Note: Descriptions are shown in the official language in which they were submitted.
CA 02250025 2006-04-03
A transdermal therapeutic system with small application area thickness and
great flexibility, and production process
SPECIFICATION
The present invention relates to a transdermal therapeutic system for the
controlled
release of active substances to human or animal skin, which stands out for its
small
application thickness and high flexibility, as well as to processes suitable
for its
production.
Systems for the controlled release of active substances to human or animal
skin are
known, among others, as so-called Transdermal Therapeutic Systems (TTS) or
'Transdermal Delivery Systems" (TDS).
Depending on their construction and type of active substance release one
differentiates between so-called bag or reservoir systems and matrix systems.
In the
former case, these systems consist of a flat bag which comprises an active
substance. One side thereof is impermeable to activate and inactivate
ingredients
and the opposite side is semipermeable and formed as a control membrane which
is
coated with an adhesive for adhesion to the skin. Owing to its complicated
construction, production of the system requires a great deal of expenditure,
since
the individual components are to be produced separately and must then be
joined to
form a system.
Moreover, the thickness of the system impairs the wearing properties.
In addition, bag-type systems involve the risk of so-called "drug dumping",
that is,
the sudden substantial active substance release to the skin, for example, as a
result
of physical destruction of the membrane or bag. EP 0 285 563 describes such a
transdermal therapeutic system for the combined application of estrogens
and gestagens.
21509993.1
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US-PS 4 624 665 describes systems comprising the active sub-
stance in microencapsulated form within the reservoir. The reser-
voir is embedded between backing layer and membrane. The edge
of the system is provided with a pressure-sensitive adhesive.
Construction and production of this system are very complicated
since the active substance must be microencapsulated and homo-
geneously distributed and then be embedded between backing
layer and membrane. In addition, the system must be provided
with an adhesive edge and covered with a protective layer.
Matrix systems usually consist of a backing layer which is imper-
meable to active substances and auxiliaries and averted from the
skin and an adhesive layer wherein active substance is distributed.
For the purpose of protecting the adhesive layer it is provided
with an antiadhesively finished protective film which has to be
removed prior to application. DE-OS 20 06 969 describes such a
system wherein contraceptive substances are incorporated in the
adhesive component or adhesive film. This publication discloses
that the adhesive film may be an acrylate.
Similar to labels, matrix systems have the disadvantage that they
are punched out from a self-adhesive laminate positioned on an
nonstick protective layer. The stampings on the protective layer
are separated in a further step to produce the finished TTS. The
regions betweeri the individual punched pieces, which consist of
active substance-containing adhesive layer and backing layer, are
to be disposed of as active substance-containing waste. DE 39 39
376, DE 29 08 432 and EP 0 400 078 B1 represent examples
providing solutions for avoiding such waste.
The thickness of the system which results from the production
method and the kind of application is a disadvantage of known
matrix systems. This thickness affects the system's flexibility and
therefore its wearing properties, whereas wearing comfort of the
system increases with decreasing thickness.
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Moreover, known matrix systems are limited by the fact that nei-
ther at the same time nor in chronological order it is possible to
provide alternative doses, active substance concentrations, or
varying chemical system compositions differing in the active sub-
stance or a special active substance combination and providing a
desired application of several active substances, which differs with
respect to time or site.
It is the object of the present invention to provide a transdermal
therapeutic matrix system that avoids the above-mentioned disad-
vantages and difficulties, has a very good flexibility including im-
proved wearing properties owing to a reduced thickness, and
which permits the production of so-called "multi-dose" units con-
sisting of several separable "single-dose" systems. These may
differ with respect to the parameters type of active substance/con-
centration of active substance/system area/system thickness/
chemical composition of the system, and they are therefore capa-
ble of providing alternative doses at the same time or in chrono-
logical order by means of a "multi-dose" unit.
In a device for releasing an active substance to a substrate this
object is achieved with the present invention by the form accord-
ing to the characterizing features of claim 1.
For this reason, the present invention meets the demands of the
object by providing a system having improved wearing properties
resulting from good flexibility owing to its small thickness. More-
over, the production technology of the system according to the
present invention makes it possible to produce so-called "multi-
dose" units consisting of separable "single-dose" systems. These
"single-dose" systems of a "multi-dose" unit may be the same or
different, the parameters causing the differences may be:
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- kind of active substance,
- active substance concentration per system,
- area of a system,
- thickness of a system, and
- chemical composition of the system.
A "multi-dose" release unit therefore enables alternative doses to
be offered at the same time or in chronological order. "Multi-dose"
units according to the present invention may also be "single-dose"
systems differing in the active substance itself or in active sub-
stance combinations, making it possible to provide a specific de-
sired application of several active substances at different times.
Therefore, the system according to the present invention offers a
lower-priced alternative to known systems.
Most surprisingly it turned out that the principle of so-called "de-
calcomanias" - "decals" or "tattoos" is particularly suitable as
active substance carriers or application systems in transdermal
therapy. The term "tattoo", formerly used in connection with "ar-
tistic" skin pigmentation, has been adopted in literature for the use
of "decalcomanias" for decoration purposes.
"Decals" are "transfer pictures" for decoration purposes known in
ceramic industry, for example. They consist of a paper substrate
which is provided with a solvent-soluble separating layer and has
lacquer layers thereon. The paper is moistened with solvent either
prior to or during joining the lacquer layer with the stoneware,
whereupon the separating layer dissolves. The lacquer layer may
now be pushed from the paper carrier to find its place on the
substrate to be decorated. The composite may be strengthened by
baking.
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A decal for the transdermal use of active substances advanta-
geously has the following structure:
A soluble separating layer is applied on a substrate consisting ei-
ther of a paper, fabric, nonwoven, or a polymeric layer permeable
to solvents, e.g., a polymeric membrane. Differentiation of this
laminate into two individual layers may be supported by a barrier
layer which prevents components from reaching the substrate
during application.
A capillary active insoluble substrate provided with a soluble sepa-
rating layer is essential. The thickness of the substrate is in the
range of 20 - 200 Nm, preferably 50-120 Nm, and according to a
preferred form 60 - 90 Nm. The separating layer has a thickness of
5 - 50 Nm, preferably 20 - 40 Nm. The separating layer connected
with the substrate is provided with an active substance-containing
film layer. This may be a laminate whose individual layers may be
different. For example, the laminate layer facing the separating
layer may be free of active substances. To achieve better contact
to the skin, the laminate layer averted from the separating layer
may be adhesive. The individual layers of the laminate may be the
same or different with respect to their polymer base.
In a "multi-dose" unit the substrate provided with the separating
layer is printed with several flat-shaped island-like regions of the
active substance-containing film layer. Suitable printing methods
include any printing method or spraying process or nozzle applica-
tion method known to the skilled artisan which permit application
of an active substance-containing film layer at the required weight
uniformity.
The active substance-containing film layer may be applied in one
or several individual printing steps; similar to a multicolor print, on-
ly partial regions of the first print may be printed.
In the embodiment according to the present invention is turned out
to be advantageous to apply the film layer by means of screen
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printing. Thus it is possible to apply several differently sized,
island-like, active substance-containing film layer regions on one
carrier section, which, like in a "multicolor print", differ in their
composition, layer thickness, and active substance (different
pigment).
Owing to the very small thickness and optimum flexibility the sys-
tem according to the present invention - in contrast to conven-
tional systems - is suitable for permanent application even on diffi-
cult sites of the body, e.g., the region of the ear, the genital re-
gion, or on toe-nails and fingernails. Owing to the possibilities of
decoration it is also possible to wear the systems on body sur-
faces which are not covered by clothes.
In a special embodiment, wherein the film layer has no additional
pressure-sensitive adhesive layer, a film layer region opposite the
separating layer has self-tackiness at the time of application. This
is achieved by the fact that the layer region is also moistened
when the separation layer dissolves, and the swollen regions of
the polymeric film layer obtain adhesive properties which enable a
bond to be formed to the skin, but which are lost on the skin-
averted side of the film layer after volatilization of the solvent.
The thickness of the film layer is in the range of 5-50,um, pref-
erably 5-30 ,um, and in a special embodiment 10-25 Nm.
The whole surface of the above-mentioned film layer or of the in-
dividual regions of the film layer or of the film layer islands is cov-
eyed with a protective layer which may have an antiadhesive fin-
ish. In case of an island-like embodiment of the film layer regions
on a common substrate in the "multi-dose" system, the protective
layer and the substrate may be perforated in the region between
the "islands", so that partial regions can be removed as a "single
dose" by tearing them off from the total system. The thickness of
the protective layer ranges from 50 - 100 Nm.
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For the purpose of application, the protective layer of the system
is removed and film layer with substrate applied on the application
site in such a manner that the substrate is averted from the
application site, whereupon it is moistened with a solvent. In a
preferred embodiment water is used as solvent. Owing to the cap-
illary properties of the carrier, the water reaches the separating
layer which has been rendered water-soluble for this case; in its
solubilized or dissolved state it loses the bond to the film layer, so
that the substrate may be peeled off the film layer, with the film
layer remaining on the site of application.
In case the separating layer is water-soluble, it has the chemical
nature, for example, of a saccharide or polysaccharide, polyhy-
droxy alcohol, polyvinyl pyrrolidone or another water-soluble poly-
mer, such as polyethylene glycol or gelatin.
In case the separating layer is fat-soluble, it is of the chemical
nature of a triglyceride or a wax. According to a special embodi-
ment for this case, the separating layer may be provided such that
it liquefies under the influence of heat and thereby loses the bond
to the film layer.
The film layer may consist of film-forming polymers. Suitable film-
forming polymers include: hydroxypropyl cellulose, hydroxypropyl
methylcellulose, polyvinyl pyrrolidone, vinylpyrrolidone-vinyl ace-
tate copolymer 40:60, ethylcellulose, acrylic-acid ester copolymers
and methacrylic acid ester copolymers with trimethylammonium
methyl acrylate, copolymers of dimethylaminomethacrylic acid and
neutral methacrylic acid esters, shellac, cellulose acetate phtha-
late, hydroxypropyl methylcellulose phthalate, polymers of meth-
acrylic acid and methacrylic acid esters, ethyl acrylate-methacrylic
acid methyl ester copolymer 70:30, methacrylic acid-methyl acry-
late copolymer 50:50, gelatin, polyvinyl acetate, methacrylate,
acrylate dispersions, polyether-polyamide block copolymer, poly-
ethylene-methyl-methacrylate block copolymer, polyurethanes,
polyester block copolymer, polyisobutylene-styrene-styrene co-
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polymers, styrene-butadiene-styrene-isoprene copolymers, ethyl-
ene-vinyl acetate copolymers, polyamide, nitrocellulose, as well as
further lacquer or film formers known to the skilled artisan. Inevi-
tably softeners are added to these film formers in accordance with
the required necessary flexibility of the film.
In the form of a laminate that layer of this film layer which faces
the application site may be pressure-sensitive adhesive by means
of components stated below. Components in this sense include
any conventional adhesive known to the skilled artisan and also
used for wound toilet in the form of dressings and patches, for ex-
ample, adhesives based on acrylates, polyisobutylene, polyure-
thanes, silicones, etc.
The protective layer which consists of a paper or polymer coated
with a silicone resin is known to the skilled artisan in different de-
signs. It is obtainable from the specialized trade as adhesive pro-
tective layer or "release liner" provided with a siliconization adapt-
ed to the adhesive.
The perforation which may be punched into the system represents
a separate variant of the system. Thereby it is possible to obtain a
unit with several equal or different dosages and periods of action.
This is particularly useful when one or several drugs or combina-
tions are to be administered over a certain period in a certain dose
strength. The substrate may be printed with the same or different
drugs and/or drug combinations in the form of spaced apart areas
by means of screen printing.
This is desirable in cyclic hormone therapy with estradiol or ges-
tagens, for example.
In the context of the present invention the term "active sub-
stances" is to be understood as chemical elements, organic and
inorganic compounds which are capable of migrating from the
components of the generic device containing them and thus cause
an intended effect. Human and veterinary medicine, as well as the
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use with plants, represent particularly important fields of applica-
tion for the device according to the present invention.
The active substances to be released preferably serve the dermal
treatment of local skin diseases, the intradermal and transdermal
treatment of diseases, the treatment of wounds, or the skin care
in cosmetic preparations. In a special embodiment, the film layer
serves as a carrier of high-volatile active substances which are re-
leased outwardly, i.e., in the direction of the side averted from the
skin. These also include flavoring substances such as perfume oils
having an active substance character in a wider sense (olfactory
substances) .
Local anaesthetics, local antibiotics, antiseptics, antimycotics, an-
tihistaminics, and antipruritic drugs; keratolytics and caustic drugs;
virustatics, antiscabietic agents, steroids, as well as different
substances for the treatment of acne, psoriasis, photodermatoses,
or precancerous stages are used for the dermal treatment of local
skin diseases. Active substances applicable by the intradermal
route include, for example, steroid and non-steroid antirheumatics,
local anaesthetics, substances stimulating the blood flow, or va-
soprotectors and vasoconstrictors to treat vascular diseases, as
well as active substances to influence processes in the subcuta-
neous fatty tissue. Transdermally applicable active substances in-
clude, for example, analgesics, anti-arrhrythmic drugs, narcotics
and their antagonists, neuroleptics, hormones or hormone substi-
tutes, antidepressants, tranquilizers, hypnotics, psychostimulants,
antiparkinson drugs, ganglionic blockers, sympathomimetics, al-
pha-sympatholytics, beta-sympatholytics, antisympathotonics,
anti-asthmatics, antiemetics, appetite depressants, diuretics, or
active substances for weight reduction, etc. Because of the small
thickness of the system according to the present invention pre-
ferred active substances are those developing their action already
at very low concentrations.
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Examples of these preferred active substances include steroids,
such as estradiol, estriol, progesterone, norethisterone, norethin-
drone, levonorgestrel and their derivatives, as well as etynodiol
diacetate, norgestarnate, gestagens, desogestrel, demegestrone,
promegestrone, testosterone, hydrocortisones and their deriva-
tives; vitro compounds, such as amyl nitrate, nitroglycerin, iso-
sorbide dinitrate; amine compounds, such as nicotine, chlorphenir-
amine, terfenadine, and triprolidine; oxicam derivatives such as
piroxicam; mucopolysaccharases such as thiomucase; opioid
substances such as buprenorphine, morphine, fentanyl and their
salts, derivatives or analogues, naloxone, codeine, dihydroergo-
tamine, lysergic acid derivatives, pizotiline; salbutamol, terbutaline;
prostaglandins, such as PGA, PGB, PGE and the PGF-series, for
example, misoprostol and enprostil, omeprazol, imipramine; benz-
amides, such as metoclopramines and scopolamine; peptides and
growth factors such as EGF, TG F, PDGF, etc; somatostatin; cloni-
din; dihydropyridines, such as nifedipine, nitrendipine, verapamil,
diltiazem, ephedrine, propanolol, metoprolol, spironolactone; thi-
azides such as hydrochlorothiazide and flunarizine.
Styptic active substances and wound-cleansing substances, such
as enzymes, antiseptics, disinfectants, and antibiotics; pain-reliev-
ing agents and anaesthetic active substances, as well as active
substances promoting wound healing to stimulate granulation, to
induce vascularization, or to promote epithelization are used for
the treatment of wounds.
In a preferred embodiment for transdermal use, the film layer
comprises a steroid hormone, preferably estradiol either alone or
combined with other drugs, which is used in transdermal applica-
tion for hormone substitution during postmenopause or for the
treatment of osteoporosis.
On the other hand, the device for the release of estradiol may also
be applied on long-term wounds, for instance crural ulcers, for the
treatment of wounds.
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In another preferred embodiment of the device according to the
present invention, the film layer comprises vegetable preparations,
such as extracts or tinctures. These may be used for the treatment
of topical skin diseases, for example, oak bark extract, walnut ex-
tract, tincture of arnica, hamamelis extract, ribwort extract, pansy
extract, thyme or sage extract; for the treatment of damaged or
injured skin, for example, St. John's wort tincture, cone flowers
tincture, chamomile flowers extract, or calendula flowers tincture;
and for the care of exhausted and damaged skin, for example,
birch leaves extract, nettle extract, coldsfoot extract, comfrey
tincture, horsetail extract, or aloe vera extract.
Vegetable preparations may also be released from the film layer
for the intradermal treatment of diseases, for example, extracts of
horse chestnut and butcher's broom in case of vein diseases, or
extracts and tinctures of arnica, calendula, and capsicum in case
of contusions, distortions, or haemorrhages. Vegetable prepara-
tions in the system according to the present invention may also be
used in transdermal therapy, for example, ginseng extract in case
of geriatric complaints; valerian tincture; extracts of melissa and
hop to cause a sedative effect in case of superexcitation, sleep
disturbances, and stress; extracts of kola and tea to achieve a
stimulative effect; or hawthorn extract to stabilize the circulatory
system.
In particular cases where the active substance or active substance
extract itself has film-forming properties, the film layer merely con-
sists of the active substance or the corresponding extract.
According to a preferred embodiment the film layer of the system
according to the present invention consists of tobacco powder
extract. Such a device can be used by smokers as an alternative
to tobacco, cigarettes or similar tobacco products. This system is
also suitable for the use with film-forming vegetable and animal
extracts, the number of which is not listed here exhaustively.
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Another special embodiment relates to the use of the system ac-
cording to the present invention as carrier of narcotics, psycho-
pharmaceuticals, and agents for treating Alzheimer's disease and
senile dementia. These highly potent drugs require a system ensur-
ing wearing properties for several days and a waste-free produc-
tion. These requirements are met by screen printing the active
substance-containing film layer and by the flexibility and layer
thickness of the system.
According to the present invention the individual film layer seg-
ments can also be marked in the form of colors, letters, numbers,
dates, codes, pictographs and the like by means of screen print-
mg.
Inevitably, there is the possibility of dyeing the film layer by means
of soluble dyes or pigments. Moreover, the system may also be
completely transparent.
The system according to the present invention may be manufac-
tured as mentioned hereunder:
A paper of 150 g (100-200 g/m2), which has been produced from
an aluminum sulfate-free pulp stock comprising in addition to
starch kaolin as filler, is superficially spread with a sizing solution
and dried. Coating is effected such that only the pores of the out-
ermost paper layer are covered.
On the paper carrier such treated a solution of polyvinyl alcohol is
applied by means of a coating bar or gravure roll, followed by dry-
ing. The paper so obtained, which is provided with the separating
layer (polyvinyl alcohol) and is present in the form of rolls for
further use, serves as substrate for the following printing process
carried out according to the screen printing method. Depending on
the design of the system, differing numbers of printing steps and
stencils are necessary. The example shown in Figure 2 is not in-
tended to limit the present invention. First, the system name is
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printed on the substrate by means of screen printing using a
commercial color.
After that, the first layer of the active substance-containing film
layer, which is on the outside after application, is printed. In the
example shown, printing is carried out using an active substance-
free polyacrylate dispersion (Polyacrylate Dispersion 30 per Cent
Ph.Eu.) with 10% acetyltriisobutyl citrate which forms a film of 5
arm after drying. The screen printing stencil is dimensioned such
that the area of the final system is defined by means of this print-
ing procedure. Then, the active substance-containing layer is
printed. This is carried out directly on the complete surface of the
polyacrylate layer. Examples of the composition of this printing
medium are listed in the following (parts by weight):
a) estriol 4
N,N-diethyl-m-toluamide 4
acetone 50
Eudragit*E 30 0 40
Plastoid*E 35 10
b) buprenorphine 10
isopropyl lanolate 10
Plastoid E 35 65
c) estradiol 4
Polyacrylate Dispersion
30 per Cent (Ph.Eu) 100
triethyl citrate
propylene glycol
acetone 10
polyvinyl pyrrolidone 4
lecithin
ethanol 20
TM (Trademark)
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In Example c), a 5 Nm-layer with Plastoid*E 35 is additionally
printed.
/Plastoid and Eudragit are trade names of Rhom GmbH).
After printing, the last layer is provided with the protective layer.
In the following details, features, and advantages of the present
invention are illustrated in greater detail with reference to the
drawings.
Figure 1 : is a sectional view of a "multi-dose" unit with three
"single-dose" systems;
Figure 2: shows a schematic production device;
Figure 3: is a sectional view of a transdermal system
according to the present invention;
Figure. 4: shows a sectional view of another transdermal
combination system.
In the Figures the numbers have the following meanings:
Figure 1: 1 substrate
1 b barrier layer
separating layer
3 film layer
3a adhesive layer
4a nonstick layer
q. protective layer
perforation
* = TM (Trademark)
CA 02250025 1998-09-25
Figure 2: 1 substrate
2 separating layer
3 nonstick layer of the film
layer laminate averted
from
the substrate
3a active substance-containing
layer of the film layer
lami-
nate
3b adhesive layer of the film
layer laminate
4 protective layer
Onto film layer (3), which has been manufactured by means of a
printing process, film layer (3a) is applied in (a) on substrate (1) by
means of screen printing (b) and is dried in (c). In (d) film layer
(3b) is applied, again by screen printing, which is dried in (e). In (f)
the protective layer (4) is laminated. In (g) cutting to form the
finished system is carried out.
Figure 3: 1 substrate
2 separating layer
3a adhesive layer free from
active substance
3b film layer free from active
substance
3 active substance-containing
film layer
4 protective layer
3a+3b +3=film layer laminate
Figure 4 1 ~ substrate
2 separating layer
3c pictorial representation
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3d active substance-containing
film layer
active substance 1
3e active substance-containing
film layer
active substance 2
4 protective layer
3c + 3d + 3e = film layer laminate
As a matter of course, the production of active substance layers, in
particular such layers having narrow outlines - which is particularly
useful with respect to process engineering and for obtaining thin-layer
and flexible systems - is not restricted to transdermal therapeutic
systems that are produced starting from a substrate provided with a
separating layer that is dissolved or liquefied upon application so that
the substrate can be removed.
Rather, it is possible to obtain flat-shaped or sheet-like systems for the
release of active substances to the skin by employing one or several
printing processes. The size of the system with respect to its area can
be determined by the first printing process; as an alternative, the size
of the systems can also be determined by one of the subsequent
printing processes. The printing process determining the size of the
system can be carried out, partially or on the entire surface, onto a
substrate that is provided with a non-stick finish.
It is of use if at least the backing layer of the finished TTS and/or the
self-adhesive matrix layer which comes into contact with the skin is/are
formed by the printing medium, which in the latter case may comprise
one or several active substances. If the backing layer of the TTS is
formed as a print layer it can be used as information carrier for printing
with marks or designations, and/or be printed in color. The backing
layer which is formed as a printing layer may be provided with a
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supporting film or sheet provided with an abhesive finish, the
abhesiveness of which is smaller than that of the printed substrate.
This means that the invention comprises systems for the controlled
release of active substances to the human or animal skin, on the basis
of systems which are based exclusively on one or several printing
methods.
Most surprisingly, it turned out that the processes of printing, for
example, T-shirts with images or letters , in particular for obtaining a
sufficiently flexible layer thickness, are also suitable for the production
of transdermal therapeutic systems if a substrate that has been
rendered abhesive is printed instead of fabrics or nonwovens. The
printing methods being employed for the production of rub-off letters,
such as Letraset~, for example, can be transformed to the production
of complete TTS, too.
The thickness of the substrate - similar to that of the substrate
provided with a separating layer - is in the range of 20 - 200 pm,
preferably 50 - 120 Nm, and 60 - 90 Nm in a particularly preferred
form, and it is rendered abhesive by a siliconized layer, for example.
To achieve an improved bond to the skin, the layer of printing media
adjacent to and in contact with the substrate may be rendered
adhesive. The active substance-containing film layer may be applied in
one or several individual printing steps, it being also possible to print
partial areas of the previous print, similar to a multicolor print.
Suitable printing methods are again all those known to the skilled
artisan which enable uniform application of an active substance-
containing film layer while maintaining the required weight uniformity.
Die individual layers of the individual printing layers to be printed may
be the same or differ in respect of their polymer base body. It has
proved to be of advantage to apply the film layer by screen-printing. In
this way it is possible to obtain several island-like active substance-
CA 02250025 1998-09-25
1$
containing film layer regions of different size on a substrate, which
regions differ in their composition, layer thickness and active
substance (different pigment) - as is similary the case in a "mufti-color
print".
The thickness of the film layer is in the range of 5 - 50 Nm, preferably
5 - 30 Nm, and in a special embodiment in the range of 10 - 25 pm,
and the layer is of rubber-like consistency.
For the purpose of application, the substrate of the system is removed,
and the remaining system is applied to the application site.
Suitable printing media include the film-forming polymers and masses
mentioned hereinabove.
This film layer may be in the form of a laminate and be rendered
pressure-sensitive adhesive by the components mentioned
hereinbelow which are contained in the layer facing the application
site. Suitable components in this connection are any commercial
adhesives known to those skilled in the art that are also used in wound
treatment in the form of dressings and patches, such as, for example,
adhesives based on acrylates, polyisobutylenes, silicones, etc.
The term "active substance" again has the same meaning as
mentioned hereinabove. All mentioned active substances and special
features of application again apply in the same manner as to the
system formed with a substrate and separating layer.
The system may be manufactured in an analogous manner as follows:
A paper of 150 g (100 - 200 g/m2), siliconized, serves as a substrate
for the printing process, which is effected using the screen-printing
method. Depending on the design of the system, a different number of
CA 02250025 1998-09-25
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printing steps and printing stencils are required. As a rule, it is the
printing medium that is employed first which comprises the active
substance, this printing medium being rendered pressure-sensitive
adhesive. The printing medium which is used thereafter at last forms
the size of the system. It is, for example, rubber-like and film-forming.
The complete print image that has been applied to the substrate may
be covered by a polypropylene film which later-on serves as a
supporting film and which is rendered abhesive.
