U.S. patent application number 10/581867 was filed with the patent office on 2007-03-22 for inhaler for basic pharmaceutical agents and method for the production thereof.
This patent application is currently assigned to LTS Lohmann Therapie-Systeme AG. Invention is credited to Michael Horstmann, Karin Ludwig, Yves-Thorsten Pryzbylla, Mohammad Sameti, Christoph Schmitz.
Application Number | 20070062548 10/581867 |
Document ID | / |
Family ID | 34638403 |
Filed Date | 2007-03-22 |
United States Patent
Application |
20070062548 |
Kind Code |
A1 |
Horstmann; Michael ; et
al. |
March 22, 2007 |
Inhaler for basic pharmaceutical agents and method for the
production thereof
Abstract
A device for the administration of basic active agents, such as
nicotine, to the human or animal body. The active agents are
administered by inhalation. The device comprises a first
preparation containing a nicotine base or/and a further basic
active agent and, a second or further preparations. At least one
preparation contains at least one volatile acid suitable for
inhalation.
Inventors: |
Horstmann; Michael;
(Neuwied, DE) ; Schmitz; Christoph; (Rheinbrohl,
DE) ; Ludwig; Karin; (Datzeroth, DE) ; Sameti;
Mohammad; (Bonn, DE) ; Pryzbylla; Yves-Thorsten;
(Nickenich, DE) |
Correspondence
Address: |
D. PETER HOCHBERG CO. L.P.A.
1940 EAST 6TH STREET
CLEVELAND
OH
44114
US
|
Assignee: |
LTS Lohmann Therapie-Systeme
AG
Lohmannstrasse 2
Andemach
DE
56626
|
Family ID: |
34638403 |
Appl. No.: |
10/581867 |
Filed: |
November 16, 2004 |
PCT Filed: |
November 16, 2004 |
PCT NO: |
PCT/EP04/12947 |
371 Date: |
June 5, 2006 |
Current U.S.
Class: |
131/270 ;
131/271 |
Current CPC
Class: |
A24F 42/60 20200101;
A61M 15/06 20130101; A61K 9/007 20130101; A61M 15/0003 20140204;
A24F 42/20 20200101; A24F 42/80 20200101; A61P 25/34 20180101 |
Class at
Publication: |
131/270 ;
131/271 |
International
Class: |
A24F 47/00 20060101
A24F047/00 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 5, 2003 |
DE |
103 56 925.1 |
Claims
1. A device for the administration of basic active agents,
particularly nicotine, to the human or animal body by inhalation,
wherein said device comprises a first preparation containing at
least one of a nicotine base and another basic active agent; and at
least one additional preparation, at least one of said at least one
additional preparation containing at least one volatile acid
suitable for inhalation, wherein said device has a first air inlet
aperture for air stream flow, a second air inlet aperture for air
stream flow and an air outlet aperture, said air inlet apertures
and said air outlet aperture having a conduit cross-section,
wherein the air stream flowing in through the first inlet aperture
predominantly flows over the said first preparation and that the
air stream flowing in through the second inlet opening
predominantly flows over said at least one additional preparation,
the two air streams combining later in a common flow path and
escaping from the device through said outlet aperture.
2. The device according to claim 1, wherein said first preparation
and said at least one additional preparation are applied at
separate locations within the device.
3. The device according to claim 1, wherein said first preparation
contains at least one of a nicotine base and another basic active
agent in combination with at least one solvent suitable for
inhalation.
4. The device according to claim 1, wherein said at least one
volatile acid is contained in the preparation in combination with
at least one solvent suitable for inhalation.
5. The device according to claim 1, wherein said at least one
volatile inhalable acid is selected from the group consisting of
acetic acid, lactic acid, malic acid and propionic acid.
6. The device according to claim 1, wherein said device releases
said nicotine base and said at least one volatile acid during the
inhalation process in approximately equimolar quantities from said
first preparation and said at least one additional preparation.
7. The device according to claim 1, wherein during an inspiration
process, which lasts from 1to 10 seconds and which reaches a
velocity of inspiration of 0.1 to 1 l/min, said device releases 5
to 250 .mu.g of said nicotine base or of another basic active agent
from said preparation into the inspired air.
8. The device according to claim 1, wherein aerosol particles are
formed in the internal space of said device during inhalation, and
wherein the size of said particles is less than 10 .mu.m.
9. The device according to claim 1, wherein said preparation and
said at least one additional preparation contain at least one
further additive which is volatile and is suitable for
inhalation.
10. The device according to claim 1, wherein at least one of said
nicotine base-containing preparation or acid(s)-containing
preparation comprises a polymer matrix wherein the active agent or
the acid(s) are contained in dissolved or dispersed form.
11. The device according to claim 10, wherein the polymer matrix is
based on polymers selected from the group consisting of
polyethylenes, polypropylenes, silicone polymers
(polydimethylsiloxanes) and poly(meth)acrylates.
12. The device according to claim 1, wherein said device is at
least partially, made from a material which is impermeable to the
active agent(s).
13. The device according to claim 1, wherein after production of
said device and during storage of said device, said device is
covered with a peelable protective layer which is impermeable to
the basic active agent(s), to form a compartment containing the
active agent(s) and a compartment containing the acid(s), both
compartments being separated from each other in a gas-tight manner
and being sealed from the ambient air.
14. The device according to claim 1, wherein the conduit
cross-sections of the air inlet apertures and of the air outlet
aperture are dimensioned such that the negative differential
pressure present in the oral cavity during the inspiration process
is at most 300 Pa.
15. The device according to claim 1, wherein said device comprises
at least one formed part produced by deep-drawing wherein oblong
recessions are provided for defining a first air supply channel and
a second air supply channel, said first air supply channel and said
second air supply channel being combined to form an air outlet
channel.
16. The device according to claim 15, wherein said device comprises
an upper part and a bottom part, each formed by deep-drawing, said
upper part and said bottom part being provided with said recessions
and being connected with each other and being opposite one another
to form said first air supply channel with an air inlet apertures,
said second air supply channel with an air inlet aperture and an
air outlet channel with an air outlet aperture.
17. The device according to claim 1, wherein said first preparation
is located in the oblong recess forming the first air supply
channel, and said second preparation is located in the oblong
recess forming the second air supply channel, wherein said first
preparation and said at least one additional preparation are
applied in the vicinity of the respective air inlet opening.
18. A method for the production of a device according to claim 1,
said method comprising the following steps: producing a formed part
by deep-drawing, said formed part comprising a first oblong,
concave recess for receiving a first preparation, and a second
oblong, concave recess for receiving a second preparation;
introducing a predetermined amount of said first preparation,
containing a nicotine base or another basic active agent, into said
first recess; and introducing a predetermined amount of said second
preparation, containing acid(s), into said second recess to produce
a filled formed part.
19. The method according to claim 18, wherein the filled formed
part is covered with a peelable protective layer impermeable to the
basic substance(s), such that a compartment containing the active
agent(s) and a compartment containing the acid(s) are formed by the
peelable layer, both compartments being separated from each other
in a gas-tight manner and being sealed from the ambient air.
20. The method according to claim 18, wherein during production of
the formed part, said method further comprises forming a further
oblong, concave recess by deep-drawing which is connected with said
two other recesses and for forming an air outlet channel.
21. The method according to claim 20, wherein the filled formed
part is connected with a formed part serving as the upper part and
having oblong recesses corresponding to those of said filled formed
part, the respective, superimposed recesses forming a first air
supply channel with an air inlet aperture, a second air supply
channel with an air inlet opening, and an air outlet channel with
an air outlet aperture.
22. Use of an inhaler according to claim 1 for smoking cessation or
for smokeless satisfaction of the craving for nicotine in cases of
situational necessity.
23. Use of an inhaler according to claim 1 for simultaneous
inhalation of a basic active agent and one or more volatile acid
compounds.
24. The device according to claim 3, wherein said another basic
active agent in combination with at least one solvent suitable for
inhalation is ethanol.
25. The device according to claim 4, wherein said at least one
solvent suitable for inhalation is ethanol.
26. The device according to claim 7, wherein said device releases
10 to 100 .mu.g, of said nicotine base or of another basic active
agent from said preparation into the inspired air.
27. The device according to claim 9, wherein said at least one
further additive which is volatile and is suitable for inhalation
is menthol.
28. The device according to claim 12, wherein said device is
entirely made from a material which is impermeable to the active
agent(s).
29. The device according to claim 12, wherein said material which
is impermeable to the active agent(s) is a polyester material which
is coated with at least one of a copolymer of acrylonitrile and
methacrylate, and a metal foil(s) or a combination of the mentioned
materials.
30. The device according to claim 14, wherein the conduit
cross-sections of the air inlet apertures and of the air outlet
aperture are dimensioned such that the negative differential
pressure present in the oral cavity during the inspiration process
is at most 200 Pa.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a National Stage application of
International Application No. PCT/EP2004/012947, filed on Nov. 16,
2004, which claims priority of German application number 103 56
925.1, filed on Dec. 5, 2003.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The invention relates to devices for administering basic
active agents, in particular nicotine, to the human or animal body
by inhalation. The invention further relates to methods for
producing such devices, as well as the use of such devices for
smoking cessation or for smokeless satisfaction of the craving for
nicotine in cases of situational necessity.
[0004] 2. Description of the Prior Art
[0005] Nicotine inhalers for administration of nicotine via the air
inhaled during inspiration have been known for several years (e.g.
U.S. Pat. No. 4,917,120 and U.S. Pat. No. 5,167,242). For some
years nicotine inhalers have also been available on the market as
smoking cessation products in several European countries
("NICORETTEO"; Pharmacia/Pfizer). The latter nicotine inhaler is,
however, not widely used since with this device only small amounts
of nicotine become effective when inhaling. This is due, in
particular, to fundamental deficiencies of the known inhaler
technologies and the tolerance that can be achieved with these
technologies. In particular, the locally irritating effects on the
mucous membranes of the respiratory passages, caused by the
alkaline properties of nicotine, are disadvantageous since they
cause an urge to cough, which results in a decreased absorption of
the nicotine vapours released by the inhaler. In this way only very
small amounts of nicotine are absorbed by the body.
SUMMARY OF THE INVENTION
[0006] It was therefore the object of the invention to provide a
nicotine inhaler which enables absorption of nicotine via the
respiratory passages and causes as little irritation and is as
intense as possible.
[0007] This object is achieved with the devices according to the
present invention, as well as with the method of production
according to the present invention.
[0008] Accordingly, a device according to the invention comprises a
first preparation which contains a nicotine base or/and another
volatile, inhalable basic active agent. The device according to the
invention further comprises a second preparation or a plurality of
further preparations, which contain at least one acid which is
volatile and suitable for inhalation. Accordingly, the devices
according to the invention are characterized in that upon inhaling,
apart from the active agent base (e.g. nicotine base), one or more
volatile acid compounds are also inhaled at the same time.
[0009] The devices according to the invention are suitable for the
administration of basic agents, in particular nicotine, to the
human or animal body by inhalation. Suitable basic agents are, for
example, selegiline or/and mecamylamine. The combination of
nicotine and mecamylamine is used with particular preference for
smoking cessation.
[0010] Due to the simultaneous presence of the first preparation,
containing a nicotine base (or another active agent base), and of a
further preparation, containing a volatile acid, the nicotine base
and the volatile acid are volatilised during inhalation, whereby
the mixing of the basic and acid vapours leads to the formation of
the corresponding nicotine salt (or of the corresponding salt of
the other active agent base) in the device. This salt enters the
respiratory passages, in the form of liquid drops or in particulate
form, along with the inhaled air. Because of the neutral reaction
of the mucous membrane to the salt, this type of inhalation shows a
considerably better tolerance than can be achieved with known
inhalation devices.
[0011] In this connection, it is preferred that said first,
nicotine base-containing preparation and said second,
acid-containing preparation are applied at separate locations
within the device. This way, it is possible to configure the air
inlet channels such that, upon inhaling, a part of the air stream
flows over the first preparation and another part of the air stream
flows over the second preparation, and that subsequently the two
air streams (with the volatilised nicotine base and acid contained
therein) combine and can thereafter be inhaled.
[0012] During inhalation, the active agent base (e.g. nicotine
base) contained in the first preparation and the volatile acid
contained in the second preparation are passively volatilised. This
process may optionally be accelerated by application of heat; means
suitable for this purpose are known to those skilled in the
art.
[0013] When the device according to the present invention is being
used, an aerosol is formed in the ambient air flowing
in--especially if there are high concentrations of the active agent
base and of the acid in the vapours. This aerosol formation is due
to the lower volatility of the nicotine salt, the salt mixture or
the salt solution drop being formed. The aerosol formation is at
the same time the reason for a substantially increased tolerance
since nicotine is no longer present in free form and can no longer
act as an alkali via the external gas phase. As a result, only the
particulate deposition of aerosol particles in the alveoli can lead
to the application of active agent in the lung and to absorption
(resorption). These aerosol droplets, either as salt components
partially dissolved in water or as a solid dispersion, exhibit a
far better tolerance due to the neutral (instead of alkaline)
mucous membrane reaction than is possible with devices known in the
state of the art.
[0014] Aerosol formation is helpful, but it is not imperative for
achieving the therapeutic result according to the invention. On the
whole, a high dilution of the supplied vapours--thus suppressing
the formation of an aerosol--can even be useful in terms of
tolerance.
[0015] The size of the aerosol particles formed by the inhalation
system according to the invention is, above all, dependent on the
velocity of the air flow (flow rate) and on the concentrations of
the individual gaseous components (basic active agent and acid,
respectively) in the mixing zone.
[0016] Advantageous for alveolar absorption are aerosol particles
of a size below 10 .mu.m (mean diameter), in particular 5 to 10
.mu.m.
[0017] According to a preferred embodiment, the inhalation device
comprises a first air inlet aperture, a second air inlet aperture
and an air outlet aperture. These apertures are arranged such that
the air stream flowing in through the first inlet opening
predominantly passes over said first preparation and that the air
stream flowing in through the second inlet opening predominantly
flows over said second or further preparation(s), the two air
streams combining later in their path and exiting the device
through said outlet aperture.
[0018] It is furthermore preferred for the device to have oblong
recesses, grooves or channels inside, whereby a first and a second
air supply channel and an air escape channel are formed. These air
flow paths each open towards the outside via said air inlet and air
outlet openings, respectively. Said first preparation is located in
the oblong recess forming the first air supply channel, and said
second preparation is located in the oblong recess forming the
second air supply channel. It is preferred for each preparation to
be applied in the vicinity of the respective air inlet opening.
[0019] Generally, an approximately equimolar ratio of the molar
evaporation rates of the two components (active substance base,
acid) is aimed at. If--as described--the nicotine-containing
preparation and the acid-containing preparation are applied in two
separate air supply channels, which are provided with associated
air inlet openings, the respective release rates can be controlled,
inter alia, by means of the flow conditions in the two channels.
For example, a release rate of 100 .mu.g/10 seconds may be provided
for an air stream flowing through the first opening and thereby the
first air supply channel; in that case--and if acetic acid is used
as an acid component--a release rate of approx. 50 mg/10 seconds
would be suitable for said second air stream.
[0020] With respect to the obtainable release rates, it is
preferred that, during one inspiration process, which lasts 1 to 10
seconds and during which an inspiration speed of 0.1 to 1 l/min is
reached, an inhalation device according to the present invention
releases 5 to 250 .mu.g, preferably 10 to 100 .mu.g, of nicotine
base or of another basic agent from said preparation into the
inspired air. For example, during one breath lasting 10 seconds and
at inspiration velocities between 0.1 and 1 l/min, it is possible
to administer 100 .mu.g of nicotine base. This release rate is
appropriate for therapeutic purposes.
[0021] To impair the process of inspiration as little as possible,
it is preferred for the device to have large passage cross-sections
throughout its configuration. This applies, in particular, to cases
where the conduit cross-sections of the air inlet apertures and of
the air outlet aperture are dimensioned such that the negative
differential pressure in the oral cavity during the process of
inspiration does not exceed 300 Pa.
[0022] As the volatile acid, acetic acid is used with preference;
other acids may be used as well, provided that they are volatile at
room temperature (approx. 15-25 .degree. C.) or can be converted to
the vapour phase by impact of heat (up to approx. 100.degree. C.)
(e.g. lactic acid, malic acid, propionic acid). Even combinations
of different acids can be used. Acetic acid, on account of its high
volatility, is used at a lower concentration and in a larger total
quantity, as well as in combination with additives. Volatile,
inhalable basic active agents are understood to be, in particular,
those agents which are volatile or which can be converted to the
vapour phase at the above-mentioned temperatures.
[0023] Furthermore, according to a specific embodiment, it is
provided that the active agent-containing preparation additionally
contains at least one solvent suitable for inhalation (preferably
ethanol) or/and at least one volatile auxiliary substance
(preferably menthol). The acid-containing preparation may likewise
contain at least one such solvent or/and at least one volatile
auxiliary substance. Suitable volatile auxiliaries are, in
particular, flavourings and perfuming substances that are felt to
be pleasant (e.g. limonene, eucalyptol, mint oil, camphor or other
substances from the terpene group; including combinations of the
afore-mentioned substances).
[0024] The invention further encompasses methods for the production
of the above-mentioned devices. These methods generally comprise
the following steps: [0025] producing a formed part by deep-drawing
or other methods of forming (e.g. injection moulding) known to
those skilled in the art, said formed part comprising a first
oblong, concave recess for receiving said first preparation, and a
second oblong, concave recess for receiving said second
preparation; [0026] introducing a predetermined amount of a first
preparation, containing a nicotine base or another basic active
agent, into the said first recess; [0027] introducing a
predetermined amount of a second preparation, containing acid(s),
into the said second recess.
[0028] The devices according to the invention can be produced in a
simple manner and at low cost by using formed parts produced by
deep-drawing. A preferred material suitable for this purpose is a
polyester material provided with a coating that is impermeable to
the basic agent, especially to nicotine. Suitable for this purpose
is, above all, a copolymer of acrylonitrile and methacrylate
(Barex.RTM.; BP). A polyethylene terephthalate-Barex laminate sheet
is used with preference.
[0029] By deep-drawing, oblong recesses are provided in a formed
part which are to form the two air supply paths. Furthermore, a
further oblong recess may be provided which is connected with the
two recesses and is to form the air outlet channel. The air supply
channels and the air outlet channel are of an essentially
cylindrical configuration, but they may also be of a geometry that
differs therefrom.
[0030] The formed part provided with the recesses forms the bottom
part of the device; the upper part may be formed by a second formed
part having correspondingly provided recesses, or by a plane film
or layer serving as a cover. The upper part and the bottom part are
connected with each other in a known manner (e.g. adhesive bonding,
sealing), after application of the preparations.
[0031] The recesses forming the air supply channels in the formed
part or formed parts may be configured, by providing additional
bulges (which may likewise be produced by deep-drawing), such that
the vaporisation rate of the respective volatile component can be
geometrically limited. This measure results in an additional
possibility of accomplishing the preferred delivery of active agent
base and acid in equimolar quantities.
[0032] The device is at least partially, but preferably entirely,
produced from a material which is impermeable to the active
agent(s), particularly from a polyester material which is provided
with the above-mentioned coating, and/or from metal foil(s), or
combinations of these materials.
[0033] Suitable as base materials for the production of said
preparations are, in principle, any materials that may be used for
making a reservoir which receives nicotine base or another active
agent base or the mentioned volatile acid and which, under the
conditions of inhalation, releases these substances by vaporisation
to the ambient air. Materials suitable for this purpose are known
to those skilled in the art.
[0034] Suitable materials are, for example, polymer materials, as
used, for example, in the production of active substance reservoirs
of transdermal therapeutic systems. In this process the active
substance (or the acid(s)) is dissolved or dispersed in a polymeric
base material (e.g. polyacrylates), optionally with addition of
auxiliary substances, and the resultant mass is coated on an inert
support and is allowed to dry. Pieces of a certain surface area and
layer thickness, with a known content of active agent or acid, are
separated from the dried active agent-containing layer. As
described, these pieces can then be inserted as the above-mentioned
preparations in a device according to the invention. The suitable
layer thickness and surface area of the sheet-like preparations
introduced into the air flow space of the device are derived from
pharmaceutical practice.
[0035] The nicotine preparation inserted in a device according to
the invention typically has a content of 10%-wt., and the dose is
typically 500 mg. The concentration and dose used in each
individual case may deviate from these example values; in
particular, the active substance content may be 1 to 80%-wt. and
the dose 10 to 1000 mg.
[0036] Suitable as polymer base materials are, in particular,
polymers from the group comprising polyethylenes, polypropylenes,
silicone polymers (polydimethylsiloxanes) and
poly(meth)acrylates.
[0037] The above-mentioned preparations may furthermore be produced
by using thermoplastic polymers, the latter being thermally
liquefied and the ingredients (basic active agent and/or acid)
being metered to the hot polymers. The still liquid preparation is
directly applied to the location intended for this purpose of the
deep-drawn inhalation device and is allowed to solidify.
[0038] According to a further variant, of the invention a mixture
of silicone polymers (polydimethyl siloxane) and crosslinking agent
(e.g. a platinum-containing crosslinking agent) is used as the base
material. Nicotine base or the volatile acid component is metered
in liquid form to this mixture in cold condition. A predetermined
amount of this mixture is applied to the respective locations
intended for this purpose. After closing the device, it is
post-treated under application of heat, whereby a three-dimensional
structure of the active agent release preparations is produced.
[0039] The active agent-containing or acid-containing preparation
is preferably applied in the vicinity of the air inlet opening of
the respective air supply channel.
[0040] The material employed to close the device is preferably a
material which is impermeable to the volatile ingredients, as
described above.
[0041] In a further preferred embodiment, the inhalation device is
covered, after production thereof, with a peelable protective layer
impermeable to the basic agent(s). This protective layer will be
removed only shortly before use, by the user himself By means of
the protective layer which has been applied a compartment
containing the basic active substance(s), and a compartment
containing the acid(s) are formed, both compartments being
separated from one another in a substantially gas-tight manner and
being sealed from the ambient air. In this manner, premature
reaction and ageing of the ingredients is prevented. Only after the
protective layer has been removed can an exchange of gas again take
place between the two compartments.
[0042] If necessary, the air inlet and air outlet apertures are
also covered with a protective film.
[0043] The devices can advantageously be used for smoker cessation
or also for smokeless satisfaction of the craving for nicotine in
cases of situational necessity.
[0044] The invention will be illustrated, by way of example and in
schematic representation, by the appended drawings. The meaning of
the reference numerals is identical in all of the drawings unless
otherwise indicated.
BRIEF DESCRIPTION OF THE DRAWINGS
[0045] FIG. 1A is a longitudinal section view of the device
according to the present invention.
[0046] FIG. 1B is a longitudinal section view of the device
according to the present invention, in an operative condition.
[0047] FIG. 1C is a cross-sectional view of the present invention
shown through plane X of FIG. 1B.
[0048] FIG. 2A is a longitudinal section view of an alternative
embodiment of the present invention.
[0049] FIG. 2B is a cross-sectional view of the present invention
shown through plane X of FIG. 2A.
[0050] FIG. 2C is a longitudinal section view of the alternative
embodiment of the present invention shown in FIGS. 2A and 2B.
[0051] FIG. 2D is a cross-sectional view of the present invention
shown through plane X of FIG. 2C.
[0052] FIG. 2E is a cross-sectional view of the present invention
shown through plane Y of FIG. 2C.
[0053] FIGS. 3A and 3B are perspective views of another alternative
embodiment of the present invention.
[0054] FIG. 3C is a plan view of the present invention as shown in
FIGS. 3A and 3B.
[0055] FIG. 4A is a perspective sectional view of yet another
alternative embodiment of the present invention.
[0056] FIG. 4B is a plan view of the present invention as shown in
FIG. 4A.
[0057] FIG. 5 is a cross-sectional view of a modified version of
the embodiment of the present invention shown in FIG. 4A.
[0058] FIG. 6 is a schematic representation of still yet another
alternative embodiment of the present invention.
DETAILED DESCRIPTION OF THE PRESENT INVENTION
[0059] FIG. 1A shows a device (1) according to the invention in its
commercial form (sectional representation). Device 1 is formed by
an outer wall (2) and has two air flow channels (a, b) which,
approximately in the middle thereof, expand to form a respective
one of the chambers (3a, 3b) and thereafter combine to form an air
escape channel (7).
[0060] In the chambers (3a, 3b) there is a nicotine-containing
preparation (5) and an acid-containing preparation (4),
respectively.
[0061] FIG. 1A shows the condition of the device prior to use. The
inlet and outlet orifices of the air flow channels (a, b) are still
closed, and the chambers (3a, 3b) are separated from each other by
membranes (13) so that mixing of the two components (4, 5) cannot
yet take place.
[0062] FIG. 1B shows (likewise in longitudinal section) the device
shown in FIG. 1A in the operative condition after opening of the
membranes (13) (e.g. by action of heat or by pushing through) and
of the inlet and outlet apertures (A, B, C). The inlet and outlet
apertures may be opened, for example, by breaking open or tearing
open along a perforation (11, 12 in FIG. 1A) provided in the device
(layer (8) is not shown in FIG. 1B).
[0063] Upon inspiring, air flows through the air inlet aperture (A)
and through the air supply channel (a), on the one hand, and
through the inlet opening (B) and the air supply channel (b), on
the other hand. The dashed arrows indicate the flow direction of
the air during inhalation. The two air supply channels (a, b)
combine to form the air escape channel (7), having the air outlet
aperture (C). In the area of the air supply channel (a) there is a
nicotine-containing preparation (5) directly behind the inlet
aperture (A), and in the area of the air supply channel (b) there
is an acid-containing preparation (4) directly behind the inlet
opening (B). When air flows through, nicotine is volatilised from
the preparation (5) in the air channel (a), and the acidic compound
contained in the preparation (4) is evaporated in air channel (b).
In the area of the air escape channel (7), the alkaline and the
acidic vapours mix, and an approximately neutral to slightly acidic
condition is achieved. The aerosol which has been formed,
consisting of ambient air and the nicotine salt contained therein,
is inhaled through the outlet opening (C), preferably via the oral
cavity.
[0064] FIG. 1C shows a cross-section in plane X of the inhalation
device schematically represented in FIG. 1B. The air inlet channels
(a, b) are preformed by deep-drawing so that they have a concave
shape. In the area of the air channels (a, b) there is the active
agent-containing preparation (5) and the acid-containing
preparation (4), respectively. The device is covered at the
underside by a flat, nicotine-impermeable layer (8).
[0065] FIG. 2A shows (in longitudinal section) a further embodiment
of an inhalation device according to the invention in its
commercial form. Inlet and outlet apertures (A, B, C) are still
closed. The middle region of the channels (a, b) expands to form a
respective chamber (3a, 3b). The chambers (3a, 3b) of the
individual preparations (4, 5) are arranged side by side and
spatially separated from one another, so that mixing of the
preparations is not yet possible (condition prior to use).
[0066] FIG. 2B shows a cross-section in plane X of the inhalation
device represented in FIG. 2A. The air inlet channels (a, b) and
chambers (3a, 3b) are preformed by deep-drawing in the outer wall
(2) and are of a concave shape. Inside the chambers (3a, 3b) there
is the active substance-containing preparation (5) and the
acid-containing preparation (4), respectively. The device is
covered at the underside by a flat, nicotine-impermeable layer
(8).
[0067] FIG. 2C is a further longitudinal section of the embodiment
shown in FIGS. 2A and 2B. The device is shown in its ready-for-use
condition. To use the device depicted in FIG. 2A, it is folded,
prior to use, along line (14), which may be provided, for example,
in the form of a perforation or weakened line, so that by folding
along the middle the two air flow channels (a, b) and chambers (3a,
3b) are positioned on top of one another in the longitudinal
direction. The apertures of the air inlet and air outlet channels,
respectively, may be opened, for example, by breaking open along a
perforation (11, 12) provided for that purpose. In this manner a
functional inhalation device is obtained. The dashed arrows
indicate the direction of air flow during inhalation. A tube or
mouthpiece (9) can be slipped on the two outlet apertures (C, C'),
thereby forming a joint air outlet channel (7') and a joint outlet
aperture (D).
[0068] FIG. 2D shows a cross-section in plane X of the operative
device shown in FIG. 2C. The chambers (3a, 3b), formed by the
deep-drawn walls (2, 2') and layers (8, 8'), are positioned on top
of each other.
[0069] FIG. 2E shows a cross-section in plane Y of the operative
device shown in FIG. 2C. The dashed arrows indicate the direction
of air flow during inhalation. During inspiration, the air streams
(A, B) flow through separated channels (a, b), passing over the
preparations (4, 5) located in the chambers (3a, 3b). The resultant
vapours or aerosols combine in the region of the air outlet channel
(7'), formed by the tube or mouthpiece (9), and leave the device
via the outlet aperture (D).
[0070] FIGS. 3A and 3B show (in perspective representation) a
further embodiment of the device according to the invention,
wherein FIG. 3B depicts a tube or mouthpiece (30) into which the
cylindrical insert (31) can be inserted. The internal space of the
insert (31) is divided, by a partitioning wall (32) extending in
the longitudinal direction, into two chambers (33, 34) which serve
to receive the active agent preparation and the acid component,
respectively (not shown). The insert is surrounded by the cylinder
barrel (35) (in FIG. 3A it is depicted partially cut open). In the
region of the rear end, an aperture (36) is provided in the barrel;
said aperture serves as an air inlet aperture. A further air inlet
aperture (37) is provided in the end face (38), which closes the
rear end of the insert (31). FIG. 3C shows this end face in plan
view. The number and arrangement of the apertures may vary.
[0071] During production, a nicotine-containing preparation is
placed in the chamber (33, 34), e.g. a carrier material impregnated
with nicotine (e.g. a sponge or filter paper), and a carrier
material impregnated with a volatile acid (preferably acetic acid)
is placed in the respective other chamber; optionally, a flavouring
agent or perfuming agent may also be incorporated therewith. All
openings, i.e. the front end (V) and the apertures (36, 37) are
closed with a suitable protective film or foil.
[0072] Prior to use, the protective films are removed and the
insert (31) is inserted into the mouthpiece (30). By sucking on the
mouthpiece, air is sucked in via the two rear apertures (36, 37).
This air flows through the two chambers (33, 34) over the carrier
materials and in doing so takes along the nicotine vapours, acid
vapours and, optionally, perfuming agent vapours. These vapours are
whirled in the region of the mouthpiece before they enter the oral
cavity. The mixing of nicotine and acid vapours facilitates
inhalation of nicotine. To this end, it is advantageous for the
mouthpiece (30) to be provided with a plurality of protrusions or
teeth (39). These are preferably arranged in several offset rows,
one after another. The mouthpiece (30) is a substantially
cylindrical sleeve open at both ends. It is preferably shorter than
the insert (31).
[0073] The protrusions or teeth (39) may also be configured as
helical, S-shaped or spiral baffles, thereby achieving better
whirling of the air and thus better mixing of the gases.
[0074] FIG. 4A shows a perspective sectional view of a further
embodiment of the device according to the invention. This device
comprises a sleeve-shaped mouthpiece (30), to which a tube (41) can
be rotatably attached or on which a tube (41) can be rotatably
slipped or into which a tube (41) can be rotatably inserted
(direction of the arrows). Preferably, the end of the mouthpiece
(40) is configured such that the tube (41) snaps in when it is
slipped onto the mouthpiece. The aperture of the mouthpiece which
faces the mouth is, as described in FIG. 3, provided with a
plurality of protrusions (39). The internal space of the mouthpiece
(40) is divided into four chambers by two partitioning walls. The
mouthpiece is open at both ends. That opening which will be
connected with the tube (41) is partially closed. Preferably, at
least one sector of the substantially circular cross-section of the
mouthpiece is closed, for example two opposite sectors, as shown in
FIG. 4B.
[0075] The slip-on tube (41) is open at both ends and inwardly
partitioned into four chambers in the same manner (by walls (44,
45)) as the mouthpiece. The nicotine-containing preparation and the
acid-containing preparation, respectively, are located in two
opposite chambers.
[0076] Also provided are embodiments where the mouthpiece and the
tube are partitioned into two or three, or more than 4, internal
spaces.
[0077] The walls or baffles (44, 45) may also be configured in a
helical shape, S-shape or spiral shape, thereby achieving a more
intense whirling of the air and consequently a better mixing of the
gases.
[0078] The nicotine-containing tube is produced by inserting the
nicotine-containing carrier material in a first chamber of the
tube, and inserting the acid-containing carrier material into the
corresponding, opposite chamber (optionally modified with a
perfuming agent). All openings are then closed with a suitable film
or foil. In addition, it is possible to fill the remaining chambers
of the tube with further active agents or perfuming agents.
[0079] For use, the protective films are removed and the tube (41)
is slipped onto the mouthpiece (40), whereby it snaps in. The tube
is rotatably engaged, so that by turning the tube (see double
arrow) relative to the mouthpiece the filled chambers can be opened
and closed. This affords the possibility for the consumer to
regulate the air stream he wishes to inhale. If necessary, the open
ends of the mouthpiece, respectively of the tube, can be closed
with detachable caps.
[0080] FIG. 5 shows (in cross-section) a modification of the
embodiment depicted in FIG. 4. The internal space of the mouthpiece
(40) and of the tube (41) is divided into four tubular chambers
(51, 52, 53, 54); (50) designates the cylindrical wall of the
mouthpiece and the tube, respectively.
[0081] In this context, it is advantageous that the carrier
materials impregnated with active agent or acid may be inserted
into the tube in the form of "cartridges". In that case, the tube
may form a unit with the mouthpiece and be permanently (but
rotatably) connected therewith, which means that the entire device
is reusable. The "cartridges" can be stored separately and may be
produced so as to have different nicotine contents (or so as to
contain different active agents).
[0082] FIG. 6 shows, in schematic representation, a further
advantageous embodiment of the device according to the invention.
The active agent-containing preparation (not shown) is located in
the first compartment (61), which forms a larger gas space wherein
the active agent vapours can accumulate. The acid-containing
preparation, possibly combined with perfuming agents, is located in
a second compartment (62). The broad arrows indicate the direction
of the air streams occurring while inhaling. Air is sucked in
through the inlet apertures (64, 65). These may be provided with
valves in order to prevent premature mixing of the ingredients
(active agent, acid) or/and prevent them from escaping to the
outside.
[0083] Upon inhaling through the mouthpiece (63), the air flows
into the device along two different paths: (i) Air flows through
lateral apertures (64) into the compartment (61) and in the process
flushes the gas space, which is presaturated with vapour pressure,
into the mixing zone in front of the mouthpiece (63); and (ii)
simultaneously, air is sucked in through the lateral apertures (65)
into the second compartment (62). In the process, this air also
flushes the auxiliary substances (acid, possibly flavouring agents)
into the mixing zone in front of the mouthpiece (63). In the mixing
zone, the two air flows mix with each other. During this mixing
process, the desired neutralisation of the active agent base takes
place.
[0084] What has been described above are preferred aspects of the
present invention. It is of course not possible to describe every
conceivable combination of components or methodologies for purposes
of describing the present invention, but one of ordinary skill in
the art will recognize that many further combinations and
permutations of the present invention are possible. Accordingly,
the present invention is intended to embrace all such alterations,
combinations, modifications, and variations that fall within the
spirit and scope of the appended claims.
* * * * *