GB2065067A - Laminated bags - Google Patents

Abstract

A bag for use in freezing physiological solutions, food or chemicals comprises a laminated sheet heat-sealed to form a bag, the sheet comprising an inner layer of unstretched film of a random copolymer of ???- olefin with ethylene containing from 1 to 20 mol% of ???- olefin of over 1 x 10<4> average molecular weight, having a density of less than 0.936 and having from 4 to 18 carbon atoms, and an outer layer of a heat-resistant polymerized film whose glass transition temperature is above room temperature. The alpha -olefin may be, amongst others, 1-butene, 4- methyl-1-pentene, or 1-octene, and the outer layer may be, amongst others, polyethylene terephthalate, polycarbonate, polycapramide, ethylene-tetrafluoroethylene copolymer, polyparabanic acid, or polyether sulfone. The inner and outer layers are united by a polyurethane-, polyester-, or epoxy-based adhesive.

Description

SPECIFICATION A container bag suitable for use in freezing or preserving physiological saline solutions for medical use The present invention relates to a plastic container bag resistant to low temperatures which may be used at low temperatures such as a liquid carbonic acid temperature of about -80 C and, more particularly, to a plastic container bag suitable for preservation by freezing of blood components such as erythrocytes, blood plasma and blood platelets; bacteria; enzymes; physiological saline solutions; foods; and chemicals.

Blood has been conventionally preserved in containers of glass, soft polyvinyl chloride, polypropylene, high density polyethylene and soon at4 6"C. When preserved under such temperature conditions, the blood deteriorates relatively quickly and can only be preserved for about 21 days.

Recently, it has become possible to preserve blood for a long period of time by preserving every blood component such as erthrocytes, blood plasma, platelets, and anti-hemophilic globulin separately at an extreme low temperature of -80 to -85 C or even to -1960C For preservation of blood at a temperature of -80 to -85"C, container bags of soft polyvinyl chloride used for preservation at 4 - 6"C are used without any modification. However, container bags of soft polyvinyl chloride are not suitable due to elution of the plastic materials in the resin and the toxicity of the remaining vinyl chloride monomers.

These container bags are also unsuitable for the following reasons. For preservation of blood by freezing, a freeze harm-preventative agent of high concentration such as glycerin is generally added to the blood and the mixture is strongly shaked before freezing. Shaking is also performed for thawing the blood. In both cases, due to the abrupt change in temperature and the strong impact, the container bags tend to be damaged and pin holes tend to form.

It is, accordingly, the primary object of the present invention to provide a container bag which may be used without any problems at extremely low temperatures such as -80 to -85 C.

To the above and other ends, the present invention provides a container bag for freezing or preserving physiological saline solutions for medical use which is resistant to extremely low temperatures and which comprises a laminated sheet heat-sealed in a container or bag form, said laminated sheet comprising an inner layer of unstretched film of a random copolymer of o-olefin with ethylene containing 1 to 20 mol % of a-olefin of over 1 x 104 molecular weight, less than 0.936 density, and having 4 - 18 carbon atoms; and an outer layer of a heat-resistant polymerized film whose glass transition temperature is above room temperature.

The attached drawings show the embodiment of the present invention wherein Fig. 1 is a sectional view of the laminated sheet, Fig. 2 is a plan view of the container bag, and Figs. 3(a) and (b) are a front view and a perspective view of the container bag, respectively.

The film for the inner layer of the container bag of the present invention consists of a random copolymer of a-olefin with ethylene containing 1 to 2 mol % of a-olefin having 4 to 18 carbon atoms. The copolymerized component, that is, the a-olefin may be 1-butene, 1-pentene, 1-hexene, 4- methyl-1-pentene, 1-octene, 1-decene, 1-dodecene, 1-tetradecene, 1-octadecene. Among these, 4-methyl-1-pentene is preferred. This resin may be obtained by the low pressure polymerization method using a Ziegler catalyst such as a TiCI4- AIC2H3CI2 or an a-TiCl3-Ti(OC2H3)4-Al(C2H5)3 based Ziegler catalyst.However, since its low temperature fracture point is less than -80 C, its molecular weight must be at least 1 x 104. The resin further must have excellent softness, impact resistance, tear strength, workability and transparency, and a density of less than 0.936 at room temperature and low temperatures. Further, since the resin must be heat-sealed for preparing a container or a bag, the resin must be in the form of unstretched film.

This film to be used as the inner layer is particularly excellent in transparency, impact resistance and tear strength as compared with high pressure method polyethylenes and medium pressure method polyethylenes. Its physical properties are superior to those of an ionomer resin whose properties are known to be good at low temperatures. The film shows excellent softness which cannot be obtained with high density polyethylenes. Thus, it provides a container bag for preservation by freezing which can come in contact with physiological saline solutions for medical purposes due to the excellent chemical resistance, small elution, and inertness of polyolefin. These advantageous characteristics of the container bag are attributed to the structure having random long chain and short chain branches obtained by the adopted method and the copolymerized component.

The film of the outer layer is a heat-resistant polymerized film whose glass transition temperature is above room temperature. It may consist of, for example, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polycarbonate, polycapramide, polyundecaneamide, polyauramide, ethylene-tetrafl uo roethylene copolymer, tetrafluoroethylene- hexafluoropropylene copolymer, perfluoroalkoxy resin, polychlorinated trifluoroethylene, polyparabanic acid, polypyromellitic imide, or polyethersulfone. This stretched or unstretched film has a melting point or softening point which is higher by at least 20"C than the heat melting temperature, 100 to 1200C, of the inner layer film.

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

In preserving physiological saline solutions for medical purposes by freezing, high speed centrifugation is performed for separating a previously added agent for preventing adverse effects caused by freezing in many cases. The presence of the strong outer layer prevents damage and so on to the container bag.

In the procedure of sprinkling liquid nitrogen or the like on the container bag for rapidly dropping the temperature of the contents inside the bag to about -80 C, the outer layer also functions to prevent cracking or damage to the container bag. The pres ent invention will now be described with reference to the accompanying drawings.

As shown in the sectional view of Fig. 1, an inner layer film 1 and an outer layer film 2 are adhered to each other with a curing adhesive 3 having resistance to heat and low temperatures, such as a polyester-based, polyurethane-based, epoxy-based adhesive or the like; or heat-sealed so that they form an integral laminated sheet.

For the adhesive, a two-liquid curing type adhesive of polyester urethane/glycol having a terminal isocyanate group is preferred from the standpoint of resistance to separation and hygiene.

The obtained sheets are superposed one on top of another so that their inner layer surfaces face each other as shown in Figs. 2 and 3, and the periphery of the laminated body is heat-sealed in a container or bag form. A necessary inlet 4 and an outlet 5 are attached to this to provide a container or a bag for preservation of physiological saline solutions for medical purposes.

Since the container bag for preservation of blood by freezing which the present invention provides requires a certain softness, the thickness of the laminated sheet is generally less than 0.5 mm. However, since the strength of the sheet of the present invention is excellent due to the integral lamination of the inner and outer layers, the overall thickness of the inner and outer layers may be less than 0.2 mm. It is preferred to use a thick film forthe inner layer and a thin film for the outer layer for ease in heat-sealing and prevention of pin holes.

The heat-sealed part is generally made thinner than the rest of the sheet. Thus, when the resin films of the inner layers alone are superposed for heatsealing, cracks may be caused by quick freezing.

However, with the container bag of the present invention, the sealed part is reinforced by the outer layer so that such problems do not occur.

The container bags of the present invention are lighter than glass bottles and may not be damaged when dropped. They are also excellent in strength and impermeability to vapor since the inner layer consists of an ethylene-based resin. Thus, the thick ness of the sheet may be made less than half of that of a currently used container bag of soft polyvinyl chloride for transport and preservation of blood (about4 mm) so that the container bag may be made lighter in weight. Disposal of the container bags of the present invention is also easy since they produce little or no toxic gas on burning as opposed to those made of vinyl chloride. The container bags of the present invention are also advantageous in that thermal transmission may be facilitated due to the thin sheet. Thus, the efficiency of sterilization and freezing may be improved.

The ethylene-a-olefin random copolymer used in the inner layer of the present invention, due to its spherulite composition of small radius, is superior in transparency to the semi-transparent white polyethylene obtained by the conventional low pressure method. The container bags of the present invention are thus improved in transmissivity of infrared light rays of 450 m,u which are generally taken as a standard of transparency, so that foreign materials inside may be easily detected.

Example 1 (1) A polyester isocyanate-based adhesive was applied in an amount of 3.8 g/m2 on a biaxially stretched polyethylene terephthalate film of 12 y thickness. An ethylene-1-butene random copolymer film of 110 CLthickness and 0.921 density was obtained by the low pressure polymerization method. The surface of this film was treated with corona discharge and was adhered to the top surface of the polyethyleneterephthalate film to provide a laminated sheet of two layers with one matte surface. The peripheries of two such sheets were heatsealed together with the ethylene-1-butene copolymer films facing inside to provide bags of 200 ml capacity.

After pouring a solution of waterimethanol = 3/1 ration in an amount of 200 ml into each bag, the opening of each bag was heat-sealed. The bags were left to stand for 5 hours in refrigerators kept at -800C, 70CC and -60 C, respectively, for completely cooling them. They were then folded into quarters and unfolded five times.

These bags were allowed to return to room temperature and were observed. No cracks or damage was observed for the respective bags kept at -80 C, -70"C, and -60 C. Nor were any pin holes or permanent folds observed.

The contents of the container bag were in a form resembling sherbet at less than -60 C. It is seen from this result that the container bag of the construction according to the present invention has sufficient softness.

(2) An inlet and an outlet each comprising a tube of 4 Q inner diameter and 0.7 m/m thickness obtained by extrusion of an ethylene-a-olefin copolymerwere clamped between the inner layers at places corresponding to the openings of the bag of 200 ml capacity obtained in Example 1. The other part of the laminated sheet was heat-sealed to provide a blood container bag. This container bag was sterilized with high pressure vapor at 1 200C for 20 minutes so as to saturate the inside with water vapor. After adding 100 ml of physiological saline solution and 100 ml of 79% glycerin solution, the opening tubes were heat-sealed. The container bag was left to stand in a refrigerator kept at -80 C for 5 hours to freeze. The frozen blood container bag was thrown into warm water at +400C and shaken for 2 minutes to be thawed.

Despite the abrupt temperature changes during the above procedures, the container bag of the present invention did not suffer separation of the sealed part, damage or leakage of the contents.

A commercially available vinyl chloride container bag was treated in the same manner as above for the purpose of comparison. The edge of the container bag was damaged when the frozen container bag was pulled from the refrigerator with a small impact, and partial cracking was observed. The container bag of the present invention, on the other hand, showed excellent characteristics.

Various properties of the laminated sheet obtained in the above embodiment of the present invention are shown in the table below: Transparency Haze (%) 3.8- 7.2 450 m,a UV Transmissivity 87 - 91.0 transmission (%) Tensile strength kg/15 mm width OT 4.72 ( 5.22 Elongation % 130 120 Tear strength 9 290 450 (Elemendo rf) Water vapor g/m2 24H140'C 3.2 permeability 90 C/mRH Oxygen permeabilityCC/ni 24H atm 105 Heat-seal strength (each seal 1500C 1 sec)kg/l 5m width 5.1 The present test was conducted according to J IS Z1707 "Food packaging plastic films".

(a) Resistance to low temperatures Piercing strength Elongation (0.5 R piano wire 30 mm/mm) Room temperature Methanol dry ice Elongation Condition (230C) (-73"C) holding rate Strength Elongation Strength Elongation g mm g mm 890 4.2 2,200 4.5 107 "Test Items" 1. Heavy metals Less than the limit 2. Ignition residue Less than 0.1 3. Elutiontest (I) Color Transparent, no color (II) Foaming Disappears within 2 minutes (III) pH Less than 1.5 (IV) Chloride Less than the limit (V) Sulfate Less than the limit (VI) Phosphate The color is lighter than that of the comparison solution.

(VII) Ammonia The color is lighter than that of comparison solution.

(VIII) Lead Lessthanthe limit (IX) Cadmium Lessthanthe limit (X) Potassium permaganate reducing Less than 1.0 ml material (Xl) Evaporated residue Less than 1.0 mg (XII) Ultra violet absorption Less than 0.10 spectrum (wavelength 220 mm The above test was conducted according to the ninth amended Japanese Pharmacopeia: general test method 39 "Test method for plastic container for transport of blood", (3) "Heavy metals", (4) "Ignition residue", and (5) "Elution test".

"Test Item" Eiution test: Result; negative The above test was conducted according to the ninth amended Japanese Pharmacopeia test method: general test method 39 "Test method for plastic containers for transport of blood" and "Elu tion test".

Example (1) A polyester isocyanate-based adhesive was applied in an amount of 3.9 gim on a biaxially stretched polyethylene terephthalate film of 12 it thickness. A random copolymer of ethylene with 4-methyl-1-pentene was directly extruded into a film of 100 it thickness and 0.922 density by the low pres sure polymerization method. The surface of this film was treated with corona discharge and was adhered over to the top surface of the polyethylene tereph thalate film to provide a laminated sheet of two layers. The peripheries of two such sheets were heat-sealed together with the ethylene-4-methyl-1 pentene copolymer films facing inside to provide bags of 200 ml capacity.After pouring a solution of water/methanol = 3/1 ratio in an amount of 200 ml into each bag, the opening of each bag was heatsealed. The bags were left to stand for 5 hours in refrigerators kept at -80 C, -70 C and -60 C, respectively, for completely cooling them. They were then folded in quarters and unfolded five times.

These bags were allowed to return to room temperature and were observed. No cracks or damage was observed for the bags kept at -80"C, -70"C, and -60 C. Norwere any pin holes or permanent folds observed.

The contents of the container bag were in a form resembling sherbet at less than -60 C. It is seen from this result that the container bag of the construction according to the present invention has sufficient softness.

(2) An inlet and an outlet each comprising a tube of 4 O1 inner diameter and 1.0 m/m thickness were obtained by extrusion of an ethylene-4-methyl-1pentene copolymer of 0.922 density by the low pressure polymerization method and were clamped between the inner layers of the sheets at places corresponding to the openings of the bag of 200 ml capacity obtained in Example 1. The other parts of the laminated sheets were heat-sealed to provide a blood container bag. This container bag was sterilized with high pressure vapor at 115"C for 60 minutes so as to saturate the inside with water vapor. After adding 100 ml of physiological saline solution and 100 ml of 79% glycerin solution, the air remaining inside the bag was ejected and the opening tubes were heat-sealed.The container bag was left to stand in a refrigerator kept at 1800C for 5 hours to freeze. The frozen blood container bag was thrown into warm water of +40"C and shaken for 2 minutes to be thawed.

Despite the abrupt temperature changes during the above procedures, the container bag of the present invention did not suffer separation of the sealed part, damage or leakage of the contents.

A commercially available vinyl chloride container bag was treated in the same manner as above for the purpose of comparison. The edge of the container bag was damaged when the frozen container bag was pulled from the refrigerator with a small impact, and partial cracking was observed. This container bag broke when it was dropped from a height of 120 cm onto a concrete floor.

When the container bag of the present invention was similarly dropped from a height of 120 cm onto a concrete floor, the container bag did not break; it only showed some pin holes at parts where it came in direct contact with the floor surface. It is seen from this that the container bag of the present invention is excellent in resistance to low temperatures.

(3) A polyester isocyanate-based adhesive was applied in an amount of 3.8 g/m on one surface of an unstretched polylauramide film of 30 Cr.thickness. An ethylene-4-methyl-1-pentene random copolymer film of 110 IL thickness and 0.922 density obtained by the low pressure polymerization method was adhered to the top surface of the polylauramide film to provide a laminated sheet of two layers. This sheet was vacuum-formed to a depth of 20 mm. Two of such vacuum-formed sheets were brought together in such a manner that the ethylene-4methyl-1 -pentene copolymer films faced each other as shown in Figs. 3(a) and (b), and the side portions were heat-sealed to obtain an ampoule-shaped container of 100 ml capacity. Distilled water was poured in an amount of 100 ml therein, and the openings were heat-sealed.The container bag was then heated at 121"C for 1 hour with a high pressure vapor sterilizer and allowed to stand until it reached room temperature. The tests according to (I) to (XII) of item (5) of the general test method of the Japanese Pharmacopeia were performed on the solution inside this container bag. With the container bag of the present invention, the light absorbency was low, 0.007 (less than the 0.08 limit of the standards) with an ultraviolet absorption spectrum of greater than 226 nm and less than 241 nm, and 0.02 (less than the 0.05 limit of the standards) when the ultraviolet absorption spectrum was greaterthan 241 nm and less than 350 nm. It is seen from this result that the container bag of the present invention is suitable as a container for medical testing solutions and the like.

Further, the medical testing solutions are generally cooled with dry ice as they are transported to the testing section, so that the excellent resistance to low temperatures of the container bag of the present invention is quite useful.

Remarks: Elution test (I) Color Transparent, no color (11) Foaming Disappears within 2 minutes (III) pH Less than 1.5 (IV) Chloride Less than the limit (V) Sulphate Less than the limit (VI) Phosphate The color is lighter than that of the comparison solution (VII) Ammonia The color is lighterthan that of the comparison solution (VIII) Lead Less than the limit (IX) Cadmium Lessthanthe limit (X) Potassium permanganate reducing material Less than 1.0 ml (XI) Evaporated Lessthanl.Omg (XII) Ultra-violet Less than 0.08 at greater absorption than 220 nm and less than spectrum 241 nm Less than 0.05 at greater than 241 nm and less than 350 nm

Claims (9)

1. A container bag suitable for use in freezing or preserving physiological saline solutions for medical use, which bag is resistant to extremely low temper atures and which bag comprises a laminated sheet heat-sealed in container or bag form, the laminated sheet comprising an inner layer of unstretched film of a random copolymer of a-olefin with ethylene containing from 1 to 20 mol % of a-olefin of over 1 x 104 average molecular weight (Mw), having a density of less than 0.936 and having from 4 to 18 carbon atoms, and an outer layer of a heat-resistant polymerized film having a glass transition temperature above room temperature.

2. A container bag according to Claim 1, wherein the outer layer comprises a film of one resin selected from polyethyleneterephthalate, polyethylene naphthalate, polybutylene terephthalate, polycarbonate, polycapramide, polyundecaneamide, polylauramide, ethylene - tetrafluoroethylene copolymer, tetrafluo roethylene - hexafl uo ropropylene copolymer, perfluoroalkoxy resin, polychlorinated trifluoroethylene, polyparabanic acid, polyether sulfone and polypyromellitic imide, the film comprising the outer layer being a stretched or an unstretched film having a melting point higher than the melting point of the resin of the inner layer.

3. A container bag according to Claim 2, wherein the film comprising the outer layer has a melting point at least 20"C higher than the melting point of the inner layer film.

4. A container bag according to Claim 1,2 or 3, wherein the inner and outer layers are adhered to each other with an adhesive.

5. Acontainerbag according to Claim 4, wherein the adhesive is a polyester-based, polyurethanebased or epoxy-based adhesive and is resistant to heat and low temperatures.

6. A container bag according to any one of the preceding claims, which has an inlet and an outlet.

7. Acontainer bag, substantially as hereinbefore described with reference to the accompanying drawings.

8. Acontainer bag, substantially as hereinbefore described in any one ofthe foregoing Examples.

9. Any novel feature or combination of features described herein.