DE3038971A1 - CONTAINER / BAG FOR PRESERVING PHYSIOLOGICAL SALINE SOLUTIONS FOR MEDICAL PURPOSES - Google Patents

Description

description

The invention relates to a plastic bag or plastic container which is resistant to low temperatures (hereinafter for the sake of simplicity half called "bag / container"), which at low temperatures, for example at the temperature of liquid carbonic acid of about -80 C, can be used; it concerns one in particular Plastic container / bag, which is used for the preservation or preservation by freezing blood components such as erythrocytes, Blood plasma and platelets, bacteria, enzymes, physiological saline solutions, foods and chemicals can be used.

Blood is usually collected in containers made of glass, soft polyvinyl chloride, Polypropylene, high density polyethylene and the like. Stored (preserved) at 4 to 6 C. When storing or preserving Under such temperature conditions, the blood decomposes relatively quickly and can only be stored or preserved for about 21 days will.

Recently, it has become possible to store blood for a long period of time or to be preserved by separately preserving each blood component, such as the erythrocytes, the blood plasma, the blood platelets and the anti homophilic globulin, at an extremely low temperature from -80 to -85 C or even down to -196 C. For preservation or preservation of blood at a temperature of -80 to -85 C, the containers or bags made of soft polyvinyl chloride, as used for preservation or preservation at 4 to 6 C, without any change. Container / bag soft polyvinyl chloride are not suitable because of the leakage

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the plastic materials in the resin and the toxicity of the residual vinyl chloride monomers. These containers / bags are also unsuitable for the following reasons: For preservation of blood by freezing generally becomes a freeze-damage contraceptive to the blood in a high concentration, such as glycerin, is added and the mixture is shaken vigorously before freezing. Vigorous shaking is also used to thaw the blood. In both cases, as a result of the abrupt change in temperature and violent impacts damage the containers / bags and arise Blowholes (fine holes).

The main aim of the present invention is therefore to provide a container or To develop bags that can be used without any problems even at extremely low temperatures, such as -80 to -85 C.

This goal and other goals are achieved according to the invention with a container or bag for freezing or preserving (preservation) of physiological saline solutions for medical purposes, which is resistant to extremely low temperatures and which is labeled is through a laminate film that is heat-sealed in the form of a container or bag and consists of an inner layer of one unstretched film made from a random copolymer of an α-olefin with ethylene that contains 1 to 20 mol / £ of an α-oil with 4 to 18 carbon

4 atoms, with a molecular weight of more than 1 χ 10 and one Density less than 0.936, and an outer layer of a heat-resistant polymer film, its glass transition temperature is above room temperature.

The invention relates to a container / bag for freezing or Preservation of physiological saline solutions for medical purposes

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Purpose that is resistant to extremely low temperatures and exists of a laminate film which is heat-sealed in the form of a container or bag, the laminate film consisting of a Inner layer of an unstretched film made of a random copolymer of an α-oil with ethylene, which contains 1 to 20 mol TS of an α-oil with 4 to 18 carbon atoms with an average molecular weight (MW) of more than 1 χ 10 and a density of less than 0.936, and an outer layer made of a heat-resistant

Polymer film with a glass transition temperature above room temperature lies.

The invention is described below with reference to the enclosed Drawing explained in more detail. Show:

Fig. 1 is a sectional view of the laminate film;

Figure 2 is a top plan view of the container / bag; and

Figures 3 (a) and (b) are front and perspective views, respectively, of the container / bag.

The film for the inner layer of the container / bag according to the invention consists of a random copolymer of an α-olefin with Ethylene, the 1 to 20 M0I- / S of an α-01efin with 4 to 18 carbon atoms contains. The copolymerized component, i.e. the α-olefin, can be! -Butene, 1-pentene, 1-hexene, 4-methyl-1-pentene, 1-octene, 1-decene, 1-dodecene, 1-tetradecene, 1-octadecene. Among them, 4-methyl-1-pentene is preferred. This resin can be hereditary

- th are using the low pressure polymerisation process, in which a Ziegler catalyst, such as a catalyst on TiCl, / -

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l ₂ or a-TiCl ₃ / Ti (OC ₂ H ₃ ) ₄ / Al (C ₂ H ₅ ) ₃ base is used.

Since the low temperature break point is below -80 C, must be

4 molecular weight, however, be at least 1 χ 10. The resin must also have excellent softness, impact resistance, tear resistance, processability and transparency, and a density of less than 0.936 at room temperature and low temperatures. Further, since the resin must be heat-sealed to make a container or a bag, it must be in the form of an unstretched film.

This film to be used as the inner layer is particularly excellent in transparency, impact resistance and tear resistance compared with polyethylenes produced by the high pressure process and polyethylenes produced by the medium pressure process, Its physical properties are those of an ionomer resin, whose properties are considered good at low temperatures, superior The film has excellent softness that with polyethylenes high density cannot be achieved. According to the invention one obtains thus a container / bag for preservation by freezing, which due to the excellent chemical resistance (resistance against chemicals), the low elution and the inertness of the polyolefin with physiological saline solutions for medical Purposes can come into contact. These beneficial properties of the container / bag give the structure arbitrary long chain and attributed to short-chain branches obtained in the process used and with the copolymerized component.

The film of the outer layer is a heat-resistant polymer film (polymerized film) whose glass transition temperature is above Room temperature. It can for example consist of polyethylene

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terephthalate, polybutylene terephthalate, polyethylene naphthalate, polycarbonate, Polycapramide, polyundecanamide, polylauramide, an ethylene / tetrafluoroethylene copolymer, a tetrafluorothylene / hexafluoropropylene copolymer, a perfluoroalkoxy resin, polychlorinated trifluoroethylene, Polyparabanic acid, polypyromellitic acid imide or polyether sulfone. This stretched or unstretched film has a melting point or softening point which is at least 20 ° C higher than the heat-melting temperature 100 to 120 ° C of the inner layer film.

The properties of these skin films are at room temperature maintained substantially below -100 C or even about -200 C, so that the skin layer films have excellent resistance to result in low temperatures when combined with the low temperature resistant inner layer resin.

In the preservation (preservation) of physiological saline solutions for medical purposes by freezing is used to separate a previously added agent to prevent the adverse effects, caused by freezing in many cases, one High speed centrifugation performed. The presence of the strong outer layer prevents damage and the like Container / bag prevented.

When spraying liquid nitrogen or the like onto the container / bag To quickly lower the temperature of the contents of the container / bag to around -80 C, the outer layer also serves to prevent cracking or damage to the container / bag.

The invention is described below with reference to the accompanying Drawings described in more detail.

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As shown in the sectional view of Fig. 1, an inner layer filter is provided 1 and an outer layer film 2 by means of a curable Adhesive 3, which is resistant to heat and low temperatures, for example an adhesive on polyester, polyurethane or Epoxy-based or the like, or they are adhesively bonded to each other bonded (welded) together by heat sealing so that they form an integral laminate sheet.

From the standpoint of peeling resistance and hygiene A hardenable polyester urethane / glycol adhesive composed of two liquid components is considered to be the preferred adhesive with a terminal isocyanate group is used.

The films obtained are placed on top of one another with their inner layer surfaces facing each other, as shown in FIGS. 2 and 3, and the circumference of the layered body (laminate body) is heat-sealed (welded) in the form of a container or bag. Attached thereto are a necessary inlet 4 and a necessary outlet 5, so that a container or bag for the preservation (keeping) of physiological saline solutions for medical purposes is obtained. Since the container / bag for the preservation of blood by freezing according to the invention must have a certain softness, the thickness of the laminate film is generally less than 0.5 mm. However, since the strength of the film according to the invention is excellent because of the integral bonding of the inner and outer layers to one another, the total thickness of the inner and outer layers can be less than 0.2 mm. It is preferable to use a thick film for the inner layer and a thin film for the outer layer in order to facilitate heat sealing and prevent the formation of pinholes.

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The heat-sealed part is generally made thinner than that Rest of the slide. If the resin films of the inner layers are superposed on each other for heat sealing alone, rapid freezing can result Cracks appear. In the bag / container according to the invention, however, the sealed part is reinforced by the outer layer so that these problems cannot occur.

The containers / bags according to the invention are lighter than glass bottles and cannot be damaged if dropped. They also have excellent strength and vapor impermeability, since the inner layer is made of an ethylene-based resin. The thickness of the foil can thus be less than half that of one The container / bag made of soft polyvinyl chloride (approx. 4 mm) currently used for the transport and preservation of blood has been reduced so that the container / bag has a lighter weight. The disposal of the container / bag according to the invention is also easy, as little or no toxic gas is produced when burned unlike those made from vinyl chloride. The invention Containers / bags also have the advantage that, due to the thin film, the heat permeability can be facilitated. Through this the efficiency of sterilization and freezing can be improved.

That used in the inner layer of the container / bag of the invention Ethylene / α-olefin random copolymers is due to the fact that it is composed of spheres with a small radius, in terms of transparency, the semi-transparent white polyethylene that is obtained using the conventional low pressure process, Superior. The containers / bags according to the invention thus have a

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improved permeability for infrared radiation of 450 ιημιη, which is generally used as a standard for transparency so that foreign materials inside can be easily detected.

The invention is explained in more detail by the following examples, without however, to be limited to that.

example 1

1.) A polyester isocyanate-based adhesive was used in an amount of

2
3.8 g / m 2 applied to a biaxially stretched polyethylene terephthalate film with a thickness of 12 μm. Using the low-pressure polymerization process, an ethylene / l-butene random copolymer film with a thickness of 110 μm and a density of 0.921 was produced. The surface of this film was corona discharge treated and adhered to the surface of the polyethylene terephthalate film to obtain a two-layer laminate sheet having a matte surface. The edges of two of these sheets were heat-sealed so that the ethylene / 1-butene copolymer films faced each other inside out to give bags with a capacity of 200 ml.

After a water / methanol (quantity ratio 3: 1) solution in a Amount of 200 ml had been poured into each bag, the opening became each pouch is heat sealed. The bags were 5 hours long stored in coolers kept at -80 C, -70 C or -60 C, to cool them down completely. Then they became four quarters 5 times folded and unfolded.

These bags were allowed to warm to room temperature and loaded

1 3 0 0 1 7/0 8 6 1

watch out. On the respective bags, which are at -80 C, -70 C and -60 C no cracks and no damage were found. There were also no cavities (fine holes) or permanent ones Wrinkles observed.

The contents of the bags were in a form at less than -60 C which resembled frozen. It can be seen from this that the container / bag with the structure according to the invention has sufficient softness.

2.) An inlet and an outlet, each consisting of a tube with a Inside diameter of 4 mm and a thickness of 0.7 mm, produced by extrusion of an ethylene / α-olefin copolymer, were clamped between the inner layers at the points corresponding to the openings of the bag obtained in the above section (l) with a Capacity of 200 ml. The remainder of the laminate film was heat sealed to make a blood container / bag. This container / bag was kept under high temperature at 120 ° C for 20 minutes Steam pressure sterilized to saturate the inside with water vapor. After adding 100 ml of a physiological saline solution and 100 ml of a 79 / Sigen glycerin solution was heat-sealed on the opening tubes. The container / bag was left in a cooler at -80 ° C for 5 hours to freeze it. The frozen one The blood container / bag was thawed into warm water at + 40 C and shaken for 2 minutes.

Despite the abrupt temperature changes during the above procedures there was no separation of the container / bag according to the invention sealed part, no damage and no leakage of the contents.

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A commercially available vinyl chloride container / bag was used for comparison treated in the same way as indicated above. The edge of the container / bag was damaged when the frozen container / bag was pulled out of the cooler with a slight push and partial cracking was observed. The inventive Containers / bags, on the other hand, exhibited excellent properties.

Various characteristics of those in the above embodiment of the invention The laminate film obtained is compiled in the following table:

transparency

UV transmission at 450 ιημιη

Tensile strength elongation

Tear strength (Elemendorf)

Haze {%) 3.8-7.2

Permeability 87-91.0

kg / 15 mm width © 4.72 0 5.22

% 130 120

290

Water vapor permeability g / m. 24 h / 40 C 3.2

90 ° C / mRH

3, 2

Oxygen permeability cm / m. 24 hours. 1 bar 105

5.1

Heat seal strength (each seal at 150 ° Qkg / 15 m width 1 sec.)

450

The test of the present invention was carried out in accordance with JIS ZI707 "Food packaging plastic films "carried out:

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α) resistance to low temperatures

Puncture resistance room temperature (23 C) Elongation (0.5 R piano wire 30 mm / mm) methanol / dry ice elongation condition

(-73 ⁰ C)

Hold rate

Strength (g) Elongation (mm) Strength (g) Elongation (mm) % 890 4.2 2 200 4.5 107

Test results

1. Heavy metals

2. Combustion residue

3. Elution Test I. Color

II. Foam disappeared within 2 minutes.

less than 1.5 below the limit below the limit

below the limit value less than 0.1 transparent, no coloring

III.pH value IV.chloride V. Sulphate VI .phosphate

VII Ammonia

VIII lead
IX.Cadmium the color was lighter than that of the comparison solution

the color was lighter than that of the comparative solution

below the limit below the limit

X. Potassium permanganate reducing material less than 1.0 ml

XI. evaporated residue less than 1.0 mg

XII. Ultraviolet absorption spectrum (wavelength 220 mm) less than 0.10

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The above test was conducted in accordance with Japanese Pharmacopeia (ninth amendment): general test method 39: "Test method for plastic container for transport of blood ", (3)" Heavy metals ", (4)" Ignition residue "and (5)" Elution test ".

"Test Results".

Elution test: Result: negative.

The above test was carried out in accordance with the Japanese Pharmacopeia Test method (ninth change): general test procedure 39 "Test method for plastic containers for drink of blood" and "Elution test".

Example 2

1.) A polyester isocyanate-based adhesive was used in an amount of 3.9 g / m 2 applied to a biaxially stretched polyethylene terephthalate film with a thickness of 12 μm. A random copolymer of ethylene with 4-methyl-1-pentene was made using the low pressure polymerization process directly to a film with a thickness of 100 μm and one Extruded density of 0.922. The surface of this film was through Corona discharge treated and applied to the top surface of the polyethylene terephthalate film glued on to form a laminate film of two layers. The edges of these two foils were so joined together heat sealed that the ethylene / 4-methyl-1-pentene copolymer films on the inside facing each other so that bags with a Capacity of 200 ml were obtained. After a water / methanol (quantitative ratio 3: l) solution in an amount of 200 ml in each After the bag had been poured, the opening of each bag was

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sealed ρ The bags were for 5 hours in at -80 C, -70 C or -60 C kept coolers to cool them down completely. Then they were folded into quarters 5 times and again unfolds.

These bags were allowed to warm to room temperature and observed. For the bags stored at -80 C, -70 C and -60 C. no cracks and no damage were found. Also, no cavities (pinholes) or permanent wrinkles were observed.

The contents of the bags were in a form at less than -60 C which resembled frozen. From this result it can be seen that the Container / bag with the structure according to the invention has sufficient softness.

2.) An inlet and an outlet, each consisting of a tube with a Inside diameter of 4 mm and a thickness of 1.0 mm were passed made by extruding an ethylene / 4-methyl-1-pentene copolymer a density of 0.922 using the low pressure polymerization method, and then they were between the inner layers the film at positions corresponding to the openings of the bag obtained in Example 1 with a capacity of 200 ml, clamped. the remaining portions of the laminated films were heat-sealed to make a blood bag. This bag was on for 60 minutes 115 C sterilized under high steam pressure to the inside with steam to satiate. After adding 100 ml of a physiological saline solution and 100 ml of a 79 / Sigen glycerol solution, the im Any air remaining inside the bag was removed and the opening tubes were heat sealed. The bag was placed in a cooler for 5 hours.

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device stored at -80 C to freeze. The frozen one Blood bags were thrown into warm water at +40 C to thaw and shaken for 2 minutes.

In spite of the abrupt temperature changes during the above processes, the bag of the present invention did not separate of the sealed part, no damage and no leakage of the contents.

For comparison, a commercially available vinyl chloride bag was placed on the treated the same way as above. The edge of the bag was damaged when the frozen bag came out of the bag with a slight push Cooler was pulled out and partial cracking was observed. This pouch broke when hit by one Height of 120 cm was dropped on a concrete floor.

If the bag according to the invention in a corresponding manner of a Dropped 120 cm high on a concrete floor, shattered the bag did not, there were only a few cavities (fine holes) in the parts with which it was in direct contact with the soil surface Contact came. It can be seen from this that the container / bag according to the invention has excellent resistance to low temperatures having.

3.) A polyester isocyanate-based adhesive was used in an amount of 3.8 g / m 2 on a surface of an unstretched polylauramide film a thickness of 30 μΐη applied. An ethylene / 4-methyl-1-pentene random copolymer film a thickness of 110 μm and a density of 0.922, made using the low pressure polymerization process was applied to the upper surface of the polylauramide film.

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sticks to form a laminot film of two layers. These Foil was vacuum formed to a depth of 20 mm. Two of these vacuum-formed sheets were combined together so that the Ethylene / 4-methyl-1-pentene copolymer films faced each other, as shown in Figures 3 (a) and (b), and the side sections were heat-sealed using an ampoule-shaped container a capacity of 100 ml.

There was distilled water in an amount of 100 ml in the container poured and the openings were heat sealed. The container was then placed in a high pressure steam sterilizer at 121 ° C for 1 hour heated and left to stand until it was back to room temperature. With the solution inside this container, the tests according to (i) to (XIl) of section (5) of the general test procedure conducted by Japanese Pharmacopeia.

In the case of the container of the present invention, the light absorptivity was low and was 0.007 (below the 0.08 limit of the standards) with an ultraviolet absorption spectrum of more than 226 nm and less than 241 nm, and it was 0.02 (was below the 0.05 limit of the standards) when the ultraviolet absorption spectrum was more than 241 nm and less than 350 nm. From this it can be seen that the container according to the invention is suitable as a container for medical test solutions and the like. Also, the medical Test solutions are generally cooled with dry ice when they are transported to the test station, so that the excellent resistance of the container according to the invention is very advantageous against low temperatures.

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Comments: Elution test

I. Color

II. Foaming

III. PH value

IV. Chloride

V. Sulphate

VI. phosphate

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VII. ammonia VIII. lead IX. cadmium X. Potassium permanganate
reducing material XI. evaporated material XII. Ultra violet absorpti-
onsspectrum

transparent, no color disappeared within 2 min. less than 1.5 below the limit value below the limit value

the color was lighter than that of the comparative solution

the color was lighter than that of the Comparison solution below the limit value below the limit

less than 1.0 ml less than 1.0 ml

less than 0.08 at more than 220 nm and less than 241 nm less than 0.05 at greater than 241 nm and less than 350 nm

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Claims (5)

PATENT LAWYERS Q Π ^ 8 Q 7 1 TER MEER-MÜLLER-STEINMEISTER Professional Representatives before the European Patent Office Mandataires agries pres! 'Office european des brevets Dipl.-Chem. Dr. N. ter Meer Dipl.-Ing. H. Steinmeister Dipl.-lng, FE Müller Siekerwall 7,
Tnftstrasse 4, D-8OOO MUNICH 22 D-48OO BIELEFELD 1 October 15, 1980 TOPPAN PRINTING CO., LTD. 1-5-1, Taito, Taito-ku, Tokyo-to T 555 Japan Containers / bags for preserving physiological saline solutions for medical purposes Claims ■ _; 1. · Container / bag for freezing or preserving physiological saline solutions for medical purposes, which is resistant to extremely low temperatures, characterized by a laminate film which is heat-sealed in the form of a container or bag and consists of an inner layer made of an unstretched film a random copolymer of a «-olefin with ethylene, which contains 1 to 20 MoI-TS cc-olefin with 4 to 18 carbon atoms with an average molecular weight (MW) of more than 1 χ 10 and a density of less than 0.936, and one outer layer made of a heat-resistant polymer film, the glass transition temperature of which is above room temperature. 130017/0861 2. Container / bag according to claim 1, characterized in that the outer layer consists of a film made of a resin, which is selected from the group polyb'thylene terephthalate, polyethylene naphthalate, Polybutylene terephthalate, polycarbonate, polycapramide, polyundecanamide, Polylauramide, ethylene / tetrafluoroethylene copolymer, tetrafluoroethylene / hexafluoropropylene copolymer, Perfluoroalkoxy resin, polychlorinated trifluoroethylene, polyparabanic acid, polyether sulfone and polypyromellitic acid imide, which is a stretched film or an unstretched film with a melting point higher than that Melting point of the resin of the inner layer. 3. Container / bag according to claim 1 or 2, characterized in that that the inner layer and the outer layer by means of an adhesive are connected to each other. 4. Container / bag according to claim 3, characterized in that it The adhesive is a polyester-based, polyurethane-based or epoxy-based adhesive that is resistant to heat and low temperatures is constant. 5. Container / bag according to one of claims 1 to 4, characterized in that that it has an inlet and an outlet. 130017/0861