Note: Descriptions are shown in the official language in which they were submitted.
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BACKGROUND OF THE I NVENTI ON
Parenteral solutions broadly cover fluid
replacement, electrolyte replacement and are vehicles for
drug medication. Solutions include blood plasma,
platelets, red cells, ~idney dialysi6 solution6, saline
solutions and nutritional products. These solutions were
initially bo~tled in glass, however, with the
introduction of the collapsible parenteral solution bag
some years ago, airborne contamination was significantly
reduced since the flexi~le bags empty without outside air
entering the system.
The general requirements of a resin used in the
manufacture of the parenteral solution bags include
flexibility, clarity, toughnes6 at low temperatures, heat
sealability, good processability, moisture vapor
permeability resistanc~ and ability to be sterilized.
The industry i~ presently employing a highly plasticized
PVC film for this purpose. Although this resin does meet
most of the requirements, a material is preferred that
has little or no plasticizer. Also the PVC film is not
very resistant to moisture vapor permeability, and
consequently, the continuing loss of moisture of the
parenteral solutions reduces their storage life
considerably. Therefore, it is required that the bag be
sealed within an ovterpouch made from a film resin
designed to have a low water vapor transmission rate
(WVTR). Currently the overpouch film is made from a
blend o~ high density polyethylene and butyl rubber and
bee~ extruded into film of a thickness of about 4-5 mil
to provide the necessary WVTR. This thickness is usually
more than needed for physical strength and adds to the
cost of the assembly. Another drawback of the overpouch
resin is that it lacks the desired clarity, an important
property needed for easy and correct identification of
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the contents of the inner bag.
It is therefore an object of the pre~ent invention
to provide a resin formulation which is suitable in the
manufacture of sterilizable overpouch films of improved
clarity and moisture vapor permeability resistance.
It i6 also an object of the present invention to
provide a film useful in the manufacture of sterilizable,
collapsible bags for direct and for indirect containment
of parenteral solutions.
It is a further object of the invention to provide
an improved collapsible intravenous bag a6sembly.
Other ob;ects are readily determined from a reading
of the specification and claims.
~HE INvENTION
In accordance with the present invention there is
provided a 6terilizable film resin composition which
compri6es a blend of:
(a) from about 10 to about 60 wt % of a
random copolymer of from about 1 to
about 6 wt % ethylene and from about
94 to about 99 wt % propylene;
(b) from about 40 to about 90 wt % of a
linear low density polyethylene
produced by copolymerization of
ethylene and at least one C4-C18
alpha-olefin and having a density
between about 0.915 and about 0.940
gm/cc.
The random copolymer component preferably has a melt
flow in the range between about 1.0 and about 5.0 g/10
min at 230C. Such polymers are readily available
commercially and their preparation need not therefore be
di cussed.
The linear low density polyethylene component,
hereinafter sometimes identified as LLDPE, is an
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interpolymer of ethylene an at least one C4-C18 alpha-
olefin in comonomer. Preferably the alpha-olefin
comonomer contains from 4 to 8 carbon atoms per molecule.
Examples of especially suitable comonomers are butene-1,
pentene-1, hexene-1, 4 methyl-pentene-1, heptene-1,
octene-1 and mixtures thereof such as butene-1/hexene-1
and butene-1/octene-1, etc. These LLDPE resins can be
produced by any of the recently introduced catalytic
proce6ses u6ing vapor, solution or slurry techniques at
low to medium pre6sures or high pressure catalytic
polymerization in autoclave or tubular reactors. The
resin preferably has a melt index from about 0.5 to about
S g/10 min. at 190C. A variety of suitable resins are
commercially available within the required density and
melt flow ranges.
One optional component of the resin blend is an
agent added in a quantity effective to produce films of
improved clarity. Examples of suitable agents are sod um
benzoate, dibenzylidene sorbitol, sorbitan monooleate and
others. Usually the agents are added in quantities
between about 0.1 and about 2 wt % based on the weight of
the total polymers. Also from about 2 to about 15 wt %
of a high density polyethylene, i.e., a homopolymer of
ethylene having a density of at least 0.945 gm/cc can be
included in the resin as another optional ingredient for
the purpose of increasing the heat seal range. This
property i6 defined a6 the time 6pan between the minimum
time to make a good seal and the maximum time before the
film burns through employing a standard heat-sealing
device.
The blend composition of present invention is easily
processable into blown or cast film products which, in
addition to high clarity, exhibit other desirable
properties such as flexibility, toughness at low
temperatures, heat sealability. Also, the films have
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good resistance to moisture vapor permeability and can
be steam sterilized at 121C , without significantly
affecting its physical properties in a detrimental way.
Finally, the films contain no additives, which would
prevent their use in food or medical applications, either
in direct or indirect contact.
When used for an inner parenteral solution
container, the film should have a thickness in the range
of from about 3 to about 10 mils, while the overpouch
need not be more than from about 1 to about 6 mils
thick. If desired, co-extruded films for either the
inner bag or the outer bag can be used to reduce 10B5 of
moisture or gases through the film walls. Materials 6uch
as fluorocarbon polymers, ethylene-vinyl alcohol
copolymers and polyvinylidene chloride materials are
examples of suitable co-extrudates.
Further improvements result from an overall
parenteral solution bag assembly which comprises an inner
sealed film bag containing the parenteral solution, an
outer sealed film bag containing a small amount of water
and enclosing the inner bag said outer bag having a width
and a length of from about 0.25 to about 1.5 inches
larger than the corresponding dimensions of the inner
bag, the outer film resin comprising a blend of:
(a) from about 10 to about 60 wt % of a
random copolymer of from about 1 to
about 6 wt % ethylene and of from
about 94 to about 99 wt % propylene;
(b) from about 40 to about 90 wt % of a
linear low density produced by
copolymPrization polyethylene of
ethylene and at least one C4-C18
alpha-olefin and having a density
; between about 0.915 and about 0.940
gm/cc.
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In one embodiment the small amount of water is added
directly to the outer pouch before the sealing operation
i8 carried out to enclose the inner bag. In another
embodiment the small amount of water is enclosed in a
separate smaller pouch manufactured from two film
layers. For economic reasons, one of the films is
suitably made from the same resin as that of the outer
bag, while the other layer should be made from a porous
material that allows vapor escape but is resistant to
liquid per~eability. Suitable materials for this purpose
are commercially available, e.g., the Tyvek (TM)
spunbonded polyethylenes available from E.I. DuPont
deNemours. ~oisture vapor is thereby permitted to escape
from the small pouch more rapidly than from the outer
bag, thu6 producing a saturated atmosphere between the
inner and outer bag, effectively eliminating the driving
force for water to escape from the inner bag and reducing
the rate at which water vaporize~ and leaves the inner
bag. The area of ~ne 6id~ of the smaller pouch should
not exceed about 50% of the corresponding inner bag area.
The a~tual amount of water to be used to inhibit
removal of water vapor from the inner bag should at least
be 6ufficient to ensure that liquid water still be
pre6ent in the space between the inner and outer bags at
the expiration date of the parenteral solution. This
amount will obviou61y vary from case to case and depends
on the maximum allowable storage life of the parenteral
solution, the 6ize of the outer bag and the water vapor
transmission rate through said bag.
An additional feature of this invention is the
ability to substitute materials other than water in the
6mall pouch. For example, a carbon dioxide absorber can
be sealed in the small pouch and help in removing carbon
dioxide from the inner bag or an oxygen generator can be
added to aid in adding oxygen to the inner bag, thereby
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considerably increasing blood platelet storage life.
Other materials and gases could also be handled and
controlled in this manner in order to improve the storage
performance of the system.
The use of the small pouch inserted in the space
between the inner and outer bags simplifies all packaging
operations to a large degree. Only one film material and
thicknes6 would be required for manufacturing and
inventorying the inner bag for all types of 601utions.
Additionally, all outer bags can be of the same resin
formulation and of one film thickness. Only different
small pouches, identifiable, e.g., by color coding, need
to be added.
In ca~e the materials packaged in the inner bag are
6ensitive to ultra violet light, a small amount of an
ultra violet screening agent can be incorporated in the
outer bag which would prevent U.V. light from reaching
the packaged products.
The film compo6itions are also high energy radiation
6terilizable.
Also, either or both of the bag~ of the parenteral
601ution bag assembly may be manufactured from other
polymer film compositions, provided that they are
6terilizable by heat or irradiation and meet the general
requirements of flexibility, toughness, heat
6ealability, etc., previously discussed.
To further illustrate the invention the following
example is provided:
EXAMPLE 1
A resin blend containing 84.75 parts LLDPE
(copolymer of ethylene and butene-1, density 0.918 g/cc,
melt index 1.0 g/10 min), 15 parts random copolymer of
97.5% propylene and 2.5% ethylene (density 0.900 g/cc,
melt flow 2.0 g/10 min). 0.25 parts dibenzylidene
sorbitol was used in preparing blown films of 2.5 mil and
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4.5 mil thicknesses. The resulting films had goo~
clarity, toughness, were easily heat sealable and
flexible. Pouches were made from these films, filled
with water, heat sealed and tossed in the air to
simulate a 10 foot drop. All pouches survive at least 6
drop6 at ambient temperatures (65F). The moisture vapor
transmission rate of the films were approximately 0.7
grams/mil/100 5 guare inches/24 hours.
Other test samples consisting of 5~ x 11" inner bags
were prepared from the 4.5 mil film. These were filled
with 1000 cc water and enclosed in 6" x 12" outer bags of
the 2.5 mil film. A portion of the samples were provided
with 70 cc water between the inner and outer bags. All
of the samples passed the steam sterilization test
carried out in an autoclave at 121C for 60 minutes.
Equally good results were obtained in experiments
with films made from a resin blend similar in all
aspects of the previous one except the LLDPE/copolymer
weight ratio was changed from about 85:15 to about
60:40.
EXAMPLE 2
5 mil films were made from resins containing varying
amounts of high density polyethylene t0.952 gm/cc) in
addition to the LLDPE and the propylene-ethylene random
copolymer used in Example 1. Strips of two layers of
these films were placed in an air oven at 250F for 1/2
to 1 hour. The strips were then taken out and inspected
for any tendency to stick to itself. These same films
were then tested in a heat sealing device to determine
their ability to be heat sealed. An impulse type sealer
made by Sentinel Industries was used for these tests.
The heating cycle was varied (in seconds) and the cooling
time (4 sec.) and air pressure (21 psig) was held
constant. The minimum time to make a good seal and the
maximum time before the film burned through were
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determined and the time difference was the sealing range.
Table 1 summarizes the data from these experiments.
As seen from the results, the addition of small
amount~ of high density polyethylene greatly increased
the heat 8 eal range.
Peel tests also showed that the seals were
considerably stronger in films made from resins
containing high density polyethylene as a third resin
component. Other film properties were not adversely
affected by this inclusion.
TABLE 1
Test Contr.1 AB C D E
C-3/C2= copolymer -- 40 4040 35 36
-wt%
LLDPE -wt% 100 6054 5060 54
HDPE -wt% -- -- 6 105 10
Oven Test(1)STICK DNS DNS DNS DNS DNS
Heat Seal
Range,Sec. 2.5 1.3 1.8 2.3 2.4 2.4
(1)
DNS - Did not stock - slight tackiness
It is to be understood that many modifications and
alterations can be made to this invention without
departing from its scope, which is defined by the
specification and appended claims.
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