JPH052333B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention relates to a blood storage container made of a composite film of a thermoplastic resin film and an addition-polymerized silicone rubber layer. [Prior Art] Glass containers have traditionally been used as blood storage containers, but these are now mostly replaced by flexible bags made of soft vinyl chloride resin. Furthermore, in recent years, some bags made of olefin resin have come into use for the purpose of increasing the shelf life of platelets.
Blood is generally stored at a low temperature of around 4℃, but there are also frozen blood bags that are used in a frozen state at extremely low temperatures such as -30℃, -80℃, and -198℃.For these purposes, polyimide, Bags made of films such as fluoroplastics and stretched polyethylene have been proposed. Extending the shelf life of precious blood is important for effective resource utilization. In a frozen state, it can be stored for at least six months or more, and storage of special blood and blood fraction components has already been put into practical use. However, it is known that it takes a lot of effort to remove the antifreeze agent such as glycerol that is added when freezing blood, and this method has not yet become completely popular. On the other hand, blood stored refrigerated at around 4 degrees Celsius loses its function over time. In particular, red blood cells, which are most needed, have a reduced oxygen-carrying function, and current blood product standards require a storage period of 21 days, after which they are wasted. It is said that a considerable amount of blood is lost in all stored blood, which is a huge loss, and various studies have been made regarding additive liquids and containers. Regarding containers, it has been reported that the gas permeability of synthetic resins used in blood storage containers has a significant impact on the functionality of blood or blood products.
In other words, in a container with poor carbon dioxide permeability, where carbon dioxide generated by the sugar metabolism of stored blood accumulates inside the container, the pH of the stored blood will decrease, and sugar metabolism will be suppressed, resulting in a decrease in blood flow. Reduce functionality.
Furthermore, it has been reported that when storing concentrated platelets, a polyethylene container with good gas permeability has a better shelf life than a container made of vinyl chloride resin. In Japanese Patent Application Laid-open No. 58-29465,
Ethylene and α-
Platelet storage containers made from olefin copolymers, ionomers, and laminates or coextrusions of ionomer/polyester elastomers and linear low density polyethylene elastomers (hereinafter referred to as olefinic resins) have been proposed. Although a container with good gas permeability, especially carbon dioxide gas permeability, is ideal as a storage container for blood and blood products, if you try to obtain it using the current flexible vinyl chloride resin container, for example, 0.08
The thickness is required to be less than 0.2 mm, and even polyolefin containers need to be thinner than 0.2 mm, making it extremely difficult to obtain a container that maintains the characteristics of a blood storage container, such as mechanical strength and heat resistance. Have difficulty. Carbon dioxide gas permeability of various thermoplastic resins and carbon dioxide gas permeability of 5000ml/
The maximum film thickness necessary to achieve ^m2.24hr.atm or more is shown in Table 1.

[Purpose of the invention]

The present invention aims to solve the problems of conventional blood storage containers as described above.
As a result of intensive studies, we have completed the present invention by applying previous research results that show that soft vinyl chloride resins, polyolefin resins, etc. and addition-polymerized silicone rubber can be strongly bonded as described above. It is something. [Structure of the Invention] That is, the present invention provides a bag-shaped container made of a composite film of one or more layers of a thermoplastic resin film and an addition-polymerized silicone rubber layer, in which the layer in direct contact with blood has a composition of Addition-polymerizable silicone containing an organohydrogenpolysiloxane having two or more hydrogen atoms in one molecule in an amount sufficient to provide 1 to 6 hydrogen atoms directly bonded to silicon atoms per vinyl group in the silicone. The composite film is made of rubber and at least one layer constituting the thermoplastic resin film layer is a porous film, and the carbon dioxide gas permeability of the composite film is 5000ml/
This invention relates to a blood storage container characterized by having a capacity of at least ²⁴ hours. It is something to do. The silicone rubber layer constituting the silicone rubber composite blood storage container according to the present invention is an addition polymerization type silicone, and the addition polymerization type silicone is composed of a vinyl group-containing polysiloxane represented by the general formula (1) and a polysiloxane containing a vinyl group represented by the general formula (1). The organohydrogen polysiloxane shown in (2) and an inorganic substance such as silica as a reinforcing agent,
A composition that can be solidified into an elastic body by addition polymerization using a platinum-based catalyst. In the formula, R ₁ to _{R 4} : 1 of the same or different type having 6 or less carbon atoms
Valid hydrocarbon group m: Positive integer In the formula, R ₅ , R ₇ to _{R 10} : Same or different monovalent hydrocarbon groups having 6 or less carbon atoms R ₆ : Hydrogen group or same or different monovalent hydrocarbon groups having 3 or less carbon atoms n: 2 An integer greater than or equal to 100. l: A positive integer less than or equal to 0 or less than 100. Among these, the number of organohydrogensiloxane units represented by general formula (2) is 0.8 or more, preferably 0.8 or more, based on the total vinyl groups represented by general formula (1). If the organohydrogen polysiloxane having two or more hydrogen atoms in one molecule is contained in an amount sufficient to provide hydrogen atoms directly bonded to silicon atoms at a ratio of 1 to 6 times, it can be further used as a thermoplastic resin. The adhesion force increases. Also, epoxy compounds as a component of what is generally called self-adhesive silicone rubber,
A cured layer obtained by adding a carboxylic acid anhydride, a silane or siloxane containing an acryloxyalkyl group represented by the general formula (3), or an oxirane compound containing an unsaturated hydrocarbon group, or after solidifying an addition polymerizable silicone composition. It is also possible to add a vinyl group-containing resin-like copolymer that is compatible with the components represented by general formulas (1) and (2) as a component for improving the physical properties of the material. For example, there are copolymer organopolysiloxanes of general formulas (4), (5) and (6). In the formula, R ₁₁ : CH ₃ or H group n: Positive integer from 1 to 3 (CH ₂ = CH) (R ₁₃ ) (R ₁₄ ) SiO _0.5 ...(4) SiO ₂ ...(5) (R ₁₅ ) ₃ SiO _0.5 ...(6) In the formula, R ₁₃ , R ₁₄ , R ₁₅ : Same or different monovalent hydrocarbon groups having 6 or less carbon atoms The gas permeability of addition polymerization type silicone rubber is 200% that of low-pressure polyethylene. The gas permeability of this material is extremely high at ~500 times higher than that of the composite film because no anchoring agent is used in the composite, but the thickness of the silicone rubber layer is 20 μ~ due to the need to maintain its strength. 1mm, preferably
It is preferable to set it to 100 to 500μ. Thermoplastic resin films composited with silicone rubber include soft vinyl chloride resin, urethane resin, polyethylene, polypropylene, polybutadiene, ethylene-vinyl acetate copolymer (EVA), cross-linked polyethylene, cross-linked EVA, and ethylene-propylene. A film comprising one or more blend resins selected from copolymers, ethylene-butadiene-propylene terpolymers, styrene-butadiene block copolymers, and styrene-butadiene-ethylene terpolymers can be used. The carbon dioxide gas permeability coefficients of these resins are in the range of 6,000 to 70,000 ml/m ² ·24 hr.0.025 mm, which puts them in the category of thermoplastic resins with high carbon dioxide gas permeability coefficients. The thickness of the film varies depending on the resin, but it can be used up to a maximum of 300μ.A patent application was filed in 1983 for olefin resin films.
As stated in No. 32607, it is preferable to have an unsaturated double bond in the molecule. For example, if a material is used that is a blend of substances with unsaturated double bonds such as polyethylene or butadiene-based polymers, This has a more favorable effect on adhesion. Also, the special request was made in 1988.
As stated in No. 244187 and Japanese Patent Application No. 59-32608, the thermoplastic resin film contains 0.01 to 10%, preferably 0.01 to 10%, of an organohydrogenpolysiloxane containing 30% or more of organohydrogensiloxane units in its components.
If it is contained in an amount of 0.5% to 2%, the adhesion with addition polymerizable silicone rubber will be further improved. The addition polymerization type silicone rubber according to the present invention adheres well to thermoplastic polyester resins, nylon resins, polycarbonate resins, etc. in addition to the above-mentioned thermoplastic resins, but these resins have strong film strength but poor gas permeability. Therefore, if you use a porous film with holes that do not impair the strength of the container itself, it can be composited without impairing gas permeability. It can often be used as at least one of the synthetic resin layers constituting a composite membrane.
Among these, open-cell porous films are effective because they provide high gas permeability even if they are thick. Additionally, if a silicone rubber layer is adjacent to a porous film layer, the silicone rubber may seep into the layer and lose its porosity, but the silicone rubber itself has excellent gas permeability. There's nothing wrong with that. However, a porous membrane with open cells is not suitable as an inner layer material, and since it is desirable that the contents of a blood storage container can be observed during use, the synthetic resin membrane that makes up the container should be transparent or It is required to be translucent. The transparency of porous materials varies depending on the pore size and distribution density, and in order to obtain a transparent or translucent porous membrane, the pore diameter should be 0.1 to 100 μ and the pore distribution density should be 10 to 10 ⁶ /cm. It is necessary to adjust it so that it is within the range of ² . The present composite film can be manufactured by coating a thermoplastic resin film with an addition-polymerizable silicone composition, heating and crosslinking the film, and the coating method may include a doctor blade method, a roll coater method, an air knife method, etc. , but is not particularly limited. Further, in order to adjust the viscosity of the addition polymerizable silicone composition, it may be diluted with a solvent such as hexane or toluene. As yet another method,
A method may also be used in which an addition polymerizable silicone composition is extruded into a film at room temperature and laminated. The carbon dioxide permeability of the composite film is determined by the partial pressure inside the blood of carbon dioxide gas generated by sugar metabolism when whole blood is stored for more than one week.
It is necessary that the value is sufficient to diffuse and eliminate carbon dioxide gas outside the container so that it remains calmly below 85 mmHg, preferably below 40 mmHg.
5000ml/ ^m2・24hr or more at ℃1 atm. However, the carbon dioxide gas permeability is 7000 to 15000ml/
It is best to set it to ^m2・24hr. The structure of the composite film is not particularly limited, but any thermoplastic resin except silicone rubber can be used for the top layer. On the other hand, for the innermost layer, it is necessary to select a resin with excellent blood compatibility and a material with excellent bag-making processability.
In particular, considering adhesion to the port portion for taking in and taking out blood, soft vinyl chloride resin and addition polymerized silicone rubber are particularly desirable. Of course, olefin resins such as polyethylene and polypropylene, and their copolymers and terpolymers can also be used. [Effects of the Invention] The blood storage container obtained using these composite films according to the present invention makes use of the high carbon dioxide gas permeability of silicone rubber, and overcomes the tearing property, which is a drawback of silicone rubber, to that of other thermoplastics. It is possible to provide an excellent blood storage container that is not supplemented by resin but also has other strength supplements.
It is extremely useful medically. This will be explained below using examples. Example 1 10 mol% of trimethylsiloxane units and 40 mol of dimethylsiloxane units were added to 100 parts of dimethylpolysiloxane, which has a viscosity of 18000 cs at 25°C and has dimethylvinylsilyl groups at both ends of the molecular chain.
%, 6 parts of polysiloxane consisting of 50 mol% of methylhydrogen siloxane units, 20 parts of silica, and an isopropyl alcohol solution of chloroplatinic acid (platinum content: 1%)
Addition-polymerizable silicone compositions containing 0.2 parts of
A composite film was obtained by pressing for 2 hours. As a comparative example, a thermoplastic resin film and a composite film were prepared by dry lamination. The film thus obtained was made into a bag by high frequency processing and heat sealing. The ports were high-frequency processed, and in the case of heat sealing, a tube made of the same material as the inner layer was used. When silicone rubber forms the inner layer, an addition-polymerized silicone of the same material is used, and the area forming the periphery of the bag is coated with a thickness of 100μ, and the bag is pressed at 110°C for 2 hours to obtain a bag. . The ports used at this time were made of soft vinyl chloride resin. Carbon dioxide permeability in composite film state
Value according to ASTM-D-1434 method, heat resistance is 121℃20
The deformation of the composite film during high-pressure sterilization for minutes was determined. The strength was determined by filling the obtained bag with 100 c.c. of water, clamping the top of the bag, and checking whether the bag broke or not when it was placed in a centrifuge. The measurement results are shown in Table 2.

【table】

[Table] Example 2 A soft vinyl chloride resin bag (VC400) was used as a comparative example, and PP (30)/Silicone (200) and porous VC (150)/Silicone (100)/VC (70) were used as Examples of the present invention. ) in a container obtained from a composite membrane of
When ACD dog whole blood was dispensed in 60 ml portions and stored at 4°C, the PH change and P50, which is the storage capacity of red blood cells, were determined. P50 was measured using a Hemox Analyzer. The measurement results are shown in Table 3.

[Table] As is clear from the above examples, by using a material with high carbon dioxide permeability as the synthetic resin film that constitutes the blood storage container,
Although it is possible to extend the shelf life of blood and blood components, the method of the present invention uses a composite film that combines and integrates a thermoplastic synthetic resin film and an addition-polymerized silicone rubber layer. By mutually reinforcing the shortcomings of individual membranes, it is possible to obtain a practical blood storage container that not only has excellent carbon dioxide permeability and blood storage properties, but also has well-balanced various physical properties such as heat resistance and mechanical strength. I can do it.

Claims (1)

[Scope of Claims] 1. In a bag-shaped container made of a composite film of one or more layers of thermoplastic resin film and an addition-polymerized silicone rubber layer, the layer that comes into direct contact with blood is made of vinyl in its composition. per base,
An addition polymerization type silicone rubber containing an organohydrogen polysiloxane having two or more hydrogen atoms in one molecule in an amount sufficient to provide 1 to 6 hydrogen atoms directly bonded to a silicon atom, and a thermoplastic resin. A blood storage container characterized in that at least one layer constituting the film layer is a porous film, and the carbon dioxide gas permeability of the composite film is 5000 ml/m ² ·24 hr ·atm or more. 2 The thermoplastic resin film is made of soft vinyl chloride resin, urethane resin, polyethylene, polypropylene, polybutadiene, ethylene-vinyl acetate copolymer, cross-linked polyethylene, cross-linked EVA, ethylene-propylene copolymer, ethylene-butadiene-propylene ter Polymer, styrene-butadiene block copolymer, styrene-butadiene
The blood storage container according to claim 1, which is a film made of one or more blended resins selected from ethylene terpolymers. 3. The blood storage container according to claim 1, wherein the thermoplastic resin film contains 0.1 to 10% of organohydrogenpolysiloxane, which contains 40% or more of organohydrogensiloxane units in its components. . 4. Claim 1, wherein the porous film has a pore diameter of 0.1 to 100μ, a pore distribution density of 10 to 10 ⁶ /cm ² , and is transparent to translucent. Blood storage container as described.