disadvantage of relatively high melting point polymer films such as polyethylene terephthalate is that the sealing strength is too low. Therefore, at present, it is necessary to sterilize the inner packaging material containing the medicinal liquid and then wrap it in the outer packaging material, which makes it difficult to ensure sterility between the inner packaging material and the outer packaging material.

0004

[Problems to be Solved by the Invention] In light of the above-mentioned circumstances, an object of the present invention is to have an outer packaging material that has both anti-blocking properties and good sealing properties, and has a form that is sealed by an inner packaging material and an outer packaging material. An object of the present invention is to provide a container containing a medical liquid that can be sterilized by high-pressure steam.

[0005]

[Means for Solving the Problems] The above objects are achieved by a container consisting of a sealed plastic container (A) containing a medicinal solution and a sealed film or sheet (B) enclosing the plastic container (A). The plastic container (A) is composed of polyethylene or ethylene-vinyl acetate copolymer, and at least the inner wall of the film or sheet (B) is composed of polyvinyl chloride and ethylene-vinyl acetate copolymer.
This is achieved by a container containing a pharmaceutical liquid, which is characterized by being formed of a vinyl acetate copolymer or a graft copolymer of polyvinyl chloride and polyurethane.

That is, as a result of studies by the present inventors, the graft copolymer of polyvinyl chloride and ethylene-vinyl acetate copolymer or the graft copolymer of polyvinyl chloride and polyurethane was originally used as a plasticizer-free flexible polyvinyl chloride. Although these are known polymers, it has become clear that these films (or sheets) are difficult to block with polyethylene or ethylene-vinyl acetate copolymer containers even under high-pressure sterilization conditions. What is particularly noteworthy is that blocking is unlikely to occur between the graft copolymer of polyvinyl chloride and ethylene-vinyl acetate copolymer as the outer packaging material and the ethylene-vinyl acetate copolymer as the inner packaging material.

[0007]

[Operation] The contents of the present invention will first be explained regarding the inner packaging material (A).

[0008] As the polyethylene used in the present invention, low-density polyethylene is preferable from the viewpoint of transparency and flexibility, and high-pressure process low-density polyethylene, propylene, butene-1, pentene-1, hexene-1, heptene-1, etc. -1,
Linear low density polyethylene containing α-olefins such as octene-1, 4-methyl-1-pentene as a comonomer component is preferred. Considering moldability, heat resistance, mechanical properties, etc., the density is 0.91 to 0.94 g/cm3, and the melt flow rate (hereinafter referred to as MFR) at a temperature of 190°C and a load of 2,160 kg is 0.1. -30, more preferably 0.2-20. For the same reason, ethylene-vinyl acetate copolymer (hereinafter referred to as EVA) also has a vinyl acetate content of 3 to 30% by weight, preferably 5% by weight.
~18% by weight, with an MFR of 0, the same as that of polyethylene.
．． It is preferable to use a number in the range of 1 to 30, preferably 0.2 to 20.

[0009] Polyethylene and EVA are generally used alone, but a mixture or a multilayered body of these may be used if necessary. Further, it may be crosslinked with radiation or an organic peroxide for the purpose of improving heat resistance, mechanical properties, etc.

[0010] The inner packaging material (A) is molded and manufactured by a commonly known melt molding method such as an extrusion method (inflation method, T-die method), an injection molding method, a blow molding method, etc.
Its thickness is usually 200 to 800 μm, preferably 250 μm.
~500 μm.

Next, in the present invention, at least the inner wall of the outer packaging material (B) is made of a graft polymer of polyvinyl chloride and ethylene-vinyl acetate copolymer (hereinafter referred to as PVC-EVA) or a graft polymer of polyvinyl chloride and polyurethane (hereinafter referred to as PVC-EVA). (hereinafter referred to as PVC-PU), which means that at least the inner wall surface of the outer packaging material, that is, the portion that can come into contact with the polyethylene or EVA of the inner packaging material, is made of PVC-EVA or PVC-PU.
It is sufficient that the material is made of U, and it has a multilayer film or multilayer sheet structure in which an inner layer made of these polymers and an outer layer made of other polymers are bonded directly or through an adhesive. There may be. In this case, other polymers can be arbitrarily selected according to the purpose of improving the mechanical properties of the film or sheet, improving the barrier properties against gases (oxygen, carbon dioxide, water vapor, etc.), and specifically, polyethylene , polypropylene, poly-1-butene, poly-4-methyl-1-pentene, ethylene-vinyl acetate copolymer, ethylene-vinyl alcohol copolymer, polyvinylidene chloride, polyacrylonitrile, nylon 6, nylon 8, nylon 1
2. Nylon 66, nylon 610, poly-m-xylylene adipamide, polyethylene terephthalate, polybutylene terephthalate, polyethylene-2,6-naphthalate, poly-1,4-cyclohexylene dimethylene terephthalate, etc., and these as main components Examples include copolymers of

[0012] PVC-EVA is usually obtained by graft polymerizing vinyl chloride onto EVA (preferably used with a vinyl acetate content of 20 to 80% by weight) as a backbone polymer; for example, It is obtained by dissolving EVA in a vinyl chloride monomer and polymerizing it with a radical polymerization initiator such as azobisisobutyronitrile. In addition, the EVA content in PVC-EVA is 20
~80% by weight, preferably 30-75% by weight. Further, the hardness of PVC-EVA is mainly determined by the vinyl acetate content, and the higher the vinyl acetate content, the softer it is. Considering moldability, mechanical properties, etc., the number average molecular weight is 30,000 to 100,000, preferably 40.0.
00 to 80,000 is preferable.

[0013] In PVC-PU, PVC is generally a branched polymer, similar to PVC-EVA. Polyurethane is molded from dicarboxylic acid components such as adipic acid, azelaic acid, and sebacic acid, and glycol components such as ethylene glycol, propylene glycol, 1,4-butanediol, 1,6-hexanediol, diethylene glycol, and polyethylene oxide. A polyester diol or one obtained by reacting a polyether diol such as polyethylene oxide, ethylene oxide-propylene oxide copolymer, or polytetramethylene oxide with toluene diisocyanate or 4,4'-diphenylmethane diisocyanate is preferable.

The manufacturing method is almost the same as PVC-EVA, and it is obtained by using this polyurethane as a backbone polymer and grafting vinyl chloride onto it. For example, polyurethane is dissolved in vinyl chloride monomer and azobisiso It can be obtained by polymerization with a radical polymerization initiator such as butyronitrile. The hardness of PVC-PU is determined by the composition and content of polyurethane. Considering moldability, mechanical properties, etc., the polyurethane content is 20 to 8.
0% by weight, preferably 30-70% by weight, and at a temperature of 1
Melt viscosity at 80°C and shear rate of 100 sec-1 is 10,000 to 50,000 poise, preferably 15
,000 to 40,000 poise is preferable.

[0015] PVC-EVA or PVC-PU is molded into a film or sheet (B) using the extrusion method (inflation method, T
It is molded and manufactured by a die method), an injection molding method, a blow molding method, etc., and a suitable molding temperature is 150 to 200°C. Further, as in the case of general PVC, calender processing and roll processing may also be applied.

[0016] In these moldings, additives commonly used to stabilize PVC, such as salts such as calcium and zinc, phosphite esters, antioxidants, and ultraviolet absorbers, are added. Needless to say, it's a good thing.

The above-mentioned graft polymer has the same flexibility as flexible PVC, and does not necessarily require the addition of a plasticizer, but if necessary, the molecular weight of polyethylene adipate, polybutylene adipate, etc. 1
,000 or more is preferable, and it is preferable to avoid adding a low molecular weight plasticizer such as diethylhexyl naphthalate, which has a molecular weight of less than 500, because it may cause migration problems.

[0018] The outer packaging material film or sheet (B) is
Thickness of PVC-EVA or PVC-PU part is 5μ
m or more, and is a single layer or a multilayer structure with other films or sheets. In addition, when used as a multilayer film or multilayer sheet, the total thickness is 0.01 to 0.5 mm.
It is preferable to adjust the thickness to about 0.05 to 0.3 mm. Further, as a sealing method for the film or sheet (B) of the outer packaging material, a sealing method normally applied to PVC films (or sheets), such as an impulse sealing method or a high frequency sealing method, can be adopted. In particular, the high frequency sealing method is easy because PVC, EVA, and polyurethane all have a high dielectric constant.

In the present invention, the atmosphere between the inner wrapping material (A) and the outer wrapping material film or sheet (B) can be arbitrarily selected depending on the application and requirements, such as vacuum (reduced pressure), nitrogen gas, carbon dioxide gas filling, etc. can. Suitable examples of the medicinal solution used include physiological saline, electrolyte solutions, dextran preparations, mannitol preparations, saccharide preparations, amino acid preparations, and the like. High-pressure steam sterilization usually uses a gauge pressure of 1.2 to 20 kg.
It is carried out at 100-130°C under a pressure of /cm2.

[0020]

[Examples] The present invention will be explained in more detail below with reference to Examples.

Examples 1 to 6 and Comparative Examples 1 to 2 (1) Experimental method (1) Molding of plastic container (inner packaging material) (A) The container was made of the materials shown in Table 1. First, the pellets shown in Table 1 were fed to an extruder-type melt extruder (manufactured by Ikegai Iron Works Co., Ltd.), extruded through a circular die with a temperature of 180°C, a diameter of 8cm, and a lip width of 1.5mm, and after cooling with water at 20°C, A tubular sheet with a thickness of 350 μm and a deposition diameter of 16 cm was obtained, and sealed using a hot plate method to form a sheet of approximately 2.5 cm x 14 cm x 3.
A container with a flat shape of 0 cm was molded. This was filled with 1000 ml of physiological saline.

(2) Forming of outer packaging material (B) (or (C)) It is composed of the materials shown in Table 2. First, the pellets shown in Table 2 were fed to an extruder-type melt extruder (manufactured by Ikegai Tekko Co., Ltd.), and at a temperature of 180°C, a diameter of 8 cm and a lip width of 1
．． The product was extruded through a 0 mm die, cooled with water at 20° C., formed into a tube with a thickness of 100 μm and a deposit diameter of 18 cm, and wound up.

(2) Preparation of a container containing a medical solution (A) was vacuum-packed with (B) (or (C)) and impulse-sealed.

[0024] Sterilization Sterilization was carried out using a retort type high-pressure steam sterilizer at a temperature of 115°C and a gauge pressure of 1.8 kg/cm2 for 30 minutes. The pressure is secured by pressurizing saturated steam with nitrogen gas.

■ Observation of Blocking Phenomenon Inner packaging material (A) and outer packaging material (B) (
Or (C)) was peeled off to determine whether blocking had occurred.

[0026]

[Table 1]

[0027]

[Table 2]

(2) Results Table 3 shows the relationship between the combinations of various packaging materials and the presence or absence of blocking. As is clear from Table 3, PVC-EVA
And PVC-PU does not cause blocking problems with EVA or polyethylene plastic containers.
It can be seen that it is an effective outer packaging material.

[0029]

[Table 3]

[0030]

As described above, the present invention provides a container comprising a sealed plastic container (A) containing a medicinal solution and a sealed film or sheet (B) enclosing the plastic container (A). The plastic container (A) is composed of polyethylene or ethylene-vinyl acetate copolymer, and the film or sheet (A) is composed of polyethylene or ethylene-vinyl acetate copolymer.
B) is a container containing a medicinal liquid characterized in that at least the inner wall is formed of a polyvinyl chloride and ethylene-vinyl acetate copolymer or a graft copolymer of polyvinyl chloride and polyurethane, so that high-pressure steam sterilization is possible. , useful for preserving aseptic conditions and preventing deterioration of medicinal solutions.
and a sealed plastic container (A
) and the film or sheet (B), and combined with the flexibility and transparency of PVC-EVA and PVC-PU, its industrial value is high.

Claims (1)

[Claims] 1. A container consisting of a sealed plastic container (A) containing a medical solution and a sealed film or sheet (B) enclosing the plastic container (A), the container comprising: ) is composed of polyethylene or ethylene-vinyl acetate copolymer, and at least the inner wall of the film or sheet (B) is composed of polyvinyl chloride and ethylene-vinyl acetate copolymer or a graft copolymer of polyvinyl chloride and polyurethane. Container containing medicinal liquid.