HllllllllllllIllllllllllllllllllllllllllllllllIllllIllllllllllllllllllllll
`US005l29894A
`[11] Patent Number:
`5,129,894
`[45] Date of Patent:
`Jul. 14, 1992
`
`ABSTRACT
`[57]
`The present invention describes package units for medi
`cal purposes, in particular for receiving and/or storing
`stenlizable preparations for parenteraluses or dialysis
`Solutions, comprising a container having at least one
`discharge spout and consisting of polyamide 66 or a
`laminate of polyamide 66 sheet and polyole?n sheet, the
`polyole?n sheet being disposed on the side facing the
`liquid to be stored and the sheet of polyamide 66 being
`disposed on the outside and the two sheets being
`bonded together in usual manner by means of an adhe
`sive. The package umts may further comprise an inner
`coratainerhor an outer colriitainer. Tlhe packagde ukrliit is
`ma e in t at a container aving at east one 156 arge
`spout is made from polyamide 66 or the aforementioned
`laminate’ Said container ?ned with the liquid to be
`stored, then sealed and sterilized and possibly subse
`quen?y Surrounded after cooling and drying with an
`outer container of polymeric material. Package units
`according to the invention may also be made in that
`from a polymeric material an inner container having at
`least one discharge spout is made, said container ?lled
`with the liquid to be stored, sealed, then surrounded
`with an outer container of polyarnide 66 or a laminate of
`l
`-
`g’kj’e??ifg‘sgiig?iigna‘i ‘t’?iys‘illee??fsi?eetiailiiniilygfiiin
`g
`the inner container and the sheet of polyamide 66 of the
`laminate representing the outer sheet, and thereafter
`sterilized.
`
`20 Claims, 1 Drawing Sheet
`
`us‘ PATENT DOCUMENTS
`3,942,529 3/1976 Waage ............................... .. 604/408
`4.131.200 12/1978 Rinfrei
`- 604/410 X
`‘1:121: -------
`4,834,721 5/1989 Onohara ................ .. 604/266
`4,337,047 6/1989 Sato et a1. ..................... .. 604/410X
`
`O SIOH Ct .
`
`.
`
`y
`
`4
`
`Umted States Patent [19]
`Sommermeyer et al.
`
`[54] PACKAGE UNITS FOR MEDICAL
`PURPOSES
`[75] Inventors; Klaus someway“, Rosbach;
`Jib-gen xoem'g, wiesbaden; Franz
`Cech, Rosbach; Reinhold Herbert,
`NewAnspach, an of Fed‘ Rep’ of
`Germany
`_
`_
`[73] Asslgmei Fresemus AG, Bad Homburg, Fed-
`Re-P- of Germany
`[21] APPL NOJ 229,012
`[22] Filed:
`Aug. 5, 1988
`[51] Int. Cl.5 .................................... .gbz/nuissssgj/o?
`[52] US. Cl. .................................. ..
`, 604/416
`_
`[58] Field of Search .............. .. 604/408, 409, 410, 403
`[56]
`References Cited
`
`Primary Examiner-Robert A. Hafer
`Assistant Examiner-Kerry Owens
`Attorney, Agent, or Firm-Pravel, Gambrell, Hewitt,
`Kimball & Krieger
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`MYLAN ET AL. - EXHIBIT 1008
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`US. Patent
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`July 14, 1992
`
`5,129,894
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`PACKAGE UNITS FOR MEDICAL PURPOSES
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`The subject of the present invention is package units
`for medical purposes, in particular for receiving and/or
`storing sterilizable preparations for parenteral use of
`dialysis solutions, including a container having at least
`one discharge spout and consisting of a polymeric mate
`rial including polyamide, which possibly have also an
`inner container or an outer container, and method for
`the production thereof.
`It has been known for a long time to employ package
`units, for example bags, in particular for medical pur
`poses for storing preparations for parenteral use or dial
`ysis solutions, instead of glass bottles, for receiving and
`sterile storing of infusion solutions to be administered
`parenterally or of dialysis solutions. For this purpose
`these bags must be completely sterile and this is usually
`achieved by heating to at least 100° C., in particular to
`about 120° C.
`This leads directly to the requirement made of the
`thermoplastic polymeric material that the latter be sta
`ble at least up to the heating temperature. In addition,
`such a storage bag must be easy to make in economical
`manner in an automatic production process and dispos
`able after use because of its low value. It should also be
`?exible, foldable and in the processed state transparent
`so that changes of the liquid contained in the bag can be
`immediately noticed.
`As material for ?lling these requirements preferably
`soft PVC containing plasticizer to improve its elastic
`properties was employed. These plasticizers, for exam
`ple diisoctylphthalate, are however the cause of worry
`ing phenomena, said plasticizers of softeners are not
`completely enclosed in the voids between the poly
`meric chains and can therefore be dissolved out of the
`polymer by the water or aqueous solution introduced
`into the bag so that contamination of the liquid con
`tained in the bag occurs. Estimates have shown that a
`patent treated for a relatively long time using such PVC
`bags will have absorbed a few g plasticizer and this in
`itself is extremely worrying physiologically and can
`lead to permanent damage in the patient. Moreover,
`such a bag consisting of soft PVC easily be attacked by
`microorganisms which in particular dissolve out the
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`plasticizers and thus regularly destroy the bag. To pre
`vent this, after ?lling such a PVC bag had to be pro
`tected from harmful organisms by a special surrounding
`package.
`These facts led to such PVC bags not being able to
`supersede to an appreciable extent the glass bottles used
`normally as storage containers for medical solutions and
`even not being allowed at all in the ?eld of medicine in
`some industrial countries.
`Attempts have therefore been made to replace the
`soft PVC by other materials. However, such attempts
`failed because these materials were either too expensive
`or had mechanical and physiological disadvantages.
`For example, their water permeability was too high and
`this led to an undesirable increase of the concentration
`of the substances contained in the solution. In addition,
`lixiviatable substances were liberated from them or they
`were easily damaged under excessive mechanical stress.
`CH-PS 444,382 describes such a plastic bag which can
`be used for therapeutical solutions to be employed par
`enterally. In this plastic bag the wall consists of a plastic
`laminate which comprises on the outside, i.e. the side
`remote from the liquid, a PVC layer and on the inside a
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`5,129,894
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`polyhalogen hydrogen synthetic resin layer. The latter
`layer does not have any pharrnacologically inadmissible
`constituents which by dissolving might pass into the
`solution contained in the bag. However, the polyhalo
`gen hydrocarbon substances employed have the disad
`vantage that they are very expensive to produce and
`process and do not fuse adequately at the welds so that
`there is still a direct contact with the PVC. This contact
`also exists moreover at the discharge opening which is
`usually completely made of PVC and with which fur
`ther PVC compound ?exible tubes can be connected.
`Moreover, as disposable bag these plastic bags represent
`an environmental hazard because burning of said bags
`leads to highly aggressive hydrocarbons.
`Polyolefms, e.g. polyethylene, have also already been
`proposed as materials for the storage package. Polyole
`fins are free from plasticizer and are thus not attacked
`by microorganisms. In addition, they have a good water
`vapour barrier and are sterilizable. Bags of polyole?ns
`are described for example in DE-PS 3,200,264 and
`DE-PS 3,305,365.
`These bags of polyole?ns unfortunately however
`have the disadvantage that they have a relatively high
`oxygen permeability and this is problematical in the
`storage of solutions which must be kept for relatively
`long times in so far as due to the oxygen permeability
`oxidation of the dissolved constituents can occur. This
`is in particular extremely critical with amino acid solu
`tions and must therefore be avoided. To overcome this
`problem it has been proposed according to DE-PS
`3,200,264 and DE-PS 3,305,365 to coat the bag sheet of
`polyole?n on its outside with one or more layer(s) re
`ducing this oxygen permeability, for example of a metal
`foil or a further polymer. Such a coating is also used for
`safety reasons because even on extremely careful pro
`duction the bag sheet can have pinholes which cannot
`be seen and which can impair the sterility of the solution
`introduced. In addition, such a covering or coating can
`also considerably improve the mechanical loadability of
`such a bag so that such a bag even when dropped from
`a height of several metres does not burst. The sheet or
`layer used is one having a higher melting point than the
`polymer facing the solution, i.e. which at the melting
`temperature of the inner sheet does not itself melt and
`consequently will not stick to a sealing tool either. Such
`an outer sheet can thus also serve as parting agent in the
`sealing of the inner sheet. Named as preferred polymers
`for coating the polyole?n sheet are polymers having a
`low water vapour permeability and a low oxygen per
`meability, such as polyamides, and as polyamide poly
`caprolactam (PA 6) is preferred, containing no stabiliz
`ing additives and thus complying in its composition
`with the requirements for use in the foodstuff sector.
`As however recent investigations on bags of such
`polyole?n/polyamide laminates have shown the lami
`nates of polyolefm and polyamide, such as laminates of
`polyethylene and polycaprolactam, have disadvantages
`in that undesirable toxic foreign constituents are re
`leased into the liquids to be stored in the sterilization
`and render the solution unemployable for its intended
`use, for example the injection. As it has been possible to
`show, these foreign constituents reach the liquid to be
`stored by migration from the outer sheet of the laminate
`through the inner sheet of the laminate facing the liquid.
`Bags of such laminates are therefore extremely dubi
`ous from the medical point of view.
`Accordingly, the problem underlying the present
`invention is to provide package units of the aforemen
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`tioned type which do not have the disadvantages of the
`chloride, polymethylmethacrylate and the like. The
`known package units or bags, are unobjectionable from
`ole?ns employed for making the above polyole?ns may
`the medical point of view and in which no migration of
`also be used as copolymers and mixed polymers with
`other vinyl compounds, for example ethylene/propy
`foreign constituents into the solution to be stored takes
`lene plastics, poly (ethylene/vinyl acetate), acryloni
`place, and which furthermore are mechanically stable,
`trile/butadiene/styrene polymers, ethylene-propylene
`transparent and heat-sterilizable and have low water
`block copolymers, styrene copolymers, copolymers
`vapour permeability and low oxygen permeability and
`containing vinylidene ?uoride and copolymers contain
`in addition cannot be attacked by microorganisms.
`ing styrene.
`According to the invention this problem is solved in
`that as polyamide polyamide 66 is employed.
`According to the invention polyole?ns are products
`Under the term “polymeric material including poly
`which are made by the vinyl polymerization of possibly
`substituted ole?n, preferably ethylene. These products
`amide” herein polyamide or polyamide—containing lami
`nate of polymeric material is meant. Thus, according to
`may also have slight additives of other polymers which
`the invention the container of the package unit accord
`do not essentially destroy or change the structure of
`ing to the invention may consist both only of polyamide
`said polyole?ns. Thus, for example, small amounts of
`66 and of a laminate of polymeric material including
`styrene-substituted or polyacrylonitrile-substituted eth
`polyamide 66.
`ylene compounds may be added. The resulting polyole
`Polyamide 66 (PA 66) means the polycondensate
`?n products are considered as belonging to the polyole
`obtained by polycondensation of hexamethylene di
`?ns speci?ed above.
`amine and adipic acid.
`According to the invention, as polyole?n preferably
`It has surprisingly been found according to the inven
`polyethylene is used as material for the inner sheet,
`tion that when using polyamide 66, in contrast to the
`possibly with slight additions of vinyl acetate in the
`other polyamides, for example polyamide 6, polyamide
`form of the copolymer of ethylene and vinyl acetate.
`11, polyamide 12 or polyamide 13, as polymeric mate
`In such a case for example the vinyl acetate content
`rial for the container for the package unit after the ster
`may be up to 10% by weight.
`ilization no foreign constituents or no ponderable
`In particular a polyethylene is used of medium or
`high density (MDPE and HDPE) which is usually
`amounts of foreign constituents are to be found in the
`made by low-pressure polymerization. The density lies
`liquid to be stored. The same is true when as polymeric
`material for the containers of the package unit polyam
`within a range of 0.91 to 0.94 g/cm3, in particular about
`0.935 g/cm3.
`ide 66 is employed in the laminate with polyole?n
`sheets, the polyolef'm sheet being disposed on the side
`Furthermore, the polyethylene preferably used ac
`facing the liquid to be stored and on the outside the
`cording to the invention has a high molecular weight
`sheet of polyamide 66, the two sheets being bonded
`and a narrow molecular weight distribution.
`together in usual manner by means of an adhesive.
`It is however to be ensured in every case that such
`Whereas for example in using bags of a laminate of
`polyolefms do not have a melting point below the steril
`polyethylene and polyamide 6, the polyethylene sheet
`ization temperature of about llO°-l20° C. Preferably,
`being used as inner sheet and the polyamide 6 sheet as
`the melting range should be above 110° C.
`outer sheet, after sterilization in the liquid to be stored
`For making the sheets suitable for the laminates the
`foreign constituents were found in an amount of 5 to 15
`usual extruding method of making sheets or hose sheets
`ppm, the respect to the product, under the same condi
`can be employed and do not present the expert with any
`appreciable problems. The polymeric inner sheet and
`tions for bags made from a laminate of polyethylene and
`polyamide 66, the polyethylene sheet being disposed on
`the polymeric outer sheet are bonded together in a
`the side facing the liquid and the polyamide 66 sheet on -
`manner known per se. Any known method suitable for
`the outside, no or no ponderable amounts (weighing
`making the laminates according to the invention can be
`accuracy <1 mg) of foreign constituents could be
`employed. Preferably, the inner and outer sheets are
`found in the liquid to be stored.
`adhered together by means of a laminating adhesive
`According to a preferred embodiment as material for
`such as polyvinylidene chloride or a polyurethane.
`- the container of the package unit according to the in
`Such a polyurethane adhesive can advantageously be a
`vention the polyamide 66 is used in a laminate with a
`two-component adhesive, the ?rst component consist
`polyole?n, the polyole?n sheet being disposed on the
`ing of a laminated adhesive and the second component
`side facing the liquid to be stored and the polyamide 66
`of an additive lacquer.
`sheet on the outside and the two sheets being bonded
`In the production technique the polyole?n used as
`together in usual manner by means of an adhesive.
`inner sheet can be extruded in the form of a hose-like
`As polyolefms which for making the package unit
`sheet and thereafter adhered to the laminated sheet of
`polyamide 66 using the laminating adhesive mentioned
`according to the invention can be used as polymer for
`above, polyurethane being preferred.
`the inner sheet, according to the invention polymers of
`ole?ns are suitable, such as ethylene, propylene, butyl
`FIG. 1 is a side view in cross-section of a polymeric
`ene and the like, which are possibly substituted. As
`laminate material according to the present invention.
`substituents for example the methyl or ethyl group, the
`FIG. 2 is a partial side view in cross-section of a
`vinyl group and halogen atoms, in particular ?uorene or
`package unit according to the present invention.
`chlorine atoms, may be present. Preferably employed as
`FIG. 3 is a partial side view in cross-section of a
`starting ole?n are ethylene and propylene, in particular
`package unit according to the present invention.
`ethylene polymerized to polyethylene being employed.
`Preferred laminates have at a temperature of about
`Speci?c examples for polyole?ns are: polyethylene,
`23' C. and a relative air humidity of 85% as a rule a
`polypropylene, poly~n-butylene, polyisobutylene, poly
`water vapour permeability according to DIN 53122 of
`4-methylpentene-l, chlorosulfonated polyethylene, pol
`< l. Such values apply to standard laminates which are
`ystyrene, halogenated polyethylene, such as polyvinyl
`advantageously up to 0.2 mm thick, with a thickness of
`?uoride, polyvinylidene ?uoride and polyvinylidene
`50 to 150 pm, in particular about 100 pm, for the poly
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`ole?n sheet and 20 to 100 pm, in particular 30 to 80 pm,
`for the polymeric laminating sheet of polyamide 66. For
`example, a particularly suitable laminate consists of a
`130 pm thick polyethylene sheet and a 50 pm thick
`sheet of polyamide 66.
`In the laminates according to the invention, particu
`larly in the preferred laminates, the oxygen permeabil
`ity is reduced, this value lying below 15 cm3/m2X day
`X bar pressure difference.
`The sheets used according to the invention for mak
`ing the laminate have been approved both by the Fed
`eral Health Office in Berlin and by the FDA (Federal
`Drug Administration) in the U.S.A. as physiologically
`harmless for use in the foodstuff sector and in the medi
`cal sector.
`The laminates of polyolefin and polyamide 66 used
`for the package units according to the invention are free
`from plasticizers and additives or constituents which
`might possibly be physiologically objectionable and in
`particular could diffuse or migrate into the aqueous
`solution. The laminates used according to the invention
`are heat-sterilizable, clear and transparent and also have
`these properties after the sterilization.
`Furthermore, they are mechanically stable and have
`low vapour permeability and a high oxygen barrier
`effect.
`The package units according to the invention or the
`containers of said package units according to the inven
`tion may have any suitable shape or form. Expediently,
`they are made in the form of bags.
`The package units or containers or bags according to
`the invention have at least one discharge spout or outlet
`nozzle which is formed in hose manner or includes a
`tube piece or insert piece. The latter may consist of
`respectively suitable material and can be formed in any
`desired manner and secured in the container or bag. For
`example, they may be formed in the manner described
`in DE-PS 3,305,365 and DE-PS 3,200,264, to which
`reference is made hereby, and consist of the materials
`speci?ed therein.
`The production and processing of the materials for
`the package units or containers according to the inven
`tion is carried out by the methods usual in plastics tech
`nology, as already explained above. Thus, for example,
`the containers may be made by an extrusion of hose-like
`sheets, corresponding cutting to size of the sheets and
`lamination and subsequent edge welding thereof. The
`containers, in which the edge provided for the dis
`charge spout remains unwelded, are subsequently fused
`to a tube piece possibly comprising a bonding layer or
`an insert piece comprising the discharge opening(s) and
`possibly surrounded by a bonding layer. When using a
`bonding layer as described for example in DE~PS
`3,305,365 the tube or insert piece is provided with such
`a bonding layer in accordance with the usual tech
`niques, as can be done for example by simply drawing
`on or pushing over the elastic material of the bonding
`layer in hose form onto the tube piece or insert piece
`and introducing it into the opened container. Thereafter
`the heat sealing of the entire still not welded edge to the
`hose connection piece or to the tube piece or insert
`piece provided with the bonding layer is carried out. If
`several tube pieces are provided this processing step is
`carried out simultaneously, corresponding sealing tools
`being of course employed. The heat sealing is carried
`out by the usual methods.
`The sterilization of the containers thus made is by the
`usual methods in an autoclave and of course to avoid
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`bursting of the containers in the autoclave an excess
`pressure must be applied to balance the pressure obtain
`ing in the container interior. For safety reasons and, if a
`bonding layer is employed, to ?x the bonding layer,
`however, a higher excess pressure is used than would be
`necessary to balance the pressure obtaining in the con‘
`tainer interior. The excess of this pressure over the
`pressure obtaining in the container is not critical but for
`example it should be at least 0.5 bar greater than the
`pressure obtaining in the container. It may be 2 to 3 bar,
`for example 2.2 bar.
`If this is necessary due to the materials employed, the
`laminates according to the invention can further be
`subjected to a crosslinking after the sealing of the con
`tainers, before the liquid to be stored is introduced and
`before the sterilization.
`In the cases where a crosslinking of the welded con
`tainer material comprising discharge spouts with hose
`connection pieces or tube or insert pieces is intended,
`said crosslinking is carried out before the sterilization, if
`a sterilization is then still necessary, by methods known
`per se as described for example in DE-PS 3,200,264 and
`EP-PS O 068 271.
`In accordance with a further embodiment, in particu
`lar in cases where a particularly high protection against
`mechanical damage is to be obtained and/or for long
`time storing of the package units, the container of the
`package unit according to the invention may be sur—
`rounded by a further container, an outer container.
`Suitable materials for such a further container or
`outer container are materials which are able to protect
`the container according to the invention, which when
`using an outer container represents the inner container,
`from mechanical damage, avoid any water vapour
`losses, prevent access of microorganisms (no fungus
`formation or sporulation), represent a gas barrier, i.e.
`oxygen barrier, are preferably substantially transparent
`and permit a long-time storage of the package units.
`Examples of such materials are metal or plastic foils
`or laminates which ful?l the aforementioned conditions.
`Preferred are foils or laminates of plastic.
`Examples for metal foils or laminates are:
`aluminium foils,
`laminates of polyethylene sheets and aluminium foils,
`laminates of polypropylene sheets and aluminium
`foils.
`Suitable as plastics are essentially the polyolefins as
`names above in conjunction with the containers accord
`ing to the invention, which when using outer containers
`represent the inner containers. Said plastics may be used
`in the form of individual sheets or in the form of lami
`nates of two or more sheets. Preferred are laminates of
`two sheets: inner sheet, i.e. the sheet facing the inner
`container, and outer sheet, i.e. the outer foil or sheet
`coming into contact with the environment.
`Particularly suitable according to the invention for
`the outer container are laminates of polyolefins as
`named above for the inner container, polyethylene
`being particularly preferred as polyolefm, and polyes
`ters, copolymers of ethylene and vinyl alcohol, copoly
`mers of ethylene and vinyl acetate. Examples of suitable
`laminates are laminates of polyethylene sheet and poly
`ester sheet, as polyester polyethylene terephthalate and
`polybutylene terephthalate being particularly suitable,
`laminates of polyethylene sheet and a sheet of copoly
`mers of ethylene and vinyl alcohol, laminates of poly
`ethylene sheet and a sheet of copolymers of ethylene
`and vinyl acetate.
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`According to the invention this outer container fur
`ther provides a double oxygen barrier and the container
`contents, i.e. the liquid or solution to be stored, are
`protected from oxidation.
`In the production of these package units according to
`the invention comprising outer container ?rstly the
`inner container is made as described above; when using
`a laminate of a polyamide 66 sheet and a polyole?n
`sheet the polyole?n sheet is arranged on the side facing
`the liquid to be stored and the sheet of polyamide 66 is
`arranged on the outer side and the two sheets are
`bonded together by means of an adhesive. Thereafter
`the inner container thus made, possibly after crosslink
`ing, is ?lled with the liquid or solution to be stored,
`sealed and sterilized as described above. After cooling
`and drying of said sterilized inner container the sealed
`and sterilized inner container ?lled with the liquid to be
`stored is provided in a manner known per se with the
`outer container.
`For example, the sterlized dried and cooled inner
`container is placed in a lower web deep-drawn corre
`sponding exactly to its contours for the outer container
`and covered with the upper web for the outer container.
`Thereafter, a vacuum is applied to the outer container,
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`which should be about 900 to 900 mbar. At the same
`time or directly thereafter the edges of the upper web
`and lower web of the outer container are welded to
`gether. When the vacuum is applied the sheet of the
`outer container bears sealingly on the laminate of the
`inner container.
`The lower web and the upper web may consist of the
`same or different material and consist preferably of the
`same material. Likewise, the upper web and the lower
`web of the outer container may have the same or differ
`ent thicknesses and are preferably of the same thickness.
`It is important for the materials of the lower web and
`upper web to be weldable together, in the case of lami
`nates the inner layers of the lower web and upper web.
`If the lower web is deep-drawn said lower web should
`be preferably somewhat thicker than the upper web.
`The upper web and the lower web have expediently
`thicknesses of 100 to 200 pm.
`In accordance with a further embodiment of the
`package units of the invention the container referred to
`above and consisting of polyamide 66 or a polymeric
`laminate including polyamide 66 may represent the
`outer container and surround an inner container of pol
`ymeric material having at least one discharge spout;
`when using a laminate including polyamide 66 for the
`outer container the side of the laminate facing the inner
`container consists of polyolefm sheet and the outer ‘side
`of the laminate of polyamide 66 sheet and the two sheets
`are bonded together in the usual manner by means of an
`adhesive.
`As material for the inner container according to this
`embodiment any polymeric material may be used which
`is suitable for storing and keeping the sterilizable prepa
`rations for parenteral use or the dialysis solutions, per
`mits sterilization and has no migratable substances. The
`container material may be in the form of individual
`sheets or in the form of laminates and is preferably
`substantially transparent. Examples of such materials
`are: polyole?ns, polyesters and copolymers thereof.
`The polyole?ns include the polyole?ns mentioned
`above, including PVC and soft PVC, polyethylene
`being preferred. As polyester polyethylene terephthal
`ate is for example suitable.
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`Particularly preferred as material for the inner con
`tainers according to this embodiment, in the form of
`individual sheets or laminates, are polyethylene, co
`polymers of ethylene and propylene and polyester, such
`as polyethylene terephthalate.
`Suitable laminates are composite sheets of the afore
`mentioned materials,
`possibly
`with embedded
`ethylene/vinyl alcohol (EVAL) barrier layers. Exam
`ples of suitable laminates are laminates of polyole?n
`sheets, in particular polyethylene, laminates of polyeth
`ylene sheet and polyester sheet, polyethylene tere
`phthalate being particularly suitable as polyester, lami
`nates of polyethylene sheet and sheet of copolymers of
`ethylene and vinyl alcohol, laminates of polyethylene
`sheet and sheet of copolymers of ethylene and vinyl
`acetate.
`The production of the package units according to this
`embodiment is carried out in that firstly the inner con
`tainer with at least one discharge spout, as described
`above, is made from the materials speci?ed above and
`then, possibly after any necessary crosslinking, ?lled
`with the liquid or solution to be stored and subsequently
`sealed. Thereafter the inner container ?lled with liquid
`and sealed is provided with the outer container of poly
`amide 66 or a polymeric laminate including polyamide
`66, when using a laminate including polyamide 66 for
`the outer container the side of the laminate facing the
`inner container consists of polyole?n sheet and the
`outer side of the laminate consists of polyamide 66
`sheet, and the two sheets are bonded together in the
`usual manner by means of an adhesive and thereafter
`subjected to the sterilization as described above.
`For example, the method is carried out in such a
`manner that the sealed inner container ?lled with the
`liquid or solution to be stored is placed in a deep-drawn
`lower web for the outer container corresponding ex
`actly to its contours and covered with the upper web
`for the outer container and thereafter a vacuum which
`should be about 900 to 980 mbar is applied to the outer
`container. Simultaneously or directly thereafter the
`edges of the upper web and lower web of the outer
`container are welded' together. When the vacuum is
`applied the sheet or laminate of the outer container
`comes to lie sealingly on the inner container. The lower
`web and the upper web of the outer container may
`consist of the same or different material and consist
`preferably of the same material. Likewise, the upper
`web and the lower web of the outer container may have
`the same or different thickness and are preferably of
`equal thickness. The important point is that the materi
`als of the lower web and upper web, in the case of
`laminates the inner layers of the lower web and upper
`web, are weldable together. If only the web is deep
`drawn said lower web should preferably be somewhat
`thicker than the upper web. The upper and lower web
`expediently have thicknesses of 100-200 pm.
`The package unit thus made ?lled with the liquid or
`solution to be stored and sealed and comprising the
`inner and outer containers is thereafter sterilized in a
`pressure autoclave at a temperature of about 120' C.
`and an excess pressure of about 2.2 bar.
`It has surprisingly been found that when using the
`outer containers as described above, in particular con
`sisting of a laminate of a polyethylene sheet and a sheet
`of polyamide 66, the polyethylene sheet being disposed
`on the side of the laminate facing the inner container
`and the sheet of polyamido 66 on the outside of the
`laminate and the two sheets being bonded together in
`
`50
`
`55
`
`65
`
`20
`
`35
`
`40
`
`45
`
`

`
`5,129,894
`
`10
`These values show that with the bag according to the
`invention compared with bags having polyamide 6 in
`stead of polyamide 66 no migration of foreign constitu
`ents into the infusion solution took place.
`
`usual manner by means of an adhesive, after the proce
`dure according to the invention package units or con
`tainers are obtained in which no or substantially no
`migration into the liquid to be stored and no oxidation
`of the liquid to be stored occurred. Likewise, no micro
`organisms were found.
`Referring now to FIG. 1, a polymeric laminate mate
`rial 10 according to the present invention has a sheet A
`of polyamide 66 which is bonded to a sheet B of poly
`olefm by an adhesive layer C.
`FIG. 2 partially illustrates a package unit 12 accord
`ing to the present invention which has a first inner con
`tainer 14 made from a polymeric laminate 10 (as in FIG.
`1) disposed in a second container 16 made from a sheet
`D, preferably a metal or plastic foil or a polymeric
`laminate. In a preferred embodiment, as previously
`described, the sheet D bears sealingly against, but is not
`bonded to, the sheet A.
`FIG. 3 partially illustrates a package unit 20 accord
`ing to the present invention wh