Note: Descriptions are shown in the official language in which they were submitted.
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DEVICE AND PATCH FOR CONTROLLED RELEASE OF VANILLIN
Background of the Invention:
Field of the Invention:
The present invention relates to a device for the controlled release of
vanillin,
ethylvanillin derivatives or mixtures thereof, to a process for producing said
device, to a device obtainable by said process, to the use of a composition
comprising vanillin, ethylvanillin or mixtures thereof, and to the use of the
device.
Numerous aromas develop pronounced effects on various receptors of
neurotransmitters (GABA, NMDA, KA, nACh). Fragrances such as geraniol
("rose") and butyl acetate ("fruit") stimulate the GABA receptor. In high
doses,
receptor stimulants of this kind even have a hypnotic and anesthetizing
effect.
Vanillin, by contrast, similarly to caffeine, inhibited said receptor. Since,
according { to current understanding, the most important physiological effects
of caffeine are
based on this inhibition, vanillin could have a similar stimulant effect to
caffeine.
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Vanillin also inhibited the nicotinic acetylcholine receptor (nACh), a
property which
it shares with the snake poison cobratoxin or the arrow poison curare.
Vanillin
also had an inhibitory effect on the glutamate receptors (NMDA, KA). This
effect
is comparable in principle with that of phencyclidine, which is also known as
a
narcotic ("Angel dusf').
As well as this receptor inhibition, in the central nervous system vanillin
also
influences the craving to consume food. In this context it is supposed that
the
vanillin is able to increase the concentration of the neurotransmitter
serotonin in
the brain (see for example Williams, J. Psychopharmacol 1998, 12(2): 115-21).
Increased brain serotonin concentration, however, leads demonstratively to a
reduced craving to consume food.
Since serotonin cannot be prepared synthetically, and since there is in any
case
virtually no possibility of uptake of said neurotransmitter into the brain,
owing to
the compartment systems located there, attempts have now been made to obtain
an increase in brain serotonin concentration through the use of the fragrance
vanillin.
Uptake of this fragrance via the blood-brain barrier is possible on account of
its
lipophilic properties. A second possible uptake pathway, besides that of the
blood-brain barrier, is the olfactory nerve (bulbus olfactorius), which allows
transneural transport into the brain (Lloyd Hastings: "Sensory
neurotoxicology:
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Use of the olfactory system in the assessment of toxicity", in;
Neurotoxicology and
Teratology 1990/12/pp. 445-9). Vanillin, accordingly, is able to enter the
central
nervous system via the nose. In the patent literature, accordingly, devices
have
been numerously described by means of which this fragrance can be vaporized in
the vicinity of the body and so breathed in continuously (uptake of vanillin
via the
olfactory nerve) or with which vanillin can be supplied continuously to the
circulation (uptake via the blood-brain barrier).
European Patent application EP-A-645 081, for example, describes an insect
control device comprising a container which is covered by a film impervious to
gaseous essential oils. Following removal of a protective layer, the
insecticidal
compositions contained in said container emerge from the container
continuously
through the film. The disadvantage of these containers is that they are not
suitable for continuous release of vanillin in the vicinity of the body.
To avoid this disadvantage, international PCT publication WO 98/17262 Al
describes a device in the form of a patch, which is intended for transdermal
administration of the active substance and the active substance is applied in
a lint-
like material. However, transdermal administrations needs official
permissions.
Furthermore, link-like materials limits the carrying comfort.
Likewise, international PCT publication WO 00/16752 describes a device for
transdermal administration of the active substance, in which the active
substance(s) are applied in a "matrix-layer", which has a thickness of 1 mm
to 10 mm, which again limits the carrying comfort.
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To avoid this disadvantages, European published patent application
EP-A-844 872 (corresponding to WO 97/03658 and US 2003/0012811 Al)
describes a device for administering vanillin that comprises lint or a similar
material impregnated with the vanillin-releasing substance, the lint being
contained in a self-adhesive patch for application to the skin, and the
exposed
surface of the patch having a central hole through which the vanillin is able
to
emerge from the lint. The disadvantage of this device, however, is that the
rate at
which the vanillin emerges cannot be adequately regulated.
Last but not least US patent application publication US 2001/0032645 Al
(corresponding to EP 1 087 735 131) disclose nasal strips and dilators
adhesively
applied in the human nose, which substantially prevents a nasal wall tissue of
a
nose from drawing in during breathing.
Summary of the invention:
The object on which the present invention is based was to overcome the
disadvantages arising from the prior art.
The object of some embodiments of the invention, moreover, was to provide a
device by means of which it is possible to release vanillin continuously in
the
vicinity of the body so that it can be taken up via the nose.
A further object of some embodiments of the invention was to provide a device
with which vanillin can be taken up continuously via the skin.
An aspect of the invention relates to a device for continuously releasing at
least
one vanillin compound such as vanillin itself (3 methoxy-4
hydroxybenzaldehyde)
or at least one vanillin derivative, preferably ethylvanillin (3 ethoxy-4
hydroxybenzaldehyde), or mixtures thereof, comprising a layer
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impermeable to the at least one gaseous vanillin compound, a
layer permeable to the at least one gaseous vanillin compound,
and a composition comprising the at least one vanillin
compound which is located between these two layers. The device
is used in the vicinity of the body of a wearer, preferably by
adhesion to the skin of the wearer. The wearer is preferably a
mammal such as a human being, a dog, a pig, a hamster, a cat,
a hare or a rabbit, a human being particularly preferred.
The layer impermeable to the at least one gaseous vanillin
compound is preferably a film comprising polyester,
polypropylene, polyethylene, ethylene-propylene copolymers,
polyamides, such as nylon 6,6, metals, such as aluminum,
polyethylene, poly(tetrafluoroethylene), polycarbonate,
polyethylene terephthalate, polybutyrate, polyurethane or
polyvinyl chloride, particular preference being given to a
film comprising polypropylene or polyethylene or to a film
comprising an ethylene-propylene copolymer. Among these films,
very particular preference is given to polyethylene films
which are obtainable under the commercial designation
Sclairfilm from DuPont, Canada. The thickness of the layer
impermeable to the at least one gaseous vanillin compound is
preferably chosen so that within a time interval of 24 hours
not more than 1%, preferably not more than 0.1%, and more
preferably not more than 0.01% by weight of the composition
can evaporate via this film at room temperature under a
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pressure of 1 bar. Preferably this layer has a thickness in a
range from 0.001 to 1 mm, more preferably in a range from 0.01
to 0.5 mm, and with further preference in a range from 0.1 to
0.25 mm.
The layer permeable to the at least one gaseous vanillin,
gaseous vanillin derivative or mixtures thereof is preferably
a film that has the property whereby within a time interval of
24 hours at least 10%, preferably at least 25%, and more
preferably at least 50% by weight of the vanillin, ethyl
vanillin or mixtures thereof that are present in the
composition can evaporate via this film at room temperature
under a pressure of 1 bar. Preferred films are films
comprising polyethylene, polyamide, ethylene-vinyl acetate
copolymer or mixtures of these monomers. The permeable layer
preferably has a thickness in a range from 0.001 to 1 mm, more
preferably in a range from 0.01 to 0.5 mm, and with further
preference in a range from 0.1 to 0.25 mm. It is further
preferred in this context that via the choice of material of
the permeable layer and its thickness the amount of the
composition evaporated through this layer in a defined time
interval at a defined temperature and under a defined pressure
can be regulated. In one particular embodiment of this device
the permeable layer has microscopic holes having a diameter in
a range between 1 and 100 A, more preferably in a range
between 10 and 50 A, which is preferably obtainable by
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bombarding the layer with heavy atoms, such as with barium atoms, for example.
The density of holes in the film, indicated in the number of holes per mm2,
and the
diameter of the holes likewise make it possible to regulate the amount of
composition evaporated through the permeable layer within a defined time
interval
at a defined temperature and under a defined pressure.
It is further preferred in this context for both the permeable layer and the
impermeable layer to have a thickness of not more than 0.1 mm, more preferably
of not more than 0.01 mm, so that the device of the invention is not rigid and
is
able when placed onto an uneven surface to conform to that surface.
According to an aspect of the invention there is provided a device in the form
of a
patch for continuously releasing at least one gaseous vanillin compound,
comprising a layer impermeable to said at least one gaseous vanillin compound,
a
layer permeable to said at least one gaseous vanillin compound, and a
composition comprising at least one vanillin compound, said composition being
located between these two layers, the device not comprising lint impregnated
with
the composition.
Although the invention is illustrated and described herein as embodied in a
device
and patch for controlled release of vanillin, it is nevertheless not intended
to be
limited to the details shown, since various modifications and structural
changes
may be made therein without departing from the spirit of the invention and
within
the scope and range of equivalents of the claims.
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The construction and method of operation of the invention,
however, together with additional objects and advantages
thereof will be best understood from the following description
of specific embodiments when read in connection with the
accompanying drawings.
Brief Description of the Drawings:
Fig. 1 shows an embodiment of the device of the invention as a
cross section, in which the impermeable layer is shaped in the
form of a vessel. With this device, continuous uptake of the
at least one vanillin compound nasally or pulmonarily is
possible.
Fig. 2 shows an embodiment of the device of the invention as a
cross section, in which the impermeable layer is shaped in the
form of a vessel. With this device, continuous uptake of the
at least one vanillin compound trans-dermally is possible.
Fig. 3 shows an embodiment of the device of the invention in
the form of a patch as a cross section. With this patch,
continuous uptake of the at least one vanillin compound
nasally or pulmonarily is possible.
Fig. 4 shows an embodiment of the device of the invention in
the form of a patch as a cross section. With this patch,
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continuous uptake of the at least one vanillin compound trans-
dermally is possible.
Description of the Preferred Embodiments:
With reference to Fig. 1, in one embodiment of the device of
the invention it comprises
- the layer impermeable to the at least one gaseous vanillin
compound, this layer having the form of a container (1),
- the layer permeable to the at least one gaseous vanillin
compound, as top layer (2), the top layer (2) adhering to the
container (1) with sufficient strength that a force F1 of at
least 0.5 N, preferably of at least 1 N, and more preferably
of at least 5 N is required to separate the top layer (2) from
the container (1),
- and the side of the container (1) opposite the top layer (2)
being provided, on its side facing away from the top layer
(2), with an adhesive,
- a first, protective liner layer (3), which attaches
adhesively to the side of the container (1) that has been
provided with the adhesive, and which can be separated from
the container (1) by peeling by hand, preferably through the
action of a force of less than 10 N, more preferably of less
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than 1 N, and with further preference of less than 0.1 N, the
adhesive remaining on the container (1),
- a second protective liner layer (4), made of a material
which is impermeable to gaseous vanillin or to gaseous
vanillin derivatives or to gaseous mixtures thereof, which
attaches adhesively to the side of the top layer (2) that is
facing away from the container (1), and can be separated from
the top layer (2) by the action of a force F2, which is smaller
than the force F1, and
- the composition (Z) in the container (1), said composition
being free from active insecticidal substances and comprising
vanillin or vanillin derivatives or mixtures thereof.
When this device, following removal of the first protective
layer (3), is adhered to the skin of the wearer, the
impermeable container (1) entering into contact with the skin
of the wearer, it allows the continuous uptake of vanillin or
vanillin derivatives or mixtures thereof through the nose
(nasal uptake) or the lungs (pulmonary uptake) of the wearer.
This is made possible by virtue of the fact that, owing to the
body temperature of the wearer, the evaporation of the
composition in the container and hence also the passage of the
at least one gaseous vanillin compound through the top layer
(2), after the second protective liner layer (4) has been
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removed, is promoted.
In the case of the above-described embodiment of the devices
of the invention, the container (1) is preferably transparent.
It is further preferred for the container (2) to have the form
of a trough whose open side possesses a flat, outwardly curved
edge. In this case the top layer (2) is attached to the flat,
outwardly curved edge of the transparent trough. In connection
with this preferred embodiment it is further preferred for the
device, besides the optionally transparent, trough-shaped
container (1), the top layer (2) and the protective layers (3)
and (4), to comprise a paper board packaging which is folded
so that the paper board is two-ply and between these two plies
in the two-ply region, accommodates the flat, outwardly bent
edges and the top layer (2) and also the protective layer (4)
or (3), respectively, while the transparent trough is arranged
visibly and transparently outside this packaging. In the case
of a transparent container (1) the latter is composed
preferably of polyethylene or polypropylene. The advantage
when using a transparent container is that the amount of
composition still present in the container can be determined
at any time for the wearer. The packaging serves preferably as
an advertising space.
With reference to Fig. 2, in another embodiment of the device
of the invention it comprises
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- the layer impermeable to the at least one gaseous vanillin
compound, which has the form of a container (5),
- the layer permeable to the at least one gaseous vanillin
compound, as top layer (6),
- the top layer (6) adhering to the container (5) with
sufficient strength that a force F1 of at least 0.5 N,
preferably of at least 1 N, and more preferably of 'at least 5
N is required to separate the top layer (6) from the container
(5),
- and the top layer (6) being provided on the side facing away
from the container (5) with an adhesive,
- a protective liner layer (7), made of a material which is
impermeable to gaseous vanillin or to gaseous vanillin
derivatives or to gaseous mixtures thereof, which attaches
adhesively to the side of the top layer (6) provided with the
adhesive and can be separated from the top layer (6) by the
action of a force F2, which is smaller than the force F1,
preferably by peeling by hand, the adhesive remaining on the
top layer (6),
the composition (Z) in the container (5), said composition
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being free from active insecticidal substances and comprising
the at least one gaseous vanillin compound.
When this device, following the removal of the protective
layer (7) is adhered to the skin of the wearer, the permeable
top layer (6) entering into contact with the skin of the
wearer, it allows the continuous, trans-dermal uptake of
vanillin or vanillin derivatives or mixtures thereof through
the wearer.
The container (1) or (5) preferably has a length x and a width
y in a range from 0.5 to 20 cm, more preferably in a range
from 1 to 10 cm, and with further preference in a range from 2
to 5 cm, and a height z in a range from 0.01 to 0.5 cm, more
preferably in a range from 0.1 to 0.4 cm, and with further
preference in a range from 0.2 to 0.3 cm. It is further
preferred for the length x and the width y of the patch to be
greater by a factor of at least 2, preferably at least 5, and
more preferably at least 10, than the height z of the
container (1) or (5) respectively. It is further preferred for
the capacity of the container (1) or (5) to be in a range from
0.0025 to 200 cm3, more preferably in a range from 0.01 to 10
cm3, and with further preference in a range from 0.1 to 1 cm3.
Preferably, the top layer (2) or (6) attaches to the container
(1) or (5), respectively, with sufficient strength that it
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cannot be grasped with the hand or torn from the container by
pulling with the hand.
The difference in adhesion between the top layer (2) or (6)
and the container (1) or (5), on the one hand, and between the
protective liner film (4) or (7) and the top layer (2) or (6),
on the other hand, which results in the force F2 required to
tear the protective film from the top layer being smaller than
the force F1 required to tear the top layer from the container,
is made possible preferably through the use of adhesives which
have different bond strengths or else by means of areas
differing in size in which adhesion takes place between the
individual components.
With reference to Fig. 3, in another preferred embodiment of
the device of the invention it is shaped as a patch and
comprises
- the layer (8) impermeable to the at least one gaseous
vanillin compound,
- the overlying layer (9), permeable to the at least one
gaseous vanillin compound, and the composition (Z) located
between both layers,
layer (8) impermeable to the at least one gaseous vanillin
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compound being provided on its side facing away from the
permeable layer (9) with an adhesive,
- a first, protective liner layer (10), which attaches
adhesively to the side of the impermeable layer (8) that has
been provided with the adhesive, and which can be separated
from this film by peeling by hand, preferably through the
action of a force of less than 10 N, more preferably of less
than 1 N, and with further preference of less 0.1 N, the
adhesive remaining on the impermeable layer (8),
- a second protective liner layer (11), made of a material
which is impermeable to the at least one gaseous vanillin
compound,, which attaches adhesively to the permeable layer
(9) on its side that is facing away from the impermeable layer
(8), and can be separated by peeling by hand, preferably by
the action of a force of less than 10 N, more preferably less
than 1 N and with further preference less than 0.1 N, from the
permeable layer (9).
When this patch is brought into the vicinity of the body, by
means for example of the adhering of said patch to the skin of
the wearer, following the removal of the first protective
layer (10), the impermeable layer (8) entering into contact
with the skin, it permits the continuous evaporation of the
composition and hence the uptake of the at least one gaseous
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vanillin compound, through the nose or the lungs of the
wearer. This is made possible by virtue of the fact that,
owing to the body temperature of the wearer, the evaporation
of the composition in the patch and hence also the passage of
the at least one gaseous vanillin compound, through the
permeable layer (9), after the second protective liner layer
(11) has been removed, is promoted.
With reference to Fig. 4, in a further embodiment of the
device of the invention it is likewise designed as a patch and
comprises
- the layer (12) impermeable to the at least one gaseous
vanillin compound,
- the underlying layer (13), permeable to the at least one
gaseous vanillin compound, and the composition (Z) located
between both layers,
- the layer (13) permeable to the at least one gaseous
vanillin compound, being provided on its side facing away from
the impermeable layer (12) with an adhesive,
- a protective liner layer (14), which attaches adhesively to
the side of the permeable layer (13) that has been provided
with the adhesive, and can be separated from this layer by
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peeling by hand, preferably by the action of a force of less
than 10 N, more preferably of less than 1 N and with further
preference of less than 0.1 N, the adhesive remaining on the
permeable layer (13).
When this patch is brought into the vicinity of the body, by
means for example of said patch being adhered to the skin of
the wearer, following the removal of the protective layer
(15), the permeable layer entering into contact with the skin,
it allows the continuous trans-dermal uptake of the at least
one gaseous vanillin compound, through the wearer.
If the device of the invention is designed in the form of a
patch, then it is preferred for this patch not to comprise any
lint or similar materials impregnated with the composition. In
this context it is further preferred for the composition to
have a dynamic viscosity in range from 102 to 106, more
preferably in a range from 103 to 105 mPa=s at 20 C in
accordance with DIN 53211.
The adhesive present in the device of the invention preferably
comprises those adhesives known to the skilled worker that can
be used to attach a patch to the skin of a wearer. Preferred
adhesives are those which are offered by Dow Corning
Corporation, USA, under the commercial designation BIO PSA,
and also acrylate-based or silicone-based adhesives which are
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approved for medical use.
The protective liner layers are preferably films which
comprise the materials listed in connection with the
impermeable layer. The thickness of these protective layers as
well corresponds preferably to that of the permeable or
impermeable layer. Particularly preferred protective layers
used are films comprising polyethylene or polypropylene.
The purpose of the protective layers attaching adhesively to
the permeable layer is to prevent evaporation of the
composition from the device before it is used for the
controlled release of the at least one gaseous vanillin
compound. These protective layers must, accordingly, be
impermeable to the at least one gaseous vanillin compound. For
this reason they preferably have a thickness such that not
more than 1%, preferably not more than 0.1%, and more
preferably not more than 0.01% by weight of the composition is
able to evaporate via this protective layer within a time
interval of 24 hours at room temperature under a pressure of 1
bar.
The composition comprised in the device of the invention is
based preferably on
-((x1) the at least one gaseous vanillin compound, in an amount
in a range from 0.1% to 100% by weight, preferably in a range
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from 1% to 50% by weight, and with further preference in a
range from 5% to 20% by weight,
-((x2) a vehicle in an amount in a range from 0% to 99% by
weight, more preferably in a range from 20% to 70% by weight,
and with further preference in an amount in a range from 40%
to 60% by weight, and
-((x3) excipients in an amount in a range from 0% to 50% by
weight, more preferably in an amount in a range from 10% to
40% by weight, and with further preference in an amount in a
range from 20% to 30% by weight,
the sum of components (al) to ((x3) being 100% by weight.
The term "vanillin compound" is used to refer to the chemical
substance vanillin, 3-methoxy-4-hydroxybenzaldehyde and its
isomers and derivatives in which one or more hydrogen atoms
are substituted by nitro groups or lower alkyl groups having
one to three carbon atoms. Preferred vanillin compounds are
vanillin, ethylvanillin, 3-ethoxy-4-methoxybenzaldehyde, and
isovanillin, 4-methoxy-3-hydroxybenzaldehyde.
The vehicle preferably comprises monohydric alcohols, such as
ethanol, polyhydric alcohols, such as glycerol, ethylene
glycols or their ether derivatives, such as diethylene glycol,
polyethylene glycol, diethylene glycol diethyl ether,
polyethylene glycol dimethyl ether, essential oils, examples
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being cedar wood oil, cedar leaf oil, thuja oil, lavender oil,
lavandin oil, lemon oil, Litsea cubeba oil (may chang oil) or
verty oil, silicone oils, waxes, fats, such as olive oil,
groundnut oil or coconut fat, or mixtures of at least two of
the aforementioned vehicles. The vehicle can further comprise
resinous and rubbery materials, such as methylcellulose,
ethylcellulose, hydroxypropyl methylcellulose, natural rubber,
butadiene - styrene copolymer rubber, and ethylene-propylene
copolymer rubber.
Excipients present are preferably substances which promote the
evaporation of the the at least one gaseous vanillin compound.
Preferred evaporation-promoting excipients are selected from
the group consisting of hexyl acetate, isobutyl acetate,
cyclohexyl acetate, prenyl acetate, isononyl acetate,
isobornyl acetate, linalyl acetate, benzyl acetate, ethyl
butyrate, camphor, ethyl caproate, methyl caproate, carenene,
limonene, the terpene oil from oranges, allyl heptanoate,
methyl hexenoate, ethyl isobutyrate, methyl pentyl ketone,
myrcene, phellandrene, pinene, butyl valerate, terpinolene,
liquid paraffins or mixtures of at least two of these
compounds. Preferred excipients are, furthermore, dyes,
preservatives, viscosity regulators, UV stabilizers, and
further aromatic compounds, coumarin for example. Further-
preferred excipients are fragrances other than the at least
one gaseous vanillin compound,, preferably selected from the
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group consisting of orange, neroli, jasmine, balm, sandalwood,
bergamot, oak moss, eucalyptus, fennel, camomile, caraway,
sage, rosemary, star anise, tea tree oil, incense, cinnamon
bark, stone pine, almond oil, jojoba or mixtures of at least
two thereof. If the composition is used in a device for trans-
dermally administering the at least one gaseous vanillin
compound, then the composition preferably also includes, as
excipients, penetration promoters, examples being mixtures of
1 menthol and propylene glycol.
In one preferred embodiment of the above-described device the
composition comprises as excipient compounds in which the at
least one gaseous vanillin compound may be included.
Excipients preferred in this context are cyclodextrins,
examples being a , R or y cyclodextrins, activated carbon, or
zeolites. In such a case these excipients and the at least one
gaseous vanillin compound are present in a molar ratio in a
range from 5:1 to 1:5, more preferably in a range from 2:1 to
1:2, and very preferably in a molar ratio of 1:1. It is
further preferred, in one embodiment according to the
invention, for the excipients serving as vehicles to be
modified in such a way that the at least one gaseous vanillin
compound is or are delivered in retarded fashion. Particularly
suitable for this purpose is a solid vehicle such as cellulose
and liquid substance absorbed by this solid vehicle, such as
water or alcohol, which is delivered over a relatively long
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period of time, and the vanillin or vanillin derivative or
mixture thereof, admixed where appropriate with a solubilizer
such as a surfactant to the liquid substance, is delivered in
a retarded fashion in comparison to a system without this
excipient combination. The preparation of the at least one
gaseous vanillin compound encapsulated in these excipients is
accomplished preferably by contacting the individual
components with one another in a suitable solvent, ethanol for
example, or else by mixing the components with one another in
the dry state, preferably by kneading, or slurrying in small
amounts of a solvent, preferably in small amounts of water.
The at least one gaseous vanillin compound is or are released
preferably by the destruction of the resultant microcapsule
structures by the action of mechanical force, preferably by
pressure, which then allows the at least one gaseous vanillin
compound to evaporate. The major advantage of encapsulating
the at least one vanillin compound is that its release can be
restricted to particular areas through application of a
pressure, by pressing with the finger, for example. In this
way it is possible to ensure the release of the at least one
gaseous vanillin compound over a relatively long period of
time.
As the composition it is preferred to use a mixture of floral
vanillin (ref. C6031/E Flora from A. Algto Ltd) as the at
least one vanillin compound and ethanol. In order to increase
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the viscosity it is possible for this mixture further to comprise viscosity
regulators,
glycol for example.
It is further preferred for at least 50%, preferably at least 75%, and more
preferably at least 99% of the capacity of the container (1) to be filled with
the
composition.
The invention also relates to a process for producing the above-described
device
for controlledly releasing the at least one gaseous vanillin compound.
If the impermeable layer is shaped in the form of a container then the device
of the
invention is produced preferably by - introducing the above-described
composition
into the above described container,
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- and subsequently sealing the container with the impermeable
layer in such a way that separation of the impermeable layer
from the container requires a force of at least 0.5 N,
preferably of at least 1 N, and more preferably of at least 5
N.
If the container, owing to the thickness of the impermeable
layer, is not rigid, then the container can first be inserted
into a corresponding mold. Subsequently the composition is
introduced into the container in the mold.
If the device is shaped in the form of a patch, then the
device of the invention is produced preferably by introducing
the composition between the permeable layer and the
impermeable layer. This is preferably accomplished by first
applying the composition to a defined area of the permeable or
impermeable layer and placing the other layer over the
composition, the permeable and impermeable layers being
connected to one another at those points at which they
directly contact one another. This joining takes place
preferably by welding or adhesive bonding.
The invention further relates to the devices obtainable by
processes described above.
The invention also relates to the use of the at least one
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gaseous vanillin compound, to regulate the craving to consume
food.
The present invention also provides for the use of an above-
described device for the trans-dermal, nasal or pulmonary
uptake of the at least one gaseous vanillin compound, to
stimulate the release of serotonin in the central nervous
system.
The invention relates, moreover, to the use of the at least
one gaseous vanillin compound, taken up trans-dermally, for
producing a treatment means, preferably a medicinal product,
for regulating the craving to consume food.
The present invention further provides for the use of an
above-described device for producing a treatment means,
preferably a medicinal product, for the trans-dermal, nasal or
pulmonary uptake of the at least one gaseous vanillin
compound, to stimulate the release of serotonin in the central
nervous system.
The invention further relates to the use of the at least one
gaseous vanillin Compound,, taken up trans-dermally, as a
treatment means, preferably a medicinal product, for
regulating the craving to consume food.
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The present invention also provides for the use of an above-
described device as a treatment means, preferably a medicinal
product, for trans-dermal, nasal or pulmonary uptake of the at
least one gaseous vanillin compound, to stimulate the release
of serotonin in the central nervous system.
Finally the present invention also relates to the use of an
above-described device in a dietary regime or in combination
with foods selected for a particular diet. For example, the
device of the invention is used together in a food-combining
diet in combination with foods suitable for the diet and
containing only protein or carbohydrates. In another diet, the
device of the invention is used with liquid food such as fruit
and vegetable juices.
The invention is now illustrated with reference to non-
limiting examples.
Examples
Example 1:
Introduced into the virtually transparent, trough-shaped
container depicted in Fig. 1, comprising a polypropylene film
0.1 mm thick and having a base area of 14 cm2 and a height of 5
mm, were 6.5 ml of a composition made up of 50% by weight
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floral vanillin and 50% by weight ethanol. Subsequently a
polyethylene film having a thickness of 200 pm was bonded to
the outwardly curved edge of the trough-shaped container. A
polypropylene protective layer 280 pm thick was provided with
an adhesive, one corner of the protective layer remaining free
of adhesive, in order to allow the film to be peeled off by
hand. Subsequently the protective film was bonded to the
polyethylene film. Adhesive was likewise applied to the
underside of the container. The device thus obtained was
subsequently adhered to the surface of the hand. Following the
removal of the protective layer, there was continuous
evaporation of ethyl vanillin via the permeable layer.
Example 2:
Introduced into the virtually transparent, trough-shaped
container depicted in Fig. 1, comprising a polypropylene film
0.1 mm thick and having a base area of 14 cm2 and a height of 5
mm, were 6.5 ml of a composition made up of 50% by weight
floral vanillin and 50% by weight ethanol. Subsequently a
polyethylene film having a thickness of 200 pm was bonded to
the outwardly curved edge of the trough-shaped container and
subsequently an adhesive was applied to the surface of this
film. The resulting device was subsequently adhered to the
surface of the hand. Following the removal of the protective
layer, there was continuous trans-dermal uptake of ethyl
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vanillin.
In both examples, in the case of a group of 10 adult test persons having a
body
mass index of between 25 and 27, over a wearing period of 45 days per unit, a
reduction in food consumption was observed over a period of 31 days. The test
persons lost on average about 0.4 kg per day.
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