Note: Descriptions are shown in the official language in which they were submitted.
CA 02278753 2007-08-13
Removat]le YrOLeCL7.ve rilm iwor klaszer SysLems, in rarilcutar
Self-Adhesive Plaster Systems, Containing Active Substances
Active ingredieat-coataining plaster systems delivering
active inQrgdients, in particular for delivering medicinal
active ixxgradiente to or through the hwaan skin are
becoming increasingly important because of their
therapeutic advantages. They can be divided roughly into
two dlasges, namoly into the trangclermal and the topical
plaster systems. in the transdermal systesas, the active
ingredient in transported through the human, or anixna], skin,
and this active ingredient then has a svatemic action. Yn,
topical plaster systems the aim is for the active
ingredient preferably to act only in the tissue below the
application site.
Soth plaster systems are at ].oagt partly aelf-ad#xesive for
attachrnent to the skin. Yn the simplest case, such systems
(Fig. 1) consist of a backing layer, of a self-adhesive
layer with active ingredient incorporated therein and of a
detachable protscting layer.
Yn another oinbodiment, the systems have the form.ot a flat
bag, with the rear side of the bag beitlg f.ripexmeable for
the active ingredient, and the side of the bag making
contact with the akin being formed by a permeabXe membrasse.
The active ingredient in such a syaaten- is present in the
form of a-liquid or semisolid foxmuXatior, in the bag. The
membrane is advmntageoue3ly provided with an adheeive layer
for attachment to the skin. xt is also neceaaary with this
eatbodisnaut ghown in Fig. 2. for at least the adhesive areas
to be covered beft,re use with a detachable protective
sheeti. For it to be possible to detach the protect.ive oheet
from the system without damagiag the latter and witfsout
exertion of great foxca, the sheet munt be provided, at
least on the side making contact 4vith the plaster, with a
special coating which, because of its abhesive property,
ensures that the forces to separate the adhesive layer and
CA 02278753 2006-08-10
- Z -
tLe protective shoot are not too large for gractical t=se.
ftuta, for all ad2t sives with the exQeption of s3licone
adhesives, thin a3.Yicaaa layers are usual and are appli,ed
to a suitable shae,t material in a spieia7, proGaas. Speoial
fluorosilicoae layerg or fluorS.ne-eaetainiag polrnexs can
be used generally but are obligatoxy !er silloone
adhesives. R"lerw are =wethermorc apeciaY requlrsaLentm to be
met by tbe sheet awaterial for aetive ingrellieat-aontainisxg
plaster 8yatamu. ginae with all these Aysterns acta.ve
ita9redient-oontaining portg also Csoale into contaat vrith C3,s
sheet material, this materipl apasat be inert td a1l the
iMortaat i,ngredients. This appliera in partfatilar to the
aotfte inUL-adfent itself, but aleo to perm.ecLtioa-iagpaoving
soiastanees which are necessary in marxy casea in orger to
inflvtence the barrier action of the human slsin, and to
pYastiaiaern vMcla are 3.nGox orated in the adhas4ve and
have an effect on the adhesiveness of tho systema on tha
skia.
The a-taadard mbLterial aMloyed for tba pxotactive shaet i.s
tiherefore pol,yester (pa:Lyetbyiene tarephtihaymte) for
virtually all plaster aystem. po= sil3oone a~Qsives, in a
tew case9 s. sheet wAd0 of iluorirai-contialuaiag polymwa ia
also used, thus saving an additional abbpaiv0 coatiag.
Thegs materia].s lsava virtualiy no untake capaoity for
aabsta:sa+ap aostinally cmed as an fayredienb of active
iaQr*dieat-ooats,i,nirg p1s ter systemps. ltateaials such aa
polyethylane, pQlypropylea$ or paper are una+ILitable in many
casas bnaauss of their uptake oapacitY for such
ametitiuents of the syebeat. For practicol handliner but
also ior seasoas s"elsti d to manufacturi.na tae3iaique ,
protoctive sboets souat have a saaiatum thickness of about
50 um. This ig a disadvaatage because polyaat*r is a
relatively eontly Material by aosrpariaars wfth other
a,at rfals mentiosred above. zhl.s appiieg in particuiar to
CA 02278753 1999-07-21
- 3 -
topical plaster systems, which may reach a size of 300 cm~
and more.
=t is therefore an object of the invention to indicate an
improved protective sheet for active ingredient-containing,
in particular self-adhesive plaster systems, which, while
having adequate mechanical strength, is impermeable to
active ingredients and ancillary substances and distinctly
reduces the costs for the polyester protective sheets used
hitherto.
The object is surprisingly achieved with the invention-in
that the protective sheet is a laminate of a paper layer
and of an abhesively coated polyester sheet. it is ensured
that the two layers hold together by using suitable
adhesives. it was possible to show by appropriate stability
tests with active ingredient-containing plaster systems
that even very thin - and therefore too thin for producing
active ingredient-containing plasters and practical use
thereof - polyester sheets, laminated onto paper, reliably
prevent constituents of the systems from migrating into the
paper, whose inertness is low. The paper layer merely
serves for mechanical strengthening of the polyester sheet
and, in this case, does not come into any contact with
parts of the system.
=n this regard, one embodiment provides for the polyester
sheet in the laminate being provided on its side which
makes contact with the plaster system with a coating which
is abhesive for the particular adhesive. Preferred
embodiments of the invention provide for the polyester
sheet having a thickness between 5 and 30 Um, preferably
between 10 and 20 pm, and the weight per unit area of the
paper layer being 30 to 150, preferably 60 to 120, g/m', it
being necessary that the total thickness be at least 50 um.
CA 02278753 2005-11-14
-3a-
In accordance with one aspect of the present invention, there is provided an
active
ingredient-containing plaster system with detachable protective sheet,
characterized
in that said protective sheet is a laminate of a paper layer and of an
abhesively
coated, 5 to 50 pm-thick polyester film.
In accordance with a further aspect of the plaster system as defined by the
present
invention, the abhesive coating consists of fluorine-containing polymers.
In accordance with another aspect of the plaster system as defined by the
present
invention, the polyester film is based on polyethylene terephthalate.
In accordance with still a further aspect of the present invention, there is
provided a
detachable protective sheet for active ingredient-containing plaster systems
with
diffusible ingredients, formed by a laminate according to any one of claims 1
to 7 of a
paper layer and an abhesively coated 5 to 50 pm thick polyester film based on
polyethylene terephthalate.
CA 02278753 1999-07-21
- 4 -
Further embodiments of the protective sheet are provided
according to the dependent claims.
Examples of embodiments of plaster systems are depicted in
Figures 1-3, which show:
Fig. 1: a section through a multilayer plaster system with
a detachable protecting layer
Fig. 2: a section through another multilayer plaster system
with a detachable protecting layer
Fig. 3: a section through the design according to the
invention of the detachable protecting layer.
The plaster system shown in Fig. 1 comprises an active
ingredient-impermeable backing layer (1), underneath which
there is.a self-adhesive, active ingredient-containing
matrix layer.(2) which.is covered on the skin side with a
detachable protecting layer (3).
Fig. 2 shows a plaster system with a different type of
construction. This has, underneath a backing layer (1)
which is impermeable for active ingredient and ancillary
substances, an active ingredient-containing liquid
reservoir (4) with a control membrane (5), to which a skin
contact adhesive layer (6) is assigned and which is covered
by a detachable protecting layer (3).
Fig. 3 shows the design according to the invention of the
protecting layer (3) in the form of a laminate which
consists of an abhesively coated polyester sheet (8) and of
a paper sheet (7).
The two sheets (7) and (8) are held together by using
suitable adhesives.
CA 02278753 1999-07-21
- 5 -
Concerning the mechanical properties of the laminate (3),
no disadvantages by comparison with considerably thicker
polyester sheets emerged in corresponding production tests.
The polyester sheet (8) used may additionally be aluminized
on one or both sides in addition to the abhesive finish.
This aluminization takes place by vapour deposition of the
aluminium in vacuo and has the advantage that the abhesive
finish or the adhesive which bonds the polyester sheet (8)
to the paper layer (7) adheres better to aluminium than to
polyester itself. The thickness of the polyester sheet (8)
can be between 5 and 50 um. The thickness of the paper
layer (7) necessarily depends on the particular
circumstances. Tables 1, 2 and 3 show the results of
stability studies with two different topical systems with
the active ingredients ketoprofen, ibuprofen and ethylene
glycol monosalicylate. The values in Table 1 and 2 prove
that the contents of the plaster have remained unchanged
over at least two years. Table 3 shows the amounts of
ethylene glycol monosalicylate found after storage of the
plasters for two years in a protective sheet according to
the invention and compares them with the amounts which had
migrated under the same storage conditions into a
commercially available protective sheet based on a laminate
of paper and siliconized polyethylene.
The results of the stability studies prove that the
laminate (3), on which the invention is based, made of
paper (7) and polyester sheet (8) meets all stability
requirements and is superior to the commercially available
laminate made of paper and polyethylene sheet. it combines
in an advantageous manner the superiority of the polyester
in respect of its inertness with the economic advantages of
paper sheets. with regard to its mechanical processability,
there are no restrictions whatsoever by comparison with
pure polyester sheets.
CA 02278753 1999-07-21
- 6 -
Table 1
Stability of the ketoprofen content in a fatty acid-
containing self-adhesive polyacrylate matrix
Storage time Storage temperature Ketoprofen content
[months] [ C] [mQ/cm']
0 / 0.663
25 0.651
3 31
40 0.657
25 0.674
6 31
40 0.644
12 25 0.629
18 25 0.659
24 25 0.663
Table 2
Stability of the ibuprofen content in a fatty acid-
containing self-adhesive polyacrylate matrix
StoraQe time Storage temperature =buprofen content
[months] [ C] [mQ/cm']
0 / 0.62
25 0.63
3 31
40 0.61
25 0.63
6 31
40 0.61
12 25 0.60
18 25 0.61
CA 02278753 1999-07-21
- 7 -
Table 3
Migration of ethylene glycol monosalicylate out of a self-
adhesive polyacrylate formulation into a siliconized
polyethylene/paper laminate and a laminate of 23 pm
siliconized polyester and 80 g paper at 250C.
Storage time Paper/polyethylene Paper/polyester
[months]
6 0.11 mg/cle 0.001 mg/cle
9 0.14 mg/cm' 0.002 mg/cie
12 0.27 mg/cie 0.002 mg/ciO
