JPH052334B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to a storage container and a storage method for blood and blood products (hereinafter referred to as blood). [Prior Art] Conventionally, blood has been collected in a glass container or a vinyl chloride bag and stored in a refrigerator at a low temperature of 4 to 6°C. In particular, vinyl chloride bags are flexible and transparent, have heat resistance that can withstand high-pressure steam sterilization, cold resistance that can withstand low temperatures during blood storage, and mechanical strength that can withstand various operations for separating blood components. Furthermore, it has been widely used around the world due to its excellent processability and hygienic properties. It is also known that blood can be stored better than glass containers. However, even when stored in such vinyl chloride bags, the function of red blood cells, especially the oxygen-carrying ability of red blood cells, decreases markedly with the number of days of storage, so the shelf life of biological products is limited to 4 ±
It is stipulated that cells should be stored for 21 days at a temperature of 2°C, but even so, if the storage temperature exceeds 2 weeks, there is a significant decline in functionality, and this deterioration is a clinical problem, especially in concentrated red blood cells that contain few plasma components. There is. Preventing the deterioration of the oxygen carrying capacity of blood is not only useful for the effective use of limited resources, but is also a fundamentally important issue that affects the effectiveness of blood transfusion itself, and has been actively researched. There is. Most of them are related to preservation solutions, such as inosine,
A method of adding adenine, adenosine, etc. to the preservation solution has been proposed. Also, since it is said that a method that maintains a high pH is advantageous, it can be used as an anticoagulant.
CPD liquid with high pH buffering effect (Citrate−
Phosphate−Dextrose) is ACD solution (Acid−
It has been found that CPD liquid is superior to Citrate-Dex-trose), and a preservation method using CPD liquid has been put into practical use. Furthermore, PEP (Phospho Enol−
Pyruvate) for ACD blood, CPD blood (ACD fluid,
By adding CPD solution to blood),
It has been reported that red blood cell function is maintained red. On the other hand, research related to blood storage containers and preservation methods is as follows: Murphy and Gardner
However, "Blood", Vol. 46, p. 209-218 (1975) states that when storing platelet concentrates, using a container made of vinyl chloride resin causes a decrease in pH and a loss of viability of platelets. , discloses that when a container made of polyethylene is used, the pH decrease is small. Further research into the conditions necessary to maintain platelet viability revealed that (1) lactic acid generated by platelet glycolysis lowers PH, and the rate of PH decline is approximately inversely proportional to the number of platelets; (2) glycolysis is suppressed by allowing carbon dioxide generated by platelet glycolysis to escape outside the storage container and increasing the oxygen partial pressure within the container; (3) glycolysis is suppressed by It is advantageous to use polyethylene, which has good gas permeability, as the material, but it has been revealed that a similar effect can be achieved with vinyl chloride resin by making it thinner so that gas can pass through it more easily. Based on these facts, Japanese Unexamined Patent Publication No. 58-29465
The publication describes a copolymer of ethylene and α-olefin, an ionomer, an ionomer/polyester elastomer, and a linear low-density polyethylene.
Platelet storage containers made from elastomeric laminates or coextrusions (hereinafter referred to as olefinic resins) are disclosed. However, this container is unsuitable for storing red blood cells as it tends to cause hemolysis. In addition, there are many studies and achievements regarding frozen preservation, and it is recognized that it is a very effective means for long-term preservation. In particular, storage under liquid nitrogen is said to be semi-permanent. However, this method has problems such as requiring a lot of effort to remove chemicals such as glycerin added as an antifreeze agent, and the high cost of containers, etc. Currently, this method is mainly used for preserving rare blood. , it is not widespread overall. As a result of studying the storage of blood, particularly whole blood and concentrated red blood cells, the present inventors found that blood and concentrated red blood cells packed in thin polyvinyl chloride or polyethylene resin containers can be stored at 4 to 6°C. As a result of intensive research, we discovered that the cell components can be stored for a considerable period of time while retaining their functions, that the partial pressure of carbon dioxide in the blood is kept low, and that there is little drop in pH. This led to the completion of the invention. [Object of the Invention] In order to improve the above-mentioned drawbacks of conventional blood storage containers, the present invention aims to improve the number of days that blood can be stored when blood, especially whole blood or concentrated red blood cells, is stored at 4 to 6°C. The object of the present invention is to provide a blood storage container made of plastic with excellent permeability to gases, particularly carbon dioxide, and a blood storage method using the same. [Structure of the Invention] That is, the present invention is a storage container for blood or blood products (hereinafter referred to as blood), which is made of a composite film composed of layers of two or more types of thermoplastic synthetic resins that mutually reinforce each other. The inner layer in contact with blood or blood products is a synthetic resin film with excellent blood compatibility and high gas permeability, and the outer layer or intermediate layer is a porous synthetic resin with a carbon dioxide permeation rate of 50,000 ml/m ² 24 hr ATM or more. The composite film has a rigidity expressed in tensile strength of 5 kg/cm or less, making it easy to handle storage containers, and a seal strength of 1.5 kg/cm or more by heat sealing, making it suitable for bag making. A blood storage container characterized by excellent properties and a carbon dioxide gas permeation rate of 5000 ml/m ² · 24 hr · atm or more at 25°C, which allows carbon dioxide gas in blood or blood products to be easily removed, and a high gas storage container. Blood is placed in the above-mentioned storage container made of a transparent synthetic resin film, and when the stored blood is stored for more than one week, the partial pressure of carbon dioxide gas is maintained at 85 mmHg or less, and 2,3-DPG is Concentration remains 2.0 μ even after 2 weeks of storage
The present invention provides a method for preserving blood, which is characterized by storing blood at a temperature of 2° C. or higher and 8° C. or lower so that the number of red blood cells is mol/mm or higher and the pH is 6.7 or higher. The above-mentioned research by the present inventors has shown that when storing blood, the partial pressure of carbon dioxide in the stored blood is 85
It has been found that storage stability is improved if the temperature is below mmHg, preferably below 50 mmHg. In order to provide such conditions, the material (the material of the storage container) and the storage method are closely related. In order to maintain the partial pressure of carbon dioxide in stored blood at 85 mmHg or less, preferably 50 mmHg or less, the material of the container should be at least 5000ml/ ^m2・24hr・atm, preferably 700 to 20000ml/ ^m2・It is desirable that the film has a carbon dioxide gas permeability of 24 hours/ATM. For example, such a film (the number in the box is the thickness) has a carbon dioxide permeation rate of 5000.
When ml/ ^m2・24hr・atm, examples include soft vinyl chloride resin (80μ), polyethylene (200μ), and polybutadiene (500μ). The film may be a single layer, but from the viewpoint of flexibility, gas permeability, biological properties, strength, etc., which are the characteristics required for blood storage containers, two or more types of films that mutually reinforce each other are recommended. By combining layers of thermoplastic synthetic resins into a composite, a storage container with better properties can be obtained. A film with excellent flexibility and mechanical strength is used as the outer layer material of the storage container, a resin layer with particularly high gas permeability is used as the middle layer (inner layer material in case of two layers), and high gas permeability is used as the inner layer material. gender, blood compatibility, biological,
It is better to use a chemically safe resin layer. Examples of resins suitable for the outer layer material include vinyl chloride resin, polypropylene, EVA (ethylene-vinyl acetate copolymer), polyurethane, SEBS (styrene-ethylene-butadiene-styrene copolymer), etc. If heat resistance that can withstand sterilization is required, vinyl chloride resin, polypropylene, SEBS, etc. are preferable. For the intermediate layer, use polybutadiene, EVA, polyurethane, etc., which have excellent gas permeability, at least twice that of vinyl chloride resin.
SEBS, vinyl chloride-vinyl acetate copolymer, etc. are suitable. However, for the outer layer or intermediate layer, a porous synthetic resin layer was selected for the purpose of significantly improving gas permeability, and in particular, the carbon dioxide permeation rate was 50,000ml/ ^m2 .
In the case of 24 hours/atm or more, the resin is not limited to those listed above, and there is a high degree of freedom in selecting the resin. However, it is desirable that the contents of the blood storage container can be observed, and it is necessary that the container be at least translucent or more transparent. The transparency of porous materials varies depending on the pores, pore size, and distribution density. In order to obtain a transparent or translucent porous membrane, the pore diameter should be 0.1 to 100μ and the pore distribution density should be 10
It is necessary to adjust the number to be in the range of ~10 ⁶ pieces/cm ² . In addition, resins with good carbon dioxide permeability that can be used as inner layer materials include soft vinyl chloride resin,
Examples include polyethylene, EVA, polyurethane, polybutadiene, styrene-butadiene block copolymer, and copolymers and blends based on these resins, but the resin used as the inner layer material does not directly interact with blood or blood components. Since it comes into contact with the resin, it must be compatible with blood and have excellent chemical and biological safety.
Even if it is a composite film consisting of two layers, its use as an inner layer material is restricted unless the chemical and biological safety of the resin used for the intermediate layer is confirmed. Examples of resins that are compatible with blood, have excellent chemical and biological safety, and can be used as inner layer materials include soft vinyl chloride resin and polyethylene, but the surface that comes into contact with blood must be coated or surface treated. Other resins may be used as long as they are blood compatible. Blood storage containers manufactured using such materials must be able to be operated without any means of pressurization or depressurization during blood collection and blood discharge, and the rigidity expressed in tensile strength of the constituent material is 5 kg/cm. In order to satisfy this requirement, for example, for high tensile strength films such as polycarbonate, nylon, and polyester, the thickness should be 0.1 mm or less, preferably 0.025 to 0.05 mm. . In addition, in the case of a multilayer composite film, it is necessary to make the inner layer and outer layer each at least 10 μ thick to maintain strength, but if it becomes too thick, the flexibility will be impaired.
Generally, it is preferable that each thickness be within 20% of the total thickness, and there is a limit to the usable total thickness of the composite film, and the range is 0.06 to 1.0 mm, preferably 0.20 to 0.40 mm. It is better to set it in mm. In addition, for the purpose of reinforcing storage containers such as blood packs, the outer periphery of the container can be covered with a porous film or mesh-like sheet material, and materials such as polyester, nylon, etc. with excellent mechanical strength can be used.
Polypropylene, polyurethane, vinyl chloride resin, etc. are suitable. Note that lamination, coextrusion, and the like can be used as a method for compositing the thermoplastic synthetic resin layers, but the manufacturing method is not particularly limited as long as each layer is integrally formed in close contact with each other. do not have. Further, the strength of a bag such as a blood bag is determined not only by the strength of the material but also by the strength of the seal during bag manufacturing. Therefore, the synthetic resin film used for the purpose of the present invention must have excellent bag-forming properties, and it is desirable that its sealing strength be 1.5 kg/cm or more in width. When storing blood by adding CPD storage solution using such a storage container, for example, the amount of carbon dioxide permeation is
For storage containers with excellent gas permeability such as 15,000 to 20,000 ml/m ² / 24 hr / ATM, the partial pressure of carbon dioxide gas will remain below 85 mmHg even after 2 weeks when stored at temperatures above 2°C and below 8°C. and the PH is
A concentration of 2,3-DPG of 6.75 or higher can maintain 2.0 μmol/ml red blood cells, and the oxygen carrying capacity of the blood remains high even after 3 weeks. However, for products with even lower carbon dioxide permeation rates, such as 7000ml/ ^m2 /24hr/atm, the partial pressure of carbon dioxide will drop after two weeks under normal storage methods.
100mmHg or more, and the concentration of 2,3-DPG is 1.5μ
It may be less than mol/ml red blood cells. However, by stirring the container during storage, the partial pressure of carbon dioxide can be kept low and the concentration of 2,3-DPG can be kept high. The stirring may be carried out continuously or intermittently, and the effect can be obtained by shaking lightly for 2 to 3 minutes a day, especially for the first few days. The effect of shaking is more pronounced in containers with lower carbon dioxide gas permeability.
It is particularly effective when the permeation amount is around 5000ml/ ^m2 /24hr/atm. Similarly, if a space is provided between adjacent storage containers in order to facilitate gas replacement, storage stability can be improved. Example 1 CPD-added blood was placed in a bag made of vinyl chloride resin film with a thickness of 400μ, 60μ, or 20μ.
Stored at ℃ for 21 days. The partial pressure of carbon dioxide (PCO ₂ ), PH, 2,3-DPG value, and P ₅₀ of the blood after storage were measured to determine the relationship between the oxygen transport function of the blood and the storage period. The results are shown in Table 1, and it can be seen that with the 20μ vinyl chloride resin single film, the blood function hardly deteriorated even after 3 weeks. Example 2 Using a blood storage bag made of a film consisting of an 80μ vinyl chloride resin layer on the inner surface and a 180μ polybutadiene layer on the outer layer, each characteristic of blood was determined using the same method as in Example 1. Ta. The results were as shown in Table 2. Example 3 The characteristics of various composite films were indexed and compared, and the results are shown in Table 3.

【table】

【table】

〔Effect of the invention〕

As is clear from the above examples, by using a material with high carbon dioxide gas permeability as the synthetic resin film constituting the blood storage container, it is possible to extend the shelf life of blood and blood components. However, according to the method of the present invention, which uses a composite film made by combining and integrating layers of two or more types of thermoplastic synthetic resins, the defects of the single layer film of each resin are mutually reinforced, and the carbon dioxide gas permeability and Not only does it have excellent blood preservation properties, but it also has heat resistance and
A practically usable blood storage container with well-balanced mechanical strength and other physical properties can be obtained, and an excellent blood storage method can also be provided.

Claims (1)

[Scope of Claims] 1. A storage container for blood or blood products, consisting of a composite film composed of two or more mutually reinforcing layers of thermoplastic synthetic resin, the inner layer in contact with the blood or blood products comprising: Synthetic resin film with excellent blood compatibility and high gas permeability, outer layer or middle layer has a carbon dioxide gas permeation rate of 50,000ml/ ^m2・24hr・atm
It is composed of a porous synthetic resin layer that is
The composite film has a stiffness expressed in tensile strength of 5.
Kg/cm or less, the storage container is easy to handle, and the seal strength due to heat sealing is 1.5
Kg/cm width or more, excellent bag-making properties, and carbon dioxide permeation rate at 25℃ of 5000ml/ ^m2・24hr・atm
The above provides a storage container for blood and blood products, characterized in that carbon dioxide gas in the blood or blood products can be easily removed. 2. Claim No. 2, characterized in that the porous synthetic resin layer has a pore diameter of 0.1 to 100 μ, a pore distribution density of 10 to 10 ⁶ pieces/cm ² , and is transparent to translucent. A storage container for blood and blood products according to item 1. 3. Consists of a composite film composed of layers of two or more types of thermoplastic synthetic resins that mutually reinforce each other, and the inner layer that comes into contact with blood or blood products is a synthetic resin film with excellent blood compatibility and high gas permeability, and the outer layer or intermediate layer The layer has a carbon dioxide permeation rate of 50000ml/ ^m2 .
It is composed of a porous synthetic resin layer with a durability of 24hr/atm or more, and the carbon dioxide gas permeation rate at 25℃ is 5000ml/
Place the blood or blood solvent in a storage container that can easily remove carbon dioxide from the blood or blood products, and store one portion of the stored blood at ^m2 /24hr/atm or more.
85mm carbon dioxide partial pressure when stored for more than a week
Hg or less, the concentration of 2,3-DPG is 2.0 μmol/m red blood cells or more even after 2 weeks of storage, and the pH is
A method for preserving blood and blood products, which is characterized by storing blood and blood products at a temperature of 2°C or higher and 8°C or lower so that the temperature is 6.7 or higher. 4. The method for preserving blood and blood products according to claim 3, wherein adjacent storage containers containing blood or blood products have a space to facilitate gas replacement. . 5. Claims 3 and 4, characterized in that the stored blood is shaken continuously or intermittently so that the carbon dioxide partial pressure of the stored blood can be maintained at 85 mmHg or less.
A method for preserving blood and blood products as described in any of the above.