Il||l|lllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllll
`
`US00589484lA
`
`United States Patent
`
`1191
`
`[11] Patent Number:
`
`5,894,841
`
`Voges
`[45] Date of Patent: *Apr. 20, 1999
`
`
`
`.. 128/203.12
`5,156,776 10/1992 Loedding et all.
`.. 128/200.23
`5,284,133
`2/1994 Burnsetal.
`
`239/102.2
`5,511,726
`4/1996 Greenspan et al.
`5,685,485
`11/1997 Moele et a1.
`......................... 239/102.2
`
`[54] DISPENSER
`
`[75]
`
`Inventor: Robert Martin Voges, Sanctuary Cove,
`Australia
`
`[73] Assignee: Ponwell Enterprises Limited,
`Wanchai, The Hong Kong Special
`Administrative Region of the People’s
`Republic of China
`
`[*] Notice:
`
`This patent issued on a continued pros-
`ecution application filed under 37 CFR
`l.53(d), and is subject to the twenty year
`patent
`term provisions of 35 USC.
`l54(a)(2).
`
`[21]
`
`[22]
`
`[86]
`
`Appl. No.:
`PCT Filed:
`
`PCT No.:
`
`08/578,707
`
`Jun. 23, 1994
`PCTIAU9-1100355
`
`§ 371 Date:
`
`Dec. 28, 1995
`
`§ 102(e) Date:
`
`[87]
`
`PCT Pub. No.:
`
`Dec. 23, 1995 '
`W095/11137
`
`PCT Pub. Date: Jan. 12, 1995
`
`[30]
`
`Foreign Application Priority Data
`Australia ................................. PL9673
`11111.29, 1993
`[AU]
`Australia .
`. PL9769
`Jul. 2, 1993
`[AU]
`
`Australia .
`PM09Q5
`Aug.31, 1993
`[AU]
`Australia ................................ PM1709
`Oct.8, 1993
`[AU]
`
`[51]
`[521
`
`[58]
`
`[56]
`
`Int. Cl.6 ..........
`U.S. Cl. ...........
`
`.......................................... A6lM 11/00
`
`..................... 128/203.12; 128/200.14;
`128/200.16; 128/203.21; 239/102.2
`Field of Search ....................... .. 128/203.12, 200.14,
`128/200.16, 200.18. 200.21. 200.23, 200.22,
`203.21, 203.26; 239/102.2, 4, 406
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`4,934,358
`4,966,579
`4,987,861
`
`6/1990 Nilsson et al.
`10/1990 Polaschegg
`1/1991 Lemire et al.
`
`..................... 128/200.23
`
`
`.......................... 119/159
`
`........ .. 128/200.14
`
`............ 239/102.2
`
`FOREIGN PATENT DOCUMENTS
`12/1981
`European Pal. OE. .
`3/1987
`European Pat. Otf. .
`9/1987
`European Pat. 05.
`11/1989
`European Pat. Off. .
`6/1991
`European Pat. Off. .
`11/1991
`European Pat. Off. .
`5/1993
`European Pat. OE.
`1/1984
`Germany .
`9/1990
`Germany .
`211986
`Japan .
`5/1994
`United Kingdom .............. .. 239/ 102.2
`7/1987
`WIPO .
`7/1989
`WIPO .
`7/1992
`WIPO .
`9/1992
`WIPO .
`3/1993
`WIPO .
`6/1993
`WIPO .
`6/1993 WIPO ................................. 239/102.2
`7/1993 WIPO .
`
`0042468
`0213753
`0234842
`0343501
`0432992
`047557
`0542723A2
`205820
`39/08909
`61-272163
`7272389
`87./04354
`89/06147
`92/11050
`92 15353
`93/03856
`93 11866
`93/10910
`93/13730
`
`Primary Examiner—John G. Weiss
`Assistant Examiner—V. Srivastava
`Attorney, Agent, or Firm—Wilson Sonsini Goodrich and
`Rosati
`
`[57]
`
`ABSTRACT
`
`A dispenser (FIG. 1, 1) comprises a reservoir (10) of a
`physiologically active substance and a droplet ejection
`device (14), for example a bubblejet or pizeoelectric device,
`which is controlled to issue a predetermined number of
`discrete droplets of the substance from ejection orifices (15)
`upon actuation. Device (14) may be actuated by a pressure
`transducer (19) responsive to inhalation and issue the drop-
`lets into an airslream (A) which enters at slot (7) and is then
`inhaled via mouthpiece (5). In other embodiments (FIG. 5)
`the dispenser is finger actuated and directed by hand for
`topical application. The number and/or frequency of drop-
`lets issued is programmatically controlled by a control
`circuit (16) whereby average and total dose of the substance
`are predetermined.
`
`42 Claims, 3 Drawing Sheets
`
`
`
`._:_,,.,Q.
`
`-
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`NU MARK Ex.1010 p.1
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`

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`U.S. Patent
`
`Apr. 20, 1999
`
`Sheet 1 of 3
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`5,894,841
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`SE_‘.w\\..\\\\\.V\w\\NLUH47’IZ!.rar////..@452A
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`9.,..h._r///.HI7/‘,//Z7
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`ESs\\\\\\\\\\\\\\\\\\\\\\\\\\\._SI.I...2HII.!.flWIfl.5\\\\\\\.Se.\\\\\\\\\\\\\\\\\\\\\\\\\\\m
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`7.6
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`NU MARK Ex.1010 p.2
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`

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`U.S. Patent
`
`Apr. 20, 1999
`
`Sheet 2 of 3
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`5,894,841
`
`AIR FLOW
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`AIR now
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`AIR FLOW
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`0
`
`%
`
`PUFF nus
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`0
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`0
`
`PUFF nus
`
`% DOSE zwscnozv
`
`PUFF TIME
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`/526.3
`
`NU MARK Ex.1010 p.3
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`

`
`U.S. Patent
`
`Apr. 20, 1999
`
`Sheet 3 of 3
`
`5,894,841
`
`NU MARK Ex.1010 p.4
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`

`
`5,894,841
`
`1
`DISPENSER
`
`FIELD OF THE INVENTION
`
`This invention relates to a hand held dispensing device.
`The device is of particular suitability for the self-
`administration of physiologically active substances by inha-
`lation and will be herein described with primary emphasis
`on that use but may be used for other purposes.
`
`BACKGROUND OF THE INVENTION
`
`There are currently three main methods for drug delivery
`via the respiratory tract. namely metered dose inhalers, dry
`powder inhalers. and nebulisers.
`
`Metered dose inhalers (“MDI”) are widely used in the
`management of asthma. The MDI comprises a drug pack-
`aged with a propellant in a pressurised aerosol container can
`having a valve which releases a volumetric metered dose of
`aerosol upon actuation. These devices are portable, small,
`and convenient to carry but deliver a dose which varies in
`quantity. delivery speed, and droplet size distribution as the
`vapour pressure of the propellant varies. The propellant
`pressure varies with temperature and decreases progres-
`sively as the content becomes depleted so that the range in
`dose variation may be substantial. Incomplete evaporation
`of the propellant may cause “sticking” and localised con-
`centration of drug droplets at an impact area, and this in turn
`can cause undesirable side effects. For example bronchos—
`teroids can cause local immuno-suppression and local fungal
`infection while local concentration of bronchodilator can
`lead to swallowing. with unwanted systemic afiects. In
`addition, the use of an MDI requires a degree of synchro-
`nisation between manual valve actuation and inhalation
`which many users find diflicult.
`
`5
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`10
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`Dry powder inhalers (“DPI”) devices rely upon a burst of
`inspired air to fluidise and draw a dose of an active powder
`into the bronchial tract. While this avoids the synchronisa-
`tion problem of the MDI, DPI’s are sensitive to humidity
`and may provoke asthma attacks in some individuals sen-
`sitive to inhaled powder. Moreover, because the force of
`inspiration varies from person to person, the dose adminis-
`tered varies.
`
`Nebulisers generate an aerosol by atomising a liquid in a
`carrier gas stream and require a continuous gas compressor
`or bulky supply of compressed gas. In general, the droplet
`size of the aerosol is a function of carrier gas pressure and
`velocity and hence cannot be easily varied independently of
`concentration of the active substance in the gas stream.
`Inhalation reduces the pressure at the nebulizer nozzle and
`thus dosage and particle size are also influenced by the
`duration and strength of each breath. Most nebulisers oper-
`ate continuously during inhalation and exhalation but special
`control systems can be employed to meter the aerosolised
`gas flow from the nebuliser to a holding chamber from
`which the user may draw a charge.
`In general the precision of dose delivery of each of these
`devices is less accurate than desirable and restricts their use
`to drugs which have broad dosage tolerance. In each case
`delivery of the active agent to the intended application site
`is overly dependent on user technique and is variable from
`dose to dose and person to person. Not only is an improved
`delivery system required to optimise current nasal and
`pulmonary therapies utilising locally acting drugs but there
`has long been recognised a potential for the administration
`of many additional
`local and systemic drugs if a more
`satisfactory means of delivery were available. Medical
`advances suggest that pulmonary delivery of drugs such as
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`peptides, proteins and analgesics might be of considerable
`advantage compared with conventional oral or injection
`delivery means. For example it has been suggested that
`insulin for diabetics may be delivered via the pulmonary
`route if a suitable means of delivery were available. The
`deposition of drug particles on lung tissue is a function of
`size, shape and density of particles or droplets. For many
`drugs, control of one or more of these factors along with
`precise dose or dose rate control would be desirable.
`However, at the present time no means of drug delivery is
`available which adequately meets such requirements.
`Many attempts have been made to provide a cigarette
`substitute which provides nicotine by inhalation but which
`avoids the need for combustion of tobacco. Provision of a
`cigarette substitute involves complexities additional to those
`involved in the administration of a therapeutic agent.
`Although it is relatively easy to administer nicotine (for
`example in tablet form, via transdermal patches and the
`like), such forms do not satisfy habitual smokers because
`they do not satisfy important complex physiological and
`psychological aflinities acquired by habitual smokers of
`combustible cigarettes.
`
`In an attempt to provide an acceptable alternative, many
`cigarette substitutes have been proposed which provide
`nicotine on inhalation without combustion of tobacco.
`Conceptually, such devices are less harmful to the inhaler
`than smoking, avoid the hazards of passive smoking among
`bystanders and avoid the fire hazard and environmental
`problems associated with cigarette smoking. However,
`despite these major advantages, no device so far proposed
`has met with consumer acceptance.
`Early cigarette substitutes employed a porous carrier
`impregnated with a liquid nicotine containing composition
`through which an air stream could be drawn to volatilize
`nicotine. This approach yielded insuflicient nicotine per
`pufi, suffered from a tendency for the carrier to dry out and
`delivered a variable amount of nicotine per puff, depending
`on factors such as air temperature, humidity, lung capacity
`of the user and amount of liquid composition remaining in
`the carrier.
`
`Subsequent devices delivered nicotine from a pressurised
`aerosol container from which nicotine can be released by
`mechanical valve actuator. In one such device the valve is
`microprocessor controlled to limit the frequency and dura-
`tion of actuation. However, the dose delivered varies with
`the vapour pressure of aerosol remaining in the container as
`well as with duration of valve actuation. The disposable
`pressure container, aerosol valve. and CFC propellant add
`considerably to active substance cost. These devices share
`the disadvantages of MDI devices previously discussed.
`In yet other devices a nicotine containing substance is
`heated to vapourise an amount of nicotine which is then
`available for inhalation. The amount of nicotine delivered by
`such devices is diflicult to control and is temperature depen-
`dant. In one such device a plurality of nicotine-containing
`pellets may be heated sequentially so that each liberates a
`predetermined dose. However, in that case, the dose is fixed
`during pellet manufacture, particle size of the aerosol is
`uncontrolled, and temperature of the inhaled air cannot be
`varied independently of dose.
`the
`Factors such as the quantity of nicotine per pull‘,
`temperature of the puff, the draw, the presence and size
`distribution of flavour particles in the puff and like factors
`are of considerable importance in satisfying habitual smok-
`ers. The various alternatives proposed to date have simply
`proved unacceptable to most smokers.
`
`NU MARK Ex.1010 p.5
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`

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`3
`
`5,894,841
`
`4
`
`To date no device has provided a satisfactory means of
`adjusting both the quantity of nicotine delivered in each puff
`in response to user demand andlor maintaining adequate
`precision and accuracy in the dose quantum metered out.
`Further the devices have failed adequately to mimic the
`sensations obtained during smoking.
`Because the requirements for a cigarette substitute are
`particularly diflicult to satisfy. the present invention is herein
`described primarily with reference to nicotine delivery, but
`it will be understood that the invention is more generally
`applicable and addresses the general need for a device which
`can precisely dispense doses and preferably which can
`dispense doses of a variety of drugs or other substances and
`which are adjustable from one individual to another or at
`diflerent times.
`
`Preferred embodiments of devices of the kind under
`consideration may be used as a less harmful form of admin-
`istration of nicotine than smoking or may be used to reduce
`or eliminate nicotine dependence among those wishing to
`give up smoking.
`It is, without limitation. an object of the present invention
`to provide a method and means for administration or self-
`administration of an active substance which avoids at least
`some of the above discussed disadvantages of prior art. It is
`an object of preferred embodiments of the invention to
`provide a method and means for dispensing the active
`substance for administration via inhalation.
`
`10
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`20
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`It is an object of other preferred embodiments of the
`invention to provide a cigarette substitute.
`
`30
`
`DISCLOSURE OF THE INVENTION
`
`the invention consists in a
`According to one aspect
`method for administering a substance to a human or animal
`subject by inhalation, said method comprising the steps of:
`(i) ejecting a predetermined number of discrete droplets of
`the substance from at least one droplet ejection device
`in response to an actuation signal. and
`(ii) entraining the droplets in an inhalation airstream.
`According to a second aspect the invention consists in a
`method for topical application of a substance to a human or
`animal subject comprising the steps of:
`(1) ejecting a predetermined number of discrete droplets
`of the substance from at least one droplet ejection
`device in response to an actuation signal, and
`(2) directing the droplets at a selected area or region of the
`subject.
`According to a third aspect the invention consists in an
`apparatus for administering a substance to a human or
`animal subject, said apparatus comprising:
`a droplet ejection device containing a substance to be
`administered, means responsive to an actuation signal to
`eject a predetermined number of discrete droplets of the
`substance. and
`means for directing the ejected droplets at, or into, the
`subject.
`The substance to be administered may be a therapeutic or
`other physiologically active agent and may be a liquid, a
`solution or a suspension for example a colloidal solid in a
`liquid carrier or an emulsion.
`In preferred embodiments of the invention, the droplet
`ejection device (“DED") device is a piezoelectric device of
`the kind used in ink jet printing or is a thermal “bubble jet”
`device of the kind used in ink jet printing.
`These devices are sometimes referred to as “droplet on
`deman ” devices. By way of example piezoelectric devices
`
`are broadly described in “Ink-Jet Printing” [M. Doring
`Philips Tech Rev 40, 192-198, 1982 No. 7]. while thermal
`devices are broadly described in “Thermal Ink—Jet Print
`Cartridge Designers Guide" (2nd Edition Hewlett Packard),
`both incorporated herein by reference.
`Briefly, a typical
`thermal device consists of a liquid-
`containing chamber provided with an array of twelve coaxi-
`ally divided nozzles and has twelve thin film resistors, a
`resistor being located directly behind each nozzle. Each
`nozzle supplies a droplet of liquid from the chamber if and
`when the corresponding resistor is energized by a short
`electrical pulse. The resistors thus function as ejection
`means. Within a few microseconds liquid in contact with the
`resistor is vapourised and forms a bubble. The vapour
`bubble grows rapidly and imparts momentum to liquid
`above the bubble. Some of this liquid is ejected as a droplet
`from the adjacent nozzle at a velocity typically exceeding 10
`meters/second. The ejected volume of liquid is automati-
`cally replaced in the chamber from a reservoir by capillary
`action or by atmospheric pressure acting on collapsible
`reservoir bladder, a piston or the like. Devices of this kind
`when used for printing eject a typical drop of about 50
`micron diameter at velocities in excess of 10 meterslsecond
`and are capable of drop ejection frequencies of up to several
`thousand droplets per second. The piezoelectric device gen-
`erates a droplet by means of a pressure wave in the fluid
`produced by applying a voltage pulse to a piezoelectric
`ceramic which in this device acts as the ejection means. As
`with the thermal device, the droplet is ejected through a fine
`aperture. The fluid is ejected in the form of a fine droplet
`whose velocity depends on the energy contained in the
`voltage pulse. In conventional ink jet applications, ejection
`velocities in excess of 2 meters/second with droplet diam-
`eters of around 150 microns and droplet ejection rates of in
`excess of 6,000 droplets per second can be achieved.
`Although conventional “droplet on demand” or “droplet
`ejection" devices such as used in ink jet printers may be
`employed in embodiments of the invention,
`the droplet
`ejection devices for use in the invention preferably differ
`from those used for printing. With printheads the ejection
`orifices are typically arranged as a rectangular matrix of, for
`example, 2x6 or 4x6 orifices the droplets being expelled in
`parallel direction from various combinations of orifice to
`form characters on a paper moving past the printhead at a
`distance of from 0.7 mm to 1.0 mm from the orifice. Droplet
`size is chosen to provide optimum print quality and high dot
`resolution. For use in the present invention there may be a
`smaller or greater number of orifices than used for printing
`and there is no need for the orifices to be arranged in a
`rectangular matrix with parallel orifice axes. The droplet
`ejection orifices may. for example, be arranged in a circle
`andlor may be directed at a converging or diverging angle to
`the axis of each other. Also for use in the present invention
`it is often preferred to eject much smaller droplets than are
`useful for printing. Additionally, the droplet ejection orifices
`may ditfer in diameter one from another so that the particle
`size of the active agent sprayed from the device may be
`controlled programmatically by selecting which orifices are
`used for droplet ejection and particle size may be varied
`from one time interval to another. Because the size of droplet
`ejected from the device in response to a predetermined
`signal is predetermined for a given liquid and device, and
`because the number and frequency of droplets ejected can be
`controlled with great precision,
`it is possible to closely
`control the total volume of liquid (dose) delivered in a given
`time interval. For example the device might deliver 1,000
`droplets of 50 micron diameter in a second. This volume can
`in principle be increased or decreased in increments of one
`droplet
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`NU MARK Ex.1010 p.6
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`5
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`5,894,841
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`6
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`In preferred embodiments of devices according to the
`invention the DED is provided with orifices of an aperture
`size selected to eject a droplet of less than 10 microns
`diameter and, more preferably, of from 1
`to 5 microns
`diameter. Droplets may be emitted from the DED from a
`selected orifice in succession or from a plurality of orifices
`simultaneously.
`In preferred embodiments the droplet delivery device or
`devices may be manually actuated or may actuate in
`response to an inhalation detector signal or other signal. The
`apparatus is provided with control means programmed to
`eject a predetermined number of droplets. The number may
`be varied in response to stored data and/or other input
`signals and programme logic may control such factors as the
`number of droplets ejected in a predetermined time interval,
`frequency of droplet ejection, the total number of droplets of
`active substance issued within a time period, or the like. The
`control means may be programmed to provide many other
`desirable functions as hereinafter described.
`The means for directing the ejected droplets at or into the
`subject may for example be a simple mouth piece provided
`with an air inlet. a nasal shroud, face mask or other spray
`directing means. The active agent is typically in solution and
`is emitted from the DED as a fine spray which may be
`combined with air and/or may be heated prior to inhalation.
`
`BRIEF DESCRIPTION OF DRAWINGS
`
`Various embodiments of the invention will now be
`described by way of example only and with reference to the
`accompanying drawings in which:
`FIG. 1 is a schematic part sectional perspective view of
`one embodiment of a dispenser (cigarette substitute) accord-
`ing to the invention; and
`
`FIG. 2 is a schematic section in an axial plane of the
`dispenser of FIG. 1: and
`
`FIGS. 3A, 3B and 3C are graphs showing the dispensation
`of an active ingredient (hatched) as a function of inhalation
`time in use of the embodiment of FIG. 1. and
`FIG. 4 is a schematic perspective view of a second
`embodiment of the invention, and
`FIG. 5 is a schematic diagram of a third embodiment of
`the invention.
`
`DESCRIPTION OF PREFERRED
`EMBODIMENTS
`
`With reference to FIGS. 1 and 2 there is shown a first
`embodiment of the invention consisting of a nicotine dis-
`penser comprising a cigarette-shaped hollow tubular body 1
`comprising connected body parts 2, 3. Body part 2 has a
`sidewall 4, a mouthpiece 5 at or adjacent one end and a
`threaded other end 6. A plurality of axially extending slots
`7 penetrate side wall 4. Body part 3 is screw threaded at one
`end for connection with threaded end 6 of body part 2. Body
`part 3 is closed or constricted at the end 9 remote from
`mouthpiece 5.
`
`Nicotine in a suitable solvent (for example water) is
`provided in a container 10 which is adapted by means of a
`spiggot shaped outlet and coupling 11, for fluid connection
`to an inlet port 12 of a droplet ejection device 14. In the
`present example, device 14 is of the kind used in a bubble
`jet printer and is provided with one or more droplet ejection
`orifices 15. Device 14 is controlled by control means 16, for
`example a microelectronic circuit or microprocessor means.
`Device 14 and control means 16 as well as other electrically-
`powered parts are energised by means of a hollow cylindri-
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`ca] battery 17 via an on-off switch 18 extending through side
`wall 14 and operable by the user. When a user inhales at
`mouthpiece 5, a stream of air “A” is drawn into body 1 via
`slots 7, through body part 2, and mouthpiece 5 into the user's
`lungs. Slots 7 may be provided with adamper or the like (not
`illustrated) to control airflow or the device may be provided
`with a porus plug to control airflow (“draw”) on inhalation
`at mouthpiece 5. A pressure sensor 19 detects a change in
`pressure in the device due to inhalation or suction at mouth-
`piece 5 and issues an actuation signal via cables (not
`illustrated) to control means 16. Control means 16 responds
`to the actuation signal by issuing an output signal or signals
`via cables (not illustrated) to device 14 according to pre-
`programmed parameters or algorithms as hereinafter
`described. The output or “dose” signal is, or includes, a set
`of “ejec ” signals for example a train of voltage pulses.
`Device 14 responds to the output signal or signals by issuing
`a plurality of droplets of nicotine solution from orifices 15
`of device 14. The liquid containing nicotine issues from
`device 14 as a fine spray of droplets which are entrained in
`the inhalation airflow from slots 7 towards mouthpiece 5.
`The spray typically comprises fine droplets which tend to
`vaporise in the airflow. Optionally, heating means 20 are
`provided. In that case the combination of air with nicotine
`droplets may be brought into thermally conductive contact
`with heating means 20 prior to leaving mouthpiece 5. This
`not only produces a sensation on inhalation similar to that
`obtained by smoking a combustible cigarette, but also serves
`to enhance the vaporisation of active substance droplets in
`the gas stream reducing droplet size.
`In the embodiment illustrated in FIGS. 1, 2 the active
`substance container 10 is a collapsible bladder which is
`housed within a protective hollow cylindrical cartridge 21
`having an air vent 22. However other forms of container (for
`example a cylinder fitted with a piston) could be used
`Cartridge 21 is optional and serves to shield bladder 10.
`Container 10 is disposable or replaceable and may be
`adapted for fluid communication with inlet 12 of device 14
`by means of a threaded. bayonet, or other suitably sealing
`connection.
`
`Optionally, battery 17 may be of annular form and
`adapted to sleeve cartridge 21 to save space. Heating means
`20 may be infrared heating plates or elements, resistance
`elements or the like.
`
`Control means 16 desirably comprises a programmable
`logic circuit for example a microprocessor together with
`associated Read Only Memory (ROM), Read and Write
`Memory (RAM), clocks, power supply and the like and is
`programmed to control the quantity of nicotine delivered by
`the DED upon inhalation, subject to predetermined criteria.
`In normal operation of the device a drop of pressure at
`mouthpiece 5 is detected by pressure sensor 19 which issues
`a signal
`indicative of inhalation (“aetuation" signal) to
`control means 16 (via cables not illustrated). Control means
`16 responds by issuing a “dose” signal to device 14 resulting
`in a spray of droplets from the device.
`
`The dose signal typically comprises a predetermined set
`of drop “eject” signals which causes one or more orifices 15
`of device 14 to eject a predetermined number of droplets.
`The dose signal may, for example, be a train of pulses (each
`pulse being a droplet eject signal) directed serially to one
`resistance heater of a thermal bubble jet device, or may be
`a sequence of pulses directed in parallel to a number of such
`resistance heaters. Since the volume of a droplet issued from
`a selected orifice 15 is predetermined for a given liquid and
`orifice, and the number of droplets ejected is controlled by
`
`NU MARK Ex.1010 p.7
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`
`7
`
`5,894,841
`
`8
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`the total volume of nicotine-containing
`the dose signal,
`liquid ejected in response to the actuation signal is precisely
`determined.
`
`Control means 16 controls the pulse spacing, pulse width,
`and pulse frequency of the “dose" signal as well as the
`number of pulses or droplet “eject” signals and therefore
`determines the time interval during which droplets enter the
`inhalation air stream i.e.
`the dose rate. The number of
`droplets issued andlor the droplet issue frequency may be
`altered by changing data stored in a control memory. Control
`means 16 may also be programmed to address specific
`resistance heaters so as to emit droplets from selected
`orifices which may difier one from another for example in
`respect of diameter or orientation.
`Control means 16 may also be programmed to provide a
`time delay between receipt of an actuation signal indicative
`of inhalation from pressure sensor 19 and the issuance of a
`“dose signal". The time delay may be varied by changing
`data stored in a control memory. By controlling the time
`delay between the leading edge of an actuation signal and
`issue of the dose signal, and by controlling the frequency of
`droplet “eject” pulses in the dose signal, the active substance
`can, for example, be injected into an inhaled air stream as a
`spike near the start (FIG. 3A) or start and end (FIG. 3B) of
`an inhalation “pufi”, or can be spread over the puff duration
`(FIG. 3C), or may be confined to the leading or trailing
`portion of a puff. This enables the change in concentration
`of nicotine during a puff of a cigarette to be more closely
`mimicked.
`
`The control means can also be programmed to prevent a
`dose signal from issue until a predetermined “non repeat"
`time has elapsed after a preceding dose signal has been
`issued, notwithstanding receipt of :1 inhalation signal. This
`provides a minimum delay between successive doses.
`The control means may also be provided with means for
`counting and storing the total number of dose signals issued
`within a predetermined time interval and if the total exceeds
`a predetermined limit (for example 30 doses in a 30 minute
`period) then the control circuit prevents further dose issue
`until a further period (e.g. 1 hour) has elapsed. This limits
`the maximum dose issued within an extended period.
`In preferred embodiments of the invention the control
`means enters a minimum energy drain mode to conserve
`battery power if for example more than 5 minutes have
`elapsed since an inhalation was detected.
`The apparatus of FIG. 1 may optionally be provided with
`means for signalling the doses remaining in the device for
`example by means of a plurality of LEDs 30 which pro-
`gressively extinguish. Each LED may for example corre-
`spond to a dose equivalent to smoking one cigarette and the
`apparatus might initially store a dose corresponding to one
`(or several) packets of cigarettes. Other indicator means e.g.
`an LCD display could be used.
`In summary the control means allows programmable
`control of factors such as:
`
`(6) Control of maximum number of doses available in a
`given period i.e. maximum dose rate (e.g. no more than 20
`doses available per hour).
`(7) Programmed variation of dose from one actuation to
`another (e.g. successive reduction in dose to reduce drug
`dependence).
`(8) Programmed variation from time to time (e.g. dose to
`decrease from day to day).
`(9) Control of nozzles from which the droplets issue (and
`hence spray pattern).
`(10) Discrimination for adequacy of inhalation (No dose
`unless accompanied by suficient inhalation air).
`It will be apparent from the above that the device can be
`programmed in other ways and to perform other functions
`by the addition of other sensors-—for example temperature
`or humidity sensors.
`In addition the control means may be provided with
`means by which control parameters may be altered or by
`which the device may be reprogrammed, for example by
`interfacing with a keyboard or an external computer.
`As will be appreciated, the microprocessor may be pre-
`programmed or may be user-programmable to control the
`operation of various DED nozzles, the heater, the airflow or
`the like in various other combinations, sequences, or as
`functions of time, temperature, or the like.
`Tubular body 1 may be made of any suitable material e.g.
`plastics, ceramics, precious metals or the like. Mouthpiece 5
`may be integral or may be soft-tip, for example of rubber or
`plastics cardboard, or paper and may be independently
`disposable. The battery may be replaceable or rechargeable.
`The dispenser as a whole may be provided as a disposable
`item or may be reusable. In the latter case,
`the product
`container and DED device will normally be replaceable or
`may be provided as a combined unit. In that case, the body
`portion will be separable e.g. via screw—threaded or bayonet
`coupling into sections to facilitate installation and removal
`of the product cartridge andlor battery. The product to be
`dispensed may be for example an aqueous solution of
`nicotine and may contain additional substances such as
`glycols, flavours or essences, for example menthol. The
`active substance may be in the form of a gel, melt, solution
`or suspension.
`If desired, more than one DED 14 may be incorporated
`whereby to produce droplet streams of difierent droplet size
`and in this case, one stream may be fully vapourised by
`heating plates 20 while a second stream may be directed so
`that the user receives the sensation of a wet vapour in
`combination with a dry vapour as occurs when smoking
`conventional cigarettes.
`It is not essential that the spray of active ingredient be
`combined with air prior to heating and if preferred the spray
`and/or the air may be separately heated and subsequently
`combined or the active ingredient may be preheated e.g. by
`heating means in thermal communication with storage con-
`tainer 10. By selective programming of the controller the
`smoking instrument can be adjusted to simulate “light” or
`“ultralight” cigarette nicotine levels or can be selectively
`adjustable therebetween. In other embodiments the air
`intake may be adjusted to vary the air to active substance
`ratio thus further to facilitate simulation of the sensation of
`smoking different kinds of cigarettes. The invention is of
`particular application for assisting those wishing to with-
`draw from cigarette smoking being programmable to pro-
`gressively reduce the dose of nicotine obtainable. Devices
`according to the invention may either be pre-programmed,
`
`45
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`50
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`55
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`(l) Predetermined number of droplets of nicotine issued
`in a single dose (dose volume).
`(2) Frequency of drop issue within a dose (dose rate).
`(3) Synchronization of the dose relative to commence-
`ment of inhalation.
`
`(4) Injection of dose as a function of time from com-
`mencement of inhalation. (Pulse spacing and frequency).
`(5) Control of maximum frequency of issue of successive
`doses or non repeat time (e.g. successive doses available at
`not