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PCT
WO 2009/082132 A2
(74) Agent: JANG, Soo-Young; Rm. 1610 Hyundai Venturetel, 642-1 Yeoksam 1-dong, Gangnam-gu, Seoul 135-910
(KR).
Korean
English
KR
^= (54) Title: MULTILAYER FILM FOR MEDICAL SOLUTION CONTAINER AND A CONTAINER COMPRISING THE SAME
FIGURE 1
<
m
00
ON
10
(57) Abstract: The present invention relates to a multilayer film for medical solution container and a container comprising the same,
more particularly, to the multilayer film for medical solution comprising an outer layer comprising polypropylene, polypropylene
copolymer or a mixture thereof; an intermediate layer comprising a mixture of 30-70% by weight of propylene-based polymer including polypropylene, polypropylene copolymer or a mixture thereof, and 30-70% by weight of a thermoplastic elastomer; and an
inner layer comprising a mixture of 50-70% by weight of propylene-based polymer including polypropylene, polypropylene copolymer or a mixture thereof, 5-20% by weight of polyethylene, and 10-45% by weight of a thermoplastic elastomer. The multilayer
film has such improved flexibility, transparency, heat resistance, sealing property and durability, as well as easy peelability and peel
strength with non-temperature sensitive that can be applied to a pouch type container for packaging and administering of medical
solutions or blood.
WO 2009/082132 A2
Published:
without international search report and to be republished
upon receipt of that report
111 III II11 III 111 Hill III III I I 11111111 III III III III III llll
WO 2009/082132
PCT/KR2008/007540
Technical Field
5
10
Background Art
Generally, a medical solution container must meet a number of
performance criteria, including flexibility, transparency, gas barrier property, drug
compatibility, heat sterilization resistance, fall impact resistance, etc.
15
The
medical solution container uses partition walls for various medical solutions kept
in each chambers not to react with other medical solution kept in other
chambers. And when the medical solution is in need to inject to a patient, the
20
administered to a patent via spike port using a syringe with sanitary and safe.
In case of administering medical solutions by connecting a few or many
medical solution bags or bottles, medical staff may mistake in injecting medical
WO 2009/082132
PCT/KR2008/007540
example, a double bag with an inner bag and outer bag, where the inner bag
contains functional medical solutions and the outer bag covers the inner bag
and blocks gas as like oxygen.
In this way, medical solution container having multiple chambers or
single inner bag wrapped by outer bag have been studied from 10 years ago in
10
Europe, and recently investigation for building up properties, i.e. fall impact
resistance as well as gas or moisture barrier function are accelerated.
In general, the inner bag needs to have various properties such as
oxygen and moisture barrier property, heat sterilization resistance, transparency,
fall impact resistance, flexibility, etc.
15
20
constitution ratio of polyolefin, however, the inner bag material has weakness in
sterilization at 121 C and exhibits extreme variation of heat seal strength to
temperature, that may make it difficult to maintain good quality, /. e. uniform
strength, in easy peelable property.
The medical solution container needs to have good properties such as
WO 2009/082132
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Moreover,
since the container is easily dropped, the inner bag must have sufficient
properties, i.e. fall impact strength, flexibility, etc.
necessary.
15
should have proper peel strength with non temperature sensitive on various
parameters such as temperature, time and pressure in case of heat seal.
Such peelable heat seal makes adhesion strength increase depending
on time or after heat sterilization, so that the partition walls of the container may
not peel easily.
20
of partition wall may be carried out at lower temperature and pressure, in short
time, in comparison with the conditions of peelable heat seal of outer layer.
The present invention has improved easy peelability through adding
styrene thermoplastic elastomer into an inner layer of multilayer film container;
WO 2009/082132
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also the present invention has improved easy peelability with non temperature
sensitive and safe quality after sterilization by adding the thermoplastic
elastomer and polyethylene.
Disclosure
Technical
Problem
15
Technical Solution
To accomplish this goal,
the present invention provides a multilayer film for a medical solution
container comprising:
an outer layer comprising polypropylene, polypropylene copolymer or a
20
mixture thereof;
an intermediate layer comprising a mixture of 30-70% by weight of
propylene-based polymer including polypropylene, polypropylene copolymer or
a mixture thereof, and 30-70% by weight of thermoplastic elastomer; and
an inner layer comprising a mixture of 50-70% by weight of
WO 2009/082132
PCT/KR2008/007540
10
Advantegeous Effect
The multilayer film of the present invention has improved flexibility,
transparency, heat resistance, sealing property, durability, as well as easy
peelability and peel strength with non-temperature sensitive.
Such multilayer film may be applied to a pouch type container for
15
having the multilayer film of the present invention can be applied to variety of
medical industry owing to its excellent competitive price.
Description of Drawings
20
WO 2009/082132
PCT/KR2008/007540
Best mode
5
The present invention now will be described more fully hereinafter with
reference to the accompanying drawings, in which some, but not all
embodiments of the invention are shown.
It is to be understood, however, that the invention is not limited to the
specific features shown and described, since the means herein disclosed
10
Like numbers
For example,
it may be added a certain layer including an adhesive layer, a barrier layer for
moisture or gas, etc. into a multilayer film.
15
20
WO 2009/082132
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isotactic,
especially
polypropylene has a melt flow index (based on ASTM D1238) of 7-9 g/10 min, a
5
10
ethylene
monomer
as
co-monomer;
and
propylene-ethylene-a-olefin
20
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The
of
SBS(styrene-butylene-styrene
copolymer),
SEBS(styrene-ethylene-butylene-styrene
SIS(styrene-isoprene-styrene
copolymer)
and
copolymer),
mixture
thereof,
copolymer),
SBC(styrene-butadiene
but
are
not
limited
block
to.
20
flexibility of the
WO 2009/082132
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peelable property.
5
10
polypropylene
20
density of 0.80-0.90, melt flow index(based on ASTM D1238) of 9-11 g/10 min
and 100% modulus of 1.0-1.2.
As used herein, the term "polyethylene" refers to any conventional
polyethylene such as low density polyethylene (LDPE), linear low density
polyethylene (LLDPE), high density polyethylene (HOPE), very low density
WO 2009/082132
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present invention, the polyethylene has 0.2-0.4 g/10 min of melt flow
index(based on ASTM D1238), 0.9-1.0 of density, 125-145 "C of melting point,
5
10
15
20
The additive may be conventional additives, but are not limited to,
prevent the additives from merging into the medical solution during heat
sterilization.
The thickness of each layer of the multilayer film is preferably
10
WO 2009/082132
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layer, intermediate layer, and inner layer is 10~60//m, 140~240JMn and lO-SO/zm,
5
respectively.
range, the property of each layer does not meet necessary criterion needed in a
medical solution container.
Contrarily, if
the thickness of outer layer exceeds the above-mentioned range, the flexibility
10
the inner layer (6) goes beyond the above-mentioned range, easy peelability of
the multilayer film deteriorates.
In addition, it is preferable to perform heat seal of the multilayer film(10)
of the present invention at lower temperature than melting points of each
15
20
Accordingly, it is
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The
resin material during extrusion that each layer shows proper properties and the
obtained multilayer has high transparency and flexibility.
co-extrusion processes: one is inflation method using circular die, and the other
is T-die method using flat die.
clearness, and T-die method is better in view point of uniform thickness of each
15
layer.
In a preferred embodiment of the present invention, the multilayer film
is fabricated at the temperature of 170~250oC, more preferably at the
temperature of 200-230 C by the co-extrusion process.
It is preferable that
melt flow rate (MFR) difference between resins for each layer is little to give
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WO 2009/082132
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multilayer film has a haze after sterilization of 25% and less (based on ASTM D
1003), a tensile strength (based on ASTM 882) of 250 kgf/cm2 and more, and
an elongation (based on ASTM 882) of 900% and more.
The multilayer film of the present invention can be used as an inner
5
container of the present invention has easy peelability under proper pressure.
10
15
an inner bag with multiple chambers containing medical solutions; and an outer
bag covering the inner bag.
film as above-mentioned.
In particular, the partition walls dividing chambers break up easily,
because the inner bag has proper easy peelability by having adequate heat
20
the partition walls of the inner bag can be open easily, so that the medical
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container, easy peelable property of the inner bag must be kept, and rapid
change of heat adhesion intensity regarding temperature change of the inner
bag must be minimized.
15
material having good properties including moisture and gas barrier property,
processibility, transparency,
mechanical
container for vertical division is preferably higher than that for horizontal division.
When the content of medical solutions is quite a few in terms with inner volume,
the container should have high peel strength. In addition, it is preferable that the
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peel strength of container wrapped not following easy peelable line is higher
that the peel strength of container wrapped following easy peelable line. For
example, ideal peel strength necessary for easy opening to adult and not
opening during transportation is 5~15N/15mm, and an adequate film having
5
10
15
The
Notwithstanding the
opening of chambers, the inner bag still keeps sealed by out line of the
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WO 2009/082132
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chambers.
After the opening, components of medical solutions in each chamber (A,
B, C) fully mix with each other by shaking the inner bag (10).
mixed mixture is administered to a patient via the outlet (20) using a syringe(set
5
solution (amino acid solution), and chamber C contains third medical solution
(fat emulsion) respectively.
glucose
solution
comprises
glucose
monohydrate
14~8.30g,
0~6.22g,
20
L-histidine 0~7.14g,
L-isoleucine
4.45~8.62g,
L-
histidine monohydrochloride
L-leucine
5.95~11.51g,
L-lysine
L-tryptophane
calcium
1.08~2.10g,
chloride
L-tyrosine
dihydrate
16
0~0.24g,
L-valine
0.84~1.64g,
sodium
WO 2009/082132
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oil
0~105g,
lecithin
11.4-12.6g,
glycerol
20.9~26.25g,
The partition walls (12) diving each chamber (A, B, C) in the container
(100) are made by heat seal method.
If the
peel strength is under the range, the partition walls are easily opened and it is
difficult to sustain partition walls.
15
test examples.
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The
raw materials of composition were melted in the co-extruder, and the multilayer
film were fabricated by passing roller on the circular tube type film blew through
a die.
HOMO
ppi)
intermediate PPW
layer
SEBS^
inner layer PPW
SEBS5)
PE'W
HOMO PP:
10
Com.
Com.
Exp. 2
Exp. 3
100wt%
100
wt%
100
wt%
100
wt%
100
wt%
100 wt%
Exp. 1
Exp. 2
50 wt% 50 wt%
50 wt% 50 wt%
60 wt% 65 wt%
25 wt% 20 wt%
15wt% 15wt%
melt flow index of 8
Exp. 3
Com.
Exp. 1
50 wt%
50 wt%
50 wt%
50 wt%
85 wt%
70 wt%
50 wt%
50 wt%
80 wt%
50 wt%
50 wt%
90 wt%
10wt% 10wt%
15wt%
15wt% 15wt% 10wt%
g/10min, density of 0.90, softening
15
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Test Example 1
The test result of peel strength (soft seal) of the multilayer films
fabricated in the Examples and Comparative Examples was shown in Table 2.
After heat-adhering the multilayer film twofold and cutting the folded
multilayer film by size of 15mm x 150mm, the cut multilayer film was peeled
10
The maximum
Exp. 1
Exp. 2
Exp. 3
Com.
Exp. 1
Com.
Exp. 2
200im
normal
Com.
Exp. 3
200/zm
poor
200/ffli
200m
200IM
200IM
Thickness, /M
poor
good
Peeling property after good
good
sterilization
0.24
0.50
Peel
140oC
strength, N 145C
0.29
0.79
0.56
0.26
1.17
0.71
0.32
2.43
2.38
2.38
1.37
2.76
150C
0
5.10
1.84
4.26
4.88
2.51
4.08
155 C
26.44
12.23
18.50
5.54
3.29
9.00
160C
Thej multilaye r films of IExamples 1~3 show*3d good p<seling prop)erty
15
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In
peelable film.
type
of medical
solution
by
roller was released to fabricate a bag, and the bag was printed using Hot
Stamping Foil.
partition wall sealing mold. One side among four sides of bag was left for space
for tube injection using outer sealing mold, the left sides of the bag was
hard-sealed.
20
And the bag was fabricated by opening the unsealed part for
tube injection, and injecting tube, and heat adhering using tube sealing mold.
At this moment, the multilayer film fabricated in example 1 was used as an inner
bag material and polypropylene film was used as an outer bag material.
Fabrication Example 1
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An each solution of glucose, amino acid and fat emulsion was prepared
by the following Tables 3 to 5.
was injected into each three chambers, and the bag was sealed to fabricate a
medical solution container.
[Table 3]
Glucose solution (g)
[Table 4]
Amino acid solution (g)
L-alanin
L-arginin
L-aspartic acid
L-glutamic acid
glycine
L-histidine
L- histidine monohydrochloride
L-isoleucine
L-leucine
L-lysine monohydrochloride
L-methionine
L-phenylalanine
L-proline
L-serine
L-threonine
L-tryptophane
L-tyrosine
L-valine
calcium chloride dihydrate
sodium glycerophosphate
magnesium sulphate heptahydrate
magnesium acetate tetrahydrate
potassium chloride
potassium acetate
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7.76
8.58
-
0.53
0.90
1.52
1.14
2.27
3.07
3.24
6.89
[Table 5]
Fat emulsion (g)
Soybean oil
MCT(medium chain triglyceride) oil
lecithin
glycerol
a-tocopherol
sodium hydroxide
sodium oleate
Industrial Applicability
The multilayer film of the present invention is usable as an inner bag for
containing medical solutions.
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10
mixture thereof.
3.
4.
of
SBS(styrene-butylene-styrene
SEBS(styrene-ethylene-butylene-styrene
SIS(styrene-isoprene-styrene
copolymer),
23
copolymer),
copolymer),
SBC(styrene-butadiene
block
WO 2009/082132
PCT/KR2008/007540
6.
wherein the melting point of outer layer, intermediate layer and inner
layer ranges 140~165oC, 130~145oC, and 130~145oC, respectively.
7.
wherein the multilayer film is used as an inner bag of double bag type
10
multiple chambers containing medical solutions; and an outer bag covering the
inner bag,
wherein the inner bag comprises the multilayer film for medical solution
15
of claim 1.
9.
20
wherein
the
glucose
solution
comprises glucose
monohydrate
WO 2009/082132
L-arginin
PCT/KR2008/007540
5.13~11.87g,
5.32~12.88g,
glycine
L-aspartic
acid
0.14~8.30g,
2.85 ~ 5.51 g,
L-histidine
L-glutamic
0~7.14g,
acid
L-histidine
monohydrochloride
5.40 11.87g,
L-methionine
3.72 7.18g,
0.84 1.64g,
sodium
wherein
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the
fat
emulsion
comprises
soybean
oil
9521 Og,
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FIGURE 1
10
1/4
WO 2009/082132
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FIGURE 2
100
2/4
WO 2009/082132
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FIGURE 3
B
B@
>ni^juo
12
100
3/4
10
WO 2009/082132
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FIGURE 4
B
*-.
AA
10
100
4/4
^^A
mm