U.S. patent application number 11/887073 was filed with the patent office on 2009-03-12 for package of freeze storage container and process for producing the same.
This patent application is currently assigned to NIPRO CORPORTION. Invention is credited to Kazuki Ishihara, Hideaki Murahashi, Naomi Nakatani, Hidenori Ozaki, Aldo Shirasu, Yoshihiro Yoshikawa.
Application Number | 20090065507 11/887073 |
Document ID | / |
Family ID | 37023884 |
Filed Date | 2009-03-12 |
United States Patent
Application |
20090065507 |
Kind Code |
A1 |
Ishihara; Kazuki ; et
al. |
March 12, 2009 |
Package of freeze Storage Container and Process for Producing the
Same
Abstract
It is demanded that packages for cryopreservation containers
which can prevent the conventional cryopreservation containers
stored at very low temperatures, namely -80 to -196.degree. C.,
from being damaged and are excellent in heat sealability be
developed. The present invention provides a package for a
cryopreservation container comprising at least an adhesive
fluoropolymer film. The package for a cryopreservation container
according to the invention makes it possible to store blood, rare
cells and vital tissues in a very low temperature environment
without any damage to the container. Further, the sealing strength
resulting from heat sealing after placing a cryopreservation
container in the packages is very good and, therefore, liquid
nitrogen can be inhibited from entering the inside and thus
contamination with bacteria, viruses or the like contained in
liquid nitrogen can be avoided and the package can be prevented
from being broken by expansion of intruder liquid nitrogen on the
occasion of thawing.
Inventors: |
Ishihara; Kazuki;
(Osaka-shi, JP) ; Murahashi; Hideaki; (Osaka-shi,
JP) ; Nakatani; Naomi; (Osaka-shi, JP) ;
Yoshikawa; Yoshihiro; (Osaka-shi, JP) ; Shirasu;
Aldo; (Osaka-shi, JP) ; Ozaki; Hidenori;
(Settsu-shi, JP) |
Correspondence
Address: |
SUGHRUE MION, PLLC
2100 PENNSYLVANIA AVENUE, N.W., SUITE 800
WASHINGTON
DC
20037
US
|
Assignee: |
NIPRO CORPORTION
Osaka-shi, OSAKA
JP
DAIKIN INDUSTRIES, LTD.
Osaka-shi, OSAKA
JP
|
Family ID: |
37023884 |
Appl. No.: |
11/887073 |
Filed: |
March 27, 2006 |
PCT Filed: |
March 27, 2006 |
PCT NO: |
PCT/JP2006/306188 |
371 Date: |
November 14, 2007 |
Current U.S.
Class: |
220/560.04 ;
156/196 |
Current CPC
Class: |
B32B 27/34 20130101;
B32B 27/32 20130101; A61M 1/0272 20130101; Y10T 156/1002 20150115;
A61J 1/10 20130101; C08F 214/26 20130101; C08F 214/18 20130101;
A01N 1/02 20130101; A01N 1/0268 20130101; A61J 1/165 20130101; B65D
81/18 20130101 |
Class at
Publication: |
220/560.04 ;
156/196 |
International
Class: |
F17C 1/16 20060101
F17C001/16; B29C 65/02 20060101 B29C065/02 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 25, 2005 |
JP |
2005-090011 |
Apr 26, 2005 |
JP |
2005-128458 |
Claims
1. A package for a cryopreservation container comprising at least
an adhesive fluoropolymer film.
2. The package for a cryopreservation container according to claim
1, wherein the adhesive fluoropolymer film is made of an adhesive
fluoropolymer containing at least one adhesive site.
3. The package for a cryopreservation container according to claim
2, wherein the at least one adhesive site is selected from the
group consisting of carbon-carbon double bond, carbonyl group
[--C(.dbd.O)], carbonyl group-containing groups or bonds, hydroxyl
group, cyano group, sulfonic acid group and epoxy group.
4. The package for a cryopreservation container according to claim
3, wherein the adhesive fluoropolymer contains at least one
reactive functional group as the adhesive site and is a copolymer
obtained by copolymerizing the following monomers (A) and (B): (A)
A fluorinated monomer containing no reactive functional group; (B)
A fluorinated monomer containing the at least one reactive
functional group.
5. The package for a cryopreservation container according to claim
4, wherein the fluorinated monomer containing no reactive
functional group is represented by the formula (1) given below:
##STR00009## (wherein X.sup.1 and X.sup.2 each is hydrogen atom or
halogen atom and Y is hydrogen atom, fluorine atom, a fluorinated
alkyl group containing 1 to 5 carbon atoms or a fluorinated
oxyalkyl group containing 1 to 5 carbon atoms).
6. The package for a cryopreservation container according to claim
5, wherein the fluorinated monomer containing no reactive
functional group comprises at least one monomer selected from the
group consisting of tetrafluoroethylene, vinylidene fluoride,
1,2-difluorochloroethylene, hexafluoropropylene, perfluoro(vinyl
methyl ether) and perfluoro(vinyl propyl ether).
7. The package for a cryopreservation container according to claim
4, wherein the fluorinated monomer containing the at least one
reactive functional group is represented by the formula (2) given
below: ##STR00010## (wherein X.sup.1 and X.sup.2 each is hydrogen
atom or halogen atom, Z is hydroxyl group, carboxyl group, cyano
group, sulfonic acid group or epoxy group and R.sub.f is a
fluorinated alkylene group containing 1 to 40 carbon atoms, a
fluorinated oxyalkylene group containing 1 to 40 carbon atoms or a
fluorinated alkylene group containing 1 to 40 carbon atoms and at
least one ether bond).
8. The package for a cryopreservation container according to claim
4, wherein the adhesive fluoropolymer is represented by the formula
(3) given below: ##STR00011## (wherein X.sup.1 and X.sup.2 each is
hydrogen atom or halogen atom, Y.sup.1 and Y.sup.2 each is hydrogen
atom, fluorine atom, a fluorinated alkyl group containing 1 to 5
carbon atoms or a fluorinated alkoxy group containing 1 to 5 carbon
atoms, Z is hydroxyl group, carboxyl group, cyano group, sulfonic
acid group or epoxy group, R.sub.f is a fluorinated alkylene group
containing 1 to 40 carbon atoms, a fluorinated oxyalkylene group
containing 1 to 40 carbon atoms or a fluorinated alkylene group
containing 1 to 40 carbon atoms and at least one ether bond and the
ratio (1+m)/n is 2 to 2000).
9. The package for a cryopreservation container according to claim
3, wherein the adhesive fluoropolymer comprises a fluorinated
monomer-derived fluorinated monomer unit and a nonfluorinated
monomer-derived nonfluorinated monomer unit.
10. The package for a cryopreservation container according to claim
9, wherein the fluorinated monomer is tetrafluoroethylene and the
nonfluorinated monomer is ethylene.
11. The package for a cryopreservation container according to claim
1 comprising: the adhesive fluoropolymer film on at least one
outermost layer and a film other than said adhesive fluoropolymer
film.
12. The package for a cryopreservation container according to claim
11, wherein the film other than the adhesive fluoropolymer film is
a low-temperature resistant resin film.
13. The package for a cryopreservation container according to claim
12, wherein the low-temperature resistant resin comprises at least
one resin selected from the group consisting of ultrahigh molecular
weight polyethylene, polyimides, polytetrafluoroethylene,
ethylene-tetrafluoroethylene copolymers and ethylene-vinyl acetate
copolymers.
14. The package for a cryopreservation container according to claim
13, wherein the low-temperature resistant resin is a polyimide.
15. A method of producing a package for a cryopreservation
container comprising shaping an adhesive fluoropolymer film into a
bag-like article by heat sealing.
16. The method of producing a package for a cryopreservation
container according to claim 15, comprising shaping a laminated
film comprising the adhesive fluoropolymer film on at least one
outermost layer and a film other than said adhesive fluoropolymer
film, into a bag-like article by heat sealing.
Description
TECHNICAL FIELD
[0001] The present invention relates to a package for a
cryopreservation container and a method of producing the same. More
particularly, it relates to a package for a cryopreservation
container which comprises a laminate film and is used for packaging
a cryopreservation container and in which the laminated film
comprises a low-temperature resistant resin film and an adhesive
fluoropolymer film, with the adhesive fluoropolymer film being
disposed at least on one outermost layer.
BACKGROUND ART
[0002] Blood, rare cells and vital tissues are generally stored at
very low temperatures, namely at about -80 to -196.degree. C. In
particular, bone marrow cells, hematopoietic stem cells and like
rare cells are effectively used in the treatment of intractable
diseases such as leukemia, and a technology of storing them for a
long period of time has been demanded. For the storage at such very
low temperatures, blood, rare cells and vital tissues are generally
stored in tightly closed containers therefor immersed mainly in
liquid nitrogen.
[0003] As for the cryopreservation containers for such storage,
vials made of polypropylene, for instance, are commercially
available for use on the laboratory level; they are inexpensive and
convenient from the handling viewpoint.
[0004] With the recent development of cord blood banks, bag-like
containers excellent in low-temperature resistance and flexibility
have been proposed. For example, containers made of a laminated
film composed of a polyimide film and fluorinated
ethylene-propylene polymer film (Patent Document 1) and containers
made of a tetrafluoroethylene-ethylene copolymer film (Patent
Document 2) have been proposed. Further, Patent Document 3
discloses cryopreservation containers molded from an electron
beam-irradiated, biaxially stretched ethylene-vinyl acetate
copolymer film. Patent Document 4 discloses cryopreservation
containers molded from a biaxially stretched, crosslinked
polyethylene film.
[0005] On the other hand, the present inventors developed
cryopreservation containers which are constituted of a laminated
film consisting of an ultrahigh molecular weight polyethylene layer
and a thermoplastic resin layer compatible with the ultrahigh
molecular weight polyethylene layer and are superior to the
cryopreservation containers disclosed in Patent Documents 1 to 4,
and applied for a patent for the same (Patent Document 5).
[0006] When blood, rare cells and vital tissues are preserved in
the cryopreservation containers mentioned above in liquid nitrogen,
the cryopreservation containers are further packaged so that the
contents may be protected in case of damage of the containers and
liquid nitrogen may be prevented from entering the cryopreservation
containers. For packaging them, packages made of a
perfluoroethylene-propene copolymer, among others, are generally
used.
[0007] However, such packages are fluororesin-made ones and
therefore the molding or processing for manufacturing them must be
carried out at elevated temperatures. In spite of this, their heat
seal strength is not so high but the sealed portions are possibly
in danger of peeling away. After packaging of a cryopreservation
container in a package, the mouth portion of the package is heat
sealed for tight closure. This mouth portion is also susceptible to
peeling and there is the possibility that liquid nitrogen may enter
the inside. This work is carried out in medical institutions such
as cord blood banks and heat sealing under severe conditions is a
burden on workers. Further, when polypropylene vials for
cryopreservation or cryopreservation containers described in Patent
Documents 1 to 4 are packaged, there is the possibility that when
the packages are damaged and liquid nitrogen enters the inside, the
cryopreservation containers may also be damaged.
[0008] Ultrahigh molecular weight polyethylene films are formed by
cutting processing and are relatively thick. When they are used as
materials for packages, the conduction of heat to the contents may
possibly be affected.
[0009] Known as materials for packages for cryopreservation
containers are polytetrafluoroethylene,
polychlorotrifluoroethylene,
tetrafluoroethylene/hexafluoropropylene copolymers,
tetrafluoroethylene/ethylene copolymers and polyimides, among
others (cf. e.g. Patent Document 6 and Patent Document 7). However,
those fluororesins which are used in preparing the conventional
packages require elevated temperatures for sealing and their
sealability is insufficient in some cases.
Patent Document 1: Japanese Patent Publication S49-008079
Patent Document 2: Utility Model Publication S55-055069
Patent Document 3: Japanese Patent Publication S55-044977
Patent Document 4: Japanese Patent Publication S62-057351
Patent Document 5: Japanese Kokai Publication H08-173505
Patent Document 6: Japanese Kokai Publication H11-139459
Patent Document 7: Japanese Kokai Publication 2003-267471
DISCLOSURE OF INVENTION
Problems which the Invention is to Solve
[0010] Therefore, it is demanded that packages for cryopreservation
containers which can prevent the conventional cryopreservation
containers stored at very low temperatures, namely -80 to
-196.degree. C., from being damaged and are excellent in heat
sealability be developed.
Means for Solving the Problems
[0011] The present inventors proposed using an adhesive
fluoropolymer film for a package for a cryopreservation
container.
[0012] The present invention relates to:
(1) a package for a cryopreservation container comprising at least
an adhesive fluoropolymer film; (2) the package for a
cryopreservation container according to (1), wherein the adhesive
fluoropolymer film is made of an adhesive fluoropolymer containing
at least one adhesive site; (3) the package for a cryopreservation
container according to (2), wherein the at least one adhesive site
is selected from the group consisting of carbon-carbon double bond,
carbonyl group [--C(.dbd.O)], carbonyl group-containing groups or
bonds, hydroxyl group, cyano group, sulfonic acid group and epoxy
group; (4) the package for a cryopreservation container according
to (3), wherein the adhesive fluoropolymer contains at least one
reactive functional group as the adhesive site and is a copolymer
obtained by copolymerizing the following monomers (A) and (B): (A)
a fluorinated monomer containing no reactive functional group; (B)
a fluorinated monomer containing the at least one reactive
functional group. (5) the package for a cryopreservation container
according to (4), wherein the fluorinated monomer containing no
reactive functional group is represented by the formula (1) given
below:
##STR00001##
(wherein X.sup.1 and X.sup.2 each is hydrogen atom or halogen atom
and Y is hydrogen atom, fluorine atom, a fluorinated alkyl group
containing 1 to 5 carbon atoms or a fluorinated oxyalkyl group
containing 1 to 5 carbon atoms); (6) the package for a
cryopreservation container according to (5), wherein the
fluorinated monomer containing no reactive functional group
comprises at least one monomer selected from the group consisting
of tetrafluoroethylene, vinylidene fluoride,
1,2-difluorochloroethylene, hexafluoropropylene, perfluoro(vinyl
methyl ether) and perfluoro(vinyl propyl ether); (7) the package
for a cryopreservation container according to (4) to (6), wherein
the fluorinated monomer containing the at least one reactive
functional group is represented by the formula (2) given below:
##STR00002##
(wherein X.sup.1 and X.sup.2 each is hydrogen atom or halogen atom,
Z is hydroxyl group, carboxyl group, cyano group, sulfonic acid
group or epoxy group and R.sub.f is a fluorinated alkylene group
containing 1 to 40 carbon atoms, a fluorinated oxyalkylene group
containing 1 to 40 carbon atoms or a fluorinated alkylene group
containing 1 to 40 carbon atoms and at least one ether bond); (8)
the package for a cryopreservation container according to (4),
wherein the adhesive fluoropolymer is represented by the formula
(3) given below:
##STR00003##
(wherein X.sup.1 and X.sup.2 each is hydrogen atom or halogen atom,
Y.sup.1 and Y.sup.2 each is hydrogen atom, fluorine atom, a
fluorinated alkyl group containing 1 to 5 carbon atoms or a
fluorinated alkoxy group containing 1 to 5 carbon atoms, Z is
hydroxyl group, carboxyl group, cyano group, sulfonic acid group or
epoxy group, R.sub.f is a fluorinated alkylene group containing 1
to 40 carbon atoms, a fluorinated oxyalkylene group containing 1 to
40 carbon atoms or a fluorinated alkylene group containing 1 to 40
carbon atoms and at least one ether bond and the ratio (1+m)/n is 2
to 2000); (9) the package for a cryopreservation container
according to (3), wherein the adhesive fluoropolymer comprises a
fluorinated monomer-derived fluorinated monomer unit and a
nonfluorinated monomer-derived nonfluorinated monomer unit; (10)
the package for a cryopreservation container according to claim 9,
wherein the fluorinated monomer is tetrafluoroethylene and the
nonfluorinated monomer is ethylene; (11) the package for a
cryopreservation container according to claim 1 comprising the
adhesive fluoropolymer film on at least one outermost layer and a
film other than the adhesive fluoropolymer film; (12) the package
for a cryopreservation container according to (11), wherein the
film other than the adhesive fluoropolymer film is a
low-temperature resistant resin film; (13) the package for a
cryopreservation container according to (12), wherein the
low-temperature resistant resin comprises at least one resin
selected from the group consisting of ultrahigh molecular weight
polyethylene, polyimides, polytetrafluoroethylene,
ethylene-tetrafluoroethylene copolymers and ethylene-vinyl acetate
copolymers; (14) the package for a cryopreservation container
according to (13), wherein the low-temperature resistant resin is a
polyimide; (15) a method of producing a package for a
cryopreservation container comprising shaping an adhesive
fluoropolymer film into a bag-like article by heat sealing; and
(16) the method of producing a package for a cryopreservation
container according to (15), comprising shaping a laminated film
comprising the adhesive fluoropolymer film on at least one
outermost layer and a film other than the adhesive fluoropolymer
film, into a bag-like article by heat sealing.
EFFECTS OF THE INVENTION
[0013] The package for a cryopreservation container according to
the invention makes it possible to store blood, rare cells and
vital tissues in a very low temperature environment without any
damage to the container. In particular, even when it is used in
combination with those cryopreservation containers (e.g.
cryopreservation containers described in Patent Documents 1 to 4)
which cannot always be said to be excellent in cryopreservation or
polypropylene vials in use on the experiment level, the package can
produce its effects. Since it is excellent in low-temperature heat
sealability, the production stability in package manufacture in a
factory is improved and workers at working places where biological
samples are stored can seal it with ease. Further, the sealing
strength resulting from heat sealing after placing a
cryopreservation container in the packages is very good and,
therefore, liquid nitrogen can be inhibited from entering the
inside and thus contamination with bacteria, viruses or the like
contained in liquid nitrogen can be avoided and the package can be
prevented from being broken by expansion of intruder liquid
nitrogen on the occasion of thawing.
BEST MODES FOR CARRYING OUT THE INVENTION
[0014] The package for a cryopreservation container according to
the invention is a bag-shaped package for packaging the
cryopreservation container for the purpose of protecting the
contents of the cryopreservation container in case of the same
being damaged and for the purpose of preventing liquid nitrogen
from entering the cryopreservation container and is constituted of
a film comprising at least an adhesive fluoropolymer layer.
[0015] The adhesive fluoropolymer film is a film molded from a
polymer whose main chain and/or side chains contain at least one
fluorine atom and that film functions as a film adhering to a
substrate or base made of an organic material. The adhesion or
adhering, so referred to herein, is the binding of the adhesive
fluoropolymer film to the organic material via physical and/or
chemical bonds, among others. From the bond strength viewpoint,
chemical bonds are preferred although the bonds are not limited
thereto. The chemical bonds include covalent bonds, ionic bonds,
coordination bonds, hydrogen bonds and intermolecular forces, among
others. Preferred bonds from the bond strength viewpoint are, but
are not limited to, covalent bonds and ionic bonds. More preferred
are covalent bonds.
[0016] The organic material mentioned above includes
general-purpose resin moldings, such as films, tubes, synthetic
fibers, synthetic rubbers and solids, made of polyethylene,
polycarbonates, polystyrene, polyvinyl chloride, polyvinyl acetate,
polyesters and low-temperature-resistant resins such as ultrahigh
molecular weight polyethylene, polyimides, polytetrafluoroethylene,
ethylene-tetrafluoroethylene copolymers and ethylene-vinyl acetate
copolymers, and naturally occurring organic matters such as natural
rubbers, natural fibers, woods, papers and leathers and, further,
adhesive fluoropolymers. Preferred ones among these from the
viewpoint of improving the low-temperature resistance of the
package itself are, but are not limited to, the adhesive
fluoropolymer film itself and ones having a function enabling their
adhesion to the low-temperature-resistant resin film.
[0017] From the moldability/processability viewpoint, the adhesive
fluoropolymer has a number average molecular weight of about 1,000
to 1,000,000, preferably about 2,000 to 500,000, more preferably
about 5,000 to 300,000. These ranges have no restrictive meaning,
however.
[0018] The adhesive fluoropolymer film can be produced by timely
selecting a proper production method according to the molecular
structure, glass transition temperature and melting point, among
others, of the adhesive fluoropolymer, as the one skilled in the
art does. For example, there may be mentioned compression molding,
injection molding, extrusion molding, T-die molding, inflation
molding, solvent casting and so forth. A method preferred from the
moldability/processability viewpoint is, but is not limited to,
compression molding. Considering the conduction of heat to the
contents, the adhesive fluoropolymer film has a thickness of about
10 to 100 .mu.m, preferably 10 to 50 .mu.m, particularly preferably
10 to 30 .mu.m. These ranges have no restrictive meaning,
however.
[0019] Preferred examples of the adhesive fluoropolymer are
copolymers derived from the following (A) and (B).
(A) A fluorinated monomer containing no reactive functional group.
(B) A fluorinated monomer containing at least one reactive
functional group.
[0020] The reactive functional group, so referred to herein, is a
functional group capable of adhering to the organic material
substrate mentioned above via a covalent bond, ionic bond,
coordination bond or hydrogen bond, for instance. For example, such
functional group includes, but is not limited to, hydroxyl group,
carboxyl group, cyano group, sulfonic acid group, epoxy group and
like groups. One preferred among these is, but is not limited to,
the hydroxyl group which is readily activated by heat.
[0021] The fluorinated monomer mentioned above is one giving a
copolymer whose main chain and/or side chains contains at least one
fluorine atom substituting for a hydrogen atom. It includes, for
example, fluorinated ethylenic monomers, fluorinated ester monomers
and fluorinated wholly aromatic monomers. Preferred ones are, but
are not limited to, fluorinated ethylenic monomers in view of their
ready availability and moldability/processability of the copolymers
obtained.
[0022] The copolymer mentioned above may be a binary one derived
from at least one (A) monomer and at least one (B) monomer by
polymerization. For example, mention may be made of a binary one
derived from one (A) monomer and one (B) monomer, a ternary one
derived from two (A) monomers and one (B) monomer, and a ternary
one derived from one (A) monomer and two (B) monomers. Preferred
ones from the production cost viewpoint are, but are not limited
to, binary or ternary ones.
[0023] As the copolymerization technique, there may be mentioned,
among others, radical copolymerization, anion copolymerization,
cation copolymerization, emulsion copolymerization and plasma
copolymerization and an appropriate technique can be timely
selected from among these according to the monomer structure,
polarity, solvent species and so forth, as the one skilled in the
art does. A preferred one among them is, but is not limited to,
radical copolymerization in view of the ease of production.
[0024] As for the constitution of the copolymer, there may be
mentioned random copolymers, block copolymers, graft copolymers and
alternating copolymers. Preferred ones are, but are not limited to,
random copolymers from the ease of production viewpoint.
[0025] Further, the occurrence ratio (copolymerization ratio)
between (A) and (B) in the above copolymer is, but is not limited
to, 1 to 2000 of (A), preferably 100 to 2000 of (A), with (B) being
taken as 1 in view of the moldability/processability of the
copolymer.
[0026] The above-mentioned fluorinated monomer (A) containing no
reactive functional group has none of the reactive functional
groups enumerated hereinabove and gives a copolymer whose main
chain and/or side chains contain at least one fluorine atom
substituting for a hydrogen atom. Preferred ones are, but are not
limited to, fluorinated ethylenic monomers containing no reactive
functional group in view of their ready availability and of the
moldability/processability of the copolymers obtained.
[0027] The fluorinated monomer (A) containing no reactive
functional group contains at least one fluorine atom and, as
examples thereof, there may be mentioned monomers represented by
the following formula (1).
##STR00004##
(In the above formula, X.sup.1 and X.sup.2 each is hydrogen atom or
halogen atom and Y is hydrogen atom, fluorine atom, a fluorinated
alkyl group containing 1 to 5 carbon atoms or a fluorinated
oxyalkyl group containing 1 to 5 carbon atoms.)
[0028] As the monomers represented by the above formula (1), there
may be mentioned, for example, tetrafluoroethylene, vinylidene
fluoride, 1,2-difluorochloroethylene, hexafluoropropylene,
perfluoro(vinyl methyl ether) and perfluoro (vinyl propyl ether).
Preferred are tetrafluoroethylene, vinylidene fluoride,
1,2-difluorochloroethylene and perfluoro (vinyl propyl ether)
Preferred ones are, but are not limited to, tetrafluoroethylene,
vinylidene fluoride, hexafluoropropylene and perfluoro (vinyl
propyl ether) in view of their ready availability and of the
moldability/processability of the copolymers obtained.
[0029] On the other hand, the fluorinated monomer (B) containing at
least one reactive functional group contains at least one of the
reactive functional groups enumerated hereinabove, and the
copolymer obtained by polymerization using the same contains at
least one fluorine atom substituting for a hydrogen atom in the
main chain and/or side chains thereof. Preferred ones are, but are
not limited to, fluorinated ethylenic monomers containing a
reactive functional group or groups in view of their ready
availability and of the moldability/processability of the
copolymers obtained.
[0030] As examples of the fluorinated ethylenic monomer (B)
containing at least one reactive functional group, there may be
mentioned monomers represented by the formula (2).
##STR00005##
(In the above formula, X.sup.1 and X.sup.2 each is hydrogen atom or
halogen atom, Z is hydroxyl group, carboxyl group, cyano group,
sulfonic acid group or epoxy group and R.sub.f is a fluorinated
alkylene group containing 1 to 40 carbon atoms, a fluorinated
oxyalkylene group containing 1 to 40 carbon atoms or a fluorinated
alkylene group containing 1 to 40 carbon atoms and at least one
ether bond.)
[0031] As the monomers represented by the above formula (2), there
may be mentioned, for example, perfluoro(4-oxa-5-hexenol) (formula
(4)), perfluoro(1,1-dihydro-6-heptenol) (formula (5)),
perfluoro(1,1,9,9-tetrahydro-2,5-bistrifluoromethyl-3,6-dio
xa-8-nonenol) (formula (6)), perfluoro (4-oxa-5-hexenoic acid)
(formula (7)),
perfluoro(3,6-dioxa-4-trifluoromethyl-7-octenonitrile) (formula
(8)), perfluoro(1,1,-dihydro-3-oxa-4-pentenesulfonic acid) (formula
(9)), 1,2-epoxy-perfluoro(1,1,2-trihydro-6-pentene) (formula (10))
and like monomers. Preferred ones are, but are not limited to,
hydroxyl group-containing ones such as perfluoro(4-oxa-5-hexenol)
(formula (4)), perfluoro(1,1-dihydro-6-heptenol) (formula (5)) and
perfluoro(1,1,9,9-tetrahydro-2,5-bistrifluoromethyl-3,6-dio
xa-8-nonenol) (formula (6)) in view of their giving copolymers
excellent in low-temperature heat sealability.
##STR00006##
[0032] Preferred constitutions of the adhesive fluoropolymer to be
used in the practice of the invention are, but are not limited to,
copolymers represented by the formula (3) given below in view of
the ease of production thereof.
##STR00007##
(In the above formula, X.sup.1 and X.sup.2 each is hydrogen atom or
halogen atom, Y.sup.1 and Y.sup.2 each is hydrogen atom, fluorine
atom, a fluorinated alkyl group containing 1 to 5 carbon atoms or a
fluorinated alkoxy group containing 1 to 5 carbon atoms, Z is
hydroxyl group, carboxyl group, cyano group, sulfonic acid group or
epoxy group, R.sub.f is a fluorinated alkylene group containing 1
to 40 carbon atoms, a fluorinated oxyalkylene group containing 1 to
40 carbon atoms or a fluorinated alkylene group containing 1 to 40
carbon atoms and at least one ether bond and the ratio (1+m)/n is 2
to 2000.) When the ratio (1+m)/n is in excess of 2000, there is the
possibility that no sufficient adhesiveness can be obtained any
longer.
[0033] More preferred constitutions of the adhesive fluoropolymer
to be used in the practice of the invention are, but are not
limited to, copolymers represented by the formula (11) given below
in view of the ease of production thereof and from the heat seal
strength viewpoint.
##STR00008##
(In the above formula, X.sup.1 and X.sup.2 each is hydrogen atom or
halogen atom, Y.sup.1 and Y.sup.2 each is hydrogen atom, fluorine
atom, a fluorinated alkyl group containing 1 to 5 carbon atoms or a
fluorinated alkoxy group containing 1 to 5 carbon atoms, R.sub.f is
a fluorinated alkylene group containing 1 to 40 carbon atoms, a
fluorinated oxyalkylene group containing 1 to 40 carbon atoms or a
fluorinated alkylene group containing 1 to 40 carbon atoms and at
least one ether bond and the ratio (1+m)/n is 2 to 2000.)
[0034] Particularly preferred constitutions of the adhesive
fluoropolymer to be used in the practice of the invention are, but
are not limited to, copolymers of tetrafluoroethylene and/or
perfluoro(vinyl propyl ether) and
perfluoro(1,1,9,9-tetrahydro-2,5-bistrifluoromethyl-3,6-dio
xa-8-nonenol) from the viewpoint of ready availability of the
monomers, the ease of production and the heat seal strength. From
the ease of production viewpoint, the copolymer constituent ratio
is a total of about 2 to 2000, preferably about 4 to 2000,
tetrafluoroethylene monomer units and/or perfluoro(vinyl propyl
ether) monomer units per
perfluoro(1,1,9,9-tetrahydro-2,5-bistrifluoromethyl-3,6-dio
xa-8-nonenol) monomer unit. The ranges given above have no
restrictive meaning, however.
[0035] In the practice of the invention, the adhesive fluororesin
film mentioned above is preferably one made of an adhesive
fluoropolymer containing at least one adhesive site.
[0036] The adhesive fluoropolymer may contain the above-mentioned
reactive functional groups as the adhesive sites.
[0037] The adhesive fluororesin film may be one forming an adhesive
fluororesin layer to be described later herein. The adhesive
fluoropolymer may be one constituting an adhesive fluororesin.
[0038] In the practice of the invention, the adhesive fluororesin
layer is made of the adhesive fluororesin.
[0039] The adhesive fluororesin, so referred to herein, is
preferably one comprising a fluoropolymer containing at least one
adhesive site.
[0040] The fluoropolymer, so referred to herein, is a polymer
containing fluorinated monomer units derived from a fluorinated
monomer or monomers in the main chain thereof. The fluoropolymer
may or may not contain nonfluorinated monomer units derived from a
nonfluorinated monomer or monomers.
[0041] The term "monomer unit" as used herein referring to the
fluoropolymer, means a monomer-derived portion constituting a part
of the molecular structure of the polymer. The tetrafluoroethylene
unit, for instance, is represented by --(CF.sub.2--CF.sub.2)--.
[0042] The above-mentioned fluorinated monomer is not particularly
restricted but may be any of fluorine atom-containing polymerizable
compounds. Thus, for example, there may be mentioned
tetrafluoroethylene [TFE], vinylidene fluoride [VdF],
chlorotrifluoroethylene [CTFE], vinyl fluoride [VF],
hexafluoropropylene [HFP], hexafluoroisobutene, perfluoro(alkyl
vinyl ether) [PAVE] species, and monomers represented by the
general formula (i):
CH.sub.2.dbd.CX.sup.3(CF.sub.2).sub.nX.sup.4 (i)
(wherein X.sup.3 represents hydrogen atom or fluorine atom, X.sup.4
represents hydrogen atom, fluorine atom or chlorine atom and n
represents an integer of 1 to 10).
[0043] The above-mentioned nonfluorinated monomer is not
particularly restricted but may be any of compounds containing no
fluorine atom and copolymerizable with the fluorinated monomers
mentioned above. For example, there may be mentioned ethylene [Et],
propylene, 1-butene, 2-butene, vinyl chloride and vinylidene
chloride.
[0044] As the above fluoropolymer, there may be mentioned the
copolymers (I) and copolymers (II) mentioned below.
(I) Copolymers resulting from polymerization of at least TFE and
Et; (II) Copolymers resulting from polymerization of at least TFE
and at least one monomer represented by the general formula
(ii):
CF.sub.2.dbd.CF-R.sub.f.sup.2 (ii)
(wherein R.sub.f.sup.2 represents --CF.sub.3 or --OR.sub.f.sup.1 in
which R.sub.f.sup.1 represents a perfluoroalkyl group containing 1
to 5 carbon atoms).
[0045] As the copolymers (I), there may be mentioned, for example,
copolymers constituted of at least 20 to 80 mole percent of TFE
units and 80 to 20 mole percent of Et units.
[0046] In the present specification, the mole percent values for
the respective monomer units are the percentages of the numbers of
moles of the respective monomers now constituting the respective
monomer units in the copolymer relative to that 100 mole percent
which corresponds to the total number of moles of all the monomers
now constituting the monomer units constituting the molecular chain
of the copolymer minus the number of moles of the monomer from
which the adhesive site-containing monomer units to be mentioned
later herein are derived.
[0047] The mole percent values given for the respective monomer
units are the values determined from a .sup.19F-NMR chart.
[0048] The copolymers (I) may contain, in the main chain thereof,
other monomer units derived from at least one other copolymerizable
monomer in addition to TFE units and Et units, and an appropriate
monomer species can be selected as the other monomer according to
the intended use of the laminate film to be obtained and can be
subjected to copolymerization.
[0049] As the other monomer, there may be mentioned HFP, CTFE,
propylene, monomers represented by the general formula (iii):
CX.sup.5.sub.2.dbd.CX.sup.6(CF.sub.2).sub.nX.sup.7 (iii)
(wherein X.sup.5 and X.sup.6 are the same or different and each
represents hydrogen atom or fluorine atom, X.sup.7 represents
hydrogen atom, fluorine atom or chloride atom and n represents an
integer of 1 to 10), and monomers represented by the general
formula (iv):
CF.sub.2.dbd.CF--OR.sub.f.sup.1 (iv)
(wherein R.sub.f.sup.1 represents a perfluoroalkyl group containing
1 to 5 carbon atoms), among others. Generally, one or two of these
are used.
[0050] The other monomer units may amount to 0 to 20 mole percent
relative to 100 mole percent of the monomer units constituting the
molecular chain of each copolymer (I).
[0051] Preferred as the above fluoropolymer are the copolymers (I)
since they are excellent in thermal stability, chemical resistance,
weather resistance, electric insulation properties, low liquid
chemical permeability and nonstickiness, among others, and
Et/TFE/HFP copolymers are more preferred since they are excellent
in thermal stability, chemical resistance, weather resistance,
electric insulation properties, low liquid chemical permeability,
nonstickiness, low-temperature processability and transparency,
among others. The HFP unit content in the Et/TFE/HFP copolymers is
preferably 5 to 20 mole percent, a more preferred lower limit is 8
mole percent and a more preferred upper limit is 17 mole percent.
The Et/TFE/HFP copolymers may contain, in addition to Et-, TFE- and
HFP-derived units, units derived from one or more of the
above-mentioned other monomer species other than HFP units within
the limits within which the favorable properties of the Et/TFE/HFP
copolymers will not be impaired.
[0052] In the present specification, the term "adhesive site" means
a functional group showing affinity for or reactivity with the
above-mentioned organic materials such as polyimide [PI] films.
[0053] In the present specification, the term "affinity" means the
ability to show such an interaction with the organic materials such
as PI films without modifying the chemical structure as hydrogen
bonding or van der Waals force and the term "reactivity" means the
ability to modify the chemical structure of the functional group,
for instance.
[0054] The adhesive sites are generally possessed by the
above-mentioned fluoropolymer in the main chain or side chains
thereof.
[0055] The adhesive sites are not particularly restricted but
include, among others, carbon-carbon double bonds, carbonyl group
[--C(.dbd.O)], carbonyl group-containing groups or bonds. In the
fluoropolymer containing such an adhesive site, the adhesive sites
may be of a kind or there may be two or more kinds of adhesive
sites.
[0056] The above-mentioned reactive functional groups may also
serve as the "adhesive sites".
[0057] As the carbonyl group-containing groups or bonds mentioned
above, there may be mentioned, for example, the carbonate group,
haloformyl group, formyl group, carboxyl group, carbonyloxy group
[--C(.dbd.O)O--], acid anhydride group [--C(.dbd.O)O--C(.dbd.O)--],
isocyanato group, amide group [--C(.dbd.O)--NH--], imide group
[--C(.dbd.O)--NH--C(.dbd.O)--], urethane bond [--NH--C(.dbd.O)O--],
carbamoyl group [NH.sub.2--C(.dbd.O)--], carbamoyloxy group
[NH.sub.2--C(.dbd.O)O--], ureido group [NH.sub.2--C(.dbd.O)--NH--]
and oxamoyl group [NH.sub.2--C(.dbd.O)--C(.dbd.O)--].
[0058] Preferred as the carbonyl group-containing groups or bonds
are carbonate groups and haloformyl groups, among others, in view
of the ease of introduction thereof and their high reactivity.
[0059] The above-mentioned carbonate group is a group having bonds
represented by [--OC(.dbd.O)O--] and is represented by
--OC(.dbd.O)O--R (in which R represents an organic group or a group
IA atom, group IIA atom or group VIIB atom). As the organic group R
in the above formula, there may be mentioned, for example, alkyl
groups containing 1 to 20 carbon atoms and alkyl groups containing
2 to 20 carbon atoms and containing at least one oxygen atom
constituting an ether bond, preferably alkyl groups containing 1 to
8 carbon atoms and alkyl groups containing 2 to 4 carbon atoms and
containing an oxygen atom constituting an ether bond, among others.
As the above carbonate group, there may be mentioned, for example,
--OC(.dbd.O)O--CH.sub.3, --OC(.dbd.O)O--C.sub.3H.sub.7,
--OC(.dbd.O)O--C.sub.8H.sub.17 and
--OC(.dbd.O)O--CH.sub.2CH.sub.2OCH.sub.2CH.sub.3.
[0060] The above-mentioned haloformyl group is represented by --COY
(in which Y represents a group VIIB atom), and --COF and --COCl,
among others, are preferred.
[0061] The number of the adhesive sites can be properly selected
according to such factors as substrate species, shape, use and
required bond strength and according to the fluoropolymer species
mentioned above. Generally, it is 3 to 1000 per 1.times.10.sup.6
carbon atoms in the main chain. When the number of carbonyl groups
is counted, the number of the adhesive sites is generally not less
than 150, preferably not less than 250, more preferably not less
than 300, per 1.times.10.sup.6 main chain carbon atoms.
[0062] In the present specification, the number of the
above-mentioned "adhesive sites" is determined by carrying out
infrared absorption spectrometry according to the method of
determining the number of carbonyl group-containing functional
group as described in International Publication WO 99/45044.
[0063] As the above-mentioned adhesive fluororesin, there may be
mentioned, for example, those fluorine-containing ethylenic
polymers containing carbonyl group-containing functional groups
which are described in International Publication WO 99/45044.
[0064] The above adhesive fluororesins can be obtained by
introducing adhesive sites on the occasion of fluoropolymer
production by polymerization and the method of introducing adhesive
sites is not particularly restricted but includes, for example, (1)
the method comprising subjecting an adhesive site-containing
monomer to copolymerization, (2) the method comprising carrying out
the polymerization in an aqueous medium in the manner of emulsion
polymerization, for instance, in the presence of an adhesive
site-containing polymerization initiator to thereby introduce the
polymerization initiator-derived adhesive site at one or each
polymer chain terminus, and (3) the method comprising heating, for
instance, the polymer on the occasion of polymerization or after
polymerization to convert carbon-carbon single bonds in the polymer
chain to double bonds to thereby provide the polymer with adhesive
sites.
[0065] The method (1) mentioned above can be carried out, for
example, by copolymerizing an adhesive site-containing monomer with
fluorinated monomer species and composition selected according to
the desired adhesive fluororesin, if desired together with a
nonfluorinated monomer in the conventional manner known in the
art.
[0066] The method of the above copolymerization is not particularly
restricted but may comprise, for example, random copolymerization,
which is carried out by introducing the adhesive site-containing
monomer into the system on the occasion of polymer chain formation
by other comonomers such as the fluorinated monomers, block
copolymerization, or graft copolymerization. In the case of graft
copolymerization, there may be mentioned, for example, the method
comprising causing addition of an unsaturated carboxylic acid,
which is to be mentioned later herein, to the fluoropolymer.
[0067] The "adhesive site-containing monomer" mentioned above means
an adhesive site-containing polymerizable monomer which may contain
one or more fluorine atoms or no fluorine atoms.
[0068] In the present specification, the "fluorinated monomers" and
"nonfluorinated monomers" mentioned above have no such adhesive
site as mentioned above.
[0069] When the adhesive site is a carbonyl group-containing group
or bond, the adhesive site-containing monomer includes, among
others, fluorine-containing monomers such as perfluoroacrylic acid
fluoride, 1-fluoroacrylic acid fluoride, acrylic acid fluoride,
1-trifluoromethacrylic acid fluoride and perfluorobutenoic acid;
and fluorine-free monomers such as acrylic acid, methacrylic acid,
acrylic acid chloride and vinylene carbonate.
[0070] As the adhesive site-containing monomer, there may further
be mentioned unsaturated carboxylic acids.
[0071] The unsaturated carboxylic acid, so referred to herein, any
compound containing at least one carbon-carbon unsaturated bond
(hereinafter also referred to as "copolymerizable carbon-carbon
unsaturated bond") enabling copolymerization and containing at
least one carbonyloxy group [--C(.dbd.O)--O--], and those
containing one copolymerizable carbon-carbon unsaturated bond in
each molecule are preferred among others.
[0072] As the unsaturated carboxylic acids, there may be mentioned,
for example, aliphatic unsaturated carboxylic acids and the
corresponding acid anhydrides. The aliphatic unsaturated carboxylic
acids may be aliphatic unsaturated monocarboxylic acids or
aliphatic unsaturated polycarboxylic acids containing two or more
carboxyl groups.
[0073] As the aliphatic unsaturated monocarboxylic acids, there may
be mentioned, for example, aliphatic monocarboxylic acids
containing 3 to 20 carbon atoms such as propionic acid, acrylic
acid, methacrylic acid, crotonic acid, and anhydrides thereof. As
the aliphatic unsaturated polycarboxylic acids, there may be
mentioned maleic acid, fumaric acid, mesaconic acid, citraconic
acid [CAC], itaconic acid, aconitic acid, itaconic acid anhydride
[IAH] and citraconic acid anhydride [CAH].
[0074] As the polymerization initiator in the method (2) mentioned
above, there may be mentioned diisopropyl peroxycarbonate,
di-n-propyl peroxydicarbonate, tert-butylperoxy isopropyl
carbonate, bis(4-tert-butylcyclohexyl) peroxydicarbonate and
di-2-ethylhexyl peroxydicarbonate, among others.
[0075] The above-mentioned adhesive fluororesin preferably has a
melting point of not higher than 200.degree. C., more preferably
not higher than 180.degree. C. from the viewpoint of the
sealability of the laminated film obtained.
[0076] In the present specification, the above-mentioned melting
point is the temperature at the melting peak maximum value obtained
by a measurement at a programming rate of 10.degree. C./minute
using a differential scanning colorimeter (product of Seiko).
[0077] In the practice of the invention, the adhesive fluoropolymer
film may further have the form of a laminated film with a film
other than the adhesive fluoropolymer film. In the practice of the
invention, the laminated film may be any one resulting from
lamination of at least the adhesive fluoropolymer film and a film
other than the adhesive fluoropolymer film, with the adhesive
fluoropolymer film forming the outermost layer of at least one
side. The number of layers may be 2 or more. From the viewpoint of
conduction of heat to the contents, that number is, but is not
limited to, 2 to 5, preferably 2 or 3.
[0078] The thickness of the laminated film depends on the number of
layers. In the case of a two-layer film consisting of a film other
than the adhesive fluoropolymer film and the adhesive fluoropolymer
film disposed on one side of the other film, the total film
thickness is, but is not limited to, about 20 to 200 .mu.m,
preferably 20 to 100 .mu.m, particularly preferably 20 to 60 .mu.m,
from the viewpoint of conduction of heat to the contents.
[0079] The thickness of the adhesive fluororesin layer mentioned
above is preferably 5 to 100 .mu.m, more preferably not thinner
than 10 .mu.m and not thicker than 50 .mu.m.
[0080] In the practice of the invention, the laminated film, when
formed by the above-mentioned thermal lamination method, generally
can have a bond strength (x) of not lower than 200 N/m, preferably
not lower than 300 N/m, more preferably not lower than 400 N/m.
[0081] In the present specification, the above-mentioned bond
strength (x) is the strength required for 180-degree peeling on a
Tensilon universal testing machine at a speed of 25 mm/minute using
10-mm-wide specimens excised from the laminated film and provided
with margins for gripping at one end by peeling the adhesive
fluororesin layer from the film other than the adhesive fluororesin
film such as a PI film using a cutter.
[0082] The film other than the adhesive fluororesin film is not
particularly restricted provided that it is not a film made of the
adhesive fluoropolymer; a low-temperature resistant resin is
preferred, however.
[0083] The low-temperature resistant resin is a resin excellent in
shock resistance at temperatures not higher than about -40.degree.
C., preferably at about -80.degree. C. and lower temperatures. For
example, mention may be made of ultrahigh molecular weight
polyethylene, polyimides, polytetrafluoroethylene,
ethylene-tetrafluoroethylene copolymers and ethylene-vinyl acetate
copolymers. From the viewpoint of conduction of heat to the
contents and of low-temperature resistance, polyimides,
polytetrafluoroethylene and ethylene-tetrafluoroethylene copolymers
are preferred. More preferred are polyimides. From the
moldability/processability viewpoint, the molecular weight of the
low-temperature resistant resin expressed in terms of number
average molecular weight is, but is not limited to, about 1,000 to
1,000,000, preferably about 2,000 to 500,000, more preferably about
5,000 to 300,000.
[0084] The shock resistance mentioned above is evaluated by the
impact test based on the free fall dart method (staircase method
(JIS K 7124-1)) using the resin film or resin sheet just after
taking out of a cryopreservation environment. Preferred as the
resin excellent in shock resistance are those showing a 50%
fracture energy (E50) of not lower than 0.1, preferably not lower
than 0.2, more preferably not lower than 1.0, in the
above-mentioned staircase method (at the temperature of liquid
nitrogen).
[0085] The polyimide mentioned above may be any one comprising a
heat-resistant polymer having imide bonds in the main chain
thereof; it includes, but is not limited to, nonthermoplastic
polyimides having imide bonds alone in the main chain, wholly
aromatic polyimides, organic solvent-soluble polyimides,
polyetherimides and polyimideamides, among others.
[0086] The above-mentioned low-temperature resistant resin film
includes, but is not limited to, those formed of a low-temperature
resistant resin by hot melting under high temperature and high
pressure conditions, extrusion or compression, or solvent
casting.
[0087] As the method of lamination of the adhesive fluoropolymer
film and the film other than the adhesive fluoropolymer film to
give the laminated film mentioned above, there may be mentioned the
hot lamination method, hot compression method, high-frequency
heating method and solvent casting method, among others. A
preferred method is, but is not limited to, the hot lamination
method from the ease of production viewpoint. The adhesive
fluoropolymer film is firmly bonded to the film other than the
adhesive fluoropolymer film, so that the adhesive fluoropolymer
film will not peel off from the film other than the adhesive
fluoropolymer film. From the safety production viewpoint, among
others, the temperature conditions in the above-mentioned hot
lamination method are, but are not limited to, about 200 to
300.degree. C., preferably about 200 to 250.degree. C.
[0088] In the practice of the invention, the laminated film can be
formed by laminating the film other than the adhesive fluoropolymer
film, for example the above-mentioned PI film, and the adhesive
fluororesin.
[0089] The lamination of the PI film or a like film other than the
adhesive fluoropolymer film and the adhesive fluororesin can be
carried out by the extrusion lamination method, for instance, and
can also be carried out by laminating the film other than the
adhesive fluoropolymer film, for example a PI film, and the
adhesive fluororesin by thermocompression bonding, for
instance.
[0090] The above-mentioned extrusion lamination may comprise, for
example, an extrusion step (a) in which the adhesive fluororesin is
melted and extruded onto the above-mentioned PI film or a like film
other than the adhesive fluoropolymer film, the compression bonding
step (b) in which the PI film or a like film other than the
adhesive fluoropolymer film and the adhesive fluororesin extruded
are inserted between rolls for compression bonding and the take-up
step (c) in which the laminate produced is taken up. Generally, the
extrusion step (a), compression bonding step (b) and take-up step
(c) are carried out in that order.
[0091] The preferred extrusion temperature range in the above
extrusion step (a) varies according to the kind of the PI film or a
like film other than the adhesive fluoropolymer film and the kind
of the adhesive fluororesin, the desired laminated film thickness
and other factors. Generally, the range is preferably not lower
than the melting point of the adhesive fluororesin used but lower
than the decomposition temperature of the same since laminated
films high in interlaminar bond strength are obtained in that
range.
[0092] In the above extrusion step (a), the rate of extrusion of
the molten adhesive fluororesin onto the PI film or a like film
other than the adhesive fluoropolymer film can be properly selected
according to the adhesive fluororesin used and the composition and
thickness, among others, of the PI film or a like film other than
the adhesive fluoropolymer film. However, the step can be carried
out within the range of 0.1 to 100 m/minute, for instance.
[0093] The above extrusion lamination, in particular the extrusion
step (a), is preferably carried out in an inert gas and/or the PI
film or a like film other than the adhesive fluoropolymer film is
dried beforehand or deprived of moisture by preheating so that the
laminated film high in interlaminar bond strength may be
obtained.
[0094] In the practice of the invention, the extrusion lamination
is considered to be characterized in that the adhesiveness of the
adhesive sites occurring in the adhesive fluororesin is displayed
in the extrusion step. When the extrusion lamination is carried out
in an inert gas and/or the PI film or a like film other than the
adhesive fluoropolymer film is dried in advance or deprived of
moisture by preheating, supposedly, the adhesiveness can be fully
displayed.
[0095] The operating conditions in the steps other than the
extrusion step (a) in the above extrusion lamination can be
properly selected in the conventional manner according to the kinds
of the PI film or a like film other than the adhesive fluoropolymer
film and the adhesive fluororesin, the intended thickness of the
laminated film and other factors.
[0096] When the lamination of the PI film or a like film other than
the adhesive fluorine-containing film and the adhesive fluororesin
is to be carried out in the manner of thermocompression, the
lamination can be carried out generally by molding the adhesive
fluororesin into a film by the extrusion molding method known in
the art, for instance, and laying the adhesive fluororesin film
obtained and the PI film or a like film other than the adhesive
fluoropolymer film one on the other and compressing the assembly
with heating.
[0097] The above-mentioned thermocompression is preferably carried
out at a temperature of 120 to 300.degree. C. Amore preferred lower
limit to that temperature is 140.degree. C., and a more preferred
upper limit thereto is 280.degree. C.
[0098] The PI film or a like film other than the adhesive
fluoropolymer film may be preheated in advance or dried beforehand
prior to the lamination by thermocompression bonding, for
instance.
[0099] When the respective layers are laminated by
thermocompression, for instance, the layers after lamination may be
heated for aging so that the interlaminar bonding may be
improved.
[0100] The heating for such aging is preferably carried out at 200
to 280.degree. C.
[0101] The above-mentioned laminated film is shaped into a
container or bag-like article by heat sealing. More specifically,
two laminated films are placed one on the other so that the
adhesive fluoropolymer films come into contact with each other and,
then, heat sealing is carried out. The capacity of the package is,
but is not limited to, about 5 to 500 ml, preferably about 10 to
300 ml, since the cryopreservation container generally has a
capacity of about 2 to 200 ml. In view of the seal strength between
the laminated films, the heat seal width is, but is not limited to,
about 2 to 20 mm, preferably about 5 to 15 mm. Also from the
viewpoint of the seal strength between the laminated films, the
heat seal temperature is about 180 to 250.degree. C., preferably
about 200 to 220.degree. C. General-purpose fluororesin films
cannot be sealed at such low temperatures as 180 to 250.degree. C.
Thus, the adhesive fluoropolymer film according to the invention
shows good sealability at low temperatures and therefore is low in
production process cost.
[0102] The package for a cryopreservation container according to
the invention is used for further packaging a cryopreservation
container containing such a biological sample as erythrocytes,
platelets, plasma or a like blood component, bone marrow fluid,
another body fluid or a cell suspension. On that occasion, the air
between the cryopreservation container and the package can
favorably be removed with ease by the packaging method using an
auxiliary device disclosed in Japanese Kokai Publication
2000-185716, for instance. The packaging method is not limited
thereto, however.
[0103] The package for a cryopreservation container according to
the invention can be produced by shaping the laminated films into a
container or bag-like article by the heat seal technique, for
instance. When laminated films having the outermost layer made of
an adhesive fluoropolymer film at least one side are used as the
above-mentioned laminated films, the package for a cryopreservation
container as obtained can be a container having the adhesive
fluoropolymer film as the outermost layer on at least one side
thereof, preferably a container having the adhesive fluoropolymer
film as the outermost layer on at least the inner side of the
container.
[0104] The package for a cryopreservation container according to
the invention can satisfactorily endure such very low temperatures
as -80 to -196.degree. C. In actually preserving such a blood
component as erythrocytes, platelets or plasma, bone marrow fluid
or another body fluid or a cell suspension, gradual cooling is
preferred so that such tissues may not be damaged. For example,
there may be mentioned the method comprising once cooling the whole
package to about -80.degree. C. in a deep freezer (refrigerator),
for instance, then transferring the same into liquid nitrogen for
preservation. The method of storage is not limited to such method,
however. On the occasion of using the stored blood or cells, for
instance, the blood or cells can be thawed using means for warming,
such as a warm bath at 37 to 40.degree. C. The method of thawing is
not limited to such, however.
[0105] In storing a biological sample in the above-mentioned
cryopreservation container, a commercially available preserving
fluid can be adequately used. In the case of storing cells, DMEM
medium, RPMY 1640 medium, 199 medium and phosphate buffer may be
mentioned as preserving fluids therefor. Preferably, about 0.5 to
2% by volume of albumin may be added. More preferably, dimethyl
sulfoxide (DMSO) may be added as an agent for protecting against
freeze damage at a final concentration of about 5 to 20% by volume.
In the case of storing an organ, Euro-Collin's solution and UW
solution, among others, may be mentioned. Preferably, dimethyl
sulfoxide (DMSO) may be added as an agent for protecting against
freeze damage at a final concentration of about 5 to 20% by volume.
The selection and preparation of such a preserving fluid can be
appropriately made by the one skilled in the art, hence are not
particularly restricted.
[0106] As a method of freezing the package for a cryopreservation
container according to the invention, there may be mentioned the
method comprising freezing the package used for further packaging
the cryopreservation container containing or storing a biological
sample at 0.degree. C. or below. Preferred as the method of
freezing is the method comprising freezing at -80.degree. C. or
below. In the above method of freezing, the package is preferably
cooled gradually to a desired temperature for freezing so that the
biological sample may not be damaged. As such a method of freezing,
there may be mentioned, for example, the method comprising cooling
the package once to about -80.degree. C. in a deep freezer
(refrigerator) and the immersing the same in liquid nitrogen. The
cryopreservation container may also contain such a preserving fluid
as mentioned above according to need. The package is then generally
freeze-preserved following freezing by the above method.
[0107] The package of the invention, which has the constitution
described hereinabove, will not be broken even at such a very low
temperature as the liquid nitrogen temperature (-196.degree. C.)
and will not show any decrease in sealability at the sealed
portion. Therefore, it will never allow such a refrigerant as
liquid nitrogen to enter the same and can prevent the contents from
being contaminated or leaking out; thus, it shows good protective
performance characteristics.
[0108] Furthermore, the above-mentioned package is tolerable in a
low temperature range not so low as the above-mentioned very low
temperatures provided that the temperature is lower than the
melting point of the adhesive fluororesin used and can show
resistance to a very wide temperature range and will never undergo
breakage or show decreases in sealability at the sealed portion
even upon rapid changes in temperature, for example when it is
placed under ordinary temperature conditions after placement at the
above-mentioned very low temperatures.
[0109] While the mechanisms why the package of the invention
produces such excellent effects as mentioned above are not clear,
the following characteristics presumably produce synergistic
effects: (1) the PI is resistant to very low temperatures and can
maintain the shape of the molded article even at very low
temperatures as the liquid nitrogen temperature, (2) the package is
excellent in the interlaminar adhesion between the PI film and the
adhesive fluororesin layer, (3) the PI film and the adhesive
fluororesin layer can be bonded directly without using any adhesive
agent and, therefore, the problems encountered in using an adhesive
agent, namely the problem of embrittlement and breakage of the
adhesive layer at such very low temperatures as the liquid nitrogen
temperature and the problem of outgas emission and substance
elution from the adhesive layer, can be avoided and (4) the package
is formed from the laminated films obtained by lamination of the PI
film and the adhesive fluororesin layer by mutual thermowelding of
the adhesive fluororesin layers and therefore is excellent in the
mutual adhesion between the adhesive fluororesin layers and has
reliable sealability.
[0110] The package for a cryopreservation container according to
the invention can be suitably used in packaging a cryopreservation
container.
[0111] The cryopreservation container can be suitably used as a
cryopreservation container for a biological sample. As the
biological sample that can be stored in the above cryopreservation
container, there may be mentioned, for example, human-derived
biological samples, biological samples derived from animals other
than humans or from plants, viruses, microorganisms and like
biological samples.
[0112] The above cryopreservation container is a container capable
of containing, in a tightly closed condition, such a biological
sample as a blood component, cells, a tissue, an organ, viruses,
bacteria, sperms, ova or fertilized ova, for instance. For example,
mention may be made of commercially available polypropylene vials
and the containers disclosed in Patent Documents 1 to 4. Preferred
ones from the low-temperature resistance viewpoint are, but are not
limited to, freezing bags for medical use which are disclosed in
Patent Document 4 and constituted of laminated films consisting of
an ultrahigh molecular weight polyethylene film and a thermoplastic
resin film compatible with the ultrahigh molecular weight
polyethylene.
[0113] As the blood component, there may be mentioned whole blood,
erythrocytes, leukocytes, plasma, platelets and platelet rich
plasma, among others. As the cells, there may be mentioned rare
cells such as hematopoietic stem cells, ES cells, mesenchymal stem
cells, mononuclear marrow cells, spermatids and egg cells as well
as common cells such as neurocytes, epithelial cells and
fibroblasts. Further, as the vital tissues, there may be mentioned
various tissues and organs such as tendons, nerves, ligaments,
esophagi, tracheas, Langerhans islands, mucoepithelial tissues,
keratoepithelial tissues, cultured corneal tissues and like
membranous tissues as well as organs. such as pancreases, hearts,
lungs, livers and kidneys. As the viruses, there may be mentioned
hepatitis B virus, hepatitis C virus, coronavirus and mosaic virus,
among others. As the bacteria, there may be mentioned Mycobacterium
tuberculosis, Haemophilus influenzae, Escherichia coli,
Staphylococcus aureus, hemolytic streptococci and Klebsiella
pneumoniae, among others. Further, sperms, ova and fertilized ova
may be mentioned in relation to the field of infertility
treatments, for instance. These blood or blood components, cells
including rare cells and other vital tissues to be stored are
selected at the workers' discretion according to the intended
purpose, hence are not particularly restricted.
[0114] As the vital tissues, there may further be mentioned, for
example, living organism-derived body fluids (blood, cerebrospinal
fluid, lymph, etc.) and components thereof (erythrocytes,
leukocytes, platelets, plasmas, sera, etc.), living
organism-derived tissues (blood vessels, corneas, menisci, cerebral
tissues, skins, subcutaneous tissues, epithelial tissues, osseous
tissues, muscular tissues, etc.), organs (eyes, lungs, kidneys,
hearts, livers, pancreases, spleens, digestive tracts, bladders,
ovaries, testicles, etc.), various cells (hematopoietic stem cells
such as cord blood- or peripheral blood-derived hematopoietic stem
cells, marrow cells, hepatocytes, splenocytes, brain cells and
other various organ cells, neurocytes, sperms, egg cells,
fertilized ova, embryonic stem cells (ES cells), cancer cells for
research and therapeutic purposes, cultured cells, stem cells, germ
cells, etc.) and so forth.
[0115] As the biological samples, there may be mentioned human
vital tissues, inheritance-related substances and, further, vital
tissues and inheritance-related substances derived from animals
including small animals such as small experimental animals;
microorganisms, bacteria, and inheritance-related substances
derived therefrom; and so forth. These are used in the research
field, for instance.
[0116] As the biological samples, there may further be mentioned
vital tissues and inheritance-related substances derived from
domestic animals and animals and those used in the fields of
researches, cultures, cultivations, horticulture and
agriculture.
[0117] As the biological samples, there may also be mentioned plant
seeds, pollens, cultured cells, shoot apex cells and
inheritance-related substances.
[0118] As the biological samples, there may further be mentioned
vital tissues and inheritance-related substances derived from
marine algae, fish and the like. These are used, for example, in
researches in the field of fishery sciences.
[0119] As the inheritance-related substances, there may be
mentioned DNAS, hosts, vectors and so forth.
[0120] The biological samples mentioned above can be used for
medical purposes; in research and development in the fields of
agriculture, animal husbandry, forestry, fishery, horticulture and
so forth; in the treatment of diseases, infertility treatment and
breeding of animals in the pet industry and animal industry and for
the cloning technology, for instance.
[0121] Thus, the cryopreservation container mentioned above can be
used in various fields such as medical treatment; researches;
animal husbandry, horticulture and agriculture; and fishery, and
the package for such cryopreservation container according to the
invention can also be used in various fields.
EXAMPLES
[0122] The following examples illustrate the present invention in
detail. These examples are, however, by no means limitative of the
scope of the invention.
Examples 1 to 4
Production of Packages for Cryopreservation Containers
[0123] A two- or three-layer film was produced by the hot
lamination method using a polyimide film and one or two films made
of a ternary system random copolymer produced from
tetrafluoroethylene, perfluoro(vinyl propyl ether) and
perfluoro(1,1,9,9-tetrahydro-2,5-bistrifluoromethyl-3,6-dio
xa-8-nonenol) (hereinafter referred to as "inner layer fluororesin
film" and "outer layer fluororesin film") as applied to one side or
both sides of the polyimide film. Sheets with a size of
100.times.95 mm were cut from each film and packages (25 ml in
capacity) for cryopreservation containers were produced by laying
one of two sheets on top of the other so that the inner layer
fluororesin films came into contact with each other and
heat-sealing 2-mm-wide margins. The polyimide film thickness and
inner layer fluororesin film thickness data are shown in Table
1.
[0124] The copolymer composition of the ternary system random
copolymer film was such that the ratio of
perfluoro(1,1,9,9-tetrahydro-2,5-bistrifluoromethyl-3,6-dio
xa-8-nonenol) monomer units to tetrafluoroethylene monomer units
plus perfluoro (vinyl propyl ether) monomer units was 1:99. The
copolymer composition was determined by .sup.19F-NMR.
Comparative Example 1
[0125] Packages made of a perfluoroethylene-propylene copolymer
were used as packages for cryopreservation containers for
comparison.
Reference Example 1
Cryopreservation Containers to be Packaged in Packages
[0126] Cryopreservation containers made of a laminated film
produced by laminating an ultrahigh-molecular-weight polyethylene
film and two low-molecular-weight polyethylene films on both sides
of the former were used.
Synthesis Example 1
Synthesis of an Adhesive Fluororesin
[0127] A 820-liter glass-lined autoclave was charged with 200 L of
pure water, the system inside was thoroughly purged with nitrogen
gas and then the nitrogen was evacuated therefrom. The autoclave
was charged with 113 kg of 1-fluoro-1,1-dichloroethane, 95 kg of
hexafluoropropylene and 85 g of cyclohexane. Then, 292 g of
perfluoro (1,1,5-trihydro-1-pentene)
[CH.sub.2.dbd.CF(CF.sub.2).sub.3H] was fed to the autoclave under
pressure using nitrogen gas, and the vessel inside temperature was
maintained at 35.degree. C. and the rate of stirring at 200 rpm.
Further, tetrafluoroethylene was fed to the autoclave until arrival
of the pressure at 7.25 kg/cm.sup.2G, followed by feeding of
ethylene until arrival of the pressure at 8 kg/cm.sup.2G.
[0128] Then, the polymerization was started by feeding 1.9 kg of a
50% (by mass) solution of di-n-propyl peroxydicarbonate in
methanol. Since otherwise the vessel inside pressure fell with the
progress of the polymerization, a
tetrafluoroethylene/ethylene/hexafluoropropylene mixed gas (mole
ratio=39.2:43.6:17.3) was additionally fed under pressure and,
while maintaining the polymerization pressure at 8 kg/cm.sup.2G in
that manner, the polymerization was continued and, during the
polymerization, 1100 g of CH.sub.2.dbd.CF(CF.sub.2).sub.3H, divided
in 20 portions, was charged using a micropump. The polymerization
was carried out for a total of 32 hours. After completion of the
polymerization, the contents were recovered and washed with water
to give 95 kg of a powdery adhesive fluororesin.
[0129] The adhesive fluororesin obtained was subjected to the
following measurements.
(1) Monomer Units
[0130] .sup.19F-NMR analysis was carried out and determinations
were made.
(2) Number of Carbonate Groups
[0131] A film with a thickness of 0.05 to 0.2 mm was prepared by
compression molding of the adhesive fluororesin powder at room
temperature. The film obtained was subjected to infrared absorption
spectrometry, and the absorbance of the peak [1809 cm.sup.-1
(.nu..sub.c.dbd.O)] assignable to the carbonyl group in the
carbonate group [--OC(.dbd.O)--O--] was measured. The number of
carbonate groups per 1.times.10.sup.6 main chain carbon atoms was
calculated based on the measured value obtained according to the
formula given below.
N=500AW/.epsilon.df
[0132] A: Absorbance at the above-mentioned .nu..sub.C.dbd.O
[0133] .epsilon.: Molar extinction coefficient at the above
.nu..sub.C.dbd.O[1.cm.sup.-1.mol.sup.-1]
[0134] (The value .epsilon.=170 was employed based on the results
with model compounds.)
[0135] W: Composition average molecular weight calculated based on
the monomer composition
[0136] d: Film density [g/cm.sup.3]
[0137] f: Film thickness [mm] measured using a micrometer.
[0138] The above infrared absorption spectrometry was carried out
by making 40 scans on Perkin-Elmer FTIR spectrometer
1760.times.(product of Perkin-Elmer). The analysis of the
absorbance of .nu..sub.c.dbd.O was carried out using Perkin-Elmer
Spectrum for Windows (registered trademark) Ver. 1.4C software.
(3) Melting Point
[0139] The measurement was carried out at a programming rate of
10.degree. C./minute using a differential scanning calorimeter
(product of Seiko) and the temperature at the maximum of the
melting peak obtained was regarded as the melting point.
[0140] The adhesive fluororesin obtained had a monomer unit
composition of
TFE/Et/HFP/CH.sub.2.dbd.CF(CF.sub.2).sub.3H=38.9/45.9/14.8/0.4, the
number of carbonate groups was 411 per 1.times.10.sup.6 main chain
carbon atoms and the melting point thereof was 171.8.degree. C.
Example 5
[0141] (1) The adhesive fluororesin obtained in the synthesis
example was molded into an adhesive fluororesin film (thickness: 25
.mu.m) through a T die mounted on a single screw extruder with a
cylinder diameter of 90 mm under the conditions of a cylinder
temperature of 170 to 230.degree. C., a die temperature of
230.degree. C. and a screw speed of 10 rpm. The adhesive
fluororesin film obtained and a polyimide film (product name:
Kapton 100H, product of Du Pont Toray, thickness: 25 .mu.m) were
laminated using a hot roll at a temperature of 250.degree. C. to
give a laminated film (length 20 m.times.width 200 mm.times.total
thickness 50 .mu.m; hereinafter referred to also as "continuous
film"). Rectangular specimens, 100 mm in the lengthwise direction
and 10 mm in the transverse direction, were cut out from the
laminated film obtained (fluororesin layer thickness: 25 .XI.m,
polyimide layer thickness: 25 .mu.m). Each specimen was provided
with margins for gripping at one end by peeling the adhesive
fluororesin layer from the polyimide layer using a cutter and
subjected to 180-degree peeling on a Tensilon universal testing
machine (product of Orientec) at a speed of 25 mm/minute. The bond
strength of the laminated film was 400 N/m. (2) Then, two
12-cm-square laminated film sheets were excised from the
above-mentioned continuous sheet and placed one on top of the other
with the adhesive fluororesin layers inside, and three sides were
fusion-bonded by heating at 210.degree. C. for 5 seconds using a
heat sealer. The seal width (bonding part width) was 1 cm. Thus, a
package (capacity: 25 ml) for a cryopreservation container was
formed. The thickness of the polyimide film and the thickness of
the adhesive fluororesin film (inner layer fluororesin film) are
shown in Table 1.
TABLE-US-00001 TABLE 1 Inner layer fluororesin film Polyimide film
Example 1 25 .mu.m 25 .mu.m Example 2 50 .mu.m 25 .mu.m Example 3
25 .mu.m 50 .mu.m Example 4 50 .mu.m 50 .mu.m Example 5 25 .mu.m 25
.mu.m
Experimental Example 1
Freezing Test
[0142] A 10% (by volume) aqueous solution of DMSO (in about 25-ml
portions) was packed in cryopreservation containers described in
Reference Example 1. These cryopreservation containers were
packaged with the packages of Examples 1 to 5 and Comparative
Example 1, respectively, and were put in aluminum cases,
respectively. The cases were allowed to stand in a deep freezer
(refrigerator) at -80.degree. C. for 4 hours for freezing the
contents. After this freezing treatment, the packages with the
respective cryopreservation containers in the aluminum cases were
transferred into liquid nitrogen and stored for 1 week. The stored
packages with the respective cryopreservation containers were taken
out of the aluminum cases and placed in a warm bath at 37 to
40.degree. C. for thawing, and each package was observed by the eye
as to whether there was any damage or liquid nitrogen intrusion or
some other trouble.
[0143] The results of this experiment are shown in Table 2. In
Comparative Example 1, the percent breakage was 2%, whereas the
packages for cryopreservation containers according to the invention
all showed no breakage at all in spite of the great number of
tests, namely 100 packages in each example.
TABLE-US-00002 TABLE 2 Number of damaged packages/ number of
packages tested Example 1 0/100 Example 2 0/100 Example 3 0/100
Example 4 0/100 Example 5 0/100 Comparative 2/100 Example 1
Experimental Example 2
Freezing Test
[0144] A cell suspension was prepared by suspending MOLT-4 cells
(obtained from RIKEN) in RPMI 1640 medium (product of Invitrogen)
to a concentration of about 1.0.times.10.sup.7 cells/ml. This cell
suspension was packed, in about 25-ml portions, in cryopreservation
containers described in Reference Example 1. These cryopreservation
containers were packaged with the packages of Example 5 and
Comparative Example 1, respectively, and were put in aluminum
cases, respectively. The cases were allowed to stand in a deep
freezer (refrigerator) at -80.degree. C. for 4 hours for freezing
the contents. After this freezing treatment, the packages with the
respective cryopreservation containers in the aluminum cases were
transferred into liquid nitrogen and stored for 1 week. The stored
packages with the respective cryopreservation containers were taken
out of the aluminum cases and placed in a warm bath at 37 to
40.degree. C. for thawing, and each package was observed by the eye
as to whether there was any damage or liquid nitrogen intrusion or
some other trouble. In each example, 10 tests were performed.
[0145] As a result, one cryopreservation container package was
found damaged in Comparative Example 1 whereas the 10
cryopreservation container packages according to the invention
showed no damage at all.
INDUSTRIAL APPLICABILITY
[0146] The package for a cryopreservation container according to
the invention makes it possible to store blood, rare cells and
vital tissues in a very low temperature environment without any
damage to the package/container. Since it has a relatively thin
film thickness, it will not reduce the conduction of heat to the
contents of the cryopreservation container in the package. Further,
the sealing strength resulting from heat sealing after placing a
cryopreservation container in the packages is very good and,
therefore, liquid nitrogen can be inhibited from entering the
inside and thus contamination with bacteria, viruses or the like
contained in liquid nitrogen can be avoided and the package can be
prevented from being broken by expansion of intruder liquid
nitrogen on the occasion of thawing.
* * * * *