JPS643500B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a low-temperature-resistant plastic film packaging that can be used at a low temperature of liquefied carbon dioxide gas temperature of approximately -80°C, and particularly for blood components such as red blood cells, plasma, and platelets, bacteria, enzymes, and other physiological solutions or foods. This invention relates to a plastic package suitable for frozen storage of medicines, etc. Conventionally, blood has been stored in containers made of glass, soft polyvinyl chloride, polypropylene, high-density polyethylene, etc., and stored at 4 to 6°C. However, blood is relatively fragile when stored at this temperature, and its storage period was generally thought to be around 21 days. In recent years, temperatures ranging from -80℃ to -85℃, or -196
By storing each blood component, such as red blood cells, plasma, platelets, and cryo, at extremely low temperatures at ℃, it has become possible to preserve it for even longer periods of time. In this method,
Conventionally, soft vinyl chloride packaging used for storage at 4 to 6°C is used as is, but soft vinyl chloride packaging prevents the elution of plastics in the resin or the residual vinyl chloride monomer. In addition to leaving concerns about toxicity, it is not appropriate for the following reasons. That is, the blood components mentioned above are
During cryopreservation, it is customary to mix a high concentration of anti-freezing agent such as glycerin, and to apply vigorous shaking after freezing. Shaking is also applied during thawing, but in both cases the bags are prone to tearing or pinholes due to rapid changes in temperature and violent shaking. The present invention has been made under these circumstances, and it is an object of the present invention to provide a package that can be used particularly at low temperatures of -80°C to -85°C and does not have the above-mentioned drawbacks. That is, the present invention has a molecular weight of 10,000 or more and a density of
1 to 20 mol% by low pressure polymerization method that is 0.936 or less
an inner layer made of an unstretched film of a random copolymer of ethylene and 1-butene containing 1-butene;
Provided is a package for frozen storage of medical physiological fluids with excellent low temperature resistance, which is made by heat-sealing a laminated film with an outer layer made of a heat-resistant polymeric film having a glass transition temperature higher than room temperature into a container or bag shape. do. The film used for the inner layer of the package of the present invention is 1
Consisting of a random copolymer of ethylene and 1-butene containing ~20 mol% of 1-butene, this resin is TiCl ₄ -AlC ₂ H ₅ Cl ₂ based or α-TiCl ₃ -
It can be obtained by _a low pressure polymerization method using a Ziegler catalyst such as Ti( _{OC2H5 ) 4} -Al( _C2H5 ) ₃ . Since the embrittlement temperature is around -80℃, its molecular weight must be 1 x 10 ⁴ or more, and the density must be 0.936 or less for flexibility, impact resistance, strength, workability, etc. at room temperature and low temperature. Must have. Further, since it is necessary to heat seal the film when producing a container or bag, it is desirable that the film be an unstretched film. Here, when the amount of 1-butene is less than 1 mol %, embrittlement is observed at low temperatures, and when it exceeds 20 mol %, it becomes a rubbery substance and does not have low temperature resistance. Neoxex (manufactured by Mitsui Petrochemical Industries) is a film suitable for the above conditions. The outer layer film is a heat-resistant polymer film whose glass transition temperature is above room temperature, such as polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polycarbonate, polycaprolamide, polyundecanamide, polylauramide, and ethylene-tetrafluoride. Ethylene copolymer, tetrafluoroethylene-hexafluoropropylene copolymer, perfluoroalkoxy resin, polychlorinated trifluoroethylene, polyparabanic acid, polypyromellitimide, or polyether sulfone, and the heat of the inner layer film It is a stretched or unstretched film with a melting point or softening temperature higher than the melting temperature of 100 to 120°C and higher than 20°C. If the glass transition humidity of the film used for the outer layer is below room temperature, the tensile strength and impact resistance of the film will be extremely reduced as it cools. When the glass transition temperature of the film is above room temperature, even if it is cooled, the decrease in tensile strength and impact resistance of the film is small and it can withstand practical use. As shown in the cross-sectional view of FIG. 1, the inner layer film 5 and the outer layer film 4 are bonded together using a heat-resistant and low-temperature curable adhesive 6 such as polyester, polyurethane, or epoxy. The composite is integrated by fusion to form a laminated sheet. As shown in FIG. 2, the laminated sheets are stacked so that the inner layer surfaces are in contact with each other, the periphery is heat-sealed into a container or bag shape, and the necessary inlet 1 and outlet 2 are provided. Obtain a bag or container for storing medical physiological fluid. The thickness of the laminated sheet is usually 0.5 mm or less because frozen blood storage bags, etc., which are the subject of the present invention, require a certain degree of flexibility. Due to its excellent strength, it is sufficient to make the total thickness of the inner and outer layers less than 0.2 mm, and from the viewpoint of heat sealability and pinhole resistance, a thick film is used for the inner layer and a thin film is used for the outer layer. is desirable. The resin of the inner layer of the packaging body of the present invention has good chemical resistance like many polyolefins, has few extractable components, and has sufficient hygiene against blood components.
On the other hand, it has unique properties such as low temperature resistance, flexibility, and strength that cannot be obtained with ordinary polyolefins. The outer layer resin has a glass transition point higher than room temperature, so even at temperatures as low as -100℃, it has the same strength and flexibility as at room temperature. It also does not cause bag breakage or pinholes even when freezing and thawing blood, which involves rapid temperature changes and violent shaking. Note that, from the viewpoint of peeling resistance at low temperatures, the adhesive is preferably a two-component curing adhesive of terminal isocyanate polyester urethane-glycol. In addition, the heat-sealed part is normally thinned, and for example, if only the inner layer resin film is overlapped and heat-sealed, cracks can be seen during rapid cooling, but in the present invention in which the outer layer is laminated, after filling. This does not occur because the seal edge of the seal is reinforced by the outer layer. The product of the present invention is lighter than those made of glass bottles, has no risk of damage when dropped, etc., and has excellent strength and water vapor permeability due to the inner layer being made of ethylene resin. It is less than half the thickness of blood containers made of soft polyvinyl chloride (approximately 0.4 mm thick), making the container lighter and easier to dispose of after use, just like with vinyl chloride containers. This is easy because no toxic gas is generated. Also, because it is thin, it has good thermal conductivity.
It has the advantage of being highly efficient in sterilization and freezing. In addition, random copolymers of ethylene and 1-butene synthesized by low-pressure polymerization have low crystallinity and excellent transparency, whereas ordinary ethylene resins are cloudy and translucent, and are commonly used in medical packaging. It has good transmittance to 450 mμ ultraviolet light, which is one of the criteria for determining the transparency of materials, and it is also excellent in this respect, such as making it easy to detect dust etc. in the contents. Example (1) A biaxially stretched polyethylene terephthalate film with a thickness of 12 μm was coated with a polyester isocyanate adhesive at 3.8 g/m ² , and a film with a thickness of 110 μm was applied.
One side of an ethylene-1-butene random copolymer film (manufactured by Neozex Mitsui Petrochemical Industries) obtained by a low-pressure polymerization method with a density of 0.921 was laminated to form a two-layer laminated film with one side matte. Obtained. This is ethylene-1-
The butene copolymer film was placed inside and the periphery was heat sealed to obtain a bag with a capacity of 200 ml. Add water/methanol = 3/1 liquid to this bag.
After adding 200ml, heat seal the opening and store at -80℃, -
The bags were left in electric refrigerators at 70°C and -60°C for 5 hours to cool completely, each bag was folded into quarters, then twisted flat at that temperature, and the process was repeated 5 times. Each bag was twisted to room temperature and its condition was observed, but under all conditions of -80℃, -70℃, and -60℃, there was no breakage or damage to the bag, and there were no pinholes or irregularities in the folds. I was not even allowed to attend. At this time, the contents were sheerbet-like at temperatures below -60°C, but it can be seen from this that the bag of this construction retains sufficient flexibility even at -80°C. (2) At the opening of the 200 ml bag obtained in Example (1), an inlet and an outlet consisting of a tube with an inner diameter of 4φ and a wall thickness of 0.7 m/m extruded from ethylene-α olefin copolymer were installed. A blood bag was obtained by heat-sealing the inner layer by sandwiching it and heat-sealing the other parts. 121 in a form where the inside is saturated with water vapor.
℃ for 20 minutes, and after adding 100 ml of physiological saline and 100 ml of 79% glycerin solution, the mouth tube was heat-sealed and left in an electric freezer at -80 ℃ for 5 hours to freeze. . Furthermore, this frozen blood bag is placed in +40℃ warm water,
It was shaken and thawed in 2 minutes. Despite being subjected to rapid temperature changes during these steps, the bag according to the present invention remained in good condition with no peeling of the seal, no damage to the bag, and no leakage of the contents. A similar operation was performed using a commercially available vinyl chloride bag, but when the frozen bag was pulled out of the freezer, the slight impact caused the edges of the bag to break, and some cracks appeared. was seen, but
The product of the present invention was good. *The physical property values of the laminated sheet obtained in the above example are shown below.

[Table] This test was conducted in accordance with JIS Z1707 "Plastic film for food packaging." (a) Low temperature resistance

[Table] "Test items" 1 Heavy metals Below the limit 2 Residue on ignition 0.1 or less 3 Extractables test (i) Properties Colorless and clear (ii) Foam Disappears within 2 minutes (iii) PH 1.5 or less (iv) Chloride Below the limit (v) Sulfate Below the limit (vi) Phosphate The color of the solution is lighter than the comparison solution (vii) Ammonia The color of the solution is lighter than the comparison example (viii) Lead Below the limit (ix) Cadmium Below the limit (x) Potassium permanganate 1.0ml or less Reducing substance () Evaporation residue 1.0mg or less () Ultraviolet absorption spectrum 0.10 or less (wavelength 220nm) This test is based on the Japan Bureau of Regulations 9th Amendment: General Test Method 39 "Test Method for Plastic Containers for Infusions" ” (3) “Heavy metals”;
The tests were carried out by applying mutatis mutandis to the sections (4) "Ignition residue" and (5) "Extractables test". "Test item" Hemolytic test Judgment: Negative This test is based on the 9th revision of the Japanese Pharmacopoeia: General test method (39)
It was carried out in accordance with the ``Hemolysis test'' section of Plastic container test method for infusion (9).

[Brief explanation of drawings]

FIG. 1 is a sectional view showing one embodiment of a laminated sheet of a package for frozen storage according to the present invention. FIG. 2 is a plan view showing the package of the present invention. DESCRIPTION OF SYMBOLS 1... Inlet, 2... Outlet, 3... Heat sealing part, 4... Outer layer, 5... Inner layer, 6... Adhesive layer.

Claims (1)

[Claims] 1. Made by a low-pressure polymerization method with a molecular weight (weight average w) of at least 1×10 ⁴ and a density of 0.936 or less,
Ethylene containing 1 to 20 mol% of 1-butene and 1-
Low-temperature resistant product made by heat-sealing a laminated film into a container or bag shape, consisting of an inner layer made of an unstretched film of a random copolymer of butene and an outer layer made of a heat-resistant polymer film whose glass transition temperature is above room temperature. Packaging for freezing and freezing preservation of medical physiological fluids with excellent properties. 2 The outer layer is polyethylene terephthalate, polyethylene naphthalate, polybutylene terephthalate, polycarbonate, polycapramide, polyundecaneamide, polylauramide, ethylene-tetrafluoroethylene copolymer, tetrafluoroethylene-hexafluoropropylene copolymer, perfluoroalkoxy A kind of resin selected from polychlorinated trifluoroethylene, polyparabanic acid, polyether sulfone, or polypyromellitimide, and consisting of a stretched or unstretched film with a melting point higher than the thermal fusion temperature of the inner layer. The package for frozen storage according to item 1 above.