EP1140494A1 - Perfectionnements relatifs a des contenants medicaux - Google Patents

Perfectionnements relatifs a des contenants medicaux

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Publication number
EP1140494A1
EP1140494A1 EP99959285A EP99959285A EP1140494A1 EP 1140494 A1 EP1140494 A1 EP 1140494A1 EP 99959285 A EP99959285 A EP 99959285A EP 99959285 A EP99959285 A EP 99959285A EP 1140494 A1 EP1140494 A1 EP 1140494A1
Authority
EP
European Patent Office
Prior art keywords
layer
film according
polypropylene
weight
ethylene units
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP99959285A
Other languages
German (de)
English (en)
Inventor
Gunnar Andersson
Vittorio Sala
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fresenius Kabi AB
Original Assignee
Fresenius Kabi AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from SE9804006A external-priority patent/SE9804006D0/xx
Application filed by Fresenius Kabi AB filed Critical Fresenius Kabi AB
Publication of EP1140494A1 publication Critical patent/EP1140494A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/32—Layered products comprising a layer of synthetic resin comprising polyolefins
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B38/00—Ancillary operations in connection with laminating processes
    • B32B38/0036—Heat treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2323/00—Polyalkenes
    • B32B2323/10—Polypropylene
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2439/00—Containers; Receptacles
    • B32B2439/80—Medical packaging

Definitions

  • the present invention relates to a multilayered film suitable for the manufacturing of flexible containers for medical fluids.
  • the film comprises polyolefins only and is assembled with coextrusion into several polyolefinic layers with complementary characteristics to build up a flexible film with high clarity. Further, the film is autoclavable and capable of forming weldings of controlled strength with conventional welding equipment.
  • a polymer material suitable for a container for medical fluids for parenteral use must comply with several important requirements.
  • the material must be possible to be permanently welded to a bag including other details of polymeric material, for example conventional saddle-formed port system and filling ports. It must also admit the formation of welded seams of different strength, in particular (weak) peelable seal seams possible to rupture manually, as well as permanently sealing welded seams, preferably by simple modifications of the welding conditions.
  • the material should be substantially impermeable for water vapor even during steam sterilization, but need not be completely airtight, since in many applications where an effective barrier against environmental oxygen is required to protect an oxygen- degradable product, it is advantageous to use a secondary outer airtight envelope enclosing the inner container filled with the product together with a sachet comprising an oxygen scavenger composition. In such a case, it is of advantage if the material of the container could permit an oxygen transfer from the degradable fluid to the oxygen scavenger for consumption of substantially all the dissolved residual oxygen in the product.
  • a polymeric material suitable for a medical container with many of mentioned characteristics would preferably comprise polyolefins, since they are cheap and chemically inert and free from potentially hazardous migrating agents compared to for examples halogenated polymers.
  • polyolefins various qualities of polyethylene and polypropylene are regarded as suitable materials.
  • polyethylenes are too soft and lack in heat resistance when heat sterilizing temperatures are reached which often is required in the pharmaceutical industry.
  • pure polypropylenes are brittle and rigid, so in practice they often need to be blended with polymers which impart a softness and flexibility to provide a material with higher mechanical processability, such as polyethylene and certain thermoplastic elastomers.
  • multilayered film materials consisting of several layers with complementary properties frequently have been developed for use in the packaging of medical fluids.
  • polypropylenes often have been combined with a supplementary elastomer to improve its flexibility and resilience.
  • an inner, sealant layer comprising polypropylene to benefit from its compatibility to stored fluids and for facilitating the manufacturing of a container by means of different welding techniques.
  • Such a material is comprised in a multilayered film, it is placed as an outer, release layer. In addition it is often requested that such a layer shall be printable in order to carry important information to the user and for this reason, it must not allow migration from the printing ink.
  • Suitable materials for such an outer layer can be found among certain polyesters and copolymers thereof and in particular cycloaliphatic polyesters.
  • an elastomer may be introduced in the inner layers. Examples of this type of multilayered films are found in EP 0 228 819 and in EP 0 199 871. Such a material suitable for medical containers is Excel ® from McGaw Inc.
  • EP 0 197 054 discloses a film having an outer high density polyethylene layer and an inner middle density polyethylene layer, suitable for autoclavable flexible containers. This film is reported to overcome difficulties in maintaining the shape of the container after autoclavation without compromising in other characteristics like impact strength and optical clarity. However, this type of film will not be suitable for welding seals of different strength as required for multi-chamber containers having easy rupturable seals as partitions between the chambers for readily mixing their contents before administration.
  • layers made from polyethylene due to their low softening temperature, hardly will be able withstand high pressure steam sterilization at 121 °C for required autoclavation periods over 15 minutes without being deformed. Moreover, polyethylene layers will reduce the impact strength of the material.
  • EP 0 216 639 describes a multi-layer film for packaging of physiologic solutions comprising at least two layers.
  • One layer consists of polyester, polypropylene or a mixture of polypropylene and elastomer.
  • the second layer consists of a mixture of polypropylene and elastomer.
  • a possible third layer placed inside of the second layer consists of polypropylene or polyethylene.
  • Films included in this patent either contain more than 90% by weight of elastomer or contain polyester or both. None is revealed about the possibility to form seals of varying strength.
  • US Patents No. 4,536,549 and 4,540,416 disclose polyolefin films and containers made therefrom.
  • the films comprise a characteristic blend of polypropylene random copolymer with 1 -6 % ethylene and a low linear low density polyethylene and provides articles which are sterilizable with high clarity and have low water vapor permeability. It is not further revealed herein if it is possible to construct sealing seams of different strength by welding these films together under different conditions.
  • EP 0 739 713 relates to coextruded, non-PVC multilayer films free from softening agents which are reported to be impact resistant, heat sterilizable, flexible, transparent, substantially impermeable to water vapor, easy to recycle and may readily be formed into medical bags with one or more chambers by its sealing and welding capacities.
  • These films principally consist of an outer layer and support layer having a softening temperature above 121 °C which surround at least one middle layer having a softening temperature below 70°C and contributes to the overall flexibility of the film.
  • the films comprise an innermost sealing layer. All layers essentially consist of a polyolefin homopolymer and/or a polyolefin copolymer.
  • an extruded seven layer film is suggested with a sealing layer comprising polypropylene random copolymer mixed with the thermoplastic elastomer styrene-ethylene-butyelene-styrene copolymer.
  • a sealing layer comprising polypropylene random copolymer mixed with the thermoplastic elastomer styrene-ethylene-butyelene-styrene copolymer.
  • US Patent No. 5,071,686 discloses a polypropylene based multilayer film for preparing flexible retortable pouches for medical solutions.
  • a modifier selected among different ethylene-based copolymers and elastomers.
  • a number of such films are exemplified that comprise an outer and an inner, sealant layer of such polypropylene compounded with a modifier surrounding an inner layer based on a high density polyethylene mixed with the modifier.
  • this material is suitable for preparing different types of both permanent and peelable welds with retained reduced strength after autoclavation at 121° C for about 30 minutes.
  • EP 0 564 206 discloses a medical container with good heat resistance, transparency and softness. These properties are reported to be obtained by mixing an amorphous polypropylene with a crystalline polyolefin in a single-layer or a multilayer film material for preparing such a container. It is however stated that a thermoplastic elastomer, such as styrene based elastomer may be added to achieve good formability and mechanical properties and nothing is revealed about the heat sealing capacity of the material. Further, a compromise between transparency and strength of the material has been made herein, since some of the clarity and transparency of amorphous polypropylene has been sacrificed for the introduction of the stronger crystalline polypropylene.
  • EP 0 369 788 describes films of seven different layers with improved moisture barrier properties, suitable for the manufacturing of medical bags filled with medical solutions which must be subjected to autoclavation before storage. These films have a drawback in their complicated structure and in their requirement of an adhesive layer between its outer layer and its inner layers. Furthermore, the films exemplified herein are not entirely based on polyolefins. As in the aforementioned EP 0 733 472, it is disclosed films for medical bags with improved clarity and flexibility which have an interior layer comprising homogenous ethylene/alphaolefin copolymer of a controlled density which require an adhesive layer and the provision of exterior layers comprising high density polyethylene.
  • WO 93/17863 describes a polymeric film suitable for the production of openable multi-chamber containers which when heat sealed readily is peeled by hand force without tearing apart and destroying the film, or risking delamination of its layers.
  • the film has a sealant layer comprising a ternary blend of an ethylene propylene copolymer, a low density polyethylene and a butene polymer. It is not further revealed herein if the film is suitable for medical fluids or if heat seals of variety of strength is accomplished.
  • US 4,279,344 reports another laminated film which solves the problem of obtaining heat seals openable by hand force which not are impaired by subsequent heat sterilization.
  • the film comprises a ionomer resin and does not comply with the requirement of being composed of only polyolefins.
  • EP 0 699 521 describes multilayer films for producing heat sterilizable flexible containers comprising five layers of ethylene-alphaolefin each of a defined density.
  • WO 95/26177 discloses multilayer film materials, which are suitable for autoclavable multi-chamber containers filled with parenteral nutrients. The films are possible heat seal by means of welding so both permanent and week seal seams can be obtained in order to provide rupturable partitions between separately formed chambers so as to enable aseptic mixing of different stored components before their administration.
  • these materials suffer from the mentioned drawbacks of comprising thermoplastic elastomers which both are costly and might have unknown effects when stored with lipophilic fluids.
  • EP 668 157 describes a multilayer polyolefin film suitable for production of heat sealable containers for nutrients, comprising a base layer which preferably is made of 90-100 % polypropylene polymer with a preferred melt point of 150 to 170°C. but can be made from propylene-ethylene copolymer with less than 10 %(wt) of ethylene.
  • the base layer is complemented with a covering or sealant layer which contributes to an improved capacity of the film to form welded heat seals and comprises a propylene-ethylene copolymer with preferably 1 -7 % (wt) of ethylene produced with specific metallocen catalysts, having a preferred lower melt point of 120 to 130°C.
  • the German Patent Application DE 44 10 235 discloses a heat sealable multilayer which may be based substantially of polyolefins.
  • the film preferably has an outer layer of polypropylene-polyethylene copolymer with 10 to 15 % (wt) ethylene with a melt temperature between 160 to 165°C and an inner, sealant layer based on a polypropylene having lower melt point of about 130°C by the addition of a temperature reducing agent.
  • a middle layer is present preferably the same polypropylene-polyethylene copolymer as the outer layer.
  • This film is firstly aimed for packaging of conventional food products and is intended to be more easily peelable for the consumer.
  • the Japanese Patent Application published as 9-85911 refers to a multilayer sealant film for packaging material consisting of polypropylene based polymers which comprise a layer of crystalline polypropylene resin. This film will have a drawback from its reduced clarity or transparency due to its addition of crystalline polypropylene.
  • WO 98/36905 Al directs a multilayer film for sterilisable fluid containers. Included are flexible, transparent, all polyolefin films for the production of containers for infusion solutions. The film is autoclavable and capable of being sealed by welding.
  • a multilayer film according to WO 98/36905 consists of different polymers and copolymers of propylene and ethylene. The film consists of an outer layer, an inner layer and n complex, intermediate layers. It is obvious from the examples of the WO 98/36905 that n is equal or greater than three and that the inner layer is shown to be made of a linear low denstity polyethylene.
  • the structure is rather complicated, the film can not be easily manufactured and it comprises all the drawbacks connected to the use of a polyethylene, e. g. linear low density polyethylene as the most inner layer is not capable of allowing seals of different but controlled strength.
  • a polyethylene e. g. linear low density polyethylene as the most inner layer is not capable of allowing seals of different but controlled strength.
  • EP 0 346 774 Al mainly deals with a container with a plurality of compartments for foods or pharmaceutical products.
  • the container is produced from a film consisting of a mixture of at least two polyolefin resins with a minimum difference in melting point of 8 degrees.
  • a two layered structure is disclosed, wherein each of the layers is comprised of a blend of polypropylene and linear low density polyethylene or polypropylene, low denstiy polyethylene and polyethylene.
  • Coextruded films are disclosed comprising an inner layer made of low density polyethylene and polypropylene and an outer layer made of linear low denstiy polyethylene. Because of the essential and dominant use of polyethylene material the resulting films and containers probably will suffer from poor transparency.
  • a first object of the present invention is to provide a film made only from polyolefin materials suitable for manufacturing flexible multi-chamber containers for storage of lipophilic parenteral fluids by welding both permanent and different peelable seal seams in a wide variety of applications with conventional equipment, including the formation of separate chambers which have partition seams rupturable by hand force of the user, in order to accomplish a safe and convenient mixing of separately stored agents within the container, just prior to the dispensing or administration of the resultant mixture.
  • a second object of the present invention is to provide a film which has low water vapor transmission, has suitable clarity and transparency and a high aesthetic value without spots and discoloration.
  • a third object of the present invention is the provision of a film which has a suitably high robustness and thickness while still having suitable mechanic properties for the production of containers for medical fluids, including a high flexibility, low brittleness and high impact resistance, also at low temperatures down to -30°C.
  • a fourth object of the present invention is to provide a film material which has little or no tendency for migration of agents from its polymeric matrix, even if subjected to long term contact with lipophilic fluids. Further, the film material should be printable with conventional printing without allowing migration of the ink into the material.
  • a fifth object of the present invention is to provide a film material which is capable of being processed into containers with a simple and economic welding technique by employing sealing bars without protective coverages, such as Teflon and silicone which frequently must be replaced when worn out.
  • a further important object of the present invention is to provide a film material with high heat resistance capable of maintain its shape when subjected to heat sterilization with pressurized steam (autoclavation) of at least 121°C for at least 15 minutes, while maintaining the aforementioned characteristics.
  • a still further object of the invention is to be able to employ only cheap polyolefin raw material for producing the films which are manufactured with simple, conventional catalysts by co-extrusion into flexible films, preferably of at least two layers with high compatibility to each other, so no adhesives or surplus adhesive layers will be necessary in order to provide a film without a tendency to delaminate.
  • a flexible polyolefin multilayered film for preparation of medical containers by self sealing comprising at least a first outer layer and a second layer, each of the layers consisting essentially only of one or more polypropylene based polymers selected from the group consisting of polypropylene homopolymers, polypropylene polyethylene copolymers having randomly distributed ethylene units and mixtures of said homopolymers and said copolymers.
  • said second layer has a melting point in the range between 120 °C and 150 °C
  • said first outer layer has a lower flexibility and a higher melting point than said second layer
  • said second layer comprises a polypropylene polyethylene copolymer with a higher amount of ethylene units than said outer layer.
  • the flexible film for preparation of medical containers by heat sealing is made only of polyolefins.
  • the outer layer is an outer part with a higher melting point than its second layer or sealant part which is aimed to be engaged in a self-sealing process when forming containers.
  • the sealant part thereby will constitute the inside of the film which when formed to a flexible container will contact the goods stored therein. For this reason, it is a prerequisite to be able to manufacture a container from the inventive film material by forming seams by heat sealing.
  • the material has an outer part, intended to face the outside environment, with a higher melting point than its sealant part, intended to face the interior of the container, so such sealant parts easily can be joined together under the influence of for example controlled heat and pressure from a conventional welding tool to form a sealing seam of adequate strength.
  • the film must have an outer part which contributes to the maintenance of the overall shape of the film by being essentially unaffected of the welding procedure, principally by having a higher melting point than the welding temperature.
  • the sealant part of the film should, however, be capable of reaching its softening temperature at the welding temperature and sealing procedure, so a heat seal can be obtained when contacting sealant parts of the film under the influence of a conventional welding equipment.
  • Softening temperature is defined herein as the temperature when the polymeric material undergoes a phase transition from its solid form to a substantially softer form. When heating the material further it will reach its melting point at which it will be completely liquefied. It is to be understood that any welding processing of materials discussed herein will be performed at a temperature above the softening temperature but below the melting point. It would also be possible to obtain welds of different strengths, i.e. permanent and peelable welds, by welding at different temperatures with the films of the present invention.
  • the films consists essentially only of polyolefins.
  • essentially only is meant that minor parts, such as about 0.01 to 1 % (by weight) of conventional non-polymeric additives, as exemplified by antioxidants and stabilizers, can be included.
  • the polyolefins are polypropylene based polymers including polypropylene homopolymers and polypropylene copolymers.
  • the polypropylene based polymers are crystalline.
  • the polypropylene copolymers have randomly distributed moieties of a comonomer.
  • the comonomer of such polypropylene copolymer is ethylene and that the polypropylene-polyethylene random copolymers are prepared from cheap granulated raw material sources made with conventional catalysts, such as Catalloy Spheripol from Montel. It is an important part of the present invention to be able to use cheap and conventional polyolefin materials which not need sophisticated production processes or the presence of exclusive catalysts which may require additional consideration with regard to that any residual trace amounts may affect the clinical quality of the stored pharmaceutical product.
  • the films according to the present invention typically have a higher amount of ethylene units in its second layer or sealant part compared to the outer layer or outer part, respectively, in order to accomplish a part with lower melting point in comparison to the outer part of the film. These characteristics contribute to obtain the welding properties of the film material into a flexible single- or multicompartment container.
  • the films according to the present invention comprise a specific layer of one or several polypropylene polymers including at least one polypropylene- polyethylene copolymer with a defined amount of ethylene units to provide a defined melting point.
  • a layer has a melting point between about 120 to 150°C and preferably between 135 and 145°C. According to a specifically preferred example the melting point is about 139-141°C.
  • the films according to the present invention are multilayer films having at least two layers, a first outer layer with a melting point above the sealing temperature and a second layer with a comparatively lower melting point than said first layer.
  • the first, outer layer has the capacity of being heat resistant to provide the film with stability during the welding and further it gives the film a hardness and a desirable impact strength. Additionally, the first layer is printable and will not allow migration of the printing ink.
  • the first layer preferably comprise one or more a polypropylene polymers selected among polypropylene homopolymers and polypropylene-polyethylene copolymers. Typically suitable amounts ethylene units in such polypropylene-polyethylene copolymers vary between 1 to 5 % (weight).
  • the first layer has a melting point exceeding about 145°C. More preferably from about 145 to 160°C and most preferably between about 145 and 150°C.
  • the second layer comprises at least one polypropylene-polyethylene copolymer with a higher amount of ethylene units than any polypropylene- polyethylene copolymer of the first layer.
  • said polypropylene-polyethylene copolymers comprise between 5 to 50 % (weight) ethylene units, more preferably between about 10 to 30 % weight.
  • the comparatively higher content of ethylene units polypropylene-polyethylene copolymer of the second layer contributes to provide the film with desired mechanical properties like flexibility.
  • the second layer is thicker than the first layer and preferably, the second layer has at least the double thickness of the first layer.
  • the second layer can constitute the sealant layer and be capable of self-sealing by means of welding.
  • the second layer has a lower melting point than the first layer which preferably is below 140°C and most preferably between about 130 to 140°C.
  • the film is sufficiently robust while being highly flexible and suitable for self-sealing by welding.
  • the film preferably has certain thickness that, on the other hand, must not compromise with the flexibility and the other mentioned necessary requirements.
  • a suitable thickness is also of importance to compensate for any migration of undesired compounds from the film. It is therefore preferred that the film has a thickness of at least 100 ⁇ m, more preferably it has a thickness of at least 150 ⁇ m and most preferably about 150 to 250 ⁇ m.
  • the second layer is the thickest and contribute most to the overall flexibility of the film, whereas the first layer can be regarded to provide it with supplementary strengthening characteristics necessary for practical use of the film.
  • one or more additional layers can be included which are comprised of polypropylene -polyethylene copolymers or of mixtures of the materials comprised in the first and the second layers.
  • the thickness of such an additional layer is substantially less than the thickness of the second layer and preferably of the same dimension as the first layer.
  • the additional layer(s) are added to the inner part of film and will consequently face the second layer.
  • at least the innermost additional layer is provided with a self-sealing capacity and can provide sealing seams with conventional welding techniques, as is described above.
  • the melting point of the said preferred additional layer(s) will be lower than the melting point of the first layer, but not necessarily lower than the melting point of the second layer.
  • the film contains a first and a second layer according to above and a third, additional sealant layer having a melting point lower than the melting point of the first layer and the same or lower melting point, than said second layer. Furthermore, in such a film, the thickness of the second layer will exceed the sum of the thickness of the first and third layers.
  • the overall dimensions of the film typically may vary so that the outer layer has a thickness of about 10 to 50 ⁇ m, the second layer has a thickness of about 100 to 200 ⁇ m and the sealant layer has a thickness of about 10 to 50 ⁇ m.
  • the first layer is defined as above and the third layer comprises a polypropylene polyethylene copolymer with a higher amount of ethylene units than any polypropylene polyethylene copolymer present in the first layer.
  • the second layer will in such case consist of a mixture of material of the first layer and the third layer. The melting point of the second layer, consequently will be lower than the melting point of the first layer, but higher than the third layer which will be engaged in the sealing process.
  • the first layer will comprise a polypropylene polyethylene copolymer with 1 to 5 % (weight) and preferably about 2 % (weight) of ethylene units and the third layer will comprise a polypropylene polyethylene copolymer with 5 to 50 %( weight), preferably between about 10 to 30 % (weight) and more preferably about 15 % (weight) of ethylene units, while the second layer will comprise a mixture of polymers comprised in the first and the third layers.
  • a mixture contains from about 95 to 5 % (weight) of the polymer comprised in the first layer and from about 5 to 95 % (weight) of a polymer comprised in the third layer.
  • Preferred mixtures contain about 90 to 75 % (weight) of the polymer comprised in the third layer and about 10 to 25 % (weight) of the polymer comprised in the first layer.
  • a most preferred mixture contain about 85 % (weight) of a polymer contained in the third layer and about 15 % (weight) of a polymer contained in the first layer.
  • a suitable film according to this first aspect is composed of:
  • a first layer consisting of a polypropylene polyethylene copolymer with 2 % (weight) ethylene units having a thickness of 20 ⁇ m;
  • a third sealant layer consisting of polypropylene polyethylene copolymer with 15 % (weight) ethylene units having a thickness of 30 ⁇ m; and
  • a second (or middle layer) consisting of a mixture of the polymers of the first and third layer which contains 85 % (weight) of the polymer of third layer and 15 % (weight) of the polymer of the first layer.
  • the first layer is the defined as above, the second layer comprises a polypropylene polyethylene copolymer with a higher amount of ethylene units than any polypropylene polyethylene copolymer present in the first layer and the third layer contain the same material as the second layer;
  • the first layer will comprise a polypropylene polyethylene copolymer with 1 to 5 % (weight) and more preferably about 2 % (weight) of ethylene units.
  • the second layer preferably will comprise a polypropylene polyethylene copolymer with 5 to 50 % (weight) and more preferably about 15 % (weight) of ethylene units.
  • a preferred film is composed of: (i) a first layer (or outer layer) consisting of a polypropylene polyethylene copolymer with 2 % (weight) ethylene units having a thickness of 20 ⁇ m; (ii) a second (middle) layer having a thickness of 140 ⁇ m consisting of a mixture of 85 % (weight) of a polypropylene polyethylene copolymer with 15 % ethylene units
  • the characteristics of the individual layers of described multilayered films comprising polypropylene polymers contribute to surprisingly favorable overall mechanical properties and suitability for applications for the pharmaceutical industry.
  • the first, outer layer contributes to stabilize the film during heat sealing and imparts a desirable hardness and impact strength to the material.
  • the second layer gives the film a suitable flexibility.
  • the optional additional layers provides further improvements in sealing capacity and further provides heat seal seams of different strength can be produced when varying welding conditions, such as welding temperature and pressure.
  • the restriction to only polypropylene polymers, such as polypropylene homopolymers and polypropylene-polyethylene copolymers of varying ethylene content in the layers leads to an excellent compatibility of the layers so no adhesives or adhesive layers are required and there is a minimized risk for delamination of the material.
  • the inventive film maintains the favorable clarity and transparency and retain the water vapor resistance of pure polypropylene in a surprisingly high manner also after being subjected to harsh heat sterilization condition by means of high pressure steam (i.e. autoclavation at about 121 °C for more than 15 minutes). It is a further advantage that the inventive films maintain their flexibility at low temperatures at about 2 to 5°C at which containers made from the film frequently will be stored. The containers will thereby be less fragile during cold transportation and the risk for accidental leakages is reduced.
  • inventive films will also comply with requirement of the European Pharmacopoeia that less than 5 % of the copolymers are extracted in a standardized test.
  • suitable materials are the film Adflex 7104 XCP from Montell of random propylene-ethylene copolymer with about 15% ethylene units and the film Daplen KFC 2008 from PCD of random propylene- ethylene copolymer having about 8% ethylene units.
  • the random propylene-ethylene copolymers Eltex 104 from Solvay about 3-4% ethylene units and a melting point of 146°C
  • Daplen KFC 2004 from PCD
  • EP1 X30F from Montell
  • Montell about 2% ethylene units and a melting point of 152°C
  • RD 701H from Borealis
  • Adflex 7104 XCP the random propylene- ethylene copolymer Softflex SD 200F from Borealis with about 15% ethylene units and melting point of 141°C and the random propylene-ethylene copolymer Daplen RAHECO K 2033 from PCD with 13% ethylene units and a melting point of 140°C are suitable material .
  • Adflex 7104 XCP the random propylene- ethylene copolymer Softflex SD 200F from Borealis with about 15% ethylene units and melting point of 141°C
  • the random propylene-ethylene copolymer Daplen RAHECO K 2033 from PCD with 13% ethylene units and a melting point of 140°C
  • mixtures or blends of these materials can be used for the preparation of films according to the present invention.
  • the manufacturing of the flexible material according to the present invention is performed by conventional coextrusion into sheet formed films of suitable dimensions.
  • the sheets can thereafter be processed into containers for medical fluids having one or several compartments according to what has been described in more detail by the International Patent Application PCT/SE97/00590 by forming different seams with heat sealing.
  • the manufacturing and filling procedures can be performed with a number of conventional methods know to persons skilled in medical packaging technology and will not be further described herein.
  • Fig. 1 shows a principal drawing of a cross-section of a film according to a three- layered embodiment of the present invention.
  • the embodiment of the inventive film showed in Fig. 1 consists of three layers 12, 14 and 16.
  • the first layer 12 consists of polypropylene ethylene copolymer having 98 % propylene and 2 % ethylene and has a thickness of 20 ⁇ m with a melting point of 139°C. This polymer is of the quality EP1C30F from Montell.
  • the third, sealant layer 16 consists of polypropylene ethylene copolymer with 15 % ethylene units and has a thickness of 30 ⁇ m and a softening temperature of 85°C. This polymer is of the quality ADFLEX 7104 XCP from Montel Europe NV.
  • the second, interior layer consists of a mixture of 85 % ADFLEX 7104 XCP and 15 % EP1C30F and has a thickness of 140 ⁇ m having a softening temperature of approximately about 95 to 100°C.
  • a film manufactured in accordance with Example 1 was welded into pouch formed flexible containers by joining sealant layers together and subjecting the joint part with a heated welding tool of a conventional design for this purpose.
  • the welding temperature of the tool was having a temperature of 130°C.
  • the tool had a contact time of about 1 second in an arrangement allowing not more than 1.2 second contact time. After cooling the seam to room temperature the so formed pouches were manually inspected for durability. It is appreciated that the pouches have sufficiently durable seams to be suitable for storing and shipping liquid pharmaceuticals.
  • Films made in accordance with Example 1 were compared for delamination with samples of the film material Excel consisting of an outer copolyester layer tied to a layer of ethylene-propylene copolymer compounded with thermoplastic elastomer SEBS. The films were wiped vigorously with pads soaked in ethanol for several minutes. After the end of this process, in some samples of the Excel film the layers showed a clear tendency to separate from each other. In contrast, films according to the present invention made in Example 1 was entirely unaffected in terms of delamination.
  • Example 1 The films made in accordance with Example 1 were tested for their flexibility and clarity. It was found by tentative flexibility tests that invention film material was only marginally less flexible than Excel. The visual clarity of pouches made of the presently invented films was compared with the guidelines of the European Pharmacopoeia for this type of material and they were found to have suitable clarity and suitably low opacity.
  • a two-layered structure was produced in accordance with the present invention.
  • the mixture of the 2 nd layer is produced by compounding the right proportions of the two materials and extruding pellets from the blend. These pellets are fed into the extruder for co-extrusion.
  • the film is produced by co-extrusion and can be considered as a two layer film. This film can be welded at 1.8 bar, 161 °C and 2 s alternatively at 4 bar, 133 °C and 2 s and is printable.
  • a film was produced according to example 5 with the exception that the film is produced by co-extrusion using 3 to 5 extruders.
  • One extruder extrude the 1 st outer layer and 2 to 4 identical extruders extrude the 2 nd layer.
  • the film can either be considered as a three or five layer a multi-layer film with the 2 nd and 3 rd layer comprising the same material according to present invention.
  • these films film can be welded at 1.8 bar, 161 °C and 2 s alternatively at 4 bar, 133 °C and 2 s and are printable.

Landscapes

  • Physics & Mathematics (AREA)
  • Thermal Sciences (AREA)
  • Laminated Bodies (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Compositions Of Macromolecular Compounds (AREA)

Abstract

La présente invention se rapporte à un film multicouche, polyoléfinique, souple et destiné à la fabrication de contenants médicaux par auto-scellement. Ce film comporte au moins une première couche externe et une seconde couche, chacune de ces couches étant principalement constituée d'un ou de plusieurs polymères à base de polypropylène sélectionnés dans le groupe comportant des homopolymères de polypropylène, des copolymères de polypropylène-polyéthylène ayant des unités d'éthylène réparties de manière aléatoire et des mélanges de ces homopolymères et copolymères. Ladite seconde couche possède un point de fusion compris entre 120 °C et 150 °C, ladite première couche externe possède une souplesse inférieure et un point de fusion supérieur à ladite seconde couche, et ladite seconde couche comporte un copolymère polypropylène-polyéthylène ayant une quantité d'unités d'éthylène supérieure à ladite couche externe. La présente invention se rapporte également à des contenants médicaux fabriqués à partir du film décrit ci-dessus ou comportant un tel film.
EP99959285A 1998-11-23 1999-11-19 Perfectionnements relatifs a des contenants medicaux Withdrawn EP1140494A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
SE9804006 1998-11-23
SE9804006A SE9804006D0 (sv) 1998-11-23 1998-11-23 Improvements related to medical containers
US11062598P 1998-12-02 1998-12-02
US110625P 1998-12-02
PCT/EP1999/008876 WO2000030850A1 (fr) 1998-11-23 1999-11-19 Perfectionnements relatifs a des contenants medicaux

Publications (1)

Publication Number Publication Date
EP1140494A1 true EP1140494A1 (fr) 2001-10-10

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP99959285A Withdrawn EP1140494A1 (fr) 1998-11-23 1999-11-19 Perfectionnements relatifs a des contenants medicaux

Country Status (4)

Country Link
EP (1) EP1140494A1 (fr)
JP (1) JP2002530225A (fr)
AU (1) AU1652000A (fr)
WO (1) WO2000030850A1 (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10124209A1 (de) 2001-05-18 2002-11-21 Wolff Walsrode Ag Polyolefinfolie mit peelfähiger Deckschicht
EP1283242A1 (fr) * 2001-08-03 2003-02-12 Amcor Flexibles Transpac N.V. Mélanges de copolymère de propylène Hétérophase et procédé pour sa production
SE528263C2 (sv) * 2004-09-13 2006-10-03 Tetra Laval Holdings & Finance Förpackningsbehållare försedd med en remsa
ATE407971T1 (de) 2005-12-30 2008-09-15 Borealis Tech Oy Propylen-polymerzusammensetzungen mit verbessertem mechanischem eigenschaftsprofil
US9004761B2 (en) 2006-05-01 2015-04-14 Baxter International Inc. Multiple chamber container with mistake proof administration system
CA2701129A1 (fr) * 2007-10-02 2009-04-09 Baxter International Inc. Films contenant des structures de microcouche
DE102013113532A1 (de) 2013-12-05 2015-06-11 Huhtamaki Films Germany Gmbh & Co. Kg Vorläuferverbundmaterial, Verbundmaterial, Verfahren zur Herstellung eines Vorläuferverbundmaterials, Verfahren zur Herstellung eines Verbundmaterials und Verwendung eines Vorläuferverbundmaterials und eines Verbundmaterials

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US4384024A (en) * 1981-03-19 1983-05-17 Imperial Chemical Industries Limited Composite heat-sealable films
JPS6024946A (ja) * 1983-07-21 1985-02-07 昭和電工株式会社 ポリプロピレン多層透明容器
DE3431364A1 (de) * 1984-08-25 1986-02-27 Alkor GmbH Kunststoffe, 8000 München Heisssiegelbare, flexible verbundfolie sowie verfahren zu deren herstellung
JPS6485652A (en) * 1987-09-29 1989-03-30 Kyoraku Co Ltd Plastic container for transfusion
US5318842A (en) * 1992-12-03 1994-06-07 Himont Incorporated Biaxially oriented propylene polymer film or sheet articles
DE19515254C2 (de) * 1995-04-26 1998-06-04 Fresenius Ag PVC-freie Mehrschichtfolie, Verfahren zur Herstellung derselben und deren Verwendung
JPH09225006A (ja) * 1996-02-27 1997-09-02 Kyoraku Co Ltd 柔軟性を有する薬液用プラスチック容器
JP3235055B2 (ja) * 1997-09-18 2001-12-04 出光石油化学株式会社 プロピレン系ランダム共重合体の多層フィルム

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Also Published As

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AU1652000A (en) 2000-06-13
JP2002530225A (ja) 2002-09-17
WO2000030850A1 (fr) 2000-06-02

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