JPH06319784A - Base material for blood bag - Google Patents

Abstract

PURPOSE:To provide a base material for a blood bag which has a better hemolysis suppressing action with excellent dynamical nature. CONSTITUTION:This base material for a blood bag is made of a polymer composition composed of crystalline polypropylene based polymer or a crystalline polybutene-1 based polymer (A), polypropylene based atactic polymer (B) and a low molecular weight organic ester based plasticizer (C).

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. The strength to be obtained, heat resistance to withstand high-pressure steam sterilization, hygiene, safety and the like. 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 treatment of PVC waste has been highlighted, and there is a great need for “non-PVC” blood bags. Various proposals have been made so far, but the stage has reached a satisfactory level. The reality is that they do not.

For example, in Japanese Patent Publication No. 3-502298, non-P
Although it is described that the composition of citrate ester in VC plastics (compositions composed of styrene elastomer, polypropylene and the like is mentioned as a specific example) has a function of suppressing the hemolysis phenomenon of red blood cells. However, within 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]

DISCLOSURE OF THE INVENTION The present invention has been made to provide a non-PVC base material for blood bags which is excellent in preservability of red blood cells.

[0006]

Means for Solving the Problems What has been clarified by the investigations of the present inventors is that the introduction of a plasticizer as a constituent component into a specific polymer combination is suitable for solving the above-mentioned problems. Layer forming a polymer composition composed of polypropylene, crystalline polybutene-1 or a crystalline copolymer (A) containing these as the main components, a polypropylene atactic polymer (B) and a low molecular weight ester plasticizer (C) The present invention has as its essence a base material for a blood bag containing as. The polypropylene atactic polymer (B) has excellent compatibility with the crystalline polymer (A) and has a proper affinity with the plasticizer (C), so that the base material of the present invention has flexibility, transparency and suppression of hemolysis. I think it is linked to the action.

Among (A) in the present invention, crystalline polypropylene or a crystalline copolymer containing the crystalline polypropylene as a main component (hereinafter referred to as polypropylene type crystalline polymer) is usually isotactic obtained by using a stereoregular polymerization catalyst. Alternatively, it is a polymer whose main component is syndiotactic polypropylene.

These are appropriately selected, but from the viewpoint of flexibility, a copolymer, particularly a copolymer rich in randomness, is advantageous.

As the comonomer, ethylene, butene-
Α-olefins having 2 to 12 carbon atoms such as 1, pentene-1, hexene-1, octene-1, decene-1, dodecene-1, and 4-methylpentene-1 are preferable, and the comonomer amount is 3 to 40 mol. %, And more preferably about 5 to 30 mol%.

A particularly preferred polypropylene-based crystalline polymer has a flexural modulus (JISK7203) of 8,000 k.
Vicat softening point below g / cm ² (JISK7206)
Is 100 ° C. or higher, which is preferable from the viewpoint of the balance of flexibility, transparency and heat resistance.

The crystalline polypropylene-based polymer has a temperature of 230 ° C. due to its moldability and mechanical properties of the molded product.
The MFR (melt flow mate) at a load of 2,160 g is preferably 0.3 to 40, more preferably 5 to 30.

Further, among (A), crystalline polybutene-1
Alternatively, a crystalline copolymer containing the same as the main component (hereinafter referred to as polybutene-1 crystalline polymer) means so-called isotactic polybutene-1 or a copolymer containing the same as the main component, and is usually produced by a known method. There is.
In the case of copolymers, the comonomers used are ethylene, propylene, pentene-1, hexene-1, octene-
Α-Olefins such as 1,4-methylpentene-1 are preferred.

These are the flexibility of crystalline polybutene-1,
It is introduced to improve the transparency, etc., but if the melting point (the melting point of homopolybutene-1 is 125 to 130 ° C.) is too low, the heat resistance deteriorates.
It is preferable to suppress it to about mol% or less, more preferably 5 mol% or less.

Considering the moldability and mechanical properties of the product, the polybutene-1 type crystalline polymer has a temperature of 190 ° C.,
The MFR at a load of 2,160 g is preferably 0.2 to 30, more preferably 0.5 to 25.

Since the polypropylene type crystalline polymer and the polybutene-1 type crystalline polymer are excellent in compatibility and miscibility at an arbitrary mixing ratio, (A) may be composed of both components.

Next, the polypropylene-based atactic polymer (B) in the present invention is also referred to as amorphous polypropylene or amorphous polypropylene, and includes those containing atactic polypropylene as a main component, as described in (A). In addition to being produced as a by-product in the production process of polypropylene-based crystalline polymer, it can be produced by radical polymerization or the like.

In the case of copolymers, the same comonomers as in (A) are used. The polypropylene atactic polymer used in the present invention has a property of 190
A melt viscosity at 300C of 300 to 200,000 cps,
It is more preferably 500 to 150,000 cps, and the softening point measured by the ring and ball method is 100 to 160 ° C, and more preferably 110 to 150 ° C.

Next, the low molecular weight organic ester plasticizer (C) in the present invention refers to a low molecular weight compound that can be used for plasticizing ordinary PVC for medical containers, and includes phthalate ester, trimesotate ester, adipate ester, sebacine. Among acid esters, azelaic acid esters, tartaric acid esters, citric acid esters, malic acid esters, etc., the molecular weight is preferably 200 to 800, more preferably 250 to
About 600 is suitable (when the molecular weight is too low, there is a problem of volatility, and when the molecular weight is too high, the molecules do not move in the composition because they do not move easily in the composition containing erythrocytes, and as a result, the hemolytic effect of erythrocytes is suppressed. Because it can be small).

Further, in consideration of the leachability, hemolysis suppressing effect, and influence on the human body, specific examples of desirable plasticizer (C) include di-n-decyl phthalate and adipic acid-n-.
Hexyl, tri-n-butyl acetyl citrate, tri-n-hexyl acetyl citrate, tri-n-butyl butyryl citrate, tri-n-hexyl butyryl citrate,
Di-n-hexyl acetylmalate, n-octyl acetylmalate, di-n-butyl diacetyl tartrate, di-n-hexyl diacetyl tartrate, di-n-butyl dibutyryl tartrate, di-n-hexyl dibutyryl tartrate, etc. Needless to say, the present invention is not limited to these compounds.

As mentioned at the outset, the container according to the invention comprises a polymer composition consisting of (A), (B) and (C) as a forming layer, but here "includes as a forming layer".
Means that the container (sheet) is composed only of the polymer composition of (A), (B) and (C), and that the container has at least one layer of the polymer composition and at least one layer of another polymer. It shows that there are both cases where it is composed of multiple layers.

In the case of (1), the polymer composition having mechanical properties such as flexibility and strength, moldability, heat sealability, and blocking resistance ((A), (B) and (C) has tackiness. , And may be blocked), etc., and the above "other polymer" which is adopted to form a multilayer body is adopted as polyethylene, ethylene-vinyl acetate copolymer, ethylene-acrylic acid ester copolymer, crystalline polypropylene system. Polymer, crystalline polybutene-1
-Based polymer, poly-4-methylpentene-1, polyester, polyamide, polyether ester (polyethylene oxide, polypropylene oxide, ethylene oxide-propylene oxide copolymer, block copolymer of polyester such as polytetramethylene oxide and polyester), polyether Amide (block copolymer of polyether and polyamide as described above),
Polyurethane (particularly polyether type is good) is mentioned.

Of note here is the "other polymer" thickness. That is, the side that comes into contact with blood (the inner wall side of the container)
It is important that the plasticizer component (C) is leached out, and it is preferable to thin the "other polymer" layer within an acceptable range. (0.08 mm or less, more preferably 0.05 m
m or less is recommended).

Whether the composition of the polymer composition is a single layer or a multi-layer; it depends on the type of (C) and the like, but generally the weight ratio of (A) and (B) is 80 to 20:20 to 8.
0, more preferably 70 to 30:30 to 70, (C)
Is preferably 0.5 to 30% by weight, more preferably 1 to 25% by weight in the polymer composition (it goes without saying that in the case of multiple layers, the proportion of (C) should be relatively large). I).

In consideration of strength, workability, operability, etc., the thickness of the sheet constituting the container is 0.08 to 0.60 mm, more preferably 0.10 to 0.60 mm.
It is good that it is 0.50 mm.

In the present invention, the blood bag means a soft plastic container for storing a liquid containing blood components, especially red blood cells, and such a product can be manufactured by a generally known method. That is, the above-mentioned polymer composition is extruded through a T die or a circular die, alone or at the same time as another polymer, and the obtained flat sheet, tubular sheet, parison, etc. are subjected to thermoforming, blowing, stretching and cutting. It may be processed into a predetermined shape and form by appropriately utilizing a technique such as fusion (heat sealing).

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, a styrene-based elastomer, an olefin-based elastomer, etc. may be added within a range not impairing the gist of the present invention.

[0029]

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 3, Comparative Examples 1 and 2) (1) Sheet Preparation of polymer composition: Polymer (A) shown in Table 1,
(B) and the plasticizer (C) are kneaded at a predetermined ratio in a temperature range of 170 to 180 ° C. using a biaxial melt kneading extruder, and the extruded strand is water-cooled and cut to form a pelletized polymer composition. The product (D) was obtained ((A) in Table 1)
(B) and (C) as well as the polymer composition (D) and the like).

Preparation of sheet: Using the pellets of (A) and (D), 18 from a single-layer or multi-layer T die
Extruded at 0-230 ℃, cooled by casting roller kept at 20 ℃, trimmed to a thickness of 0.35 m
A sheet having a width of m and a width of 200 mm was wound at a speed of 4 m / min.

Measurement of mechanical properties of the sheet: The sheet was cut into a dumbbell shape and the tensile breaking strength and tensile elastic modulus were measured according to JIS K7113. The results are shown in Table 2.

Sheet heavy metal and eluate test: The test was carried out according to the Japanese Pharmacopoeia General Test Method "Plastic Container Test Method for Infusion Solution".

(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 inner dimensions of 50 mm × 80 mm was heat-sealed. Made,
After autoclave sterilization at 115 ° C. for 30 minutes, it was dried.

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
Aseptically dispensed into the above-mentioned mini-bags in ml in a clean bench and stored at 4 ° C for 3 weeks, the amount of plasma hemoglobin in each mini-bag was measured by a conventional method, and the hemolysis level was evaluated.

As a control in this test,
A mini bag having the same shape was prepared and used for an experiment in the case of not containing a plasticizer (Comparative Example 1) and in the case of a polyvinyl chloride sheet containing diethylhexyl phthalate (DEHP) 55PHR (Comparative Example 2).

[0037]

[Table 1]

(3) Results of evaluation of physical properties and results of hemolysis experiment (see Table 2) All the sheets were manufactured smoothly, and excellent transparency was obtained. Further, as shown in Table 2, the strength and flexibility of the sheet were at practically sufficient levels. It was also confirmed that heavy metals and eluates also cleared the standards.

Further comparing the hemolysis levels from Table 2,
It can be seen that the substrate of the present invention is comparable to the commonly used DEHP plasticized polyvinyl chloride bag (Comparative Example 2) in its practicality. On the other hand, a polymer composition consisting of only (A) and (B) (Comparative Example does not contain a plasticizer (C), the polymer composition (E)) has a high hemolysis level and is a container for storing red blood cells. Has been confirmed to be unsuitable for.

[0040]

[Table 2]

[0041]

As described above, the base material for a blood bag of the present invention is a crystalline polypropylene polymer or a crystalline polybutene-1 polymer (A), a polypropylene atactic polymer (B) and a low molecular organic ester. The polymer composition composed of the plasticizer (C) is used to effectively suppress hemolysis, and it has sufficient mechanical properties such as flexibility and strength, and substantially contains chlorine. Since it is not used, it is easy to dispose of after use, and it is expected to make a great contribution to the field of blood preservation, and its industrial value is high.

Claims (1)

[Claims] 1. A crystalline polypropylene, a crystalline polybutene-1 or a crystalline copolymer (A) containing these as a main component, and a polypropylene atactic polymer (B).
And a base material for a blood bag, which contains as a forming layer a polymer composition composed of a low molecular weight organic ester plasticizer (C).