JPS6022942B2 - Manufacturing method for sterile storage containers - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for manufacturing a sterile storage container, and particularly to a method for manufacturing a sterile storage container suitable as a container for long-term storage of physiological solutions.

Containers for storing physiological solutions such as blood, such as infusion bags, are often made of vinyl chloride resin, but the added plasticizer may migrate to the contents or remain in the gun resin. There are concerns about toxicity due to residual pinyl chloride monomer in the fat.

In addition, after filling the infusion bag with the contents, for example, 12
High-pressure steam sterilization is sometimes performed for 100 to 20 minutes, but in the case of vinyl chloride resin bags, the internal pressure cannot be supported.
There is a risk of the bag breaking, so the entire bag is further covered with polyester or nylon 6 during sterilization.
There are also problems such as the need for close packaging with a heat-resistant film such as -6 film. In addition, regarding blood storage bags, in recent years, instead of storing for 4 to 600 days or 21 days (ACD blood storage), red blood cells are frozen and stored for -80 to 18,500 days.
The development of technology for storing liquids at low temperatures is progressing, and from this point of view as well, there is a demand for the use of materials with good low-temperature properties in place of conventional vinyl chloride resins.

Therefore, as a substitute for vinyl chloride resin, polyethylene film that has been cross-linked in advance and has improved heat resistance,
Although it has been proposed to use an ethylene-vinyl acetate copolymer film, there are problems in that the heat sealing temperature becomes very high and it is difficult to obtain sufficient sealing strength. This invention was made in view of the above circumstances, and is safe as a storage container for physiological solutions, etc., without fear of toxicity, has sufficient heat-sealing strength, and has excellent high- and low-temperature characteristics. The purpose of the present invention is to provide a method for manufacturing a good sterile storage container.

In other words, "This invention has an inner layer of a thermoplastic synthetic resin film that has heat sealability at a temperature of 200 q or less, is crosslinked at an irradiation dose in the range of 2.5 to 50 Mrad, and exhibits a heat-resistant effect, and 200 q or more. A heat-resistant synthetic resin film having a melting point and an outer layer are bonded together to form a laminate sheet, two of the laminate sheets are stacked so that the inner layer films are in contact with each other, and the periphery is heat-sealed at a temperature of 200 oo or less. After forming the container, it is irradiated with electron beams or r-rays in the range of 2.5 to 50 Mrad from one or both sides while keeping the inner layer film below the softening and fusing temperature in air or an inert gas atmosphere. Crosslink the L inner layer film,
The present invention provides a method for manufacturing a sterile storage container, which is characterized by being heat resistant and sterilized at the same time.

Synthetic resins that have heat resistance and are not substantially affected by deterioration of physical properties at irradiation doses in the range of 2.5 to 50 MMd include, for example, polyester to polyimide resins. As the outer layer,
These resins are used.

When laminating these resin films for the inner layer and the resin film for the outer layer, use a reaction-curing adhesive such as polyester, polyurethane, or epoxy, which has heat resistance and low temperature resistance, and is suitable for the dose used. A material that is stable against electron beam and y-ray irradiation may be used for attachment. These two laminated sheets are stacked so that the inner layer films are in contact with each other, and at the same time, if necessary, the spout tube or inlet tube is sandwiched between them, or a part of the laminated sheet is made into a cylindrical or Heat-seal the surrounding area in a bag shape to form a container at a temperature of 200°C or less, then soften the inner layer film in air or in an inert gas atmosphere such as nitrogen as necessary.
Examples of thermoplastic synthetic resins that can be heat-sealed at a temperature of 200 oo or less while maintaining the bonding temperature, and that can be cross-linked at an irradiation dose in the range of 2.5 to 50 Mrad to achieve a heat-resistant effect include, for example, low-density synthetic resins. Polyolefin resins such as polyethylene, medium-high density polyethylene to isotactic polybutene-1, ethylene-vinyl acetate copolymer,
Ionomer resins, etc. On the other hand, if it has a melting point of 200 pm or more and does not melt and decompose at a temperature of 20,000 or less, 2.8 Mmd to 50 Mrad from one or both sides of the container.
By irradiating electron beams or Y-rays with an irradiation dose in the range of 200 to 3000 yen, only the inner layer resin is crosslinked and made heat resistant, and at the same time the entire container is sterilized. This is required due to the relationship between
This is because it is preferable from the viewpoint of manufacturing technology such as efficiency. The irradiation dose by electron beam or y-ray is 2.5 to 5 Mr.
The reason for setting it as ad is that an irradiation dose of 2.9 MMad or less will not provide sufficient sterilization effect, and an irradiation dose of 50 MMad or more may cause problems such as deterioration of the inner layer resin and outer layer resin or adhesive, which is not preferable. .

Note that cross-linking of resins with electron beams and electron beams varies depending on the type of resin used, so it should be determined appropriately depending on the individual resin used. It is necessary to select a material that does not have a negative impact on the contents.

According to this invention, an uncrosslinked thermoplastic synthetic resin film is used as the inner layer of the container, and this is heat-sealed while being held by the outer layer of the heat-resistant synthetic resin film.
Sealing is extremely easy and reliable.
Furthermore, by undergoing crosslinking after sealing, the tensile strength of the entire inner layer film increases, and the sealing strength can be improved.

In addition, this crosslinking improves the heat resistance of the inner layer resin itself, thereby further improving the heat resistance of the entire container. Furthermore, since it is irradiated with electron beams etc. while laminated with an outer layer film that is strong and has good heat resistance, the irradiation work is easy without problems such as wrinkles and deformation of the film, which would be problems with this type of film alone. becomes. Further, since the container is sterilized in a sealed state at the same time as the irradiation with such an electron beam or the like, it is advantageous in terms of the manufacturing process. Example 1 A low-density polyethylene film with a thickness of 0.06 that was treated with corona discharge on one side and a 0.025-thick willow aromatic polyimide film coated with a polyester isocyanate adhesive 2.72 / gono (pyromellitic acid) Anhydride and striped polymer of diaminodiphenyl ether) are pasted together to form a two-layer laminated film, and a spout/injection opening made of modified high-density polyethylene is attached to this, and then the polyethylene film is placed inside. Heat seal the surrounding area with 150℃-0.79 sand and 50℃
A bag with a capacity of 0 was produced.

While cooling the package to below 60 pm, an electron beam was irradiated from both sides of the bag with an irradiation dose of 3 mmrad. The bag body irradiated with electron beam (inventive product) and the bag body before irradiation (comparison product) were filled with 500 skin of physiological saline through the injection port, and then sealed.
The heat resistance was evaluated by high-pressure steam sterilization at 21° C. for 20 minutes.

The bag of the comparative product was torn from the seal, the liquid inside leaked out, and the polyethylene film of the inner layer was stuck, but the product of the present invention was in good condition with no bag breakage or deformation. The heat seal strength of the non-crosslinked comparative product was 3.4k9/15 skin, but the inventive product has improved to 5.4k9/15 skin, and especially with 12000, the comparative product has almost no heat seal strength. Although it does not show strength, the product of the present invention had a strength of 3.1k9/15 ribs.

Furthermore, when we checked the heat sealability of a laminated sheet made by laminating 0.06-side low-density polyethylene that had been crosslinked in advance (30 Mrad) with an aromatic polyimide film, we found that 150oo-0.79 sand 2.2k9/15 side, heat seal temperature 2200
Even when the sealing strength was increased to 0, the maximum strength was only 2.7k9/15 ribs, which was lower than that of ordinary polyethylene. Furthermore, regarding the product of the present invention obtained in this example, the following tests were carried out: a cylindrical test (tsumugi toxicity, twill-dish property), an eluate test, an erythrocyte survival test, a platelet survival test (Riesecker method), a blood coagulation test, and a serum preservation test. As a result of UV absorption tests, etc., no abnormalities were observed.

Claims (1)

[Scope of Claims] 1. An inner layer of a thermoplastic synthetic resin film that has heat-sea suitability at a temperature of 200° C. or lower and is crosslinked at an irradiation dose in the range of 2.5 to 50 Mrad to exhibit a heat-resistant effect; 2.
A heat-resistant synthetic resin film outer layer having a melting point of 00°C or higher is laminated to form a laminate sheet, two of the laminate sheets are stacked so that the inner layer films are in contact with each other, and the surrounding area is heated to a temperature of 200°C or lower. After heat sealing to form a container body, it is heated in air or in an inert gas atmosphere from one or both sides while keeping the inner layer film below the softening and fusing temperature.
．． A method for producing a sterile storage container, which comprises irradiating an electron beam or r-ray in a range of 5 to 50 Mrad to crosslink and make the inner film resistant to heat, and at the same time sterilize it. 2. The inner layer of the thermoplastic synthetic resin film is made of one selected from low-density polyethylene, medium-high density polyethylene, isotactic polybutene-1, ethylene-vinyl acetate copolymer, and ionomer resin, as described in claim 1. Method for manufacturing sterile storage containers. 3. Claim 1, wherein the heat-resistant synthetic resin film outer layer is one selected from polyester and polyimide resin.
Method for producing sterile storage containers as described in Section 1.