GB2133018A

GB2133018A - Heat-sterilizable polyolefin compositions and articles manufactured therefrom

Info

Publication number: GB2133018A
Application number: GB08333774A
Authority: GB
Inventors: Kiyoshi Hatttori; John H Myers
Original assignee: El Paso Polyolefins Co
Current assignee: El Paso Polyolefins Co
Priority date: 1982-12-20
Filing date: 1983-12-19
Publication date: 1984-07-18
Also published as: CA1249692A; GB2133018B; IT8324187A1; NO834692L; FR2537981B1; IT1170004B; AU561153B2; DE3345686A1; GB8333774D0; IT8324187A0; NO168119B; AU2558684A; CA1258050C; FR2537981A1; NO168119C

Abstract

Heat-sterilizable films are made from a polymer blend of 10 to 60 wt % of a random propylene-ethylene copolymer containing from 1 to 6 wt % ethylene-derived units and 40 to 90 wt % of a linear low density polyethylene. The films are especially useful in the manufacture of collapsible parenteral solution bags and overwraps. A parenteral solution bag assembly comprises an inner sealed plastic film bag containing a parenteral solution, an outer sealed bag enclosing the inner bag and in the space between the outer and inner bags a quantity of a substance sufficient to control removal of a component from or to control the addition of a component to the parental solution through the inner bag film wall.

Description

SPECIFICATION Heat-sterilizable polyolefin compositions and articles manufactured therefrom Parenteral solutions can be used to provide fluid replacement or electrolyte replacement and are vehicles for drug medication. Solutions include blood plasma, platelets, red cells, kidney dialysis solutions, saline solutions and nutritional products. These solutions were initially bottled in glass, but, with the introduction of the collapsible parenteral solution bag some years ago, airborne contamination was significantly reduced since the flexible bags empty without outside air entering the system.

The general requirements of a resin for use in the manufacture of parenteral solution bags include flexibility, clarity, toughness at low temperatures, heat sealability, good processability, moisture vapor permeability resistance and ability to be sterilized. The industry is presently employing a highly plasticized PVC film for this purpose. Although this resin does meet most of the requirements, a material is preferred that has little or no plasticizer. Also the PVC film is not very resistant to moisture vapor permeability, and consequently the continuing loss of moisture of the parenteral solutions reduces their storage life considerably. Therefore, it is required that the bag be sealed within an overpouch made from a film resin designed to have a low water vapor transmission rate (WVTR).Currently the overpouch film is made from a blend of high density polyethylene and butyl rubber which is extruded into film of 100 to 1 26 pm (4-5 mil) thick to provide the necessary WVTR. This thickness is usually more than needed for physical strength and adds to the cost of the assembly. Another drawback of the overpouch resin is that it lacks the desired clarity, an important property needed for easy and correct identification of the contents of the inner bag.

The present invention seeks to provide a resin composition which is suitable for use in the manufacture of sterilizable overpouch films of improved clarity and moisture vapor permeability resistance. The invention also seeks to provide a film useful in the manufacture of sterilizable, collapsible bags for direct and for indirect containment of parenteral solutions, as well as an improved collapsible intravenous bag assembly.

In accordance with the present invention there is provided a sterilizable film resin composition which comprises a blend of: (a) from 10 to 60 wt % of a random copolymer of from 1 to 6 wt % ethylene and of from 94 to 99 Wt % propylene; (b) from 40 to 90 wt % of a linear low density polyethylene produced by copolymerization of ethylene with at least one C4-C18 alpha-olefin comonomer and having a density between 0.915 and 0.940 gm/cc.

The random copolymer component (a) preferably has a melt flow between 1.0 and 5.0 g/10 min at 230on. Such copolymers are readily available commercially and their preparation need not therefore be discussed.

The linear low density polyethylene component (b), hereinafter sometimes identified as LLDPE, is an interpolymer of ethylene and at least one C4-C,8 alpha-olefin comonomer. Preferably the alpha-olefin comonomer contains from 4 to 8 carbon atoms per molecule. Examples of especially suitable comonomers are butene-1, pentene-1, hexene-1, 4methyl-pentene-1, heptene-1, octene-1 and mixtures thereof such as butene-1 /hexene-1 and butene-1 /octene-1.

These LLDPE resins can be produced by any of the recently introduced catalytic processes using vapor, solution or slurry techniques at low to medium pressures or high pressure catalytic polymerization in autoclave or tubular reactors. The resin preferably has a melt index from 0.5 to 5 g/10 min. at 190"C. A variety of suitable resins are commercially available within the required density and melt flow ranges.

One optional component of the resin blend is an agent added in a quantity effective to produce films of improved clarity. Examples of suitable agents are sodium benzoate, dibenzylidene sorbitol and sorbitan monooleate. Usually the agents are added in quantities between 0.1 and 2 wt % based on the weight of the total polymers.

Also, from 2 to 1 5 wt % of a high density polyethylene, i.e. a homopolymer of ethylene having a density of at least 0.945 gm/cc can be included in the resin as another optional ingredient for the purpose of increasing the heat seal range. This property is defined as the time span between the minimum time to make a good seal and the maximum time before the film burns through employing a standard heat-sealing device.

The composition of the present invention is easily processable into blown or cast film products which, in addition to high clarity, exhibit other desirable properties such as flexibility, toughness at low temperatures and heat sealability. Also, the films have good resistance to moisture vapor permeability and can be steam sterilized at 121"C, without significantly affecting their physical properties in a detrimental way. Finally, the films contain no additives, which would prevent their use in food or medical applications, either in direct or indirect contact.

When used for an inner parenteral solution container, the film should be 76 to 250 itm (3 to 10 mils) thick, while the overpouch need not be more than 25 to 150 ,um (1 to 6 mils) thick. If desired, co-extruded films for either the inner bag or the outer bag can be used to reduce loss of moisture or gases through the film walls. Materials such as fluorocarbon polymers, ethylenevinyl alcohol copolymers and polyvinylidene chloride materials are examples of suitable coextrudates.

Further improvements result from an overall parenteral solution bag assembly which comprises an inner sealed film bag containing the parenteral solution, an outer sealed film bag, preferably containing a small amount of water, enclosing the inner bag said outer bag having a width and a length of from 0.6 to 3.8 cm (0.25 to 1.5 inches) larger than the corresponding dimensions of the inner bag, the sealed plastic film bag being of the composition of the invention.

In one embodiment a small amount of water is added directly to the outer pouch before the sealing operation is carried out to enclose the inner bag. In another embodiment a small amount of water is enclosed in a separate smaller pouch manufactured from two film layers. For economic reasons, one of the films is suitably made from the same resin as that of the outer bag, while the outer layer should be made from a porous material that allows vapor to escape but is resistant to liquid permeability. Suitable materials for this purpose are commercially available, e.g. the "Tyvek" (Registered Trade Mark) spunbonded polyethylenes available from E.

I. Du Pont de Nemours. Moisture vapor is thereby permitted to escape from the small pouch more rapidly than from the outer bag, thus producing a saturated atmosphere between the inner and outer bag, effectively eliminating the driving force for water to escape from the inner bag and reducing the rate at which water vaporizes and leaves the inner bag. The area of one side of the smaller pouch should not exceed about 50% of the corresponding inner bag area.

The actual amount of water to be used to inhibit removal of water vapor from the inner bag should at least be sufficient to ensure that liquid water is still present in the space between the inner and outer bags at the expiration date of the storage life of the parenteral solution. This amount will obviously vary from case to case and depends on the maximum allowable storage life of the parenteral solution, the size of the outer bag and the water vapor transmission rate through said bag.

An additional feature of this invention is the ability to substitute materials other than water in the small pouch. For example, a carbon dioxide absorber can be sealed in the small pouch and help in removing carbon dioxide from the inner bag or an oxygen generator can be added to aid in adding oxygen to the inner bag, thereby considerably increasing blood platelet storage life.

Other materials and gases could also be handled and controlled in this manner in order to improve the storage performance of the system.

The use of the small pouch inserted in the space between the inner and outer bags simplifies all packaging operations to a large degree. Only one film material and thickness would be required for manufacturing and inventorying the inner bag for all types of solutions. Additionally, all outer bags can be of the same resin formulation and of one film thickness. Only different small pouches, identifiable for example by color coding, need to be added.

In case the materials packaged in the inner bag are sensitive to ultra violet light, a small amount of an ultra violet screening agent can be incorporated in the outer bag which would prevent U.V. light from reaching the packaged products.

The film compositions are also high energy radiation sterilizable.

Also, either or both of the bags of the parenteral solution bag assembly may be manufactured from other polymer film compositions, provided that they are sterilizable by heat or irradiation and meet the general requirements of flexibility, toughness and heat sealability previously discussed.

To further illustrate the invention the following Examples are provided: EXAMPLE 1 A resin blend containing 84.75 parts LLDPE (copolymer of ethylene and butene-1, density 0.918 g/cc, melt index 1.0 g/10 min), 15 parts random copolymer of 97.5% propylene and 2.5% ethylene (density 0.900 g/cc, melt flow 2.0 g/1 0 min). 0.25 parts dibenzylidene sorbitol was used in preparing blown films 63.5 or 114,um (2.5 mil or 4.5 mil) thick. The resulting films had good clarity, toughness, were easily heat sealable and flexible. Pouches were made from these films, filled with water, heat sealed and tossed in the air to simulate a 3.05 m (10 foot) drop.All pouches survive at least 6 drops at ambient temperatures (18"C or 65"C). The moisture vapor transmission rates of the films were approximately 11.5 g/ym/m2/24 hours (0.7 grams/mil/100 square inches/24 hours).

Other test samples consisting of 1 3 X 28 cm (5 x 11 inches) inner bags were prepared from the 114,um (4.5 mil) thick film. These were filled with 1000 cc water and enclosed in 1 5 X 30 cm (6 x 1 2 inches) outer bags of the 63.5m (2.5 mil) thick film. A portion of the samples were provided with 70 cc water between the inner and outer bags. All of the samples passed the steam sterilization test carried out in an autoclave at 121 C for 60 minutes.

Equally good results were obtained in experiments with films made from a resin blend similar in all aspects to the previous one except the LLDPE/copolymer weight ratio was changed from about 85:15 to about 60:40.

EXAMPLE 2 1 30 um (5 mil) films were made from resins containing varying amounts of high density polyethylene (0.952 gm/cc) in addition to the LLDPE and the propylene-ethylene random copolymer used in Example 1. Strips of two layers of these films were placed in an air oven at 120"C (250"F) for 0.5 to 1 hour. The strips were then taken out and inspected for any tendency to stick together. These same films were then tested in a heat sealing device to determine their ability to be heat sealed. An impulse type sealer made by Sentinel Industries was used for these tests. The heating cycle was varied (in seconds) and the cooling time (4 sec.) and air pressure (145 kPa gauge or 21 psig) was held constant.The minimum time to make a good seal and the maximum time before the film burned through were determined and the time difference was the sealing range. The Table summarizes the data from these experiments.

As seen from the results, the addition of small amounts of high density polyethylene greatly increased the heat seal range.

Peel tests also showed that the seals were considerably stronger in films made from resins containing high density polyethylene as a third resin component. Other film properties were not adversely affected by this inclusion.

TABLE Test Contr.1 A B C D E C3=/C2= copolymer - 40 40 40 35 36 -wt% LLDPE-wt% 100 60 54 50 60 54 HDPE-wt% - - 6 10 5 10 Oven test(1) STICK DNS DNS DNS DNS DNS Heat Seal Range, Sec. 2.5 1.3 1.8 2.3 2.4 2.4 DNS-Did not stock-slight tackiness

Claims

1. A sterilizable film resin composition comprising a blend of: (a) from 10 to 60 wt % of a random copolymer of from 1 to 6 wt % ethylene and of from 94 to 99 wt % propylene; (b) from 40 to 90 wt % of a linear low density polyethylene produced by copolymerization of ethylene with at least one C4-C,8 alpha-olefin comonomer and having a density between 0.915 and 0.940 gm/cc.

2. A composition according to claim 1 wherein the random ethylene-propylene copolymer (a) has a melt flow of 1.0 to 5.0 g/10 min at 230"C.

3. A composition according to claim 1 or 2 wherein the comonomer of the linear low density polyethylene component (b) is at least one C4-C8 alpha-olefin.

4. A composition according to claim 3 wherein the linear low density polyethylene (b) is a copolymer of ethylene and butene-1.

5. A composition according to any one of the preceding claims, wherein the linear low density polyethylene (b) has a melt index of from 0.5 to 5 g/10 min. at 190"C.

6. A composition according to any one of the preceding claims also containing an agent to impart improved clarity.

7. A composition according to claim 6 wherein the agent to impart improved clarity is dibenzylidene sorbitol in an amount from 0.1 to 2 wt % based on the total polymer weight.

8. A composition according to any one of the preceding claims which also contains from 2 to 1 5 wt % of a high density polyethylene homopolymer having a density of at least 0.945 gm/cc.

9. A composition according to claim 1 substantially as described with reference to Example 1 or 2.

10. A sterilizable film produced from a composition as claimed in any one of the preceding claims.

11. A film according to claim 10 produced by co-extrusion of said composition with a coextrudate resin selected from fluorocarbon polymers, ethylene-vinyl alcohol copolymers and polyvinylidene chloride resins.

1 2. A sterilizable parenteral solution bag assembly comprising an inner sealed plastic film bag containing a parenteral solution; an outer sealed bag enclosing the inner bag, said outer bag having a width and a length from 0.6 to 3.8 cm (0.25 to 1.5 inches) larger than the corresponding dimensions of the inner bag; the sealed plastic film bag being of a composition as claimed in any one of claims 1 to 9; and in the space between the outer and inner bags a quantity of a substance sufficient to control removal of a component from or to control the addition of a component to the parenteral solution through the inner bag film wall.

1 3 An assembly according to claim 1 2 wherein said substance is water in sufficient quantity to inhibit removal of water in vapor form from the parenteral solution.

14. An assembly according to claim 1 2 wherein said parenteral solution is blood platelets and said substance is an oxygen generating compound in sufficient quantity to add oxygen through the inner bag film wall to the blood platelets.

1 5. An assembly according to claim 1 2 wherein said parenteral solution is blood platelets and said substance is a carbon dioxide absorber in sufficient quantity to remove carbon dioxide from the blood platelets through the inner bag film wall.

1 6. An assembly according to claim 1 2 wherein said substance is enclosed within a sealed pouch positioned in the space between the inner and outer bag and at least one wall of said pouch is permeable to vapors and gases but resistant to liquid permeability.