CA 02751350 2011-09-01
SPECIFICATION
ADHESIVE PATCH AND ADHESIVE PREPARATION
TECHNICAL FIELD OF THE INVENTION
[0001]
The present invention relates to an adhesive patch
comprising a support and an adhesive layer formed on at least
one surface of the support, and an adhesive preparation.
BACKGROUND OF THE INVENTION
[0002]
lo In recent years, various adhesive patches and adhesive
preparations have been developed. Adhesive preparation and
adhesive preparation are highly superior in terms of
protection of wound surface, continuous transdermal
administration of a drug, drug metabolism by first-pass
through the liver, and avoidance of various side effects.
[0003]
In general, adhesive patches and adhesive preparations
have a support made of a woven fabric, a non-woven fabric, a
plastic film and the like and an adhesive layer laminated on
the support, and are generally provided with a release liner
laminated on the adhesive layer. They are provided in a
package made of a packaging material such as a resin film and
the like.
[0004]
In such adhesive patches and adhesive preparations, the
adhesive layer is required to have a certain thickness in
consideration of the wound surface protection effect, and the
effective drug content. However, when the adhesive layer
becomes thick, the end of the adhesive patch and the like is
easily rubbed against clothes and the like and turned up, as
well as the components of the adhesive layer ooze or protrude
from the end of the adhesive patch and the like, i.e., cold
flow, thus posing problems during adhesion to the skin.
[0005]
Cold flow occurs depending on the property of the
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adhesive layer. It often occurs when, in particular, an
adhesive patch or adhesive preparation is under a load for a
long time, that is, when an adhesive patch and the like are
contained in a package and stored for a long period and the
like.
[0006]
Adverse effects of cold flow include, for example,
difficulty in taking out an adhesive patch and the like from a
package, which is caused by adhesion of oozed or protruded
/o adhesive layer components to the inside of the package,
turning and staining of adhesive patch and the like during
adhesion to the skin, a lower medicinal effect of the adhesive
preparation due to an outflow of the drug and the like.
Therefore, adhesive patches and adhesive preparations
Is desirably have an end not easily rubbed against clothes, do
not permit easy cold flow, and have an adhesive layer
retaining the original shape.
[0007]
As a technique to handle such problem, JP-A-11-1432
20 (patent document 1) discloses an adhesive patch having a dry
edge, which has a release liner extended from the end of a
support and an adhesive layer. In such adhesive patch, oozing
and protruding of an adhesive layer component from the end of
an adhesive layer in contact with a release liner can be
25 suppressed to some extent. However, in such adhesive patch,
oozing and protruding of an adhesive layer component from the
end of an adhesive layer in contact with a support may occur,
and the preparation is not entirely satisfactory.
[0008]
30 JP-A-6-63071 (patent document 2) discloses a covering
material for wound (dressing material) which is contoured and
has an adhesive layer fitting to the skin. In one example of
this covering material for wound, the end is cut flatly, and
therefore, oozing and protruding of an adhesive layer
35 component from the end may occur, which results in the
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attachment of the component to the inner surface of the
package.
[0009]
In another example described in patent document 2, the
end of the covering material is covered with a support. In
such adhesive patch, however, the end of a support covers the
end of an adhesive layer and, at the end of the adhesive patch,
the end of the support aligns with the end of the release
liner. Therefore, when in use, the release liner may not be
lo easily detached from the end thereof with fingers. In addition,
since the end of the support needs to be able to bend and
cover the end of an adhesive layer, the degree of freedom of
selection of the material and shape thereof, particularly
thickness and the like, is low. Particularly, when the
adhesive layer is thick, it is not easy to cover the end of
the adhesive layer with the end of the support extended
therefor in an industrial production stage. In fact, the
thickness of the end of the adhesive layer of the adhesive
patch in this example is molded to be thinner than that of the
central part, and the thickness of the end of the adhesive
layer is inferred to be difficult to maintain.
[Document List]
[patent documents]
[0010]
patent document 1: JP-A-11-1432
patent document 2: JP-A-6-63071
[SUMMARY OF THE INVENTION]
Problems to be Solved by the Invention
[0011]
Thus, the development of an adhesive patch and an
adhesive preparation, which satisfy (i) easiness in taking out
from package, (ii) releaseability of a release liner from an
adhesive layer during use, and (iii) high adhesion performance
to the skin is desired.
[0012]
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The present invention has been made in view of such
situation, and the problem to be solved is to provide an
adhesive patch or an adhesive preparation, which is
characterized in that
(i) oozing or protruding of an adhesive layer component from
the end of an adhesive patch and the like is suppressed,
attachment of the adhesive patch and the like to the inner
surface of a package is suppressed during preservation in the
package, and the preparation can be taken out easily from the
package;
(ii) the frequency of rubbing of the end against clothes etc.
is reduced during adhesion to the skin, the end is not turned
up easily, sufficient skin adhesion is ensured, and the
preparation is highly resistant to the detachment from the
skin surface; and
(iii) during use, the release liner can be easily detached
from the adhesive layer.
Means of Solving the Problems
[0013]
The present inventors have conducted intensive studies in
an attempt to solve the above-mentioned problems, and found
that the aforementioned problems can be achieved when, in at
least one lateral end of an adhesive patch and the like, the
lateral end of an adhesive layer is located toward the central
part side of the adhesive patch and the like from the lateral
end of the support, and the distance between the upper end of
the support and the lower end of the release liner of the
adhesive patch and the like at said end part is greater than
the thickness of the adhesive patch and the like in the
central part, which resulted in the completion of the present
invention.
[0014]
Accordingly, the present invention relates to the
following [1] to [9].
[1] An adhesive patch comprising a support, an adhesive layer
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on at least one surface of the support, and a release liner on
a surface of the adhesive layer opposite from the support,
wherein
(a) the lateral end of the adhesive layer is exposed,
(b) in at least one lateral end, the lateral end of the
adhesive layer is located toward the central part side of the
adhesive patch from the lateral end of the support, and
(c) when placed horizontally with the release liner facing
down, a distance A between the upper end of the support and
JO the lower end of the release liner at said lateral end of the
adhesive patch is greater than a thickness B of the central
part of the adhesive patch.
[2] The adhesive patch of the above-mentioned [1], wherein, in
at least one lateral end, the lateral end of the adhesive
layer is located on the central part side of the adhesive
patch at 1 m - 1000 m from the lateral end of the support.
[3] The adhesive patch of the above-mentioned [1], wherein, in
at least one lateral end, the distance A between the upper end
of the support and the lower end of the release liner at said
lateral end of the adhesive patch is greater than a thickness
C of the adhesive patch at the lateral end of the adhesive
layer.
[4] The adhesive patch of the above-mentioned [1], wherein, in
at least one lateral end, the thickness C of the adhesive
patch at the lateral end of the adhesive layer is equal to the
thickness B of the central part of the adhesive patch.
[5] The adhesive patch of the above-mentioned [1], wherein, in
at least one lateral end, the end of the adhesive layer has a
concave shape.
[6] The adhesive patch of any of the above-mentioned [1] to
[5], wherein the adhesive layer comprises a rubber-based
adhesive.
[7] The adhesive patch of any of the above-mentioned [1] to
[6], wherein the adhesive layer is not crosslinked.
[8] The adhesive patch of any of the above-mentioned [1] to
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[7], wherein the adhesive layer comprises an organic liquid
component.
[9] An adhesive preparation comprising the adhesive patch of
any of the above-mentioned [1] to [8], wherein the adhesive
layer contains a drug.
Effect of the Invention
[0015]
In the adhesive patch or adhesive preparation of the
present invention, in at least one lateral end, the lateral
/o end of the adhesive layer is located toward the central part
side of the adhesive patch and the like from the lateral end
of the support. Therefore, oozing or protruding of an adhesive
layer component from the end of the adhesive patch or adhesive
preparation does not occur easily and the cold flow phenomenon
is suppressed during the preservation of the adhesive patch or
adhesive preparation. As a result, attachment of the adhesive
patch and the like to the inner surface of the package is
suppressed, and the adhesive patch and the like can be easily
taken out from the package. In addition, stickiness to hand
and sticky feeling at the applied site, which cause an
unpleasant feeling, occur less often when in use.
[0016]
Moreover, in the adhesive patch and adhesive preparation
of the present invention, the lateral end of the adhesive
layer is exposed and is not covered with a support or a
release liner. This combined with the aforementioned improved
easiness in taking out the adhesive patch and the like from a
package, which is attributable to the suppression of oozing
and protrusion of an adhesive layer component, the adhesive
patch and the like of the present invention permits easy
detachment of the release liner from the end thereof with
fingers when in use.
[0017]
Still more difficult to predict, an adhesive patch and
the like wherein, in at least one lateral end, distance A
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81595658
between a support upper end and a release liner lower end is
greater than distance B of the central part of the adhesive
patch and the like, do not drop off easily for a long time
when applied to the skin.
BRIEF DESCRIPTION OF THE DRAWINGS
Nola]
Fig. 1 is a schematic sectional view of one embodiment of
the adhesive patch or adhesive preparation of the present
invention.
io Fig. 2 is a schematic sectional view of one embodiment of
the adhesive patch or adhesive preparation of the present
invention.
Fig. 3 is a schematic sectional view of one embodiment of
the adhesive patch or adhesive preparation of the present
is invention.
Fig. 4 is a schematic sectional view of one embodiment of
the adhesive patch or adhesive preparation of the present
invention.
Fig. 5 is a schematic sectional view of one embodiment of
20 the adhesive patch or adhesive preparation of the present
invention.
Fig. 6 shows that an adhesive patch package is opened by
cutting two sides with scissors or along a V-shaped notch, and
the adhesive patch is taken out.
25 [Description of Embodiments]
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CA. 02751350 2011-09-01
[0019]
In the present specification, an "adhesive patch" is a
concept encompassing not only preparations aiming at
transdermal absorption of a drug but also a material for
medical care or hygiene of skin such as a skin protection
sheet and the like, which does not contain an active
ingredient such as a drug and the like. One containing a drug
is to be particularly referred to as a "adhesive preparation".
[0020]
As a material for medical care or skin hygiene of the
adhesive patches of the present invention, adhesive plaster,
tape for skin, dressing material for covering wound and the
like can be mentioned. They are provided in the form of film,
sheet, pad and the like. The adhesive preparation can also be
provided as a transdermal absorption type preparation aiming
at a local or systemic action, which is of either a matrix
type or a reservoir type. The dosage form may vary and may be
a patch type, an adhesive tape type, a sheet type and the like.
When simply referred to as an "adhesive patch" in the
following, the term also encompasses an adhesive preparation.
In addition, a laminate of an adhesive layer and a support is
to be referred to as an "adhesive patch main part".
[0021]
Now the present invention is explained in the
following by referring to the attached drawings. In Fig. 1 -
Fig. 5, each element is schematically shown, and therefore,
the ratios of the size and the like of elements are different
from those of actual adhesive patch and the like.
[0022]
The adhesive patch of the present invention has a
substantially flat planar shape. The flat shape of the
adhesive patch of the present invention includes, but is not
limited to, for example, about rectangle, polygon such as
triangle, pentagon and the like, or a shape defined by about
straight lines, a shape defined by curved lines such as
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ellipse, circular shape and the like, a combination thereof
and the like. The size of the adhesive patch is not limited,
and can be selected as appropriate according to the use,
application site and the like of the adhesive patch. For
example, when the adhesive patch has an about rectangular
shape, the length of one side thereof is generally 15 mm - 90
mm, and the length of the other side is generally 15 mm - 90
mm. In the present specification, when plural distinguishable
areas are present in the flat plane of the adhesive patch of
/o the present invention, an area containing the center of
gravity of the flat plane of the adhesive patch is referred to
as a central part, and an area containing the contoured part
of the flat plane of the adhesive patch, which is present
outside the aforementioned central part, is referred to as a
peripheral part. In addition, the thickness of the adhesive
patch central part is the thickness of the core part of the
adhesive patch, namely, at the gravity center of the flat
plane of the adhesive patch.
[0023]
The adhesive patch of the present invention has an
adhesive layer on at least one surface of a support and a
release liner on the opposite surface of the adhesive layer.
The lateral end of the adhesive layer is exposed and, in at
least one lateral end of the adhesive patch, the lateral end
of the adhesive layer is located toward the central part side
of the adhesive patch from the lateral end of the support.
That is, in Fig. 1 schematically showing the cross section of
the adhesive patch of the present invention, a line segment cd
binding an upper end c of the support 1 and a lower end d of a
release liner 3 at the lateral end of an adhesive layer 2 is
located toward the central part side of the adhesive patch
from a line segment ab binding an upper end a of the support 1
and a lower end b of the release liner 3. Such shape can be
formed by contouring the adhesive layer as mentioned above
during formation of an adhesive layer on a support or a
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release liner. For example, an adhesive layer is formed such
that the contoured part of the adhesive layer is located
toward the central part side of an adhesive patch from a part
corresponding to the contoured part of a support of the
adhesive patch. Alternatively, in an adhesive patch wherein
the lateral ends of a support and an adhesive layer are on the
same flat plane, the aforementioned shape is formed by
breaking away one part of the lateral end of the adhesive
layer. In the present specification, the cross section shown
m in each drawing is that of an adhesive patch cut in the
perpendicular direction from the surface of support 1.
[0024]
In the adhesive patch of the present invention, moreover,
when the adhesive patch is placed on the horizontal plane with
/5 a release liner facing downward, distance A between the upper
end of a support and the lower end of a release liner at the
above-mentioned lateral end of the adhesive patch, namely, the
length of the perpendicular line ab' drawn from an upper end a
of support 1 to the lower end of release liner 3 in Fig. 1 is
20 greater than the length of thickness B in the adhesive patch
central part, i.e., a perpendicular line ef drawn from the
upper end e of the support 1 to the lower end of release liner
3 in the adhesive patch core part in Fig. 1. In the present
invention, A is preferably 101% - 200%, more preferably 101% -
25 150%, of B. Being difficult to predict, when an adhesive patch
having the aforementioned constitution is applied to the skin,
it does not drop off easily for a long time. When a part free
of an adhesive layer is formed in an end part of the adhesive
patch, the skin adhesive force at the end of the adhesive
30 patch generally decreases and the adhesive patch is expected
to drop off from the skin with ease. According to the present
invention having the aforementioned shape, however, when an
adhesive patch is applied to the skin, the lateral end of the
support pushes up the clothes somewhat and keeps the clothes
35 off from the lateral end. Thus, the adhesive patch main part
CA 02751350 2011-09-01
does not drop off from the skin for a long time. As a method
for achieving such shape, a method including laminating a
support preliminarily molded in the aforementioned shape on an
adhesive layer, and a method including laminating a tabular
support on an adhesive layer, and molding the adhesive patch
in the aforementioned shape can be used.
[0025]
In a preferable embodiment of the present invention, in
at least one lateral end of the adhesive patch, the lateral
lo end of the adhesive layer is located at 1 gm - 1000 gm, more
preferably 100 gm - 800 gm, toward the central part side of the
adhesive patch from the lateral end of the support. That is,
in Fig. 1, the length of a line segment ac connecting an upper
end a of the support 1 and an upper end c of the support 1 in
the lateral end of an adhesive layer 2 is 1 gm - 1000 gm, more
preferably 100 gm - 800 gm. When the lateral end of the
adhesive layer 2 is located at 1 gm - 1000 gm from the lateral
end of the support 1, oozing or protruding of an adhesive
layer component from the lateral end of the adhesive patch can
be sufficiently suppressed during the preservation of the
adhesive patch, and the adhesive force at the lateral end of
the adhesive patch does not decrease often.
[0026]
Moreover, in another preferable embodiment of the present
invention, when an adhesive patch is placed on a horizontal
plane with a release liner facing down, in at least one
lateral end of the adhesive patch, distance A between the
support upper end and the release liner lower end at the
lateral end is greater than thickness C of the adhesive patch
at the lateral end of the adhesive layer. That is, in Fig. 2
showing a schematic sectional view of the adhesive patch of
the embodiment, the length of a perpendicular line ab' drawn
from an upper end a of support 1 to the lower end of release
liner 3 at the lateral end of the adhesive patch is greater
than perpendicular line cd' drawn from upper end c of the
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CA. 02751350 2011-09-01
support 1 to the lower end of release liner 3, in the lateral
end of the adhesive layer 2. In the present invention, A is
preferably 101% - 200%, more preferably 101% - 150%, of C. In
the adhesive patch of this embodiment, C is greater than B.
[0027]
Depending on the production method and molding method of
the adhesive patch, moreover, an adhesive patch may contain a
peripheral part and a central part thicker than the peripheral
part. In this case, even when thickness C of the adhesive
patch at the lateral end of the adhesive layer is thinner than
thickness B of the adhesive patch central part in , when
distance A between the support upper end and the release liner
lower end at the lateral end is greater than thickness B of
the adhesive patch at the central part of the adhesive layer,
/5 by placing an adhesive patch on a horizontal plane with a
release liner facing down, the adhesive patch is encompassed
in the adhesive patch of the present invention.
[0028]
A schematic sectional view of the adhesive patch of
another embodiment is shown in Fig. 3. In the adhesive patch
of this embodiment, in at least one lateral end of the
adhesive patch, thickness C of the adhesive patch at the
lateral end of the adhesive layer is the same as thickness B
of the central part of the adhesive patch. As a result, the
effects of the present invention: (i) an adhesive patch does
not easily attach to an inner wall surface of a package, and
the adhesive patch can be easily taken out from the package,
(ii) the release liner can be easily detached from the
adhesive patch main part, (iii) the adhesive patch main part
does not drop off easily from the skin, have been clarified
more. Even when the adhesive patch has a peripheral part and a
central part, when distance A between support upper end and
release liner lower end at the lateral end of the adhesive
patch is larger than thickness B of the adhesive patch central
part and thickness C of the adhesive patch at the lateral end
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of the adhesive layer is equal to thickness B of the adhesive
patch central part, the adhesive patch is encompassed in this
embodiment of the adhesive patch.
[0029]
In another preferable embodiment of the present invention,
an adhesive layer end in at least one lateral end of the
adhesive patch has a concave shape. To be specific, in Fig. 4
showing a schematic sectional view of the adhesive patch of
the embodiment, the cross section of the lateral end of the
/o adhesive layer 2 has a recessed circular arcuate on the
central part side. With this constitution, the release liner
can be easily detached from the adhesive patch. While the
aforementioned constitution can be formed by various methods,
for example, the side face of the adhesive layer can be
is processed by laser irradiation and the like.
[0030]
While the support used for the adhesive patch of the
present invention is not particularly limited, a support which
is substantially drug impermeable, namely, a support made of a
20 material which does not permit an active ingredient, an
additive and the like in the adhesive layer to pass through
the support and be lost from the back face of the adhesive
patch to cause a decreased content is preferable.
[0031]
25 In the present invention, a single film of a resin or a
metal foil, or a laminate thereof is used as a support. To
improve adhesiveness (anchoring property) between a support
and an adhesive layer, a laminate of a porous material and a
resin film is preferably used. In this case, an adhesive layer
30 is laminated on the porous material of the laminate. Porous
materials have concaves and convexes, and have voids (air
bubbles) in itself. Since an adhesive layer can enter into the
aforementioned voids, they can effectively suppress oozing or
protruding of adhesive layer components.
35 [0032]
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Examples of the above-mentioned porous material include
porous film and sheet. When the sheet has a thickness of not
less than 200 pm, a porous film is preferably used. The
aforementioned porous film may be a single layer film or a
laminate film, and one having an anchoring property to
suppress movement of the adhesive layer to the porous material
can be preferably used. Specific examples include paper, woven
fabric, non-woven fabric, knitted fabric, mechanically
perforation-treated film and metal foil, laminates thereof and
the like. Of these, paper, woven fabric, non-woven fabric, and
laminates thereof are particularly preferable from the aspects
of handling performance and the like, and non-woven fabric is
especially preferable.
[0033]
The porous material and resin film may be made of the
same materials or different materials. These can be laminated
according to a known method. They may contain various
additives such as antioxidant, pigment, antistatic agent and
the like as appropriate as long as the characteristics of the
invention are not impaired. In addition, the surface thereof
may be subjected to a corona discharge treatment, an
ultraviolet irradiation treatment and the like.
[0034]
Examples of the material of the aforementioned porous
material and resin film constituting the support include
polyester-based resin such as poly(ethylene terephthalate) and
the like; polyamide-based resin such as nylon and the like;
olefin-based resin such as polyethylene, polypropylene and the
like; vinyl-based resin such as polyvinylidene chloride
including Saran (registered trade mark of Asahi Kasei
Corporation or Dow Chemical Company, USA), polyvinyl chloride,
ionomer resin including Surlyn (registered trade mark of
DuPont, USA) and the like; acrylic resin such as ethylene-
ethyl acrylate copolymer and the like; fluorocarbon resin such
as polytetrafluoroethylene and the like; combinations thereof
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and the like.
[0035]
As mentioned later, when a production method
characterized by pressing and heating of an area corresponding
to the peripheral part of an adhesive patch is employed,
porous material and resin film constituting a support are
preferably made of a material that deforms by heating and
softening and maintains the deformed shape after cooling, so
that adhesive layer components can moderately move and a
/o desired shape can be molded. As such material, a thermoplastic
resin, for example, a polyester-based resin; an olefin-based
resin such as polypropylene, polyethylene and the like are
preferable, and a polyester-based resin, for example,
poly(ethylene terephthalate), is particularly preferable.
[0036]
The thickness of the porous material is preferably within
the range of 10 - 100 pm so as to afford improved anchoring
property, flexibility of the entire adhesive patch, attaching
operability and the like. When a woven fabric or non-woven
fabric is used as a porous material, the basis weight thereof
is preferably 5 - 50 g/m2, more preferably 10 - 30 g/m2, to
secure sufficient voids and achieve anchoring property.
[0037]
The thickness of the above-mentioned porous material is
measured by staining an adhesive patch with an aqueous
ruthenium acid solution, imaging a section produced with a
freezing microtome with a super high-resolution field emission
scanning electron microscope (FE-SEM) at 50- to 1000-power,
and reading the gauge scale. In this case, concaves and
convexes are present on the surface of the porous material. In
a sectional image, 10 convexes are selected at random, and an
average of the thickness of the porous material at the
convexes is calculated and taken as the thickness of the
porous material.
[0038]
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In the present invention, moreover, the basis weight of
the porous material is deteLmined by multiplying the thickness
of the above-mentioned porous material by the specific gravity
(apparent specific gravity) of the porous material and
calculating the weight of the porous material per unit area.
[0039]
A resin film to be laminated on a porous material may be
a single layer film or a laminate film. A nonporous film made
of a resin impermeable to the active ingredient is preferable.
lo Such resin films suppress permeation of adhesive layer
components through the back face of the support to reduce the
content thereof. In addition, when the adhesive layer contains
a drug, they are preferably used to achieve an effect of what
is called an occlusive dressing technique (ODT).
/5 [0040]
While the thickness of the resin film is not particularly
limited, it is preferably 1 - 45 pm. When it is not less than
1 pm, the moldability becomes good, operability becomes
superior, and handling is facilitated. On the other hand, when
20 it is not more than 45 pm, an uncomfortable feeling occurs
less often during application to the skin, due to the rigidity
of the resin film. As mentioned later, when a production
method characterized by pressing and heating of an area
corresponding to the peripheral part of an adhesive patch is
25 employed, good moldability is observed. In the present
invention, the thickness of the resin film is measured in the
same manner as for the above-mentioned porous material.
[0041]
Thus, as a support preferably used in the present
30 invention, a laminate film of a polyester-based film with 1 -
45 pm thickness (more preferably, poly(ethylene terephthalate)
film) and a non-woven fabric made of polyester-based resin
(more preferably, poly(ethylene terephthalate)) having a basis
weight of 10 - 30 g/m2 can be mentioned.
35 [0042]
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In consideration of the skin-following ability and
comfortableness during application of an adhesive patch, the
total thickness of the support is preferably 5 - 200 pm.
[0043]
The constituent components of the adhesive layer and
production method thereof are explained below. The amount of
each component described in the following for the production
of the adhesive layer is a ratio in wt% of the amount of each
component relative to the amount of whole components except
/o solvent.
[0044]
The adhesive layer can be formed by adding an adhesive
together with components such as a drug, a tackifier, an
organic liquid component and the like as necessary to a
solvent and mixing them to give a composition for formation of
an adhesive layer, forming layers thereof by a method such as
coating and the like, and drying the layers. The adhesive
layer is preferably a hydrophobic adhesive layer in view of
adhesion to the skin, and therefore, an anhydrous adhesive
layer is preferable. From such aspect, the aforementioned
solvent is preferably an organic solvent.
[0045]
While the adhesive constituting the adhesive layer is not
particularly limited, examples thereof include acrylic
adhesives comprising acrylic polymer; styrene-diene-styrene
block copolymers (e.g., styrene-isoprene-styrene block
copolymer, styrene-butadiene-styrene block copolymer, etc.);
rubber-based adhesives such as polyisoprene, polyisobutylene,
polybutadiene and the like; silicone-based adhesives such as
silicone rubber, dimethylsiloxane-based, diphenylsiloxane-
based and the like; vinyl ether-based adhesives such as
poly(vinyl methyl ether), poly(vinyl ethyl ether), poly(vinyl
isobutyl ether) and the like; vinyl ester-based adhesives such
as vinyl acetate-ethylene copolymer and the like; polyester-
based adhesives comprising carboxylate component such as
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dimethyl terephthalate, dimethyl isophthalate, dimethyl
phthalate, etc., and polyvalent alcohol components such as
ethylene glycol, etc. and the like.
[0046]
The adhesive layer may be a cross-linked adhesive layer
obtained by subjecting the aforementioned adhesive layer to a
cross-linking treatment, or a non-cross-linked adhesive layer
obtained without a cross-linking treatment in the present
invention. Here, the cross-linking treatment refers to a known
lo treatment which can form bonds between molecules or in a
molecule in an adhesive layer component constituting the
adhesive layer. The crosslinking treatment simultaneously
enables maintenance of sufficient skin adhesive force of an
adhesive patch and reduction of skin irritation such as
pulling feeling of the skin and physical scraping of the
stratum corneum of the skin during peeling off of the adhesive
patch from the skin surface. Examples of the cross-linking
treatment include a chemical crosslinking treatment using a
crosslinking agent, a treatment for ion cross-linking, and a
physical crosslinking treatment using electron beam,
ultraviolet light and the like. Examples of the crosslinking
agent include metal salts such as zinc acetate and the like,
an epoxy compound, an amide compound, an amine compound, acid
anhydride, peroxide, an isocyanate compound and the like.
[0047]
When the adhesive layer is a non-cross-linked adhesive
layer, adhesive layer components tend to ooze or protrude from
the end of the adhesive patch. Even when the adhesive layer is
a non-cross-linked adhesive layer, the adhesive patch of the
present invention can effectively suppress oozing or
protruding of the adhesive layer components, and is
particularly advantageous in such case.
[0048]
Similarly, when the adhesive layer comprises a rubber-
based adhesive, adhesive layer components tend to ooze or
18
CA 02751350 2011-09-01
protrude from the end of the adhesive patch, and the adhesive
patch of the present invention is particularly advantageous in
such case.
[0049]
To achieve appropriate adhesive force and dissolution
property of drugs, a mixture of the same component or
different components having different average molecular
weights can be used as a rubber-based adhesive. To explain
with polyisobutylene as an example, a mixture of high
lo molecular weight polyisobutylene having a viscosity average
molecular weight of 1,800,000 - 5,500,000, medium molecular
weight polyisobutylene having a viscosity average molecular
weight of 40,000 - 85,000 and, where necessary, lower
molecular weight polyisobutylene is preferable. The viscosity
/5 average molecular weight in the present invention is
calculated by measuring flow time at 20 C using Ubbelohde
viscometer with capillary 1, calculating a Staudinger index
(JO according to the following Schulz-Blaschke equation
(equation (1)), and then assigning the aforementioned Jo value
20 to the following Mark Houwink-Sakurada equation (equation (2)).
Jo=isp/c(l+Anw) (1)
wherein, isp=t/t0-1
t; flow time of solution (by Hagenbach-couette
correction equation)
25 to; flow time of solvent (by Hagenbach-couette
correction equation)
C; concentration of solution (g/cm3)
A; specific constant of polymer solution
Jo=kMv' (2)
30 Mv; viscosity average molecular weight
k, a; specific constant of polymer
[0050]
In the case of polyisobutylene, A=0.31, k=3.06x10-2,
a=0.65 are inserted into the above-mentioned equation (1) and
35 equation (2), and Mv value can be calculated from Jo value.
19
CA. 02751350 2011-09-01
[0051]
When polyisobutylene is used as an adhesive, a high
molecular weight polyisobutylene is generally added at 10 wt%
- 80 wt%, preferably 10 wt% - 50 wt%, a medium molecular
weight polyisobutylene is generally added at 0 wt% - 90 wt%,
preferably 10 wt% - 80 wt%, and a low molecular weight
polyisobutylene is generally added at 0 wt% - 80 wt%,
preferably 0 wt% - 60 wt%. A generally used adhesive layer
becomes stiff when the proportion of a high molecular weight
io component increases, and soft when the proportion of a low
molecular weight component increases.
[0052]
To confer an adequate adhesiveness to the adhesive layer,
for example, a tackifier such as rosin-based resin,
/5 polyterpene resin, chroman-indene resin, petroleum-based resin,
terpene-phenol resin, xylene resin and the like may be
contained. These may be used alone or in a mixture of two or
more kinds thereof. Examples of the aforementioned petroleum-
based resin include aliphatic (05-based) petroleum resin,
20 aromatic (09-based) petroleum resin, copolymer series (C5-C9-
based) petroleum resin and alicyclic saturated hydrocarbon
resin obtained by partially or completely hydrogenating
aromatic (C9-based) petroleum resin. As the alicyclic
saturated hydrocarbon resin, one having a softening point by
25 ring and ball method of 90 - 150 C is preferable. While the
amount of the tackifier is not particularly limited, it is,
for example, 10 wt% - 40 wt% from the aspects of imparting of
appropriate adhesiveness and cost-effectiveness.
[0053]
30 When desired, the adhesive layer can contain an organic
liquid component. An organic liquid component is not
particularly limited as long as it is liquid at room
temperature (259:), or is a mixture of two or more kinds which
finally becomes liquid at room temperature (25 C). Examples of
35 the organic liquid component include glycols such as ethylene
CA 02751350 2011-09-01
glycol, propylene glycol, butylene glycol, diethylene glycol,
dipropylene glycol, triethylene glycol, tripropylene glycol,
poly(ethylene glycol), poly(propylene glycol) and the like;
vegetable fats and oils such as olive oil, castor oil and the
like; animal fats and oils such as liquid lanolin;
hydrocarbons such as squalane and liquid paraffin; various
surfactants; ethoxylated stearyl alcohol; glycerol monoesters
of fatty acids such as oleic acid monoglyceride, caprylic acid
monoglyceride and lauryl acid monoglyceride; dialkyl esters of
/o polyalkylene glycol such as polyethylene glycol dilaurate,
polyethylene glycol diisostearate, polypropylene glycol
diisostearate, polypropylene glycol dioleate and the like;
glycerol diesters such as glycerol diacetate and the like;
glycerol triesters such as glyceroltriacetate and the like, or
a mixture thereof; alkylesters of fatty acid such as triethyl
citrate and the like; long chain alcohols such as isostearyl
alcohol, oleyl alcohol and the like; higher fatty acids such
as caprylic acid, oleic acid, linoleic acid; alkylesters of
higher fatty acid such as isopropyl myristate; pyrrolidones
such as N-methylpyrrolidone, N-dodecylpyrrolidone; sulfoxides
such as decylmethylsulfoxide; and the like. These can be used
alone or in a mixture of two or more kinds thereof.
[0054]
The content of the above-mentioned organic liquid
component is preferably 10 wt% - 60 wt, more preferably 15 wt%
- 60 wt%, most preferably 20 wt% - 60 wt%. When the content of
the component is not less than 10 wt%, the adhesive layer is
easily plasticized, and adhesive layer components easily ooze
or protrude from the end of the adhesive layer. Therefore, the
present invention capable of effectively suppressing such
phenomenon is advantageous in such cases. When an organic
liquid component is contained in a proportion of more than 60
wt%, an adhesive layer may not be able to maintain a given
shape.
[0055]
21
CA 02751350 2011-09-01
While the organic solvent to be used for the production
of an adhesive layer in the present invention is not
particularly limited, one compatible with the above-mentioned
components constituting the adhesive layer and permitting easy
volatilization in a drying step is preferable. Examples of the
organic liquid solvent include aromatic hydrocarbons such as
benzene, toluene, xylene and the like; aliphatic hydrocarbon
such as n-hexane and the like; esters such as ethyl acetate
and the like; alcohols such as methanol, ethanol, isopropanol
lo and the like; ethers such as diethyl ether, tetrahydrofuran
and the like; ketones such as acetone and the like; and the
like. These may be used alone or in a mixture of two or more
kinds thereof.
[0056]
While the method of mixing the aforementioned respective
components is not limited, examples thereof include kneading
machines such as kneader, planetary mixer, Henschel mixer,
roll mill; dispersing machines such as colloid mill,
homogenizer and the like; stirring machines such as propeller-
type blade stirring machine and the like; and the like. These
can be used alone or in a combination of two or more kinds
thereof.
[0057]
A composition to form an adhesive layer can be applied
with, for example, a conventionally-used coater such as a
rotogravure roll coater, a reverse roll coater, a kiss-roll
coater, a dip roll coater, a bar coater, a knife coater, a
spray coater and the like. For promotion of crosslinking
reaction, improvement of production efficiency and the like,
the aforementioned composition is preferably dried under
heating. Depending on the kind of the support to be coated
with the composition, the drying temperature is, for example,
about 40 C - 150 C.
[0058]
The aforementioned drying may be performed by air-drying,
22
CA 02751350 2011-09-01
or according to a known method using a dryer, hot air, far-
infrared radiation and the like.
[0059]
In the adhesive patch of the present invention, an
adhesive layer has a thickness of 50 gm - 500 gm, more
preferably 100 gm - 300 gm, in the core part of the adhesive
patch. Moreover, the thickness of the adhesive layer in the
entire central part of the adhesive patch is preferably within
the aforementioned range. When an adhesive layer has a
/o thickness within the aforementioned range, it is superior in
the skin protection effect, can sufficiently contain an active
ingredient such as a drug and the like, and is superior in the
skin adhesion performance.
[0060]
A release liner to protect the adhesive surface can be
laminated on the adhesive surface of the adhesive layer of the
adhesive patch main part, before applying the adhesive patch
main part to the skin. The release liner is not particularly
limited, and examples of the material thereof include those
known per se in the field. Specific examples thereof include
plastic films of polyester-based resin film such as
poly(ethylene terephthalate); vinyl-based resin film such as
poly(vinyl chloride), poly(vinylidene chloride), polystyrene
and the like; acrylic resin film such as various acrylic and
methacrylic polymers; polycarbonate resin film; polyimide
resin film; cellulose-based resin film such as acetyl
cellulose, regenerated cellulose (cellophane), celluloid and
the like; a laminate film of high-quality paper, glassine
paper and the like and polyolefin-based film and the like. For
safety, economic efficiency and drug-transfer properties, a
polyester-based resin film is preferably used. The thickness
of the aforementioned release liner is generally 10 gm - 200 gm,
preferably 25 m - 100 gm.
[0061]
The release liner is preferably treated for easy peeling
23
CA 02751350 2011-09-01
on the interfacial surface side with an adhesive layer, so as
to facilitate peeling from the adhesive layer. While the easy
peeling treatment is not particularly limited, a known method
can be applied. For example, a treatment method for forming a
peeling-treated layer using a release agent containing a
curable silicone resin as a main component by a coating method
such as bar coating, gravure coating and the like can be
mentioned.
[0062]
The thickness of the aforementioned peeling-treated layer
is preferably 0.01 m - 5 pm to ensure releaseability and
uniformity of the coating. The thickness of the release liner
having a peeling-treated layer is generally 10 m - 200 m,
preferably 50 pm - 100 m, from the aspect of handling property.
/5 [0063]
The release liner in the adhesive patch of the present
invention may have an extended part outwardly extending over
the adhesive patch main part. Since the extended part
decreases the frequency of contact of the end of the adhesive
patch main part against the inside of the package when the
adhesive patch is contained in the package, even when an
adhesive layer component oozes or protrudes from the end of
the adhesive patch main part, adhesion thereof to the inside
of package which causes difficulty in taking the adhesive
patch out from the package can be suppressed. To provide such
effects, at least one part of the peripheral part of the
adhesive patch main part preferably has a release liner with
an extended part, and more preferably, the whole peripheral
part of the adhesive patch main part has a release liner with
an extended part. The length of the aforementioned extended
part of the release liner is preferably about 0.5 mm - 10 mm,
more preferably about 1 mm - 3 mm, so as to achieve the
aforementioned effects and ensure smooth insertion into a
package.
[0064]
24
CA 02751350 2011-09-01
The release liner may also have a back split part. The
aforementioned back split part is made by forming a broken
line on the surface on the opposite side from the contact
surface of the release liner with the adhesive layer. The
shape of the aforementioned broken line may be linear or curve
(e.g., wave shape), or a combination of these. The broken line
may be a solid line or a dashed line, or a combination of
these. Since a release liner has a back split part, the
release liner can be easily removed when the adhesive patch is
m used.
[0065]
In the present invention, an adhesive layer may contain a
drug when desired to form an adhesive preparation. The drug
here is not particularly limited, and any of drugs for
systemic action and drugs for local action can be used. A drug
that can be administered to a mammal such as human and the
like through the skin, that is, a transdelmal absorptive drug
is preferable. Such drugs specifically include, for example,
general anesthetics, antipsychotic agents, antidepressants,
mood stabilizers, psychostimulants, hypnotics, antianxiety
drugs, antiepileptic drugs, therapeutic drugs for migraine,
antiemetic drugs, drugs for dizziness, local anesthetics,
muscle relaxants, autonomic drugs, antispastic drugs,
therapeutic drugs for Parkinson's disease, corticosteroids,
nonsteroidal antiinflammatory drugs, analgesic-antipyretics,
antirheumatic drugs, anti-histamine drugs, antiallergic agents,
cardiac stimulants, antiarrhythmic drugs, diuretics,
depressors, vasoconstrictors, vasodilators, therapeutic drugs
for angina pectoris, anapnoics, bronchodilators, therapeutic
drugs for bronchial asthma, antitussives, expectorants,
hormone drugs, hematinics, hemostatic drugs, antithrombotic
drugs, therapeutic drugs for gout.hyperuricemia, therapeutic
drugs for diabetes, therapeutic drugs for hyperlipidemia,
antineoplastic drugs, immunosuppressive drugs, antibacterial
agents, chemical therapy drugs, antifungal agents, antiviral
CA. 02751350 2011-09-01
drugs, antiparasitic drugs, narcotics, stop smoking aids and
the like. These drugs may be used in a free form or a salt
form.
[0066]
The content of the above-mentioned drug in the adhesive
preparation is not particularly limited as long as the effect
of the drug for transdermal absorption can be sufficiently
exerted, and the adhesion property and the like of an adhesive
layer are not impaired. It is preferably 0.1 wt% - 60 wt%,
..zo more preferably 0.5 wt% - 40 wt%, of the adhesive layer. When
it is lower than 0.1 wt%, a sufficient treatment effect may
not be obtained, and when it is higher than 60 wt%, skin
irritation may occur, as well as a treatment effect may not be
improved, thus providing economical disadvantages.
[0067]
As the production method of the adhesive patch, various
methods are available as mentioned in the above explanation of
the shape and the like of the adhesive patch. However, for
industrial production, for example, the following method is
preferable for high production efficiency.
[0068]
First, a composition for foLmation of an adhesive layer
is applied to one surface of a release liner and dried to give
an adhesive layer. A support is laminated thereon to give an
original sheet for punching out of adhesive patch.
Alternatively, a composition for formation of an adhesive
layer is applied to one surface of a support and dried to give
an adhesive layer. A support is laminated thereon to give an
original sheet for punching out of adhesive patch. A method of
the above-mentioned lamination is not particularly limited and,
for example, a known method such as application of primer and
the like, adhesion, fusion bonding, melt-bonding, pressure
bonding and the like can be mentioned.
[0069]
Then, an original sheet for punching out of adhesive
26
CA. 02751350 2011-09-01
patch is stamped from the support side by pressing with a
heated stamp having a predetermined shape. After stamping, the
aforementioned original sheet is punched out at a
predetermined punching position to give the adhesive patch of
the present invention. The predetermined shape of the
aforementioned stamp is such a shape as presses at least an
area corresponding to the peripheral part of the adhesive
patch during pressing. By pressing an area corresponding to
the peripheral part, an adhesive layer in the peripheral part
/o, of the adhesive patch can be decreased or removed. In addition,
an adhesive patch wherein distance A between support upper end
and release liner lower end at the lateral end of the adhesive
patch is greater than thickness B of the central part of the
adhesive patch can be efficiently obtained by pressing the
aforementioned original sheet with a stamp and removing the
stamp, since the support has a restoring force.
[0070]
As mentioned above, an adhesive patch wherein distance A
between support upper end and release liner lower end at the
lateral end is greater than thickness B of the central part of
the adhesive patch can be preferably obtained by using a
heated stamp. A schematic sectional view of an adhesive patch
obtained by the aforementioned method is shown in Fig. 5. By
stamping with a heated stamp, a support containing a part
adjacent to the adhesive patch central part side of the
pressed area is softened with heat. As a result, the adhesive
layer in the pressed area is released, and formation of a thin
peripheral part 5 having a smaller thickness than the central
part 4 is encouraged. The aforementioned shape of the once-
formed adhesive patch is later allowed to cool or cooled
otherwise and maintains its shape. Thus, a preferable
embodiment of the present invention contains, as shown in Fig.
5, a central part and a peripheral part 5 having a smaller
thickness than the central part 4. While the temperature of
the heated stamp varies depending on the material and
27
CA 02751350 2011-09-01
thickness of a support, composition of an adhesive layer and
the like, it is preferably 90 C - 200 C, more preferably 120 C
[0071]
To form a concave lateral end of the adhesive layer and
remove adhesive layer of the peripheral part, the pressure
during pressing and pressing time are preferably controlled.
The pressure during pressing varies depending on the material
and thickness of a support, composition of an adhesive layer
lo and the like. It is preferably 10N/10cre - 1,000,000N/10 cm?
(1.0x104N/re - 1.0x109N /re), more preferably 500N/10 cm' -
10,000N/10 cm' (5.0x105N/m2 - 1.0x107N/m2). The pressing time
also varies depending on the material and thickness of a
support, composition of an adhesive layer and the like. It is
/5 preferably 0.05 second - 5 seconds, more preferably 0.1 second
- 2 seconds.
[0072]
During stamping, the gap between the stamp and the
stamping table is preferably the total thickness of a support,
20 the peripheral part of an adhesive layer and a release liner
pm.
[0073]
The preferable shape of a stamp is any containing a
planar section as a pressing surface that contacts and presses
25 an adhesive patch, and is not particularly limited as long as
it can specifically press only a peripheral part of the
adhesive patch. The planar section as a pressing surface has a
shape corresponding to the peripheral part of the adhesive
patch. For example, the shape of the stamp consists of a
30 surrounding first rectangle (square, oblong figure) on the
coax and a smaller second rectangle similar thereto, and the
corresponding sides of the first and second rectangles are
disposed in parallel to each other. While the material of the
stamp is not particularly limited, iron is preferable.
.3.5 Stainless steel may develop heat distortion and the processing
28
Ch 02751350 2011-09-01
thereof may be difficult. Aluminum and brass can be processed
easily, but may be unpreferably inferior in the duration of
the stamp.
[0074]
The punching means for an adhesive patch and the like is
not particularly limited, and a punching-out method using a
laser, a press-cutting blade and the like can be mentioned.
Since adjustment of cutting size and position adjustment are
easy and a clear end surface can be obtained, an original
m sheet is preferably punched out with a press-cutting blade
dies set (male type and female type).
[0075]
In a preferable embodiment of the adhesive patch of the
present invention, the release liner has an extended part in
at least one part of the peripheral part of the adhesive patch
main part and, in a more preferable embodiment, the release
liner has an extended part in the whole peripheral part of the
adhesive patch main part. An extended part of such at least
one part of the peripheral part can be easily foLmed by
punching out only the adhesive patch main part using a press-
cutting blade dies set (male type and female type) having a
required shape and then punching out the release liner.
[0076]
The length of the extended release liner can be adjusted
by changing the size difference in the press-cutting blade
dies set male type and female type. The length of the extended
release liner can be extended by increasing the size
difference. When a back split part is set on a release liner,
the central part of a release liner is half-cut with a die
roll, and a broken line is formed only in the release liner.
[0077]
The adhesive patch and adhesive preparation of the
present invention are preferably preserved in a package. Such
package can be produced using a packaging material generally
used for packaging of adhesive patches. Examples of the
29
CP. 02751350 2011-09-01
packaging material include polyolefin-based resin film such as
polyethylene film, polypropylene film, polymethylpentene film
and the like; vinyl-based resin film such as polyvinyl
chloride film, polyvinylidene chloride film, polyvinyl alcohol
film, polystyrene film, polyacrylonitrile film, ionomer film
and the like; polyester-based resin film such as poly (ethylene
terephthalate) film and the like; polyamide-based resin film
such as nylon film and the like; cellulose-based resin film
such as cellophane and the like; polycarbonate resin film; and
lo laminate film thereof; laminate film thereof and aluminum and
the like. An adhesive patch can be housed in a package
produced using the aforementioned packaging materials, and
tightly sealed by a known method such as heat sealing and the
like.
Examples
[0078]
The present invention is explained in more detail in
the following by referring to Examples and Comparative
Examples, which are not to be construed as limitative.
[0079]
[Examples 1, 2 and Comparative Examples 1 - 3] Adhesive
preparations
(1) Production of adhesive sheet
<Production of a composition for formation of an adhesive
layer>
High molecular weight polyisobutylene (viscosity average
molecular weight; 4,000,000, 0.620 kg), alicyclic saturated
hydrocarbon resin (softening point by ring and ball method;
120 C - 160 C, 1.127 kg), toluene (4.456 kg) and n-hexane
(4.726 kg) were weighed, and stirred in a blending tank for
not less than 24 hr. Medium molecular weight polyisobutylene
(viscosity average molecular weight; 55,000, 1.071 kg) was
weighed, cast into the blending tank and the mixture was
stirred for not less than 24 hr. Thereafter, isopropyl
myristate (1.232 kg) and toluene (0.270 kg) were weighed, cast
CA. 02751350 2011-09-01
into the blending tank and the mixture was stirred for not
less than 4 hr to give a composition for forming an adhesive
layer.
<Production of original sheet for punching out>
The above-mentioned composition was applied to an easy-
release treated surface of a release liner (thickness 75 gm)
made from poly(ethylene terephthalate) (hereinafter to be
indicated as "PET") with a coater consisting of a back roll and
a comma roll, such that the thickness of the adhesive layer
/o after drying was 160 gm, and dried. The obtained adhesive
surface of the adhesive layer was adhered to a PET non-woven
fabric surface of a support, which is a laminate of a 3.5 gm-
thick PET film and a PET non-woven fabric (basis weight: 10g/m2
- 20g/m2), by pressure bonding to give an original sheet for
/5 punching out of adhesive patch.
[0080]
(2) Formation of adhesive patch by punching and packaging
machine
The above-mentioned original sheet for adhesive patch
20 punching out was punched out by a punching and packaging
machine equipped with a stamping part (hot-pressing + stamping
metal mold) and a die set metal mold (male type, female type)
to give an adhesive patch. The stamping width of the stamping
part, heating temperature and pressure during stamping were
25 adjusted as shown in Table 1 to give the adhesive patches of
Examples 1 and 2, and Comparative Examples 1 - 3.
31
CA. 02751350 2011-09-01
[0081]
Table 1
stamping heating pressure
during pressing
sample width temperature stamping time
(mm) of stamp ( C) (N/10 cm2) (second)
Example 1 3 150 10,000 0.25
Example 2 3 150 10,000 0.10
Comparative
3 >200 10,000 0.25
Example 1
Comparative
3 >200 10,000 5.00
Example 2
Comparative
3 <90 10,000 0.05
Example 3
[0082]
[Experimental Example 1] Evaluation of adhesive patch shape
Each adhesive patch of Example and Comparative Example
was stained with an aqueous ruthenium acid solution, and cut
with a frozen microtome (LR-85 manufactured by YAMATO KOHKI
INDUSTRIAL CO., LTD.). The section was taken by FE-SEM (S-4800
manufactured by Hitachi, Ltd.) at 50-power to 1000-power. In
io the electron micrograph of each adhesive patch, the gauge
scales of the peripheral part and the central part were read,
whereby the thicknesses of the PET film and the PET non-woven
fabric, and the thickness (total of thickness of adhesive
layer and thickness of support) of the adhesive patch main
/5 part were measured. In this case, concaves and convexes are
present on the surface of the PET non-woven fabric. In a
sectional image, 10 convexes are selected at random, and an
average of the thickness of the PET non-woven fabric at the
convexes was calculated and taken as the thickness of the PET
20 non-woven fabric. Then, the thickness of the PET film and the
thickness of the aforementioned PET non-woven fabric were
subtracted from the thickness of the adhesive patch main part,
and the thicknesses of the adhesive layer at the peripheral
part and the central part were determined. In addition,
25 distance A between the upper end of the support and the lower
end of the release liner at the lateral end of the adhesive
patch, and the distance between the lateral end of the
32
81595658
adhesive layer on the central part side, from the lateral end
of the support was measured.
[0083]
From the sectional images of the end of respective
adhesive patches of the Examples and Comparative Examples, the
respective adhesive patches of Examples and Comparative
Examples were observed for
(1) whether, in a lateral end, the lateral end of the adhesive
layer is located toward the central part side of the adhesive
/0 patch from the lateral end of the support,
(2) whether the distance between the upper end of the support
and the lower end of the release liner at the lateral end is
greater than the thickness of the central part of the adhesive
patch, and
/5 (3) whether the end of the adhesive layer has a concave shape.
When the observation result is a 'yes', Y is marked and when
the result is a 'no', N is marked in Table 2. In each adhesive
patch, the thickness of the central part of the adhesive layer
was the same as that of the adhesive layer after drying the
20 original sheet for punching out, and was 160 gm. In the
adhesive patches of Examples 1 and 2, moreover, distance A
between the upper end of the support and the lower end of the
release liner at the lateral end was within the range of 101%
- 150% of the thickness of the central part of the adhesive
25 patch. In the adhesive patch of Example 1, the lateral end of
the adhesive layer was located at 500 gm toward the central
part side of the adhesive patch from the lateral end of the
support. On the other hand, in the adhesive patch of Example 2,
the lateral end of the adhesive layer was located at 50 gm
30 toward the central part side of the adhesive patch from the
lateral end of the support.
[0084]
[Experimental Example 2] Evaluation of performance of taking-
33
CA 2751350 2018-03-02
81595658
out of adhesive patch from package
As shown in Fig. 6, two sides of the adhesive patch
package were opened with scissors or along V-shaped notches.
The adhesive patch was taken out while holding a corner
s thereof, and the performance of taking-out of the adhesive
patch from the package was evaluated according to the
following three-step evaluation criteria.
<Evaluation criteria>
0; no oozing or protruding of adhesive layer components;
io easy taking out was possible
A; oozing or protruding of adhesive layer components in
a part of adhesive patch; taking out was possible
x; remarkable oozing or protruding of adhesive layer
components; taking out was difficult
15 [0085]
[Experimental Example 3] Evaluation of skin adhesion
performance
A specialized estimator took out an adhesive patch from a
package, adhered the patch to the chest for 24 hr from the
20 morning, and evaluated the adhesion state according to the
following three-step evaluation criteria. During adhesion of
the adhesive patch, the estimator behaved as usual. When the
estimator took a bath in the morning, the patch was adhered
avoiding immediately after taking a bath (within 30 min). The
25 same one estimator evaluated each adhesive patch of Example
and Comparative Example once.
<Evaluation criteria>
0; adhesive patch did not drop off for 24 hr; end of
adhesive patch did not turn up
30 A; adhesive patch did not drop off for 24 hr; end of
adhesive patch turned up
x; adhesive patch dropped off within 24 hr
[0086]
[Experimental Example 4] Evaluation of releaseability of a
35 release liner
34
CA 2751350 2018-03-02
CA 02751350 2011-09-01
Five male panelists (50 years of age or above) detached a
release liner from an adhesive patch, and evaluated the
releaseability thereof by sensory evaluation. The evaluation
results were summarized by the following criteria.
<Summary criteria of evaluation>
0; all panelists felt easy detachability
A; part of panelists felt difficulty in detachment
x; all panelists felt difficulty in detachment
[0087]
The evaluation results of the above-mentioned
Experimental Examples 2 - 4 are also shown in Table 2.
00881
Table 2
shape of lateral end of adhesive patch
evaluation results
lateral end of adhesive
distance between upper concave
perfor- skin release-
end of support and end of
C-)layer is located toward mance in adhe- ability
sample lower end of release
adhesive
central part side of
taking sion of
t.,
liner at lateral end is layer at
...3
adhesive patch from
out from perfor- release in
H
lateral end of support greater than thickness lateral
package mance liner w
In
of central part end
0
ts)
0
Example 1 Y Y Y
0 0 0 H
I
Example 2 Y Y Y
0 0 A 0
1/40
1
, .
0
Comparative
H
Example 1
Y N Y
0 x A
_
Comparative
Example 2
Y N N
0 x x
,
Comparative
Example 3 N N N
x x x
36
CA. 02751350 2011-09-01
[0089]
From Table 2, it is clear that, in the adhesive patches
of Examples 1 and 2 of the present invention, the lateral end
of the adhesive layer was located toward the central part side
of the adhesive patch from the lateral end of the support, at
the lateral end; the distance between the upper end of the
support and the lower end of the release liner at the lateral
end was greater than the thickness of the central part of the
adhesive patch; and the end of the adhesive layer was concave
lo in the lateral end. These adhesive patches received good
evaluation results as to the taking out performance from a
package and skin adhesion performance. The adhesive patch of
Example 1 wherein the lateral end of the adhesive layer is
located at 500 gm on the central part side of the adhesive
1.5 patch from the lateral end of the support received still
higher evaluation with regard to the releaseability of the
release liner, as compared to the adhesive patch of Example 2
wherein the lateral end of the adhesive layer is located at 50
gm on the central part side of the adhesive patch from the
20 lateral end of the support. In contrast, the adhesive patch of
Comparative Example 1 wherein the distance between the upper
end of the support and the lower end of the release liner at
the lateral end is not greater than the thickness of the
central part of the adhesive patch received lower evaluation
25 with regard to the skin adhesion performance. Furthermore, the
adhesive patch of Comparative Example 2 wherein the end of the
adhesive layer is not concave in the lateral end received
lower evaluation also with regard to the releaseability of the
release liner. The adhesive patch of Comparative Example 3
30 wherein the lateral end of the adhesive layer is not located
toward the central part side of the adhesive patch from the
lateral end of the support, at the lateral end; the distance
between the upper end of the support and the lower end of the
release liner at the lateral end is not greater than the
35 thickness of the central part of the adhesive patch; and the
37
Ch 02751350 2011-09-01
end of the adhesive layer is not concave in the lateral end
did not receive good evaluation with regard to the taking-out
performance from a package, skin adhesion performance and
releaseability of a release liner.
10090]
[Examples 3 and 4] Patch preparation
To the above-mentioned composition for formation of an
adhesive layer was added 1 part by weight of indomethacin
(anti-inflammatory agent) per 100 parts by weight of the whole
blended components except toluene, whereby a composition for
formation of an adhesive layer for a transdermal absorptive
preparation was prepared. Using the aforementioned composition
and in the same manner as in the above-mentioned Examples 1
and 2, adhesive preparations were obtained. The adhesive
/5 preparations of Examples 3 and 4 afford effects similar to
those of the adhesive patches of the above-mentioned Examples
1 and 2 in the taking-out performance from a package, skin
adhesion performance and releaseability of a release liner.
INDUSTRIAL APPLICABILITY
[0091]
As described in detail in the above, the present
invention can provide an adhesive patch or adhesive
preparation, which is free of oozing and protruding of an
adhesive layer component from an end, suppresses occurrence of
so-called cold flow phenomenon during preservation, does not
easily attach to the inner surface of a package, can be taken
out with ease from a package, and less often causes an
unpleasant feeling due to stickiness to the hand and sticky
feeling on the application site during use. In addition, the
present invention can provide an adhesive patch or adhesive
preparation which ensures sufficient skin adhesion, is highly
resistant to the detachment from the skin surface, and permits
easy detachment of the release liner, wherein the frequency of
rubbing of the end against clothes etc. is reduced during
adhesion to the skin, and the end is not turned up easily.
38
CA. 02751350 2011-09-01
[Explanation of symbols]
[0092]
1 support
2 adhesive layer
3 release liner
4 central part
5 peripheral part
a upper end of support at lateral end of adhesive patch
b lower end of release liner at lateral end of adhesive
/o patch
b' intersection point of perpendicular line drawn from
upper end a of support at lateral end of adhesive patch to
lower end of release liner, and lower end of release liner
c upper end of support at lateral end of adhesive layer
d lower end of release liner at lateral end of adhesive
layer
d' intersection point of perpendicular line drawn from
upper end c of support at lateral end of adhesive layer to
lower end of release liner, and lower end of release liner
e upper end of support at core part of adhesive patch
f intersection point of perpendicular line drawn from
upper end e of support at core part of adhesive patch to lower
end of release liner, and lower end of release liner
A distance between upper end of support and lower end of
release liner at lateral end of adhesive patch
B thickness of central part of adhesive patch
C thickness of adhesive patch at lateral end of adhesive
layer
39
