U.S. patent application number 08/796755 was filed with the patent office on 2001-07-19 for medical multilayer sealant films and methods for producing the same.
Invention is credited to INOUE, FUJIO, IZUMI, MASAMITSU, KASHIYAMA, SHIGETOSHI.
Application Number | 20010008686 08/796755 |
Document ID | / |
Family ID | 12665767 |
Filed Date | 2001-07-19 |
United States Patent
Application |
20010008686 |
Kind Code |
A1 |
INOUE, FUJIO ; et
al. |
July 19, 2001 |
MEDICAL MULTILAYER SEALANT FILMS AND METHODS FOR PRODUCING THE
SAME
Abstract
A multilayer sealant film for use in the medical field at least
comprises as its innermost layer a first layer comprising at least
one resin selected from the group consisting of linear low-density
polyethylene, low-density polyethylene, polypropylene and
polybutene-1, and a third layer comprising an ethylene-vinyl
alcohol copolymer and laminated to the outer side of the first
layer with a second layer serving as an adhesive layer and
comprising a resin containing, as a main component, at least one of
an amorphous polyolefin, adherent polyolefin and ethylene-vinyl
acetate copolymer. The ethylene-vinyl alcohol copolymer forming the
third layer functions as a barrier for preventing contaminants from
migrating from outside of the third layer toward the first layer
(innermost layer). Further, it is possible to improve the
formability of the multilayer film since the difference in density
between the resin for forming the first layer and the resin for
forming the second layer is set to be 0.02 g/cm.sup.3 or less.
Inventors: |
INOUE, FUJIO; (NARUTO-SHI,
JP) ; IZUMI, MASAMITSU; (NARUTO-SHI, JP) ;
KASHIYAMA, SHIGETOSHI; (NARUTO-SHI, JP) |
Correspondence
Address: |
ARMSTRONG,WESTERMAN, HATTORI,
MCLELAND & NAUGHTON, LLP
1725 K STREET, NW, SUITE 1000
WASHINGTON
DC
20006
US
|
Family ID: |
12665767 |
Appl. No.: |
08/796755 |
Filed: |
February 6, 1997 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
08796755 |
Feb 6, 1997 |
|
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|
08545606 |
Nov 6, 1995 |
|
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Current U.S.
Class: |
428/216 ;
264/171.27; 264/171.28; 428/215; 428/349; 428/35.4; 428/36.7;
428/520 |
Current CPC
Class: |
A61J 1/2027 20150501;
Y10T 428/1383 20150115; B32B 27/18 20130101; Y10T 428/31928
20150401; B32B 27/08 20130101; B32B 27/306 20130101; A61J 1/2093
20130101; A61J 1/2024 20150501; A61J 1/10 20130101; Y10T 428/24975
20150115; Y10T 428/24967 20150115; B32B 2323/046 20130101; B32B
27/32 20130101; Y10T 428/31913 20150401; B32B 7/12 20130101; Y10T
428/2826 20150115; Y10T 428/31935 20150401; Y10T 428/1341 20150115;
B32B 2309/105 20130101; B32B 2439/80 20130101 |
Class at
Publication: |
428/216 ;
428/215; 428/349; 428/520; 428/35.4; 428/36.7; 264/171.27;
264/171.28 |
International
Class: |
B32B 007/02; B32B
027/30; B32B 027/32; B29D 022/00; B29D 023/00 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 15, 1994 |
JP |
43511/1994 |
Claims
1. A medical multilayer sealant film which is a multilayer sealant
film having as the innermost layer a first layer comprising at
least one resin selected from the group consisting of linear
low-density polyethylene, low-density polyethylene, polypropylene
and polybutene-1, the sealant film being characterized in that a
third layer comprising an ethylene-vinyl alcohol copolymer is
laminated to the outer side of the first layer with a second layer
serving as an adhesive layer and comprising a resin containing, as
a main component, at least one of an amorphous polyolefin, adherent
polyolefin and ethylene-vinyl acetate copolymer, wherein the
difference in density between the resin constituting the first
layer and the resin constituting the second layer is 0.02
g/cm.sup.3 or less.
2. A sealant film according to claim 1, wherein a co-extrusion
inflation process is used to form the multilayer film comprising a
first layer, a second layer and a third layer, and wherein the lay
flat width of the film is set to be 420-1100 mm and the film
take-off speed is set to be 7.0-15.0 m/min during formation of the
film.
3. A sealant film as defined in claim 1 or 2 wherein the first
layer comprises linear low-density polyethylene or low-density
polyethylene, and the second layer comprises an adherent
polyethylene or ethylene-vinyl acetate copolymer.
4. A sealant film as defined in any one of claims 1 to 3 wherein
the first layer has a thickness of 10 to 40 .mu.m, the second layer
has a thickness of 5 to 25 .mu.m, and the third layer has a
thickness of 10 to 25 .mu.m.
5. A sealant film as defined in any one of claims 1 to 4 which is
characterized in that a fifth layer comprising at least one resin
selected from the group consisting of linear low-density
polyethylene, low-density polyethylene, polypropylene and
polybutene-1 is laminated to the outer side of the third layer with
a fourth layer serving as an adhesive layer and comprising a resin
containing, as a main component, at least one of an amorphous
polyolefin, adherent polyolefin and ethylene-vinyl acetate
copolymer, wherein the difference in density between the resin
constituting the forth layer and the resin constituting the fifth
layer is 0.02 g/cm.sup.3 or less.
6. A sealant film as defined in claim 5 wherein the fourth layer
comprises an adherent polyethylene or ethylene-vinyl acetate
copolymer, and the fifth layer comprises linear low-density
polyethylene or low-density polyethylene.
7. A sealant film as defined in claim 5 or 6 wherein the fourth
layer has a thickness of 5 to 25 .mu.m, and the fifth layer has a
thickness of 10 to 40 .mu.m.
8. A sealant film as defined in any one of claims 1 to 7 wherein
the film is 50 to 80 .mu.m in overall thickness.
9. A film for medical containers which comprises as the innermost
layer of a film for a medical container a sealant film defined in
any one of claims 1 to 8.
10. A film for packaging medical containers which comprises as the
innermost layer of a film for packaging a sealant film defined in
any one of claims 1 to 8.
11. A film for covering medical containers which comprises at the
innermost layer of a film for a cover a sealant film as defined in
any one of claims 1 to 8.
12. A product formed from a film as defined in claim 9, 10 or
11.
13. A method of producing a medical multilayer sealant film
employing a co-extrusion inflation process, the medical multilayer
sealant film having, as the innermost layer, a first layer
comprising at least one resin selected from the group consisting of
linear low-density polyethylene, low-density polyethylene,
polypropylene and polybutene-1, and the sealant film being
characterized in that a third layer comprising an ethylene-vinyl
alcohol copolymer is laminated to the outer side of the first layer
with a second layer serving as an adhesive layer and comprising a
resin containing, as a main component, at least one of an amorphous
polyolefin, adherent polyolefin and ethylene-vinyl acetate
copolymer, wherein the difference in density between the resin used
for forming the first layer and the resin used for forming the
second layer is 0.02 g/cm or less, and wherein the lay flat width
of the film is set to be 420 mm-1100 mm and the film take-off speed
is set to be 7.0-15.0 m/min during formation of the film
Description
TECHNICAL FIELD
[0001] The present invention relates to medical multilayer sealant
films, and more particularly to a medical multilayer sealant film
which is useful as a material for forming the innermost layer of
films for medical containers, medical container packaging films and
medical container covering films and methods for preparing the
same.
BACKGROUND ART
[0002] From the viewpoint of preventing deterioration of medicinals
or breakage of containers and ensuring see-through properties,
single-layer films or multilayered films which are excellent in gas
barrier properties, moisture impermeability, heat resistance,
impact resistance and transparency have heretofore been used
generally as plastic film materials, for example, for making
medical containers, packaging medical containers or covering
medical containers. These film materials include as a component a
base film. Examples of resin material for the base film is, for
example, nylon, polyethylene terephthalate, polyvinyl alcohol or
the like.
[0003] Further in order to give improved heat-sealing properties,
it has been practice to laminate a sealant film to the base film of
the film material with a silicone, epoxy, urethane, urethane-epoxy,
acryl or like adhesive. Chiefly used as the sealant film in this
case is a film of resin having a low melting point and low density,
such as low-density polyethylene. Such a resin film affords a high
heat-sealing strength, permits sealing at a low temperature, gives
a specified heat-sealing strength despite adhesion of dust or the
like, and is therefore excellent in quality and properties as a
sealant film.
[0004] With the film material comprising the base film, adhesive
layer and sealant film, the base film and the adhesive often
contain contaminants.
[0005] These contaminants and causes for contamination are as
follows.
[0006] (1) Various additives added to the material to be formed
into the base film for giving improved properties to the film. Such
additives are phthalic acid esters [(such as dioctyl phthalate
(DOP), di-n-butyl phthalate (DNBP), diethyl phthalate (DEP),
diethylhexyl phthalate (DEHP)], chlorinated paraffin, adipic acid
esters, fatty acid amide, phosphorus derivatives antioxidants,
phenol derivatives antioxidants, etc.
[0007] (2) It is likely that the extruder die will be coated with a
rust inhibitor or release agent (such as silicone oil). The rust
inhibitor or release agent adheres to and contaminates the base
film when it is formed.
[0008] (3) Contamination due to adhesion of the contaminant or
contaminant-containing water to the outer surface of the base
film.
[0009] (4) In the case where the base film contains nylon resin,
adipic acid or caprolactam as a component of the nylon resin.
[0010] (5) A reaction product present in the adhesive.
[0011] The sealant film providing the innermost layer of the film
material conventionally available has no barrier properties to
these contaminants, so that if the base film and/or the adhesive
contains the contaminant, the contaminant migrates to the inside of
the innermost layer through the adhesive layer and the sealant
film.
[0012] Accordingly, the products prepared from the film material,
such as medical containers, medical container packaging bags or
medical container covers, are unable to protect the contents, such
as medicinals, from contamination with contaminants.
[0013] Further if the medicinal is contaminated with contaminants,
decomposition of the medicinal, a change in its appearance,
deterioration or like problem is likely to arise.
DISCLOSURE OF THE INVENTION
[0014] An object of the present invention is to provide a
formability-improved medical multilayer sealant film having
excellent heat-sealing properties and barrier properties to the
foregoing contaminants.
[0015] Another object of the invention is to provide contamination
preventing film for medical containers, medical container packaging
film and medical container covering film which include the sealant
film as the innermost layer.
[0016] Still another object of the invention is to provide
contamination preventing products, such as a medical container, a
medical container packaging bag (hereinafter referred to as a
"packaging bag") and a medical container cover (hereinafter
referred to as a "cover"), which include the sealant film as the
innermost layer.
[0017] Still another object of the invention is to provide a highly
productive method of producing the above multilayer sealant film of
high quality.
[0018] Other features of the present invention will be clarified by
the following description.
[0019] The present invention provides a medical multilayer sealant
film which is a multilayer sealant film having as the innermost
layer a first layer comprising at least one resin selected from the
group consisting of linear low-density polyethylene, low-density
polyethylene, polypropylene and polybutene-1, the sealant film
being characterized in that a third layer comprising an
ethylene-vinyl alcohol copolymer is laminated to the outer side of
the first layer with a second layer serving as an adhesive layer
and comprising a resin containing, as a main component, at least
one of an amorphous polyolefin, adherent polyolefin and
ethylene-vinyl acetate copolymer, and in that the difference in
density between the resin constituting the first layer and the
resin constituting the second layer is 0.02 g/cm.sup.3 or less.
[0020] Still further, the present invention provides a method of
producing a medical multilayer, wherein a co-extrusion inflation
process is used to produce the above constructed multilayer sealant
film, and wherein the lay flat width of the film is set to be 420
mm-1100 mm and the film take-off speed is set to be 7.0-15.0 m/min
when forming the film.
[0021] The sealant film of the present invention may comprise, in
addition to the three-layer structure of the first to third layers,
a fourth layer and a fifth layer successively formed over the outer
side of the third layer constituting the outermost layer of the
structure.
[0022] In this case, the resin mentioned for the second layer is
used for forming the fourth layer, and the resin mentioned for the
first layer is used for forming the fifth layer, and the difference
in density between both resins needs to be 0.02 g/cm.sup.3 or
less.
[0023] The sealant film of the present invention is usable for
forming the innermost layer of films for medical containers,
medical container packaging films and medical container covering
films.
[0024] The term "films for medical containers" as used herein
refers to films for use in forming medical containers.
[0025] The term "medical container packaging films" refers to films
for forming packaging bags which wraps and seals off a medical
container entirely (hereinafter referred to as "packaging
films").
[0026] The term "medical container covering films" refers to films
for forming a cover which wraps in at least one compartment of a
medical container locally adheres to the container (hereinafter
referred to as "covering films").
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] FIG. 1 is a sectional view showing a medical multilayer
sealant film of the three-layer type according to the
invention.
[0028] FIG. 2 is a sectional view showing a medical multilayer
sealant film of the five-layer type according to the invention.
[0029] FIG. 3 is a view in vertical section showing an example of
medical container formed from a film including a sealant film of
the invention.
[0030] FIG. 4 is a view in vertical section showing an example of
packaging bag prepared from a like film.
[0031] FIG. 5 is a view in vertical section showing another example
prepared from the same film.
[0032] FIG. 6 is a view in vertical section showing an example of
cover prepared from a like film.
[0033] FIG. 7 is a view in vertical section showing the sealant
film of the invention as locally adhered to the base film of a
packaging film or covering film.
BEST MODE OF CARRYING OUT THE INVENTION
[0034] Embodiments of the present invention will be described below
with reference to the accompanying drawings.
[0035] FIG. 1 shows an example of medical multilayer sealant film
having a three-layer structure and embodying the present
invention.
[0036] A first layer 1 providing the innermost layer has desirable
heat-sealing properties and is made from at least one resin
selected from the group consisting of linear low-density
polyethylene, low-density polyethylene, polypropylene and
polybutene-1. Among these, linear low-density polyethylene or
low-density polyethylene is preferable.
[0037] The first layer 1 may comprise a mixture of at least two
resins which are different in miscibility.
[0038] To be suitable, the preferred density of the resin to be
used for forming the first layer 1 is 0.895-0.945 g/cm.sup.3, for
example.
[0039] The thickness of the first layer 1 is at least 10 .mu.m, and
is suitably determined preferably from the range of about 10 to
about 40 .mu.m.
[0040] To prevent contaminants from migrating from outside toward
the innermost layer (first layer), a third layer 3 having barrier
properties to contaminants is formed over the outer side of the
first layer 1 with a second layer 2 interposed therebetween.
[0041] The third layer 3 is made from an ethylene-vinyl alcohol
copolymer (also termed saponified ethylene-vinyl acetate copolymer)
having barrier properties to contaminants. It is suitable that the
thickness of this layer be at least 10 .mu.m, preferably about 10
to about 25 .mu.m. The ethylene copolymerization mole ratio of the
resin can be selected from a wide range, and is preferably 29 to
44% in view of flexibility, barrier properties to contaminants,
etc.
[0042] Although the ethylene-vinyl alcohol copolymer for forming
the third layer 3 can be made into a two-layer film along with the
first layer 1 by co-extrusion, this method is not desirable since
the resulting film is much inferior to usual co-extruded films in
interlaminar strength. According to the invention, therefore, the
second layer 2 which is highly adherent to the third layer 3 and
the first layer 1 (innermost layer) is provided between the two
layers.
[0043] The second layer 2 comprises a resin containing, as a main
component, at least one of an amorphous polyolefin, adherent
polyolefin, and ethylene-vinyl acetate copolymer which is improved
in adhesion when required, and is preferably 5 to 25 .mu.m, more
preferably 5 to 15 .mu.m, in thickness.
[0044] The amorphous polyolefin to be used for forming the second
layer 2 is, for example, an ethylene-.alpha.-olefin copolymer
(hereinafter referred to as an "amorphous polyethylene") having a
density of 0.880 to 0.890 g/cm.sup.3, propylene-.alpha.-olefin
copolymer (hereinafter referred to as an "amorphous polypropylene")
having a density of 0.880 3 to 0.890 g/cm.sup.3, or the like. Among
these, the amorphous polyethylene is desirable. Examples of the
.alpha.-olefins are, for example propylene, 1-butene, 1-pentene,
1-hexene, 4-methyl-1-pentene, 1-heptene, 1-octene, 1-nonene,
1-decene, 1-undecene, 1-dodecene and the like which have 3 to 12
carbon atoms. Among these, 1-butene is desirable for forming the
copolymer. However, propylene is excluded in the case of
propylene-.pi.-olefin copolymer.
[0045] The adherent polyolefin is prepared by graft-polymerizing
maleic acid with polyethylene, polypropylene or like polyolefin and
improved in adhesion. Examples of such polyolefins are adherent
polyethylene, adherent polypropylene, etc., among which adherent
polyethylene is preferred.
[0046] The ethylene-vinyl acetate copolymer exhibits good adhesion
or poor adhesion depending on the ethylene copolymerization mole
ratio of the resin. The copolymer is used as it is in the former
case, whereas in the latter case, maleic acid is graft-polymerized
with the copolymer to impart improved adhesion.
[0047] The densities of the adherent polyolefin and the
adhesion-improved ethylene-vinyl acetate copolymer are
approximately 0.890-0.945 g/cm.sup.3. If there is too great a
difference in density between the resin used for forming the first
layer and the resin used for forming the second layer, the
formability decreases. Accordingly, the density difference
therebetween needs to be 0.02 g/cm.sup.3 or less. For the purpose
of adjusting the resin densities, the resin used for forming the
first layer or high density polyethylene may be added to the resin
used for forming the second layer.
[0048] The first layer 1 and the second layer 2 are formed inwardly
of the third layer 3 having barrier properties to contaminants and
are therefore undesirable if containing contaminants. Accordingly,
the foregoing resins for forming the first layer 1 and the second
layer 2 are used without adding thereto additives which will become
contaminants.
[0049] The third layer 3 is formed also without using any additive,
so that no additive migrates from the third layer 3 inward.
[0050] It is required that the medical multilayer sealant film of
the present invention at least have a three-layer structure
comprising the first layer 1 (innermost layer), second layer 2 and
third layer 3 as shown in FIG. 1. Another layer can be laminated to
the outer side of the third layer 3 when so required.
[0051] A suitable known plastic resin layer can be selected for use
as the other layer in this case. Presence of a contaminant in this
layer poses no particular problem.
[0052] To retain transparency and flexibility of the sealant film
of the invention, it is desired to laminate as the other layer a
fifth layer 5 which comprises at least one resin selected from the
group consisting of linear low-density polyethylene, low-density
polyethylene, polypropylene and polybutene-1 using a fourth layer 4
serving as an adhesive layer and comprising an amorphous
polyolefin, adherent polyolefin, or ethylene-vinyl acetate
copolymer which is improved in adhesion when required, as seen in
FIG. 2. In this case, the difference in density between the resins
for the forth and fifth layers is set to be 0.02 g/cm.sup.3 or less
from the view point of formability. The thickness of the fourth
layer 4 is suitably selected from the range preferably of 5 to 25
.mu.m, more preferably of 5 to 15 .mu.m. The thickness of the fifth
layer 5 is suitably selected from the range preferably of 10 to 40
.mu.m, more preferably of 10 to 20 .mu.m.
[0053] The overall thickness of the medical multilayer sealant film
of the type shown in FIG. 1, as well as of the type shown in FIG.
2, is suitably selected from the range of 50 to 80 .mu.m.
[0054] In order to realize high productivity, the multilayer
sealant film of the present invention is formed by using a
water-cooled or air-cooled co-extrusion inflation process.
[0055] According to the present invention, since the difference in
density between the resins for forming the first and second layers
is small, i.e., 0.02 g/cm.sup.3 or less, whereby the formability of
the multilayer film is improved. Accordingly, it is possible to
increase the lay flat width of the film, during formation, up to
420-1100 mm, and also it is possible to maintain the film take-off
speed at a relatively high, i.e., 7.0-15.0 rm/min during formation
of the film, thereby producing the above-mentioned multilayer
sealant film with high productivity. Further, because of the
improved formability, the resultant product has no wrinkle and
therefore has high quality.
[0056] A film for medical containers, packaging film or covering
film is obtained by laminating a base film to the outer layer of
the present sealant film.
[0057] The sealant film of the invention can be laminated to the
base film by dry lamination or wet lamination. Further in the case
where the outermost layer of the present sealant film has
heat-sealing properties, and the innermost layer of the base film
has heat-sealing properties, heat-sealing means may be used for
adhering the films.
[0058] When the above-mentioned films are formed into suitable
shapes in the usual manner, various products are available which
include medical containers, packaging bags and covers like the
examples shown in FIGS. 3 to 6.
[0059] FIG. 3 shows a medical container film prepared by laminating
a sealant film A of the invention to a base film B, and a medical
container a formed from the film. Various known films for use in
making medical containers are usable as the base film B.
[0060] FIGS. 4 and 5 show a packaging film with the invention
sealant film A laminated to the base film B.sub.1 and packaging
bags b formed from the film. Medical containers a.sub.1, a.sub.2
are enclosed in the respective bags b. FIG. 5 shows a
double-chamber container a.sub.2 as enclosed in a folded state.
[0061] In the case where the medicinals within the medical
containers a.sub.1 and a.sub.2 are very susceptible to degradation
due to oxygen and moisture, the base film B.sub.1 to be used for
forming the packaging bags b needs to be film having gas barrier
properties and moisture impermeability to preclude the degradation
of the medicinals in the containers a.sub.1 and a.sub.2.
[0062] Usable as the base film B.sub.1 having high gas barrier
properties and moisture impermeability is a composite film
comprising a polyolefin film and aluminum foil laminated thereto
and impervious to oxygen and water vapor, a single or multi-layered
resin film material comprising polyethylene terephthalate (PET),
polyvinylidene chloride, polyvinyl alcohol, polyamide,
ethylene-vinyl acetate copolymer as saponified or the like, or a
laminated film material of the resin film and the above composite
film.
[0063] Other materials favorably usable include a composite film
which comprises a polyvinyl alcohol film, polyethylene
terephthalate film or saponified ethylene-vinyl acetate copolymer
film, and a silicon oxide layer formed on the film by vacuum
deposition.
[0064] Given below are examples of multilayer films comprising such
a composite film.
[0065] (I) A multilayer film comprising a composite film prepared
by forming a silicon oxide layer on a polyvinyl alcohol film by
vacuum deposition, and a PET film (outermost layer) formed on the
silicon oxide layer of the composite film by dry lamination.
[0066] (II) A multilayer film which comprises a composite film
prepared by forming a silicon oxide layer on a polyvinyl alcohol
film by vacuum deposition, and the multilayer film (I) and which is
prepared by dry lamination with the polyvinyl alcohol film of the
film (I) superposed on the silicon oxide layer of the composite
film.
[0067] The packaging bag b is used also for protecting the medical
container a.sub.1 or a.sub.2 from an external impact. Used as the
base film B.sub.1 in this case is a single-layer or multilayer film
material which includes as a component a film of PET, nylon,
polyethylene, polypropylene or the like having a high impact
strength.
[0068] FIG. 6 shows a covering film which comprises the sealant
film A of the invention and a base film B.sub.2 laminated thereto,
and a cover c formed from the covering film and enclosing one
chamber of the double-chamber container a.sub.2 therewith.
[0069] The cover c is used for the same purpose as the. packaging
bag b, so that like the base films B.sub.1, B.sub.2 to be used is a
film material having high gas barrier properties and moisture
impermeability.
[0070] For use in the packaging film or the covering film, the
sealant film A is adhered to the base film B.sub.1 or B.sub.2 over
the entire surface thereof as seen in FIGS. 4 to 6, or locally
thereto so as to provide a space between the base film B.sub.1 or
B.sub.2 and the film A as shown in FIG. 7.
[0071] Although the sealant film, medical containers, packaging
bags and cover embodying the invention are herein described with
reference to FIGS. 1 to 7, the mode of practicing the invention as
these embodiments, the shape or size thereof, etc. are in no way
limited but the invention can of course be embodied variously
without departing from the principle feature of the invention.
[0072] The present invention provides products made from a film
material comprising the sealant film of the invention and a base
film laminated to the outer layer thereof, i.e., medical
containers, packaging bags and covers, such as those shown in FIGS.
3 to 6. The sealant film has barrier properties to contaminants and
therefore eliminates the likelihood that the contaminants present
in the base film and/or those from outside will penetrate into the
medical container to prevent the contaminants from contaminating
the medicinal.
[0073] The medical containers shown in FIGS. 3 to 6 are used for
containing common medicinals, which may be powder preparations,
liquid preparations or solid preparations.
[0074] Examples of powder preparations include antibiotics,
anticancer agents, proteins, peptides, steroids, fibrinolytic
agents and vitamins. Examples of antibiotics are cephazolin,
.beta.-lactam type such as ampicillin, carbapenem type such as
imipenem, aminoglycoside type such as kanamycin, polypeptide type
such as vancomycin and macrolide type such as erythromycin.
Examples of liquid preparations are physiological saline, glucose
solution, distilled water for injection, electrolytic solutions,
amino acid solutions, fat emulsions, etc.
[0075] Incidentally, the powder preparations such as antibiotics
among the above-mentioned medicinals are necessary to be dissolved
in the physiological saline or the glucose solution for injection
into a patient when being used. Therefore, there has been recently
developed a multi-compartment container having two compartments as
shown in FIGS. 6 in order to render their operations simple.
[0076] FIGS. 6 shows multi-compartment container. The upper
compartment thereof accommodates an antibiotic easy to be adversely
affected by even a little amount of contaminants, and the lower
compartment accommodates a solvent such as physiological saline or
glucose solution. Only the upper compartment is double-covered with
the cover.
[0077] Embodiments of the invention and comparative examples will
be described below, followed by a test example wherein they were
used.
[0078] [Embodiment 1] (FIG. 1 type) Using a water-cooled
co-extrusion inflation machine, a sealant film was prepared which
had a three-layer structure comprising an outermost layer, i.e., a
15-.mu.m-thick third layer of ethylene-vinyl alcohol copolymer
(manufactured by Nihon Goseikagaku Co., Ltd., brand name: SOANOL,
44% in ethylene copolymerization mole ratio, hereinafter referred
to as "EVOH (1)"), an intermediate layer, i.e., a 10-.mu.m-thick
second layer of adherent polyethylene (manufactured by Mitsui
Petrochemical Industries, Ltd., brand name: ADMER, 0.940 g/cm.sup.3
in density, hereinafter referred to as "PE (.sub.1)"), and an
innermost layer, i.e., a 40-.mu.m-thick first layer of linear
low-density polyethylene (manufactured by Mitsui Petrochemical
Industries, Ltd., brand name: ultzex, 0.940 g/cm.sup.3 in density,
hereinafter referred to as "L-LDPE (1)"). In the same manner as in
Embodiment 1, the sealant films of Embodiments 2 to 8 and
Comparative Example 1 were formed.
[0079] [Embodiment 2] (FIG. 1 type)
[0080] Third layer (outermost layer): EVOH (1), 15 .mu.m in
thickness
[0081] Second layer (intermediate layer): PE(1), 0.940 g/cm.sup.3
in density and 10 .mu.m in thickness
[0082] First layer (innermost layer): linear low-density
polyethylene (manufactured by Mitsui Petrochemical Industries,
Ltd., brand name: ultzex), 0.930 g/cm.sup.3 in density and 40 .mu.m
in thickness
[0083] [Embodiment 3] (FIG. 1 type)
[0084] Third layer (outermost layer): EVOH (1), 15 .mu.m in
thickness
[0085] Second layer (intermediate layer): PE(1), 0.940 g/cm.sup.3
and 10 .mu.m in thickness
[0086] First layer (innermost layer): linear low-density
polyethylene (manufactured by Mitsui Petrochemical Industries,
Ltd., brand name: ultzex), 0.920 g/cm.sup.3 in density and 40 .mu.m
in thickness
[0087] [Embodiment 4] (FIG. 1 type)
[0088] Third layer (outermost layer): EVOH (1), 15 .mu.m in
thickness
[0089] Second layer (intermediate layer): adherent polypropylene
(manufactured by Mitsui Petrochemical Industries, Ltd., brand name:
ADMER), 0.910 g/cm and 10 .mu.m in thickness
[0090] First layer (innermost layer): polypropylene (manufactured
by Mitsui Petrochemical Industries, Ltd. and sold by Grand Polymer,
Ltd., brand name: HIPOL), 0.910 g/cm.sup.3 in density and 40 .mu.m
in thickness
[0091] [Embodiment 5] (FIG. 1 type)
[0092] Third layer (outermost layer): EVOH (manufactured by Nihon
Goseikagaku Co., Ltd., brand name: SOANOL, 38% in ethylene
copolymerization mole ratio, hereinafter referred to as "EVOH
(2)"), 15 .mu.m in thickness
[0093] Second layer (intermediate layer): adherent polyethylene
(manufactured by Mitsui Petrochemical Industries, Ltd., brand name:
ADMER, 0.930 g/cm.sup.3 in density)+amorphous polyethylene
(manufactured by Mitsui Petrochemical Industries, Ltd., brand name:
TAFMER A, 0.880 g/cm.sup.3 in density), 0.9125 g/cm.sup.3 in
density and 10 .mu.m in thickness
[0094] First layer (innermost layer): linear low-density
polyethylene (manufactured by Mitsui Petrochemical Industries,
Ltd., brand name: ultzex, 0.940 g/cm.sup.3 in
density)+polypropylene (manufactured by Mitsui Petrochemical
Industries, Ltd. and sold by Grand Polymer, Ltd., brand name:
HIPOL, 0.910 g/cm.sup.3 in density), 0.925 g/cm.sup.3 in density
and 40 .mu.m in thickness
[0095] [Embodiment 6] (FIG. 1 type)
[0096] Third layer (outermost layer): EVOH (manufactured by Kuraray
Co., Ltd., brand name: EVAL type-F, 32% in ethylene
copolymerization mole ratio, hereinafter referred to as "EVOH
(3)"), 15 .mu.m in thickness
[0097] Second layer (intermediate layer): adherent ethylene-vinyl
acetate copolymer (manufactured by Mitsui Petrochemical Industries,
Ltd., brand name: ADMER), 0.908 g/cm.sup.3 in density and 10 .mu.m
in thickness
[0098] First layer (innermost layer): low-density polyethylene
(manufactured by Mitsui Petrochemical Industries, Ltd., brand name:
MIRASON), 0.908 g/cm.sup.3 in density and 40 .mu.m in thickness
[0099] [Embodiment 7] (FIG. 1 type)
[0100] Third layer (outermost layer): EVOH (3), 10 .mu.m in
thickness
[0101] Second layer (intermediate layer): adherent polypropylene
(manufactured by Mitsui Petrochemical Industries, Ltd., brand name:
ADMER, 0.910 g/cm in density)+amorphous polyolefin (manufactured by
Mitsui Petrochemical Industries, Ltd., brand name: TAFMER, 0.890
g/cm.sup.3 in density), 0.909 g/cm.sup.3 in density and 10 .mu.m in
thickness First layer (innermost layer): polypropylene
(manufactured by Mitsui Petrochemical Industries, Ltd. and sold by
Grand Polymer, Ltd., brand name: HIPOL), 0.910 g/cm.sup.3 in
density and 40 .mu.m in thickness
[0102] [Embodiment 8]
[0103] Third layer (outermost layer): EVOH (manufactured by Kuraray
Co., Ltd., brand name: EVAL, 44% in ethylene copolymerization mole
ratio, hereinafter referred to as "EVOH (4)"), 10 .mu.m in
thickness Second layer (intermediate layer): the same as in
Embodiment 7, 0.909 g/cm3 in density and 20 .mu.m in thickness
[0104] First layer (innermost layer): the same as in Embodiment 7,
0.910 g/cm.sup.3 in density and 40 .mu.m in thickness
COMPARATIVE EXAMPLE 1
[0105] Single Layer (sealant film): L-LDPE (1), 50 .mu.m in
Thickness
[0106] The films of Embodiments 1 to 8 were prepared by
water-cooled co-extrusion inflation with a flat width of 420 mm
(Ex. 1), 450 mm (Ex. 2), 500 mm (Ex. 3), 540 mm (Ex. 4), 680 mm
(Ex. 5), 800 mm (Ex. 6), 1080 mm (Ex. 7) and 1100 mm (Ex. 8) and
Comparative Example 1 were prepared by water-cooled co-extrusion
inflation with a flat width of 540 mm. The film take-off speed for
Embodiments 1, 2 and 7, and Comparative Example 1 was 7 to 10
m/min, and the film take-off speed for Embodiments 3 to 6 and 8 was
9 to 15 m/min.
EXPERIMENTAL EXAMPLE
[0107] The base film X stated blow was united to the sealant films
of Embodiments 1-8 over the outer layer thereof by dry lamination
to obtain films as Embodiments 1X -8X.
[0108] The base film Y given below was united to the sealant films
of Embodiment 1 and Comparative Example 1 over the outer layer
thereof to obtain films as Embodiment 1Y and Comparative Example
1Y. (The dry lamination process was used for Embodiment 1, and
heat-sealing means for Comparative Example 1.)
[0109] The base film Z given below was laminated to the sealant
film of Comparative Example 1 by heatsealing means to obtain a film
as Comparative Example 1Z
[0110] X. L-LDPE (1), 300 .mu.m in thickness
[0111] Y. Oriented nylon (ONy), 15 .mu.m/urethane-epoxy resin
(adhesive)/low-density polyethylene (LDPE), 40 .mu.m in
thickness
[0112] Z. Polyethylene terephthalate (PET), 12 .mu.m/urethane-epoxy
resin (adhesive)/(LDPE), 50 .mu.m in thickness
[0113] When the sealant film of the invention is laminated to the
base films X and Y. the film surfaces to be united are treated by
corona discharge first and then subjected to the usual dry
lamination process.
[0114] The oriented nylon (ONy) film, polyethylene terephthalate
(PET) film and low-density polyethylene (LDPE) film for
constituting the base films, and the urethane-epoxy resin
(adhesive) for use in dry lamination were all those generally
available commercially.
[0115] The films of Embodiments 1X-8X, Embodiment 1Y, Comparative
Example 1Y and Comparative Example 1Z were used for making medical
containers wherein the sealant film served as the innermost layer,
and the containers were tested by the following contamination
experiments.
[0116] Contamination Experiment 1: DOP, di-n-butyl phthalate (DNBP)
and diethyl phthalate (DEP) used as contaminants were applied by
coating or spraying to the outer surface of the medical container
(externally measuring 10 cm.times.10 cm) which was filled with 1 g
(potency) of cephazolin sodium (CEZ), and thereafter preserved at
40.degree. C. and 75% RH (relative humidity) for 3 months. The CEZ
filled in was checked for the migration of the contaminants by GLC
(Gas Liquid Chromatography) and the GC-MS (Gas Liquid
chromatography-Mass Spectrography) method.
[0117] Contamination Experiment 2: After a die rust inhibitor (KG
type, manufactured by Kobe Gosei Co., Ltd.) was sprayed onto the
outer surface of the medical container as filled with 1 g (potency)
of CEZ, it was preserved under the condition of 40.degree. C. in
temperature and 75% in RH for two weeks. Then, it was checked
whether contaminants were migrated into the filled CEZ by GLC and
the GC-MS method.
[0118] Contaminant Extraction Method and Extract Analysis
Method:
[0119] Special-grade n-hexane (manufactured by Wako Junyaku Co.,
Ltd.) was purified by distillation to remove the influence of DOP
or DNBP present in the reagent. The CEZ contained was first fully
dissolved in 10 to 20 ml of purified ultrapure water (manufactured
by Millipore limited, brand name: MILLIQ), and the solution was
placed into a separating funnel washed with a sufficient amount of
purified ultrapure water. After purified ultrapure water was
further added to the solution to a combined amount of 150 ml, 150
ml of the purified n-hexane was further added. The contaminants
were allowed to fully migrate into the n-hexane fraction. The
n-hexane fraction was concentrated to 10 ml, and a portion thereof
was subjected to GLC analysis under the conditions given below.
[0120] The remaining n-hexane fraction was concentrated again to
dryness, resulting solid was dissolved again in 0.2 ml of n-hexane
as purified by distillation, and the solution was subjected to the
GC-MS method to be described below.
[0121] Tables 1 and 2 show the results of these analyses.
[0122] The sealant film used for comparative examples, i.e., the
single-layer film of L-LDPE (1), was checked for contamination by
cutting out a piece approximately 1 cm square from the film,
subjecting 2 g of the piece to extraction with 150 ml of n-hexane
as purified by distillation, concentrating the extract to dryness
and dissolving again the dry solid in the n-hexane purified by
distillation and analyzing it by GLC and the GC-MS method, whereby
the film was found totally free from any contaminants.
[0123] (Devices Used)
[0124] Products of Hewlett-Packard Co.
[0125] HP5890 Series II gas chromatograph
[0126] HP3396 Series II integrator
[0127] HP7673 Controller
[0128] (Analysis Conditions)
[0129] The conditions for gas chromatographic analysis were as
follows.
[0130] Column: Ultra Alloy (HT) 30 m.times.0.25 mm ID.times.0.25
.mu.m
[0131] Column temp.: 60.degree. C..fwdarw.10.degree. C./min temp.
rise.fwdarw.300.degree. C.
[0132] Column flow rate: 1.30 ml/min
[0133] Carrier gas: He 4.0 kg/cm
[0134] Inlet temp.: 200.degree. C.
[0135] Detector: FID
[0136] Detector temp.: 310.degree. C.
[0137] Sensitivity: RANGE=0 ATT=0
[0138] Injection method: Splitless high-pressure injection
[0139] Inlet pressure: 30 psi (0 min)-99 psi/min-20 psi (constant
flow)
[0140] Spit ratio: 38:1
[0141] Amount injected: 1 .mu.l of solution
[0142] (Measuring Conditions) GC-MS
[0143] Device: HP-5890/5971A-GC-MS (manufactured by Hewlett-Packard
Co., LTD.)
[0144] Column: J & W DB-1.times.30 m.times.0.25 mm.times.0.25
.mu.m
[0145] Column temp.: 100.degree. C. -10.degree. C./min -280.degree.
C.
[0146] Inlet temp.: 280.degree. C.
[0147] Detector temp.: 280.degree. C.
[0148] Detector: MSD
[0149] Amount injected: 2 pl, splitless
1TABLE 1 Result of Contamination Experiment 1 DOP DNBP DEP CAP EPO
Embodiment 1X GLC - - - - - GC-MS - - - - - Embodiment 2X GLC - - -
- - GC-MS - - - - - Embodiment 3X GLC - - - - - GC-MS - - - - -
Embodiment 4X GLC - - - - - GC-MS - - - - - Embodiment 5X GLC - - -
- - GC-MS - - - - - Embodiment 6X GLC - - - - - GC-MS - - - - -
Embodiment 7X GLC - - - - - GC-MS - - - - - Embodiment 8X GLC - - -
- - GC-MS - - - - - Embodiment 1Y GLC - - - - - GC-MS - - - - -
Comp. Ex. 1Y GLC 0 0 0 0 0 GC-MS 0 0 0 0 0 Comp. Ex. 1Z GLC 0 0 0 -
0 GC-MS 0 0 0 - 0
[0150]
2TABLE 2 Result of Contamination Experiment 2 RUST INHIBITOR CAP
EOP Embodiment 1X GLC - - - GC-MS - - - Embodiment 2X GLC - - -
GC-MS - - - Embodiment 3X GLC - - - GC-MS - - - Embodiment 4X GLC -
- - GC-MS - - - Embodiment 5X GLC - - - GC-MS - - - Embodiment 6X
GLC - - - GC-MS - - - Embodiment 7X GLC - - - GC-MS - - -
Embodiment 8X GLC - - - GC-MS - - - Embodiment 1Y GLC - - - GC-MS -
- - Comp. Ex. 1Y GLC 0 0 0 GC-MS 0 0 0 Comp. Ex. 1Z GLC 0 - 0 GC-MS
0 - 0
[0151] CAP: Caprolactam, EPO: epoxy compound
[0152] Rust inhibitor components: The peak obtained by analyzing
the inhibitor alone is compared with the retention time of fragment
data. Meanings of the symbols in Tables 1 and 2:
[0153] The contaminants were not recognized.
[0154] The analysis gave a peak having the same retention time as
an authentic substance corresponding to the contaminant, or data of
the same fragment as the authentic substance corresponding to the
contaminant.
[0155] The present invention provides medical multilayer sealant
films retaining satisfactory heat-sealing properties. Use of films
including the sealant film affords medical containers, packaging
bags and covers which effectively prevent contamination.
[0156] Further, although the sealant film obtained according to the
above forming method has an increased lay flat width of 420 mm, 450
mm, 500 mm, 540 mm, 680 mm, 800 mm, 1080 mm and 1100 mm and the
film take-off speed is set to be relatively high, i.e., 7-15 m/min,
there occurs no wrinkle in the obtained film at all, thereby
obtaining improved film formability.
* * * * *