(19) TZZ_Z_T

(11) EP 1 450 885 B1

(12) EUROPEAN PATENT SPECIFICATION

(45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61M 15/08 (2006.01) A61M 11/00 (2006.01) 22.04.2015 Bulletin 2015/17 A61M 15/00 (2006.01) A61M 16/06 (2006.01)

(21) Application number: 02778422.2 (86) International application number: PCT/US2002/031450 (22) Date of filing: 30.09.2002 (87) International publication number: WO 2003/026559 (03.04.2003 Gazette 2003/14)

(54) NASAL NASALER VERNEBLER NEBULISEUR NASAL

(84) Designated Contracting States: (56) References cited: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR EP-A- 0 539 674 EP-A- 0 734 719 IE IT LI LU MC NL PT SE SK TR EP-A- 0 747 078 WO-A-01/36033 WO-A-01/49350 WO-A-98/26827 (30) Priority: 28.09.2001 US 325971 P WO-A-99/47273 GB-A- 1 069 048 09.05.2002 US 379428 P US-A- 3 362 405 US-A- 4 299 784 US-A- 4 454 880 US-A- 4 461 425 (43) Date of publication of application: US-A- 4 809 692 US-A- 5 203 323 01.09.2004 Bulletin 2004/36 US-A- 5 309 900 US-A- 5 435 282 US-A- 5 458 135 US-A- 5 485 828 (73) Proprietor: Kurve Technology, Inc. US-A- 5 577 497 US-A- 5 755 218 Lynnwood, WA 98036 (US) US-A- 5 785 049 US-A- 5 855 202 US-A- 5 950 623 US-A- 6 112 746 (72) Inventor: GIROUX, Marc US-B1- 6 202 643 US-B1- 6 240 917 Lynnwood, WA 98036 (US)

(74) Representative: EP&C P.O. Box 3241 2280 GE Rijswijk (NL)

Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 1 450 885 B1

Printed by Jouve, 75001 PARIS (FR) 1 EP 1 450 885 B1 2

Description [0007] WO-A-99/47273 discloses a medication processing system and method, wherein a vortex cham- BACKGROUND ber is provided, which enables a turbulent flow and which substantially eliminates the formation of orbital [0001] This invention relates to devices for administra- 5 rings on the inner walls put in the vortex chamber. tion of therapeutic agents to the nasal cavity and para- [0008] WO-A-98/26827 discloses a , in nasal sinuses of a patient. which a circulatory section and a cyclone chamber are [0002] In the United States, sixty million people suffer provided for effecting separation of the heavier particles from chronic and allergic and are treated from lighter particles. The circulating flow is arranged so by means of , antibiotics, , 10 that the air/powder mixture enters the cyclone chamber and pain relievers. Many of these would work more at relatively high speed. effectively in relieving symptoms if they could be directly applied to all of the affected areas. However, the devices SUMMARY OF THE INVENTION utilized thus far to deliver these drugs have proven to be extremely inadequate, if not useless, in reaching all areas 15 [0009] The invention provides a particle dispersion needed especially the deep nasal cavity and paranasal chamber comprising a housing having an external sur- sinuses where it is critical in the treatment of some of face and an internal channel having a user output open- these diseases. There is a need for a more effective de- ing, and a plurality of directional air outputs positioned vice to administer these medicines to all the areas of the along and communicating with the internal channel, the nasal cavity and paranasal sinuses. 20 direction of the air outputs suitable to create a vortical [0003] A current delivery system consists of a pressu- flow of aerosolized particles within the internal channel, rized canister (MDI) that ejects the medicine into the nos- and is characterized in that said internal channel of the trils in short bursts, or streams of atomized liquid in an particle dispersion chamber is configured as vortex con- aqueous nasal spray. The efficacy of medicine adminis- tinuing channel to provide for continuation of the vortical tered in this manner is limited due to difficulties in the 25 flow from the air outputs to and including the user output medicine reaching very little of the nasal mucosa and no openingsuch thatsaid aerosolized particles emerge from part of paranasal sinuses where it needs to be delivered said particle dispersion chamber in said vortex move- to fully treat the condition. In cases of severe congestion ment. or nasal polyps, the medicine often does not proceed beyond the nostril and will not be effectively absorbed 30 BRIEF DESCRIPTION OF THE DRAWINGS into the bloodstream or the necessary area of the nasal cavity and paranasal sinuses. Current systems also do [0010] The foregoing aspects and many of the attend- not allow particle sizes to be small enough to reach high ant advantages will become more readily appreciated as into the nasal cavity and paranasal sinuses. There is a the same become better understood by reference to the need for delivery system alternatives to better deliver 35 following detailed description, when taken in conjunction more of the medicine to the nasal cavity and paranasal with the accompanying drawings, wherein: sinuses and of the sufferers of these diseases, and oth- ers. FIGURE 1 is a top planar view of one embodiment [0004] A nebulizer is, for example, a machine that con- of the nasal nebulizer; verts medicine into a mist, or vapor, of very tiny particles 40 to deliver a to the lungs during an attack by breathing FIGURE 2 is a frontal elevational view of the nasal the medicine from a pipe attachment or, in the case of nebulizer; young children, a face mask. The particle size is impor- tant in that it allows passage of the drug through heavily FIGURE 3 is a side elevational view of the nasal congested airways over a period of about 10 minutes 45 nebulizer; which allows for deep penetration. are used by asthmatics in case of an asthma attack. FIGURE 4 is a bottom planar view of the nasal neb- [0005] Nasal nebulizers are currently in use for antibi- ulizer; otics and are ineffectively delivered due to the fact they do not deliver into the paranasal sinuses nor as far into 50 FIGURE 5 is a side cross-sectional view of the nasal the nasal cavity as this device due to the lack of additional nebulizer of Fig. 1 along line A-A showing internal technology enclosed herein. components thereof; [0006] WO-A-01/36033 discloses an internal vortex mechanism for an inhaler device. The vortex mechanism FIGURE 6 is a front view of one embodiment of the is provided to obtain a circumferential-swirling turbulent 55 nasal adapter; boundary layer flow along the inner surface of a chamber in order to limit impaction and sticking of medication to FIGURE 7 is a rear view of the nasal adapter; the inner surface of the chamber.

2 3 EP 1 450 885 B1 4

FIGURE 8 is a side view of the tubing and nasal DETAILED DESCRIPTION OF THE PREFERRED EM- adapter; BODIMENT

FIGURE 9 is a side view of another embodiment of [0011] Current methods are ineffective the nebulizer showing the cartridge chamber; 5 at penetrating very far into the nasal cavity and not at all into the paranasal sinuses. The nebulizer 25 has the abil- FIGURE 10 is a top view of the nebulizer showing ity to deliver the same drugs presently prescribed for dis- the cartridge chamber; eases as very tiny particle doses of medicine via a nasal adapter 10 that allows more efficacious sinus penetration FIGURE 11 shows one embodiment of the particle 10 for the user. The particle sizes, time of application and dispersion chamber, the tubing, and the nasal adapt- particle dispersion technology allows the medicine to per- er; meate the nasal cavity and most of the paranasal sinus- es. All medicines currently applied by direct action to the FIGURE 12 shows a further embodiment of the nasal nasal cavity and paranasal sinuses could be adapted for adapter, particle dispersion chamber, and tubing; 15 use with the nebulizer 25, and that would include over- the-counter nasal medicines for allergy and colds and flu. FIGURE 13 shows yet another embodiment of the [0012] For the user with the secondary condition of na- nasal adapter, particle dispersion chamber, and tub- sal polyps, this allows far more effective application of ing; the medicine, which is often blocked by the polyp from 20 penetrating even as much as the contemporary systems FIGURE 14a shows another embodiment of the na- can. -based are designed to also sal adapter, particle dispersion chamber, and tubing; slow the re-growth of these polyps following their remov- al. Currently, they are largely ineffective at accomplishing FIGURE 14b shows a bottom view of one embodi- this, often not being able to slow the growth at all. The ment of the baffle; 25 apparatus and method described herein will be signifi- cantly more effective in slowing the re-growth of the pol- FIGURE 15 shows yet another embodiment of a na- yps following their removal. sal adapter, particle dispersion chamber, and tubing; [0013] Many of the side effects of some medicines are eradicated by this method. With many sprays, the pro- FIGURE 16 shows an inhaler with one embodiment 30 pellant causes a drying of the nasal passages leading to of a particle dispersion chamber. bleeds. With the use contemporary devices that lead to bleeds, a secondary spray of is added to the treat- FIGURE 17 shows a nasal spray with one embodi- ment in order to try and control the bleeding. Further, ment of a particle dispersion chamber. steroids in pill form have many unpleasant side effects 35 such as internal bleeding, a redistribution of fluid to the FIGURE 18 shows a nasal inhaler with one embod- head, neck and back causing unsightly "humps," and iment of a particle dispersion chamber. easy bruising, to name a few. An effective use of the nebulizer 25 does not have these side effects associated FIGURE 19 shows a dry powder spinhaler with one with steroids in pill form. embodiment of a particle dispersion chamber. 40 [0014] The nebulizer 25 will allow medicine to be ad- ministered to the nasal cavity and paranasal sinuses via FIGURE 20 shows a dry powder inhaler with one very small particles that will penetrate deeply into the embodiment of a particle dispersion chamber. nasal cavity and most regions of the paranasal sinuses. It will also expose the patient to a more effective absorp- FIGURE 21 shows the results of a sinus ventilation 45 tion of the drug, increasing effectiveness, and will allow study using a prior art drug delivery apparatus; and multiple conditions to be treated in a far more effective manner. Since the medicine is delivered in a treatment FIGURE 22 shows the results of the sinus ventilation and not an attack scenario, the application or delivery study using an embodiment of the nebulizer with a time is only 2-3 minutes rather than the 10-15 minutes particle dispersion chamber for delivery of medica- 50 used during an asthma attack. Multiple dose levels of the ment to the sinus cavity. medicine will be placed in the nebulizer 25, a week supply for example, and the unit will run for a prescribed time, FIGURE 23 shows a side view of one embodiment for example but not limited to three minutes, and will then of the cartridge. shut itself off. The machine will be designed with multiple 55 dose capability and a timer 4 with a pause feature 5. The FIGURE 24 shows a prior art cartridge. pause feature 5 allows the user to stop the treatment under way to deal with a short, minor happenstance and then resume the treatment for the remaining time. The

3 5 EP 1 450 885 B1 6 timer 4 will be variable to accommodate the drug being occasional use as originally intended. As shown in Figure administered and/or prescribed by the physician. 2, in one embodiment, it has been designed thinner and [0015] The nebulizer25 is capable ofdelivering particle shorter with a hip-hugging curve 7 when in use in hands- sizes ranging from 2-50 microns, and in anther aspect, free position. As shown in Figure 8, for hands-free oper- from 2-15 microns, in order to keep the medicine inside 5 ation, the nasal adapter is equipped with elastic bands the nasal cavity and the sinus chambers and prevent too 17 that go around the head to hold the adapter in place much from passing through the chambers and into the while the treatment is delivered. As shown in Figure 5, lungs. the nasal adapter can be attached to a hose 9 built into [0016] Referring now to the accompanying drawings, the device that can extend the reach to a standing person as shown in Figures 6-8, a nasal adapter 10 has been 10 or a sitting person. In one aspect, the hose 9 is an ac- designed to attach to the outflow tube 15 of the nebulizer cordion hose. In another embodiment, it can also be op- 25 to allow it to fit over the nasal openings and the nose erated with the nasal adapter 10 attached directly to the itself restricting the flow of medicine to the nose alone. unit outflow and held by hand to the nose for the duration The nasal adapter 10 limits various unwanted occurrenc- of the treatment. es such as delivery of any medicament to the eyes and 15 [0020] As shown in Figure 4, an additional feature will face surrounding the nose and into the general environ- be the multiple dose compartment 8 arrangement in ment. which multiple doses of a medicament or compound may [0017] Use of a nasal adaptor 10 also limits the spread be placed inside the nebulizer 25. For example, in the and growth of bacteria or microorganisms. Use of a nasal case of chronic sinusitis, a week’s worth of medicine will adaptor 10 that fits over the nasal openings reduces the 20 be placed into the nebulizer 25. As shown in Figure 3, spread of bacteria that can be picked up from inside the the nebulizer 25 has been designed with a timer 4 so that nasal openings into or onto the delivery device if the nasal it will run for a programmed period of time and then turn adaptor 10 were placed inside the nasal openings as is itself off. As shown in Figure 3, a pause feature 5 has the case with current MDI’s or AQ sprays. Further, use been added to allow for dealing with minor disturbances of a disposable nasal adaptor 10 that fits over the nasal 25 and then resuming the treatment The time allotted will openings reduces the occurrence of re-inoculation of the depend upon the optimum time needed for the drug being nasal openings with bacteria present on a nasal adaptor dispensed and it has been designed to prevent evapo- 10, when not properly cleaned, is reinserted into the nasal ration for the duration of the predetermined supply. As openings. Also, use of a disposable nasal adaptor 10 that shown in Figure 10, the device can also be used in a fits over the nose reduces the extent of bacteria or mi- 30 single-dose application. croorganisms picked up from inside the nasal openings [0021] Figures 9 and 10 show one embodiment of the which can grow in the any tubing 80 associated with the nebulizer 25. The nebulizer 25 may have a variety of nebulizer 25. dimensions but in one aspect, the nebulizer 25 is approx- [0018] As shown in Figure 7, the nasal adapter 10 has imately 76.2 mm (three inches) wide and approximately been designed with a lip 14 of material to seal the area 35 132 mm (four inches) high. The nebulizer 25 will generally around the nose keeping the aerosolized medicine away include a power supply 30, a pump 35, a pump connector from the eyes and restricting the flow to the nasal pas- 40, a medicine chamber 45, a lid 50 for covering the med- sages. Inone aspect of this embodiment, the nasal adapt- icine chamber and a nebulizing stem 55 for introduction er 10 is approximately 38.1 mm (1 © inches) wide across into a cartridge 60 inserted into the medicine chamber the bridge of the nose and 38.1 mm© ( inches) long. 40 45. A nasal adapter 10 of varying sizes is associable with Other dimensions for the bridge width and length are en- the nebulizer 25. visioned. Further, in one aspect of the lip 14, the lip 14 [0022] Figure 23 shows one embodiment of the car- on the nasal adapter 10 is approximately 31.8 mm (1/8 tridge 60. The cartridge 60 is shaped so that it fits into inch) long and is capable of forming a seal between the the medicine chamber 45 and can spin freely therein. It nasal adapter 10 and the face surrounding the nose. Oth- 45 is provided with an opening 65 so that the nebulizing er lip 14 widths are envisioned. In one aspect of this em- stem 55 can be introduced into the cartridge 60 and ac- bodiment, the outflow tube 15 has an internal diameter cess the medicament contained in the cartridge 60 of 14.3 mm (9/16 of an inch) and is tapered to fit or co- through the opening 65. Figure 23 shows the cartridge operate with the hose 9. Other diameters of the outflow 60 for use with the nebulizer 25. As shown in Figure 23, tube 15 are envisioned and the device is not to be re- 50 the cartridge 60 is generally a three-dimensional octag- stricted to the above-mentioned diameter. As shown in onal shape filled with a medicament. In one embodiment, Figure 8, in one aspect, the nasal adapter 10 has been the cartridge 60 is formed from plastic, preferably biode- designed with exhaust valves or vent holes 13 on either gradable. As shown in Figure 24, the prior art cartridges side below the curve of the nose allowing necessary vent- for containing medicament are generally of three-dimen- ing while keeping the aerosolized medicine away from 55 sional shape and have a twist opening located at the the eyes. proximal or distal end of the cartridge. Rather, the im- [0019] The nebulizer 25 has been greatly improved by proved cartridges 60 may have a twist opening located being designed to accommodate daily use rather than on the surface of one of the octagons forming the top and

4 7 EP 1 450 885 B1 8 bottom of the cartridge. In another embodiment, the car- a particle dispersion chamber 85. The particle dispersion tridge 60 may have a weakened perforated area on the chamber 85 is associated with a nasal adapter 10. As surface of the cartridge 60 through which the nebulizing the nebulized particles travel from the medicine chamber stem 55 can be easily introduced. As shown in Figure 45 through the compressed air tubing 80, they reach the 23, the novel shape of the cartridge 60 allows for it to fit 5 particle dispersion chamber 85. As the particles are within the medicine chamber 45 of the nebulizer 25. The passed through the particle dispersion chamber 85, they cartridge 60 then sits in the medicine chamber 45 and is are swirled into a vortex and emerge from the chamber capable of spinning while seated in the medicine cham- 85 while still in the vortex into the nasal cavity and the ber 45. The nebulizing stem 55 can be introduced into paranasal sinuses. In this process, the individual parti- the cartridge 60 at the cartridge opening 65 caused by 10 cles are themselves caused to spin and are caught up in the removal of the twist-off cap 70. Using the cartridge the vortex. The particles advantageously enter the nasal 60 in the nebulizer 25 facilitates the delivery of proper cavity at many angles. The particles also bounce or ric- dosage by providing a cartridge 60 pre-packaged with a ochet within the nasal cavity allowing the particles to proper dosage amount; the dosage being variable by reach previously impossible areas. medicament, ailment, patient and the like. Also, the car- 15 [0026] In one embodiment of the particle dispersion tridge 60 facilitates the use of the nebulizer 25 with a chamber 85 as shown in Figure 11, as the particles exit variety of various medicaments. Since the cartridge 60 the compressed air tubing 80 and enter the particle dis- is placed into the medicine chamber 45, the medicine persion chamber 85, they come into contact with a variety chamber 45 itself does not fill with a variety of different of air outputs 90. The air outputs 90 may be positioned medications. This eases the cleaning process of the med- 20 either randomly along the particle dispersion chamber icine chamber 45. It also prevents the intermixing of dif- 85 or in a set array. The air outputs 90 are, for example, ferent medicaments in the medicine chamber 45. For ex- a plurality of air jets which spurt, blow or vent, or the like, ample, by using the cartridge 60, the same nebulizer 25 into the particle dispersion chamber 85 and cause the can be used to deliver two different medications at dif- nebulized particles within the chamber 85 to randomly ferent times to different patients with more certainty that 25 move in a vortex. This random movement of the particles the different medications would not intermix in the med- in a vortex continues while the particles travel through icine chamber 45. Without the use of the cartridge 60, the nasal adapter 10, eventually into the nose and into when the medicine chamber 45 is filled first with one med- the nasal cavity and paranasal sinuses. icament and later with another medicament for delivery [0027] In a further embodiment, as shown in Figure 12, via use of the nebulizer 25, if the medicine chamber 45 30 the nebulized particles once again travel through the tub- is not properly and thoroughly cleaned, the two different ing 80 and into the particle dispersion chamber 85. In the medicamentsinserted into the medicinechamber 45 may embodiment shown in Figure 12, the particle dispersion intermix, causing possibly hazardous or toxic situations. chamber 85 contains at least an air output 90 and a dis- The use of the cartridge 60 greatly reduces the chances persion blade 95. The dispersion blade 95 may have solid of intermixing of two medicaments and facilitates or in- 35 blades or blades made of netting or openings. Movement creases the ease of cleaning of the medicine chamber 45. of the dispersion blade 95 is created through spurts or [0023] Inother embodiments, rather thanusing thecar- jets of air exiting from the air output 90. Alternatively, tridge 60, the nebulizer 25 is capable of accepting a multi- movement of the dispersion blade 95 can be created us- dose cartridge 75. In use, the multi-dose cartridge 75 ing a motor. A variety of other equivalent movement may be filled with, for example, a week’s supply of a par- 40 mechanisms varying from magnetic to a wind-up spring ticular medicament. The nebulizer 25 would then be pro- can be used to create movement of the dispersion blade vided with a dosing system so that each time medicament 95. As the dispersion blade 95 rotates within the particle is dispensed from the multi-dose cartridge 75, it is dis- dispersion chamber 85, the nebulized particles exiting pensed in a dose-specific amount. In other aspects of from the tubing 80 into the dispersion chamber 85 come this embodiment, the multi-dose cartridge 75 may be45 into contact with the movement from the dispersion filled with enough medicament for a daily dose, bi-weekly blades 95 and are caused to randomly move within the dose, a weekly dose, a bi-monthly dose, and other variety dispersion chamber 85 in a vortex. As the particles exit of dosage amounts. the particle dispersion chamber 85 and the nasal adapter [0024] In another aspect of the embodiment of the car- 10, they enter the nasal cavity and paranasal sinuses tridge 60, it is envisioned that the cartridge 60 may be an 50 and the paranasal sinuses still exhibiting random motion octagonal shape, a circular shape, an oval shape, and in the vortex. any other variety of shape which would be cooperative [0028] As shown in Figure 13, a plurality of dispersion with the medicine chamber 45. blades 95 and outlets 90 may be located in the particle [0025] As shown in Figures 11-15, the nebulizer 25 dispersion chamber 85. This plurality of blades 95 may includes a tube 80 for delivering compressed air in co- 55 rotate all clockwise, all counterclockwise, or in opposite operation with nebulized particles from the medicine directions from one another around an axis of rotation. chamber 45. The tube 80 may also deliver any other gas The dispersion blades 95 create motion of the nebulized or combination of gases. The nebulizer 25 also includes particles in a vortex within the particle dispersion cham-

5 9 EP 1 450 885 B1 10 ber 85. The nebulized particles exit the particle dispersion chamber 85 can be associated with the nasal spray in- chamber 85 and nasal adapter 10 still in a vortex and haler 125. enter into the nasal cavity and paranasal sinuses. [0034] Figure 18 shows an inhaler 110 having a pump [0029] In the embodiment shown in Figure 14, the neb- 35, a pressurized canister 115 of medicine, and an ac- ulized particles exit the tubing 80 and come into contact 5 tuator 120. To the inhaler 110 can be attached a particle with a baffle 100 located in the particle dispersion cham- dispersion chamber 85. The embodiment of Figure 18 ber 85. The baffle 100 is shaped so as to create move- shows an inhaler 110 having a particle dispersion cham- ment of the particles while in a vortex. As shown in Figure ber 85 with a plurality of air outports 90, although other 14,the baffle 100 isgenerally serpentine shape. Although embodiments of the particle dispersion chamber 85 can in Figure 14 the baffle 100 is shown in a generally ser- 10 be associated with the inhaler 110. pentine or helix shape, it is understood that any baffle [0035] Figure 19 shows a dry powder inhaler 135 hav- 100 shape which would create motion of the nebulized ing a mouthpiece 11 and a pump 35. To the dry powder particles in a vortex as they exit the dispersion chamber inhaler 135 can be attached a particle dispersion cham- 85 is equivalent. For example, a helixical shaped baffle ber 85. The embodiment of Figure 19 shows the dry pow- 100 may create motion of the particles in a vortex. 15 der inhaler 135 having a particle dispersion chamber 85 [0030] The embodiment shown in Figure 15 includes with a plurality of air outports 90, although other embod- a particle dispersion chamber 85 having a plurality of iments of the particle dispersion chamber 85 can be as- directional output nozzles 105. The directional output sociated with the dry powder inhaler 135. nozzles 105 spray, spurt, vent, jet, or the like, air into the [0036] Figure 20 shows a dry powder inhaler 140 hav- particle dispersion chamber 85 so as to create a vortex 20 ing a mouthpiece 11 and a pump 35. To the dry powder of nebulized particles. The particles remain in a vortex inhaler 140 can be attached a particle dispersion cham- and continue to travel in a manner even when exiting the ber 85. The embodiment of Figure 20 shows the dry pow- particle dispersion chamber 85 and introduced into the der inhaler 140 having a particle dispersion chamber 85 nasal cavity and paranasal sinuses. with a plurality of air outports 90, although other embod- [0031] The particle dispersion chambers 85 described 25 iments of the particle dispersion chamber 85 can be as- herein can also be adopted for use with current pressu- sociated with the dry powder inhaler 135. In a pulmonary rized canister inhalers, dry powder inhalers, inhaler and application using a dry powder inhaler 140, the particle other mechanisms for which medicine is breathed dispersion chamber 85 serves to break down the parti- through the nose, mouth, or both including inhaling and clesfurther reducing clumping and increasing theamount exhaling through the same orifice or alternating between 30 that reaches the lungs. In pulmonary inhaler versions, the orifices. A small pump 35, either hand-primed, elec- the medicament is greater dispersed and increases the tric, or battery powered or otherwise, is attached to a opportunities for it to get into the throat without been housing and is prepared to be actuated. Tubing 80 which blocked by the tongue. leads to air ports 90 lead from the pump 35 to a particle [0037] In an embodiment, there are two air outputs 90, dispersion chamber 85 placed over the exit off the actu- 35 or jets, and a third jet is used to spin the particles prior ator 120. The pump fires when the unit is actuated and to them entering the chamber 45. This is designed to get creates a vortex of the particles prior to the medicament the individual particles spinning prior to being put into the entering the nostril where it can be swirled into the nasal vortex in the chamber 45. This will allow the particles to cavity. The pump 35 can be fired by hand and timed with get better "bounce" in the nasal cavity and deeper pen- the breathing process of the user with such versions as 40 etration and larger coverage area into the nasal cavity a dry powder inhaler which uses the user’s breathing to and the sinuses. This will be done for specific medica- release the powder into the system. ments that could benefit from this action and will be turned [0032] Figure 16 shows an inhaler 110 having a mouth- off for medicaments that would not benefit from it. piece 11, a pump 35, a pressurized canister 115 of med- [0038] In another embodiment, prior to the nebulized icine, and an actuator 120. To the inhaler 110 can be 45 particles entering the dispersion chamber 85, they will attached at the mouthpiece 11 a particle dispersion pass through a charge station where they will gain a neg- chamber 85. The embodiment of Figure 16 shows an ative or positive charge which causes the particles to inhaler 110 having a particle dispersion chamber 85 with repel each other and does not allow them to recombine a plurality of air outports 90, although other embodiments into larger particles. This will cause the particles to repel of the particle dispersion chamber 85 can be associated 50 each other in the chamber 85, the nasal cavity, and si- with the inhaler 110. nuses allowing for deeper penetration and larger cover- [0033] Figure 17 shows a nasal spray 125 having a age area. This will be done for specific medicaments that pump 35, a particle dispersion chamber 85 with a plurality could benefit from this action and will be turned off for of air ports 90, a nasal spray actuator 120, and a nasal medicaments that would not benefit from it. spraymedicine container130. The embodimentof Figure 55 [0039] In one manner of operation, a cartridge 60 con- 17 shows a nasal spray inhaler 125 having a particle taining a medicament or the medicament itself is placed dispersion chamber 85 with a plurality of air outports 90, into the medicine chamber 45 of the nebulizer 25 shown although other embodiments of the particle dispersion in Figure 1. The nasal adapter 10 is fitted over the nose

6 11 EP 1 450 885 B1 12 of the user and the nebulizer 25 is activated. The user should follow with one to four slow, long deep breaths breathes using the BT. More particularly in operation: through the nose. Preferably, the user should follow with three long, slow, deep breaths through the nose. More 1. In Figure 1, the lid 50 is lifted to the medicine cham- preferably, the user should follow with two long, slow ber 45 and the prescribed dosage of medicine is 5 deep breaths through the nose. Most preferably, the user poured in. The lid 50 is then closed. should follow with one long, slow, deep breath through the nose. The above discussed breathing, breath hold- 2. The nasal adapter 10 is lifted from its compartment ing, pressure creation, and slow, long deep breaths are 2, shown in Figure 1, in the topside of the nebulizer then repeateduntil the treatment iscomplete. It is advised 25 to the required height. 10 that when dealing with severe cases of sinus congestion, the user should be instructed to breathe through the 3. As shown in Figure 11, the nasal adapter 10 is mouth as needed to maintain necessary oxygen intake. placed over the nose and pressed into place to seal Although the BT involves breathing in through the nose, in the nebulized particles. it is understood that infants, children, the elderly and oth- 15 ers with serious breathing problems may perform the BT 4. As shown in Figure 3, the timer 4 is set to the through the mouth or through cooperatively the mouth required time for the drug being used. and nose. [0041] The nebulizer 25 disclosed herein is capable of 5.As shown in Figure 3,the start button 6 is activated, delivering nebulized particles far into the ethmoid, max- for example, by being depressed. 20 illary and sphenoid sinus. The sphenoid sinus is located furthest from the nasal cavity. The ethmoid, maxillary and 6. The user breathes using the BT, but inhaling and sphenoid sinuses have not been penetrated in the past exhaling out the mouth as needed to maintain oxy- through any other prior art technology. The delivery of gen levels. medicament to the ethmoid, maxillary and sphenoid si- 25 nuses has been shown through sinus ventilation studies. 7. When the timer 4 stops the nebulizer 25, if it is being used for a single dose treatment, the nasal Example 1. adapter 10 is replaced in its compartment 2 and the medicine chamber 45 is cleaned. The nebulizer 25 [0042] A 21-year-old female subject was provided with should be allowed to dry fully before reusing. If using 30 the nebulizer 25 and was instructed to perform the Con- for a multiple dose treatment, it should be cleaned trolled Particle Dispersion Breathing Technique (BT). A after each dosage is complete. TC-DTPA aerosol radiopharmaceutical was provided in the nebulizer 25 in a dose of 10 mci. After performance [0040] The nebulizer 25 disclosed herein is capable of of the BT, a technesium imaging test was performed on delivering nebulized particles far into the nasal cavity and 35 the nasal sinuses of the subject. The technesium imaging the paranasal sinuses. In another method of operation, test was performed at Swedish Medical Center in Seattle, the user uses the nebulizer 25 in conjunction with a Con- Washington. The technesium imaging test allows for trolled Particle Dispersion Breathing Technique (BT). identification of nebulized particles in the ethmoid and The BT provides for the nebulized particles to reach sphenoid sinuses. The findings of the technesium imag- deeply into the nasal cavity and paranasal sinuses. The 40 ing tests were of tracer activity in the ethmoid and sphe- BT includes placing the nasal adapter 10 of the nebulizer noid sinuses bilaterally. There was no activity in the max- 25 over the nose of the patient and activating the neb- illary or frontal sinuses. Communication betw een the na- ulizer 25. As nebulized particles begin to flow out of the sal airway and ethmoidal and sphenoid sinuses was doc- particle dispersion chamber 85, the user should take ap- umented. proximately one to five quick breaths, preferably two to 45 four quick breaths, and even more preferably three Example 2. breaths, through the user’s nose. The breath(s) should be held for approximately one to five seconds and more [0043] A 25-year-old male subject was provided with preferably for three seconds. Using the back of the throat, the nebulizer 25 and instructed to perform the Controlled the user should then create pressure in their sinuses such 50 Particle Dispersion Breathing Technique (BT). The neb- as when relieving pressure due to a change in altitude ulizer 25 was provided with TC-DTPA aerosol at a dose when traveling in a car or plane. This allows the medicine of 15 mci. The technesium imaging test was performed to remain in the nasal cavity and aids in delivery of the at Swedish Medical Center in Seattle, Washington. The medicine to the sinuses. The breathing, breath holding, technesium imaging test allows for identification of neb- and pressure creation should be performed from two to 55 ulized particles in the ethmoid and sphenoid sinuses. The four times in succession and preferably for two times in findings of the technesium imaging study were that pro- succession.After the breathing,breath holding, and pres- ton activity was greater in the ethmoid, maxillary and sure creation are performed in succession, the user sphenoid sinuses bilaterally greater right than left. There

7 13 EP 1 450 885 B1 14 was no tracer activity in the frontal sinuses. The aerosol 5. The particle dispersion chamber (85) of claim 1 fur- was delivered via a nasal mask communicated with the ther comprising a dispersion blade (95) located with- ethmoid and sphenoid sinuses bilaterally but not with the in the internal channel. frontal sinuses. [0044] A representative sinus-bent image for the sub- 5 6. The particle dispersion chamber (85) of claim 5 jects in Examples 1 and 2 is provided in Figure 22. Figure wherein the dispersion blade (95) is solid. 22 shows delivery to the ethmoid, maxillary and sphenoid sinuses via the nebulizer 25. Prior art Figure 21 shows 7. The particle dispersion chamber (85) of claim 5 no penetration into any of the paranasal sinuses and far wherein the dispersion blade (95) is netting. less penetration of the nasal cavity. The exposed area 10 in Fig. 22 using the nebulizer 25 is significantly larger 8. The particle dispersion chamber (85) of claim 1 fur- with more absorption area. Most notably, the drug pen- ther comprising a baffle (100) located within the in- etrated the ethmoid and sphenoid sinuses. The drug de- ternal channel. livered through the nebulizer 25 and via the BT did pro- vide a path to the throat. 15 9. The particle dispersion chamber (85) of claim 8 [0045] All of these features have been built into the wherein the baffle (100) is helical shape. device for use as a nasal nebulizer for the treatment of chronic sinusitis, , colds and flu, pain relief 10. The particle dispersion chamber (85) of claim 1 fur- and for any developments in which introduction of drugs ther comprising: via the nasal passages will be aided. In one potential 20 embodiment the nebulizer 25 will be used to deliver var- an inhaler (110) having a mouthpiece (11), the ious medicaments with a narrow range of particle sizes. mouthpiece associated with the particle disper- sion chamber.

Claims 25 11. The particle dispersion chamber (85) of claim 1 fur- ther comprising: 1. A particle dispersion chamber (85) comprising: a nasal spray inhaler (10) having an actuator, a housing having an external surface and an in- the actuator associated with the particle disper- ternal channel having a user output opening; 30 sion chamber. and a plurality of directional air outputs (90, 105) po- 12. The particle dispersion chamber (85) of claim 1 fur- sitioned along and communicating with the in- ther comprising: ternal channel, the direction of the air outputs suitable to create a vortical flow of aerosolized 35 a dry powder inhaler (115) having a mouthpiece particles within the internal channel, character- (11), the mouthpiece associated with the particle ized in that dispersion chamber. said internal channel of the particle dispersion chamber (85) is configured as vortex continuing 13. A particle dispersion device for nasal delivery of aer- channel to provide for continuation of the vortical 40 osolized particles comprising: flow from the air outputs to and including the user output opening such that said aerosolized a nasal adapter (10); particles emerge from said particle dispersion the particle dispersion chamber (85) of any of chamber in said vortex movement. the claims 1-12 in communication with the nasal 45 adapter, 2. The particle dispersion chamber (85) of claim 1 an outflow tube (80) in communication with the wherein the air outputs (90, 105) are positioned ran- particle dispersion chamber; and domly along the internal channel of the particle dis- a housing, the housing having a medicine cham- persion chamber. ber (45) in which the medicine is aerosolized in 50 communication with the outflow tube. 3. The particle dispersion chamber (85) of claim 1 wherein the air outputs (90, 105) are positioned in a 14. The device of claim 13 wherein the particle disper- set array along the internal channel of the particle sion device is capable of delivery of particles sizes dispersion chamber. ranging from about 2 to about 50 microns, or about 55 2 to about 15 microns. 4. The particle dispersion chamber (85) of claim 1 wherein the air outputs (90, 105) are jets. 15. The device of claim 13 wherein the nasal adapter (10) has a lip.

8 15 EP 1 450 885 B1 16

16. The device of claim 13 wherein the nasal adapter mer (85) als Wirbel fortsetzender Kanal ausge- (10) has a with of about 38,1 mm (1 © inches) across staltet ist, um die Fortsetzung der wirbelartigen a bridge of the nasal adapter and a length of about Strömung aus den Luftaustritten zu und ein- 38,1 mm (1© inches). schließlich der Austrittsöffnung für den Anwen- 5 der bereitzustellen, so dass die aerosolisierten 17. The device of claim 15 wherein the lip is about 3,18 Teilchen in der Wirbelbewegung aus der Teil- mm (1/8 inch) long and capable of forming a seal. chendispersionskammer austreten.

18. The device of claim 13 wherein the outflow tube (80) 2. Teilchendispersionskammer (85) nach Anspruch 1, has an internal diameter of about 14,3 mm (9/16 of 10 wobei die Luftaustritte (90, 105) statistisch entlang an inch) and a first tapered end. des inneren Kanals der Teilchendispersionskammer positioniert sind. 19. The device of claim 13 wherein the nasal adapter (10) has a plurality of exhaust vents. 3. Teilchendispersionskammer (85) nach Anspruch 1, 15 wobei die Luftaustritte (90, 105) in einer Gruppie- 20. The device of claim 13 further comprising a band, rungsanordnung entlang des inneren Kanals der the band connected to the nasal adapter (10), where- Teilchendispersionskammer positioniert sind. by the band is capable of securing the nasal adapter to the face of a user. 4. Teilchendispersionskammer (85) nach Anspruch 1, 20 wobei die Luftaustritte (90, 105) Düsen sind. 21. The device of claim 13 further comprising a hose, thehose in communication with theoutflow tube (80). 5. Teilchendispersionskammer (85) nach Anspruch 1, ferner umfassend ein Dispersionsblatt (95), das in- 22. The device of claim 21 wherein the hose is an ac- nerhalb des inneren Kanals angeordnet ist. cordion hose. 25 6. Teilchendispersionskammer (85) nach Anspruch 5, 23. The device of claim 13 further comprising a shut-off wobei das Dispersionsblatt (95) massiv ist. timer. 7. Teilchendispersionskammer (85) nach Anspruch 5, 24. The device of claim 13 further comprising a pause 30 wobei das Dispersionsblatt (95) Netzgewebe ist. feature. 8. Teilchendispersionskammer (85) nach Anspruch 1, 25. The device of claim 13 wherein the medicine cham- ferner umfassend einen Prallkörper (100), der inner- ber (45) is a multi-dose compartment. halb des inneren Kanals angeordnet ist. 35 26. The device of claim 13 further comprising 9. Teilchendispersionskammer (85) nach Anspruch 8, a lid (50) for covering the medicine chamber (45); wobei der Prallkörper (100) spiralförmig ist. a cartridge (60) capable of insertion into the medicine chamber; and 10. Teilchendispersionskammer (85) nach Anspruch 1, a nebulizing stem (55) connected to the lid, the stem 40 ferner umfassend: capable of insertion into the cartridge. einen Inhalator (110) mit einem Mundstück (11), wobei das Mundstück mit der Teilchendispersi- Patentansprüche onskammer assoziiert ist. 45 1. Teilchendispersionskammer (85), umfassend: 11. Teilchendispersionskammer (85) nach Anspruch 1, ferner umfassend: ein Gehäuse mit einer Außenfläche und einem inneren Kanal mit einer Austrittsöffnung für den einen Nasensprayinhalator (10) mit einem Stel- Anwender; 50 lantrieb, wobei der Stellantrieb mit der Teilchen- und eine Vielzahl gerichteter Luftaustritte (90, dispersionskammer assoziiert ist. 105), die entlang des inneren Kanals positioniert sind und mit diesem kommunizieren, wodurch 12. Teilchendispersionskammer (85) nach Anspruch 1, die Richtung der Luftaustritte geeignet ist, um ferner umfassend: eine wirbelartige Strömung von aerosolisierten 55 Teilchen innerhalbdes inneren Kanals zu erzeu- einen Trockenpulverinhalator (115) mit einem gen, dadurch gekennzeichnet, dass Mundstück (11), wobei das Mundstück mit der der innere Kanal der Teilchendispersionskam- Teilchendispersionskammer assoziiert ist.

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13. Teilchendispersionsvorrichtungzur nasalenAbgabe 25. Vorrichtung nach Anspruch 13, wobei die Medika- von aerosolisierten Teilchen, umfassend: mentenkammer (45) ein Multidosisfach ist.

einen Nasenadapter (10); 26. Verfahren nach Anspruch 13, ferner umfassend die Teilchendispersionskammer (85) nach ei- 5 einen Deckel (50), um die Medikamentenkammer nem der Ansprüche 1-12 in Kommunikation mit (45) zu bedecken; dem Nasenadapter, eine Kartusche (60), die in die Medikamentenkam- ein Austrittrohr (80) in Kommunikation mit der mer eingesetzt werden kann; und Teilchendispersionskammer; und einen mit dem Deckel verbundenen Vernebelungs- ein Gehäuse, wobei das Gehäuse eine Medika- 10 schaft (55), wobei der Schaft in die Kartusche ein- mentenkammer (45) aufweist, in der das Medi- gesetzt werden kann. kament in Kommunikation mit dem Austrittrohr aerosolisiert wird. Revendications 14. Vorrichtung nach Anspruch 13, wobei die Teilchen- 15 dispersionsvorrichtung in der Lage ist, Teilchengrö- 1. Chambre de dispersion de particules (85) ßen im Bereich von etwa 2 bis etwa 50 Mikrometer comprenant : oder etwa 2 bis etwa 15 Mikrometer abzugeben. une enveloppe ayant une surface externe et un 15. Vorrichtung nach Anspruch 13, wobei der Nasena- 20 canal interne ayant une ouverture de sortie dapter (10) eine Lippe aufweist. d’utilisateur ; et une pluralité de sorties d’air directionnelles (90, 16. Vorrichtung nach Anspruch 13, wobei der Nasena- 105) positionnées le long du et communiquant dapter (10) eine Breite von etwa 38,1 mm (1,5 Zoll) avec le canal interne, la direction des sorties über einen Rücken des Nasenadapters und eine 25 d’air étant appropriée pour créer un écoulement Länge von etwa 38,1 mm (1,5 Zoll) aufweist. tourbillonnaire de particules en aérosol à l’inté- rieur du canal interne, 17. Vorrichtung nach Anspruch 15, wobei die Lippe etwa caractérisée par le fait que ledit canal interne 3,18 mm (1/8 Zoll) lang ist und eine Dichtung bilden de la chambre de dispersion de particules (85) kann. 30 est configuré en tant que canal de continuation de tourbillons pour permettre la continuation de 18. Vorrichtung nach Anspruch 13, wobei das Austritt- l’écoulement tourbillonnaire à partir des sorties rohr (80) einen Innendurchmesser von etwa 14,3 d’air jusqu’à et y compris l’ouverture de sortie mm (9/16 Zoll) und ein erstes, sich verjüngendes d’utilisateur de telle sorte que lesdites particules Ende aufweist. 35 en aérosol émergent de ladite chambre de dis- persion de particules dans ledit mouvement 19. Vorrichtung nach Anspruch 13, wobei der Nasena- tourbillonnaire. dapter (10) eine Vielzahl von Abluftdurchlässen auf- weist. 2. Chambre de dispersion de particules (85) selon la 40 revendication 1, dans laquelle les sorties d’air (90, 20. Vorrichtung nach Anspruch 13, ferner umfassend 105) sont positionnées de façon aléatoire le long du ein Band, wobei das Band mit dem Nasenadapter canal interne de la chambre de dispersion de parti- (10) verbunden ist, wodurch das Band den Nasen- cules. adapter am Gesicht eines Anwenders befestigen kann. 45 3. Chambre de dispersion de particules (85) selon la revendication 1, dans laquelle les sorties d’air (90, 21. Vorrichtung nach Anspruch 13, ferner umfassend ei- 105) sont positionnées en un réseau défini le long nen Schlauch, wobei der Schlauch in Kommunikati- du canal interne de la chambre de dispersion de par- on mit dem Austrittrohr (80) ist. ticules. 50 22. Vorrichtung nach Anspruch 1, wobei der Schlauch 4. Chambre de dispersion de particules (85) selon la ein Ziehharmonikaschlauch ist. revendication 1, dans laquelle les sorties d’air (90, 105) sont des jets. 23. Vorrichtung nach Anspruch 13, die ferner eine Aus- schalt-Zeitschaltung umfasst. 55 5. Chambre de dispersion de particules (85) selon la revendication 1, comprenant en outre une lame de 24. Vorrichtung nach Anspruch 13, die ferner eine Pau- dispersion (95) située à l’intérieur du canal interne. senfunktion umfasst.

10 19 EP 1 450 885 B1 20

6. Chambre de dispersion de particules (85) selon la 15. Dispositif selon la revendication 13, dans lequel revendication 5, dans laquelle la lame de dispersion l’adaptateur nasal (10) a une lèvre. (95) est pleine. 16. Dispositif selon la revendication 13, dans lequel 7. Chambre de dispersion de particules (85) selon la 5 l’adaptateur nasal (10) a une largeur d’environ 38,1 revendication 5, dans laquelle la lame de dispersion mm (1 © pouce) à un pont de l’adaptateur nasal et (95) est un filet. une longueur d’environ 38,1 mm (1 © pouce).

8. Chambre de dispersion de particules (85) selon la 17. Dispositif selon la revendication 15, dans lequel la revendication 1, comprenant en outre un déflecteur 10 lèvre est d’environ 3,18 mm (1/8 pouce) de long et (100) situé à l’intérieur du canal interne. est capable de former un joint d’étanchéité.

9. Chambre de dispersion de particules (85) selon la 18. Dispositif selon la revendication 13, dans lequel le revendication 8, dans laquelle le déflecteur (100) est tube d’écoulement de sortie (80) a un diamètre in- de forme hélicoïdale. 15 terne d’environ 14,3 mm (9/16 d’un pouce) et une première extrémité effilée. 10. Chambre de dispersion de particules (85) selon la revendication 1, comprenant en outre : 19. Dispositif selon la revendication 13, dans lequel l’adaptateur nasal (10) a une pluralité d’évents un inhalateur (110) ayant un embout (11), l’em- 20 d’échappement. bout étant associé à la chambre de dispersion de particules. 20. Dispositif selon la revendication 13, comprenant en outre une bande, la bande étant reliée à l’adaptateur 11. Chambre de dispersion de particules (85) selon la nasal (10), ce par quoi la bande est capable de fixer revendication 1, comprenant en outre : 25 l’adaptateur nasal au visage d’un utilisateur.

un inhalateur à pulvérisation nasale (10) ayant 21. Dispositif selon la revendication 13, comprenant en un actionneur, l’actionneur étant associé à la outre un tuyau souple, le tuyau souple étant en com- chambre de dispersion de particules. munication avec le tube d’écoulement de sortie (80). 30 12. Chambre de dispersion de particules (85) selon la 22. Dispositif selon la revendication 21, dans lequel le revendication 1, comprenant en outre : tuyau souple est un tuyau souple en accordéon.

un inhalateur à poudre sèche (115) ayant un em- 23. Dispositif selon la revendication 13, comprenant en bout (11), l’embout étant associé à la chambre 35 outre un minuteur d’arrêt automatique. de dispersion de particules. 24. Dispositif selon la revendication 13, comprenant en 13. Dispositif de dispersion de particules pour une ad- outre une fonction pause. ministration nasale de particules en aérosol, com- prenant: 40 25. Dispositif selon la revendication 13, dans lequel la chambre de médicament (45) est un compartiment un adaptateur nasal (10) ; à doses multiples. la chambre de dispersion de particules (85) se- lon l’une quelconque des revendications 1 à 12 26. Dispositif selon la revendication 13, comprenant en en communication avec l’adaptateur nasal, 45 outre : un tube d’écoulement de sortie (80) en commu- nication avec la chambre de dispersion de un couvercle (50) pour recouvrir la chambre de particules ; et médicament (45) ; une enveloppe, l’enveloppe ayant une chambre une cartouche (60) capable d’une introduction de médicament (45) dans laquelle le médica- 50 dans la chambre de médicament ; et ment est mis sous forme d’aérosol en commu- unetige de nébulisation (55) reliéeau couvercle, nication avec le tube d’écoulement de sortie. la tige étant capable d’une introduction dans la cartouche. 14. Dispositif selon la revendication 13, dans lequel le dispositif de dispersion de particules est capable55 d’administrer des dimensions de particules compri- ses dans la plage allant d’environ 2 à environ 50 microns, ou d’environ 2 à environ 15 microns.

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REFERENCES CITED IN THE DESCRIPTION

This list of references cited by the applicant is for the reader’s convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.

Patent documents cited in the description

• WO 0136033 A [0006] • WO 9826827 A [0008] • WO 9947273 A [0007]

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