JPH06277263A - Container for preserving blood platelet - Google Patents

Abstract

PURPOSE:To provide the container for preserving blood platelets having high resilience and excellent strength and gas permeability by using a layer consisting of a polymer plastic material composed of an ethylene/vinyl acetate copolymer and a thermoplastic elastomer and a layer consisting of a polymer for reinforcement. CONSTITUTION:The double-layered structure made of the layer consisting of the polymer plastic material composed of the ethylene/vinyl acetate copolymer and the thermoplastic elastomer and the layer consisting of the polymer for reinforcement is used as the container forming layer to be adequately used as the container for preserving the blood platelets. The ethylene/vinyl acetate copolymer which contains preferably about 12 to 35 pts.wt. vinyl acetate and having about 2 to 35 melt flow rate at 190 deg.C and under 2160g load is used by taking moldability into consideration. The thermoplastic elastomer of, for example, a polyolefin base, polystyrene base or 1,2-polybutadiene base is used.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a gas-permeable soft plastic container suitable for long-term storage of platelets.

[0002]

2. Description of the Related Art The demand for blood fractionation and component transfusion is increasing due to reasons such as effective use of blood and reduction of the burden on transfusion recipients, but one of the problems is the preservation of platelets.
For example, when platelets are stored in a polyvinyl chloride blood storage bag using di-2-ethylhexyl phthalate, which is a conventional mainstream, as a plasticizer, the gas permeability of the bag, especially the oxygen gas permeability is small, so that the pH is rapidly increased. It is pointed out that it causes a rapid decrease in blood pressure and accelerates the decline in platelet function.
As a countermeasure, the following proposals for a container (bag) for storing platelets have been submitted, and it is well known that some of them have already been put to practical use.

Increasing the specific surface area of the bag relative to the platelet reserve.

Thinning of the sheet forming the bag (eg:
JP-A-58-29465).

Adoption of a sheet made of a material (polymer) having good gas permeability (eg, JP-A-54-88950, JP-A-58-501035, JP-A-62-144660).
JP-A No. 2-1279).

[0006]

However, the problems of operability and storability associated with the increase in bag size are
There is a decrease in mechanical properties. In addition, the most effective one is a block copolymer (so-called SEBS) formed from polystyrene segment and ethylene butylene copolymer segment, polypropylene and a polymer composition mainly composed of ethylene vinyl acetate copolymer or ethylene acrylic ester copolymer. Although it is a bag made of a sheet of material, it has been pointed out that the bag lacks flexibility and has poor operability since polypropylene having high rigidity is used as a constituent component of the composition.

The present invention has been made to solve the above-mentioned problems in conventional platelet storage containers, and to provide a platelet storage container which is rich in gas permeability and flexibility and is excellent in operability. Is.

[0008]

DISCLOSURE OF THE INVENTION What has been clarified by the study of the present inventors is that a polymer composition of ethylene vinyl acetate copolymer (hereinafter referred to as EVA) and a thermoplastic elastomer has an extremely good gas permeability. The problem in terms of strength of the composition is that it can be solved by forming a multilayer with a reinforcing polymer.

That is, the present invention is a container for preserving platelets, which comprises a layer comprising a polymer composition (C) of EVA (A) and a thermoplastic elastomer (B) and a layer comprising a polymer (D) for reinforcement as forming layers. Is the main point.

The EVA (A) in the present invention has a vinyl acetate content of 10 to 35% by weight, more preferably 12%.
It is preferably about 35% by weight. This is because when the vinyl acetate content is low, the gas permeability of the polymer composition with the thermoplastic elastomer tends to be low, and when the vinyl acetate content is high, the strength is too low and the moldability is poor.

Considering formability, MFR (melt flow rate) at a temperature of 190 ° C. and a load of 2,160 g
Is preferably 1 to 40, more preferably about 2 to 35.

Next, as the thermoplastic elastomer in the present invention, a polyolefin-based, polystyrene-based or 1,2-polybutadiene-based thermoplastic elastomer is suitable, and in the polyolefin-based elastomer, an ethylene-propylene-based copolymer (hereinafter referred to as EP), In the polystyrene-based elastomer, a block copolymer of polystyrene and ethylene-propylene copolymer (triblock type SEPS is preferable) or a block copolymer of polystyrene and ethylene butylene copolymer (triblock type SEBS is preferable), 1,2
In the polydiene system, the amount of 1,2-bonds is 85% or more, more preferably 90% or more syndiotactic-1,2-
Polybutadiene (hereinafter referred to as 1,2-PB) is a typical example, and these are usually produced by a known method.

EP is used as a third component, if necessary, 5-ethylidene-2-norbornene, dicyclopentadiene,
1,4-cyclohexadiene and the like are used, and in consideration of imparting gas permeability, moldability and mechanical properties, the propylene content is 20 to 40% by weight, the MFR at a temperature of 230 ° C. and a load of 2,160 g is 0. It is preferable to select 2 to 10, more preferably 0.5 to 8.

SEPS and SEBS are usually block copolymers of polystyrene and polyisoprene (SI
S), a block copolymer of polystyrene and polybutadiene (SBS) is hydrogenated to produce. Considering the same matters as EP, the polystyrene content occupies 10 to 40% by weight, and the MFR at a temperature of 230 ° C. and a load of 2,160 g is 0.1 to 50, more preferably 0.2 to 40. Is preferred.

Further, 1,2-PB is obtained by a method of solution polymerization using a Ziegler type catalyst, and one having an MFR of about 1 to 10 at a temperature of 150 ° C. and a load of 2,160 g is preferably used.

One of the constituent layers of the multilayer sheet constituting the container of the present invention is a polymer composition (C) of the above (A) and (B).
It is appropriate that (A) is 20 to 85% by weight, more preferably 25 to 80% by weight, and (B) is 80 to 15% by weight, more preferably 75 to 20% by weight.
If the amount of (A) is too small, the mechanical properties (particularly strength) of the sheet will be poor, and the reinforcing polymer (D) layer will have to be made thicker, resulting in insufficient flexibility and gas permeability. Because it will be. On the other hand, if the amount of (B) is too small, the gas permeability will be significantly reduced.

Next, the other of the constituent layers of the multilayer sheet constituting the container of the present invention is a layer of the reinforcing polymer (D),
As (D), in addition to the role of maintaining the strength of the sheet, flexibility and gas permeability are also taken into consideration.

Low density polyethylene, linear low density polyethylene, EVA, ethylene ethyl acrylate copolymer,
Ethylene methyl methacrylate copolymer, polybutene-
1. Polyether ester (block copolymer of polyether and polyester such as polyethylene oxide, polypropylene oxide, polytetramethylene oxide), polyether amide (block copolymer of polyether and polyamide as described above), polyurethane (especially polyether) Type is good). In particular, polyetheresters, polyetheramides and polyurethanes have excellent "blood compatibility", so the parts that come into direct contact with platelets (ie the inner wall side of the platelet storage container)
It is preferable to use these as the forming layer.

It should be noted here that the reinforcing polymer (D) is used.
Most of them have a low oxygen gas permeability, and it is preferable to reduce the thickness of the reinforcing polymer (D) within an allowable range (the thickness of the reinforcing polymer (D) is 0.12 mm.
It is recommended that the thickness is less than 0.10 mm, more preferably less than 0.10 mm. ).

In order to exhibit a good function as a container for storing platelets, the oxygen gas permeation amount of the sheet constituting the container is 1,800 ml / m ² · day · atm (a
t22 ° C) or higher, more preferably 2,000 ml / m ²
・ Day ・ atm (at 22 ° C) or higher is desirable. Considering this requirement, strength, flexibility, etc., (A)
And (B), the thickness of (C), the thickness of (D), etc. are determined. (Generally, the strength, workability, operability, or in the case of a multi-layered body varies depending on the layer structure, but 0.10
A range of up to 0.40 mm is suitable. ) The container for storing platelets of the present invention can be manufactured by a generally known method. That is, (C) and (D) are extruded through a multi-layer T die or a circular die, and the obtained flat sheet, tubular sheet, parison, etc. are subjected to thermoforming, blowing, stretching, cutting and fusion (sealing). It may be processed into a predetermined shape and form by appropriately utilizing such a method.
A laminating method may be applied to manufacture the multilayer sheet. Needless to say, the inner surface and outer surface of the container may be roughened (embossing) and / or an antiblocking agent, a slip agent or the like may be added to prevent blocking between the sheets.

Further, it is possible that a thermoplastic elastomer or the like is added to (D) in an amount within the range not impairing the gist of the present invention.

[0022]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.

(Examples 1 to 7, Comparative Examples 1 to 3) (1) Sheet Preparation of polymer composition: pellets of polymer (raw material) were used at a predetermined ratio of 150 using a twin-screw melt-kneading extruder. ℃
The extruded strands kneaded in the temperature range of 220 ° C to 220 ° C were water-cooled, cut and dried to obtain a pelletized polymer composition (C) (in Table 1, (A) and (B), (A) )
Polymer compositions (C) of (1) and (B), polyether amide (D), etc. are also shown).

Preparation of sheet: Using the pellets (C) and (D), extruded from a multi-layer T-die at 180 to 210 ° C., cooled by a casting roller kept at 20 ° C., and trimmed to a thickness of 0. 0.26 mm, width 200 mm
Was wound at a speed of 5 m / min.

Evaluation of sheet: 2 using a fully automatic gas permeability measuring device (L100-3001 manufactured by Lissie)
The oxygen gas permeability at 2 ° C. × 65% RH was measured.
Further, it was cut into a dumbbell shape, and the tensile breaking strength and the tensile elastic modulus were measured according to JIS K7113. The results are shown in Table 2.

(2) Evaluation of container Preparation of container: The sheet of (1) was cut and sealed to prepare a bag having an effective surface area of 300 cm ² .

Platelet preservation experiment: concentrated platelets (PC) 2
Each unit (platelet number 4 × 10 ¹⁰ ) was dispensed into each bag and stored by horizontal shaking at 22 ° C. (a shaker using an eight shaker manufactured by Yayoi Co., Ltd., shaking number 30 rpm), 0, 2
Preserved PC was collected every 4, 48, 72, 96, 120 and every 24 hours, and the platelet count (manufactured by Toa Medical Electronics Co.,
Automatic blood cell counter, Sysmex MODEL CC-
180), pH (Horiba Seisakusho, pH meter H
ORIBA / F8DP type), aggregation ability (ADP, collagen, ADP + collagen) and low osmotic shock recovery rate (% HSR), plasma LDH activity (platelet leak rate),
Plasma glucose and plasma lactate concentrations, mean platelet volume (MVP) and morphology (morphological score)
Was evaluated. The expiration date of platelets was determined by comprehensively judging these items. In particular, the determination was made with a high degree of importance for pH change (time until pH decrease occurs). The results are shown in Table 3.

[0028]

[Table 1]

[0029]

[Table 2]

[0030]

[Table 3]

(3) Results of evaluation of physical properties and results of storage performance of platelets (see Tables 2 and 3) As shown in Table 2, a layer comprising a polymer composition of (A) and (B) and a reinforcing polymer ( The sheet containing D) as a forming layer showed good gas permeability.

As shown in Table 3, a container prepared from a sheet comprising a layer composed of the polymer composition of (A) and (B) and a sheet containing the reinforcing polymer (D) as a forming layer was used for long-term platelet storage. Is possible (generally, the storage time required for a platelet storage container is 120 hours or more, and it is understood that the container of the present invention satisfies this requirement).

A container made of a layer comprising a polymer composition of (A) and (B) and a sheet containing a reinforcing polymer (D) as a forming layer has high flexibility and practical strength. It has excellent operability because it is within the range.

[0034]

As described above, the container for storing platelets of the present invention is excellent in the good gas permeability of the polymer composition layer of EVA and the thermoplastic elastomer and the mechanical properties of the reinforcing polymer layer. It is expected to make a significant contribution to the field of platelet storage and has a high industrial value because it is highly flexible, has a practically sufficient range in strength, and has excellent operability. .

[0035]

Claims (1)

[Claims] 1. A layer comprising a polymer composition (C) of an ethylene vinyl acetate copolymer (A) and a thermoplastic elastomer (B) and a layer comprising a reinforcing polymer (D) as forming layers. Container for storing platelets