U.S. patent application number 10/185949 was filed with the patent office on 2003-04-24 for atomizer for applying liquids onto eyes.
This patent application is currently assigned to Boehringer Ingelheim Pharma KG. Invention is credited to Diestelhorst, Michael, Hochrainer, Dieter, Martin, Isolde, Zierenberg, Bernd.
Application Number | 20030078551 10/185949 |
Document ID | / |
Family ID | 7689762 |
Filed Date | 2003-04-24 |
United States Patent
Application |
20030078551 |
Kind Code |
A1 |
Hochrainer, Dieter ; et
al. |
April 24, 2003 |
Atomizer for applying liquids onto eyes
Abstract
The present invention relates to atomizers for administering
liquids to the cornea or conjunctiva of the eye, special eye
adapters for atomizers and the use of atomizers for
ophthalmological administration. The atomizers according to the
invention are free from propellant gas and have an energy reservoir
for supplying the energy needed for the atomization process.
Inventors: |
Hochrainer, Dieter; (Bingen,
DE) ; Zierenberg, Bernd; (Bingen, DE) ;
Diestelhorst, Michael; (Koeln, DE) ; Martin,
Isolde; (Ingelheim, DE) |
Correspondence
Address: |
BOEHRINGER INGELHEIM CORPORATION
900 RIDGEBURY ROAD
P. O. BOX 368
RIDGEFIELD
CT
06877
US
|
Assignee: |
Boehringer Ingelheim Pharma
KG
Ingelheim
DE
|
Family ID: |
7689762 |
Appl. No.: |
10/185949 |
Filed: |
June 28, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60348785 |
Oct 23, 2001 |
|
|
|
Current U.S.
Class: |
604/295 |
Current CPC
Class: |
A61M 11/006 20140204;
B05B 11/3091 20130101; A61M 11/00 20130101; A61M 11/008 20140204;
B05B 11/308 20130101; Y10T 137/7909 20150401; B05B 11/3001
20130101; A61F 9/0026 20130101; A61H 35/02 20130101; A61M 15/007
20140204; A61M 2210/0612 20130101; Y10T 137/7916 20150401 |
Class at
Publication: |
604/295 |
International
Class: |
A61M 035/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 29, 2001 |
DE |
101 31 178.8 |
Claims
What is claimed is:
1. An atomizer that does not require the use of a propellant for
administering liquids to the cornea or conjunctiva of the human or
animal eye comprising: an upper housing part, a locking mechanism,
a spring housing, a spring, a pump housing which is secured in the
upper housing part and which comprises at one end a nozzle body
with a nozzle or nozzle arrangement, a hollow plunger with valve
body, a power takeoff flange in which the hollow plunger is secured
and which is located in the upper housing part, a locking mechanism
situated in the upper housing part, a spring housing with a spring
contained therein, which is rotatably mounted on the upper housing
part by means of a rotary bearing, a lower housing part which is
fitted onto the spring housing in the axial direction, a storage
vessel for the liquid to be administered, and an adapter in the
form of a cavity surrounded by a wall with two openings, wherein
one opening surrounds the nozzle in such a way that a jet spray
emerging therefrom is conveyed exclusively into the cavity and the
second opening, which is opposite from the first, and which has an
outer contour which is such that the opening surrounds the visible
part of the eye of a person or animal without directly touching the
eye.
2. The atomizer according to claim 1, characterised in that the
outer contour of the second opening of the adapter is oval in plan
view and in cross section takes the form of a concave curved line
with a longer end and a shorter end.
3. The atomizer according to claim 1, characterised in that the
adapter is indivisibly attached to the atomizer as an integral part
thereof.
4. The atomizer according to claim 1, characterised in that the
adapter is fitted onto a projection close to the nozzle.
5. The atomizer according to claim 1, characterised in that the
average particle size in the spray mist produced thereby is between
about 1 and about 20 microns.
6. The atomizer according to claim 1, characterised in that the
average speed of the particles in the spray mist produced, at a
spacing from the nozzle of about 1 to about 5 cm, is no more than
about 50 metres per second.
7. The atomizer according to claim 1, characterised in that
openings in the adaptor are provided in the side wall of the
adapter.
Description
[0001] The present invention relates to atomisers for applying
liquids to the cornea of the eye or to the connective tissue of the
eye, special eye adapters for atomizers and the use of atomizers
for ophthalmological administration. The atomizers according to the
invention are free from propellant gas and have an energy reservoir
for supplying the energy required for the atomizing process.
PRIOR ART
[0002] For treating dry eyes, for moistening the surface of the eye
for contact lens wearers, for numerous eye diseases or methods of
investigating the eye it is usual to administer medicaments in the
form of an aqueous formulation as eye drops. For this form of
administration, liquid dispensers have been developed in which the
formulation is supplied from a storage bottle through a dropper,
for example (dropper bottles or EDO-Ophthiols). The aqueous
formulation usually flows out of the dropper opening as a result of
manual pressure being applied to the compressible storage bottle.
First, a drop forms on the opening, which does not break away from
the dropper and drop into the eye until a certain relationship is
reached between the size of the dropper opening, the surface
tension and the weight of the drop. Usually, aqueous eye drops have
a volume of about 0.05 ml.
[0003] This method of dropping liquids onto the eye has various
disadvantages. On the one hand, not all patients find it easy to
administer drops of liquid into their own eyes. This is partly
because they have to lean their head back (recline the head) and
then let the drop fall into the eye from above. Children and old
people in particular find this very difficult.
[0004] In addition, it happens occasionally that a patient will
accidentally stick the applicator of the dropper bottle into their
eye.
[0005] A further disadvantage is that the formulation administered
is initially only applied to one point on the cornea, which feels
unpleasant, not only because of the local pressure produced on the
surface of the eye.
[0006] Often, the patients themselves cannot tell whether they have
successfully administered the prescribed amount of eye drops or
not. As a rule a patient only realises whether any liquid has
reached the target organ when an excess of the formulation comes
out of the eye and is noticed, for example, either by tasting it or
as liquid on the cheeks. However, once this stage has been reached,
an excessive dose has already been given, which may lead to
unwanted systemic side effects.
[0007] In connection with this, it is important to note that the
surface of the eye is coated with about 7 microlitres of a film of
liquid. Any application of an additional liquid consequently causes
some of the total liquid on the eye to flow away through the tear
duct. This naturally occurs particularly when larger amounts of
liquid, such as e.g. 40 microlitres or more of eye drops are
applied. If a pharmacologically effective liquid enters the tear
duct, it can be absorbed systemically by the body, i.e. the
pharmacologically active ingredients are absorbed directly by the
body. This may lead to allergic or toxicological effects. In
conventional applications about 80% of the liquid administered is
displaced out of the eye and some of it enters the tear duct.
[0008] Another disadvantage is that during the instilling of the
drops the patient has to consciously fight their blink reflex. If
they do not manage to do so, the formulation is delivered not to
the eye but to the eyelid and further drops have to be given, which
may in turn lead to overdosing with the consequences described
above and cause undesirable systemic side effects.
[0009] Another disadvantage of this method is that there may be
short-term irritation of the eyes at the site where the drops are
instilled.
[0010] The conventional application devices are also not protected
against the entry of germs into the formulation for administration,
which means that preservatives have to be added to the
formulations. Preservatives may lead to chronic inflammation of the
conjunctiva or the underlying Tenon's membrane in long-term or
chronic use. There may be morphological changes in this tissue,
which are a major drawback particularly in operations, as the wound
healing process is disrupted and/or scarring may occur.
[0011] U.S. Pat. No. 5,588,564 discloses a pump spray provided with
an adapter for administering a spray jet to the eye. As the spray
duration of this system is short, there is a danger that the
solution will not be sprayed onto the eye but onto the eyelid, as a
result of the blink reflex. Neither the pump spray nor the adapter
has means for protecting the eye from possible injury by the
comparatively hard spray jet.
[0012] U.S. Pat. No. 5,921,444 discloses a spray device with a
fitting for administering a liquid to an eye. The disadvantages of
this system are similar to those described above.
[0013] WO 96/00050 discloses an applicator for applying liquids to
an eye, wherein the spray device is located within a housing one
side of which is constructed so that it can fit round an eye. The
aerosol droplets produced with the device have a diameter of at
least 20 micrometres. The spray duration of this system is less
than {fraction (1/20)}.sup.th of a second (page 13), which has the
disadvantages described above.
[0014] EP 0911056 discloses an atomizer for placing over an eye
with an adapter which has a shutter or deflector plate positioned
so that the spray jet does not strike the cornea directly. However,
on the one hand a protector of this kind will become dirty very
quickly and is difficult to clean and on the other hand it
militates against exact and reproducible metering.
DESCRIPTION OF THE INVENTION
[0015] Thus, the problem on which the present invention is based is
to apply aqueous solutions or ophthalmologically effective
formulations by means of a single form of application to the
surface of the eye in such a way as to reduce the local irritation
of one area of the cornea compared with conventional methods of
applying eye drops.
[0016] Another problem is to develop a process with which eye drops
can be administered in a manner which is more pleasant for the user
than is known from the prior art.
[0017] Another problem is to develop a process in which the liquid
to be administered can be applied uniformly over the eye.
[0018] Another problem of the invention is to minimise
overdosing.
[0019] Yet another objective is to minimise the risk of injury to
the eye during application of the eye drops.
[0020] The present invention solves this problem by providing
atomizers which convert a small amount of the comparatively highly
concentrated formulation to be applied through a nozzle into a soft
spray mist with small particle sizes and travelling at low speed
and bring this spray mist into contact with the surface of the
eye.
[0021] The atomizers according to the invention comprise, close to
the nozzle from which the spray mist emerges, an adapter which
fixes the distance from the nozzle to the eye and prevents the
aerosol cloud from being blown away by wind.
[0022] Another criterion for these atomizers is that the pulse of
particles of spray mist leaving the adapter must not be so great
that the cornea can be damaged. In other words, the force with
which the aerosol mist hits the eye is not great enough to feel
unpleasant and make the patient close their eyelid.
[0023] In connection with the word "force" it should be noted that,
because of the large number of droplets arriving one after another
in an extremely short interval, it is not the force of the
individual droplets that matters but rather the force with which
the cloud of droplets as a whole strikes the eye.
DETAILED DESCRIPTION OF THE INVENTION
[0024] To guarantee this, the particles leaving the nozzle of the
atomizer must not exceed a certain mass and velocity, or the
atomizer and adapter must be constructed so that the speed of the
droplets leaving the nozzle is reduced accordingly, as they travel
from the nozzle to the eye. A spray duration of at least 0.5
seconds, preferably at least 1 second, is also important, as this
spreads the force of the droplets hitting the eye over a longer
period, thus reducing it, and any blinking that may occur during
this period will keep only a comparatively small proportion of the
cloud of droplets away from the eye.
[0025] The upper limit of the force of the cloud of droplets
hitting the eye should not exceed 5 milliNewtons, preferably 2.5
milliNewtons. Preferably, the force is on average less than 0.5
milliNewtons and more preferably less than 0.05 milliNewtons. Most
preferably, the process according to the invention produces a spray
mist which corresponds to an aerosol of water droplets with an
average diameter of about 2 to 20 microns.
[0026] The forces specified correspond to a pulse of the particles
with an upper limit of less than 5*10 ({circle over ( )}-4)
kilogram*metre per second (within the scope of the present
specification the symbol {circle over ( )} denotes the mathematical
term written as a superscript, i.e. for example 10 ({circle over (
)}-2) represents 0.01, etc.). Preferably, the pulse is on average
between 10 ({circle over ( )}-4) kilogram*metre per second and 10
({circle over ( )}-10) kilogram*metre per second, more preferably
not more than 5*10 ({circle over ( )}-5) kilogram*metre per second,
specifically 5*10 ({circle over ( )}-7) kilogram*metre per
second.
[0027] In the most preferred case, a soft spray mist is produced by
the process according to the invention which corresponds to an
aerosol of water droplets with a mean diameter of about 1-15
microns. The preferred particle size of the aerosol is 1 to 10
microns, more preferably 3 to 8 microns. All the data relating to
the particle size relates to the average particle size in the form
of the average aerodynamic diameter.
[0028] By the aerodynamic diameter is meant the kinetic diameter of
a gas particle or, as in this case, an aerosol droplet, which
corresponds to the diameter of a sphere with a density of 1 g
cm.sup.-3, which, under the effect of external mechanical forces in
equilibrium, has the same speed of migration relative to the
dispersing agent (gas or air in this case) as the particles under
investigation.
[0029] Within the scope of the present invention, the aerosol cloud
meets the surface of the eye at a distance from the nozzle of 1 to
5 cm, preferably 1 to 3 cm, most preferably 1.5 to 2.5 cm.
[0030] The applicator according to the invention is an atomizer
comprising an adapter around its nozzle for placing over the
eye.
[0031] The adapter is a cavity surrounded by a wall with two
openings. One opening surrounds the nozzle of the atomizer so that
a spray jet leaving the nozzle is conveyed exclusively into the
cavity. Preferably, the nozzle is centrally arranged within the
opening. Through the second opening, which is generally opposite
the first opening, the spray jet leaves the cavity to make contact
with the eye. The outer contour of the second opening is preferably
constructed so that it surrounds the visible part of the human eye,
preferably without pressing on the surface of the eye.
[0032] To meet this criterion, this second opening is preferably of
the following configuration, if the adapter is connected to the
atomizer:
[0033] In plan view the openings of the adapter are round to oval
in shape.
[0034] The opening closest to the eye is shaped so as to surround
the eye entirely, i.e. one part of the opening is longer than the
other. In cross section, the opening thus takes the form of a
concave line one end of which is at a greater spacing from the
nozzle than the other end.
[0035] In its simplest embodiment, the adapter is a funnel-shaped
tube with two opposite openings, the opening on the tapering side
surrounding the nozzle of the atomizer and thus being surrounded by
the nozzle opening of the adapter. The opening on the other side of
the adapter is large enough to fit round the outer contour of an
eye.
[0036] The adapter may be permanently connected to the atomizer via
the first opening, e.g. if the edge of this opening is welded onto
part of the inhaler or if the casing of the atomizer and the
adapter constitute a single component. The adapter is then an
integral part of the atomizer and this first opening is then in
practice only a non-open part of the atomizer.
[0037] The adapter may also be constructed as a detachable element.
In this case, the atomizer may have, close to the nozzle, one or
more projections onto which the adapter can be fitted over the
first opening. Such a projection may be, for example, a ring
surrounding the nozzle with a height ranging from a few mm to a few
cm (up to 5 cm), preferably with a height from 1-2.5 cm.
[0038] The side of the adapter attached to the atomizer may be
constructed so that it can be fitted directly onto the nozzle
holder or is fixed to another element in the vicinity of the
nozzle.
[0039] The other end of the adapter is constructed so that it can
be placed on a person's face in such a way as to completely
surround the visible part of the eye while covering as little of
the skin of the face as possible. This ensures that the majority of
the spray mist reaches the surface of the eye without wetting the
facial skin very much. Preferably, the opening on this side of the
adapter is oval.
[0040] On the outlet side of the adapter, openings may optionally
be formed in the side wall of the adapter through which excess
spray mist can escape. These openings preferably have a diameter of
up to 1 cm, more preferably up to 0.5 cm.
[0041] Moreover, the adapter is designed so that it cannot damage
the face or the eye.
[0042] Within the scope of the present invention, preferred
atomizers are those wherein a quantity of less than 100
microlitres, preferably less than 50 microlitres, most preferably
less than 20 microlitres of active substance solution can be
atomized by preferably one actuation to form an aerosol with an
average particle size of less than 20 microns, preferably less than
10 microns.
[0043] Preferably, atomizers as designated by the trade mark
Respimat.RTM. are used.
[0044] The method according to the invention is characterised inter
alia in that the quantity of formulation to be administered can be
restricted to a few microlitres.
[0045] An apparatus of this kind for propellant-free atomizing of a
metered amount of a liquid pharmaceutical composition is described
in detail, for example, in International Patent Application WO
91/14468 "Atomizing Device and Methods" and also in WO 97/12687,
cf. FIGS. 6a and 6b and the associated description. In an atomizer
of this kind, a pharmaceutical solution is converted into an
aerosol with an average particle size (average aerodynamic
diameter) of less than 20 microns, and sprayed, by the application
of high pressures of up to 500 bar. Reference is specifically made
to the abovementioned publications in their entirety for the
purposes of the present specification.
[0046] In atomizers of this kind, the solution formulations are
stored in a reservoir. It is essential that the formulations of
active substance used are sufficiently stable when stored and at
the same time are of a nature such that they can be administered
directly for the medical purpose in question, if possible without
any further manipulation. Moreover, they should not contain any
ingredients which could interact with the atomizer in such a way
that the atomizer or the pharmaceutical quality of the solution, or
of the aerosol produced, might be harmed.
[0047] To atomize the solution, a special nozzle is used as
described for example in WO 94/07607 or WO 99/16530, both of which
are specifically referred to at this point.
[0048] The preferred atomizer essentially consists of an upper
housing part, a pump housing, a nozzle, an adapter, a locking
mechanism, a spring housing, a spring and a storage container, the
outstanding features of the atomizer being:
[0049] a pump housing which is secured in the upper housing part
and which comprises at one end a nozzle body with the nozzle or
nozzle arrangement,
[0050] a hollow plunger with valve body,
[0051] a power takeoff flange in which the hollow plunger is
secured and which is located in the upper housing part,
[0052] a locking mechanism situated in the upper housing part,
[0053] a spring housing with the spring contained therein, which is
rotatably mounted on the upper housing part by means of a rotary
bearing,
[0054] a lower housing part which is fitted onto the spring housing
in the axial direction, and
[0055] an adapter in the form of a cavity with two opposite
openings, the smaller opening closely surrounding at least the
point of emergence of the aerosol from the nozzle and the larger
opening having a contour which enables this opening to be fitted
over an eye.
[0056] The hollow plunger with valve body corresponds to a device
disclosed in WO 97/12687. It projects partially into the cylinder
of the pump housing and is axially movable within the cylinder.
Reference is made in particular to FIGS. 1 to 4, especially FIG. 3,
and the relevant parts of the description. The hollow plunger with
valve body exerts a pressure of 5 to 60 MPa (about 50 to 600 bar),
preferably 10 to 60 MPa (about 100 to 600 bar) on the fluid,
comprising the measured amount of active substance solution, at its
high pressure end at the moment when the spring is actuated.
Volumes of 10 to 50 microlitres are preferred, while volumes of 5
to 20 microlitres are particularly preferred and a volume of 15
microlitres per spray is most particularly preferred.
[0057] The valve body is preferably mounted at the end of the
hollow plunger facing the valve body.
[0058] The nozzle in the nozzle body is preferably microstructured,
i.e. produced by microtechnology. Microstructured valve bodies are
disclosed for example in WO-94/07607; reference is hereby made to
the contents of this specification, particularly FIG. 1 therein and
the associated description.
[0059] The nozzle body consists for example of two sheets of glass
and/or silicon firmly joined together, at least one of which has
one or more microstructured channels which connect the nozzle inlet
end to the nozzle outlet end. At the nozzle outlet end there is at
least one round or non-round opening 2 to 10 microns deep and 5 to
15 microns wide, the depth preferably being 4.5 to 6.5 microns
while the width is preferably 7 to 9 microns.
[0060] In the case of a plurality of nozzle openings, preferably
two, the directions of spraying of the nozzles in the nozzle body
may extend parallel to one another or may be inclined relative to
one another in the direction of the nozzle opening. In a nozzle
body with at least two nozzle openings at the outlet end the
directions of spraying may be at an angle of 20 to 160.degree. to
one another, preferably 60 to 150.degree., most preferably 80 to
100.degree..
[0061] The nozzle openings are preferably arranged at a spacing of
10 to 200 microns, more preferably at a spacing of 10 to 100
microns, most preferably 20 to 50 microns. Spacings of 22 to 28
microns are most preferred. The jets will therefore meet directly
in front of the nozzle openings.
[0062] As already mentioned, the liquid pharmaceutical preparation
is under an entry pressure of up to 600 bar, preferably 200 to 300
bar, at the entry to the nozzle body and is atomized into an
inhalable aerosol through the nozzle openings. The preferred
particle sizes of the aerosol are up to 20 microns, preferably 3 to
10 microns.
[0063] The locking mechanism contains a spring, preferably a
cylindrical helical compression spring, as a store for the
mechanical energy. The spring acts on the power takeoff flange as
an actuating member the movement of which is determined by the
position of a locking member. The travel of the power takeoff
flange is precisely limited through two stops. The spring is
preferably biased, via a power step-up gear, e.g. a helical thrust
gear, by an external torque which is produced when the upper
housing part is rotated counter to the spring housing in the lower
housing part. In this case, the upper housing part and the power
takeoff flange have a single or multiple V-shaped gear.
[0064] The locking member with engaging locking surfaces is
arranged in a ring around the power takeoff flange. It consists,
for example, of a movable, mouldable ring of plastic or metal. The
ring is arranged in a plane at right angles to the atomizer axis.
After the biasing of the spring, the locking surfaces of the
locking member move into the path of the power takeoff flange and
prevent the spring from relaxing. The locking member is actuated by
means of a button. The actuating button is connected or coupled to
the locking member. In order to actuate the locking mechanism, the
actuating button is moved parallel to the annular plane, preferably
into the atomizer; this causes the ring to move in the annular
plane. Details of the construction of the locking mechanism are
given in WO 97/20590.
[0065] The lower housing part is pushed axially over the spring
housing and covers the mounting, the drive of the spindle and the
storage container for the fluid.
[0066] When the atomizer is actuated the upper housing part is
rotated relative to the lower housing part, the lower housing part
taking the spring housing with it. The spring is thereby compressed
and biased by means of the helical thrust gear and the locking
mechanism engages automatically. The angle of rotation is
preferably a whole-number fraction of 360 degrees, e.g. 180
degrees. At the same time as the spring is biased, the power
takeoff part in the upper housing part is moved along by a given
distance, the hollow plunger is withdrawn inside the cylinder in
the pump housing, as a result of which some of the fluid is sucked
out of the storage container and into the high pressure chamber in
front of the nozzle.
[0067] If desired, a number of exchangeable storage containers
which contain the fluid to be atomized may be pushed into the
atomizer one after another and used in succession. The storage
container contains the aqueous aerosol preparation according to the
invention.
[0068] The atomizing process is initiated by pressing gently on the
actuating button. As a result, the locking mechanism opens up the
path for the power takeoff member. The biased spring pushes the
plunger into the cylinder of the pump housing. The fluid leaves the
nozzle of the atomizer in atomized form.
[0069] Some of the elements of the atomizer which come into contact
with the liquid being administered as it travels from the storage
container to the nozzle may optionally be made of oligodynamically
active ingredients or may be coated with germicidal materials.
Alternatively or in addition, a germ-repellent filter may be formed
in this pathway. The advantage of such embodiments is that no germs
can get into the storage container from outside and therefore there
is no need to add preservatives. This is particularly advantageous
for long-term application, as already explained.
[0070] Further details of construction are disclosed in PCT
Applications WO 97/12683 and WO 97/20590, to which reference is
hereby made.
[0071] The components of the atomizer (nebulizer) are made of a
material which is suitable for its purpose. The housing of the
atomizer and, if its operation permits, other parts as well are
preferably made of plastics, e.g. by injection moulding. For
medicinal purposes, physiologically safe materials are used.
DESCRIPTION OF THE FIGURES
[0072] FIG. 1 diagrammatically shows an adapter (1) the lower part
(2) of which is placed on one or more projections disposed in a
circular to elliptical arrangement surrounding the nozzle or is
fixedly connected thereto.
[0073] The other end of the adapter (3) is constructed so that it
can be fitted over the eye socket like a negative.
[0074] As already indicated, the adapter may be of a kind in which
the pulse of the particles of spray mist is reduced, particularly
wherein the speed of the particles is reduced.
[0075] In the simplest case this is achieved by increasing the
distance between the two openings of the adapter.
[0076] FIGS. 2 and 3 show the atomizer with which the aqueous
ophthalmological aerosol preparations may advantageously be
administered to the eye.
[0077] FIG. 2 shows a longitudinal section through the atomizer
with the spring biased, while FIG. 3 shows a longitudinal section
through the atomizer with the spring relaxed.
[0078] The upper housing part (9) contains the pump housing (10) on
the end of which is mounted the holder (11) for the atomizer
nozzle. In the holder is the nozzle body (12) and a filter (13).
The hollow plunger (15) fixed in the power takeoff flange (14) of
the locking mechanism projects partially into the cylinder of the
pump housing. At its end the hollow plunger carries the valve body
(16). The hollow plunger is sealed off by means of the seal (17).
Inside the upper housing part is the stop (18) on which the power
takeoff flange abuts when the spring is relaxed. On the power
takeoff flange is the stop (19) on which the power takeoff flange
abuts when the spring is biased. After the biasing of the spring
the locking member (20) moves between the stop (19) and a support
(21) in the upper housing part. The actuating button (22) is
connected to the locking member. The upper housing part ends in the
outlet aperture (23) on which the adapter (1) is placed with its
small opening (2). Close to the opening (3) which faces the eye
during use, air vents (24) are provided. The open side of the
adapter can be closed off by a cover which completely surrounds the
openings (3) and (24) from the outside or inside, as selected (not
shown).
[0079] The spring housing (25) with compression spring (26) is
rotatably mounted on the upper housing part by means of the snap-in
lugs (27) and rotary bearing. The lower housing part (28) is pushed
over the spring housing. Inside the spring housing is the
exchangeable storage container (29) for the fluid (30) which is to
be atomized. The storage container is sealed off by the stopper
(31) through which the hollow plunger projects into the storage
container and is immersed at its end in the fluid (supply of active
substance solution).
[0080] The spindle (32) for the mechanical counter is mounted in
the covering of the spring housing. At the end of the spindle
facing the upper housing part is the drive pinion (33). The slider
(34) sits on the spindle.
[0081] The atomizer described above is suitable for atomizing the
ophthalmological aerosol preparations to produce an aerosol
suitable for administration to the eye.
[0082] Any known ophthalmologically active formulations are
suitable as the formulation which may be administered using the
atomizers according to the invention. These formulations may also
differ from the prior art in that the active substances may be more
highly concentrated if desired. As mentioned hereinbefore, the
quantity of formulation to be administered may be reduced by the
process according to the invention from about 50 microlitres in the
case of the devices known from the prior art to about 10-20
microlitres or less. This means that the active substance
formulations may be about five times more concentrated as a result
of the process according to the invention.
[0083] In the simplest case the formulation is simply water (water
for injections) or isotonic water or other agents for moistening
the eye. In other words, there is no pharmacologically active
substance present.
[0084] Suitable co-solvents may be, inter alia, ethanol,
polyethyleneglycols, polypropyleneglycols, ethyleneglycols and
propyleneglycols.
[0085] The active substances may be, for example, active substances
selected from among the antibiotics and anti-infective agents,
anticholinergics, antiglaucoma agents, antimycotics, antiseptics,
anaesthetics, eye tonics, corticoids and steroids, film-forming
agents, vaso-active substances, homoeopathic medicines, mydriatics,
NSAID (antiphlogistics), prostaglandins, artificial tears, vitamins
and/or virostatics.
[0086] Furthermore, any pharmacologically and ophthalmologically
acceptable pharmaceutical excipients may be added to the
formulations. These include inter alia arufil, benzalkonium
chloride, boric acid, calcium chloride, carbomer, chlorhexidine
digluconate, citric acid, EDTA, edetic acid salts; glucose,
glutathione disulphide, hydroxyethylcellulose, hypromellose,
potassium chloride, magnesium chloride, magnesium sulphate,
magrocol, mannitol, sodium acetate, sodium chloride, sodium
dihydrogen phosphate, sodium hydrogen carbonate, sodium hydroxide,
sodium monohydrogen phosphate, sodium tetraborate, sodium
thiosulphate, phenylmercury borate, polyethylene oxide,
polyoxyethylene-polyoxypropylene copolymer, polysorbate, polyvinyl
alcohol, povidone, hydrochloric acid, sorbitol, thiomersal and
tyloxapol.
[0087] In the case of formulations which contain preservatives,
benzalkonium chloride is preferred over EDTA and the salts
thereof.
[0088] Among the advantages of the process according to the
invention are the fact that:
[0089] the risk of irritation or damage to the cornea or the
conjunctiva of the eye is reduced when formulations are
administered to the eye in this manner;
[0090] ophthalmological formulations are applied uniformly to the
surface of the eye, thereby improving absorption by the cornea or
the conjunctiva;
[0091] the ophthalmological formulations can be more highly
concentrated than conventional eye drops, so that the cornea or
conjunctiva of the eye is or are subjected to smaller amounts of
unpleasant-feeling foreign matter;
[0092] the dosage can be reproduced very exactly;
[0093] the amount delivered is comparatively small;
[0094] overdosing is avoided;
[0095] systemic side effects are reduced as a result of the small
amount applied;
[0096] there is no need for a pumping action towards the eye in
order to initiate the spray jet, or the storage bottle has to be
pressed manually, i.e. there is no risk that the applicator will
accidentally be pressed into the eye;
[0097] no additional force is needed to trigger the spray, as the
processes of tensioning the device and administering the
formulation are separated from each other in time and
functionally;
[0098] each spray actuation is carried out consciously, so that the
patient knows how many actuations have been done;
[0099] the aerosol particles have a low pulse and meet the surface
of the eye with little force;
[0100] the spray duration is long-lasting and therefore the loss of
formulation caused by blinking is slight;
[0101] there is no need to recline the head to administer the
formulation;
[0102] there may not be any need for preservatives.
EXAMPLE
[0103] The volume of a spray jet delivered with the atomizer
described above, known by the trade mark Respimat.RTM. is e.g. 12
microlitres and the mass is therefore 0.000012 kg. At a distance of
2 cm from the nozzle the speed of the cloud of droplets as a whole
is 3.3 m/s and the pulse is roughly 0.0004 kg*m/s. With a spray
duration of 1.2 s a force K of 0.033 milliNewtons is thus obtained,
corresponding to a weight of about 3.3 mg.
[0104] By comparison, an atomizer which delivers a mass of 0.0001
kg of 0.1 ml and has an average spray duration of 0.12 seconds
would generate a cloud of particles with a force of 7.5
milliNewtons, corresponding to a weight of about 750 mg. This
presupposes that the nozzle diameter is 0.344 mm and the droplets
produced are 100 microns in size. This results in a speed of the
cloud of particles of about 9 m/s. The large droplets are hardly
slowed down at all before making contact with the eye.
* * * * *