CA1275883C - Apparatus for producing a spray of droplets of a liquid - Google Patents
Apparatus for producing a spray of droplets of a liquidInfo
- Publication number
- CA1275883C CA1275883C CA000530183A CA530183A CA1275883C CA 1275883 C CA1275883 C CA 1275883C CA 000530183 A CA000530183 A CA 000530183A CA 530183 A CA530183 A CA 530183A CA 1275883 C CA1275883 C CA 1275883C
- Authority
- CA
- Canada
- Prior art keywords
- liquid
- shield electrode
- spray
- edge
- chamber
- 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.)
- Expired - Lifetime
Links
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
- B05B5/002—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means comprising means for neutralising the spray of charged droplets or particules
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- 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
- A61M11/001—Particle size control
-
- 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
- A61M15/02—Inhalators with activated or ionised fluids, e.g. electrohydrodynamic [EHD] or electrostatic devices; Ozone-inhalators with radioactive tagged particles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
- B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
- B01J2/04—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops in a gaseous medium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
- B05B5/025—Discharge apparatus, e.g. electrostatic spray guns
- B05B5/0255—Discharge apparatus, e.g. electrostatic spray guns spraying and depositing by electrostatic forces only
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
- B05B5/08—Plant for applying liquids or other fluent materials to objects
- B05B5/087—Arrangements of electrodes, e.g. of charging, shielding, collecting electrodes
Abstract
APPARATUS FOR PRODUCING A SPRAY OF DROPLETS OF A LIQUID
ABSTRACT
Apparatus, for example an inhaler, is disclosed in which a spray is formed electrostatically from an outlet 6 to achieve uniform droplet size. The spray is then discharged for its intended use - in the example inhaling.
The spray is discharged completely by corona produced by a sharp discharge electrode 16 which is charged to a polarity opposite that of the liquid. In order to prevent the corona from spoiling the formation of the spray itself, the liquid at the outlet 6 is protected by a neutral shield electrode 8. The spray issues through a hole 14 in the shield electrode. The hole is sufficiently small to prevent corona getting through, yet sufficiently large to allow the spray through.
ABSTRACT
Apparatus, for example an inhaler, is disclosed in which a spray is formed electrostatically from an outlet 6 to achieve uniform droplet size. The spray is then discharged for its intended use - in the example inhaling.
The spray is discharged completely by corona produced by a sharp discharge electrode 16 which is charged to a polarity opposite that of the liquid. In order to prevent the corona from spoiling the formation of the spray itself, the liquid at the outlet 6 is protected by a neutral shield electrode 8. The spray issues through a hole 14 in the shield electrode. The hole is sufficiently small to prevent corona getting through, yet sufficiently large to allow the spray through.
Description
~277S88~
APPARATUS FOR PRODUCING A SPRAY GF DROPLETS OF A LIQUID
FIELD OF THE INVENTION
This invention relates to apparatus for producing a spray of droplets of a liquid.
BACKGROUND OF THE INVENTION
~ lectrostatic spraying apparatus is described in British patent specification No. 1,569,707, which apparatus comprises a spray head having a conducting or semiconducting surface; means for electrically charging the sprayhead surface to a potential of the order of 1-20 kilovolts; means for delivering spray liquid to the surface; a field-intensifying electrode mounted adjacent to the surface; and means for connecting the field-intensifying electrode to earth, the electrode being so sited relative to the surface that when the surface is charged, the electrostatic field thereat causes liquid thereon to atomise without substantial corona discharge to form electrically charged particles which are projected past the electrode.
In use of such apparatus, as the liquid leaves the surface, it is or becomes charged due to the voltage applied to the surface. The charge produces a repulsive force within the liquid, which overcomes the surface tension thereof causing the liquid to form into one or more cones, sometimes called Taylor cones, dependent on the configuration of the surface. A ligament of liquid is repelled from the tip of the or each cone. The ligament then breaks up into droplets.
The size of the droplets in the spray is distributed over a narrow range compared to other sprayers. The size of the droplets which is obtained depends on the resistivity and the viscosity of the liquid ~o be sprayed, on the electrical field strength at the spray head, and on the flow rate of the liquid through the spray head. The presence of the field-intensifying electrode adjacent the surface defines the electric field largely independent of the ~5 ~L275~83 distance of the sprayhead from the target. Therefore the droplet size is largely independent of the distance from the target and can be defined by adjusting the resistivity and the viscosity of the liquid and the voltage applied to the spray head.
The production of a spray of droplets having a narrow size range can be very useful. For example the behaviour o the droplets will be more uniform if the range of sizes is narrow. There are, however, applications when the fact that the droplets are charged is unwanted. ~ritish patent specification No. 2,018,627B describes a system for producing a spray which is at least partially discharged.
To do this an earthed spike is introduced near the ~prayhead. In use an ionic discharge is induced from the spike which discharges the spray at least partially.
A particular application in which it would be useful to produce a non-charged spray of droplets having a narrow distribution of size, is in inhalers to administer drugs to a patient, for example for the treatment of asthma, ~0 bronchitis and emphysema. Owing to the fine tubular structure in the lungs the depth to which a particular droplet will penetrate the lungs depends on the size of the droplets. Droplets of the order of 5 microns will reach only the upper respiratory tract, which is quite satisfactory for the treatment of asthma, but for the treatment of emphysema, it is necessary for the droplets to reach the alveoli in the lower respiratory tract, and for this purpose, droplets in the range 0.5 to 2 microns are required. Current state of the art aerosol inhalers produce a wide spectrum of droplet sizes extending up to 37 microns.
Current state of the art nebulizers will produce droplets of the required small size, but only in conjunction with droplets of larger sizes, so that with current nebulizers, only a proportion of an anti emphysema drug will reach the required site of action in the alveoli.
Naturally, it is desired that the spray produced be ~2~58~33 3 6354~-227 completely discharged for such an application. Charged spra~y would deposit in the mouth or throat, which would be unpleasant, and would not he inhaled.
In practice, we found it difficult to discharge all of the droplets produced. It was possible, using an earthed needle to discharge a large part of the spray. However, when it was attempted to discharge all the droplets, the ionic discharye ~or corona) from the needle reached the cone. This discharged the cone itsel which depleted or destroyed the formation of a ligament and thus of a spray.
SUMMARY OF TH~ INVENTION
This problem is overcome in apparatus for producing a spray of droplets of a li~uid, in accordance with the invention, which apparatus comprises: a spraying edge; means for supplying apparatus for producing a spray of droplets of a liquid comprising: a spraying edge; means for supplying the liquid to the spraying edge; a shield electrode spaced from the spraying edge and having an orifice through which li~uid sprayed from the edge can issue; means for producing a charge ~o a high potential of one polarity relative to the shield electrode in liquid at the spraying edge, to define an electric field between the edge and the shield electrode sufficient to cause the liquid to issue from the edge as at least one cone from which electrostatic forces repel through the orifice a ligament which breaks up into a spray of charged droplets; a sharp discharge electrode located on the other side of the shield electrode from the spraying edge and directed toward the orifice of the shield electrode; means for charging the discharge electrode to a high potential of the other ~Z~ 383 4 635~-2~7 polarity relative to the shield electrode, such as to produ~e a corona to discharge the spray, the shield electrode beiny of sufficient overall dimensions and having a sufficiently small orifice to shield the edge and the cone of liquid from the corona.
As an example, the sprayiny edge may be connected to a positive output of a high voltage supply, the shield electrode to earth and the discharge electrode to a negative output. In one alternative, the spraying edge may be connected to a positive high voltage output of the supply, the discharge electrode to a 10~7er voltage output and the shield electrode to an intermediate voltage output.
To have the desired shielding effect, the orifice in the shield electrode must be quite small. We found it surprising that the spray did not merely deposit on the shield. Indeed it will if the orifice is too small. We found it is possible to choose an orifice size which is large enough to allow the spray of droplets through ~ithout substantial deposition on the shield electrode, ~hilst at the same time is small enough to prevent the corona reaching the cone of liquid at the spraying edge.
The shield electrode may be constrained to earth potential or may perhaps float.
The spray itself does not pxesent sufficient space charge to induce an ionic discharge (corona), so because the shield electrode isolates the di~charge electrode from the spraying edge, an ionic discharge can not be induced if the discharge electrode is earthed. Means are therefore provided to charge the discharge electrode to a potential of polarity suitable to discharge the spray. All the droplets in the spray can be i2758~3 discharged without upsetting the formation of a ligament.
In one form, the invention provides an inhaler for producing a spray oî droplets of a liquid to be inhaled, comprising: a housing; a shield an inhaler for producing a spray of droplets of a liquid to be inhaled, comprising: a housing; a shield electrode mounted within said housing so as to define ~lith the walls of said housing a chamber within the houslng, said shield electrode having an orifice defined therethrough; at least two apertures defined in said walls and æpaced apart so as to define an air passage through the chamber so that droplets in the chamber can travel out of the chamber while air enters the chamber; a spraying edge; means for supplying a li~uid to be sprayed to the spraying edge, said spraying edge directing sprayed liquid toward the orifice in the shield electrode, said spraying edge being spaced from said shield electrode and defined exteriorly of said chamber so that liquid sprayed from the spraying edge can issue into the chamber through said orifice in said shield electrode; means for producing a charge to a high potential of one polarity relatlve to the shield electrode in liquid at the spraying edge, to define an electric field between the spraying edge and the shield electrode sufficient to cause the liquid to issue from the spraying edge as at least one cone from which electrostatic forces repel through the orifice a ligament which breaks up into a spray of charged droplets; a sharp discharge electrode mounted within said chamber and spaced from the shield electrode, said sharp discharge electrode being defined on the opposite side of the shield electrode from the spraying edge; means for charging the discharge electrode to a high ~7.5~383 5a 63~2-2270 potential o~ an opposite polarity relative to the shield electrode, so as to produce a corona to discharge ~he spray, the shield electrode being of sufficient overall dimensions and haSJing a sufficiently small orifice to define a means for shielding the edge and the cone of llquid from the corona.
Problems can arise when i~ is attempted to put the spraying edge, shield electrode and discharge electrodes inside a chamber. For example, there is a tendency for the spray to deposit on the chamber walls. There is more than one mechanism which may produce this effect. Obviously there may be some deposits due to collisions between the discharged droplets and the chamber walls. A much greater deposit may be caused, however, if the spray is not completely discharged due, for example to the voltage on the discharge electrode not being high enough or being poorly directed. Any droplets remaining charged ~7ill deposit on the chamber walls. To assist the discharge of the spray, the chamber is preferably swept completely by corona to the shield electrode, so that there are substantially no pockets where drople~s could escape being dlscharged. To this end, the 2Q discharge electrode is preferably positioned at the chamber wall and protrudes into the chamber ~rom the wall by a small amount.
The chamber wall at w7hich the discharge electrode is positioned is also pre~erably concave with respect to the chamber, so that there is little or none of the chamber behind the corona.
Droplets may also be caused to deposit on the chamber walls if the-~7alls become charged by corona from the discharge electrode. This may be caused by the discharge electrode being at ~2~5883 5b 53542-2270 too high a voltage, so that there is spare corona after the spray has all been discharged, or by the discharge electrode being poorly directed or positioned. The ~7alls become charged oppositely to the spray, which attracts both charged and discharged droplets. The walls may become so highly charged as to produce a reduction in ~S8~3 the corona discharge from the discharge electrode. In turn that may cause less than all of the spray to be discharged, This effect may be reduced or prevented by choosing a material for the chamber walls which is less than completely insulating so that if corona produces unwanted charge on the walls, this can leak away. Additionally or alternatively, the shield electrode may be cup shaped, inside or forming part of the chamber walls extending towards the discharge electrode.
BRIEF DESCRIPTION OF THE DRAWINGS
An embodiment of the invention, given by way of example, will now be described with reference to the accompanying drawing, in which:
Figure 1 shows schematically and partly in section, an inhaler embodying the invention;
Figure 2 shows an enlarged section of part of the apparatus of claim l;
Figure 3 is a schematic cross section through an alternative spraying edge 7 for the apparatus of Figure l;
and Figure 4 illustrates schematically the effect of discharging the spray in a prior art electrode arrangement.
DETAILED DESC~IPTION
Referring to Figures l and 2 (which are not to scale), liquid which it is desired to atomise is supplied via an insulating pipe 2 to an outlet 6 for the liquid. In the apparatus illustrated the outlet 6 is a metal capillary tube and is thus electrically conducting. The end of the outlet provides a spraying edge from which the liquid is sprayed.
Spaced from and in front of the spraying edge 7 is a shield electrode 8. The ou~le~ 6 and the shield electrode 8 are connected to respective terminals of a high voltage generator 10 which in use charges the spraying edge 7 to a high voltage of one polarity, preferably positive, with respect to the shield electrode 8. The voltage between the spraying edge 7 and the shield electrode 8 produces a ~S~383 sufficient electric field strength between them to draw a cone 11 of liquid from the spraying edge. The liquid leaving the spraying edge becomes charged, negative charge being conducted away by the conducting spraying edge 7, leaving a net positive charge on the liquid. The charge on the liquid produces internal repulsive electrostatic forces which overcome the surface tension of the liquid forming a cone of liquid from the tip of which issues a li~ament 12.
At a distance from the spraying edge, the mechanical forces produced on the ligament due to travelling through the air cause it to break up into charged droplets of closely similar size. The shield electrode 8 replaces the field intensifying electrode described in the above mentioned British patent specification No. 1,569,707.
In order to produce the very small droplets necessary for an inhaler, the electric field strength produced between the spraying edge and the shield electrode needs to be high.
For example, the voltage between the shield electrode 8 and the spraying edge may be in the region of 5 ~v, whilst the spacing between them may be less than 5mm, say, 2mm. It is known that air ionises differently at the different polarities and that the threshold is higher for positive potentials. In order to produce the small droplets referred to, the electric field strength is found to be so high that if the spraying edge 7 is charged negative relative to the shield electrode 8, there is a substantial risk of corona from the spraying edge and/or the cone 11 which interferes with or destroys the stability of the ligament. We have found that suitably small droplets can be produced when the spraying edge is charged positive, without the risk of corona from the spraying edge 7 or cone 11.
The formulations used in inhalers have a resistivity which is much lower than that usually used for electrostatic spraying. In most prior art applications5 say, paint spraying or spraying agricultural pesticides, in order to obtain a useful flow rate, the liquids to be sprayed usually ~7588~
have resistivities in the range 106 to 101 ohm cm. The formulations which might be used in an inhaler are expected to have resistivities in the range 5x103 to 108 ohm cm.
Although spraving of liquids which have a resistivity at the low end of the range is known from, say, US patent specification No. 1,958,406 it only works at low flow rates which have not been of much practical use. If the flow rate is too high, the ligament becomes unstable. We have found, however, that a stable ligament can be produced, and the apparatus can be made to spray satisfactorily, if the flow rate is low enough, a situation which is appropriate to inhalers, but not perhaps to agricultural or paint sprayers.
It is likely that suitable formulations will have resistivities in the range 105 to 107 ohm cm. Given that a stable spray can be produced, the lower resistivities assist in the production of a small droplet size. All other parameters equal, we find that the lower the resistivity, the smaller the droplet size.
The shield electrode has an orifice 14 aligned with the spraying edge 7 and sufficiently large that the ligament or the droplets pass through, dependent on whether the ligament breaks up before or after the shield electrode, to produce a spray of droplets in a chamber 15 beyond the shield. If the orifice were too small the droplets or ligament would deposit on the shield electrode 8. Previous expectations as expressed in the above mentioned ~ritish patent specification No. 1,569,707 would have been that with the shield electrode positioned downstream of the atomising tip of the ligament, droplets would deposit on the shield electrode even with an orifice very substantially larger than illustrated. A small orifice is required in the present apparatus for reasons explained belowO
In order to produce a spray which is inhalable, the droplets which issue through the orifice 14 must be discharged. This is effected by a discharge electrode in the form of a needle 16. In the embodiment illustrated, the ~2~75883 _ 9 _ needle is directly in the path of the spray. In alternati~e embodiments, one or more discharge electrodes may be positioned out of the direct path of the spray. The discharge electrode is connected to the high voltage generator 10 which, in use, charges the discharge electrode 16 to a high potential relative to the shield electrode 8 and of opposite polarity to that of the spraying edge, in this case negative. The shield electrode may be provided with a connection to earth, perhaps via a leakage path through the user of the inhaler, or may be left floating.
The discharge electrode 16 is driven to a sufficiently high voltage relative to the shield electrode 8 as to produce a cor~na discharge. The negative ions so produced discharge droplets in the spray issuing through the orifice 14.
The distinction between charged droplets and discharged droplets is very obvious visually. Any droplets remaining charged in the spray, are highly mobile in a predictable path. Discharged particles appear as a cloud or smoke which drifts unpredictably in the air currents.
If a prior art field intensifying electrode were used in the place of the present shield electrode, there would be considerable difficulty in discharging all the droplets in the spray. Why this is so can be understood by considering what happens as the voltage on the discharge electrode is increased from a voltage insufficient to cause ionic discharge.
Figure 4 shows an enlarged and schematic view of what would happen. A prior art field intensifying or field adjusting electrode is illustrated at 27. At the larger scale used in Figure 4, the ligament 12 can be seen oscillating at 28 due to mechanical disturbance of passing through the air. The ligament breaks up into into droplets which separate into a spray bounded approximately by a cone indicated in broken outline a~ 30. Within the spray, the charged droplets are highly mobile in predictable paths ~758~3~
generally to the right of Figure 4. At a threshold the voltage is sufficiently high that the electric field strength around the sharp tip of the needle ionises the surrounding air leaving free negative ions. These discharge surrounding droplets in an area bounded, say, by broken line 32. The discharged droplets are easily identifiable visually. They lose their predictable mobility, becoming a drifting smoke which is very distinct from the charged droplets. As the voltage is increased droplets are discharged further from the discharge electrode, so that more of the spray is discharged as indicated by7 say, broken line 34. When the voltage applied to the needle is sufficiently high that the boundary of the discharged droplets, indicated by broken line 36, reaches the edge of the spray cone 30, the spray (which is travelling to the right in Figure 3) would be completely discharged.
Unfortunately, at this point the corona uncontrollably jumps to the cone 11 and/or the spraying edge 7, which discharges the cone 11. Since it was the charge on the liquid which overcame the surface tension thereof to form the cone 11 and repel the ligament 12 therefrom, discharging the cone 11 destroys the spray.
The shield electrode 8 is arranged to shield the spraying edge 6 and the cone 11 from the corona thus enabling all the droplets in the spray to be discharged without danger of the cone being discharged. To achieve this, the orifice 14 must not be too large otherwise corona will find its way through. As mentioned above, the orifice must not be too small either, otherwise the droplets will not spray through the orifice but will deposit on the shield electrode. We have found it entirely possible to balance these conflicting requirements so that the orifice can be at the same time neither too large nor too small. With a flow rate of about 40 microlitres per minute, we found that the apparatus could be made to work with a hole 14 having a diameter in the range 2mm to lcm. At the small end of the ~L~75~383 range, there h?as 2 greater tendenc~ to spray onto the shield electrode At the larger end of the range, there was a greater tendenc~ for the corona to leak through the hole to the cone 11. Complete discharge of the spray can be ensured by adiusting the position of the needle 16 and the voltage applied thereto. We found no need in the arrangement illustrated for the voltage to be more than 10 Kv and that it could, indeed, be well below that.
The overall dimensions of the shield electrode must be sufficient to prevent corona reaching the cone 11 or spraying edge 7 round the outside of the electrode.
The shield electrode 8 may be metallic but need not necessarily be of such a good conductor as that. What is required is that the shield electrode should be sufficiently conducting to remove any charge which may accumulate due to the ionic discharge.
The outlet 6, shield electrode 8 and discharge electrode 16 are contained within a capsule 50 having a volume of about 200 ml, defining the walls of the chamber 15. In order to reduce interference with the electrical fields produced between the spraying edge and the shield electrode on the one hand, and the discharge electrode and the shield electrode on the other hand, the capsule is made of an insulating or semi-insulating material. Polyethylene plastics is an example of a very highly insulating material.
In order that any charge received by the capsule may leak away, it may be preferred to use a less insulating material for example polycarbonate~ polyethylene terephthalate or polyacetal. The shield electrode may be cup shaped extending inside the walls towards the discharge electrode, or may form part of the walls.
Two holes 52 and 54 provide an air passage through the chamber 15 transverse to the direction in which the spraying edge sprays. The discharged spray can thus be removed in an airstream across the chamber and inhaled. The airstream may be produced by the user inhaling or, if necessary or ~27s8a3 preferred, by a fan (not sho-~n).
The discharge electrode 16 has a sha.p tip which jus~
projects into the chamber 15. The wall containing the discharge electrode is concave with respect to the chamber.
Both these features are intended to reduce the volume of the chamber which is behind (to the right in Figure 2) of the corona discharge. It is desired that the corona discharge sweeps as much of the chamber 15 as possible ~ithout being so directed as to charge the walls of the chamber which would be both wasteful and could charge the walls so interfering with the formation of corona as mentioned above.
To facilitate the user inhaling the discharged spray, the air passage communicates with a face mask 56 as shown in Figure 1. A non return valve, for example a flap (not shown), may be placed between the face mask and the capsule to prevent exhaled breath blowing the discharged droplets out through the hole 54.
Also shown in Figure 1 is a supplies pack 38, ~hich in this case is shown separate. The liquid supply tube 2 and the high voltage electrical leads are bundled together as indicated schematically. A mobile emphysema patient, for example, can put the supplies pack in a pocket and move about whilst using the mask. The supplies pack contains the high voltage generator lO and delivery means 40 for supplying metered amounts of the liquid to be inhaled.
The flow rate of the liquid supplied to the outlet 6 is required to be very accurate. Accuracy is required both so that the patient gets the correct dose, and so that the droplet size remains accurate.
In order to achieve the required accurate flow rate, the delivery means 40 comprises a syringe 42 containing the liquid. The syringe is replaceable when empty. The syringe has a plunger 44, which is driven directly by a friction wheel 45. This is driven by a stepping motor and reduction gearbox 46 controlled by an ~7S88~
electrical controller 48 which may include means for setting the rate, or alternatively the rate may be fixed. This general arrangement is already used in a metered pump for administering successive doses of insulin. The pump is manufactured by Muirhead Vactric Components Ltd. of Beckenham, Kent.
Although the outlet capillary tube 6 is metallic in ~he above example, it is possible to use an insulating tube, especially when the liquid to be atomised has a resistivity towards the lower end of the range. In this case an electrode contacts the liquid upstream of the spraying edge.
The liquid is itself sufficiently conducting to carry the charge to the spraying edge so to define the electric field between the spraying edge and the shield electrode 8. The ~5 lower the resistivity of the liquid the further upstream contact can be made with the liquid.
Although illustrated as one integral piece the capsule 50 may be formed as two separable parts to facilitate cleaning.
A further form of spraying edge is illustrated in Figure 3. This spraying edge comprises an outer insulating tube 18 tapered externally at one end 20. A conducting core 22 is connected to the high voltage generator 10 by a lead 23. The core 22 tapered to a point 24 at one end. The point 24 projects slightly beyond the outer insulating tube so defining an annular orifice 26 therewith. The arrangement produces a single ligament from the tip oL the projecting point of the core.
All the examples of spraying edges described above are arranged to produce a single ligament principally because of the very low flow rate which may be required in the particular application of an inhaler. In applications where higher flow rates may be required, it may be appropriate to use a spraying edge which produces a plurality of ligaments.
One form of spraying edge which produces a plurality of ligaments is a linear nozzle (not shown). In this form ~2'75~3~3 liquid is fed to a a linear edge at which the intense electric field is formed. The linear edge may be fed wi~n liquid from a slot at or spaced from the edge. A linear nozzle is illustrated in British patent specification No.
1569707. If the edge is plane, ligaments form along its leng~h at intervals determined by various factors including the field strength and the flow rate. It is possible to position the ligaments to some extent by means of irregularities in the edge, for example teeth, which provide local intensification of the field from which the ligaments issue.
To illustrate the use of a linear nozzle, Figure 2 could still be considered a cross section through the apparatus, the outlet 6, shield electrode 8 and discharge electrode 16 all extending linearly at right angles to the plane of the paper. In effect the outlet would be a slot feeding a linear edge. It is possible to space the slot back from the edge, as would be the case if the arrangement of Figure 3 were considered to be a section through a linear nozzle. The spraying edge would then be a linear edge instead of a point described above, and the annular orifice would be a slot above and below the edge. The edge could be fed from a slot on just one side. In such arrangements the orifice 14 in the shield electrode is in the form of a slot and the discharge electrode is ei~her in the form of an edge or a row of discrete points as that illustrated.
Formulations suitable for use with an inhaler embodying the invention, are likely to have a resistivity in the range 5x103 to 108 ohm cm.
~27S883 Predominantly aqueous formulations are not completely satisfactor~, since the droplet size is so small that evaporation takes place very quickly. Water also has a high surface tension which makes it difficult to spray. Suitably the formulation comprises an acceptable organic diluent and the amount of water, if present, comprises not more than about 50% of the total diluent, more suitably less than 20%
and preferably less than 10%.
The formulation consists of a suitable, pharmaceutically acceptable, solvent e.g. dimethyl isosorbide, glycerol, propylene glycol and polyethylene glycol of average molecular weight up to about 600 admixed with water or ethanol. In addition the formulations may contain a suitable pharmaceutically acceptable surfactant e.g. polyethoxy-ethylated castor oils ("Cremophors"),*
polyoxyethylene-polyoxypropylene block copolymers ("Pluronics"* "Synperonics"), polyoxyethylene sorbitan derivatives ("Tweens")* polyoxyethylene oleyl ethers ("Brijs"~ and sorbitan esters of fatty acids ("Spans"). Such materials are preferably present at not more than 1%
concentration.
An inhaler embodying the invention is suitable for the administration to a patient of any drug which can be administered via the lungs, either to have a direct effect on the lungs, for example for the treatment of asthma, emphysema or bronchitis, or for absorption from the lung into the bloodstream in order to produce a systemic therapeutic effect else~here in the body. Examples of drugs which have a direct effect on the lung for the treatment of asthma, emphysema or bronchitis are bronchospasm relaxants such as adrenaline9 isoprenaline, orciprenaline, ephedrine, phenylephrine3 diphenhydramine, terbutalene, isoetharine, etafedrine, methoxyphenamine, theophylline, aminophylline, salbutamol, sodium cromoglycate, ipratropium bromide, beclomethasone, betamethasone valerate, fenoterol, reproterol, pirbuterol, budesonide, ketotifen and compounds * Trad~k ~L2~7~i8~3 as defined and claimed in published European patent specification No. 189 305, particularly those compounds defined in claims 4, 5 and 6. Examples of drugs which can be administered systemically via the lungs include polypeptide drugs, for example luteinising hormone-releasing hormone, and synthetic analogues thereof.
Suitably the active ingredient is in the formulation in a concentration range of 0.1 to 20%, and preferably 5 to 10%, but the required concentration depends, naturally, upon the potency of the particular drug being used.
APPARATUS FOR PRODUCING A SPRAY GF DROPLETS OF A LIQUID
FIELD OF THE INVENTION
This invention relates to apparatus for producing a spray of droplets of a liquid.
BACKGROUND OF THE INVENTION
~ lectrostatic spraying apparatus is described in British patent specification No. 1,569,707, which apparatus comprises a spray head having a conducting or semiconducting surface; means for electrically charging the sprayhead surface to a potential of the order of 1-20 kilovolts; means for delivering spray liquid to the surface; a field-intensifying electrode mounted adjacent to the surface; and means for connecting the field-intensifying electrode to earth, the electrode being so sited relative to the surface that when the surface is charged, the electrostatic field thereat causes liquid thereon to atomise without substantial corona discharge to form electrically charged particles which are projected past the electrode.
In use of such apparatus, as the liquid leaves the surface, it is or becomes charged due to the voltage applied to the surface. The charge produces a repulsive force within the liquid, which overcomes the surface tension thereof causing the liquid to form into one or more cones, sometimes called Taylor cones, dependent on the configuration of the surface. A ligament of liquid is repelled from the tip of the or each cone. The ligament then breaks up into droplets.
The size of the droplets in the spray is distributed over a narrow range compared to other sprayers. The size of the droplets which is obtained depends on the resistivity and the viscosity of the liquid ~o be sprayed, on the electrical field strength at the spray head, and on the flow rate of the liquid through the spray head. The presence of the field-intensifying electrode adjacent the surface defines the electric field largely independent of the ~5 ~L275~83 distance of the sprayhead from the target. Therefore the droplet size is largely independent of the distance from the target and can be defined by adjusting the resistivity and the viscosity of the liquid and the voltage applied to the spray head.
The production of a spray of droplets having a narrow size range can be very useful. For example the behaviour o the droplets will be more uniform if the range of sizes is narrow. There are, however, applications when the fact that the droplets are charged is unwanted. ~ritish patent specification No. 2,018,627B describes a system for producing a spray which is at least partially discharged.
To do this an earthed spike is introduced near the ~prayhead. In use an ionic discharge is induced from the spike which discharges the spray at least partially.
A particular application in which it would be useful to produce a non-charged spray of droplets having a narrow distribution of size, is in inhalers to administer drugs to a patient, for example for the treatment of asthma, ~0 bronchitis and emphysema. Owing to the fine tubular structure in the lungs the depth to which a particular droplet will penetrate the lungs depends on the size of the droplets. Droplets of the order of 5 microns will reach only the upper respiratory tract, which is quite satisfactory for the treatment of asthma, but for the treatment of emphysema, it is necessary for the droplets to reach the alveoli in the lower respiratory tract, and for this purpose, droplets in the range 0.5 to 2 microns are required. Current state of the art aerosol inhalers produce a wide spectrum of droplet sizes extending up to 37 microns.
Current state of the art nebulizers will produce droplets of the required small size, but only in conjunction with droplets of larger sizes, so that with current nebulizers, only a proportion of an anti emphysema drug will reach the required site of action in the alveoli.
Naturally, it is desired that the spray produced be ~2~58~33 3 6354~-227 completely discharged for such an application. Charged spra~y would deposit in the mouth or throat, which would be unpleasant, and would not he inhaled.
In practice, we found it difficult to discharge all of the droplets produced. It was possible, using an earthed needle to discharge a large part of the spray. However, when it was attempted to discharge all the droplets, the ionic discharye ~or corona) from the needle reached the cone. This discharged the cone itsel which depleted or destroyed the formation of a ligament and thus of a spray.
SUMMARY OF TH~ INVENTION
This problem is overcome in apparatus for producing a spray of droplets of a li~uid, in accordance with the invention, which apparatus comprises: a spraying edge; means for supplying apparatus for producing a spray of droplets of a liquid comprising: a spraying edge; means for supplying the liquid to the spraying edge; a shield electrode spaced from the spraying edge and having an orifice through which li~uid sprayed from the edge can issue; means for producing a charge ~o a high potential of one polarity relative to the shield electrode in liquid at the spraying edge, to define an electric field between the edge and the shield electrode sufficient to cause the liquid to issue from the edge as at least one cone from which electrostatic forces repel through the orifice a ligament which breaks up into a spray of charged droplets; a sharp discharge electrode located on the other side of the shield electrode from the spraying edge and directed toward the orifice of the shield electrode; means for charging the discharge electrode to a high potential of the other ~Z~ 383 4 635~-2~7 polarity relative to the shield electrode, such as to produ~e a corona to discharge the spray, the shield electrode beiny of sufficient overall dimensions and having a sufficiently small orifice to shield the edge and the cone of liquid from the corona.
As an example, the sprayiny edge may be connected to a positive output of a high voltage supply, the shield electrode to earth and the discharge electrode to a negative output. In one alternative, the spraying edge may be connected to a positive high voltage output of the supply, the discharge electrode to a 10~7er voltage output and the shield electrode to an intermediate voltage output.
To have the desired shielding effect, the orifice in the shield electrode must be quite small. We found it surprising that the spray did not merely deposit on the shield. Indeed it will if the orifice is too small. We found it is possible to choose an orifice size which is large enough to allow the spray of droplets through ~ithout substantial deposition on the shield electrode, ~hilst at the same time is small enough to prevent the corona reaching the cone of liquid at the spraying edge.
The shield electrode may be constrained to earth potential or may perhaps float.
The spray itself does not pxesent sufficient space charge to induce an ionic discharge (corona), so because the shield electrode isolates the di~charge electrode from the spraying edge, an ionic discharge can not be induced if the discharge electrode is earthed. Means are therefore provided to charge the discharge electrode to a potential of polarity suitable to discharge the spray. All the droplets in the spray can be i2758~3 discharged without upsetting the formation of a ligament.
In one form, the invention provides an inhaler for producing a spray oî droplets of a liquid to be inhaled, comprising: a housing; a shield an inhaler for producing a spray of droplets of a liquid to be inhaled, comprising: a housing; a shield electrode mounted within said housing so as to define ~lith the walls of said housing a chamber within the houslng, said shield electrode having an orifice defined therethrough; at least two apertures defined in said walls and æpaced apart so as to define an air passage through the chamber so that droplets in the chamber can travel out of the chamber while air enters the chamber; a spraying edge; means for supplying a li~uid to be sprayed to the spraying edge, said spraying edge directing sprayed liquid toward the orifice in the shield electrode, said spraying edge being spaced from said shield electrode and defined exteriorly of said chamber so that liquid sprayed from the spraying edge can issue into the chamber through said orifice in said shield electrode; means for producing a charge to a high potential of one polarity relatlve to the shield electrode in liquid at the spraying edge, to define an electric field between the spraying edge and the shield electrode sufficient to cause the liquid to issue from the spraying edge as at least one cone from which electrostatic forces repel through the orifice a ligament which breaks up into a spray of charged droplets; a sharp discharge electrode mounted within said chamber and spaced from the shield electrode, said sharp discharge electrode being defined on the opposite side of the shield electrode from the spraying edge; means for charging the discharge electrode to a high ~7.5~383 5a 63~2-2270 potential o~ an opposite polarity relative to the shield electrode, so as to produce a corona to discharge ~he spray, the shield electrode being of sufficient overall dimensions and haSJing a sufficiently small orifice to define a means for shielding the edge and the cone of llquid from the corona.
Problems can arise when i~ is attempted to put the spraying edge, shield electrode and discharge electrodes inside a chamber. For example, there is a tendency for the spray to deposit on the chamber walls. There is more than one mechanism which may produce this effect. Obviously there may be some deposits due to collisions between the discharged droplets and the chamber walls. A much greater deposit may be caused, however, if the spray is not completely discharged due, for example to the voltage on the discharge electrode not being high enough or being poorly directed. Any droplets remaining charged ~7ill deposit on the chamber walls. To assist the discharge of the spray, the chamber is preferably swept completely by corona to the shield electrode, so that there are substantially no pockets where drople~s could escape being dlscharged. To this end, the 2Q discharge electrode is preferably positioned at the chamber wall and protrudes into the chamber ~rom the wall by a small amount.
The chamber wall at w7hich the discharge electrode is positioned is also pre~erably concave with respect to the chamber, so that there is little or none of the chamber behind the corona.
Droplets may also be caused to deposit on the chamber walls if the-~7alls become charged by corona from the discharge electrode. This may be caused by the discharge electrode being at ~2~5883 5b 53542-2270 too high a voltage, so that there is spare corona after the spray has all been discharged, or by the discharge electrode being poorly directed or positioned. The ~7alls become charged oppositely to the spray, which attracts both charged and discharged droplets. The walls may become so highly charged as to produce a reduction in ~S8~3 the corona discharge from the discharge electrode. In turn that may cause less than all of the spray to be discharged, This effect may be reduced or prevented by choosing a material for the chamber walls which is less than completely insulating so that if corona produces unwanted charge on the walls, this can leak away. Additionally or alternatively, the shield electrode may be cup shaped, inside or forming part of the chamber walls extending towards the discharge electrode.
BRIEF DESCRIPTION OF THE DRAWINGS
An embodiment of the invention, given by way of example, will now be described with reference to the accompanying drawing, in which:
Figure 1 shows schematically and partly in section, an inhaler embodying the invention;
Figure 2 shows an enlarged section of part of the apparatus of claim l;
Figure 3 is a schematic cross section through an alternative spraying edge 7 for the apparatus of Figure l;
and Figure 4 illustrates schematically the effect of discharging the spray in a prior art electrode arrangement.
DETAILED DESC~IPTION
Referring to Figures l and 2 (which are not to scale), liquid which it is desired to atomise is supplied via an insulating pipe 2 to an outlet 6 for the liquid. In the apparatus illustrated the outlet 6 is a metal capillary tube and is thus electrically conducting. The end of the outlet provides a spraying edge from which the liquid is sprayed.
Spaced from and in front of the spraying edge 7 is a shield electrode 8. The ou~le~ 6 and the shield electrode 8 are connected to respective terminals of a high voltage generator 10 which in use charges the spraying edge 7 to a high voltage of one polarity, preferably positive, with respect to the shield electrode 8. The voltage between the spraying edge 7 and the shield electrode 8 produces a ~S~383 sufficient electric field strength between them to draw a cone 11 of liquid from the spraying edge. The liquid leaving the spraying edge becomes charged, negative charge being conducted away by the conducting spraying edge 7, leaving a net positive charge on the liquid. The charge on the liquid produces internal repulsive electrostatic forces which overcome the surface tension of the liquid forming a cone of liquid from the tip of which issues a li~ament 12.
At a distance from the spraying edge, the mechanical forces produced on the ligament due to travelling through the air cause it to break up into charged droplets of closely similar size. The shield electrode 8 replaces the field intensifying electrode described in the above mentioned British patent specification No. 1,569,707.
In order to produce the very small droplets necessary for an inhaler, the electric field strength produced between the spraying edge and the shield electrode needs to be high.
For example, the voltage between the shield electrode 8 and the spraying edge may be in the region of 5 ~v, whilst the spacing between them may be less than 5mm, say, 2mm. It is known that air ionises differently at the different polarities and that the threshold is higher for positive potentials. In order to produce the small droplets referred to, the electric field strength is found to be so high that if the spraying edge 7 is charged negative relative to the shield electrode 8, there is a substantial risk of corona from the spraying edge and/or the cone 11 which interferes with or destroys the stability of the ligament. We have found that suitably small droplets can be produced when the spraying edge is charged positive, without the risk of corona from the spraying edge 7 or cone 11.
The formulations used in inhalers have a resistivity which is much lower than that usually used for electrostatic spraying. In most prior art applications5 say, paint spraying or spraying agricultural pesticides, in order to obtain a useful flow rate, the liquids to be sprayed usually ~7588~
have resistivities in the range 106 to 101 ohm cm. The formulations which might be used in an inhaler are expected to have resistivities in the range 5x103 to 108 ohm cm.
Although spraving of liquids which have a resistivity at the low end of the range is known from, say, US patent specification No. 1,958,406 it only works at low flow rates which have not been of much practical use. If the flow rate is too high, the ligament becomes unstable. We have found, however, that a stable ligament can be produced, and the apparatus can be made to spray satisfactorily, if the flow rate is low enough, a situation which is appropriate to inhalers, but not perhaps to agricultural or paint sprayers.
It is likely that suitable formulations will have resistivities in the range 105 to 107 ohm cm. Given that a stable spray can be produced, the lower resistivities assist in the production of a small droplet size. All other parameters equal, we find that the lower the resistivity, the smaller the droplet size.
The shield electrode has an orifice 14 aligned with the spraying edge 7 and sufficiently large that the ligament or the droplets pass through, dependent on whether the ligament breaks up before or after the shield electrode, to produce a spray of droplets in a chamber 15 beyond the shield. If the orifice were too small the droplets or ligament would deposit on the shield electrode 8. Previous expectations as expressed in the above mentioned ~ritish patent specification No. 1,569,707 would have been that with the shield electrode positioned downstream of the atomising tip of the ligament, droplets would deposit on the shield electrode even with an orifice very substantially larger than illustrated. A small orifice is required in the present apparatus for reasons explained belowO
In order to produce a spray which is inhalable, the droplets which issue through the orifice 14 must be discharged. This is effected by a discharge electrode in the form of a needle 16. In the embodiment illustrated, the ~2~75883 _ 9 _ needle is directly in the path of the spray. In alternati~e embodiments, one or more discharge electrodes may be positioned out of the direct path of the spray. The discharge electrode is connected to the high voltage generator 10 which, in use, charges the discharge electrode 16 to a high potential relative to the shield electrode 8 and of opposite polarity to that of the spraying edge, in this case negative. The shield electrode may be provided with a connection to earth, perhaps via a leakage path through the user of the inhaler, or may be left floating.
The discharge electrode 16 is driven to a sufficiently high voltage relative to the shield electrode 8 as to produce a cor~na discharge. The negative ions so produced discharge droplets in the spray issuing through the orifice 14.
The distinction between charged droplets and discharged droplets is very obvious visually. Any droplets remaining charged in the spray, are highly mobile in a predictable path. Discharged particles appear as a cloud or smoke which drifts unpredictably in the air currents.
If a prior art field intensifying electrode were used in the place of the present shield electrode, there would be considerable difficulty in discharging all the droplets in the spray. Why this is so can be understood by considering what happens as the voltage on the discharge electrode is increased from a voltage insufficient to cause ionic discharge.
Figure 4 shows an enlarged and schematic view of what would happen. A prior art field intensifying or field adjusting electrode is illustrated at 27. At the larger scale used in Figure 4, the ligament 12 can be seen oscillating at 28 due to mechanical disturbance of passing through the air. The ligament breaks up into into droplets which separate into a spray bounded approximately by a cone indicated in broken outline a~ 30. Within the spray, the charged droplets are highly mobile in predictable paths ~758~3~
generally to the right of Figure 4. At a threshold the voltage is sufficiently high that the electric field strength around the sharp tip of the needle ionises the surrounding air leaving free negative ions. These discharge surrounding droplets in an area bounded, say, by broken line 32. The discharged droplets are easily identifiable visually. They lose their predictable mobility, becoming a drifting smoke which is very distinct from the charged droplets. As the voltage is increased droplets are discharged further from the discharge electrode, so that more of the spray is discharged as indicated by7 say, broken line 34. When the voltage applied to the needle is sufficiently high that the boundary of the discharged droplets, indicated by broken line 36, reaches the edge of the spray cone 30, the spray (which is travelling to the right in Figure 3) would be completely discharged.
Unfortunately, at this point the corona uncontrollably jumps to the cone 11 and/or the spraying edge 7, which discharges the cone 11. Since it was the charge on the liquid which overcame the surface tension thereof to form the cone 11 and repel the ligament 12 therefrom, discharging the cone 11 destroys the spray.
The shield electrode 8 is arranged to shield the spraying edge 6 and the cone 11 from the corona thus enabling all the droplets in the spray to be discharged without danger of the cone being discharged. To achieve this, the orifice 14 must not be too large otherwise corona will find its way through. As mentioned above, the orifice must not be too small either, otherwise the droplets will not spray through the orifice but will deposit on the shield electrode. We have found it entirely possible to balance these conflicting requirements so that the orifice can be at the same time neither too large nor too small. With a flow rate of about 40 microlitres per minute, we found that the apparatus could be made to work with a hole 14 having a diameter in the range 2mm to lcm. At the small end of the ~L~75~383 range, there h?as 2 greater tendenc~ to spray onto the shield electrode At the larger end of the range, there was a greater tendenc~ for the corona to leak through the hole to the cone 11. Complete discharge of the spray can be ensured by adiusting the position of the needle 16 and the voltage applied thereto. We found no need in the arrangement illustrated for the voltage to be more than 10 Kv and that it could, indeed, be well below that.
The overall dimensions of the shield electrode must be sufficient to prevent corona reaching the cone 11 or spraying edge 7 round the outside of the electrode.
The shield electrode 8 may be metallic but need not necessarily be of such a good conductor as that. What is required is that the shield electrode should be sufficiently conducting to remove any charge which may accumulate due to the ionic discharge.
The outlet 6, shield electrode 8 and discharge electrode 16 are contained within a capsule 50 having a volume of about 200 ml, defining the walls of the chamber 15. In order to reduce interference with the electrical fields produced between the spraying edge and the shield electrode on the one hand, and the discharge electrode and the shield electrode on the other hand, the capsule is made of an insulating or semi-insulating material. Polyethylene plastics is an example of a very highly insulating material.
In order that any charge received by the capsule may leak away, it may be preferred to use a less insulating material for example polycarbonate~ polyethylene terephthalate or polyacetal. The shield electrode may be cup shaped extending inside the walls towards the discharge electrode, or may form part of the walls.
Two holes 52 and 54 provide an air passage through the chamber 15 transverse to the direction in which the spraying edge sprays. The discharged spray can thus be removed in an airstream across the chamber and inhaled. The airstream may be produced by the user inhaling or, if necessary or ~27s8a3 preferred, by a fan (not sho-~n).
The discharge electrode 16 has a sha.p tip which jus~
projects into the chamber 15. The wall containing the discharge electrode is concave with respect to the chamber.
Both these features are intended to reduce the volume of the chamber which is behind (to the right in Figure 2) of the corona discharge. It is desired that the corona discharge sweeps as much of the chamber 15 as possible ~ithout being so directed as to charge the walls of the chamber which would be both wasteful and could charge the walls so interfering with the formation of corona as mentioned above.
To facilitate the user inhaling the discharged spray, the air passage communicates with a face mask 56 as shown in Figure 1. A non return valve, for example a flap (not shown), may be placed between the face mask and the capsule to prevent exhaled breath blowing the discharged droplets out through the hole 54.
Also shown in Figure 1 is a supplies pack 38, ~hich in this case is shown separate. The liquid supply tube 2 and the high voltage electrical leads are bundled together as indicated schematically. A mobile emphysema patient, for example, can put the supplies pack in a pocket and move about whilst using the mask. The supplies pack contains the high voltage generator lO and delivery means 40 for supplying metered amounts of the liquid to be inhaled.
The flow rate of the liquid supplied to the outlet 6 is required to be very accurate. Accuracy is required both so that the patient gets the correct dose, and so that the droplet size remains accurate.
In order to achieve the required accurate flow rate, the delivery means 40 comprises a syringe 42 containing the liquid. The syringe is replaceable when empty. The syringe has a plunger 44, which is driven directly by a friction wheel 45. This is driven by a stepping motor and reduction gearbox 46 controlled by an ~7S88~
electrical controller 48 which may include means for setting the rate, or alternatively the rate may be fixed. This general arrangement is already used in a metered pump for administering successive doses of insulin. The pump is manufactured by Muirhead Vactric Components Ltd. of Beckenham, Kent.
Although the outlet capillary tube 6 is metallic in ~he above example, it is possible to use an insulating tube, especially when the liquid to be atomised has a resistivity towards the lower end of the range. In this case an electrode contacts the liquid upstream of the spraying edge.
The liquid is itself sufficiently conducting to carry the charge to the spraying edge so to define the electric field between the spraying edge and the shield electrode 8. The ~5 lower the resistivity of the liquid the further upstream contact can be made with the liquid.
Although illustrated as one integral piece the capsule 50 may be formed as two separable parts to facilitate cleaning.
A further form of spraying edge is illustrated in Figure 3. This spraying edge comprises an outer insulating tube 18 tapered externally at one end 20. A conducting core 22 is connected to the high voltage generator 10 by a lead 23. The core 22 tapered to a point 24 at one end. The point 24 projects slightly beyond the outer insulating tube so defining an annular orifice 26 therewith. The arrangement produces a single ligament from the tip oL the projecting point of the core.
All the examples of spraying edges described above are arranged to produce a single ligament principally because of the very low flow rate which may be required in the particular application of an inhaler. In applications where higher flow rates may be required, it may be appropriate to use a spraying edge which produces a plurality of ligaments.
One form of spraying edge which produces a plurality of ligaments is a linear nozzle (not shown). In this form ~2'75~3~3 liquid is fed to a a linear edge at which the intense electric field is formed. The linear edge may be fed wi~n liquid from a slot at or spaced from the edge. A linear nozzle is illustrated in British patent specification No.
1569707. If the edge is plane, ligaments form along its leng~h at intervals determined by various factors including the field strength and the flow rate. It is possible to position the ligaments to some extent by means of irregularities in the edge, for example teeth, which provide local intensification of the field from which the ligaments issue.
To illustrate the use of a linear nozzle, Figure 2 could still be considered a cross section through the apparatus, the outlet 6, shield electrode 8 and discharge electrode 16 all extending linearly at right angles to the plane of the paper. In effect the outlet would be a slot feeding a linear edge. It is possible to space the slot back from the edge, as would be the case if the arrangement of Figure 3 were considered to be a section through a linear nozzle. The spraying edge would then be a linear edge instead of a point described above, and the annular orifice would be a slot above and below the edge. The edge could be fed from a slot on just one side. In such arrangements the orifice 14 in the shield electrode is in the form of a slot and the discharge electrode is ei~her in the form of an edge or a row of discrete points as that illustrated.
Formulations suitable for use with an inhaler embodying the invention, are likely to have a resistivity in the range 5x103 to 108 ohm cm.
~27S883 Predominantly aqueous formulations are not completely satisfactor~, since the droplet size is so small that evaporation takes place very quickly. Water also has a high surface tension which makes it difficult to spray. Suitably the formulation comprises an acceptable organic diluent and the amount of water, if present, comprises not more than about 50% of the total diluent, more suitably less than 20%
and preferably less than 10%.
The formulation consists of a suitable, pharmaceutically acceptable, solvent e.g. dimethyl isosorbide, glycerol, propylene glycol and polyethylene glycol of average molecular weight up to about 600 admixed with water or ethanol. In addition the formulations may contain a suitable pharmaceutically acceptable surfactant e.g. polyethoxy-ethylated castor oils ("Cremophors"),*
polyoxyethylene-polyoxypropylene block copolymers ("Pluronics"* "Synperonics"), polyoxyethylene sorbitan derivatives ("Tweens")* polyoxyethylene oleyl ethers ("Brijs"~ and sorbitan esters of fatty acids ("Spans"). Such materials are preferably present at not more than 1%
concentration.
An inhaler embodying the invention is suitable for the administration to a patient of any drug which can be administered via the lungs, either to have a direct effect on the lungs, for example for the treatment of asthma, emphysema or bronchitis, or for absorption from the lung into the bloodstream in order to produce a systemic therapeutic effect else~here in the body. Examples of drugs which have a direct effect on the lung for the treatment of asthma, emphysema or bronchitis are bronchospasm relaxants such as adrenaline9 isoprenaline, orciprenaline, ephedrine, phenylephrine3 diphenhydramine, terbutalene, isoetharine, etafedrine, methoxyphenamine, theophylline, aminophylline, salbutamol, sodium cromoglycate, ipratropium bromide, beclomethasone, betamethasone valerate, fenoterol, reproterol, pirbuterol, budesonide, ketotifen and compounds * Trad~k ~L2~7~i8~3 as defined and claimed in published European patent specification No. 189 305, particularly those compounds defined in claims 4, 5 and 6. Examples of drugs which can be administered systemically via the lungs include polypeptide drugs, for example luteinising hormone-releasing hormone, and synthetic analogues thereof.
Suitably the active ingredient is in the formulation in a concentration range of 0.1 to 20%, and preferably 5 to 10%, but the required concentration depends, naturally, upon the potency of the particular drug being used.
Claims (12)
1. Apparatus for producing a spray of droplets of a liquid comprising: a spraying edge; means for supplying the liquid to the spraying edge; a shield electrode spaced from the spraying edge and having an orifice through which liquid sprayed from the edge can issue; means for producing a charge to a high potential of one polarity relative to the shield electrode in liquid at the spraying edge, to define an electric field between the edge and the shield electrode sufficient to cause the liquid to issue from the edge as at least one cone from which electrostatic forces repel through the orifice a ligament which breaks up into a spray of charged droplets; a sharp discharge electrode located on the other side of the shield electrode from the spraying edge and directed toward the orifice of the shield electrode; means for charging the discharge electrode to a high potential of the other polarity relative to the shield electrode, such as to produce a corona to discharge the spray, the shield electrode being of sufficient overall dimensions and having a sufficiently small orifice to shield the edge and the cone of liquid from the corona.
2. An inhaler for producing a spray of droplets of a liquid to be inhaled, comprising: a housing; a shield electrode mounted within said housing so as to define with the walls of said housing a chamber within the housing, said shield electrode having an orifice defined therethrough; at least two apertures defined in said walls and spaced apart so as to define an air passage through the chamber so that droplets in the chamber can travel out of the chamber while air enters the chamber; a spraying edge; means for supplying a liquid to be sprayed to the spraying edge, said spraying edge directing sprayed liquid toward the orifice in the shield electrode, said spraying edge being spaced from said shield electrode and defined exteriorly of said chamber so that liquid sprayed from the spraying edge can issue into the chamber through said orifice in said shield electrode; means for producing a charge to a high potential of one polarity relative to the shield electrode in liquid at the spraying edge, to define an electric field between the spraying edge and the shield electrode sufficient to cause the liquid to issue from the spraying edge as at least one cone from which electrostatic forces repel through the orifice a ligament which breaks up into a spray of charged droplets; a sharp discharge electrode mounted within said chamber and spaced from the shield electrode, said sharp discharge electrode being defined on the opposite side of the shield electrode from the spraying edge; means for charging the discharge electrode to a high potential of an opposite polarity relative to the shield electrode, so as to produce a corona to discharge the spray, the shield electrode being of sufficient overall dimensions and having a sufficiently small orifice to define a means for shielding the edge and the cone of liquid from the corona.
3. An inhaler as claimed in claim 2, including a face mask and means connecting the face mask to one of said apertures.
4. An inhaler as claimed in claim 2, wherein the discharge electrode is positioned at the chamber wall opposite the spraying edge and protrudes into the chamber from the wall by a small amount, the chamber wall being insulating or semi-insulating at least in the vicinity of the discharge electrode.
5. An inhaler as claimed in claim 4, wherein the chamber wall at which the discharge electrode is positioned is concave with respect to the chamber.
6. An inhaler as claimed in claim 4, wherein the air passage is transverse to the direction of spray.
7. An inhaler as claimed in claim 2, further comprising means on the spraying edge to produce a spray having a droplet size of from 2 to 5 microns diameter when used with a liquid having a resistivity in the range from 5 x 103 ohm cm. to 108 ohm cm.
8. An inhaler as claimed in claim 7, wherein the liquid sprayed from the spraying edge has a resistivity in the range from 105 to 107 ohm cm.
9. An inhaler as claimed in claim 2, wherein the spraying edge includes means to produce a single ligament.
10. An inhaler as claimed in claim 9, wherein the spraying edge comprises an annular orifice arranged to feed liquid to the surface of a pointed core extending from the annular orifice toward the chamber, so that, in use, the single ligament issues from the point of the core.
11. An inhaler as claimed in claim 10, wherein the spraying edge comprises the end of a capillary tube.
12. An inhaler as claimed in claim 2, wherein the means for charging the liquid is arranged to charge the liquid to a positive potential relative to the shield electrode.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB868604328A GB8604328D0 (en) | 1986-02-21 | 1986-02-21 | Producing spray of droplets of liquid |
| GB8604328 | 1986-02-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1275883C true CA1275883C (en) | 1990-11-06 |
Family
ID=10593447
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000530183A Expired - Lifetime CA1275883C (en) | 1986-02-21 | 1987-02-20 | Apparatus for producing a spray of droplets of a liquid |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US4829996A (en) |
| EP (2) | EP0234841A3 (en) |
| JP (2) | JPH0824714B2 (en) |
| AT (1) | ATE56156T1 (en) |
| AU (2) | AU594429B2 (en) |
| CA (1) | CA1275883C (en) |
| DE (1) | DE3764662D1 (en) |
| DK (1) | DK164847C (en) |
| ES (1) | ES2016969B3 (en) |
| FI (2) | FI870640A (en) |
| GB (1) | GB8604328D0 (en) |
| GR (1) | GR3000843T3 (en) |
| IE (1) | IE59596B1 (en) |
| IL (1) | IL81572A (en) |
| NO (2) | NO870660L (en) |
| NZ (2) | NZ219305A (en) |
| PT (1) | PT84320B (en) |
| ZA (2) | ZA871146B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7193124B2 (en) | 1997-07-22 | 2007-03-20 | Battelle Memorial Institute | Method for forming material |
| US7977527B2 (en) | 1996-07-23 | 2011-07-12 | Baltelle Memorial Institute | Dispensing device and method for forming material |
Families Citing this family (156)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8614566D0 (en) * | 1986-06-16 | 1986-07-23 | Ici Plc | Spraying |
| DE3735787A1 (en) * | 1987-09-22 | 1989-03-30 | Stiftung Inst Fuer Werkstoffte | METHOD AND DEVICE FOR SPRAYING AT LEAST ONE JET OF A LIQUID, PREFERABLY MOLTED METAL |
| US4981625A (en) * | 1988-03-14 | 1991-01-01 | California Institute Of Technology | Monodisperse, polymeric microspheres produced by irradiation of slowly thawing frozen drops |
| US5115971A (en) * | 1988-09-23 | 1992-05-26 | Battelle Memorial Institute | Nebulizer device |
| US5096615A (en) * | 1988-07-19 | 1992-03-17 | The United States Of America As Represented By The United States Department Of Energy | Solid aerosol generator |
| US5503372A (en) * | 1989-11-27 | 1996-04-02 | Martin Marietta Energy Systems, Inc. | Nozzle for electric dispersion reactor |
| EP0501725B1 (en) * | 1991-03-01 | 2001-06-13 | The Procter & Gamble Company | Spraying of liquids |
| US5196171A (en) * | 1991-03-11 | 1993-03-23 | In-Vironmental Integrity, Inc. | Electrostatic vapor/aerosol/air ion generator |
| GB9115275D0 (en) * | 1991-07-15 | 1991-08-28 | Unilever Plc | Colour cosmetic spray system |
| GB9115276D0 (en) * | 1991-07-15 | 1991-08-28 | Unilever Plc | Skin treatment system |
| GB9115278D0 (en) * | 1991-07-15 | 1991-08-28 | Unilever Plc | Liquid spraying apparatus and method |
| US5173274A (en) * | 1991-08-16 | 1992-12-22 | Southwest Research Institute | Flash liquid aerosol production method and appartus |
| US5247842A (en) * | 1991-09-30 | 1993-09-28 | Tsi Incorporated | Electrospray apparatus for producing uniform submicrometer droplets |
| US5320094A (en) * | 1992-01-10 | 1994-06-14 | The Johns Hopkins University | Method of administering insulin |
| JP2878898B2 (en) * | 1992-04-03 | 1999-04-05 | 信越化学工業株式会社 | Rare earth element oxide particles |
| US5326598A (en) * | 1992-10-02 | 1994-07-05 | Minnesota Mining And Manufacturing Company | Electrospray coating apparatus and process utilizing precise control of filament and mist generation |
| GB9224191D0 (en) * | 1992-11-18 | 1993-01-06 | Unilever Plc | Cosmetic delivery system |
| GB9225098D0 (en) | 1992-12-01 | 1993-01-20 | Coffee Ronald A | Charged droplet spray mixer |
| US6105571A (en) | 1992-12-22 | 2000-08-22 | Electrosols, Ltd. | Dispensing device |
| GB9226717D0 (en) * | 1992-12-22 | 1993-02-17 | Coffee Ronald A | Induction-operated electro-hydrodynamic spray device with means of modifying droplet trajectories |
| US6880554B1 (en) | 1992-12-22 | 2005-04-19 | Battelle Memorial Institute | Dispensing device |
| US5447708A (en) * | 1993-01-21 | 1995-09-05 | Physical Sciences, Inc. | Apparatus for producing nanoscale ceramic powders |
| EP0706352B1 (en) * | 1993-06-29 | 2002-03-20 | Ponwell Enterprises Limited | Dispenser |
| SE9400257D0 (en) * | 1994-01-27 | 1994-01-27 | Astra Ab | spacer |
| GB9406171D0 (en) * | 1994-03-29 | 1994-05-18 | Electrosols Ltd | Dispensing device |
| GB9406255D0 (en) * | 1994-03-29 | 1994-05-18 | Electrosols Ltd | Dispensing device |
| US6729334B1 (en) | 1994-06-17 | 2004-05-04 | Trudell Medical Limited | Nebulizing catheter system and methods of use and manufacture |
| IL114154A0 (en) * | 1994-06-17 | 1995-10-31 | Trudell Medical Ltd | Nebulizing catheter system and methods of use and manufacture |
| US5642730A (en) * | 1994-06-17 | 1997-07-01 | Trudell Medical Limited | Catheter system for delivery of aerosolized medicine for use with pressurized propellant canister |
| GB9413281D0 (en) * | 1994-07-01 | 1994-08-24 | Univ Southampton | Electrostatically pre-charged polymer powder paints |
| US5520715A (en) * | 1994-07-11 | 1996-05-28 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | Directional electrostatic accretion process employing acoustic droplet formation |
| US5560543A (en) * | 1994-09-19 | 1996-10-01 | Board Of Regents, The University Of Texas System | Heat-resistant broad-bandwidth liquid droplet generators |
| GB9511514D0 (en) * | 1995-06-07 | 1995-08-02 | Ici Plc | Electrostatic spraying |
| SE504458C2 (en) * | 1995-06-21 | 1997-02-17 | Lars Gunnar Nilsson | Inhalator for electrical dosing of substances |
| KR0144599B1 (en) * | 1995-07-01 | 1998-07-15 | 윤덕용 | Liquid-drop generator and device for preparing fine-partides |
| US5669433A (en) * | 1995-09-08 | 1997-09-23 | Aeroquip Corporation | Method for creating a free-form metal three-dimensional article using a layer-by-layer deposition of a molten metal |
| US5718951A (en) * | 1995-09-08 | 1998-02-17 | Aeroquip Corporation | Method and apparatus for creating a free-form three-dimensional article using a layer-by-layer deposition of a molten metal and deposition of a powdered metal as a support material |
| US5787965A (en) * | 1995-09-08 | 1998-08-04 | Aeroquip Corporation | Apparatus for creating a free-form metal three-dimensional article using a layer-by-layer deposition of a molten metal in an evacuation chamber with inert environment |
| US5617911A (en) * | 1995-09-08 | 1997-04-08 | Aeroquip Corporation | Method and apparatus for creating a free-form three-dimensional article using a layer-by-layer deposition of a support material and a deposition material |
| US5746844A (en) * | 1995-09-08 | 1998-05-05 | Aeroquip Corporation | Method and apparatus for creating a free-form three-dimensional article using a layer-by-layer deposition of molten metal and using a stress-reducing annealing process on the deposited metal |
| US5873523A (en) * | 1996-02-29 | 1999-02-23 | Yale University | Electrospray employing corona-assisted cone-jet mode |
| US6079634A (en) * | 1996-05-30 | 2000-06-27 | The Procter & Gamble Company | Electrostatic spraying |
| CA2296334C (en) * | 1996-07-23 | 2010-03-16 | Electrosols Ltd. | A dispensing device and method for forming material |
| US6252129B1 (en) | 1996-07-23 | 2001-06-26 | Electrosols, Ltd. | Dispensing device and method for forming material |
| US6433154B1 (en) * | 1997-06-12 | 2002-08-13 | Bristol-Myers Squibb Company | Functional receptor/kinase chimera in yeast cells |
| JP4433100B2 (en) * | 1997-06-20 | 2010-03-17 | ニューヨーク ユニヴァーシティ | Electrostatic spraying of substance solutions in mass production of chips and libraries |
| GB2327895B (en) * | 1997-08-08 | 2001-08-08 | Electrosols Ltd | A dispensing device |
| US6598603B1 (en) * | 1997-12-31 | 2003-07-29 | Astra Aktiebolag | Method for treating respiratory diseases |
| ES2248985T3 (en) | 1998-03-05 | 2006-03-16 | Zivena, Inc. | PULMONARY DOSAGE SYSTEM. |
| FR2776538B1 (en) * | 1998-03-27 | 2000-07-21 | Centre Nat Rech Scient | ELECTROHYDRODYNAMIC SPRAYING MEANS |
| US6234167B1 (en) | 1998-10-14 | 2001-05-22 | Chrysalis Technologies, Incorporated | Aerosol generator and methods of making and using an aerosol generator |
| GB2345010B (en) * | 1998-12-17 | 2002-12-31 | Electrosols Ltd | A delivery device |
| US20020081732A1 (en) | 2000-10-18 | 2002-06-27 | Bowlin Gary L. | Electroprocessing in drug delivery and cell encapsulation |
| US7615373B2 (en) | 1999-02-25 | 2009-11-10 | Virginia Commonwealth University Intellectual Property Foundation | Electroprocessed collagen and tissue engineering |
| KR20020005721A (en) | 1999-04-23 | 2002-01-17 | 추후기재 | High mass transfer electrosprayer |
| BR0010262A (en) * | 1999-05-03 | 2002-01-15 | Battelle Memorial Institute | Composition to form an aerosol, process for preparing and aerosolizing a composition, and aerosol generating device |
| JP2000331617A (en) * | 1999-05-21 | 2000-11-30 | Olympus Optical Co Ltd | Barrier rib manufacturing device for plasma display device |
| WO2000078447A1 (en) | 1999-06-18 | 2000-12-28 | Tsi Incorporated | Aerosol charge adjusting apparatus employing a corona discharge |
| US6753454B1 (en) | 1999-10-08 | 2004-06-22 | The University Of Akron | Electrospun fibers and an apparatus therefor |
| AU4439101A (en) * | 2000-04-03 | 2001-10-15 | Electrosols Ltd | Devices and formulations |
| US6883516B2 (en) | 2000-04-27 | 2005-04-26 | Chrysalis Technologies Incorporated | Method for generating an aerosol with a predetermined and/or substantially monodispersed particle size distribution |
| CA2409093C (en) * | 2000-05-16 | 2009-07-21 | Regents Of The University Of Minnesota | High mass throughput particle generation using multiple nozzle spraying |
| US6629524B1 (en) | 2000-07-12 | 2003-10-07 | Ponwell Enterprises Limited | Inhaler |
| DE10040551A1 (en) * | 2000-08-15 | 2002-02-28 | Bayer Ag | Process for the production of polyurethane particles |
| EP1315756A2 (en) | 2000-09-01 | 2003-06-04 | Virginia Commonwealth University Intellectual Property Foundation | Electroprocessed fibrin-based matrices and tissues |
| US6565342B1 (en) * | 2000-11-17 | 2003-05-20 | Accurus Scientific Co. Ltd. | Apparatus for making precision metal spheres |
| AU3664102A (en) * | 2000-12-01 | 2002-06-11 | Battelle Memorial Institute | Method for stabilizing biomolecules in liquid formulations |
| US6491233B2 (en) | 2000-12-22 | 2002-12-10 | Chrysalis Technologies Incorporated | Vapor driven aerosol generator and method of use thereof |
| US6701921B2 (en) | 2000-12-22 | 2004-03-09 | Chrysalis Technologies Incorporated | Aerosol generator having heater in multilayered composite and method of use thereof |
| US6501052B2 (en) | 2000-12-22 | 2002-12-31 | Chrysalis Technologies Incorporated | Aerosol generator having multiple heating zones and methods of use thereof |
| US6681998B2 (en) | 2000-12-22 | 2004-01-27 | Chrysalis Technologies Incorporated | Aerosol generator having inductive heater and method of use thereof |
| US6799572B2 (en) | 2000-12-22 | 2004-10-05 | Chrysalis Technologies Incorporated | Disposable aerosol generator system and methods for administering the aerosol |
| US7077130B2 (en) | 2000-12-22 | 2006-07-18 | Chrysalis Technologies Incorporated | Disposable inhaler system |
| US7674429B2 (en) | 2001-01-22 | 2010-03-09 | Johnsondiversey, Inc. | Electrostatic disinfectant delivery |
| SE0101478D0 (en) * | 2001-04-25 | 2001-04-25 | Astrazeneca Ab | Fluid dispensing apparatus and methods |
| US7247338B2 (en) * | 2001-05-16 | 2007-07-24 | Regents Of The University Of Minnesota | Coating medical devices |
| US6568390B2 (en) | 2001-09-21 | 2003-05-27 | Chrysalis Technologies Incorporated | Dual capillary fluid vaporizing device |
| US6640050B2 (en) | 2001-09-21 | 2003-10-28 | Chrysalis Technologies Incorporated | Fluid vaporizing device having controlled temperature profile heater/capillary tube |
| US6620405B2 (en) * | 2001-11-01 | 2003-09-16 | 3M Innovative Properties Company | Delivery of hydrogel compositions as a fine mist |
| US6804458B2 (en) * | 2001-12-06 | 2004-10-12 | Chrysalis Technologies Incorporated | Aerosol generator having heater arranged to vaporize fluid in fluid passage between bonded layers of laminate |
| US6681769B2 (en) | 2001-12-06 | 2004-01-27 | Crysalis Technologies Incorporated | Aerosol generator having a multiple path heater arrangement and method of use thereof |
| US6701922B2 (en) | 2001-12-20 | 2004-03-09 | Chrysalis Technologies Incorporated | Mouthpiece entrainment airflow control for aerosol generators |
| JP2006507921A (en) | 2002-06-28 | 2006-03-09 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | Method and apparatus for fluid dispersion |
| SE0300514D0 (en) * | 2003-02-26 | 2003-02-26 | Astrazeneca Ab | Powder generating apparatus and methods |
| US7849850B2 (en) * | 2003-02-28 | 2010-12-14 | Battelle Memorial Institute | Nozzle for handheld pulmonary aerosol delivery device |
| EP1462801A3 (en) * | 2003-03-24 | 2005-01-05 | Tepnel Lifecodes | Methods for determining the negative control value for multi-analyte assays |
| GB0307428D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Compartmentalised combinatorial chemistry |
| GB0307403D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Selection by compartmentalised screening |
| US20060078893A1 (en) | 2004-10-12 | 2006-04-13 | Medical Research Council | Compartmentalised combinatorial chemistry by microfluidic control |
| EP1610888A2 (en) | 2003-04-10 | 2006-01-04 | President And Fellows Of Harvard College | Formation and control of fluidic species |
| US7367334B2 (en) | 2003-08-27 | 2008-05-06 | Philip Morris Usa Inc. | Fluid vaporizing device having controlled temperature profile heater/capillary tube |
| BRPI0414004A (en) | 2003-08-27 | 2006-10-24 | Harvard College | electronic control of fluidic species |
| AU2004203870B2 (en) * | 2003-09-17 | 2011-03-03 | Fisher & Paykel Healthcare Limited | Breathable Respiratory Mask |
| EP1680173B1 (en) * | 2003-10-31 | 2011-01-12 | Trudell Medical International | System for manipulating a catheter for delivering a substance to a body cavity |
| US8166911B2 (en) * | 2003-11-04 | 2012-05-01 | Illinois Institute Of Technology | Method and apparatus for electrostatic spray deposition for a solid oxide fuel cell |
| US20050221339A1 (en) | 2004-03-31 | 2005-10-06 | Medical Research Council Harvard University | Compartmentalised screening by microfluidic control |
| US9477233B2 (en) | 2004-07-02 | 2016-10-25 | The University Of Chicago | Microfluidic system with a plurality of sequential T-junctions for performing reactions in microdroplets |
| US7968287B2 (en) | 2004-10-08 | 2011-06-28 | Medical Research Council Harvard University | In vitro evolution in microfluidic systems |
| US7360724B2 (en) * | 2004-10-20 | 2008-04-22 | The Procter & Gamble Company | Electrostatic spray nozzle with internal and external electrodes |
| JP4690418B2 (en) * | 2004-11-10 | 2011-06-01 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | Multiphase nanoparticles |
| US7748343B2 (en) * | 2004-11-22 | 2010-07-06 | The Board Of Trustees Of The University Of Illinois | Electrohydrodynamic spraying system |
| EP2062651A3 (en) | 2004-12-28 | 2009-07-01 | Daikin Industries, Ltd. | Electrostatic spraying device |
| US8079838B2 (en) * | 2005-03-16 | 2011-12-20 | Horiba, Ltd. | Pure particle generator |
| KR100673979B1 (en) * | 2005-03-17 | 2007-01-24 | 안강호 | Apparatus and method for manufacturing ultra-fine particles |
| US20070017505A1 (en) * | 2005-07-15 | 2007-01-25 | Lipp Brian A | Dispensing device and method |
| EP2363205A3 (en) | 2006-01-11 | 2014-06-04 | Raindance Technologies, Inc. | Microfluidic Devices And Methods Of Use In The Formation And Control Of Nanoreactors |
| DE602007009811D1 (en) * | 2006-01-27 | 2010-11-25 | Harvard College | COALESCENCE FLUIDER DROPLET |
| EP1988941A2 (en) | 2006-01-31 | 2008-11-12 | Nanocopoeia, Inc. | Nanoparticle coating of surfaces |
| CA2637883C (en) * | 2006-01-31 | 2015-07-07 | Regents Of The University Of Minnesota | Electrospray coating of objects |
| US9108217B2 (en) | 2006-01-31 | 2015-08-18 | Nanocopoeia, Inc. | Nanoparticle coating of surfaces |
| WO2007094835A1 (en) | 2006-02-14 | 2007-08-23 | Ventaira Pharmaceuticals, Inc. | Dissociated discharge ehd sprayer with electric field shield |
| US9562837B2 (en) | 2006-05-11 | 2017-02-07 | Raindance Technologies, Inc. | Systems for handling microfludic droplets |
| EP2530168B1 (en) | 2006-05-11 | 2015-09-16 | Raindance Technologies, Inc. | Microfluidic Devices |
| WO2008021123A1 (en) | 2006-08-07 | 2008-02-21 | President And Fellows Of Harvard College | Fluorocarbon emulsion stabilizing surfactants |
| US9040816B2 (en) | 2006-12-08 | 2015-05-26 | Nanocopoeia, Inc. | Methods and apparatus for forming photovoltaic cells using electrospray |
| WO2008097559A2 (en) | 2007-02-06 | 2008-08-14 | Brandeis University | Manipulation of fluids and reactions in microfluidic systems |
| US7361207B1 (en) * | 2007-02-28 | 2008-04-22 | Corning Incorporated | System and method for electrostatically depositing aerosol particles |
| WO2008130623A1 (en) | 2007-04-19 | 2008-10-30 | Brandeis University | Manipulation of fluids, fluid components and reactions in microfluidic systems |
| EP4047367A1 (en) | 2008-07-18 | 2022-08-24 | Bio-Rad Laboratories, Inc. | Method for detecting target analytes with droplet libraries |
| EP2210659A1 (en) * | 2009-01-26 | 2010-07-28 | Nederlandse Organisatie voor toegepast -natuurwetenschappelijk onderzoek TNO | Effective droplet drying |
| EP3415235A1 (en) | 2009-03-23 | 2018-12-19 | Raindance Technologies Inc. | Manipulation of microfluidic droplets |
| WO2011042564A1 (en) | 2009-10-09 | 2011-04-14 | Universite De Strasbourg | Labelled silica-based nanomaterial with enhanced properties and uses thereof |
| EP2517025B1 (en) | 2009-12-23 | 2019-11-27 | Bio-Rad Laboratories, Inc. | Methods for reducing the exchange of molecules between droplets |
| US20110174304A1 (en) * | 2010-01-21 | 2011-07-21 | Triplett Ii Michael D | Electrohydrodynamic aerosolization device having a time varying voltage |
| US9366632B2 (en) | 2010-02-12 | 2016-06-14 | Raindance Technologies, Inc. | Digital analyte analysis |
| US9399797B2 (en) | 2010-02-12 | 2016-07-26 | Raindance Technologies, Inc. | Digital analyte analysis |
| EP2534267B1 (en) | 2010-02-12 | 2018-04-11 | Raindance Technologies, Inc. | Digital analyte analysis |
| US10351905B2 (en) | 2010-02-12 | 2019-07-16 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
| EP2561333B1 (en) | 2010-04-19 | 2015-11-25 | Battelle Memorial Institute | Electrohydrodynamic spraying |
| US9562897B2 (en) | 2010-09-30 | 2017-02-07 | Raindance Technologies, Inc. | Sandwich assays in droplets |
| US9364803B2 (en) | 2011-02-11 | 2016-06-14 | Raindance Technologies, Inc. | Methods for forming mixed droplets |
| US9150852B2 (en) | 2011-02-18 | 2015-10-06 | Raindance Technologies, Inc. | Compositions and methods for molecular labeling |
| DK2707062T3 (en) * | 2011-05-13 | 2018-01-08 | Sanofi Aventis Deutschland | DEVICE FOR PHARMACEUTICAL DISPENSER DEVICE |
| US8841071B2 (en) | 2011-06-02 | 2014-09-23 | Raindance Technologies, Inc. | Sample multiplexing |
| EP3709018A1 (en) | 2011-06-02 | 2020-09-16 | Bio-Rad Laboratories, Inc. | Microfluidic apparatus for identifying components of a chemical reaction |
| US8658430B2 (en) | 2011-07-20 | 2014-02-25 | Raindance Technologies, Inc. | Manipulating droplet size |
| US8985051B2 (en) | 2011-12-15 | 2015-03-24 | Honeywell Asca Inc. | Apparatus for producing a spray of changed droplets of aqueous liquid |
| JP5271437B1 (en) | 2012-05-14 | 2013-08-21 | ナガセテクノエンジニアリング株式会社 | Electrostatic coating apparatus and liquid coating method |
| CN103084919B (en) * | 2013-02-07 | 2016-08-03 | 浙江工业大学 | Cutting fluid aerosol micro lubricating method and apparatus |
| JP2014223603A (en) * | 2013-05-15 | 2014-12-04 | 光弘 高橋 | Production method of powder, and device therefor |
| NL2010830C2 (en) * | 2013-05-21 | 2014-11-26 | Alvimedica Vascular Res B V | Method and device for depositing a material on a target and medical device obstainable therewith. |
| US11901041B2 (en) | 2013-10-04 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Digital analysis of nucleic acid modification |
| US9944977B2 (en) | 2013-12-12 | 2018-04-17 | Raindance Technologies, Inc. | Distinguishing rare variations in a nucleic acid sequence from a sample |
| CN104752148B (en) * | 2013-12-30 | 2017-10-10 | 同方威视技术股份有限公司 | Corona discharge component, ionic migration spectrometer, the method using corona discharge component progress corona discharge |
| US11193176B2 (en) | 2013-12-31 | 2021-12-07 | Bio-Rad Laboratories, Inc. | Method for detecting and quantifying latent retroviral RNA species |
| JP6659595B2 (en) * | 2014-06-20 | 2020-03-04 | スプレイング システムズ カンパニー | Electrostatic spraying system |
| FR3023177B1 (en) * | 2014-07-04 | 2016-08-12 | Centre Nat De La Rech Scient (C N R S) | PROCESS FOR THE PREPARATION OF CO-CRYSTALS BY FLASH EVAPORATION |
| JP6431418B2 (en) * | 2015-03-20 | 2018-11-28 | 花王株式会社 | Fine particle production method and production apparatus |
| JP6112130B2 (en) * | 2015-03-25 | 2017-04-12 | トヨタ自動車株式会社 | Electrostatic nozzle, discharge device, and method for manufacturing semiconductor module |
| JP6384378B2 (en) * | 2015-03-25 | 2018-09-05 | オムロンヘルスケア株式会社 | Ultrasonic nebulizer |
| DE102015110732A1 (en) * | 2015-07-03 | 2017-01-05 | Claudia Röttger-Lanfranchi | Connector for use in a ventilation system |
| US10647981B1 (en) | 2015-09-08 | 2020-05-12 | Bio-Rad Laboratories, Inc. | Nucleic acid library generation methods and compositions |
| AR106558A1 (en) * | 2015-11-03 | 2018-01-24 | Spraying Systems Co | APPARATUS AND SPRAY DRYING METHOD |
| WO2018161071A1 (en) * | 2017-03-03 | 2018-09-07 | Idealchain, Llc | Facile encapsulation of dyes via air-controlled electrospray |
| WO2019105812A1 (en) * | 2017-11-30 | 2019-06-06 | Philip Morris Products S.A. | Systems for generating a liquid aerosol |
| CN109332029B (en) * | 2018-11-27 | 2024-03-29 | 奥普家居股份有限公司 | Electrostatic atomizing device |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US398327A (en) * | 1889-02-19 | Nard huguet de vars | ||
| GB117077A (en) * | 1917-06-16 | 1918-11-21 | Fritz Diebold | Improvements in the Atomising of Liquid Substances into very Small Particles. |
| US1958406A (en) * | 1926-12-27 | 1934-05-15 | William A Darrah | Electrical spraying device |
| US2302289A (en) * | 1938-12-06 | 1942-11-17 | Union Oil Co | Electrified spray method and apparatus |
| US2525347A (en) * | 1945-02-09 | 1950-10-10 | Westinghouse Electric Corp | Electrostatic apparatus |
| NL193390A (en) * | 1953-12-24 | |||
| US2803248A (en) * | 1956-01-24 | 1957-08-20 | Siemens Ag | Space inhalation device |
| US3232292A (en) * | 1962-10-12 | 1966-02-01 | Arizona Nucleonics Inc | Ionized aerosols |
| JPS4718405Y1 (en) * | 1968-07-11 | 1972-06-26 | ||
| US3698635A (en) * | 1971-02-22 | 1972-10-17 | Ransburg Electro Coating Corp | Spray charging device |
| CH550022A (en) * | 1973-02-15 | 1974-06-14 | Battelle Memorial Institute | Spray-forming tiny spherical granules - eg paraffin granules of 100 microns dia and liquid-contg capsules of 500 microns dia, using annular electrodes |
| US3941312A (en) * | 1973-11-23 | 1976-03-02 | Research and Development Laboratories of Ohno Company Limited | Ink jet nozzle for use in a recording unit |
| GB1569707A (en) * | 1976-07-15 | 1980-06-18 | Ici Ltd | Atomisation of liquids |
| US4264641A (en) * | 1977-03-17 | 1981-04-28 | Phrasor Technology Inc. | Electrohydrodynamic spraying to produce ultrafine particles |
| US4133854A (en) * | 1977-06-16 | 1979-01-09 | The United States Of America As Represented By The United States Department Of Energy | Method for producing small hollow spheres |
| GB2018627B (en) * | 1978-04-17 | 1982-04-15 | Ici Ltd | Process and apparatus for spraying liguid |
| CY1287A (en) * | 1978-09-26 | 1985-07-05 | Ici Plc | Electrostatic spraying of liquid |
| SU1061822A1 (en) * | 1982-02-23 | 1983-12-23 | Всесоюзный научно-исследовательский институт ветеринарной санитарии | Sprayer for electrolizing fog drops |
| EP0109224A3 (en) * | 1982-11-02 | 1985-08-07 | Ransburg Japan Limited | Rotary liquid sprayer |
-
1986
- 1986-02-21 GB GB868604328A patent/GB8604328D0/en active Pending
-
1987
- 1987-02-04 IE IE29987A patent/IE59596B1/en not_active IP Right Cessation
- 1987-02-15 IL IL81572A patent/IL81572A/en not_active IP Right Cessation
- 1987-02-16 FI FI870640A patent/FI870640A/en not_active Application Discontinuation
- 1987-02-16 FI FI870639A patent/FI84886C/en not_active IP Right Cessation
- 1987-02-17 DE DE8787301361T patent/DE3764662D1/en not_active Expired - Lifetime
- 1987-02-17 AT AT87301361T patent/ATE56156T1/en not_active IP Right Cessation
- 1987-02-17 NZ NZ219305A patent/NZ219305A/en unknown
- 1987-02-17 EP EP87301360A patent/EP0234841A3/en not_active Ceased
- 1987-02-17 EP EP87301361A patent/EP0234842B1/en not_active Expired - Lifetime
- 1987-02-17 NZ NZ219306A patent/NZ219306A/en unknown
- 1987-02-17 ES ES87301361T patent/ES2016969B3/en not_active Expired - Lifetime
- 1987-02-17 ZA ZA871146A patent/ZA871146B/en unknown
- 1987-02-17 ZA ZA871147A patent/ZA871147B/en unknown
- 1987-02-18 DK DK082587A patent/DK164847C/en not_active IP Right Cessation
- 1987-02-18 NO NO870660A patent/NO870660L/en unknown
- 1987-02-18 NO NO870658A patent/NO172835C/en unknown
- 1987-02-19 PT PT84320A patent/PT84320B/en unknown
- 1987-02-19 AU AU69062/87A patent/AU594429B2/en not_active Expired
- 1987-02-19 AU AU69061/87A patent/AU582949B2/en not_active Ceased
- 1987-02-20 CA CA000530183A patent/CA1275883C/en not_active Expired - Lifetime
- 1987-02-20 JP JP62036009A patent/JPH0824714B2/en not_active Expired - Lifetime
- 1987-02-20 JP JP62036010A patent/JPS62254830A/en active Pending
- 1987-02-24 US US07/017,416 patent/US4829996A/en not_active Expired - Lifetime
- 1987-02-24 US US07/017,423 patent/US4795330A/en not_active Expired - Fee Related
-
1990
- 1990-09-20 GR GR90400069T patent/GR3000843T3/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7977527B2 (en) | 1996-07-23 | 2011-07-12 | Baltelle Memorial Institute | Dispensing device and method for forming material |
| US7193124B2 (en) | 1997-07-22 | 2007-03-20 | Battelle Memorial Institute | Method for forming material |
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Legal Events
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