JPS61226046A - Blood bag - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] (Industrial application field) The present invention relates to blood bags that are blood compatible.

[Conventional technology]

In recent years, blood collection and storage using plastic bags has rapidly become popular, replacing the conventional blood collection and storage using silicone resin-coated glass bottles. In particular, plastic bags are safer than glass bottles because the entire process of blood collection, separation, storage, and transfusion can be performed in a closed cycle. In addition, plastic bags are superior in terms of handling and workability in component blood transfusions, which are currently increasing in number.

By the way, as is well known, blood has a self-protective effect, and when blood comes into contact with a different interface other than the inner wall of a blood vessel, platelets adhere to the different interface, aggregation, and gelation of plasma, that is, formation of fibrin crosslinks, occur.

In conventional blood bags, platelets in the blood aggregate on the inner surface of the blood bag, and the number of platelet floating cells in the blood decreases to about 60 to 70% 10 hours after blood collection. For this reason, the expiration period of current platelet products is set at 6 hours after manufacture, and from the point of view of effective blood utilization, it is desired to develop a blood bag that can store nTI fluid cells for a longer period of time. . In order to solve these problems, Japanese Patent Application Laid-Open No. 55-1519
Although Japanese Patent No. 68 proposes a method of subjecting the surface of the bag to low-temperature plasma treatment, the effect is not sufficient.

[Problem that the invention seeks to solve]

An object of the present invention is to provide a blood bag that has excellent blood compatibility and has less adhesion to blood cells such as platelets.

[Means for solving problems]

As a result of various studies to achieve the above object, the present inventors have discovered that the object can be achieved by bonding a predetermined amount of a water-soluble and substantially nonionic polymer to the inner surface of a blood bag. This discovery led to the present invention.

That is, the present invention provides a blood bag formed from a transparent or translucent plastic film or sheet, the inner surface of which contains a water-soluble and substantially nonionic polymer in a range of 1 to 100 pg/d. This is a blood bag characterized by being connected.

The water-soluble and substantially nonionic polymer used in the present invention is a polymer that is water-soluble at room temperature or under elevated temperature and has little or no ionic groups. Even water-soluble polymers cannot be used if they contain a large amount of ionic groups because of poor blood compatibility. Examples of preferred polymers include acrylamide polymers such as polyacrylamide and polydimethylacrylamide, methacrylamide polymers such as polymethacrylamide, polyvinylpyrrolidone, partially saponified and fully saponified polyvinyl alcohol, polyethylene glycol, and dextran. You can give things like

Among these, polyacrylamide polymers, polyvinylpyrrolidone and polyvinyl alcohol are particularly preferred in terms of blood compatibility. These polymers can be used alone or in combination of two or more. Further, the polymer may be a homopolymer or a copolymer.

Such a water-soluble and substantially nonionic polymer needs to be bound to the inner surface of the blood bag in a range of 1 to OO)t(p'crA, preferably 10 to 5
It is 0 μg/cA. If the binding force of the polymer is outside this range, the platelets will become too sticky and cannot be used.

Various conventionally known methods can be used to bond the water-soluble and substantially nonionic polymer to the surface of the blood bag, and the conditions are adjusted so that the amount of bonding falls within the above-mentioned range. Just choose.

Specific examples of this method include a method in which radicals or peroxides are generated on the surface of the blood bag substrate, and a monomer is brought into contact with this to perform graft polymerization, and a method in which a polymer is generated in advance. An example of this method is to place the base material on the surface of the base material and chemically bond it onto the surface of the base material. As a method for generating radicals or peroxides, (1)
Methods of irradiating with high-energy radiation such as electron beams and gamma rays, (2) methods of irradiating with ultraviolet rays, (3) low-temperature plasma discharge treatment, (4) corona discharge treatment, (5) ozone treatment, and (6) benzoyl peroxide treatment. There is a method of adding a radical polymerization initiator such as Polymerization is carried out by allowing the monomer to coexist when the substrate is subjected to these treatments, or by bringing the monomer into contact with the substrate after the treatment. The amount of bonding can be adjusted by adjusting the processing conditions of the substrate, the contact time of the monomer, the temperature, etc.

Monomers used include acrylamide, dimethylacrylamide, methacrylamide, vinylpyrrolidone, vinyl acetate and ethylene oxide. Vinyl acetate is converted into polyvinyl alcohol by saponification after polymerization.

Methods for chemically bonding a polymer onto the surface of a bag base material include a method in which the reactive groups on the surface of the base material are directly reacted with reactive groups on the polymer, and a method in which the reactive groups on the base material surface are bonded to each other through other compounds. There is a way to combine them. This method is suitable for polymers having hydroxyl groups in the molecule, such as polyvinyl alcohol, polyethylene glycol, and dextran, and a method of bonding to a base material having hydroxyl groups via a diisocyanate compound is preferably used.

The material of the blood bag substrate made of transparent or translucent plastic film or sheet used in the present invention is not particularly limited, and various thermoplastic plastic materials can be used. Specific examples include polyethylene, ethylene-vinyl acetate copolymer or completely or partially saponified product thereof, polypropylene, propylene copolymer, polyvinyl chloride, polyvinylidene chloride, polyacrylonitrile, polyethylene terephthalate, polybutylene terephthalate. , nylon 6
, nylon 66 and nylon 12. Among these, ethylene-vinyl acetate copolymer and polyvinyl chloride are preferably used.

In the present invention, it is important to adjust the binding amount of the water-soluble and substantially nonionic polymer so that it falls within the above-mentioned range, but the method for measuring the polymer binding amount is as follows:
For example, there are methods as described below.

(1) A sample is chemically treated to release part or all of the bound polymer, and the released product is quantified.

(2) The sample is dissolved in a solvent that dissolves the base material but not the polymer, and the polymer is separated and quantified.

(3) The monomer to be graft polymerized or the polymer before bonding is labeled with a radioactive isotope, and the amount of radioactivity in the sample is measured after the bonding process.

(4) Total reflection infrared absorption spectrum (ATR, -IR)
Measure and use the calibration curve prepared in advance.

Since a suitable measuring method varies depending on the material of the substrate used and the type of water-soluble polymer to be bonded, an appropriate method may be selected depending on each case.

In manufacturing the blood bag of the present invention, a water-soluble and substantially nonionic polymer may be bonded to the surface of the film or sheet that is the material of the blood bag in advance, and then the blood bag may be manufactured. A water-soluble and substantially non-ionic polymer may be bonded to the inner surface of the blood bag after it has been manufactured.

The blood bag of the present invention contains an anticoagulant, a blood preservation solution, and the like in order to prevent blood from coagulating.

Examples include ACD solution, which has sodium citrate as its main component and citric acid and glucose added to it; CPD solution, which has sodium phosphate added thereto; and EDTA solution, which consists of tetrapotassium salt solution of ethylenediaminetetraacetic acid. used.

Further, the blood bag is sterilized in advance by a method such as autoclave sterilization before use.

(Function) It is not clear why binding a predetermined amount of a water-soluble and substantially nonionic polymer to the inner surface of a blood bag reduces the adhesion of blood cells such as platelets, but it is possible to It is presumed that this is due to the development of a surface with low interaction with blood cells.

(Example) Example 1 A transparent sheet made of ethylene-vinyl acetate copolymer with a vinyl acetate content of 10% by weight was washed with ethanol and then subjected to argon gas plasma treatment using a low-temperature plasma surface treatment device. The processing conditions were: output 11.5W
, the gas flow rate was 20c4', the kitchen pressure was 0.04 Torr, and the processing time was 30 seconds. The sheet treated with plasma in this manner was immersed in a 10% aqueous solution of acrylamide, and graft polymerization was performed at 50°C for 2 hours under nitrogen gas to obtain a sheet with polyacrylamide bonded to the surface. .

The amount of polyacrylamide bonding in the obtained sheet was measured by the following method. In other words, the sheet was immersed in 1.5N hydrochloric acid and treated in an autoclave at 2.5 atm for 30 minutes to hydrolyze the polyacrylamide. Thereafter, the mixture was neutralized with sodium hydroxide, a ninhydrin solution was added, and the mixture was reacted again for 5 minutes in an autoclave at 3 atm, and the absorbance of the reaction solution at 570 nm was measured. The amount of polyacrylamide bound was calculated from this measured value and a previously determined calibration curve. As a result, the amount of polyacrylamide bound was 15 pg/cl.

In the same manner, sheets with various amounts of polyacrylamide bonds were prepared by changing the plasma treatment time and graft polymerization time.

0.1 yet of platelet-rich plasma from which calcium ions had been removed was placed on these sheets and untreated sheets, and after washing with physiological saline, the stickiness of the platelets was observed using a scanning electron microscope. The results are shown in Table 1. Shown below.

Table 1゜Table 1. As is clear from the above, when no polyacrylamide is bound at all or when the bound amount exceeds 100 μg/d, a large amount of platelets adhere to the polyacrylamide, but the bound amount is 1 to 1 μg/d.
It can be seen that in the range of 00 μg/c4, almost no adhesion was observed, indicating excellent blood compatibility.

Example 2 Using dibutyltin dilaurate as a catalyst, hexamethylene diisocyanate was bonded to the surface of an ethylene-vinyl alcohol copolymer film (ethylene content: 30 mol %) by a urethanization reaction. This has a polymerization degree of 1700
of polyvinyl alcohol is bonded by a urethanization coupling reaction, and the amount of polyvinyl alcohol bonded is 26
A film of pg/ctA was obtained.

This film was examined for platelet adhesion in the same manner as in Example 1, but no adhesion was observed. On the other hand, a large amount of platelets adhered to the rice-treated film that did not bind polyvinyl alcohol.

(Effects of the Invention) Compared to conventional blood bags, the blood bag of the present invention has less adhesion and aggregation of blood cells such as platelets and is impaired in blood compatibility, so platelets and granulocytes can be stored stably for a long period of time. It is.

Claims (2)

[Claims] (1) A blood bag formed from a transparent or translucent plastic film or sheet, the inner surface of which contains 1 to 100% of a water-soluble and substantially nonionic polymer.
A blood bag characterized by being bound in a range of μg/cm^2. (2) The blood bag according to claim 1, wherein the amount of the polymer bound is 10 to 50 μg/cm^2.