EP1408899A1 - Nebuliseurs servant a appliquer des liquides sur la cornee - Google Patents

Nebuliseurs servant a appliquer des liquides sur la cornee

Info

Publication number
EP1408899A1
EP1408899A1 EP02754756A EP02754756A EP1408899A1 EP 1408899 A1 EP1408899 A1 EP 1408899A1 EP 02754756 A EP02754756 A EP 02754756A EP 02754756 A EP02754756 A EP 02754756A EP 1408899 A1 EP1408899 A1 EP 1408899A1
Authority
EP
European Patent Office
Prior art keywords
nebulizer
nozzle
adapter
eye
spring
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP02754756A
Other languages
German (de)
English (en)
Inventor
Bernd Zierenberg
Dieter Hochrainer
Isolde Martin
Michael Diestelhorst
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim Pharma GmbH and Co KG
Original Assignee
Boehringer Ingelheim Pharma GmbH and Co KG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boehringer Ingelheim Pharma GmbH and Co KG filed Critical Boehringer Ingelheim Pharma GmbH and Co KG
Publication of EP1408899A1 publication Critical patent/EP1408899A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
    • B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
    • B05B11/109—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle the dispensing stroke being affected by the stored energy of a spring
    • B05B11/1091—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle the dispensing stroke being affected by the stored energy of a spring being first hold in a loaded state by locking means or the like, then released
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/006—Sprayers or atomisers specially adapted for therapeutic purposes operated by applying mechanical pressure to the liquid to be sprayed or atomised
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0065—Inhalators with dosage or measuring devices
    • A61M15/0068—Indicating or counting the number of dispensed doses or of remaining doses
    • A61M15/007—Mechanical counters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
    • B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
    • B05B11/1042—Components or details
    • B05B11/108—Means for counting the number of dispensing strokes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
    • A61F9/0026—Ophthalmic product dispenser attachments to facilitate positioning near the eye
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H35/00—Baths for specific parts of the body
    • A61H35/02—Baths for specific parts of the body for the eyes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/006—Sprayers or atomisers specially adapted for therapeutic purposes operated by applying mechanical pressure to the liquid to be sprayed or atomised
    • A61M11/008—Sprayers or atomisers specially adapted for therapeutic purposes operated by applying mechanical pressure to the liquid to be sprayed or atomised by squeezing, e.g. using a flexible bottle or a bulb
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2210/00—Anatomical parts of the body
    • A61M2210/06—Head
    • A61M2210/0612—Eyes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
    • B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
    • B05B11/1001—Piston pumps
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/7722—Line condition change responsive valves
    • Y10T137/7837—Direct response valves [i.e., check valve type]
    • Y10T137/7904—Reciprocating valves
    • Y10T137/7908—Weight biased
    • Y10T137/7909—Valve body is the weight
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/7722—Line condition change responsive valves
    • Y10T137/7837—Direct response valves [i.e., check valve type]
    • Y10T137/7904—Reciprocating valves
    • Y10T137/7908—Weight biased
    • Y10T137/7909—Valve body is the weight
    • Y10T137/7913—Guided head
    • Y10T137/7915—Guide stem
    • Y10T137/7916—With closing stop

Definitions

  • the present invention relates to nebulizers for the application of liquids to the cornea or the eye connective tissue, special eyewear for nebulizers and the use of nebulizers for ophthalmological application.
  • the nebulizers according to the invention are free of propellant gas and have an energy store for providing the necessary energy for the nebulisation process.
  • aqueous formulation for the treatment of dry eyes, moistening of the ocular surface of contact lens wearers, many ophthalmic diseases or eye examination methods, medicaments are usually administered via an aqueous formulation as eye drops.
  • liquid dispensers have been developed in which the formulation is e.g. is discharged from a storage bottle via a spout (dropper bottles or EDO ophthiols).
  • the aqueous formulation usually flows from the spout opening due to manual pressure being exerted on the squeezable supply bottle. At this first forms a drop that breaks off only at a certain ratio between the size of the Tüllenö Maschinen Maschinen, surface tension and weight of the drop of the spout and then dripping into the eye.
  • aqueous eye drops have a volume of about 0.05 ml.
  • This method of dripping liquids onto an eye has several disadvantages.
  • Another disadvantage is that the applied formulation is initially applied only to one site of the cornea of the eye, which is not only because of the local pressure generated on the ocular surface is perceived as unpleasant.
  • the ocular surface is coated with a liquid film of about 7 microliters.
  • Each application of an additional liquid thus leads to the fact that a portion of the total liquid on the eye drains through the tear duct.
  • larger quantities of liquid such as e.g. Eye drops of 40 microliters and more can be applied.
  • a pharmacologically active fluid enters the lacrimal duct, it can be systemically ingested by the body, i. the pharmacologically active ingredients are absorbed directly by the body. This can lead to allergic or toxicological effects.
  • about 80% of the applied amount of liquid is displaced from the eye and thus reach partially into the tear duct.
  • Another disadvantage is that the patient must consciously fight against his blink reflex when he drops. If he does not succeed, he drips the application formulation not on the eye, but on the eyelid and he has to dribble again, which in turn leads to an overdose with the consequences described above and can cause unwanted systemic side effects.
  • Another disadvantage of this method is that it comes at the drop to a brief irritation of the eyes.
  • the conventional application devices are also not protected against the penetration of germs in the application formulation, so that the formulations preservatives must be added.
  • Preservatives may cause chronic inflammation of the connective tissue of the eye or the underlying tenon when used for long-term or chronic use. This can lead to morphological changes of these tissues, which are particularly at operations of great disadvantage, since the wound healing process is hindered and / or it can cause scarring.
  • US 5588564 discloses a pump spray provided with a cap for applying a spray to an eye. Since the spraying time of this system is short, there is a danger that the solution is not sprayed on the eye, but because of the blinking reflex on the eyelid. Neither the pump spray nor the attachment have facilities that can protect the eye from possible injury to the relatively hard spray.
  • US 5921444 discloses a spray device with an attachment for applying a liquid to an eye.
  • the disadvantages of this system are similar to those described above.
  • WO 96/00050 discloses an applicator for liquids on an eye, in which the spraying device lies within a housing, one side of which is adapted to comprise an eye.
  • the aerosol droplets generated by the device have a diameter of at least 20 microns.
  • the spraying time of this system is less than 1/20 second (page 13), which has the disadvantages described above.
  • EP 0911056 discloses a nebulizer for placement on an eye with an attachment having a baffle positioned so that the spray does not impinge directly on the cornea. Such protection pollutes but on the one hand very quickly and can only be cleaned poorly, on the other hand it prevents an exact and reproducible dosage.
  • the object of the present invention is to apply aqueous solutions or ophthalmologically effective formulations to the ocular surface by a single application form in such a way that the local irritation of a spot of the cornea is reduced compared to the usual application methods for eye drops.
  • a further object is to develop a method by which eye drops can be applied in a more comfortable way for the user than known from the prior art.
  • a further object is to develop a method in which the liquid to be applied is applied uniformly to the eye. can.
  • Another object of the invention is to minimize overdoses.
  • Another task is to minimize the risk of injury to the eye when applying the eye drops.
  • the present invention solves this problem by providing nebulizers which transfer a small amount of the relatively concentrated formulation to be administered via a nozzle into a soft spray cloud having small particle sizes and slow velocity and bringing this spray cloud into contact with the ocular surface.
  • the nebulizers according to the invention have, in the vicinity of the nozzle, from which the 0 spray cloud emerges, an adapter which fixes the distance nozzle eye and prevents blowing away of the spray cloud by wind. Another criterion for these nebulizers is that the momentum of particles of the cloud of mist emerging from the adapter is not so high that the cornea of the eye can be injured. In other words, the force with which the aerosol cloud hits the eye is not so high that it feels uncomfortable and therefore the eyelid is closed.
  • Droplets do not exceed a certain mass and velocity, or the nebulizer and adapters are designed to reduce the velocity of the droplets emerging from the nozzle on the way from the nozzle to the eye. Also important is a spraying time of at least 0.5 seconds, preferably at least 1 second, because on the one hand distributes the force of the impinging on the eye droplets over a longer period of time and thus less and on the other hand a possible eyelid during this time only a relatively small part the cloud of droplets away from the eye.
  • the upper limit of the force of the fog droplet cloud impacting the eye should not exceed 5 millinewtons, preferably 2.5 millinewtons.
  • the force is on average less than 0.5 millinewtons, and more preferably less than 0.05 millinewtons.
  • a spray is generated in the process according to the invention, which corresponds to an aerosol of water droplets with an average diameter of about 2 to 20 microns.
  • the indicated force values correspond to an impulse of the particles with an upper limit value of less than 5 * 10 ( ⁇ -4) kilogram * meter per second (in the context of the present invention description the sign ⁇ stands for the mathematical expression "high", ie for example 10 ( ⁇ -2) stands for 0.01 etc.). More preferably, the average pulse is between 10 ( ⁇ -4) kilograms * meters per second and 10 (O) kilograms * meters per second, more preferably it is at most 5 * 10 ( ⁇ -5) kilograms * meters per second, at 5 * 10 ( ⁇ -7) kilograms * meters per second.
  • the method according to the invention produces a soft spray which corresponds to an aerosol of water droplets with an average diameter of approximately 1-15 micrometers.
  • the preferred particle size of the aerosol is 1 to 10 microns, more preferably 3 to 8 microns. All particle size data refer to mean particle size in terms of mean aerodynamic diameter.
  • Aerodynamic diameter is understood to mean the kinetic diameter of a gas particle or aerosol drop corresponding to the diameter of a sphere of density 1 g cm "3 which, when exposed to external mechanical forces in equilibrium of forces, has the same migration rate with respect to the dispersion medium (here gas or air ) as the examined particles.
  • the aerosol cloud hits the ocular surface at a distance from the nozzle of 1 to 5 cm, preferably 1 to 3 cm, particularly preferably 1.5 to 2.5 cm.
  • the applicator according to the invention represents a nebulizer in which an adapter for placement on an eye is formed around its nozzle.
  • the adapter constitutes a cavity surrounded by a wall with two openings.
  • the one opening surrounds the nozzle of the nebulizer in such a way that a spray jet emerging therefrom is conducted exclusively into the cavity.
  • the nozzle is centrally surrounded by the opening.
  • the spray jet leaves the cavity to meet the eye.
  • the outer contour of the second opening is preferably formed so that it surrounds the visible part of the human eye, preferably without exerting pressure on the eye surface.
  • this second opening is preferably of the following shape when the adapter is connected to the nebuliser:
  • the openings of the adapter have a round to oval shape.
  • the eye-facing opening is shaped so that it completely encloses the eye, i. one part of the opening is drawn longer than the other.
  • the opening thus presents itself as a concave line, one end of which has a greater distance from the nozzle than the other end.
  • the adapter is a funnel-shaped tube with two opposite openings,. wherein the opening on the tapered side surrounds the nozzle of the nebulizer and is thereby encased by the nozzle opening of the adapter.
  • the opening of the other side of the adapter is so large that it encloses the outer contours of an eye.
  • the adapter may be permanently connected to the nebulizer via the first opening, e.g. in that the edge of this opening is welded onto a part of the nebulizer or in that the shell of the nebulizer and the adapter constitute a single element.
  • the adapter is then an integral part of the nebulizer and this first opening is in fact only a non-open portion of the nebulizer.
  • the adapter can also be designed as a removable element.
  • one or more projections are formed in the vicinity of the nozzle in the nebulizer, on which the adapter can be attached via the first opening.
  • a projection may, for example, be a ring extending around the nozzle and having a height of a few mm to a few cm (up to 5 cm), preferably a height of 1 to 2.5 cm.
  • the side of the adapter connected to the nebulizer can be designed so that it can be placed directly on the nozzle holder or attached to another element in the vicinity of the nozzle.
  • the other end of the adapter is designed so that it can be placed on a person's face in such a way that it completely surrounds the visible region of the eye lying in the face, covering as little facial skin as possible. This ensures that most of the spray reaches the ocular surface without significantly moistening the facial skin.
  • the opening of this side of the adapter is oval.
  • openings in the side wall can escape through the excess spray. These openings preferably have a diameter of up to 1 cm, more preferably of up to 0.5 cm.
  • the adapter is also such that it can not injure the facial skin or the eye.
  • nebulizers in which an amount of less than 100 microliters, preferably less than 50 microliters, more preferably less than 20 microliters of active substance solution, preferably one stroke to an aerosol with an average particle size of less than 20 microns , preferably less than 10 microns, can be atomized.
  • the method according to the invention is characterized i.a. characterized in that the amount of the formulation to be applied can be limited to a few microliters.
  • Such a device for propellant-free nebulization of a metered amount of a liquid drug is, for example, in the international Patent application WO 91/14468 "Atomizing Device and Methods" as well as in WO 97/12687, there Figures 6a and 6b and the associated description, described in detail.
  • a drug solution is transferred by means of a high pressure of up to 500 bar into an aerosol with an average particle size (average aerodynamic diameter) of less than 20 micrometers and sprayed.
  • average particle size average aerodynamic diameter
  • the solution formulations are stored in a reservoir. It is necessary that the active substance formulations used have a sufficient storage stability and at the same time are such that they can be applied directly for the medical purpose as far as possible without further manipulation. Furthermore, they must not contain any components which may interact with the nebulizer in such a way that the nebuliser or the pharmaceutical grade of the solution or of the aerosol produced could be damaged.
  • a special nozzle is used, as described, for example, WO 94/07607 or WO 99/16530, both of which are hereby expressly incorporated by reference.
  • the preferred nebulizer consists of a housing top, a pump housing, a nozzle, an adapter, a locking mechanism, a spring housing, a spring, and a reservoir, the salient features of the nebulizer being:
  • a pump housing which is fastened in the housing upper part and which carries at its one end a nozzle body with the nozzle or nozzle arrangement
  • a locking mechanism which is located in the upper part of the housing, a spring housing with the spring located therein, which is rotatably mounted on the upper housing part by means of a rotary bearing,
  • a housing lower part which is plugged onto the spring housing in the axial direction and - an adapter in the form of a cavity with two opposite
  • Openings wherein the smaller opening surrounds at least the exit point of the aerosol from the nozzle and the larger opening has a contour which makes it possible to put this opening over an eye.
  • the hollow piston with valve body corresponds to a disclosed in WO 97/12687 devices. It partially protrudes into the cylinder of the pump housing and is arranged axially displaceably in the cylinder. In particular, reference is made to FIGS. 1-4, in particular FIG. 3, and the associated parts of the description.
  • the hollow piston with valve body exerts on its high pressure side at the time of release of the spring 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, the measured drug solution , Volumes of from 10 to 50 microliters are preferred, with volumes of from 5 to 20 microliters being particularly preferred, and a volume of 15 microliters per stroke is particularly preferred.
  • the valve body is preferably attached to the end of the hollow piston, which faces the nozzle body.
  • the nozzle in the nozzle body is preferably microstructured, i. produced by microtechnology.
  • Microstructured nozzle bodies are disclosed, for example, in WO-94/07607; This document is hereby incorporated by reference, in particular to Figure 1 and the description thereof.
  • the nozzle body consists e.g. made of two firmly interconnected plates
  • Glass and / or silicon at least one plate of which has one or more microstructured channels communicating with the nozzle inlet side
  • nozzle outlet side Connect the nozzle outlet side.
  • the jet directions of the nozzles in the nozzle body can be parallel to one another or they are inclined towards one another in the direction of the nozzle opening.
  • the jet directions may be inclined at an angle of 20 degrees to 160 degrees to each other, preferably an angle of 60 to 150 degrees, particularly preferably 80 to 100 °.
  • the nozzle orifices are preferably located at a distance of 10 to 200 microns, more preferably at a distance of 10 to 100 microns, more preferably 20 to 50 microns. Most preferred are 22 to 28 microns.
  • the jets hit each other accordingly immediately in front of the nozzle openings.
  • the liquid pharmaceutical preparation is at an inlet pressure of up to 600 bar, preferably 200 to 300 bar, at the inlet of the nozzle body and is atomized via the nozzle openings into an inhalable aerosol.
  • the preferred particle sizes of the aerosol are up to 20 microns, preferably 3 to 10 microns.
  • the locking mechanism includes a spring, preferably a cylindrical helical compression spring, as a memory for the mechanical energy.
  • the spring acts on the output flange as a jump piece whose movement is determined by the position of a locking member.
  • the path of the output flange is precisely limited by two stops.
  • the spring is preferably transmitted via a force translating gear, e.g. a fferschubgetriebe, stretched by an external torque that is generated when turning the upper housing part against the spring housing in the lower housing part.
  • the upper housing part and the output flange contain a single or multi-start wedge gear.
  • the locking member with engaging locking surfaces is arranged annularly around the output flange. It consists for example of a sliding ring made of plastic or metal. The ring is arranged in a plane perpendicular to the atomizer axis. After the tensioning of the spring, the locking surfaces of the locking member push in the path of the output flange and prevent the relaxation of the spring.
  • the locking member is triggered by a button.
  • the release button is connected or coupled to the locking member.
  • the shutter button is parallel to the ring plane, and preferably in the atomizer, moved; while the ring is moved in the ring plane. Constructive details of the locking mechanism are described in WO 97/20590.
  • the lower housing part is pushed in the axial direction over the spring housing and covers the storage, the drive of the spindle and the reservoir for the fluid.
  • the upper housing part When actuating the atomizer, the upper housing part is rotated against the lower housing part, wherein the lower housing part entrains the spring housing.
  • the spring is compressed and tensioned via the screw slide, and the lock engages automatically.
  • the angle of rotation is preferably an integer fraction of 360 degrees, e.g. 180 degrees.
  • the driven part Simultaneously with the tensioning of the spring, the driven part is displaced in the upper housing part by a predetermined path, the hollow piston is withdrawn within the cylinder in the pump housing, whereby a subset of the fluid from the reservoir is sucked into the high-pressure chamber in front of the nozzle.
  • the storage container contains the aqueous aerosol preparation according to the invention.
  • the sputtering process is initiated by lightly pressing the shutter button.
  • the blocking mechanism clears the way for the stripping section.
  • the tensioned spring pushes the piston into the cylinder of the pump housing.
  • the fluid exits the nozzle of the atomizer in atomized form.
  • a portion of the elements of the nebulizer that come in contact with the liquid to be applied on its way from the reservoir to the nozzle be made of oligodynamically active ingredients or be coated with germicidal materials.
  • a germ repellent filter may be formed in this way.
  • Such embodiments have the advantage that no germs can penetrate from the outside into the pre-ram and thus can be dispensed with the addition of preservatives. This is particularly advantageous for long-term applications, as described above.
  • the components of the atomizer are made of a functionally suitable material.
  • the housing of the atomizer and, as far as the function permits, other parts are preferably made of plastic, e.g. by injection molding. Physiologically harmless materials are used for medical purposes.
  • FIG. 1 shows an adapter (1) is schematically shown, the lower region (2) is placed on one or more circular to elliptical projections in the vicinity of the nozzle or with this (this) is firmly connected.
  • the other end of the adapter (3) is designed so that it can be placed like a negative on the eye socket.
  • the adapter may be such as to reduce the momentum of the particles of the spray, in particular by reducing the velocity of the particles.
  • FIGS. 2 and 3 describe the nebulizer with which the aqueous ophthalmic aerosol preparations can advantageously be applied to the eye.
  • FIG. 2 shows a longitudinal section through the atomizer with the spring tensioned
  • FIG. 3 shows a longitudinal section through the atomizer with a relaxed spring.
  • the upper housing part (9) contains the pump housing (10), at the end of which the holder (11) for the atomizer nozzle is mounted.
  • the nozzle body (12) In the holder is the nozzle body (12) and a filter (13).
  • the hollow piston (15) fastened in the output flange (14) of the locking mechanism projects partially into the cylinder of the pump housing.
  • the hollow piston carries the valve body (16).
  • the hollow piston is sealed by means of the seal (17).
  • Within the housing upper part is the stop (18) on which the output flange rests with a relaxed spring.
  • the stop (19) At the output flange is the stop (19) on which the output flange rests when the spring is tensioned. After tensioning the spring, the locking member (20) slides between the stop (19) and a support (21) in the upper housing part.
  • the release button (22) is in communication with the locking member.
  • the upper housing part ends in the outlet opening (23), to which the adapter (1) with its small opening (2) is attached. In the vicinity of the opening (3) facing the eye in use, air outlet openings (24) are formed.
  • the open side of the adapter can be closed with a cap which optionally surrounds the openings (3) and (24) completely from outside or inside (not shown).
  • the spring housing (25) with compression spring (26) is rotatably mounted by means of the snap lugs (27) and pivot bearing on the upper housing part.
  • the lower housing part (28) is pushed.
  • the replaceable reservoir (29) for the fluid to be atomized (30).
  • the nebulizer described above is suitable for nebulizing the ophthalmic aerosol preparations to form an aerosol suitable for application to the eye.
  • all known opthalmologically active formulations are suitable. Such formulations may also differ from the prior art in that the active ingredients are optionally present in a higher concentration. As described above, the amount of the formulation of about 50 microliters to be applied in the case of the devices known from the prior art can be reduced to about 10-20 microliters and less by the method according to the invention. This means that the active substance formulations can be concentrated by about five times higher by the method according to the invention.
  • the formulation is merely water (water for injections), or isotonic water or other eye moisturizer. That a pharmacologically active substance is not available.
  • Suitable co-solvents include, inter alia, ethanol, polyethylene glycols, polypropylene glycols, ethylene glycols, propylene glycols.
  • Active ingredients include, for example, drugs from the group of antibiotics and anti-infectives, anticholinergics, Antiglaukomatosa, antifungals, antiseptics, anesthetics, eye tonics, corticosteroids and steroids, film formers, vascular active substances, homeopathic remedies, mydriatics, NSAID (anti-inflammatory drugs), prostaglandins, tear substitutes, vitamins and / or antivirals in question.
  • all pharmacologically and ophthalmologically compatible pharmaceutical excipients may be added to the formulations.
  • arufil benzalkonium chloride
  • boric acid calcium chloride, carbomer, chlorhexidine digluconate, citric acid, EDTA, editic acid salts
  • Glucose glutathione disulfide, hydroxyethyl cellulose, hypromellose, potassium chloride, magnesium chloride, magnesium sulfate, magrocol, mannitol, sodium acetate, sodium chloride, sodium dihydrogen phosphate, sodium bicarbonate, sodium hydroxide, sodium monohydrogen phosphate, sodium tetraborate, sodium thiosulfate, phenylmercuriborate, polyethylene oxide, polyoxyethylene-polyoxypropylene block polymer, polysorbate, polyvinyl alcohol, povidone, Hydrochloric acid, sorbitol, thimerosal, tyloxapol.
  • benzalkonium chloride is preferred over EDTA and its salts.
  • - ophthalmic formulations are applied evenly to the ocular surface to improve absorption through the cornea or connective tissue of the eye;
  • the ophthalmic formulations can be concentrated more highly than conventional eye drops, so that the cornea or the connective tissue is confronted with less foreign matter which is perceived as unpleasant;
  • the dosage can be reproducibly performed very accurately
  • each spray is done consciously so that the patient knows how many strokes he has performed; - the aerosol particles have a low momentum and hit the ocular surface with little force;
  • a reclination of the head for applying is not necessary; - If necessary, can be dispensed preservatives.
  • the volume of a ausense Sprüh Stammes with the previously described nebulizer the Respimat ® brand is for example, 12 microliters, and the mass thus 0.000012 kg.
  • the velocity of the cloud of droplets as a whole is 3.3 m / s and the momentum is about 0.0004 kg * m / s.
  • a spray duration of 1.2 s this results in a force K of 0.033 millinewtons corresponding to the weight of about 3.3 mg.
  • a nebulizer that exerts a mass of 0.0001 kg or 0.1 ml and has a mean spray time of 0.12 seconds would generate a particle cloud with a force of 7.5 millinewtons corresponding to the weight of about 750 mg. It is assumed that the nozzle diameter is 0.344 mm and the droplets produced have a size of 100 micrometers. This results in a particle cloud velocity of approx. 9 m / s. The large droplets are hardly slowed down until they hit the eye.

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Abstract

La présente invention concerne des nébuliseurs servant à appliquer des liquides sans agent conservateur sur la cornée ou sur le tissu conjonctif de l'oeil, lesdits nébuliseurs étant pourvus d'articles oculaires spécifiques, ainsi que l'utilisation de nébuliseurs en ophtalmologie. Les nébuliseurs de la présente invention sont exempts de gaz et possèdent un accumulateur d'énergie conçu pour fournir l'énergie nécessaire au processus de nébulisation.
EP02754756A 2001-06-29 2002-06-26 Nebuliseurs servant a appliquer des liquides sur la cornee Withdrawn EP1408899A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10131178 2001-06-29
DE10131178A DE10131178A1 (de) 2001-06-29 2001-06-29 Vernebler zur Applikation von Flüssigkeiten in die Augen
PCT/EP2002/007038 WO2003002045A1 (fr) 2001-06-29 2002-06-26 Nebuliseurs servant a appliquer des liquides sur la cornee

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EP1408899A1 true EP1408899A1 (fr) 2004-04-21

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EP (1) EP1408899A1 (fr)
JP (1) JP2004533304A (fr)
AR (1) AR034660A1 (fr)
CA (1) CA2451835A1 (fr)
DE (1) DE10131178A1 (fr)
MX (1) MXPA03011454A (fr)
PE (1) PE20030523A1 (fr)
WO (1) WO2003002045A1 (fr)

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WO2003002045A1 (fr) 2003-01-09
PE20030523A1 (es) 2003-07-01
CA2451835A1 (fr) 2003-01-09
US20080097359A1 (en) 2008-04-24
US7314187B2 (en) 2008-01-01
US20030078551A1 (en) 2003-04-24
JP2004533304A (ja) 2004-11-04
US20060258993A1 (en) 2006-11-16
US20040010239A1 (en) 2004-01-15
MXPA03011454A (es) 2004-04-05
DE10131178A1 (de) 2003-01-16
AR034660A1 (es) 2004-03-03

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