CA2393039C - Autoclavable, pvc-free multilayer film, in particular for the packaging of liquid, medicinal products, production process, and use - Google Patents

Abstract

The invention relates to an autoclavable PVC-free multilayer film, to be especially used for packing aqueous, liquid, medicinal products. The inventive film comprises at least three layers, namely an outer layer (A), an inner layer (I) and an interposed intermediate layer (M), each of which consists of 60 to 100 % by weight of a thermoplastic elastomer, the weight indications relating to the total weight of the respective layer. The inventive film is characterized in that it does not have a yield point measurable according to DIN EN ISO 527-1 to 527-3 after superheated steam sterilization at 121 °C or more. The invention further relates to a method for producing said film and to its use as packing material for packing water-based parenteral liquids or liquid lipophilic emulsions.

Description

1, r r Autoclavable, PVC-free multilayer film, in particular for the packaging of liquid, medicinal products, production process, and use Description The invention relates to an autoclavable, PVC-free multilayer film, in particular for the packaging of liquid, medicinal products, the film having at least three layers, namely an outer layer (A), an inner layer (I), and, arranged between these, a middle layer (M), each of which is composed of from 60 to 100 percent by weight, based on the total weight of the respective layer, of polypropylene materials, and of from 40 to 0 percent by weight of a thermoplastic elastomer, preferably from the styrene block copolymers group. The invention further relates to processes for producing these multilayer films and to the use of multilayer films in accordance with the invention.
There are many multilayer or multiply films for packaging materials, in particular medicinal liquids or solutions, such as saline, amino acid solutions, lipophilic emulsions, dialysis solutions, blood substitute solutions, blood, and the like.

Fundamentally, multilayer films and the packaging obtainable from them, such as bags or similar vessels, are intended to comply with a complex set of requirements. They have to have high flexibility so that filled bags can be discharged completely solely through the effect of gravity. They are intended to have good transparency and, where appropriate, also to have low water-vapor permeability, to be physiologically non-hazardous, and to be mechanically stable. They have to be autoclavable and sterilizable, where appropriate even above 121 C, and finally they also have to be capable of sealing by continuously heated tools, of impulse welding, and/or of sealing by ultrasound.

The films do not necessarily have to be impermeable to oxygen. For applications in which a highly effective oxygen barrier is important use may where appropriate be made of a secondary means of packing, which provides an effective oxygen barrier and encapsulates the inner film pack. If there is an oxygen scavenger between the inner film pack and the secondary packaging it can be preferable for transport of oxygen to be possible through the film of the inner pack. In this way the residual oxygen can be removed efficiently from a sensitive packaged product without difficulty during storage.

For some applications it can be advantageous to be able to control the strength of the weld using simple means (sealing temperature, sealing time, and sealing pressure). By this means it is possible in particular to produce peelable and/or permanent welds using one and the same film material, without other means of assistance. It can also be useful for the outer layer of the film to be capable of easy and permanent printing using conventional pigments, so that important information can be provided for the user.

One of the factors to be avoided here is migration of the pigments into the interior of the packaging.
Suitable materials for outer layers with these properties are found, inter alia, in the polyesters group, in particular the group of the cycloaliphatic polyesters and copolymers of these. Examples of this type of multilayer films are found in EP 0 228 819 (American National Can Company and Kendall McGraw Laboratories) or in EP 0 199 871 (W.R. Grace).

EP 0216 639 (Wihuri Oy) discloses multilayer films with at least two layers for packaging medicinal solutions.

kl One layer is composed of polyester, polypropylene, or a mixture of polypropylene and elastomer. A second layer is composed of a mixture of polypropylene and elastomer. A possible third layer is composed of polypropylene or polyethylene. The films disclosed comprise either more than 90 percent by weight of elastomer or polyester or both.

Although the use of polyester materials can give films whose mechanical properties make them useful, increasing importance is also being placed on properties such as complete recyclability and the use of materials which are more environmentally compatible.

Specifically, the avoidance of raw materials such as PVC, which is attended by the problems of plasticizers, or polyester materials, where the fact that more than one grade of material is present makes recycling more difficult, has led to the development of polyolefin films of varying degrees of usefulness. As a first approximation, polyolefins may be classified as chemically inert materials which are cost-effective, environmentally compatible, and free from hazardous additives which can migrate. However, to comply with the abovementioned set of requirements, many of the films called polyolefin films need a large number of additives which are expensive or are difficult to recycle. The amount which has to be added of some of these additives is such that the term polyolefin film becomes inapplicable. Other polyolefin films comply with only minimum requirements in one or other respect, so that the mechanical properties of the films, for example, or the optical properties, and/or also the bag-manufacturing characteristics (sealing properties, manufacturing speed, and the like) are unsatisfactory.
Polyethylene materials and films based on them and/or comprising them are often too soft or insufficiently heat-resistant. Polypropylene materials are often brittle and somewhat inflexible.

DE 33 05 198 Al (W.R. Grace & Co.) relates to a multilayer polyolefin film. The disclosure includes a three-ply embodiment with a core layer essentially consisting of linear low-density polyethylene, and two outer layers essentially consisting of a mixture of 80%
by weight of an ethylene-propylene copolymer and 20% by weight of a propylene homopolymer. LNIDPE may replace the LLDPE used in the core layer. Neither material is particularly dimensionally stable. This makes the multilayer film described suitable as a shrinkable packaging. However, the lack of heat resistance prohibits use as a packaging for medicinal products, since the materials have to withstand sterilization by superheated steam at temperatures of 121 C or above.

US 4,643,926 (W.R. Grace & Co., Cryovac Div.) discloses flexible, three-ply films for packaging medicinal solutions and parenteralia, a sealable layer being provided made from ethylene-propylene copolymer or from flexible copolyester, and one or more inner layers encompassing elastomeric polymers, and an outer layer made from ethylene-propylene copolymer or from a flexible copolyester. Films as in US 4,643,926 and packaging manufactured therefrom, such as bags or the like, have excellent mechanical properties. However, as far as is currently known the combinations of materials disclosed for the layers make the presence of at least one adhesion promoter layer necessary. For this, use may be made of an ethylene-methacrylate copolymer (EMA) or an ethylene-vinyl acetate copolymer (EVA), for example, but this in turn leads to the disadvantage that the film is not heat-sterilizable without radiation-crosslinking. Finally, it can be concluded from the materials selected that disposal of the films is not simple.

DE 2918507 (Baxter Travenol Labs) relates to multilayer, flexible plastic films which can be autoclaved, and also to bags manufactured therefrom.
The film has at least one first layer which is composed of a blend made from 30 to 90 percent by weight of a rubbery copolymer having olefin blocks and polystyrene blocks, and from 10 to 70 percent by weight of a polyolefin whose Vicat point is above 120 C, and has a second layer made from a polyolefin which is semicrystalline with a view to low water-vapor permeability.
US 4,778,697 (American National Can Company and Baxter Travenol Labs) (corresponds to DE 3674367 and EP-A 0 229 475) and US 5,071,686 (Baxter Travenol Labs) disclose multiply films with, for example, three layers. In some plies of the film an elastomer or an ethylene-based copolymer is blended with polypropylene, and in other layers with polyethylene. A multitude of film structures is disclosed by way of example, but all of these comprise polyethylene in the widest sense, whether in the form of HDPE or of ethylene-based copolymer. From the mechanical parameters given in the specification it is clear that only a few compositions permit adequate mechanical properties to be obtained so that, for example, films can pass a drop test on a bag in its sterilized and filled condition, without damage.
However, these very compositions which can be used have high proportions of HDPE in the middle layer (70 or 80 percent by weight). The high HDPE content of the middle layer is likely to give the disadvantage of typical polypropylene behavior, i.e. a pronounced yield point for the sterilized film. The first layer is thicker (60%) than the second layer (20%) and the third layer (20%).

WO 98/36905 (Baxter International Inc.) concerns coextruded multiply films for sterilizable liquid containers. WO 98/36905 shows that at least a five-ply structure is needed to obtain a film with a balanced property profile. The outer layer is polypropylene, where appropriate with a small ethylene or alpha-olefin content; the inner layer is polyethylene with, where appropriate, small alpha-olefin contents; the intermediate layer has a complex structure and is composed of a number of plies, namely at least three plies, all of the complex intermediate plies being composed of polyolefins, and the content of ethylene units increasing from the outer to the inner layers, while the softening point of the materials of the layers decreases in the direction mentioned. The examples of WO 98/36905 demonstrate that the inner layer, which is composed of LLDPE, is thicker than the outer layer and thicker than the entirety of the complex intermediate layers. This makes the LLDPE the determinant material of the film. However, LLDPE is a material whose melting behavior would classify it as rather "crystalline". In other words, LLDPE has a definite melting point, whereas polypropylene materials have a softening range. When LLDPE is used in the sealing layer a disadvantage is that seals of different strength cannot be produced. However, in the case of polypropylene materials the lack of sharpness of the softening range makes this possible merely by varying the time or temperature during the sealing process.
LLDPE inner layers are therefore disadvantageous.
Furthermore, manufacture of a structure having at least five layers cannot be regarded as particularly advantageous. A structure which even with only three layers can meet all of the requirements would be preferable. Finally, as illustrated in the examples of WO 98/36905, the composite is susceptible to delamination. Although the forces for delamination in the examples of WO 98/36905 are greater than in the comparative examples, it would be desirable to have a film which does not delaminate at all.

EP-A 0 345 774 (Material Engineering Technology Labs) relates to containers manufactured from polyolefins.
The films involved appear to be sealable two-ply films, each of the plies being a blend of PP and LLDPE or PP, LDPE, and PE. Coextruded films are also described and have an inner ply made from LDPE and PP, and also an outer layer LLDPE. HDPE may also be used. Due to the use of HDPE, LDPE, and LLDPE in the individual layers of the material, it has to be assumed that the films may sometimes be opaque. When the use of PE materials dominates, there can also be problems with autoclavability. Finally, the sealing times given in the examples, in the range of up to 10 seconds or above, appear relatively long, indeed prohibitive for industrial production.

According to US 5,478,617 (Otsuka Pharmaceutical Factory, Inc.), multilayer films of sterilizable containers for medicinal applications have an outer layer comprising a linear ethylene-alpha-olefin copolymer, an intermediate layer comprising linear ethylene-alpha-olefin copolymer, and an inner layer made from polypropylene with linear ethylene-alpha-olefin copolymer. All of the layers comprise a predetermined amount of HDPE. In the examples LLDPEs and isotactic PPs are used, besides HDPE. Although the film is intended to be transparent, flexible, and autoclavable and moreover is intended to permit the manufacture of peelable welds, it has disadvantages which may primarily be the result of the selection of materials. For example, LLDPEs and isotactic PPs exhibit the typical mechanical weaknesses known for polypropylenes. In particular, it is unlikely that a drop test would be passed. Besides this, the use of HPDE is an indication of an "opaque" film rather than a high-transparency film, at least after autoclave treatment of the film or of a bag composed thereof.
US 4,892,604 (Baxter International Inc.) describes sterilizable plastic vessels for medicinal purposes made from a thin multiply film. The first layer of the film is the inner layer in contact with the medicinal product. It has been made from polyethylene-vinyl acetate (EVA) which is free from plasticizers. The second layer has higher melting point than the first and is composed of HDPE, for example. For the container to be used, the inner EVA layer has to be radiation-crosslinked.

PVC-free multilayer film structures are also known from EP-A 0 739 713 (Fresenius AG). They have an outer layer, a supporting layer, and also at least one middle layer arranged between these. The outer and supporting layer here comprise polymers whose Vicat softening points are above about 121 C, and the middle layer here comprises polymers whose softening point is below about 70 C. The Vicat points mentioned are preferably based not simply on polymers present in the individual layers but on the entirety of the material of the respective layer. The film described is usually also supplemented by a sealable layer, the overall result being a structure having four layers, six layers, etc. It is immediately noticeable that all of the layers may comprise grades of PE. However, if the amount of PE in the individual layers becomes excessive the probability increases of disadvantageous tensile performance with a pronounced yield point. The rubbery middle layer (Vicat below 70 C) is intended to provide flexibility. This is achieved through SEBS and the use of similar materials in the middle layer. However, the sterilized film continues to exhibit a pronounced yield point and therefore has the mechanical disadvantages associated therewith.

With respect to the materials to be used, when the prior art is considered the picture is one of an increasing trend toward the use of polypropylene materials. Possible reasons for this may be found, as mentioned above, in the fact that the softening ranges and melting points of polyethylenes are often inadequate for sterilization by superheated steam. In addition, the barrier properties of many polypropylenes with respect to water vapor are generally more advantageous than those of polyethylenes. Finally, attention also has to be paid to the more advantageous optical properties of polypropylenes. A practical method for attempting to mitigate the disadvantages of polypropylene is copolymerization of propylene with other monomers, or use of a blend of polypropylene with other polymers. However, this procedure has not hitherto led to the desired results, namely a soft and flexible material with very high mechanical processability and also extremely good dynamic and static strength.

DE 196 40 038 Al, and also the corresponding WO 97/34951 (Sengewald Verpackungen GmbH) disclose multiply films and their use, and processes for their production, the multiply film having a polymer outer layer, a polymer middle layer, and a hot-sealable polymer inner layer, with at least one bonding layer made from a compounded polypropylene material and/or from a blend of a polypropylene homo- and/or copolymer with at least one thermoplastic elastomer and/or polyisobutylene, and with an inner layer made from a compounded polypropylene material made from a polypropylene homo- and/or copolymer with at least one thermoplastic elastomer. An example of a structure encompasses an outer ply (15 m) made from PP
homopolymer, a bonding layer (95 m) made from compounded PP material, namely PP homopolymer with SEBS
as TPSE and plasticizer, and also an inner layer (40 m) made from PP homopolymer and SEBS as TPSE.
Although WO 97/34951 gives no teaching concerning the amount of SEBS in the middle layer or in the inner layer, it nevertheless appears that the proportion has to be relatively high, since the compounded materials used for the bonding layer and the inner layer, CA WITON MED PR 3663 and, respectively, CA WITON MED PR
3530, have relatively high SEBS contents. Although the use of SEBS is advantageous for flexibility and mechanical parameters (drop test and cuff test), compounded SEBS materials are relatively expensive. In addition, to improve recycling prospects for the materials it would be advantageous to minimize the number of grades of plastic used. The use of plasticizers also appears to be essential.

EP-A-O 564 206 (Terumo K. K.) discloses medicinal containers with a multilayer structure. A three-ply structure is presented, the outer and the inner layer being composed of at least one crystalline polyolefin, and the intermediate layer of at least one crystalline polyolefin and one amorphous polyolefin. Apart from the fact that the use of crystalline polyolefins in the inner and the outer layer means that the containers described do not have the transparency nowadays regarded as standard (transparency greater than 92-96%
(some of the films given as examples would have to be termed rather opaque, transparency being improved by sufficient addition of hydrogenated petroleum resins), the structure indicated is also disadvantageous for other reasons. The crystalline polyolefins used in the examples are exclusively isotactic propylene homo- and copolymers and isotactic butylene homopolymers. Now it is known that crystalline polypropylenes and polybutylenes are particularly likely to exhibit typical polypropylene behavior insofar as mechanical properties are concerned. In particular, the materials mentioned usually have a relatively high modulus of elasticity, and also a yield point in the tensile test.
It is unlikely, therefore, that bags filled with liquid would survive undamaged in a drop test from a height of

2 m. Furthermore, the appearance of bags in accordance with EP-A 0 564 206 filled with saline after sterilization by superheated steam is merely described in the disclosure as "not substantially deteriorated".
It may therefore be concluded that there is indeed an }

= - 11 -adverse change after sterilization by superheated steam.

The large number of films described in the prior art is indeed part of the evidence that no ideal film appears to have been found hitherto for producing packaging for oleaginous medicinal solutions, preferably for aqueous solutions. All of the known films, including in particular those which have actually achieved commercial significance, have the disadvantage - as described above - of one or other shortcoming. If the desire is to avoid PVC because of its plasticizer problems and polyester and polyamides because of their lack of satisfactory recyclability, the films then provided by the prior art are based on polyolefin materials. When use of polyethylene materials predominates, the result can be problems with sterilization by superheated steam. The temperatures during this procedure can on occasion markedly exceed the 121 C described above, for example 125 C or even higher. When "excursions" of this type occur, however, there is the problem that the melting point of a polyethylene-based material may be too low. Changes in transparency, permeability, and mechanical behavior of the film can make the material useless.

The melting points of polypropylene-based materials are generally markedly higher than those of PE. However, PP-based materials pose problems with respect to mechanical properties. As well as complying with various pharmaceutical and optical requirements placed upon the films and packaging produced from them, for example bags and the like, such as those known as i.v.
bags, films also have to withstand certain, highly varied, mechanical stresses in order to comply with the (mechanical) product requirements for bags.

Two requirements placed upon the "i.v. bag" product are particularly demanding in relation to a plastic film.

Firstly, a filled bag has to be able to pass a drop test to DIN ISO 58363-15:1996 without damage. This involves extremely high dynamic stressing of the film of the bag. Secondly, a filled bag also has to be able to withstand what is known as a "pressure cuff test"
without damage. This involves long-term pressurization of a filled bag onto which a cuff is placed. Unlike the dynamic drop test, this extreme stress is of static type. The two criteria are firstly not per se compatible with the properties of a single plastic material, and have not hitherto been satisfactorily achieved even by composite films made from exclusively polyolefin-based - materials, or preferably polypropylene-based materials. The "static pressure cuff test" here has to be regarded overall as a more demanding practical criterion than, for example, the DIN test method for strength under pressure to DIN ISO 58363-15, which is easily complied with if the pressure cuff test is passed.
In view of the prior art described and discussed herein, the invention provides a multilayer film for the packaging of liquid, medicinal products which is substantially based on polyolefin materials and which permits the manufacture of packaging which is as resistant as possible to dynamic loads and also.with respect to long-term static loads.

if possible the films of the invention should be capable of use for packaging which is statically and dynamically more stable than known films or film composites based on polypropylene materials.

The static and dynamic strength of the novel films should if possible also be as high as that of known films not based on polyolefin materials, for example films or film composites comprising polyesters, polyamides, or polyvinyl chloride.

Even at temperatures below room temperature, e.g. at 0 C, the novel films are intended to retain excellent to good mechanical properties. These include high flexibility at low temperatures, low brittleness at low temperature, and high impact strength at the low temperatures mentioned.

The novel multilayer films should preferably.have the minimum number of layers and therefore be capable of production with maximum simplicity and minimum cost.

The multiply films of the invention are moreover intended to comprise a minimum number of grades of material and advantageously to be based on polypropylene materials having minimum proportions of other monomer units.

The materials of the individual layers are moreover intended to be composed of the minimum number of individual substances. If a blend or compounded material is used for a layer, the blend is intended to comprise a minimum of varieties of polymer or of copolymer.
The novel film is intended to have high transparency.
It is intended to be autoclavable and to be able to withstand sterilization by superheated steam, even at temperatures of 121 C or above, without damage, i.e.
without disadvantageous changes in transparency and flexibility. For example, it is intended that there be no crystallization of the film and a minimum of, or preferably no, other surface effects, such as discoloration, whitening, or opacification, as a result of the heat treatment.

Finally, the film is intended to be completely pharmaceutically and medicinally non-hazardous. This includes the intention that it have no additives which could be seen as medicinally hazardous. In particular, the novel film is intended to have no tendency toward migration of additives out of the film into the products for whose storage it is used, even when storage times are long and the products involve lipophilic liquids.

The invention provides a printable film which can be printed, easily, simply, and permanently using conventional processes and pigments, without any possibility that the pigments or dyes will come into contact with the stored products.

In addition, the film of the invention is intended to permit welded bonds which have a maximum of optional peelability or non-peelability.

The film of the invention is also intended to permit control of weld strength by simple means (sealing temperature and sealing time). In this connection it is intended that the film of the invention also be capable of use for the manufacture of containers which have, at the same time, both permanent seal seams and seams which can be separated by a variable force.
In particular, it is intended that the film be sealable both by continuously heated tools and by impulse welding.

The novel film is also intended to be weldable without the use of protective coverings made from TefloriM
silicone, or the like. It has hitherto been necessary to renew these protective coverings frequently. The novel film is moreover intended to have sufficiently great "processing latitude". This includes a requirement that adequate strength of the weld be achievable even when there is little constancy of temperature during welding. The extent of processing latitude is also, and especially, highly important during the production of peelable seams.

Besides this, the novel film is intended to permit the production of fully collapsible bags.

Finally, it is intended that packaging made from the film of the invention be recyclable in its entirety, ideally without downcycling, i.e. it is intended that an absolute minimum of environmentally incompatible materials be used.

Films of the invention are moreover also intended to have low water-vapor permeability. They are intended not only to have clarity and high transparency but also to have a pleasant feel when touched, and also high aesthetic quality in other respects, i.e. to have no discoloration or specs.

Lastly, it is intended that not only aqueous liquids but also oleaginous or lipophilic liquids be capable of storage in containers made from films of the invention.
The invention provides a process which produces multilayer films of the invention and which is intended to be capable of being carried out with maximum simplicity and at minimum cost.

The intention here is that the novel film preferably be capable of production using coextrusion techniques, while the compatibility of the materials means that there is no need to use adhesion promoters or laminating adhesives or additional layers which have this function.
The invention provides the use of films of the invention.

These aspects, and also other aspects which, although they have not been specifically mentioned, are self-evident or readily derivable from the introductory discussion of the prior art, are achieved via a multilayer film of the invention, i.e., an autoclavable, PVC-free multilayer film having at least three layers, comprising an outer layer (A), an inner layer (I), and, arranged therebetween, a middle layer (M), each of which is composed of from 60 to 100 percent by weight of a polypropylene material and of from 40 to 0 percent by weight of a thermoplastic elastomer, each of the percentages being based on the total weight of the respective layer, wherein the multilayer film has no yield point measurable to DIN EN ISO 527-1 to -3 after sterilization using superheated steam at 121 C or at a higher temperature in the hot-water sprinkle process.

Surprisingly and unexpectedly, a multilayer film, in particular for the packaging of liquid, medicinal products, having at least three layers, namely an outer layer (A), an inner layer (I), and, arranged between these, a middle layer (M), each of which is composed of from 60 to 100 percent by weight of polypropylene materials and of from 40 to 0 percent by weight of a thermoplastic elastomer, each of the percentages being based on the total weight of the respective layer, where the multilayer film has no yield point measurable to DIN EN ISO 527-1 to -3 after sterilization using superheated steam at 121 C or at higher temperatures, provides an at least three-ply film from which it is possible to produce medicinal packaging which gives excellent compliance with all of the requirements placed by standards institutes and industrial processors with respect to the physical properties of the packaging and at the same time can be composed entirely of polypropylene materials. It is also possible to achieve many other added advantages. These include:

= The film of the invention has extremely high dynamic and static strength. Packaging made from a film of the invention survives a drop test to DIN ISO 58363-15:1996 undamaged and is similarly undamaged when resisting a long-term static load (pressure cuff test).

= For the first time it is possible to provide a film which is composed solely of polypropylene materials and which has a level of mechanical properties which equals that of polyester-containing multilayer films or multilayer films comprising polyethylenes.

= The optical properties such as clarity, transparency, or defects, of the film of the invention are excellent, even and in particular after sterilization using superheated steam. No additives are needed here to improve transparency.
= The autoclavability of the films of the invention is excellent. Even sterilization using superheated steam at temperatures above 120 C or 121 C is withstood without damage and without significant impairment of the level of mechanical properties.

= Since the number of grades of material present in the film has been minimized it is relatively easy to recycle the film completely, inter alia because neither polyesters nor polyamides nor PVC are present.

= The film of the invention is extremely flexible, therefore permitting problem-free manufacture of what are known as collapsible containers.

The film of the invention has problem-free sealability, both using continuously heated tools and also impulse-weldable.

= Compared with some known structures, the materials of the inner layer permit shorter sealing times, so that the cycle time for each item of packaging to be manufactured (empty bags and the like) falls, and therefore the productivity of the welding lines rises correspondingly.
= The sealable layer of the film of the invention permits the strength of the welded bonds to be influenced and controlled via control of sealing temperature and sealing time.
= In some circumstances the film of the invention is also suitable for manufacturing bags for the storage of oleaginous or lipophilic liquids.

= The film of the invention has relatively low water-vapor permeability, and for certain applications this means that there is no requirement for other barrier layers. However, depending on the desired application, other layers can be combined with the film structure of the invention for barrier purposes (water-vapor barriers, oxygen barriers, or other barriers).

= There is a considerable reduction in the cost of the film per unit area by minimizing the use of, or completely omitting, any content of thermoplastic elastomers from the group of styrene block copolymers, in all of the layers or in most of the layers, of the film specification of the invention.

= The film of the invention may be manufactured as a flat film. With this it has an outstandingly uniform thickness profile, and this has a very favorable effect on the behavior of the film in machinery.

= Combined with its excellent optical properties (gloss, clarity, transparency), the film of the invention has excellent printability and quite exceptional structural integrity.

In particular, the multilayer film of the invention has no yield point measurable to DIN EN ISO 527-1 to -3 after sterilization using superheated steam at 121 C or at higher temperatures. For the purposes of the present invention, the term "yield point" is the term used in the standard cited. "Yield point" in the context of the invention means a certain yield stress as in 4.3.1 (definitions) in EN ISO 527-1:1996. In particular, the yield stress cited is by definition the first value in the tensile stress/elongation curve at which strain rises without any rise in stress. Since this value is not attained with films of the invention there is no yield point. With films of the invention, after sterilization using superheated steam there is no detectable stress at which extension of the specimen begins to occur without any further rise in stress. The behavior of the films of the invention in the tensile test, in particular in the test in accordance with Part 3 of DIN EN ISO 527 "Priifbedingungen filr Folien und Tafeln" [Test Conditions for Films and Panels], German edition of October 1995, corresponds to curve d in Part 1 of DIN EN ISO 527 "Bestimmung der Zugeigenschaften" (Determination of Tensile Properties), German edition of April 1996. Curve d in the stress/strain curves depicted there represents a tough material without yield point, contrasting with brittle materials (curve a) and tough materials with yield point (curves b and c) . With this, the invention for the first time provides a polypropylene film for medicinal applications which, as a packaging film, exhibits quasi-elastomeric behavior even after sterilization using superheated steam. With this, the film of the invention combines two principles which are per se incompatible, something hitherto believed to be impossible.

Another feature, inter alia, of films of the invention is that they lack any yield point either in the transverse direction (TD) or in the machine direction (MD). The direction TD or MD refers to the production of the f i lms .

As described, the film of the invention can be sterilized using superheated steam, without damage. To test for the presence of any yield point to DIN EN
ISO 527-1 to -3, the films of the invention were subjected to sterilization using superheated steam at 121 C. The sterilization process used during the studies cited is known to the skilled worker in particular by the term "hot-water sprinkle process". Of course, the autoclavability and sterilizability of the films of the invention extends to other temperatures and other, or modified, methods. Examples of these even include sterilization methods which function using in very general terms light, certain portions of the visible light spectrum, or by virtue of other radiation.

In order that the entire multilayer film of the invention has no yield point, the invention preferably uses a relatively thick middle layer and uses inner and outer layers which are thinner in comparison. A
particular feature of the films of the invention is therefore a certain relationship between the thickness of the middle layer and the total thickness of the film. Accordingly, the relationship between the thicknesses of the middle layer (M) and the total thickness of the films, which is the total of the thicknesses of the layers (A), (M) and (I), is in the range from 40 to 80%. If. the proportion of the middle layer (M), based on the total thickness, is below 40%, the consequence can be that the flexibility of the bag becomes inadequate. If the proportion of the middle layer (M), based on the total thickness of the multilayer film, is above 80%, static strength can be insufficient and it is very likely that a filled bag using a film of this type will begin to fail the pressure cuff test.
Preferred multilayer films of the invention are characterized in that the proportion by thickness of the middle layer (M), based on the total thickness of the film, is from 45 to 75%, preferably from 50 to 70%, and particularly preferably from 50 to 65%. The middle layer therefore preferably predominates in terms of thickness. Using a comparatively thick middle layer, specifically in the preferred and particularly preferred ranges, the multilayer films obtained have a balanced property profile in respect of dynamic and static mechanical parameters, and also flexibility.
Taking different thickness ranges, it can also be preferable for the proportion by thickness of the middle layer (M), based on the total thickness of the film, to be from 60 to 80%, preferably from 60 to 75%, particularly preferably from 65 to 75%. This variant is preferred especially when particularly good dynamic properties are desired.
There are also preferred thickness ratios between the middle layer or intermediate layer (M) and the inner layer (I) and the outer layer (A).

In preferred embodiments of the multilayer film of the invention, the proportion by thickness of the outer layer (A), based on the total thickness of the film, is in the range from 30 to 7.5%.
Also of particular interest for the invention are multilayer films characterized in that the proportion by thickness of the inner layer (I), based on the total thickness of the film, is in the range from 30 to 12.5%.

Taking as a basis a preferred thickness of the layer (M) of from 40 to 70%, based on the total thickness of the film, the resultant preferred proportion by thickness for the layer (A), and also for the layer (I), is from 30 to 15%. In view of the particularly advantageous thickness range of from 50 to 65% for the middle layer, the resultant thicknesses for the outer layer (A) and the inner layer (I) are each in the range from 25 to 17.5%.

Taking as a basis a preferred thickness of from 60 to 80% for the layer (M), based on the total thickness of the film, the resultant proportion by thickness for the layer (A) in one embodiment, based on the total thickness of the film, is from 15 to 7.5%, while an advantageous proportion by thickness for the layer (I), based on the total thickness, is preferably from 25 to 12.5%.
The multilayer films of the invention may be manufactured with a wide range of absolute thickness.
Depending on the desired use, preference may be given to relatively thick multilayer films whose total thickness is above 300 m, but it is also possible to manufacture relatively thin films whose total thickness is below 120 pm. One preferred embodiment of the invention is characterized in that the total thickness of the film is in the range from 120 to 300 m, fl preferably from 150 to 250 m, particularly preferably from 170 to 230 m.

The middle layer may preferably provide the entire multilayer structure with sufficient flexibility. To this end, a feature of the middle layer (M) is that the modulus of elasticity of the material of the middle layer (M) is less than or equal to 250 MPa, advantageously less than or equal to 150 MPa, preferably less than or equal to 135 MPa, particularly preferably less than or equal to 100 MPa, in each case measured to DIN EN ISO 527-1 to -3. In this connection, the modulus of elasticity to ISO 527-1 to -3 is determined for a film and a corresponding test specimen manufactured solely from the material of the layer. If the layer (M) is composed of more than one polymeric material (blend or compounded material), the value given applies to the blend or compounded material. If the modulus of elasticity of the middle layer is greater than 150 MPa, the flexibility of the entire multilayer film can be inadequate. Multilayer films of the invention which are of particular interest are those in which the modulus of elasticity of the middle layer (M) is in the range from 30 to 80 MPa, preferably from 30 to 60 MPa, more preferably from 35 to 55 MPa, with preference from 35 to 50 MPa, and particularly preferably from 40 to 45 MPa, in each case measured to DIN EN ISO 527-1 to -3.

With regard to the middle layer (M), preference is given to the use of those polypropylene materials or those compounded materials made from polypropylene materials with thermoplastic elastomers, preferably with styrene block copolymers, which have a maximum of toughness in their elasticity behavior. In one variant it can be advantageous to use materials whose yield point is less than or equal to 8 MPa determined using a type 2 test specimen and a separation rate of 200 mm/min. However, it can also be preferable to use materials which are even tougher. It is therefore sometimes particularly advantageous if the material selected for the middle layer (M) has no yield point measurable to DIN EN ISO 527-1 to -3, using a type 2 test specimen and a separation rate of 200 mm/min, after sterilization using superheated steam at 121 C or at higher temperatures in the hot-water sprinkle process, and also preferably prior to the appropriate sterilization using superheated steam. As far as the elasticity of the materials is concerned, by selecting material appropriately, it is possible to obtain multilayer films which, while maintaining the abovementioned thickness ratios between the layers, permit the use of even relatively brittle, i.e. low-toughness, materials for the outer layer (A).

Particular multilayer films of the invention are obtained, inter alia, when the modulus of elasticity of material of the outer layer (A) is greater than the modulus of elasticity of material of the middle layer (M). The modulus of elasticity of the material of the outer layer (A) is preferably greater than 250 MPa, more preferably greater than 300 MPa, particularly preferably greater than 400 MPa, in each case measured to DIN EN ISO 527-1 to -3.

Particular ranges for the modulus of elasticity of the outer layer (A) are characterized in that the modulus of elasticity of the material of the outer layer (A) is in the range from 300 to 600 MPa, preferably from 400 to 600 MPa, still more preferably from 450 to 550 MPa, with preference from 450 to 500 MPa, and particularly preferably from 400 to 450 MPa, in each case measured to DIN EN ISO 527-1 to -3.
In as far as use is made of the middle layer (M) made from a material which has no, or a very minor, yield point detectable in the tensile stress/elongation curve, it can be advantageous to combine with this middle layer (M) an outer layer (A) which has an even higher modulus of elasticity, which may then assume advantageous values above 1000 MPa, particularly preferably above 1150 MPa. Preferred ranges are then from 900 to 1300 MPa, and values in the range from 1000 to 1150 MPa for the modulus of elasticity appear still more advantageous.

Of course, the value for the modulus of elasticity for the individual layers (A), (M), and (I) is that which can be determined on test specimens to DIN EN ISO 527-1 to -3. The values given here relate to test specimens which have not been exposed to any sterilization. For the purposes of the application, from the juncture at which yield point or modulus of elasticity of films is significant, the values are generally those determined on films which have been subjected to sterilization. In the event that the values are intended to apply to unsterilized films, this has been especially stated in particular cases where it applies.

With regard to the thermal behavior (structural stability when exposed to heat during autoclaving), and also to the sealability of the inner layer (I), the invention permits excellent control over the entire range of properties demanded. The melting point of the outer layer (A). is preferably higher than the melting point of the inner layer (I).

It can also be preferable to select the layers (A), (M), and (I) so as to permit there to be a gradient for the melting points of the individual layers. In this context, multilayer films of particular interest are those in which the melting point of the layer (M) is lower than the melting point of the layer (A) and higher than the melting point of the layer (I), each of the melting points being determined for a single-layer film made from the material of the respective layer (A), (M) and (I) to DIN 3146-C1b. Of course, melting points are mentioned in the context of the invention even when some of the materials used do not have a "sharp melting point" in the traditional sense as known for crystalline materials. In the context of the invention, melting point means a melting point in the sense of the standard DIN 3146-C1b, i.e. a transition in the DSC (differential scanning calorimeter).
Particularly preferred multilayer films of the invention have a melting point of the layer (M) in the range from 130 to 160 C, preferably from 135 to 157.5 C, particularly preferably from 140 to 156 C, the melting point being determined for a single-layer film made from the material of the layer (M) to DIN 3146-C1b. The melting points here do not permit any direct deductions to be made concerning the softening of the material.

The Vicat point may be utilized to describe softening behavior. The softening point is understood to be the temperature at which glasses and amorphous or semicrystalline polymers convert from the glassy or low-elasticity state to an elastomeric state. One particular embodiment of the multilayer film of the invention can have layers (A), (M) and (I) with Vicat points which for the layer (M) are generally in the range from 35 to 75 C, preferably from 35 to 70 C, more preferably from 40 to 65 C, very particularly preferably from 45 to 60 C, while the layers (A) and (I) have Vicat points in the range below or equal to 121 C, in each case determined to DIN 53460. Of particular interest in this context is the phenomenon that multilayer films of the invention readily withstand sterilization at 121 C using superheated steam although the Vicat points of all of the layers may be below 121 C. The pressure parameters usually prevailing during sterilization using superheated steam may, inter alia, contribute substantially to the retention of the structural integrity of the film or of containers produced therefrom during the treatment.

In the widest sense, each layer of the multilayer film of the invention is composed of from 60 to 100% by weight of polypropylene materials and of from 40 to 0 percent by weight of thermoplastic elastomers, preferably selected from the styrene block copolymers group.
The polypropylenes or polypropylene materials which may be used include homopolymers of propylene and copolymers of propylene with up to 25 percent (w/w) of ethylene, and include a mixture (alloy, blend) made from polypropylene with up to 25 percent (w/w) of polyethylene. The copolymers may in principle be random copolymers or block copolymers.

If the polypropylene materials used are homopolymers of propylene or copolymers of propylene with ethylene, it can be preferable for certain embodiments to provide a content of ethylene units in the range from 1 to 5 percent by weight, very particularly preferably from 1.5 to 3 percent by weight, still more preferably from 1.6 to 2.5 percent by weight, based in each case on the total weight of the copolymer. In particular for the outer layer (A), this structure can be regarded as advantageous for gloss, transparency, clarity, and printability. The makeup of the outer layer is particularly preferably such that the proportion of ethylene units is in the range from 1 to 5 percent by weight, the remainder of the material of the outer layer being composed of units derived from propylene.

In the individual layers of the multilayer film of the invention there may optionally be a subordinate amount of a thermoplastic elastomer present, the thermoplastic elastomer preferably - as mentioned repeatedly above -having been selected from the styrene block copolymers ^.

group. Other thermoplastic elastomers which may be used for the purposes of the invention include polyetheresters (TPEE), polyurethanes (TPU), polyetheramides (TPEA), and also EPDM/PP blends and butyl rubber/PP blends, and olefin-based thermoplastic elastomers (TPOE). EPDM stands for terpolymers made from ethylene, propylene, and a non-conjugated diene and/or ethylene-alpha-olefin copolymer. Butyl rubber means copolymers of isobutylene with isoprene. It is possible to use solely a member of the groups mentioned of elastomeric compounds. It is possible to use mixtures of two or more compounds from a single group, or else mixtures of two or more compounds from more than one group of compounds.
In one embodiment of the invention, the use of block copolymers of styrene is preferred. Styrene block copolymers which may be used include, inter alia, styrene-ethylene/butylene-styrene triblock copolymers (SEBS), styrene-butylene-styrene diblock copolymers (SBS), styrene-ethylene/propylene-styrene triblock copolymers (SEPS), styrene-isoprene-styrene triblock copolymers (SIS), and mixtures made from two or more of the abovementioned components. Among the styrene block copolymers mentioned, preference is given to the use of SEBS, since this thermoplastic elastomer is particularly suitable for applications in the medical sector.

The proportion of the thermoplastic elastomer may vary from layer to layer. The middle layer (M) preferably has a minimum proportion of thermoplastic elastomer.
The resultant preferred ranges are from 20 to 0 percent by weight, particularly advantageously from 10 to 0 percent by weight, very particularly advantageously less than 5 percent by weight, and the layer (M) is most preferably totally free from thermoplastic elastomer which is not within the polypropylene materials for the purposes of the invention. The s preferred proportion of polypropylene material is accordingly from 80 to 100 percent by weight, still more preferably from 90 to 100 percent by weight, advantageously more than 95 percent by weight, and most preferably 100 percent by weight, based in each case on the total weight of the layer (M).

Similar considerations also apply to the structure of the outer layer (A). The outer layer (A) preferably has a minimum proportion of thermoplastic elastomer. The resultant preferred ranges are from 20 to 0 percent by weight, particularly advantageously from 10 to 0 percent by weight, very particularly advantageously less than 5 percent by weight, and the layer (A) is most preferably totally free from thermoplastic elastomer. The preferred proportion of polypropylene material is accordingly from 80 to 100 percent by weight, still more preferably from 90 to 100 percent by weight, advantageously more than 95 percent by weight, and most preferably 100 percent by weight, based in each case on the total weight of the layer (A).

With regard to the makeup of the inner layer (I), the fundamental principle is again that a minimum proportion of thermoplastic elastomer is desirable. In one embodiment of the inner layer (I), therefore, the preferred ranges are again from 20 to 0 percent by weight, particularly advantageously from 10 to 0 percent by weight, very particularly advantageously less than 5 percent by weight, and the layer (I) is most preferably free from thermoplastic elastomer. The preferred proportion of polypropylene material in the layer (I) is accordingly from 80 to 100 percent by weight, still more preferably from 90 to 100 percent by weight, advantageously more than 95 percent by weight, and most preferably 100 percent by weight, based in each case on the total weight of the layer (I).

However, for controlled alteration of sealing properties and control of the welds it can be in certain respects advantageous to provide from about 10 to 30 percent by weight, preferably from 15 to 25 percent by weight, and particularly advantageously about 20 percent by weight of thermoplastic elastomer in the inner layer (I). Accordingly, the advantageous contents of polypropylene materials in the inner layer (I) are from 90 to 70, from 85 to 75, and particularly advantageously about 80 percent by weight, based in each case on the total weight of the layer (I).

Based on the statements above, an embodiment of the very greatest interest results when the layers (A) and (M) are composed of 100 percent by weight, and the layer (I) of from 90 to 70 percent by weight, of polypropylene materials, in each case based on the total weight of the respective layer. It is particularly preferable for the remaining 10 to 30 percent by weight of the layer (I) to be composed of one or more SEBS(s).

A particularly advantageous multilayer film is therefore characterized in that the layers (A) and (M) are composed of 100 percent by weight, and the layer (I) of from 60 to 100 percent by weight, preferably from 70 to 90 percent by weight, of one or more polymers selected from the group consisting of homopolymers of polypropylene (homo-PPs), random copolymers of polypropylene (random-co-PPs), block copolymers of polypropylene, flexible homopolymers of polypropylene (FPOs), flexible copolymers of polypropylene (co-FPOs), while the layer (I) is also composed of from 40 to 0 percent by weight, preferably from 30 to 10 percent by weight, of styrene-ethylene/butylene-styrene block copolymer (SEBS).

Of particular interest for the realization of the invention are those homopolymers and especially copolymers of propylene with ethylene which have high flexibility. Examples of outstandingly highly suitable materials include substantially amorphous binary random copolymers which are composed of from 10 to 30 percent by weight of ethylene and from 70 to 90 percent by weight of propylene, the tacticity index m/r of the copolymers being in the range from 3.0 to 4.0, and the copolymers having what is known as a "propylene inversion value" of about 0.15 or below, determined by 13C NMR measurement. One way of obtaining random copolymers of propylene with ethylene which meet the specification mentioned is to use, for the polymerization, certain catalyst systems which, inter alia, comprise a solid catalyst component made from magnesium halide support base and aluminum halide and titanium tetrahalide, and a cocatalyst component made from a trialkylaluminum compound and alkylaluminum halide. By way of example, US 4,858,757 of August 22, 1989 relates to polymers of this type. US 4,736,002 and US 4,847,340 of April 5, 1988 and, respectively, July 11, 1989 disclose preparation processes. The patents mentioned have been transferred to Rexene Products Company.

The flexible homopolymers of propylene (FPOs) and the flexible copolymers of propylene with ethylene (co-FPOs) from the company Huntsmann, obtainable with the protected name Rexflex fpo, are among the particularly preferred propylene materials for the invention.
In relation to the entire multilayer structure of the films of the invention, it is not insignificant that the resultant film has a high content of polypropylene materials, due to the thickness ratios of the layers to one another. In one advantageous embodiment, the film of the invention is composed of at least 90 percent by weight of polypropylene materials, based on the total weight of the multilayer film. Even more advantageous are films whose entirety is composed of more than 92 percent by weight, of 94 percent by weight or above, of 96 percent by weight or above, or of at least 97.5 percent by weight, of polypropylene materials.

Particular films of the invention have the following structure by way of example:
(A) a first or outer layer made from polypropylene copolymer having from 2 to 3 percent by weight of ethylene units;
(M) a second or middle layer made from a polypropylene homopolymer with defined tacticity;
(I) a third or sealable layer made from a blend made from polypropylene and from an elastomeric material.
A structure of this type for a film has proven particularly advantageous for the production of containers, bags, or the like which are intended for the storage of lipophilic liquids for parenteral nutrition.

Films which are particularly advantageous in this context have the following structure:

(A) a first or outer layer made from polypropylene copolymer having from 2 to 3 percent by weight of ethylene units, with a thickness of from 10 to m;
(M) a second or middle layer made from a polypropylene 30 homopolymer with defined tacticity and a thickness of from 100 to 200 m;
(I) a third or sealable layer made from a blend made from polypropylene and from an elastomeric material with from 0 to 40 percent by weight, preferably from 10 to 30 percent by weight, particularly preferably about 20 percent by weight, in each case based on the total weight of the layer (I), of thermoplastic elastomer, preferably of a thermoplastic elastomer based on a styrene block copolymer, particularly preferably on an SEBS, with a thickness in the range from 20 to 80 .m.

Very particularly advantageous films for this purpose are those with one of the following structures:

TM
(A) a first or outer layer made from Rexene PP
23M10CS264 (Huntsman Corp.), thickness: about 20 m;
(M) a second or middle layer made from Rexflex FPO
WL110 (Huntsman Corp.) with defined tacticity and a thickness of about 140 m;
(I) a third or sealable layer made from a blend made from 80 percent by weight of polypropylene and percent by weight of SEBS with a thickness of about 40 m.

The following films are of very particular interest, 20 inter alia, for the production of containers for the storage of water-based parenteral liquids:

(A) a first or outer layer made from polypropylene homopolymer, preferably from the flexible polypropylene homopolymers family;
(M) a second or middle layer made from a polypropylene copolymer from the flexible polypropylene copolymers family with a small content of ethylene units;
(I) a third or sealable layer made from a blend made from polypropylene and from an elastomeric material.

Particularly advantageous films for this purpose are those with a structure as follows:

(B) a first or outer layer made from polypropylene homopolymer with a thickness of from 20 to 60 m;

(M) a second or middle layer made from a polypropylene copolymer having a content of ethylene units in the range from 1 to 3 percent by weight and a thickness of from 60 to 180 pm;
(I) a third or sealable layer made from a blend made from polypropylene and from an elastomeric material with from 0 to 40 percent by weight, preferably from 10 to 30 percent by weight, particularly preferably about 20 percent by weight, based in each case on the total weight of the layer (I), of thermoplastic elastomer, preferably of a thermoplastic elastomer based on a styrene block copolymer, particularly preferably on an SEBS, with a thickness in the range from 20 to 80 m.

Films very particularly advantageous for this purpose have a structure as follows:

(A) a first or outer layer made from WL113 from the company Huntsman. Thickness: about 30 m;
(M) a second or middle layer made from WL210 from the company Huntsman having an ethylene content of about 1.6 percent by weight and a thickness of about 130 m;
(I) a third or sealable layer made from a blend made from 80 percent by weight of polypropylene and 20 percent by weight of SEBS with a thickness of about 30 m.
Other very particularly advantageous films for this purpose are those with a structure as follows:

(A) a first or outer layer made from WL113 from the company Huntsman. Thickness: about 50 m;
(M) a second or middle layer made from WL210 from the company Huntsman having an ethylene content of about 1.6 percent by weight and a thickness of about 90 m;

(I) a third or sealable layer made from a blend made from 80 percent by weight of polypropylene and 20 percent by weight of SEBS with a thickness of about 50 m.
In addition, other very particularly advantageous films for this purpose are those with a structure as follows:
(A) a first or outer layer made from WL113 from the company Huntsman. Thickness: about 50 pm;
(M) a second or middle layer made from WL210 from the company Huntsman having an ethylene content of about 1.6 percent by weight and a thickness of about 90 m;
(I) a third or sealable layer made from a polypropylene random copolymer Z9450 from the company Fina with a thickness of about 50 pm.

Using the invention it is also in particular, and in a particular embodiment, possible, as described above, successfully to realize films composed entirely, i.e.
of 100 percent by weight, of polypropylene materials.
The optional restriction to at least 90 percent by weight of polypropylene materials achieves excellent compatibility of the layers to one another, and there is therefore no need for any adhesion promoters or adhesion-promoting layers. The risk of delamination of the layers is thus reduced.

The properties of the individual layers make a certain contribution to the very advantageous property profile of the entire multilayer film, but it is not possible to derive all of the properties of the film directly from the properties of the individual layers.
In one preferred version of the invention, the outer layer (A) may contribute to the stability of the film during welding, and give the material the desired stiffness and yield stress and impact strength. The middle layer (M) may give the film suitable flexibility, while the inner layer (I) permits peelable seams of varying defined strength, these being capable of being controlled as desired as a function of welding conditions, such as temperature, pressure, and time.

The multilayer film of the invention preferably has three layers. This structure is easy and simple to manufacture and suffices for all applications. However, the film of the invention may also be given a structure which has five plies, seven plies or even more plies.
Particular multilayer films of the invention are, inter alia, characterized in that they are composed of five layers with the sequence (Al-Ml-AZ-M2-I) or of seven layers with the sequence (Al-Ml-A2-M2-A3-M3-I ), the thickness of (M) and (A) being the sum of the values for (Mi) and, respectively, (Ai). The overall thickness is in the range stated earlier above. A1, A2 and A3 are sub-layers of layer A, and Ml, M2 and M3 are sub-layers of layer M.
Films whose sequence of layers complies with the following pattern: (Al-Ml-M2-Az-I) may likewise be advantageous. This structure has proven particularly advantageous when the layers Mi are composed of flexible homopolymers of propylene.

The film of the invention may be manufactured by standard processes known per se. Preferred processes for producing a multilayer film of the invention encompass coextruding the layers (A) to (I) with one another, or laminating them to one another.

Particularly advantageous processes are those in which the film of the invention is coextruded as a flat or blown film or is laminated as a flat film.

The film of the invention is therefore preferably produced in a manner known per se, and it is possible here to produce webs of suitable dimension. The webs may then be used for the production of containers for .

medicinal purposes. The containers to be manufactured for medicinal liquids may have one or more compartments. The wide variety of processes known per se may be used for the production and filling of the bags or containers.

The film of the invention has broad scope of application. Conceivable possible uses include bags for the storage of liquid substances for nutritional purposes, or of medicinal solutions or liquids. One preferred use is as a pack for the bagging of water-based parenteral liquids. Other possible uses relate to the bagging of liquid lipophilic emulsions, for example as a pack for lipophilic medicinal solutions.
More specifically, possible uses encompass the bagging and storage of medicinal liquids and solutions, such as saline, blood, blood substitute solutions, dialysis solutions, amino acid solutions, fat solutions, emulsions, and also substances which are pasty or viscous, i.e. are flowable.

The invention is illustrated in more detail below using Examples and Comparative Examples.
1. Methods for determining the physical parameters of the materials used The physical parameters listed below for materials were measured, or tabulated values from the producers were adopted. The method of determining the values for the materials given in Table 1 was as given in the respective standard to which reference is made. Insofar as the standard permits various determination methods, the variant used for determination in each case was that usual in the appropriate field. The following specifications were used for the determination of properties:

a) MFR in [g/10 min] was determined to DIN ISO 1133;
MFR is identical with MFI (melt index); melt index was determined for 21.6 N load at 230 C (previously DIN 53 735:1983-01);
b) Vicat point in [ C] was determined to DIN ISO 306/A;
this is the Vicat softening point, which is the temperature at which a steel needle with a circular cross section of 1 mm2 and a length of at least 3 mm penetrates vertically into the test specimen to a depth of 1 mm and a force of 1 kp is applied (previously DIN 53 460:1976-12);
c) melting point was determined in [ C] to DIN 3146-C1b;
DSC measurement, maximum of melting curve, heating rate 20 K/min;
d) density is given in [g/cm3], determined to DIN
ISO 1183;
e) modulus of elasticity [MPa] is determined in relation to the individual materials in accordance with DIN ISO 527-1 to -3; this is in particular the modulus of elasticity determined from the tensile test, with computer-aided evaluation in accordance with note 1 in 4.6 of EN ISO 527-1:1996. For films, in particular multilayer films, the determination was carried out by a method based on DIN ISO 527-1 to -3, the modulus of elasticity being determined by the secant method conventional in plastics technology;
f) yield point in [MPa] is determined in accordance with DIN ISO 527-1 to -3; the test velocity used was always 200 mm/min (traverse separation velocity);
the test specimen was of type 2;
g) thickness of films in [ m] in accordance with DIN
ISO 4593, and in the case of films whose thickness is less than 0.01 mm in accordance with DIN
ISO 4591.

Table 1 below gives the results of the analysis of physical parameters for the films of the invention, for some materials from films of the Comparative Examples, and for some materials not used in the Examples or Comparative Examples.

Table 1: Properties of the materials used in the films of inventive examples and in the films of the Comparative Examples Material MFR Vicat Melting Density Modulus of Yield [g/10 [ C) point [g/cm3] elasticity [Mpa]
min] [ C] [Mpa]
PPC1 5 * 128 0.89 480 15 PPC2 10 * 150 0.9 1055 28 PPC3 5 52 148 0.89 43 no yield PPH2 8 154 161-165 0.9 650-750 40-60 PPH3 6 119 160 0.89 441 24 PPH4 10 102 159 0.89 317 12.8 PPT1 6.5 116 132 0.89 770 16 PPT2 8 144 0.89 1100 24 PPT3 8 110 138-142 0.90-0.91 200 10.5 PPC1/ 4 102 * 0.9 * *

PPH5 16 63 155 0.88 94 6 PPH6 5.5 67 156 0.89 117 7 PPH7 6 74 156 0.89 131 7.7 PPH8 1.5 64 152 0.89 97 6.4 PPH9 1.5 69 154 0.89 124 8 PPH10 1.8 116 158 0.89 428 16 PPH11 3.5 69 155 0.89 117 8 PPC4 1.5 49 145 0.88 55 no yield PPC5 8.5 50 147 0.88 45 5.2 PPC6 8 122 138-142 0.90-0.91 370 5.2 PPC7 8 153 148-154 0.90-0.91 550 5.2 PPH13 8 152 162-166 0.90 670 5.2 *Not measurable according to information from producer PPC1: Z9450 from the company Fina is a random polypropylene copolymer PPC2: PP23M10cs264 from the company Huntsman is a random polypropylene copolymer PPC3: WL210 from the company Huntsman is a random polypropylene copolymer from the REXflex FPO

polymer family with a proportion of 1.6% of ethylene units.
PPC4: WL203 from the company Huntsmann is a random polypropylene copolymer from the REXflex FPO
polymer family.
PPC5: WL223 from the company Huntsmann is a random polypropylene copolymer from the REXflex FPO
polymer family.
PPC6 KFC2008 from the company Borealis is a random polypropylene copolymer.
PPC7 KFC2004 from the company Borealis is a random polypropylene copolymer.
PPH2: HD601F from the company Borealis is a polypropylene homopolymer having more than 99.8%
of polypropylene polymer.
PPH3: WL113 from the company Huntsmann is a polypropylene homopolymer from the REXflex FPO
polymer family.
PPH4: WL107 from the company Huntsmann is a polypropylene homopolymer from the REXflex FPO
polymer family.
PPT1 TD 120 H from the company Borealis is a -C2/C4 terpolymer having more than 99.7% of polypropylene copolymer.
PPT2 RD 418H-03 from, the company Borealis is a C3/C4 random copolymer having more than 99.5% of polypropylene copolymer.
PPT3 K2033 from the company Borealis is a heterophasic polypropylene copolymer (RAHECO).

NPPOONPOINA from the company Ferro Corporation is a compounded material made from 80% of PPC1 and 20% of TPE1 (w/w) TPE1 Kraton v1652 from the company Shell Nederland Chemie B.V. is a linear styrene-(ethylene-butylene)-styrene block copolymer (SEBS).
PPH5: WL101 from the_ company Huntsman is a polypropylene homopolymer from the REXflex FPO
polymer family.

PPH6: WL102 from the company Huntsmann is a polypropylene homopolymer from the REXflex FPO
polymer family.
PPH7: WL110 from the company Huntsmann is a polypropylene homopolymer from the REXflex FPO
polymer family.
PPHB: WL111 from the company Huntsmann is a polypropylene homopolymer from the REXflex FPO
polymer family.
PPH9: WL114 from the company Huntsmann is a polypropylene homopolymer from the REXflex FPO
polymer family.
PPH10: WL116 from the company Huntsmann is a polypropylene homopolymer from the REXflex FPO
polymer family.
PPH11: WL117 from the company Huntsmann is a polypropylene homopolymer from the REXflex FPO
polymer family.
PPH13: KFC201 from the company PCD is a polypropylene homopolymer.

2. Production of films Films were produced in a manner known per se from the materials described above and, where appropriate, from other materials not given in Table 1. The principle for the production of flat films or blown films was as follows:

Flat (cast) film.
The PP pellets were introduced via a feed system to the extruders for producing the individual layers. The materials were plastified by heat and friction, converted in a manifold block into the layer structure described above, and cast via a slot die onto a water-cooled rotating roller.
Layer thicknesses and overall thickness are determined via extruder throughput and take-off speed of the chill roll.

The cooled film is wound on a winder to give parent rolls.

Water-cooled blown film:
The PP pellets were introduced via a feed system to the extruders for producing the individual layers. The materials were plastified by heat and friction, converted in a blowing head into the layer structure described above, and molded via an annular die to give a bubble which is cooled in a water-cooled calibrator.
Layer thicknesses and overall thickness are determined via extruder throughput and take-off speed of the take-off equipment.
The cooled film is wound on a winder to give parent rolls.

Films of the invention were obtained and had the makeups and properties given in Table 2, or appropriate I commercially available films of the Comparative Examples were analyzed:

Table 2: Makeup of inventive and non-inventive films.

Ex./ Inner layer Middle layer Outer layer Contp. (I) (M) (A) No.
Prop. Thick- Prop. Prop. Thick- Prop. Prop. Thick- Prop.
by Mat. ness by by Mat. ness by by Mat. ness by wt. [Eun] thick- wt. [ m] thick- wt. ( m] thick-ness [$] ness [$] ness [$] [~] [$]

Comp. 19 11 100 PEC1 132 78 100 PETl 19 11 Comp. 70 PPC2 50 PPC2 Comp. 80 PPC1 40 24 100 PPH4 100 59 100 PPC2 30 18

3 20 TPE1 Ex. 80 PPC1

4 20 TPE1 Table 2: continuation Ex./ Inner layer Middle layer Outer layer Comp. (I) (M) (A) No.
Prop. Thick- Prop. Prop. Thick- Prop. Prop. Thick- Prop.
by Mat. ness by by Mat. ness by by Mat. ness by wt. [ m] thick- wt. [{an] thick- wt. [ m] thick-[~] ness [$] ness [~l ness [$] [$] [~]
Comp. 70 PPC2 50 PPC2 Ex. 80 PPC1 30 16 100 PPC3 130 68 100 PPH3 30 16 Ex. 80 PPC1 Ex.

COmp. 100 PPTl 50 28 70 PPT3 100 56 100 PPT2 30 17 Comp. 100 PPT1 50 28 30 PPT3 100 56 100 PPT2 30 17 Comp. 100 PPT1 50 28 30 PPT3 100 56 100 PPH2 30 17 Ex. 80 PPC1 40 20 100 PPH7 140 70 100 PPC2 20 10 Ex. 100 PPC6 40 20 100 PPH7 140 70 100 PPC7 20 10 Comp. 80 PPC1 154 77 100 TPE2 20 10 100 PET2 26 13 PPH
Comp. 20 12 70 PPH
15 100 PPH 25 12.5 50 TPE1 125 62.5 12 50 25 Ex. 80 PPC1 40 20 100 PPCol 140 70 100 PPC7 20 10 Table 2: further continuation:

Ex./ Inner layer Middle layer Outer layer Comp. (I) (M) (A) No.
Prop. Thick- Prop. Prop. Thick- Prop. Prop. Thick- Prop.
by Mat. ness by by Mat. ness by by Mat. ness by wt. ( m] thick- wt. ( m] thick- wt. [ m] thick-[$] ness [$] ness [~] ness [~] [8] [$]
Ex. 80 PPC1 Ex. 80 PPC1 40 20 80 PPT3 140 70 100 PPC7 20 10 Comp. means comparative example;
in particular Comp. 1 refers to a commercially available film from the producer Cryovac known by the abbreviated term M312, the structure of which is assumed to be that disclosed by US 4,643,926 or EP 0 199 871;
Comp. 14 refers to a commercially available film with the trade name Excel from the company B. Braun McGaw in accordance with EP 0 228 819;
Comp. 15 refers to a commercially available film from the company Sengewald, the structure of which is assumed to be covered by DE 196 40 038 Al;
Ex. means inventive example;
PPH1: 41E4cs278 from the company Huntsman is a polypropylene homopolymer.
TPE2 Kraton G1657 from the company Shell Nederland Chemie B.V. and is a linear styrene-(ethylene-butylene)-styrene block copolymer (SEBS).
TPE3 Tuftec H1085L from the company Asahi Chemical Industry Co is a hydrogenated styrene butadiene block copolymer.
PEC1 SLP 9069 from the company Exxon Chemical is an ethylene-alpha-olefin.

PET1 Ecdel 9965 from the company Eastman Chemical Company is a copolyester ether.
PET2 Copolyester material.
PPH12 Polypropylene homopolymer.
PZ1 Medicinal white oil.
PPT4 ROBY P0004967 from the company Montell (Basell) is a heterophasic polypropylene copolymer.
PPC8 Engage 8200 from the company Dow is a polyolefin copolymer.
PPCoI XS 115 from the company Ferro is a compounded material made from random copolymer/EVA/heterophasic polypropylene 3. Determination of properties of films:
The tensile behavior of the commercially available films, and also of the films of the inventive examples or other films produced in-house for comparative purposes, were tested in accordance with DIN ISO 527-1 to -3. The results of these experiments are shown in Table 3.

__ __ ~.

II ~

Table 3: Results of tensile experiments for sterilized films of the invention and sterilized comparative films:

Examples & Modulus of elasticity Yield point in N/mm Comparisons (Mpa) in N/mm2 DIN ISO 527-1 to 3 DIN ISO 527-1 to 3 MD TD MD TD
Comp. 1 99.03 98.01 None None Comp. 2 382.35 171.39 18.6 None Comp. 3 87.8 119.9 11.6 10.2 Ex. 4 187.22 275.54 None None Comp. 5 325.48 241.13 14.17 14.88 Ex. 6 191.01 170.44 None None Ex. 7 109.41 93.1 None None Ex. 8 212.08 191.78 None None Comp. 9 403.75 421.55 20.04 19.39 Comp. 10 347.27 354.57 16.74 16.75 Comp. 11 400.51 375.92 17.97 16.44 Ex. 12 195.74 158.25 None None Ex. 13 166.55 183.70 None None Comp. 14 377.7 293.8 18.69 16.53 Comp. 15 311.0 250.1 15.84 None Ex. 16 72.43 56.04 None None Ex. 17 187.66 119.34 None None Ex. 18 246.74 148.71 None None MD indicates measured in machine direction. TD are measurements transverse to the machine direction.

It is seen that films of the invention do not have any yield point either in machine direction or in a direction transverse thereto. With the exception of a single Comparative Example (Comp. 1) all of the other Comparative Examples have a yield point in both directions (MD and TD), as for example Comp. 5 or 14, or only in machine direction (MD), as for example Comp. 2 or Comp. 15. Comp. 1 which does not have a yield point of any kind in the sterilized state does, however, have a disadvantageous material mix (polyester outer layer). The invention therefore for the first time provides films for medicinal solutions which are composed exclusively of polyolefin materials, optionally with small proportions of rubber materials, and which combine excellent stiffness and yield stress with excellent impact strength. It is therefore possible to avoid PVC and PET entirely without losing their mechanical properties.
4. Production of bags from films A selection of the films of the invention and of comparative materials was used to produce bags for packaging liquid, medicinal products. These, known as i.v. bags, where produced in the following way:

Specimens were cut to size at appropriate lengths from the films obtained as described above herein, and were welded permanently to one another at all of the edges by thermal contact welding, to give a bag with two flexible connector tubes. The two connector tubes are tightly sealed, using pluggable connectors.

The films are welded in welding equipment, by heated welding jaws. The parameters for temperature, time, and pressure per unit area for the welding process are to be determined in a few exploratory experiments.

Each of the finished bag specimens from the welding process was filled with 1 liters of water. The finished, filled bags were sterilized. The sterilization took place in an autoclave at 121 C for from 15 to 30 min with wet steam (hot-water sprinkle process).

5. Methods for testing physical properties of the bags:

a) Drop test According to DIN 58363-15 (infusion containers and accessories), the bags have to survive, without damage, a drop onto a hard, non-springy plate with a smooth surface. Depending on the fill quantity, the requirements applicable are those described below in Table 4:

Table 4: Requirements for drop test to DIN 58363-15 Nominal fill quantity in ml Drop height in m at room temperature up to 750 2.0 above 750 up to 1500 1.5 above 1500 up to 2500 1.0 above 2500 0.5 The test is passed if a visual examination shows that no bag breaks and no liquid escapes.

b) Pressure cuff test The pressure cuff test is an application-related test which is used as follows in the case of pressure infusions and patient monitoring:

For a pressure infusion, infusion bags have to withstand a gauge pressure of about 400 mm Hg for about 1 h in the commercially available pressure cuffs.

For patient monitoring, the bags have to withstand a gauge pressure of 39 996.71 Pa (300 mmHg) for 7 days at a temperature of 20-28 C. Increased gauge pressures up to 53 328.95 Pa (400 mmHg) may occur for short periods of about 1 h.

The bags obtained as in 4. were subjected to a drop test as in 5a) and a pressure cuff test as in 5b). Bags made from films of the invention passed the tests 5a) and 5b) satisfactorily, whereas with the bags made from non-inventive films there was the possibility of some failures.

6. Comparison of properties from Example 12 and Comparative Example 14 The two films had the same materials for the inner layer (I) or sealable layer, but differed with respect to the materials of the middle layer (M) and of the outer layer (A).

First, the processability and the tensile properties of the two films were compared. Both films permit the production of welds of varying strength by altering the welding temperature. At low welding temperatures, i.e.
116-118 C, peelable seams are obtained, whereas at higher welding temperatures, i.e. from 126 to 130 C, permanent seal seams are obtained. The extent of processing latitude for contour seams can be determined by manufacturing bags under various welding conditions (pressure, temperature, time), filling them with water, sterilizing them, and then subjecting them to a drop test. If the weld breaks apart that indicates that the welding temperature was incorrect. If the film tears, that indicates that the impact strength of the material was too low. The results of these tests are given in Table 5:

Table 5: Results of drop tests Size of Welding Height Autoclaved Passed/ Passed/
bags temperature [m] [Yes/No] Total Total [ml] [ C] [Ex. 12] [Comp. 14]
500 126 2.0 Yes 40/40 39/40 500 128 2.0 Yes 40/40 40/40 500 130 2.0 Yes 40/40 38/40 1000 130 1.5 Yes 5/5 4/5 1000 130 1.5 No 5/5 5/5 The results from Table 5 clearly demonstrate that there is sufficient processing latitude for commercial production and that the film retains its properties even after sterilization. In addition, its properties are the same as or better than the properties of a known film using polyester (Comp. 14). In particular, films of Example 12 and Comparative Example 14 have the same flexibility in the filled state. The film of Ex. 12 moreover complies with the European Pharmacopoeia (Ph Eur. 3.2.7 and others). The water-vapor permeability of the film of the example is sufficient for the storage time for products in containers made from the film to be at least one year of storage. The film of the invention has excellent transparency prior to and after sterilization. Despite this, the cost of the raw materials (polymer materials) for producing the film of Example 12 is only about half as great as the cost of the raw materials for the film of Comp. 14. This is substantially attributable to a lower total amount of SEBS and to a reduction in the compounding steps prior to extrusion.

Claims (22)

CLAIMS:

1. An autoclavable, PVC-free multilayer film having at least three layers, comprising an outer layer (A), an inner layer (I), and, arranged therebetween, a middle layer (M), each of which is composed of from 60 to 100 percent by weight of a polypropylene material and of from 40 to 0 percent by weight of a thermoplastic elastomer, each of the percentages being based on the total weight of the respective layer, wherein the multilayer film has no yield point measurable to DIN EN ISO 527-1 to -3 after sterilization using superheated steam at 121°C or at a higher temperature in the hot-water sprinkle process.

2. The multilayer film as claimed in claim 1, wherein the proportion, by thickness, of the middle layer (M), based on the total thickness of the film, is in the range from 40 to 80%.

3. The multilayer film as claimed in claim 2, wherein the proportion, by thickness, of the middle layer (M), based on the total thickness of the film, is in the range from 45 to 75%.

4. The multilayer film as claimed in claim 2, wherein the proportion, by thickness, of the middle layer (M), based on the total thickness of the film, is in the range from 60 to 80%.

5. The multilayer film as claimed in any one of claims 1 to 4, wherein the proportion, by thickness, of the outer layer (A), based on the total thickness of the film, is in the range from 30 to 7.5%.

6. The multilayer film as claimed in any one of claims 1 to 5, wherein the proportion, by thickness, of the inner layer (I), based on the total thickness of the film, is in the range from 30 to 12.5%.

7. The multilayer film as claimed in any one of claims 1 to 6, wherein the total thickness of the film is in the range from 120 to 300 µm.

8. The multilayer film as claimed in any one of claims 1 to 7, wherein the modulus of elasticity of the material of the middle layer (M) is less than or equal to 250 MPa, measured to DIN EN ISO 527-1 to -3.

9. The multilayer film as claimed in any one of claims 1 to 8, wherein the material of the middle layer (M) has no yield point measurable to DIN EN ISO 527-1 to -3, using a type 2 test specimen and a separation rate of 200 mm/min, after sterilization using superheated steam at 121°C or at a higher temperature in the hot-water sprinkle process.

10. The multilayer film as claimed in claim 9, wherein the material of the middle layer (M) has no yield point measurable to DIN EN ISO 527-1 to -3, using a type 2 test specimen and a separation rate of 200 mm/min, prior to sterilization using superheated steam.

11. The multilayer film as claimed in any one of claims 1 to 8, wherein the material of the middle layer (M) has a measurable yield point of less than or equal to 8 MPa to DIN EN ISO 527-1 to -3, using a type 2 test specimen and a separation rate of 200 mm/min.

12. The multilayer film as claimed in any one of claims 1 to 11, wherein the modulus of elasticity of the material of the outer layer (A) is greater than 250 MPa, in each case measured to DIN EN ISO 527-1 to -3.

13. The multilayer film as claimed in any one of claims 1 to 12, wherein the melting point of the outer layer (A) is higher than the melting point of the inner layer (I), each of the melting points being determined on a single-layer film or a test specimen made from the material of the respective layers (A) and (I) to DIN 3146-C1b.

14. The multilayer film as claimed in claim 13, wherein the melting point of the middle layer (M) is lower than the melting point of the outer layer (A) and higher than the melting point of the inner layer (I), each of the melting points being determined for a single-layer film or a test specimen made from the material of the respective layers (A), (M) and (I) to DIN 3146-C1b.

15. The multilayer film as claimed in any one of claims 1 to 14, wherein the melting point of the middle layer (M) is in the range from 130 to 160°C, the melting point being determined for a single-layer film or a test specimen made from the material of the middle layer (M) to DIN 3146-C1b.

16. The multilayer film as claimed in any one of claims 1 to 15, wherein each of the layers (A), (M) and (I) has a Vicat point, which for the middle layer (M) is in the range from 35 to 75°C, and for the layers (A) and (I) is in the range below or equal to 121°C.

17. The multilayer film as claimed in any one of claims 1 to 16, wherein the layers (A) and (M). are composed of 100 percent by weight, and the inner layer (I) is composed of from 60 to 100 percent by weight of one or more polymers selected from the group consisting of a homopolymer of polypropylene (homo-PPs), a random copolymer of polypropylene (random-co-PPs), a block copolymer of polypropylene, a flexible homopolymer of polypropylene (FPOs), a flexible copolymer of polypropylene (co-FPOs), and the inner layer (I) is also composed of from 40 to 0 percent by weight of a styrene-ethylene/butylene-styrene block copolymer (SEBS).

18. The multilayer film as claimed in any one of claims 1 to 17, comprising five layers with the sequence A1-M1-A2-M2-I or A1-M1-M2-A2-I, or seven layers with the sequence A1-M1-A2-M2-A3-M3-I, the thickness of the layers (M) and (A) being the sum of the values for (M i) and (A i), respectively, and wherein A1, A2 and A3 are sub-layers of the outer layer (A) and M1, M2 and M3 are sub-layers of the middle layer (I).

19. A process for producing a multilayer film as claimed in any one of claims 1 to 18, in which the layers (A), (I) and (M) are coextruded with one another or laminated to one another.

20. The process as claimed in claim 19, wherein the film is coextruded in the form of a flat or blown film, or laminated in the form of a flat film.

21. Use of the multilayer film as claimed in any of claims 1 to 18, as a means of packaging for the bagging or storage of water-based parenteral liquids.

22. Use of the multilayer film as claimed in any of claims 1 to 18, as a means of packaging for the bagging or storage of liquid lipophilic emulsions.