Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
1,
CA 02393039 2002-05-30
r r
WO 01/42009 PCT/EPOO/12465
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
CA 02393039 2002-05-30
7- - 2 -
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
CA 02393039 2002-05-30
3 -
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.
11
CA 02393039 2002-05-30
- 4 -
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
CA 02393039 2002-05-30
- 5 -
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,
CA 02393039 2002-05-30
- 6 -
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,
CA 02393039 2002-05-30
- 7 -
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
CA 02393039 2002-05-30
- 8 -
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
CA 02393039 2002-05-30
9 -
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
CA 02393039 2002-05-30
- 10 --
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
CA 02393039 2002-05-30
}
= - 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.
CA 02393039 2008-04-04
25259-101
- 12 -
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.
CA 02393039 2002-05-30
- 13 -
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
CA 02393039 2008-04-04
25259-101
- 14 -
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
CA 02393039 2008-04-04
25259-101
- 15 -
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.
CA 02393039 2008-04-04
25259-101
- 16 -
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
CA 02393039 2002-05-30
- 17 -
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.
CA 02393039 2002-05-30
- 18 -
= 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
CA 02393039 2002-05-30
- 19 -
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
CA 02393039 2002-05-30
- 20 -
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
CA 02393039 2002-05-30
- 21 -
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).
CA 02393039 2002-05-30
- 22 -
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
CA 02393039 2002-05-30
- 23 -
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
CA 02393039 2002-05-30
- 24 -
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
CA 02393039 2002-05-30
- 25 -
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
CA 02393039 2002-05-30
- 26 -
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
CA 02393039 2002-05-30
- 27 -
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
^.
CA 02393039 2002-05-30
- 28 -
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
CA 02393039 2002-05-30
- 29 -
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).
CA 02393039 2002-05-30
- 30 -
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
CA 02393039 2002-05-30
- 31 -
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
CA 02393039 2002-05-30
- 32 -
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
CA 02393039 2008-04-04
25259-101
- 33 -
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;
CA 02393039 2002-05-30
- 34 -
(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;
CA 02393039 2002-05-30
- 35 -
(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
CA 02393039 2008-04-04
25259-101
- 36 -
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
41
CA 02393039 2002-05-30
.
- 37 -
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:
CA 02393039 2002-05-30
- 38 -
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,
CA 02393039 2002-05-30
- 39 -
and for some materials not used in the Examples or
Comparative Examples.
CA 02393039 2002-05-30
- 40 -
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 * *
TPE1
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
CA 02393039 2008-04-04
25259-101
- 41 -
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).
PPC1/TPE1
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.
CA 02393039 2002-05-30
- 42 -
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.
CA 02393039 2002-05-30
- 43 -
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
[$] [~] [$]
80 PPC1
Comp. 19 11 100 PEC1 132 78 100 PETl 19 11
20 TPE1
1
Comp. 70 PPC2 50 PPC2
85 PPH1
2 15 TPE2 53 27 15 TPE2 110 68 32 16
15 TPE3 35 TPE3 15 TPE3
Comp. 80 PPC1 40 24 100 PPH4 100 59 100 PPC2 30 18
3 20 TPE1
Ex. 80 PPC1
40 24 100 PPC3 100 59 100 PPH3 30 18
4 20 TPE1
CA 02393039 2002-05-30
- 44 -
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 [$] ness [~l ness
[$] [$] [~]
Comp. 70 PPC2 50 PPC2
85 PPH1
15 TPE2 30 18 15 TPE2 110 68 40 24
TPE3 35 TPE3 15 TPE3
Ex. 80 PPC1 30 16 100 PPC3 130 68 100 PPH3 30 16
6 20 TPE1
Ex. 80 PPC1
50 26 100 PPC3 90 48 100 PPH3 50 26
7 20 TPE1
Ex.
100 PPC1 50 26 100 PPC3 90 47 100 PPH3 50 26
8
COmp. 100 PPTl 50 28 70 PPT3 100 56 100 PPT2 30 17
9 30 PPC3
Comp. 100 PPT1 50 28 30 PPT3 100 56 100 PPT2 30 17
10 70 PPC3
Comp. 100 PPT1 50 28 30 PPT3 100 56 100 PPH2 30 17
11 70 PPC3
Ex. 80 PPC1 40 20 100 PPH7 140 70 100 PPC2 20 10
12 20 TPE1
Ex. 100 PPC6 40 20 100 PPH7 140 70 100 PPC7 20 10
13
Comp. 80 PPC1 154 77 100 TPE2 20 10 100 PET2 26 13
14 20 TPE1
PPH
Comp. 20 12 70 PPH
15 100 PPH 25 12.5 50 TPE1 125 62.5 12 50 25
13
30 PZ1 30 TPE1
Ex. 80 PPC1 40 20 100 PPCol 140 70 100 PPC7 20 10
16 20 TPE1
CA 02393039 2002-05-30
- 45 -
Table 2: further continuation:
Ex./ Inner layer Middle layer Outer layer
Comp. (I) (M) (A)
No.
Prop. Thick- Prop. Prop. Thick- Prop. Prop. Thick- Prop.
by Mat. ness by by Mat. ness by by Mat. ness by
wt. ( m] thick- wt. ( m] thick- wt. [ m] thick-
[$] ness [$] ness [~] ness
[~] [8] [$]
Ex. 80 PPC1
40 20 100 PPT4 140 70 100 PPC2 20 10
17 20 TPE1
Ex. 80 PPC1 40 20 80 PPT3 140 70 100 PPC7 20 10
18 20 TPE1 20 PPC8
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.
CA 02393039 2002-05-30
- 46 -
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 ~
CA 02393039 2002-05-30
- 47 -
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,
CA 02393039 2002-05-30
- 48 -
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).
CA 02393039 2002-05-30
- 49 -
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.
CA 02393039 2002-05-30
- 50 -
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:
CA 02393039 2002-05-30
51 -
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.
