JPH06319785A - Base material for blood bag - Google Patents

Abstract

PURPOSE:To obtain a base material for a blood bag which has a better hemolysis suppressing action with excellent dynamical nature by incorporating a polymer component comprising a thermoplastic polyester and a low molecular weight organic ester based plasticizer as formation layer. CONSTITUTION:This base material for a non-PVC based blood bag replaces that for the PVC (polyvinylchloride) hard to discard is made to contain a polymer composition comprising thermo-plastic polyester and a low molecular weight organic ester based plasticizer as formation layer. The thermoplastic polyester herein used is below 0 deg.C in glass transition temperature considering softness of the bag, affinity to an ester based plastic material and the like. The low molecular weight organic ester based plasticizer B herein used is phthalicacid di-n-decyl, adipic acid di-n-hexyl, acetyl citrate tri-n-butyl or the like considering infusing property, hemolysis suppressing action, effect on human bodies and the like comprehensively.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a substantially chlorine-free substrate for blood bags, which is suitable for storing and storing blood components, especially erythrocyte-containing liquid.

[0002]

2. Description of the Related Art The properties required for a blood bag include transparency for observing the state of the content liquid (blood component), flexibility for facilitating operations such as blood collection, blood transfusion, and blood component separation, and resistance to these operations. Strength, hygiene, safety, etc. can be mentioned. Since soft polyvinyl chloride containing a plasticizer (hereinafter referred to as soft PVC) almost satisfies the above-mentioned required performance, even though disposal after use is regarded as a problem, it is still a material for blood bags. Occupies the mainstream of.

Especially in the preservation of red blood cell components, soft P
Although the plasticizer in VC has an action of suppressing the morphological change of red blood cells and hemolysis, it does not have such action in other polymer systems such as polyethylene and polypropylene system.
Soft PVC is used exclusively as a bag material. On the other hand, however, the problem of treating PVC waste has been greatly highlighted, and blood bag "non-PVC"
There is a great need for “commodification”, and various proposals have been made so far, but the reality is that they have not reached the stage where they can be fully satisfied.

For example, in Japanese Patent Publication No. 3-502298, non-P
Although it is described that a composition of VC plastic (a specific example is a composition composed of styrene-based elastomer, polypropylene, etc.) and citric acid ester has a function of suppressing the hemolysis phenomenon of red blood cells. However, in the range that the present inventors have tried, the plasticizer in the soft PVC is inferior in the hemolytic suppression effect and is not practical.

[0005]

SUMMARY OF THE INVENTION In view of the above circumstances, the present invention has been made to provide a non-PVC base material for blood bags which is excellent in storability of red blood cells.

[0006]

DISCLOSURE OF THE INVENTION What has been clarified by the study by the present inventors is that the introduction of a plasticizer into a thermoplastic polyester leads to a material that solves the above problems. And a low molecular weight organic ester-based plasticizer (B) as a formation layer, the present invention has been made to have a skeleton as a blood bag substrate.

In the present invention, an appropriate affinity between the polyester (A) and the ester plasticizer (B) controls the amount of the plasticizer (B) which is leached into the blood component (that is, acts as a hemolytic inhibitor). I believe that.

In the present invention, the thermoplastic polyester (A) refers to a generally known polyester having a substantially linear structure, and includes malonic acid, succinic acid, glutaric acid, adipic acid,
Pimelic acid, suberic acid, azelaic acid, sebacic acid,
Dodecanedioic acid, dimer acid (hydrogenated product is preferred),
Dicarboxylic acids such as terephthalic acid, isophthalic acid, Na5-sulfoisophthalic acid, naphthalenedicarboxylic acid or alkyl esters thereof, ethylene glycol, trimethylene glycol, propylene glycol,
1,4-butanediol, neopentyl glycol,
1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 1,10-decanediol, 1,12-dodecanediol, diethylene glycol , 1,4-cyclohexanedimethanol, 2,2-
Low-molecular glycols such as bis (p-β-hydroxyethoxyphenyl) propane and bis (p-β-hydroxyethoxyphenyl) sulfone, low-molecular oxy acids such as ε-hydroxycaproic acid, and low-molecular lactones such as ε-caprolactone And polyethers having an ester-forming functional group (carboxyl group, alkoxycarbonyl group, hydroxyl group, etc.) at the end, such as polyethylene oxide, polypropylene oxide, ethylene oxide-propylene oxide copolymer, polytetramethylene oxide (polytetrahydrofuran), etc. They can be obtained in appropriate combination by a commonly known technique such as esterification, transesterification, polycondensation and the like.

The glass transition temperature (hereinafter referred to as Tg) of the polyester (A) is 0 ° C. or lower in consideration of the flexibility of the bag and the affinity with the ester plasticizer (B). preferable.

Generally, the more aromatic components (the less aliphatic components) the more hard segments, so Tg
The introduction of a soft component (soft component) such as polyether has a great effect on lowering Tg. (Polyether has a number average molecular weight of 500 to 5
It is recommended that 50,000, more preferably 800 to 30,000, is obtained in the sense that a uniform polyester can be obtained).

Needless to say, trifunctional or higher functional compounds such as trimellitic acid, trimesic acid, trimethylolpropane and pentaerythritol may be introduced as long as the "thermoplasticity" is maintained.

The polyester (A) has an intrinsic viscosity of 0.4 to 4.0, more preferably measured in a mixed solvent of phenol / sym-tetrachloroethane and the like at 25 ° C., more preferably from the viewpoint of sheet forming ability and mechanical properties. 0.5-3.0
Is preferred.

Next, the low molecular weight organic ester type plasticizer (B) in the present invention refers to a low molecular weight organic ester type compound used for plasticizing ordinary PVC for medical containers, and includes phthalic acid ester, trimellitic acid ester and adipine. Acid ester,
Among sebacic acid ester, azelaic acid ester, tartaric acid ester, citric acid ester, malic acid ester and the like, those having a molecular weight of preferably 200 to 800, more preferably about 250 to 600 are suitable. If the molecular weight is too low, there is a problem of volatility, and if the molecular weight is too high, it is difficult for the molecules to move in the composition so that it does not easily leach into the erythrocyte-containing liquid, and as a result, the hemolytic effect of erythrocytes may be reduced. Because.

Considering synthetic properties such as leachability, hemolysis-suppressing action, and human influence, specific examples of desirable plasticizer (B) include di-n-decyl phthalate and di-n adipate.
-Hexyl, tri-n-butyl acetylcitrate, tri-n-hexyl acetylcitrate, tri-n-hexyl butyrylcitrate, di-n-hexyl acetylmalate, di-n-octyl acetylmalate, dibutyrylmalate Examples include -n-hexyl, di-n-butyl diacetyl tartrate and di-n-hexyl dibutyryl tartrate, but it goes without saying that the present invention is not limited to these compounds.

As described at the beginning, the blood bag substrate of the present invention contains the polymer composition composed of (A) and (B) as a forming layer. A case where the base material (sheet) for the bag is composed only of the composition of (A) and (B), and the base material has at least one layer of the composition and at least one layer of another polymer. It means that it may be the body.
In the case of, the mechanical properties of the bag (flexibility, strength, etc.),
It is used to control and improve moldability, heat sealability, blocking resistance, heat resistance, and the like.

The above-mentioned thermoplastic polyester (A) is most preferable as the "other polymer" forming the multilayer body, but polyethylene, ethylene vinyl acetate copolymer, ethylene-acrylic acid ester copolymer, polypropylene, poly-4-methylpentene are preferable. -1, polyamide, polyether amide (block copolymer of polyether and polyamide), polyurethane and the like.

Of note here is the thickness of the "other polymer" layer. That is, it is important that the plasticizer component (B) leaches out on the side that comes into contact with blood (the side of the inner wall of the bag), and the "other polymer" layer should be thin within an allowable range (0.08 mm). Or less, more preferably 0.0
5mm or less is recommended).

The composition of the polymer composition differs depending on the type of (A) or (B) and whether it is a single layer or a multilayer.
It is preferable that (B) occupy 0.5 to 30% by weight, more preferably 1 to 25% by weight in the polymer composition (in the case of multiple layers, the proportion of (B) should be relatively large. Needless to say). The thickness of the sheet (base material) constituting the bag is 0.08 to 0.06 mm, more preferably 0.1, in consideration of strength, workability, operability and the like.
It is good that it is 0 to 0.50 mm.

In the present invention, the blood bag is a blood component,
In particular, it means a soft plastic container for storing a liquid containing red blood cells, but such a product can be manufactured by a generally known method. That is, the polymer composition is extruded alone or simultaneously with other polymers through a T-die or a circular die, and the obtained flat sheet, tubular sheet, parison, etc. are subjected to thermoforming, blowing, stretching, cutting, A method such as fusion (heat sealing) may be appropriately used to process the material into a predetermined shape and form.

A laminating method may be applied to manufacture the multilayer sheet.

Needless to say, in order to prevent blocking between the sheets, the inner surface or outer surface of the container may be roughened (embossing), an antiblocking agent, a slip agent or the like may be added.

Further, to the extent that the gist of the present invention is not impaired,
It is possible that another polymer is further added to the polymer composition of (A) and (B).

Since both (A) and (B) have an ester bond, in order to suppress the transesterification reaction between (A) and (B), at the time of preparation or molding of the polymer composition. The temperature is preferably 200 ° C. or lower, more preferably 190 ° C. or lower.

[0024]

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 4 and Comparative Examples 1 and 2) (1) Preparation of thermoplastic polyester (A) for sheet Dimethyl adipate, dimethyl terephthalate, 1,4-
A predetermined amount of butanediol and polytetramethylene oxide having hydroxyl groups at both ends and a number average molecular weight of 1,500 is charged into a polymerization vessel equipped with a stirring rod, and tetra-n-butyl titanate is added in an amount of 0.2 × 10 4 to 1 mol of the dicarboxylic acid component.
^-4 mol processing-esterification reaction was carried out at 150 to 200 ° C under normal pressure for 4 hours. Next, the system was gradually depressurized to reach 0.1 Torr in 1 hour, and a polycondensation reaction (deglycolization reaction) was performed at 230 ° C. for 2.5 hours to obtain two types of polyester. Table 1 shows the composition, intrinsic viscosity (η) and Tg.

Note that (η) uses an Ubbelohde viscometer,
It was measured in a mixed solvent of phenol / sym-tetrachloroethane and the like at 25 ° C., and Tg was measured by a DSC3100 type differential scanning calorimeter manufactured by Mac Science at a temperature rising rate of 10 ° C./min.

Polyester (A ₁ ) (A ₂ ) prepared in the preparation of polymer composition, di-n-decyl phthalate (DnDP) (B ₁ ) as a plasticizer, and tri-n-hexyl butyryl citrate (BTHC) )
(B ₂ ) was kneaded in a temperature range of 170 to 180 ° C. at a ratio shown in Table 2 using a twin-screw melt-kneading extruder, and the extruded strand was water-cooled, cut, dried, and pelletized polymer. Compositions (C ₁ ) to (C ₄ ) were obtained.

Preparation of sheet: Using the pellets of (A ₁ ) (A ₂ ) and (D ₁ )-(D ₄ ), extruded from a single-layer or multi-layer T die at 180 ° C. and kept at 20 ° C. After cooling with a casting roller, a sheet having a thickness of 0.28 mm and a width of 200 mm was trimmed and wound up at a speed of 6 m / min.

(2) Evaluation of container Preparation of container: Using the sheet obtained above, a rectangular mini bag (capacity 50 ml) having an effective surface area of about 80 cm ² and internal dimensions of 50 mm × 80 mm was prepared by the heat sealing method. Made,
It was sterilized with ethylene oxide gas (65 ° C. × 5 hours).

Hemolysis experiment: 400 ml of whole blood was collected from a healthy person in a blood collection bag containing an anticoagulant, and a red blood cell concentrate (CRC) was prepared by a conventional method. 50 CRC after adjustment
Each ml was aseptically dispensed into the mini bag in a clean bench, and stored at 4 ° C. for 3 weeks, and the amount of plasma hemoglobin in each mini bag was measured by a conventional method to evaluate the hemolysis level.

As a control in this test,
When no plasticizer is included (Comparative Example 1) and di-2-phthalic acid
Soft PV containing Ethylhexyl (DEHP) 55PHR
With respect to the case of the C sheet (Comparative Example 2), a mini bag having the same shape was produced and subjected to an experiment.

[0032]

[Table 1]

[0033]

[Table 2]

(3) Experimental Results The polyester, polymer composition and sheet were all produced smoothly, and a flexible and highly uniform sheet was obtained.
It was also confirmed that heavy metals and eluates also cleared the Japanese Pharmacopoeia General Test Method “Plastic Test Method for Infusions”.

Further, comparing the hemolysis levels of the bags as shown in Table 3, the base material of the present invention is D
It can be seen that the bag made of EHP plasticized PVC (Comparative Example 2) is comparable to the practicality thereof. On the other hand, the bag made of only thermoplastic polyester (Comparative Example 1) has a high hemolysis level and is not suitable as a container for storing red blood cells.

[0036]

[Table 3]

[0037]

As described above, the base material for a blood bag of the present invention is a hemolytic inhibitory action of a polymer composition composed of a thermoplastic polyester (A) and a low molecular weight organic ester plasticizer (B). It is a highly versatile product, is versatile, and has virtually no chlorine, making it easy to dispose of after use, and is expected to make a major contribution to the field of blood preservation. Some have high value.

Claims (1)

[Claims] 1. A substrate for a blood bag, which comprises, as a forming layer, a polymer composition composed of a thermoplastic polyester (A) and a low molecular weight organic ester plasticizer (B).