JPS6339258B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a heat-resistant and cryogenic-resistant container that can be used at temperatures ranging from a high temperature of about 200°C to an extremely low temperature of liquid nitrogen temperature of about -196°C. This invention relates to plastic containers suitable for frozen storage of enzymes and other physiological solutions, foods, drugs, etc.

Conventional blood preservation methods include blood preservation using an ACD anticoagulant (preservation in a glass bottle or soft vinyl chloride container containing ACD solution), slow freezing method (preservation in a soft vinyl chloride container at -80 to -85℃), Methods such as storage in containers made of vinyl chloride are known, but in the former method, blood metabolism progresses during storage,
Blood has a short usable period of 21 days after blood collection, and the latter method adds cryoprotectants such as high-concentration glycerin, which lowers the recovery rate of red blood cells due to washing during use, and the quality of red blood cells may deteriorate for several years. Both methods are unsuitable for long-term blood preservation, as they have drawbacks such as a decrease in blood pressure.

Therefore, a rapid cryopreservation method has been developed in which physiological solutions such as blood components are flash frozen in liquid nitrogen and stored at extremely low temperatures of about -150 to -200°C.
However, in this case, a storage container is required that can withstand such extremely low temperatures, can be sterilized at high temperatures, and is easy to use. For example, the soft vinyl chloride containers used for conventional blood storage are
It is not resistant to extremely low temperatures of 196°C, and even the slightest impact will cause cracks when frozen. Additionally, due to the processing of metal containers such as aluminum and stainless steel, it is difficult to seal and open the spout opening of the container, which may cause liquid nitrogen to flow into the container, and the condition of the storage solution may be affected due to the opaque nature of the container. There is a problem in that the storage solution cannot be seen from the outside and the quality of the storage solution cannot be confirmed before taking it out, and the manufacturing cost is high.

Fluorine-based resins and polyimides are known as polymeric materials with good high and low temperature resistance, and a bag-like container consisting of an inner layer of tetrafluoroethylene-hexafluoropropylene copolymer and an outer layer of a polypyromellitimide laminate is used to store blood. In some cases, it is used for frozen preservation. In particular, polyimide has heat resistance with almost no melting point and cryogenic resistance with flexibility even at liquid helium temperatures (4〓), making it an excellent material.Although polyimide is transparent, it is resistant to browning. Because it is colored, some contents cannot be seen through from the outside. In addition, polyimide has one of the lowest thermal conductivities among polymer materials, which slows down the freezing speed, which affects the recovery rate and performance of stored liquid contents, and makes heat sealing conditions more severe, resulting in poor sealing. It is also a cause of trouble. Polyimide is also very expensive in terms of price.

This invention was made in view of the above circumstances, and can withstand use at high temperatures of about 200°C and extremely low temperatures of about -200°C, and can withstand rapid temperature changes during rapid freezing and rapid thawing. be able to tolerate the
The purpose is to provide a relatively inexpensive container with good transparency.

That is, the present invention comprises an inner layer made of an ethylene-tetrafluoroethylene copolymer or a tetrafluoroethylene-hexafluoropropylene copolymer, and a polyparabanic acid resin layer laminated on the outside of the inner layer. The present invention provides a heat-resistant and cryogenic-resistant container characterized by:

The polyparabanic acid resin used in the present invention has a high thermal conductivity of 2 to 3 times that of polyimide resin, and has few of the drawbacks of polyimide, and is colored pale yellow.
The haze value is 1.3-1.4% for a 50μ film, which shows excellent transparency, and the glass transition point is 290°C, which means it has good heat resistance. Furthermore, unlike polyimide, polyparabanic acid resin is thermoplastic and can be shaped by vacuum molding, etc., which also improves the difficulty of attaching pouring and inlet ports such as tubes. There are many advantages. In terms of low temperature resistance, it is practically comparable to polyimide and has flexibility even at -200°C, so there is no problem in using it in the range of about 200°C to -200°C, which is the object of the present invention.

Ethylene-tetrafluoroethylene copolymer (ETFE) and tetrafluoroethylene-hexafluoropropylene copolymer (FEP) as inner layer materials are heated at 265 to 270°C, respectively.
and has a moderate melting point of 260-280℃, 200℃
In addition to being fully compatible with high-temperature sterilization operations up to Can be sealed. ETFE and FEP are flexible and maintain good physical properties at extremely low temperatures of -196°C, are less toxic, have good hygiene, and are chemically stable, so even if red blood cells are stored for a long period of time, the contents will remain Adverse effects such as deterioration are hardly a problem.

The thickness of the inner layer ETFE or FEP used in this invention is 0.025 from the viewpoint of seal strength and pinhole resistance.
mm or more, and from the viewpoint of facilitating quick freezing, it is preferably 0.075 mm or less. In addition, it is preferable to use polyparabanic acid in the outer layer in a range of 0.012 to 0.075 mm, but from the viewpoint of stability, strength, and thermal conductivity of the container seal, the inner layer is ETFE or
The FEP is preferably relatively thick and the polyparabanic acid resin outer layer is relatively thin, and the total thickness is preferably 0.125 mm or less, more preferably 0.100 mm or less.

ETFE and FEP can be made into bags as a single layer film, but they are suitable for quick freezing.
If the thickness is less than 0.100 mm, the heat and pressure during heat sealing or impulse sealing will cause the sealing part to become thinner, making it easier to break and sealing strength may not be achieved.Also, the film may not touch the seal bar during sealing. This may make it difficult to perform a continuous and stable sealing operation, and the sealing surface may become dirty. Therefore, in this invention, this ETFE
Alternatively, these problems were solved by laminating polyparabanic acid resin on the outside of FEP.

Although polyparabanic acid resin is essentially a thermoplastic resin, it has remarkable heat resistance comparable to that of polyimide, and has extremely strong physical properties, so it can be used without adhering to the seal bar during sealing, and can be used as an inner layer.
It is possible to minimize the thinning of the sealing part of ETFE or FEP film, and furthermore, polyparabanic acid resin has a tensile yield strength 2 to 8 times that of ETFE or FEP film of the same thickness.
The strength of the entire container can be significantly increased,
The container can be prevented from being damaged even by rough handling at low temperatures.

To make such a laminate sheet, ETFE or
The FEP film inner layer 1 and the outer polyparabanic acid film 2 may be bonded together using a heat-resistant, cryogenic-resistant, reaction-curing adhesive 3, such as a polyester, polyurethane, or epoxy adhesive.

When making a bag-like container using this laminate, the first
As shown in the figure, the ETFE or FEP films of this laminate are stacked so that one side is in contact with each other, and
A bag-like container can be obtained by heat-sealing the periphery with a liquid inlet and a spout 4 interposed at appropriate locations between them. In addition, as shown in Figure 2, this laminate is molded into a 10mm film using vacuum forming or pressure forming.
After performing shallow drawing and forming the inlet and outlet of the seal part into a tube shape, the ETFE or FEP film is stacked so that one side is in contact with the other and the surrounding area is heat-sealed to create a special inlet. - Can be used as a convenient container for storing liquids without a spout. When this container contains blood or the like, it is subjected to steam sterilization or dry heat sterilization before use.

Example 1 An ethylene-tetrafluoroethylene copolymer film with a thickness of 0.05 mm that had been subjected to corona discharge treatment on one side (Afrex manufactured by Asahi Glass Co., Ltd., with a molar ratio of tetrafluoroethylene
0.025 mm thick polyparabanic acid film coated with 3.5 g/ ^m2 of polyester isocyanate adhesive (manufactured by Exxon Chemical)
TRADLON) to obtain a two-layer laminated film. A tube-shaped spout/injection spout made of ethylene-tetrafluoroethylene copolymer was attached to this, and the container was heat-sealed with the ETFE layer inside to obtain a 400 ml bag-like container (actual volume: 1000 ml). This bag at 180℃
- After dry heat sterilization for 1 hour, add 400 ml of concentrated red blood cell solution, and then add 400 ml of 29% glycerin solution.
After heat-sealing the mouth and stirring vigorously to mix, the bag was placed vertically into a liquid nitrogen tank while regulating the thickness of the bag to 20 mm with an aluminum holder, and was flash frozen. Freezing was completed in about 2 minutes. Remove the frozen blood bag from the holder and transfer it to the liquid nitrogen storage tank 2
After being stored at -150°C or lower for several days, it was thawed in warm water at +40°C with shaking. Despite being subjected to rapid temperature changes and shocks during these steps, the bags according to the present invention were in good condition without any problems such as breakage, peeling of the seal, or leakage of the contents. Furthermore, when the sample was thawed after being stored at -150°C for 6 months, there was no problem in the recovery rate of red blood cells. Further, the bag obtained in this example was subjected to an acute toxicity test, a pyrogenic substance test, and a microbial permeation test using prescribed methods, and no abnormalities were observed.

Example 2 A polyester isocyanate adhesive was applied at 3.8 g/m ² to a 0.051 mm thick tetrafluoroethylene-hexafluoropropylene copolymer film (Teflon FEP-C type manufactured by DuPont) that had been adhesively treated on one side. A two-layer laminate sheet was obtained by laminating polyparabanic acid films with a thickness of 0.050 mm. This was made using a tray-shaped mold with a sealing part around the entire circumference in a brim shape with a depth of 5 mm, and a part of the sealing part being squeezed into a semicircular shape.
Pressure molding was performed with FEP on the inside, and the resulting tray-shaped molded sheets were stacked so that the FEP surfaces were in contact with each other, and the periphery was heat-sealed to obtain a container with a capacity of 400 ml.
After filling this with 380 ml of a solution of water:glycerin = 1:1, heat the tube-shaped injection/outlet part provided in the seal part, flash-freeze it in liquid nitrogen, and then immerse it in hot water at 40℃. Thawing was repeated three times and a thermal shock test was conducted to check for peeling and damage of the seal.

As a result, the time required for freezing was within 3 minutes in all cases, and there was no peeling of the seal or damage to the container.

As detailed above, the heat-resistant and cryogenic-resistant container according to the present invention has good heat-sealability, is easy to manufacture, can withstand high-temperature sterilization operations at 200°C, and is flexible even at cryogenic temperatures of -200°C. It has various advantages such as sufficient mechanical strength and no problems such as toxicity, and it is also possible to form ampoules, which was not possible with conventional polyimide laminates. It is suitable as a container for low temperature storage.

[Brief explanation of the drawing]

The drawings show embodiments of the present invention; FIG. 1 is a cross-sectional view of a bag-like container, FIG. 2 a is a perspective view of a pressure-molded laminated sheet, and FIG. is a plan view, and c is a cross-sectional view thereof. 1...Inner layer, 2...Outer layer, 3...Adhesive, 4...
...Liquid pouring inlet.

Claims (1)

[Claims] 1. An inner layer made of an ethylene-tetrafluoroethylene copolymer or a tetrafluoroethylene-hexafluoropropylene copolymer, and a polyparabanic acid resin layer laminated on the outside of the inner layer. A heat-resistant and cryogenic-resistant container characterized by being formed. 2. The container according to item 1 above, wherein the inner layer has a thickness of 0.025 to 0.075 mm. 3. The container according to item 1 or 2 above, wherein the outer layer has a thickness of 0.012 to 0.075 mm.