U.S. patent application number 13/183233 was filed with the patent office on 2013-01-17 for patch package.
This patent application is currently assigned to Nitto Denko Corporation. The applicant listed for this patent is Toshiharu IZAKI, Masakatsu KONNO, Ryohei SAKURABA, Minoru SUZUKI, Hiroyuki YAEGASHI, Keiji YAMAMOTO. Invention is credited to Toshiharu IZAKI, Masakatsu KONNO, Ryohei SAKURABA, Minoru SUZUKI, Hiroyuki YAEGASHI, Keiji YAMAMOTO.
Application Number | 20130015092 13/183233 |
Document ID | / |
Family ID | 47518312 |
Filed Date | 2013-01-17 |
United States Patent
Application |
20130015092 |
Kind Code |
A1 |
SUZUKI; Minoru ; et
al. |
January 17, 2013 |
PATCH PACKAGE
Abstract
The present invention relates to a patch package having a patch
and a packaging film sandwiching the patch, wherein the packaging
film is tightly sealed in two or more flat heat-sealed parts, and
respective adjacent two or more flat heat-sealed parts are
separated across a non-sealed part.
Inventors: |
SUZUKI; Minoru; (Osaka,
JP) ; YAMAMOTO; Keiji; (Osaka, JP) ; KONNO;
Masakatsu; (Osaka, JP) ; YAEGASHI; Hiroyuki;
(Osaka, JP) ; IZAKI; Toshiharu; (Osaka, JP)
; SAKURABA; Ryohei; (Osaka, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
SUZUKI; Minoru
YAMAMOTO; Keiji
KONNO; Masakatsu
YAEGASHI; Hiroyuki
IZAKI; Toshiharu
SAKURABA; Ryohei |
Osaka
Osaka
Osaka
Osaka
Osaka
Osaka |
|
JP
JP
JP
JP
JP
JP |
|
|
Assignee: |
Nitto Denko Corporation
Ibaraki-shi
JP
|
Family ID: |
47518312 |
Appl. No.: |
13/183233 |
Filed: |
July 14, 2011 |
Current U.S.
Class: |
206/497 |
Current CPC
Class: |
A61F 13/00076 20130101;
B65D 75/30 20130101 |
Class at
Publication: |
206/497 |
International
Class: |
B65D 65/00 20060101
B65D065/00 |
Claims
1. A patch package comprising a patch and a packaging film
sandwiching the patch, wherein the packaging film is tightly sealed
in two or more flat heat-sealed parts, and respective adjacent flat
heat-sealed parts of the two or more flat heat-sealed parts are
separated across a non-sealed part, and wherein each of the two or
more flat heat-sealed parts has a band-like shape, the band-like
flat heat-sealed parts have a band width of 0.4 mm-1.0 mm, and the
non-sealed part has a band-like shape and has a band width of 2.0
mm-10 mm.
2. The patch package of claim 1, further comprising an embossed
heat-sealed part outside the outermost flat heat-sealed part of the
two or more flat heat-sealed parts.
3. The patch package of claim 2, wherein the outermost flat
heat-sealed part and the embossed heat-sealed part are separated
across a non-sealed part.
4. The patch package of claim 2, wherein the two or more flat
heat-sealed parts, or the two or more flat heat-sealed parts and
the embossed heat-sealed part form a pattern surrounding the
patch.
5. The patch package of claim 4, wherein the patch is sandwiched
between two packaging films, and the two or more flat heat-sealed
parts, or the two or more flat heat-sealed parts and the embossed
heat-sealed part form a pattern surrounding the entire periphery of
the patch.
6. The patch package of claim 4, wherein the patch is sandwiched by
a double-folded packaging film, and the two or more flat
heat-sealed parts, or the two or more flat heat-sealed parts and
the embossed heat-sealed part are not formed in a bent part of the
packaging film.
7.-9. (canceled)
10. The patch package of claim 1, having three flat heat-sealed
parts, or three flat heat-sealed parts and an embossed heat-sealed
part.
11. The patch package of claim 1, wherein the patch is a patch
preparation containing a drug.
12. The patch package of claim 3, wherein the two or more flat
heat-sealed parts, or the two or more flat heat-sealed parts and
the embossed heat-sealed part form a pattern surrounding the
patch.
13. The patch package of claim 12, wherein the patch is sandwiched
between two packaging films, and the two or more flat heat-sealed
parts, or the two or more flat heat-sealed parts and the embossed
heat-sealed part form a pattern surrounding the entire periphery of
the patch.
14. The patch package of claim 12, wherein the patch is sandwiched
by a double-folded packaging film, and the two or more flat
heat-sealed parts, or the two or more flat heat-sealed parts and
the embossed heat-sealed part are not formed in a bent part of the
packaging film.
15.-17. (canceled)
18. The patch package of claim 12, having three flat heat-sealed
parts, or three flat heat-sealed parts and an embossed heat-sealed
part.
19. The patch package of claim 18, wherein the patch is a patch
preparation containing a drug.
Description
TECHNICAL FIELD OF THE INVENTION
[0001] The present invention relates to a patch package wherein a
patch is packed with a packaging film. More particularly, the
present invention relates to a patch package wherein packaging
films facing across a patch are hermetically-sealed in a flat
heat-sealed part.
BACKGROUND OF THE INVENTION
[0002] In recent years, various patchs have been developed to
protect and heal a wound, a pressure ulcer, a thermal burn ulcer, a
peel off-wound and the like on the human skin. In addition, as a
means of administering a drug to a body, a method comprising
adhering a patch containing a drug to a body to allow transdermal
absorption of the drug from the skin has been developed. Such a
drug-containing patch (hereinafter sometimes to be referred to as a
patch preparation) comprises a support made of a plastic film such
as polyester, polyethylene and the like or a non-woven fabric, an
adhesive layer containing a transdermally absorbable drug, which is
laminated on one surface of the support, and a coating material
covering an exposed surface of the adhesive layer. Generally, a
patch and a patch preparation are indivisually packed (tightly
sealed) in a package made of a packaging film, for the purpose of
protecting the patch, preventing volatilization of the contained
drug and/or avoiding influences of humidity, oxygen etc. on the
drug (decomposition, oxidation etc.) and the like.
[0003] Patches are generally packed (tightly sealed) individually
by a heat sealing treatment of a packaging film surrounding the
patch by a packaging machine. However, depending on the kind of a
packaging film and a packaging method, the heat sealing treatment
may not be sufficient, which causes a problem of pinholes sometimes
developed in the part subjected to the heat sealing treatment
(hereinafter sometimes to be referred to as a heat-sealed
part).
[0004] To solve the above-mentioned problem, for example,
JP-A-2006-44793 proposes a patch package wherein an embossed
heat-sealed part and a flat heat-sealed part in a packaging film
surround the periphery of the patch, as shown in FIG. 6A and FIG.
6B. However, when the seal width of the flat heat-sealed part is
increased in an attempt to decrease development of pinholes and
improve air-tightness, the possibility of developing air bubbles in
the flat heat-sealed part becomes high to possibly degrade the
appearance thereof.
SUMMARY OF THE INVENTION
[0005] The present invention aims to solve the above-mentioned
problems, and provides a patch package which is free of pinholes,
superior in air-tightness, and has a good appearance of a flat
heat-sealed part.
[0006] The present inventors have conducted intensive studies of
the aforementioned problems and found a particular effect of
improved air-tightness by providing, in a packaging film
sandwiching a patch, at least two flat heat-sealed parts in a
pattern surrounding the patch, and providing a non-sealed part
between the adjacent flat heat-sealed parts, as compared to when a
seal width of the flat heat-sealed part is simply increased. In
addition, they have found that the non-sealed part acts as an
escape of bubbles, that may be generated during formation of the
flat heat-sealed part, to decrease the sealing defect in the flat
heat-sealed part, whereby a superior flat heat-sealed part free of
bubbles can be obtained. The present invention has been completed
based on these findings.
[0007] Accordingly, the present invention provides the following.
[0008] [1] A patch package comprising a patch and a packaging film
sandwiching the patch, wherein the packaging film is tightly sealed
in two or more flat heat-sealed parts, and respective adjacent flat
heat-sealed parts of the two or more flat heat-sealed parts are
separated across a non-sealed part. [0009] [2] The patch package of
the above-mentioned [1], further comprising an embossed heat-sealed
part outside the outermost flat heat-sealed part of the two or more
flat heat-sealed parts. [0010] [3] The patch package of the
above-mentioned [2], wherein the outermost flat heat-sealed part
and the embossed heat-sealed part are separated across a non-sealed
part. [0011] [4] The patch package of any one of the
above-mentioned [1]-[3], wherein the two or more flat heat-sealed
parts, or the two or more flat heat-sealed parts and the embossed
heat-sealed part form a pattern surrounding the patch. [0012] [5]
The patch package of any one of the above-mentioned [1]-[4],
wherein the patch is sandwiched between two packaging films, and
the two or more flat heat-sealed parts, or the two or more flat
heat-sealed parts and the embossed heat-sealed part form a pattern
surrounding the entire periphery of the patch. [0013] [6] The patch
package of any one of the above-mentioned [1]-[4], wherein the
patch is sandwiched by a double-folded packaging film, and the two
or more flat heat-sealed parts, or the two or more flat heat-sealed
parts and the embossed heat-sealed part are not formed in a bent
part of the packaging film. [0014] [7] The patch package of any one
of the above-mentioned [1]-[6], wherein each of the two or more
flat heat-sealed parts has a band-like shape. [0015] [8] The patch
package of the above-mentioned [7], wherein the band-like flat
heat-sealed parts have a band width of 0.4 mm-1.0 mm. [0016] [9]
The patch package of any one of the above-mentioned [1]-[8],
wherein the non-sealed part has a band-like shape and has a band
width of 1.5 mm-10 mm. [0017] [10] The patch package of any one of
the above-mentioned [1]-[9], having three flat heat-sealed parts,
or three flat heat-sealed parts and an embossed heat-sealed part.
[0018] [11] The patch package of any one of the above-mentioned
[1]-[10], wherein the patch is a patch preparation containing a
drug.
[0019] The patch package of the present invention is free of
pinholes, superior in air-tightness, and has a good appearance of
the flat heat-sealed part. In addition, the patch package provides
an effect of high suppression of oxidation and decomposition for a
drug easily decomposed by oxygen or moisture.
[0020] Furthermore, in the patch package of the present invention,
each flat heat-sealed part can be certainly formed at a uniform
seal width. Therefore, it affords an effect of remarkable reduction
of percent defective of flat heat sealing in industrial production
of the patch package.
[0021] In the patch package of the present invention, moreover,
even when one of the two or more flat heat-sealed parts develops
pinholes and the like, the remaining flat heat-sealed part ensures
sufficient air-tightness. Thus, it affords an effect of remarkable
reduction of percent defective of flat heat sealing in industrial
production of the patch package.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1A is a plane view showing embodiment 1 of the present
invention.
[0023] FIG. 1B is a sectional view along I-I line in FIG. 1A.
[0024] FIG. 2A is a plane view showing embodiment 2 of the present
invention.
[0025] FIG. 2B is a sectional view along II-II line in FIG. 2A.
[0026] FIG. 3 is a plane view showing embodiment of the present
invention.
[0027] FIG. 4 is a plane view showing embodiment 4 of the present
invention.
[0028] FIG. 5A is a plane view showing embodiment 5 of the present
invention.
[0029] FIG. 5B is a sectional view along IV-IV line in FIG. 5A.
[0030] FIG. 6A is a plane view showing a packaging structure of a
conventional patch package.
[0031] FIG. 6B is a sectional view along line in FIG. 6A.
[0032] FIG. 7 shows the relationship between the preservation
period and water content of patches tightly sealed in the patch
packages of Examples and Comparative Examples.
[0033] In the Figures, 1 is a package, 2 is a patch, 3 is a first
flat heat-sealed part, 4 is a second flat heat-sealed part, 5 is a
third flat heat-sealed part, 6 is a first non-sealed part, 7 is a
second non-sealed part, 8 is a third non-sealed part, 9 is an
embossed heat-sealed part, and 10 is a packaging film.
DETAILED DESCRIPTION OF THE INVENTION
[0034] The present invention is explained in detail in the
following.
[0035] The patch package of the present invention comprises a patch
and a packing film sandwiching the patch, and has a structure
wherein the packaging film is tightly sealed in two or more flat
heat-sealed parts. Two packaging films having approximately the
same shape may be placed on top of each other and a patch may be
insetted between the two packaging films. Alternatively, one
packaging film may be folded in two and a patch may be insetted
therebetween. In the present invention, the flat heat-sealed part
is where a packaging film is flat heat sealed around a patch, and
is generally formed in a pattern surrounding the patch. For
example, when a patch is packed by being sandwiched between two
packaging films, the flat heat-sealed part is formed in a pattern
surrounding the entire periphery, of the patch. Particularly, when
a package having a quadrate plane shape is to be obtained, a flat
heat-sealed part is formed in two packaging films on four sides of
the periphery of the patch (four-sided seal). In addition, when a
patch is sandwiched by a double-folded packaging film, and the
package has a quadrate plane shape, a flat heat-sealed part is
formed on three sides of the packaging film except the bent part of
the film (three-sided seal). The four-sided seal is advantageous in
that it can control the insersion position of a patch when it is
sandwiched between the packaging films.
[0036] The patch package of the present invention generally has at
least two flat heat-sealed parts, preferably 2-5 parts and
particularly preferably 2 or 3 parts, from the aspect of easy
production. While the shape of the flat heat-sealed part (the shape
of flat heat-sealed part on the flat plane when the package is seen
in a planar view) is not particularly limited, it is preferably a
band-like shape. In the case, the width of the flat heat-sealed
part (band width) is generally 0.4 mm-1.0 mm, preferably 0.4 mm-0.6
mm. When the width (band width) is less than 0.4 mm, the effect of
preventing development of pinholes becomes low. When the width
exceeds 1.0 mm, the pressure in the heat sealing treatment is
dispersed during formation of the flat heat-sealed part and the
heat sealing treatment becomes incomplete. As a result, pinholes
may be developed, and air bubbles easily enter into the flat
heat-sealed part, which is not preferable for the appearance
thereof. While the width of the band-like flat heat-sealed part may
be uniform or vary, it is preferably uniform. In addition, in two
or more band-like flat heat-sealed parts, the width (band width)
and pattern of the flat heat-sealed parts may be same or different,
and they are preferably the same.
[0037] The patch package of the present invention has two or more
flat heat-sealed parts, and respective adjacent flat heat-sealed
parts are separated across a non-sealed part. With a non-sealed
part between the adjacent flat heat-sealed parts, air bubbles
developed when forming the flat heat-sealed parts can be released
into the non-sealed part, and the flat heat-sealed part can be
formed beautifully. While the shape of the non-sealed part (the
shape of non-sealed part on the flat plane when the package is seen
in a planar view) is not particularly limited, it is preferably a
band-like shape. In this case, the width (band width) of the
non-sealed part is generally 1.5 mm-10 mm, preferably 2.0 mm-10 mm.
When the width (band width) of the non-sealed part is not less than
1.5 mm, a patch contained in the package has enhanced
preservability. In addition, when the width is not more than 10 mm,
a package having good handling property which uses a saved amount
of the packaging film can be obtained. When two or more non-sealed
parts are present, the width (band width) and pattern of respective
non-sealed parts may be the same or different, and preferably the
same.
[0038] The packaging structure of the present invention may have an
embossed heat-sealed part on the circumference of the package. That
is, it may have a structure wherein an embossed heat-sealed part is
present at the outside of the outermost flat heat-sealed part (that
is, the flat heat-sealed part at the farthest position from the
patch) in the packaging films sandwiching the patch. The embossed
heat-sealed part is a heat-sealed part having concaves and
convexes. Examples of the concaves and convexes include patterns
such as general straw mat pattern, lattice pattern, straight line
pattern, wave shape pattern, point-like pattern and the like. To
obtain an appropriate seal strength, a combination of a straw mat
pattern and a straight line pattern is preferable. The pitch of the
above-mentioned pattern can be set within the range of 0.2 mm-2 mm,
preferably 0.4 mm-0.8 mm, in the case of, for example, a straw mat
pattern. When the pitch of the straw mat pattern is narrower than
0.2 mm, molding using a heat block metal mold for forming an
embossed heat-sealed part becomes difficult. When the pitch is
wider than 2 mm, pinholes are easily developed and the appearance
of the resulting packaging structure is not beautiful. The embossed
heat-sealed part is also generally formed in a pattern surrounding
the patch. When, for example, a patch is packed by being sandwiched
between two packaging films, the embossed heat-sealed part is also
formed at the outside of the outermost flat heat-sealed part in a
pattern surrounding the entire periphery of the patch.
[0039] When the above-mentioned embossed heat-sealed part is
present, a non-sealed part may be present between the outermost
flat heat-sealed part and the embossed heat-sealed part to separate
them. While the shape of the non-sealed part is not particularly
limited, a band-like shape is preferable. In this case, the width
(band width) of the non-sealed part is generally 1.5 mm-10 mm,
preferably 2.0 mm-10 mm. When the width of the non-sealed part is
not less than 1.5 mm, a package has enhanced preservability for a
patch contained in the package. In addition, when the width is not
more than 10 mm, a package having good handling property which uses
a saved amount of the packaging film can be obtained.
[0040] The embossed heat-sealed part is preferably provided at the
outer periphery of the package.
[0041] The shape of the patch package (planar shape) of the present
invention is not particularly limited and, for example, a quadrate
(square, rectangle etc.), a polygon (triangle, hexagon etc.), a
circular shape, an ellipse, other figures and the like can be
mentioned. The shape of the patch package (planar shape) and the
shape of the patch to be packed (planar shape) may be the same or
different, and can be appropriately selected as long as the
tight-sealing property of the package can be maintained.
[0042] A preferable embodiment of the patch package of the present
invention is explained in detail in the following by referring to
the drawings. However, the following explanation is merely
illustrative, and the present invention, application thereof and
use thereof are not limited thereby. In the drawings, the size of
each part in the drawings, the size ratio between respective parts
and the like do not necessarily match with those of the actual
parts.
[0043] One embodiment of the patch package of the present invention
is shown in FIG. 1A and FIG. 1B. A patch 2 is sandwiched between
two packaging films 10, and the two packaging films 10 are flat
heat sealed around the patch 2 to surround the patch 2, whereby the
first flat heat-sealed part 3 and the second flat heat-sealed part
4 are formed. In other words, the patch 2 is packed in package 1
tightly sealed with double flat heat-sealed parts. Here, the first
flat heat-sealed part 3 and second flat heat-sealed part 4 are
formed at given intervals, and a first non-sealed part 6 is
provided between the first flat heat-sealed part 3 and the second
flat heat-sealed part 4. That is, the first flat heat-sealed part 3
and the second flat heat-sealed part 4 are separated across the
first non-sealed part 6.
[0044] Another embodiment of the patch package of the present
invention is shown in FIG. 2A and FIG. 2B. The package 1 of this
embodiment further has an embossed heat-sealed part 9 in the outer
periphery of the package. That is, the package is different from
the patch package shown in FIG. 1A and FIG. 1B in that it has an
embossed heat-sealed part 9 outside a flat heat-sealed part at the
most distant position from patch 2 (first flat heat-sealed part 3).
A non-sealed part does not exist between the first flat heat-sealed
part 3 and the embossed heat-sealed part 9, and the first flat
heat-sealed part 3 and the embossed heat-sealed part 9 are
continuously formed. In the patch package of this embodiment, since
the outer periphery of the package is the embossed heat-sealed part
9, the package can be opened easily with hand by tearing the outer
periphery of the package. In addition, the embossed heat-sealed
part 9 may have a pattern (straw mat pattern, lattice pattern,
straight line pattern, wave shape pattern, point-like pattern
etc.), and the pattern makes a more beautiful appearance of the
package.
[0045] Another embodiment of the patch package of the present
invention is shown in FIG. 3. The package 1 of this embodiment is
different from the patch package shown in FIG. 2A and FIG. 2B in
that it further has a third flat heat-sealed part 5 on the side of
the package central part of the second flat heat-sealed part 4 and
a second non-sealed part 7 between the second flat heat-sealed part
4 and the third flat heat-sealed part 5. That is, an embossed
heat-sealed part 9, a first flat heat-sealed part 3, a first
non-sealed part 6, a second flat heat-sealed part 4, a second
non-sealed part 7 and a third flat heat-sealed part 5 are
sequentially formed from the outer periphery to the central part of
the package. In the patch package of this embodiment, the
preserving property of a patch 2, which is the content, can be
enhanced, since the package is tightly sealed by triple flat
heat-sealed parts (first flat heat-sealed part 3, second flat
heat-sealed part 4 and third flat heat-sealed part 5) and an
embossed heat-sealed part 9.
[0046] Another embodiment of the patch package of the present
invention is shown in FIG. 4. The package 1 of this embodiment is
different from the patch package shown in FIG. 2A and FIG. 2B in
that it has a non-sealed part (third non-sealed part 8) between the
first flat heat-sealed part 3 and the embossed heat-sealed part 9.
That is, an embossed heat-sealed part 9, a third non-sealed part 8,
a first flat heat-sealed part 3, a first non-sealed part 6, and a
second flat heat-sealed part 4 are sequentially formed from the
outer periphery to the central part of the package. In the patch
package of this embodiment, the package is tightly sealed by the
double flat heat-sealed parts, and the embossed heat-sealed part 9
in the outer periphery of the package is separated from the first
flat heat-sealed part 3 by the presence of the third non-sealed
part 8. With the third non-sealed part 8, the first flat
heat-sealed part 3 can be formed without an influence of the
embossed heat sealing 9. As a result, the first flat heat-sealed
part 3 can secure stronger sealing. In addition, since air bubbles
can be easily released from the first flat heat-sealed part 3, the
package can be finished more beautifully.
[0047] Another embodiment of the patch package of the present
invention is shown in FIG. 5A and FIG. 5B. The package 1 of this
embodiment is comprised of a double-folded packaging film 10, and
an embossed heat-sealed part 9, a first flat heat-sealed part 3, a
first non-sealed part 6 and a second flat heat-sealed part 4 are
sequentially formed from the outer periphery to the central part of
the package 1, on the three sides except the side where the bent
part of the packaging film 10 is formed. The bent part of the
double-folded packaging film 10 may have roundness except the end
to be heat sealed, as shown in FIG. 5B. In this embodiment, the
package 1 packing the patch 2 is tightly sealed by the bent part,
and the double flat heat-sealed parts and the embossed heat-sealed
part, which are formed to surround the patch 2 except the bent
part, in the packaging film 10.
[0048] In the present invention, the method of a heat sealing
treatment is not particularly limited, and a known method can be
used. The method of the heat sealing treatment is generally divided
into a rotation method, a box motion method and a butt-sealing
method, according to the movement of the main spindle.
[0049] A patch package of the present invention having a quadrate
planar shape can be produced by using a general four-sided seal
packaging machine.
[0050] One example of the method of producing a patch package by
performing a heat sealing treatment according to the rotation
method by using a general four-sided seal packaging machine is as
follows. First, two long packaging films are placed to face each
other, and a patch is inserted between these packaging films to be
sandwiched in the vertical direction. Then, the both ends in the
longitudinal direction of the two layered packaging films are
heated by a heat block. The heated both ends are heat sealed by
pressure-bonding with a flat roll having a given width and free of
concaves and convexes to form a flat heat-sealed part. By a heat
sealing treatment of a little outside of the flat heat-sealed part
formed by pressure-bonding with the same flat roll, a second flat
heat-sealed part can be formed. By repeating a similar operation,
flat heat-sealed parts can be formed in triplicate, quadruplicate
or more. By changing the width of the roll to be used, moreover,
the width of the flat heat-sealed part can be changed. Furthermore,
a little outside of the outermost heat-sealed part formed is heat
sealed by pressure-bonding with a roll having a pattern such as a
straw mat pattern and the like to form an embossed heat-sealed part
(whereby a heat-sealed part is completed on the both ends).
Thereafter, a heat sealing treatment is performed by
pressure-bonding a metal mold bar integrally having a flat heat
sealing treatment surface free of concaves and convexes and a flat
heat sealing treatment surface having a pattern such as a straw mat
pattern and the like in a direction orthogonal to the longitudinal
direction of the packaging film, so that the flat heat-sealed part
will be formed inside and the embossed heat-sealed part will be
formed outside, whereby a flat heat-sealed part and an embossed
heat-sealed part are simultaneously formed (that is, heat-sealed
parts orthogonal to the above-mentioned both ends are formed).
Thereafter, the packaging film is cut such that each package
contains one patch to complete four-sided seal packages.
[0051] One example of the method of producing a patch package by
performing a heat sealing treatment according to the butt-sealing
method by using a general four-sided seal packaging machine is as
follows. First, two packaging films are placed to face each other,
and a patch is inserted between these packaging films to be
sandwiched in the vertical direction. Then, a heat sealing
treatment is performed by heating and pressure-bonding a heat block
metal mold capable of simultaneously forming heat-sealed parts on 4
sides (having a flat heat sealing treatment surface free of
concaves and convexes, and a heat sealing treatment surface having
a pattern such as a straw mat pattern etc.) against a packaging
film, whereby an embossed heat-sealed part and a flat heat-sealed
part are simultaneously formed. In this case, by using a heat block
metal mold having plural (2 or more) flat heat sealing treatment
surfaces, two or more flat heat-sealed parts can be simultaneously
formed. When the flat heat-sealed parts and the embossed
heat-sealed part are sequentially formed, heat block metal molds
each having a heat sealing treatment surface corresponding to
respective flat heat-sealed part or the embossed heat-sealed part
is used. In this case, the width and shape of each heat-sealed part
can be freely set according to the shape of the heat sealing
treatment surface. Furthermore, when plural packages are to be
simultaneously produced, treatment surfaces in the number
corresponding to that of the packages to be produced may be formed
on the heat block metal mold. Thereafter, a packaging film is
punched with a punching edge to complete four-sided seal
packages.
[0052] In the box motion method, a heat sealing treatment in the
above-mentioned butt-sealing method is performed while continuously
transporting a packaging film.
[0053] For production of the patch package of the present
invention, either the butt-sealing method or the box motion method
is preferably used to suppress development of pinholes as far as
possible. When the patch package has a quadrate planar shape, a
heat sealing treatment simultaneously forming heat-sealed parts on
four sides is most preferable.
[0054] In the production of the patch package of the present
invention, two or more flat heat-sealed parts may be simultaneously
formed or sequentially formed. When they are simultaneously formed,
however, the heat sealing treatment tends to be incomplete due to
dispersed pressure during the heat sealing treatment, leading to
higher possibility of development of pinholes. Thus, the sequential
formation is preferable. When two or more flat heat-sealed parts
are formed sequentially, the order of formation is not particularly
limited. However, the formation from the outer periphery side to
the central part side of the package is preferable.
[0055] While the conditions of pressure bonding temperature,
pressure bonding pressure, pressure bonding time and the like in
the above-mentioned heat sealing treatment vary depending on the
constitution of the packaging film (e.g., thickness of packaging
film, kind of thermally adhesive resin constituting thermally
adhesive resin layer etc.) and the like, they can be set as
appropriate so as to obtain a desired band width and a desired seal
strength. The pressure bonding temperature is generally within the
range of 100.degree. C. to 250.degree. C. When the pressure bonding
temperature is lower than 100.degree. C., the thermally adhesive
resin layer does not thermally adhere, and when the pressure
bonding temperature is higher than 250.degree. C., the appearance
of the resulting package tends to be poor due to the developments
of wrinkles and bubbles, deformation and deterioration of the
substrate film constituting the packaging film, and the like. The
pressure bonding pressure is generally 0.2 MPa-2 MPa, preferably
0.3 MPa-1.5 MPa. When the pressure bonding pressure is lower than
0.2 MPa, pinholes are easily developed, and an appropriate seal
strength tends to be difficult to achieve. In addition, when the
pressure bonding pressure is higher than 2 MPa, a packaging film is
deteriorated easily.
(Packaging Film)
[0056] The packaging film of the packaging structure of the present
invention is not particularly limited as long as it can form a
heat-sealed part by a heat sealing treatment and can tightly seal
the patch. Preferably, it has a substrate film layer and a
thermally adhesive resin layer laminated on one side of the
substrate film layer. The packaging film optionally has a dry
lamination adhesive layer between the substrate film and the
thermally adhesive resin layer to adhere them to each other. When
the substrate film and the thermally adhesive resin layer are
sufficiently adhered by thermal adhesion, the dry lamination
adhesive layer may not be present.
[0057] As the substrate film layer, a film or sheet of a resin,
which is superior in the mechanical, physical, chemical and other
properties, particularly has a sufficient intensity and strength
and heat resistance, and is superior in transparency, can be used.
Specifically, for example, a film or sheet of one or more kinds of
resin selected from polyester resins, polyamide resins, polyaramid
resins, polyolefin resins such as polyethylene, polypropylene and
the like, polystyrene resins, polyacrylic and polymethacrylic
resins, polycarbonate resins, polyacetal resins, fluororesins,
polyacrylonitrile resins, polyvinyl alcohol resins and the like can
be mentioned. As such film or sheet of the above-mentioned resins,
a film stretched in a monoaxial direction of the longitudinal
direction or transverse direction can be used. Examples of the
stretching method include known methods such as a flat method, an
inflation method and the like, and the draw ratio thereof is about
2-10 fold. The thickness of the film is generally 5 .mu.m-100
.mu.m, preferably, 10 .mu.m-50 .mu.m. In the present invention, the
above-mentioned resin film may be applied with a forward printing
or reverse printing, and the like of a desired printed picture such
as character, graphic, symbol, picture, pattern and the like by a
general printing method.
[0058] As the dry lamination adhesive layer, a conventional dry
lamination adhesive can be used, and a two-pack-curable adhesive is
preferably used. Particularly, polyester urethane polyol/aromatic
polyisocyanate adhesives, polyetherpolyurethane/epoxi adhesives,
polyetherurethane polyol/aliphatic polyisocyanate adhesives,
polyester/aliphatic isocyanate adhesives, polyester/aromatic
isocyanate adhesives are more preferable, and polyester urethane
polyol/aromatic polyisocyanate adhesives are still more preferable.
To color a packaging film, a suitable amount of any pigment or dye
can be added to a dry lamination adhesive layer.
[0059] A dry lamination adhesive layer can be formed by printing or
coating a solution of a dry lamination adhesive to a surface of a
substrate film layer or a thermally adhesive resin layer by gravure
coating, roll coating, knife coating, spray coating, gravure
printing, flexo printing, screen printing, offset printing, or
other general printing method or coating method, and drying the
printed or coating film. The thickness of the dry lamination
adhesive layer is generally 1.0 g/m.sup.2-30 g/m.sup.2, preferably
2.0 g/m.sup.2-20 g/m.sup.2.
[0060] As a resin constituting the thermally adhesive resin layer,
a resin that can be melted with heat and adhered to each other can
be used. Specifically, for example, low density polyethylene,
intermediate density polyethylene, high density polyethylene,
linear low density polyethylene, polypropylene, ethylene-vinyl
acetate copolymer, ionomer resin, ethylene-acrylic acid copolymer,
ethylene-ethyl acrylate copolymer, ethylene-methacrylic acid
copolymer, ethylene-methyl methacrylate copolymer,
ethylene-propylene copolymer, methylpentene polymer, polybutene
polymer, acid denatured polyolefin resin (polyolefin resin such as
polyethylene, polypropylene and the like denatured with unsaturated
carboxylic acid such as acrylic acid, methacrylic acid, maleic
acid, fumaric acid, maleic anhydride and the like), polyvinyl
acetate resin, poly(meth)acrylic resin, polyvinyl chloride resin,
polystyrene resin, acrylonitrile resin (e.g., acrylonitrile-styrene
copolymer (AS resin), acrylonitrile-butadiene-styrene copolymer
(ABS resin) etc.), thermally adhesive poly(ethylene terephthalate)
resin and the like can be used. Thermally adhesive resins most
preferably used in the present invention include polyolefin resins
and acrylonitrile resins such as low density polyethylene,
intermediate density polyethylene, high density polyethylene,
linear low density polyethylene, polypropylene and the like. A film
or sheet made from the above-mentioned resins, or a coating film of
a resin composition containing the above-mentioned resins as a main
component and the like can constitute the thermally adhesive resin
layer. The thickness thereof is generally 1 .mu.m-50 .mu.m. When
applied to a patch containing a drug, it is preferably 3 .mu.m-40
.mu.m, more preferably 5 .mu.m-30 .mu.m. When the thickness of the
thermally adhesive resin layer is smaller than 1 .mu.m, heat
sealing property is degraded to permit easy development of
pinholes, and when it is thicker than 50 .mu.m, the drug in he
patch is transferred into or adsorbed to a thermally adhesive resin
layer at a higher proportion.
[0061] The packaging film of the present invention can have a
middle substrate layer as necessary. Examples of the substrate
constituting the middle substrate layer include materials that do
not allow permeation of water vapor, water, gas and the like, and
the like, which may be a single substrate or a composite substrate
made of a combination of two or more kinds of substrates.
Specifically, for example, a resin film having a vapor deposition
film of an inorganic oxide such as silicon oxide, aluminum oxide
and the like, which shows barrier property against water vapor, gas
and the like; a film or sheet of a resin such as low density
polyethylene, intermediate density polyethylene, high density
polyethylene, linear low density polyethylene, polypropylene,
ethylene-propylene copolymer and the like, which shows barrier
property against water vapor, water and the like; a film or sheet
of a resin such as polyvinylidene chloride, polyvinyl alcohol,
ethylene-vinyl acetate copolymer saponified product and the like,
which shows gas barrier property; a resin film having a vapor
deposition film of aluminum; aluminum foil and the like can be
used. While the thickness of the above-mentioned film or sheet can
be appropriately set, it is generally 5 .mu.m-300 .mu.m, preferably
10 .mu.m-100 .mu.m. The thickness of the above-mentioned vapor
deposition film of inorganic oxide is preferably 10 nm-300 nm, and
the thickness of the above-mentioned aluminum vapor deposition film
is preferably about 10 nm-40 nm. Examples of the resin film
supporting the above-mentioned vapor deposition film include a
polyester film, a polyamide film, a polyolefin film, a polyvinyl
chloride film, a polycarbonate film, a polyvinylidene chloride
film, a polyvinyl alcohol film, an ethylene-vinyl acetate copolymer
saponified product film and the like. The thickness of the aluminum
foil is preferably 3 .mu.m-30 .mu.m, more preferably 5 .mu.m-10
.mu.m.
[0062] A patch package using a packaging film made of an aluminum
vapor deposition film or an aluminum foil as a middle substrate
layer does not permit clear identification of the patch from the
outside. Thus, the patch in the package cannot be tested with ease,
and the presence or absence of a pinhole in the flat heat-sealed
part cannot be confirmed with ease by visual inspection or image
inspection. For packages difficult for appearance tests, ensured
heat sealing during production is more important. In this sense,
the patch package of the present invention is advantageous.
[0063] The packaging film in the patch package of the present
invention is preferably transparent, since identification of the
packed patch from the outside and confirmation of the presence or
absence of a pinhole in the flat heat-sealed part are facilitated.
Furthermore, it is preferably transparent, since the heat-sealed
part of the packaging film can be clearly distinguished from other
parts based on the transmission of light and difference in the
refractive index (state of formation of heat-sealed part can be
easily judged visually during heat sealing treatment). The flat
heat-sealed part has higher transparency than other parts, since no
gap is present between the upper and lower films and scattering of
light can be suppressed. Thus, when the flat heat-sealed part is
formed without a pinhole, the flat heat-sealed part can be
considered to extend continuously. Furthermore, the presence or
absence of a pinhole can be automatically examined by photographing
the packaging structure and processing (binarizing) the images.
(Acrylonitrile Resin Layer)
[0064] When the packaging film of the present invention packs a
patch containing a drug (i.e., "patch preparation"), the thermally
adhesive resin layer is preferably an acrylonitrile type resin film
layer (hereinafter sometimes to be referred to as an acrylonitrile
type resin layer), since adsorption and passage of the drug is
small and the content can be preserved well. The acrylonitrile
resin used for the acrylonitrile type resin layer in the present
invention is not particularly limited as long as not less than 50
wt % per total resin weight is comprised of acrylonitrile
components. Thus, examples of the acrylonitrile resin include (i)
polyacrylonitrile, (ii) a mixture or polymer alloy of
polyacrylonitrile and other resin, (iii) a copolymer containing
acrylonitrile as a main structural unit, (iv) a composition of a
combination of at least two of the aforementioned (i)-(iii), and
the like. Of these, any of the above-mentioned (ii)-(iv) is
preferable in view of the suitable flexibility and rigidity as a
packaging material of a patch, as well as heat sealability. Here,
"acrylonitrile as a main structural unit" means that not less than
50 wt % of the total copolymer weight is acrylonitrile.
[0065] Acrylonitrile imparts non-adsorbability and gas barrier
property to the acrylonitrile type resin layer, and adds rigidity
to confer easy-to-tear property. Thus, the acrylonitrile type resin
may be 100 wt % comprised of the acrylonitrile component. However,
to achieve desired elasticity, impact resistance, tensile strength
and the like of a package, a rubber component such as butadiene and
the like and/or a (meth)acrylic acid alkyl ester component wherein
the alkyl group has a carbon number of 1-6, and the like are
preferably contained along with not less than 50 wt % of an
acrylonitrile component. The rubber component imparts impact
absorbability and suitable flexibility to acrylonitrile type
resins, and the (meth)acrylic acid alkyl ester component lowers the
melting point of the acrylonitrile type resin layer to improve heat
sealability. In the (meth)acrylic acid alkyl ester wherein the
alkyl group has a carbon number of 1-6, the alkyl group may be a
straight chain or branched, and one or more kinds thereof can be
used. Preferably, for example, methylacrylate, methylmethacrylate,
ethylacrylate, ethylmethacrylate, (1- or 2-)propylacrylate, (1- or
2-)propylmethacrylate, (1- or 2-)butylacrylate, (1- or
2-)butylmethacrylate and the like can be mentioned. Of these,
methylacrylate is particularly preferable, since it has broad
utility, and can easily impart flexibility to a packaging material
of a patch.
[0066] The acrylonitrile type resin is preferably a copolymer
comprising acrylonitrile as a main structural unit since it affords
uniform property of acrylonitrile type resin layer. The copolymer
preferably contains, as a structural unit, at least acrylonitrile,
a rubber component such as butadiene and the like and/or a
(meth)acrylic acid alkyl ester wherein the alkyl group has a carbon
number of 1-6. The copolymer preferably has an acrylonitrile
content of 50-90 wt %, and a particularly preferable copolymer
composition contains 50-90 wt % of acrylonitrile, 2-12 wt % of a
rubber component such as butadiene and the like, and 8-38 wt % of a
(meth)acrylic acid alkyl ester wherein the alkyl group has a carbon
number of 1-6. In addition, the form of copolymerization of the
copolymer is not particularly limited, and it may be random
copolymerization, block copolymerization, or graft
copolymerization. Of these, graft copolymerization is preferable,
since it efficiently affords both the characteristics of
polyacrylonitrile showing superior non-adsorbability of
physiologically active components, and the characteristics of a
rubber component having superior impact absorbability. As long as
the characteristics are not inhibited, random copolymerization and
block copolymerization may be added as appropriate.
[0067] The composition of the acrylonitrile type resin in the
present invention is analyzed by the following method.
(Acrylonitrile Content)
[0068] The acrylonitrile content is obtained by cutting out an
acrylonitrile type resin layer from a packaging material,
subjecting the sample to CHN elemental analysis and calculating the
content from the nitrogen content. Furthermore, the molecular
structure and weight ratio of the rubber component and the
(meth)acrylic acid alkyl ester component wherein the alkyl group
has a carbon number of 1-6 are determined from the .sup.1H-NMR and
.sup.13C-NMR (in deuterated DMSO, 80.degree. C.) spectrum ratio,
and the weight ratio of 3 components is determined.
(Thickness of Acrylonitrile Type Resin Layer)
[0069] The thickness of the acrylonitrile type resin layer is
appropriately set according to the kind and the like of the patch
and is not particularly limited. To ensure nonpermeability and
nonadsorbability of the physiologically active component in the
patch, moisture permeability and suitable flexibility and rigidity
of the layer as a packaging material of the patch, the thickness is
preferably 10 .mu.m-100 .mu.m, more preferably 10 .mu.m-80 .mu.m,
most preferably 10 .mu.m-50 .mu.m.
(Patch)
[0070] While the patch in the present invention is not particularly
limited, it is preferably adhered to the skin or mucosa to treat or
prevent diseases. More preferably, it has an adhesive layer, a
support laminated on one surface of the adhesive layer, and a
release-treated liner laminated on the other surface of the
adhesive layer. The adhesive layer may contain a transdermally
absorbable drug.
[0071] As an adhesive constituting the adhesive layer, one that can
be adhered to the skin or mucosa for a given time period, such as
one showing adhesiveness in a normal state, one showing
adhesiveness under moistening conditions, one showing adhesiveness
under heating and the like can be used. To be specific,
water-soluble adhesive base mainly containing polyvinyl alcohol,
polyvinylpyrrolidone, poly-N-vinyl acetamide, polyethylene oxide,
polyacrylamide, polyacryl acid salt, agar, xanthan gum and the
like, water-swellable adhesive base mainly containing crosslinked
water-soluble polymer, ethylcellulose, hydroxypropylcellulose,
alginic acid ester and the like, and water-nonsoluble adhesive base
mainly containing acrylic polymer, rubber polymer, silicone
polymer, vinylether polymer, vinylester polymer and the like can be
used. These adhesives and adhesive bases may contain, as necessary,
known additives such as tackifier (e.g., rosin, denatured rosin,
petroleum resin, polyterpene resin, polystyrene resin, polybutene
resin, liquid polyisobutylene, glycerol and the like), plasticizer
(e.g., liquid paraffin, fatty acid ester and the like), absorption
promoter, surfactant, filler, water and the like to improve
adhesiveness.
[0072] The thickness of the adhesive layer is generally 10
.mu.m-200 .mu.m, preferably 15 .mu.m-150 .mu.m.
[0073] When a patch preparation containing a drug in an adhesive
layer is obtained, the drug is not particularly limited as long as
it can be contained in an adhesive or an adhesive base in a
dissolution state, supersaturated crystallization state or
dispersion state, and the adhesive or adhesive base maintains
adhesiveness. For example, corticosteroids, analgesic
anti-inflammatory agent, sedative hypnotic, tranquilizer,
antihypertensive agent, hypotensive diuretic, antibiotic, systemic
anesthetic, antibacterial agent, antifungal agent, vitamin,
coronary vasodilator, antihistamine agent, antitussive, sex
hormone, antidepressant, brain circulation improver, antiemetic,
antitumor agent, biological drug and the like can be mentioned.
[0074] While the content of the drug in an adhesive layer can be
appropriately set according to the kind of the drug, it is
generally 1 wt %-80 wt %, preferably about 2 wt %-70 wt %. When the
content is less than 1 wt %, drug release in an amount effective
for the treatment or prophylaxis cannot be expected. When it
exceeds 80 wt %, adhesiveness decreases to prevent sufficient
adhesion, which limits a theraprutic or prophylactic effect and is
economically disadvantageous.
[0075] The support layer is not particularly limited as long as it
does not produce a feeling of strangeness. Specifically, a single
film or laminate film (solid film) made from one or more kinds of
synthetic resins selected from polyester, polyolefin (polyethylene,
polypropylene and the like), polyvinyl chloride, plasticized
polyvinyl chloride, plasticized vinyl acetate-vinyl chloride
copolymer, polyvinylidene chloride, ethylene-vinyl acetate
copolymer, acetyl cellulose, ethylcellulose, ethylene-ethyl
acrylate copolymer, polytetrafluoroethylene, polyurethane, ionomer
resin and the like can be mentioned. In addition, porous film or
sheet, non-woven fabric, woven fabric and the like, which are made
from rubber, the above-mentioned synthetic resin, polyester (e.g.,
poly(ethylene terephthalate) etc.), polyamide (nylon etc.), can be
mentioned. Moreover, laminates of these porous film or sheet,
non-woven fabric, woven fabric and the like on a single film or
laminate film made from the above-mentioned synthetic resins
(composite film) can be mentioned. The thickness of the support
layer is generally 1 .mu.m-1000 .mu.m. In the case of a single film
or laminate film made from the above-mentioned synthetic resins,
the thickness is preferably 1 .mu.m-100 .mu.m, and in the case of
the above-mentioned composite film, it is preferably 100 .mu.m-1000
.mu.m. The materials constituting the support layer in the present
invention are not limited to the above-mentioned water insoluble
materials, and water-soluble materials such as polyvinyl alcohol,
polyvinylpyrrolidone, poly-N-vinylacetamide, polyethylene oxide,
polyacrylamide, polyacryl acid salt, agar, xanthan gum and the like
may also be used as long as they are nontoxic.
[0076] The exposed surface of the adhesive layer of the patch of
the present invention is desirably covered and protected by a
release liner until immediately before adhesion to the skin
surface, to prevent adhesion of the adhesive layer to instruments,
container and the like during production, adhesion of the adhesive
layer to the packaging film during transport or preservation, and
degradation of the patch. When in use, the release liner is
detached to expose the surface of the adhesive layer, which is then
adhered to the target site for administration. The release liner is
not particularly limited as long as it is detached easily from the
adhesive layer when in use. For example, a film of polyester,
polyvinyl chloride, polyvinylidene chloride, poly(ethylene
terephthalate) and the like, paper such as high-quality paper,
glassine paper and the like, or a laminate film of high-quality
paper or glassine paper etc. and polyolefin and the like, which has
undergone a detach treatment by application of a silicone resin,
fluororesin and the like to the surface to be in contact with the
adhesive layer, are used. The thickness of the release liner is
generally 10 .mu.m-200 .mu.m, preferably 50 .mu.m-100 .mu.m.
[0077] The production method of the patch is not particularly
limited and, for example, a method including dissolving or
dispersing a drug, an adhesive and the like in a solvent, applying
the obtained solution or dispersion to one surface of a support,
drying the support to form an adhesive layer on the surface of the
support, laminating a release liner on the adhesive layer and the
like can be mentioned. In addition, the patch can be produced by
applying the above-mentioned solution or dispersion to a protective
release liner, drying the release liner to form an adhesive layer
thereon and adhering the support to the adhesive layer.
[0078] The total thickness of the patch to be packed is generally
50 .mu.m-2000 .mu.m, preferably 100 .mu.m-1000 .mu.m. When the
thickness of the patch is less than 50 .mu.m, the development of a
pinhole can also be suppressed even by producing a patch package by
a conventional technique. Therefore, the present invention is
particularly useful when the thickness of the patch is not less
than 50 .mu.m. When the thickness of the patch is more than 2000
.mu.m, distortion of the packaging film due to the thickness cannot
be suppressed in the flat heat-sealed part, and pinholes are
developed easily.
EXAMPLES
[0079] The present invention is explained in detail in the
following by referring to Examples and Comparative Examples, which
are not to be construed as limitative. In the following, "part" and
"%" mean "parts by weight" and "wt %", respectively.
(Preparation of Sample)
[0080] Under an inert gas atmosphere, acrylic acid 2-ethylhexyl (75
parts), N-vinyl-2-pyrrolidone (22 parts), acrylic acid (3 parts)
and azobisisobutyronitrile (0.2 part) in the adhesive solid content
(100 parts by weight) were subjected to solution polymerization in
ethyl acetate at 60.degree. C. to give a solution of an acrylic
adhesive in ethyl acetate (adhesive solid content: 28%). Then, 80.3
kg of the solution of an acrylic adhesive in ethyl acetate and 27.8
kg of isopropyl myristate were mixed, and the viscosity was
adjusted with ethyl acetate to give a coating solution. The
obtained coating solution was applied to a poly(ethylene
terephthalate) (hereinafter to be referred to as PET) release liner
such that the thickness after drying was 150 .mu.m and dried to
form an adhesive film layer on the release liner. The adhesive
layer of the release liner was adhered to a PET non-woven fabric
surface of a PET support comprised of a laminate film of a PET
non-woven fabric and a PET film, and the resulting product was
preserved at 70.degree. C. for 48 hr to give an original coated
fabric having a 4 layer constitution of PET film/adhesive layer/PET
non-woven fabric/PET film. The original coated fabric was cut out
in a 63.5 mm.times.63.5 mm square (all corners had roundness
(radius 6 mm)) to give a patch.
[0081] As a packaging film, a laminate film of transparent
poly(ethylene terephthalate) film (thickness: about 12
.mu.m)/aluminium foil (thickness: about 15 .mu.m)/acrylonitrile
type resin film (copolymer of acrylonitrile, butadiene and
methylacrylate, thickness: about 30 .mu.m) was used. A patch was
contained, and a flat heat sealing treatment and an embossed heat
sealing treatment were performed under the conditions shown in the
following Table 1 (common treatment conditions) and Table 2
(separate treatment conditions) to tightly seal the packaging
films, whereby the patch packages of Examples 1 and 2, and
Comparative Examples 1-3 were obtained.
[0082] The flat heat-sealed part and embossed heat-sealed part were
formed in a band-like shape, in a pattern surrounding the entire
pheriphery of the patch. The size of the obtained patch packages
was a 94 mm.times.94 mm square (all corners had roundness (radius 5
mm)).
TABLE-US-00001 TABLE 1 item set value sealing temperature (up/down)
(.degree. C.) 150/150 pressure bonding time [sec] 0.277 pressure
bonding pressure [MPa] 0.33 embossed heat sealing width [mm] 45
straw mat pattern pitch [mm] 0.6 straw mat pattern height [mm] 0.3
heat sealing treatment method butt-sealing method packaging machine
four-sided seal packaging machine
TABLE-US-00002 TABLE 2 width [mm] number of width [mm] of flat flat
heat- of non- heat-sealed sealed parts sealed similar part [parts]
part Fig. Example 1 0.5 2 1.0 FIG. 2 Example 2 0.5 2 2.0 FIG. 2
Comparative 0.5 1 FIG. 6 Example 1 Comparative 1.0 1 FIG. 6 Example
2 Comparative 2.0 1 FIG. 6 Example 3
(Air-Tightness)
[0083] The patch packages of Examples 1 and 2, Comparative Examples
1-3 were preserved at 40.+-.2.degree. C. and under relative
humidity of 75.+-.5% for 3 months, and the water content [ppm] of
each patch was measured at the start of preservation, and 1 month,
2 months and 3 months later. The measurement method of the water
content of the patch was as follows. The package was opened, the
patch was removed and the release liner was removed to give a test
piece, which was cast in a moisture vaporization apparatus. The
above-mentioned treatment was completed immediately after opening
of the package. The test piece was heated at 140.degree. C. in the
moisture vaporization apparatus, the moisture generated thereby was
introduced into a titration flask with nitrogen as a carrier, and
the water content (ppm; weight ratio of moisture to total weight of
test piece) of the test piece was measured by the Karl Fischer
coulometric titration method.
[0084] The results are shown in Table 3 and FIG. 7.
TABLE-US-00003 TABLE 3 preservation 1 month 2 months 3 months start
time later later later Example 1 2381 2569 2890 3172 Example 2 2432
2783 2957 Comparative 2864 3462 4038 Example 1 Comparative 2672
3155 3494 Example 2 Comparative 2547 2943 3062 Example 3
[0085] The water content of the patches tightly sealed in the patch
packages of Examples 1 and 2 (total width of flat heat-sealed part:
1.0 mm) were lower than not only the water content of the patch
tightly sealed in a conventional patch package (width of flat
heat-sealed part: 0.5 mm, Comparative Example 1) but also that of
the patch tightly sealed in the patch package of Comparative
Example 2 wherein the width of the flat heat-sealed part was 2
times (1.0 mm) that of conventional patch packages, and of the same
level as that of the patch tightly sealed in the patch package of
Comparative Example 3 wherein the width of the flat heat-sealed
part was 4 times (2.0 mm) that of conventional patch packages. The
results of Table 3 show superiority of the packaging structure of
the present invention having two thin flat heat-sealed parts in the
sealability to conventional packaging structures having only one
thick (larger width) flat heat-sealed part, since the two thin flat
heat-sealed parts are certainly formed at a uniform seal width and,
even if one of them develops pinholes, the other flat heat-sealed
part can suppress the leakage. As is clear from such results, the
packaging structure of the present invention can retain superior
air-tightness for a long time.
(Appearance of Flat Heat-Sealed Part)
[0086] The presence or absence of bubbles in the flat heat-sealed
parts of the patch packages of Examples 1 and 2, and Comparative
Examples 1-3 was evaluated. The absence or presence of bubble was
visually evaluated.
[0087] The results are shown in Table 4.
TABLE-US-00004 TABLE 4 number of evaluation bubble no bubble
Example 1 10 0 10 Example 2 0 10 Comparative 0 10 Example 1
Comparative 2 8 Example 2 Comparative 10 0 Example 3
[0088] The flat heat-sealed parts of the patch packages of Examples
1 and 2 did not show a bubble in any of 10 samples. In contrast,
the flat heat-sealed parts of the patch packages of Comparative
Example 2 showed a bubble in 2 out of 10 samples, and the patch
package of Comparative Example 3 showed a bubble in all 10 samples.
The results of Table 4 show that a pinhole failure is easily
developed when the width of flat heat sealing is not less than 1
mm. Therefore, when only one flat heat-sealed part having a width
of 1 mm is formed, the sealability may not be ensured. As is clear
from such results, the packaging structure of the present invention
solves the sealing defects due to pinholes, and can form a
beautiful flat heat-sealed part.
[0089] As is clear from the Examples, the patch package of the
present invention is free of pinholes, superior in air-tightness,
and has good appearance of the flat heat-sealed part. Particularly,
the patch package is highly useful when a patch contains a drug
easily decomposed by oxygen or moisture, since it can highly
suppress oxidation and decomposition due to its long-term
preservation.
* * * * *