U.S. patent application number 11/008119 was filed with the patent office on 2005-06-16 for medical freezer bag.
Invention is credited to Akimoto, Yoshiyuki, Sasaki, Yuji, Shirasu, Akio, Takeda, Kazuyuki, Wada, Seiichi, Yoshikawa, Yoshihiro.
Application Number | 20050129887 11/008119 |
Document ID | / |
Family ID | 34510564 |
Filed Date | 2005-06-16 |
United States Patent
Application |
20050129887 |
Kind Code |
A1 |
Yoshikawa, Yoshihiro ; et
al. |
June 16, 2005 |
Medical freezer bag
Abstract
A medical freezer bag having a sufficient strength, which is not
damaged at -196.degree. C., the temperature of liquid nitrogen, and
is excellent in low temperature resistance and molding
processability, and whole blood, body fluids, and cell suspensions
can be aseptically or nontoxically preserved at extremely low
temperatures, is provided. The freezer bag is made from a
three-layer film where both sides of an ultra-high molecular weight
polyethylene film are welded respectively with a thermoplastic
resin film having a lower melting point than that of the ultra-high
molecular weight polyethylene and having compatibility with the
ultra-high molecular weight polyethylene.
Inventors: |
Yoshikawa, Yoshihiro;
(Osaka, JP) ; Shirasu, Akio; (Osaka, JP) ;
Wada, Seiichi; (Osaka, JP) ; Akimoto, Yoshiyuki;
(Osaka, JP) ; Sasaki, Yuji; (Osaka, JP) ;
Takeda, Kazuyuki; (Osaka, JP) |
Correspondence
Address: |
KUBOVCIK & KUBOVCIK
SUITE 710
900 17TH STREET NW
WASHINGTON
DC
20006
|
Family ID: |
34510564 |
Appl. No.: |
11/008119 |
Filed: |
December 10, 2004 |
Current U.S.
Class: |
428/35.4 ;
428/35.2 |
Current CPC
Class: |
B32B 27/32 20130101;
B32B 2250/03 20130101; B32B 7/02 20130101; Y10T 428/1341 20150115;
B32B 27/08 20130101; B32B 2439/80 20130101; A61J 1/10 20130101;
B32B 2323/04 20130101; Y10T 428/1334 20150115 |
Class at
Publication: |
428/035.4 ;
428/035.2 |
International
Class: |
B65D 001/00 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 12, 2003 |
JP |
2003-414853 |
Claims
What is claimed is:
1. A medical freezer bag comprising a three-layer film where each
of both sides of an ultra-high molecular weight polyethylene film
is welded to a thermoplastic resin film having a lower melting
point than that of the ultra-high molecular weight polyethylene and
having compatibility with the ultra-high molecular weight
polyethylene.
2. The medical freezer bag according to claim 1, wherein the
thermoplastic resin is an ethylene-vinyl acetate copolymer, an
ethylene-methacrylic ester copolymer, or a linear low-density
polyethylene.
3. The medical freezer bag according to claim 1, wherein the
ultra-high molecular weight polyethylene has a measured viscometric
weight average molecular weight of 1,000,000 or more, or a weight
average molecular weight of 3,000,000 or more measured based on a
light scattering method.
4. The medical freezer bag according to claim 1, wherein the
three-layer film has a thickness of approximately 50 to 500
.mu.m.
5. The medical freezer bag according to claim 4, wherein the
three-layer film has a thickness of approximately 100 to 250
.mu.m.
6. A method of molding a medical freezer bag, characterized by
molding (1) a three-layer film obtained by welding each of both
sides of an ultra-high molecular weight polyethylene film with a
thermoplastic resin film having a lower melting point than that of
the ultra-high molecular weight polyethylene and having
compatibility with the ultra-high molecular weight polyethylene,
and (2) a port member.
7. A method of storing a medical freezer bag, characterized by
filling the medical freezer bag with blood, a body fluid, or a cell
suspension; and storing the medical freezer bag at a temperature
ranging from approximately -80 to -196.degree. C., wherein the
medical freezer bag comprises a three-layer film where each of both
sides of an ultra-high molecular weight polyethylene film is welded
to a thermoplastic resin film having a lower melting point than
that of the ultra-high molecular weight polyethylene and having
compatibility with the ultra-high molecular weight polyethylene.
Description
TECHNICAL FIELD OF THE INVENTION
[0001] The present invention relates to a medical freezer bag
including a three-layer film where both sides of an ultra-high
molecular weight polyethylene film are welded respectively, i.e.,
laminated with thermoplastic resin films having a lower melting
point than that of the ultra-high molecular weight polyethylene and
having compatibility with the ultra-high molecular weight
polyethylene.
BACKGROUND OF THE INVENTION
[0002] As a method of storing blood components in a frozen state, a
method of storing blood components at extremely low temperatures
ranging from approximately -80 to -196.degree. C. with the addition
of a freezing damage preventive agent such as dimethyl sulfoxide
has been known. Under this kind of storage at extremely low
temperatures, there is a need for a freezer bag which can be used
at extremely low temperatures and can be sterilized and is easy to
use. A soft polyvinyl chloride bag used for blood preservation
becomes brittle at -40.degree. C. and is damaged by an extremely
slight shock from the outside at extremely low temperatures.
[0003] Therefore, a bag including a laminate film composed of a
polyimide film and a fluorinated ethylene propylene polymer film
(JP Sho 49-8079 B), a bag including a copolymer film of
tetrafluoroethylene and ethylene (Japanese Utility Model Examined
Publication No. Sho 55-55069), and so on, have been proposed as
bags for storing blood components at extremely low temperatures
ranging from -80 to -196.degree. C. However, polyimide, among
polymeric materials, is one of those having the lowest thermal
conductivity. Thus, the freezing speed of the polyimide is low and
influences the quality of ingredients. Moreover, a polyimide resin
and a fluorocarbon resin have extremely high melting points. Thus,
they have poor molding processability.
[0004] Proposed as freezer bags made of resins other than polyimide
resins and fluorocarbon resins are one using a biaxially-stretched
ethylene-vinyl acetate copolymer film with electron beam
irradiation (JP Sho 55-44977 B) and one using a biaxially-stretched
cross-linked polyethylene film (JP Sho 62-57351 B). However, the
stretched film is wrinkled as the film is shrunk at a sealing
portion and at the periphery thereof by a heat-sealing operation.
In actual use, there is a disadvantage in that the bag is often
damaged through rough handling and the contents thereof cannot be
safely preserved. In addition, the above laminate film is bonded
using an adhesive agent such as a polyester-, polyurethane-, or
epoxy-based adhesive agent, so that bonded layers may be hardened
during preservation at low temperatures and thus the laminated film
may be peeled off. Therefore, it is not suitable as a freezer
bag.
[0005] An ultra-high molecular weight polyethylene is very
excellent in shock resistance, wear resistance, self-swelling
property, chemical resistance, and low temperature resistance, and
is nontoxic, but has an extremely high melt viscosity. Thus, in a
typical method of producing a film, a powdered raw material resin
is molded into a block shape by means of press-molding or the like,
followed by cutting processing. The film formed as described above
may have a rough surface, so that molding processing is by no means
carried out with ease. If there is mold flash, polyethylene may be
peeled off from the surface of the film. When the film is used as a
medical bag, the polyethylene will become the cause of
contamination with foreign matters. Besides, the process of
press-molding tends to incorporate air into the film and thus a
pinhole may be formed in the film cut in a subsequent step.
[0006] In addition, when heat sealing is made between sheets or
between a sheet and a port member, because the ultra-high molecular
weight polyethylene has a molecular weight as high as 1,000,000 or
more, it is difficult to produce tangled molecular chains because
of poor fluidity of a polyethylene molecular chain. Therefore, heat
sealing is difficult and thus there is a problem in stable
production of a bag.
SUMMARY OF THE INVENTION
[0007] Development of a medical freezer bag having excellent low
temperature resistance and molding processability has been
demanded. More specifically, there is a need for a medical freezer
bag having a sufficient strength, which is not damaged even at a
temperature of -196.degree. C., i.e., at the temperature of liquid
nitrogen.
[0008] The present invention has been made in consideration of the
conventional technology described above and relates to a medical
bag with excellent molding processability, which allows the
preservation of blood, body fluids, and cell suspensions at
extremely low temperatures without damaging the bag.
[0009] That is, the present invention relates to:
[0010] (1) a medical freezer bag comprising a three-layer film
where both sides of an ultra-high molecular weight polyethylene
film are welded respectively with a thermoplastic resin film having
a lower melting point than that of the ultra-high molecular weight
polyethylene and having compatibility with the ultra-high molecular
weight polyethylene;
[0011] (2) the medical freezer bag according to the item (1),
wherein the thermoplastic resin is an ethylene-vinyl acetate
copolymer, an ethylene-methacrylic ester copolymer, or a linear
low-density polyethylene;
[0012] (3) the medical freezer bag according to the item (1),
wherein the ultra-high molecular weight polyethylene has a measured
viscometric weight average molecular weight of 1,000,000 or more,
or a weight average molecular weight of 3,000,000 or more measured
based on a light scattering method;
[0013] (4) the medical freezer bag according to the item (1),
wherein the three-layer film has a thickness of approximately 50 to
500 .mu.m;
[0014] (5) the medical freezer bag according to the item (4),
wherein the three-layer film has a thickness of approximately 100
to 250 .mu.M;
[0015] (6) a method of molding a medical freezer bag, characterized
by molding (1) a three-layer film obtained by welding both sides of
an ultra-high molecular weight polyethylene film with thermoplastic
resin films having a lower melting point than that of the
ultra-high molecular weight polyethylene and having compatibility
with the ultra-high molecular weight polyethylene, and (2) a port
member; and
[0016] (7) a method of storing a medical freezer bag, characterized
by filling the medical freezer bag with blood, a body fluid, or a
cell suspension; and storing the medical freezer bag at extremely
low temperatures ranging from approximately -80 to -196.degree. C.,
wherein the medical freezer bag comprises a three-layer film where
both sides of an ultra-high molecular weight polyethylene film are
welded with thermoplastic resin films having a lower melting point
than that of the ultra-high molecular weight polyethylene and
having compatibility with the ultra-high molecular weight
polyethylene.
EFFECTS OF THE INVENTION
[0017] The medical freezer bag of the present invention allows the
preservation of blood, body fluids, and cell suspensions at
extremely low temperatures without damaging the bag and is
excellent in molding processability.
DETAILED DESCRIPTION OF THE INVENTION
[0018] The medical freezer bag of the present invention is a bag
for the preservation of blood, body fluids, and cell suspensions at
extremely low temperatures, characterized by including a
three-layer film composed of: an ultra-high molecular weight
polyethylene film; and thermoplastic resin films laminated on both
sides of the ultra-high molecular weight polyethylene film, the
thermoplastic resin films having a lower melting point than that of
the ultra-high molecular weight polyethylene and having
compatibility with the ultra-high molecular weight polyethylene
(hereinafter, simply referred to as a thermoplastic resin). The
total thickness of the three-layer film described above is
approximately 50 to 500 .mu.m, preferably 100 to 250 .mu.m. The
film of the medical freezer bag of the present invention may be
composed of at least the three layers as described above. If
required, an additional thermoplastic resin film may be laminated
on both sides or one side of the film.
[0019] The term "ultra-high molecular weight polyethylene" used in
the present invention means polyethylene that satisfies a
viscometric weight average molecular weight of 1,000,000 or more or
a molecular weight of 3,000,000 or more based on a light scattering
method. The upper limit is not specifically defined, but at the
present time, approximately 6,000,000 (viscometric molecular
weight) may be the upper limit attainable by a person skilled in
the art. The ultra-high molecular weight polyethylene is very
excellent in shock resistance, wear resistance, self-swelling
property, chemical resistance, and low temperature resistance, and
non-toxicity as compared with a general-purpose low-density
polyethylene and so on.
[0020] Furthermore, the ultra-high molecular weight polyethylene
film has a high viscosity due to its high molecular weight, so that
it can be molded into a block shape by subjecting a powdered raw
material resin to a press-molding process or the like and then
molded into a film shape by a cutting process. The thickness of the
film is preferably that sufficient to prevent the generation of
pinholes, retain sealing strength, and endure rapid freezing and
thawing. Specifically, the thickness of the film is preferably
about 25 to 250 .mu.m, more preferably about 50 to 150 .mu.m.
[0021] The term "thermoplastic resin film" used in the present
invention means a film which can be adhered to the ultra-high
molecular weight polyethylene film, and is improved to such a
degree that it cannot be peeled therefrom, and has excellent
molding processability. Therefore, there is selected a film having
a lower melting point than that of the ultra-high molecular weight
polyethylene (approximately 134 to 138.degree. C.) and having
compatibility with the ultra-high molecular weight polyethylene.
The term "compatibility" means a state in which a single peak of
glass transition temperature (Tg) of the ultra-high molecular
weight polyethylene and the thermoplastic resin, which is
determined by measurement with a differential scanning calorimeter
(DSC), is observed. In the case of incompatibility, plural peaks of
glass transition temperature (Tg) are observed. The thickness of
thermoplastic resin film is about 12.5 to 125 .mu.m, preferably
about 25 to 75 .mu.m.
[0022] Preferable examples of the thermoplastic resin include
low-density polyethylene and intermediate-density polyethylene, and
furthermore ethylene copolymers such as an ethylene-vinyl acetate
copolymer and an ethylene-methacrylic ester copolymer, a
thermoplastic resin composition including polyethylene and a
hydrogenerated product of styrene butadiene rubber, and a
thermoplastic resin composition of polypropylene and a
hydrogenerated product of styrene butadiene rubber. Among them, a
low-density polyethylene and ethylene-vinyl acetate copolymer are
preferable and linear low-density polyethylene is more preferable.
Here, the used density range of the low-density polyethylene is a
density range of about 0.910 to 0.925 g/cm.sup.3.
[0023] The linear low-density polyethylene can be polymerized under
moderate conditions using a catalyst such as a Ziegler-Natta
catalyst and a metallocene catalyst. The linear low-density
polyethylene has a molecular structure in which a branching
structure of general low-density polyethylene is suppressed, so
that the molded product thereof is excellent in heat sealing
strength, low temperature resistance, and stress-cracking
resistance (a property in which degradation cannot take place
easily even if it is left in the outside environment for a long
period of time). The above polyethylene is processed into the shape
of a film, after the catalyst is removed, or in a state that a
small amount of the catalyst remains therein without the removal of
the catalyst after polymerization. However, as the freezer bag of
the present invention is for medical use, it is preferable to use a
catalyst which remains in the film as little as possible.
[0024] A method of producing a three-layer film is carried out by a
thermal welding process. Specifically, the thermoplastic resin
heat-melted with a heat roller or the like is pushed out onto both
sides of the ultra-high molecular weight polyethylene film,
followed by bonding them together under pressure. The temperature
of the heat roller is preferably about 150 to 250.degree. C., more
preferably about 170 to 200.degree. C.
[0025] In a method of molding a medical freezer bag with the above
three-layer film, two sheets of the three-layer film cut into the
same dimensions are overlapped with each other such that a port
member for allowing the introduction and discharge of blood, body
fluids, or cell suspensions is sandwiched between them and the edge
portions are welded by means of heat sealing and formed into a bag
shape. At this time, the port member may be preferably provided on
a corner because the waste of blood, body fluids, or a cell
suspensions, which are valuable, can be lowered as much as
possible. Preferably, the port member is prepared using a material,
such as ultra-low-density polyethylene, which is compatible with a
thermoplastic resin film constituting an inner layer and flexible
to some extent. In addition, two or more port members may be
provided as needed.
[0026] An example of the medical freezer bag of the present
invention is formed such that a three-layer film is formed by
putting an ultra-high molecular weight polyethylene film of 75.mu.m
in thickness between linear low-density polyethylene films of 50
.mu.m in thickness and adhering the films, cutting the three-layer
film into sheets of 150.times.200 mm and then layering two sheets
of the three-layer film and subjecting their edge portions to a
heat welding process by using a heat sealing process.
[0027] Furthermore, another example of the medical freezer bag of
the present invention is formed such that a three-layer film is
prepared by forming a linear low-density polyethylene film of 75
.mu.m in thickness on one side of an ultra-high molecular weight
polyethylene film of 100 .mu.m in thickness and putting a copolymer
film of an ethylene-vinyl acetate copolymer on the other side
thereof and adhering the films, and cutting the resultant laminate
to a size of 150.times.200 mm, followed by overlapping two sheets
thereof and heat-welding their edge portions by a heat sealing
process.
[0028] The above three-layer film is formed such that the
thermoplastic resin having a low melting point is laminated on each
of both sides of the ultra-high molecular weight polyethylene, so
that the peeling of the ultra-high molecular weight polyethylene
forming a rough surface can be prevented. Furthermore, in an inner
layer, it can be processed easily and stably into a bag shape by
using a heat sealing process, etc. and is capable of preventing the
peeling of the ultra-high molecular weight polyethylene and the
contamination thereof into the blood, body fluids, or cell
suspensions. Furthermore, because the thermoplastic resin provides
a smooth surface, there is no fear that living tissues such as
blood erythrocytes and cells are damaged. Furthermore, on the outer
layer, a polyethylene label or the like is easily attached by
heat-sealing, and the contamination by foreign matter from the
outside is prevented.
[0029] The medical freezer bag of the present invention is suitable
for preserving blood components such as erythrocytes, platelets,
and plasma, a marrow liquid or such other body fluids, and cell
suspensions. Even though the medical freezer bag of the present
invention may be sustainable at extremely low temperatures from -80
to -196.degree. C., it is preferable to gradually lower the
temperature so as not to damage the tissues in the case of actually
preserving blood components such as erythrocytes, platelets, and
plasma, a marrow liquid or such other body fluids, and cell
suspension solutions. After being temporarily cooled down to
approximately -80.degree. C. by a deep freezer (freezing machine),
they are transferred into liquid nitrogen for preservation. To use
the blood, cells, and the like that have been preserved, for
example, they can be thawed by heating means, for example, a warm
bath at 37 to 40.degree. C.
[0030] Hereinafter, the present invention will be described in
detail based on certain examples. However, the present invention is
not limited to these examples.
EXAMPLE 1
[0031] Both sides of a 75 .mu.m-thick cut film made of ultra-high
molecular weight polyethylene (approximately 1,500,000 in weight
average molecular weight based on viscometric method) (New Light,
manufactured by SAXIN CORPORATION, Ltd. Japan) were laminated with
a 50 .mu.m-thick linear low-density polyethylene films (Moretec,
manufactured by Idemitsu Kosan Co., Ltd. Japan) by a
heat-laminating process to prepare a three-layer film. The film was
cut into sheets of 150.times.200 mm in dimensions and then two
sheets thereof were layered and the edge portions of the sheets
were heat-welded by a heat-sealing process to prepare a medical
freezer bag of 100 ml in capacity.
EXAMPLE 2
[0032] The outer side of a 75 .mu.m-thick cut film made of
ultra-high molecular weight polyethelene (approximately 1,000,000
in weight average molecular weight based on viscometric method)
(New Light, manufactured by SAXIN CORPORATION, Ltd. Japan) was
laminated with a 50 .mu.m-thick linear low-density polyethylene
film (Moretec, manufactured by Idemitsu Kosan Co., Ltd. Japan), and
the inner side of the cut film was laminated with a 50 .mu.m-, 75
.mu.m-, or 100 .mu.m-thick linear low-density polyethylene film
(Moretec, manufactured by Idemitsu Kosan Co., Ltd. Japan) by a
heat-laminating process to prepare a three-layer film. The film was
cut into sheets of 150.times.200 mm in dimensions and then two
sheets thereof were layered and the edge portions of the sheets
were heat-welded by a heat-sealing process to prepare medical
freezer bags of 100 ml in capacity.
TEST EXAMPLE
[0033] The medical freezer bag prepared in Example 1 was filled
with 100 ml of an aqueous 5%(v/v) dimethylsulfoxide (DMSO)
solution, and deaeration was carried out sufficiently and then the
medical freezer bag was placed in an aluminum case. The bag placed
in the aluminum case was left standing in a deep freezer (freezing
machine) at -80.degree. C. for 4 hours to freeze the bag.
Subsequently, the frozen bag was transferred into liquid nitrogen
and stored for 1 week. The bag stored was taken out of the aluminum
case and defrosted in a warm bath at 37 to 40.degree. C., followed
by visual observation to confirm whether or not the bag was
damaged, the liquid nitrogen was mixed therein, or the like. As a
comparative example, each of a commercially available 100-ml bag
made of an ethylene-vinyl acetate copolymer (EVA) and a bag made of
polyethylene (PE) was subjected to the same experiment while being
visually observed 10 times.
[0034] The results of the experiment are listed in Table 1. For the
ethylene-vinyl acetate copolymer bag (EVA, thickness of the film:
375 .mu.m; Nexell Co. U.S.A.), 20% of the sample bags were damaged.
For the polyethylene bag (PE, thickness of the film: 70 .mu.m;
CharterMed Co. U.S.A.), 10% of the sample bags were damaged. In
contrast, even though as many as 200 samples of the medical freezer
bag of the present invention were subjected to the test conditions,
no damaged samples were observed.
1 TABLE 1 Example EVA PE Number of damaged bags/number 0/200 2/10
1/10 of samples
[0035] According to the present invention, a medical freezer bag
having a sufficient strength, which is not damaged at -196.degree.
C., the temperature of liquid nitrogen, and which is excellent in
low temperature resistance and molding processability, can be
provided, and thus blood, body fluids, and cell suspensions can be
aseptically or nontoxically preserved at extremely low
temperatures.
* * * * *