MXPA01007126A - Dosing and delivering system - Google Patents

Abstract

The present invention relates to a dispensing device (1) for a fluid (10), the dispensing device (1) comprising a reservoir (11), a shaft (12), a back seal (13), a damper (14), a piston (151) and a one-way valve (16), the back seal (13) sealing a first end of the reservoir and being displaceable along the shaft, the valve being on the second end of the reservoir, the piston being fixed to one end of the shaft, the piston being located between the valve and the damper, the damper being also fixed to the shaft, the damper being located between the piston and the back seal, whereby the piston has an opened position (151) and a closed position (152), theopen position allowing fluid communication between the valve and the part of the reservoir between the piston and the back seal, the displacement of the piston between the opened and the closed position being induced by a displacement of the shaft along its own axis, the pressure in the area comprised between the valve and the piston reducing when the piston is moved from its closed position towards its opened position, the damper collapsing when the piston is moved from its closed position towards its opened position, the only fluid flow from the part of the reservoir situated between the damper and the back seal and the part of the reservoir situated on the other side of the damper being a connecting passage (140) situated in the damper (14) when the piston is moved from its opened position towards its closed position.

Description

DOSAGE AND SUPPLY SYSTEM TECHNICAL FIELD This invention relates to a mechanical assembly for dosing and supplying a fluid.

BACKGROUND OF THE INVENTION Devices for dosing and supplying a fluid are widely used in consumer goods or in the pharmaceutical industry. Said devices for dosing and supplying a fluid must allow a good control of the quantity of dosed fluid, as well as a good control of the supply of this dosage of the fluid. In particular, in the pharmaceutical industry, precise control of quantity and supply are critical. In addition, it is desired to produce said devices in a reproducible and economical manner. An objective of this invention is to provide accurate dosing and delivery of a fluid by means of an economical dosing and delivery device. In accordance with the present invention, this objective is achieved in a fluid dispensing device, the dispensing device comprising a reservoir, an arrow, a back seal, a gate, a piston and a unidirectional valve, the back seal sealing a first end of the reservoir and being displaceable along the arrow, the valve being at the second end of the reservoir, the piston being fixed to one end of the arrow, the piston being located between the valve and the gate, the gate being also fixed to the arrow, the gate being located between the piston and the rear seal, whereby the piston has an open position and a closed position, the open position allowing fluid communication between the valve and the part of the tank between the piston and the seal Subsequently, the displacement of the piston between the open position and the closed position is induced by a displacement of the along its own axis, the pressure in the area between the valve and the piston decreasing as the piston moves from its closed position to its open position, the gate collapsing when the piston moves from its closed position to its position open, the only fluid flow from the part of the tank located between the gate and the rear seal and the part of the tank located on the other side of the gate being a connection passage located in the gate when the piston moves from its position open towards its closed position. A device formed in accordance with the invention has a number of advantages. Since the device comprises a piston having an open position and a closed position that allows fluid communication between the valve and the reservoir, the amount of fluid to be dispensed must be precisely controlled by displacing the desired amount of fluid from the reservoir. the reservoir towards the valve part by the displacement of the piston from the closed position to the open position, the absence of a direct connection between the reservoir and the valve, avoiding the emptying of the reservoir through the valve without control. Furthermore, since the pressure in the area between the valve and the piston decreases when the piston moves from its closed position to its open position, the displacement of the piston to the open position will require the application of a minimum value of sufficient force to overcome or at least to balance the pressure reduction and the internal frictional forces of the system, in order to avoid the unwanted displacement of the piston. The delivery of the dose is also precisely controlled by the combination of the use of a unidirectional valve, the piston, the gate and the posterior seal. Of course, the unidirectional valve will allow to supply the fluid only when the piston has moved forward towards the valve, the speed of displacement of the piston being regulated by the size of the connecting passage provided in the compound combined with the viscosity of the fluid and the Applied mechanical force (eg, spring force), thus allowing control of the rate of supply of fluid through the valve.

DETAILED DESCRIPTION OF THE INVENTION The invention will now be described with reference to the accompanying drawings, in which: Figure 1 is a cross-sectional plan view illustrating a dispensing device according to the invention, the piston being in the open position. Figure 2 is a cross-sectional plan view illustrating a dispensing device according to the invention, the piston being in the closed position. The invention relates to a dispensing device 1 or 2 for a fluid 10. Fluid is to be understood as including liquids having various viscosities. Preferred fluids in the preferred embodiment of the invention are pharmaceutical fluids, but other applications are contemplated, such as air renewal devices, for example. The dispensing device 1 or 2 comprises a reservoir 11. The reservoir is typically a chamber in which fluid 10 will be found. In a preferred embodiment, the reservoir is substantially impermeable to gases, thereby preventing or limiting the production of chemical compounds due to contact with O2 or H2O vapor, for example, or to retain air outside the device, to avoid discrepancies in the amount of fluid to be dosed. The dispensing device further comprises an arrow 12, the arrow being typically an elongated element having as its main axis the most elongated direction, the arrow also normally comprising a part having a constant cross section in a plane normal to the main axis to allow translation of a rear seal 13, or being for example threaded to allow the helical displacement of the rear seal 13 along the arrow 12. The device further comprises a rear seal 13, the rear seal 13 allowing the sealing of the tank 11, substantially in independent of the amount of fluid 10 contained in the reservoir 11. This can be achieved, for example, by having a main part of the reservoir 11 having a constant cross section in a plane perpendicular to the main axis of the arrow 12, the posterior seal 13 having a substantially identical cross section, the cross section of the rear seal 13 being preferably marginally longer than the constant cross section of the reservoir 11 to achieve sealing, so that the displacement of the rear seal 13 along the arrow 12 makes it possible to seal the reservoir 11 along the cross section constant at any level in the main part of the reservoir 11 having the constant cross-section, thus allowing to seal in a gas-tight manner, a variable volume. In a preferred embodiment, the rear seal 13 is made of a flexible and elastic material that has the shape of an umbrella, or even more preferably a double umbrella shape, so that the seal is constantly pressing against the tank 11 on the perimeter of the cross section.

The device 1 or 2 further comprises a gate 14. The gate is preferably a part made of a flexible material and having the shape of a parasol that favors collapse during the movement in one direction, and the damping during the displacement in the other direction. . A piston 151 or 152 is also included in the device of the invention. The piston 151 or 152 is typically a part having a constant cross section that is in a plane perpendicular to its main axis, this piston 151 or 152 being elongated along the main axis, the piston 151 or 152 being displaced in a part of the reservoir 11 which has a cross section in a plane normal to the main axis of the piston 151 or 152 which is substantially equal, but preferably marginally smaller than the cross section of the piston 151 or 152, to allow a good seal. Normally, the main axis of the piston 151 or 152 is parallel and even aligned with the main shaft of the arrow 12. The device further comprises a unidirectional valve 16. By unidirectional valve it should be understood that in normal use, the valve 16 will allow the passage of the fluid only in one direction. In a preferred embodiment, the valve 16 is a "self-sealing" valve as described, for example, in principle, in EP-A-0 597 601, EP-A-0 395 380 or EP-A-0 160 336 A necessary feature of the device of the invention is that the rear seal 13 seals a first end of the reservoir 11. This allows the use of a gas-tight reservoir, which is useful to allow the stability of the fluid product 10, and necessary for operation of the device, as will be described below. The rear seal 13 must also be movable along the arrow 12, said displacement including linear or helical displacement, for example. The valve 16 is at the second end of the reservoir 11. Of course, the reservoir is usually elongated along the main direction of the arrow, and comprises only two ends, the first being sealed by the rear seal 13, and the other comprising the valve 16. The piston 151 or 152 is fixed to one end of the arrow 12. Of course, the piston 151 or 152 is used in the device 1 or 2 according to the invention, to push a dose 100 of product towards the valve 16. To achieve this, the piston 151 or 152 is located between the valve 16 and the gate 14. The gate 14 is also fixed to the arrow 12, the gate 14 being located between the piston 151 or 152 and the rear seal 13. Of course, the gate 14 is located in the part 110 of the tank 11, which does not contain a dose 100 ready to be dispensed. Of course, the device 1 or 2 according to the invention is mainly intended for multiple use, so that the gate 14 is located in the part of the tank 11 that contains a plurality of doses that are not ready to be dispensed, since they are not located between the piston and the valve. It should be noted that device 1 or 2 could also be suitable for individual use. For the device of the invention to be functional, the piston 151 or 152 has an open position 151 and a closed position 152, the open position 151 allowing fluid communication 153 between the valve 16 and the reservoir part 11 between the piston 151 and the rear seal 13. This fluid communication 153 allows a dose of product 100 to be placed between the piston 151 and the valve 16 before being supplied. The displacement of the piston between the open position 151 and the closed position 152 is induced by a displacement of the arrow 12 along its own axis, which is the main axis. The pressure in the area 100 between the valve 16 and the piston decreases when the piston moves from its closed position 152 to its open position 151, thereby generating a partial vacuum. This allows to "suck" a dose 100 of product from the part of the reservoir 11 located between the piston and the rear seal in the part 100 between the valve and the piston when the piston advances in the open position 151. The gate 14 collapses when the piston moves from its closed position 152 to its open position 151. This makes it possible to facilitate the preparation assortment, and avoids excessive opposing forces when the operator operates the device, whereby movement or displacement of the piston from its closed position towards its open position will allow the fluid communication 153 between the part of the reservoir between the piston and the posterior seal and the part 100 between the valve and the piston, to fill this latter part with fluid by means of pressure reduction or partial vacuum mentioned above, the dose of fluid 100 being "sucked" in this part by the pressure reduction through the fluid communication gone 153, being ready to be dispensed when pushed by the piston through the valve. Since the only fluid flow from the part of the tank located between the gate and the rear seal and the part of the tank located on the other side of the gate is a connection passage 140 located in the gate 14, when the piston moves from its open position to its closed position, said movement leading to the supply of the fluid ready to be dispensed, is damped by the limitation on the fluid flow in the connection passage 140 located in the gate 14. Of course, to supply the dose 100 located between the piston and the valve 16, the piston has to move from its open position 151 to its closed position 152, thereby moving the gate 14 as the gate 14 and the piston are fixed to the arrow 12, the gate 14 moving through the fluid 10, thereby creating an imbalance in the sealed reservoir 11 between the part of the reservoir located between the gate 14 and the posterior seal. or 13 and the part of the reservoir 11 located between the gate 14 and the piston, this imbalance being compensated for by a flow in the connection passage 140 located in the gate 14, thereby controlling the ejection or delivery rate of the dose 100. ready to be dispensed through valve 16, by controlling the movement of the piston. Of course, the piston will have a maximum speed that depends marginally on the compressibility, and mainly on the viscosity of the fluid and on the geometrical and / or mechanical characteristics of the device. Of course, for example, the larger the connection passage 140 or greater is the forward force applied to the arrow 12, the greater the maximum speed. In a preferred embodiment, the arrow is made of an electrically conductive material, such as metal, for example. Of course, in a more preferred embodiment, the fluid is electrically charged before being dispensed. The device according to the invention is particularly suitable for this application, since fluid loading will be facilitated by flow control. In particular, there is a maximum speed beyond which fluid loading becomes difficult or impossible, so that a damped supply allows a good load. Preferably, the charging speed is coupled to the fluid flow rate to achieve efficient electrohydrodynamic atomization of the fluid. In a preferred embodiment, the volume comprised between the piston in the open position and the valve is less than 100 μl. In another preferred embodiment, the supply control is such that the volume of fluid dispensed in each assortment operation varies by less than 10% between each assortment operation. Even more preferably, the variation is less than 5%.

In another preferred embodiment, a compressed spring is located at the end of the arrow opposite the end to which the piston is attached, applying a force on the arrow in a direction substantially parallel to the axis thereof. In another preferred embodiment, the connection passage is a single opening provided in the gate, even more preferably a circular opening. A more preferred embodiment of the invention is obtained by integrating the device of the invention to the spraying device, as described in pending applications GB9806937.0 and GB9806939.6. Said spraying device is particularly suitable for the treatment of discomforts affecting the nasal region, such as hay fever or congestion due to colds. Recently, it has been recognized that the mucous membranes of the nasal cavity can be used as a delivery site for drugs directed to other areas of the body. See, for example, WO 92/11049, which describes a pen-shaped device for nasal administration, particularly of insulin. A form of spray is often convenient for such treatments. The treatment of the eyes can also be effected conveniently by means of a spray device. Preferred volume dosages for such applications are generally low, down to less than 10 μl. Typically, it will be necessary to repeat the dosage to make the treatment fully effective. Achieving a clean flow from start to finish from spray devices that supply such low volumes can be difficult. Typical problems encountered include residual dripping from a valve after application, with the potential for later contamination, and plugging of the valve. The use of an elastomeric valve, particularly a slot valve, provides a clean flow from end to end without plugging, particularly by the combination of the valve (clean start) and sudden pressure reduction by the pressure relief area (end clean), even if the sprayed fluid comprises a particulate solid finally divided. Preferably, the spraying device is adapted to provide one or more unit dosages of a fluid, each dose having a volume in the range of about 1 to about 100 μl, the device comprising a self-sealing elastomeric valve having a fluid side and a supply side, the valve opening to allow fluid passage when pressure is applied to fluid on the fluid side, and sealing when pressure is removed. Preferably, the spray device is an electrostatic spray device which charges the spray before it enters the nostrils.

Fluids The device of the invention preferably comprises a fluid reservoir containing a pharmaceutically acceptable fluid, the fluid comprising a pharmaceutically acceptable treatment agent selected from medicaments, flavors, salts, surfactants, and mixtures thereof. The fluid optionally comprises other adjuvants dissolved or dispersed therein. The fluid can be aqueous or non-aqueous. Suitable aqueous fluids include water and mixtures of water with water miscible solvents such as glycerol, propylene glycol, or alcohols such as ethanol or isopropyl alcohol. Aqueous emulsions can also be used, either water-in-oil or oil-in-water emulsions. Preferably, the fluid is an aqueous solution, dispersion or emulsion of oil in water. Suitable non-aqueous fluids comprise polyethylene glycols, glycerol, propylene glycol, dimethyl isosorbide, silicone oils, ketones, ethers, and mixtures thereof. Although not limited to any particular resistivity scale, the invention has particular application in low resistivity fluids, especially those having an overall resistivity of less than 1 x 108 ohms.cm, preferably those having a resistivity of less than 1 x 104. ohms.cm, more preferably less than 1 x 103 ohms.cm. If necessary, the fluid may comprise a resistivity modifier, such as a pharmaceutically acceptable salt, to achieve overall resistivity within the desired scale.

The fluid is preferably a pharmaceutically acceptable intranasal vehicle. Preferably, the nasal composition is isotonic, that is, it has the same osmotic pressure as blood and tear fluid. The desired isotonicity of the compositions of this invention can be achieved using, for example, the sodium chloride already present, or other pharmaceutically acceptable agents such as dextrose, boric acid, citric acid, sodium tartrate, sodium citrate, sodium phosphate. , potassium phosphate, propylene glycol, or other organic or inorganic solutes. Sodium chloride is particularly preferred for pH regulators that contain sodium ions. Other examples of sodium chloride equivalents are described in Remington's Pharmaceutical Sciences pp. 1491-1497 (Alfonso Gennaro, eighteenth edition, 1990), which is incorporated herein by reference.

Medications The fluid can comprise a wide range of medications. By "drug" is meant a drug or other substance intended to have a therapeutic effect on the body. Suitable levels of the medicament are from 0.001 to 20%, preferably from 0.01 to 5%, more preferably from 0.1 to 5%. It will be appreciated that the levels of specific drugs will depend on many factors including their potency, safety profile, solubility / ease of dispersion, and desired effect. The drug, when used, may be one that is intended to have an effect at the site of application, such as a decongestant, antihistamine or anti-inflammatory drug, or may be used for systemic absorption such as an antiviral, antidepressant, antiemetic medication. or antipyretic, or a hormone, or the like. The medicament can be soluble in the fluid, or it can be a liquid or solid in finely divided insoluble particles dispersed within the fluid. Suitable decongestants include: oxymetazoline, tramazoline, xylometazoline, naphazoline, tetrahydrazoline, pseudoephedrine, ephedrine, phenylephrine, their pharmaceutically acceptable salts, such as the hydrochlorides, and mixtures thereof. Preferred decongestants are selected from oxymetazoline, xylometazoline, their pharmaceutically acceptable salts, and mixtures thereof. Especially preferred for use herein is oxymetazoline hydrochloride, which is soluble in water. When used in the compositions of the present invention, the decongestant is preferably present at a concentration of from about 0.01% to about 3.0%, more preferably from about 0.01% to about 1%. Antihistamines useful for the present invention include, but are not limited to, fast-acting histamine H-1 receptor antagonists. Said antihistamines of H-1 receptors can be selected from the following antihistamine groups: alkylamines, ethanolamines, ethylenediamines, piperazines, phenothiazines and piperidines. Examples of useful fast-acting antihistamines include acrivastine, carbinoxamine, diphenhydramine, chlorpheniramine, brompheniramine, dexchlorpheniramine, doxylamine, clemastine, promethazine, trimeprazine, metdilazine, hydroxyzine, pyrilamine, tripelenamine, meclizine, triprolidine, azatadine, cyproheptadine, rocastin, phenindamine, or salts pharmaceutically acceptable, and mixtures thereof. Other useful antihistamines include terfenadine, azelastine, cetirizine, astemizole, ebastine, ketotifen, yodoxamide, loratadine, levocabastine, mequitazine, oxatomide, setastine, taziphiline, temelastin, or pharmaceutically acceptable salts, and mixtures thereof. When used in the compositions of the present invention, the antihistamine component is preferably present at a concentration of from about 0.01% to about 3.0%, more preferably from about 0.01% to about 1%. The medicament can also be an anti-inflammatory agent such as a corticosteroid. Particularly preferred agents within this class are glucocorticoids selected from the group consisting of beclomethasone, flunisolide, fluticasone, memetasone, budesonide, pharmaceutically acceptable salts, and mixtures thereof. When used in the compositions of the present invention, the anti-inflammatory agent is preferably present at a concentration of from about 0.001% to about 0.1%, more preferably from about 0.01% to about 0.1%. Also useful herein are xanthine derivatives such as caffeine and methylxanthine, and the like; antiallergic; mucolytics; anticholinergic; non-opiate analgesics such as acetaminophen, acetylsalicylic acid, ibuprofen, etodolac, fenbuprofen, fenoprofen, ketorolac, flurbiprofen, indomethacin, ketoprofen, naproxen, pharmaceutically acceptable salts, and mixtures thereof; opioid analgesics such as butorphanol; leukotriene receptor antagonists; mast cell stabilizers such as sodium cromolyn, nedocromil and lodoxamide; lipoxygenase inhibitor compounds; and nicotine, insulin and calcinotine. Other examples of suitable medicaments can be found in WO97 / 46243, EP-A-780127, US-A-5, 124,315, US-A-5,622,724, US-A-5,656,255 and US-A-5,705,490.

Flavors Several flavoring and / or aromatic components (eg, aldehydes and esters) can be used in the fluids of the invention. These include, for example, menthol, camphor, eucalyptol, benzaldehyde (cherry, almond); citral (lemon, lime); neral decanal (orange, lemon); aldehyde C-8, aldehyde C-9 and aldehyde C-12 (citrus fruits); tolyl aldehyde (cherry, almond); 2,6-dimethyl-octanal (green fruits); 2-dodecenal (citrus, tangerine); and herbal components such as thyme, rosemary and mugwort oils. Other aromatic components suitable for use in the present invention include those described in the U.S.A. 4,136,163 to Watson et al., The U.S. Patent. 4,459,425 to Amano et al., And the patent of E.U.A. 4,230,688 to Rowsell et al .; which are incorporated herein by reference. Mixtures of these aromatic components can also be used.

Surfactants The fluid may also comprise one or more pharmaceutically acceptable surfactants. Such surfactants may be useful for dispersing or emulsifying medicaments or flavorings, for enhancing absorption through the nasal membrane, or as treatment agents, for example, for softening cerumen. The surfactants can be anionic, nonionic, cationic or amphoteric, and are preferably nonionic. Typical nonionic surfactants useful herein include: Polyoxyethylene derivatives of partial fatty acid esters of sorbitol anhydrides, such as polysorbate 80; polyoxyethylene derivatives of fatty acids such as polyoxyethylene stearate 50, as well as oxyethylated tertiary phenol octyl phenol formaldehyde polymer (available from Sterling Organics as Tyloxapol), or mixtures thereof. The usual concentration is from 0.1% to 3% by weight.

Salts The fluid may also comprise one or more pharmaceutically acceptable salts. The salt may be mineral salts such as, for example, sodium chloride, or salts of organic acids such as sodium citrate.

Other adiuvants The fluid may further comprise other ingredients such as thickeners, humectants, suspension aids, potting aids, chelating agents and preservatives. The viscosity of the compositions can be maintained at a selected level, using a pharmaceutically acceptable thickening agent. Suitable thickener agents include, for example, xanthan gum, methylcellulose, microcrystalline cellulose, carboxymethylcellulose, chitosan, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, carboxyvinyl polymer, carbomer, and the like, or pharmaceutically acceptable salts thereof. Mixtures of said thickening agents can also be used. The preferred concentration of the thickener will depend on the agent selected. The important point is to use an amount that allows to achieve the selected viscosity. Viscous compositions are usually prepared from solutions by the addition of said thickening agents. Fluids useful in the present invention can also comprise from about 0.01% to about 5% of a humectant to inhibit drying of the mucous membrane and prevent irritation. Any of a variety of pharmaceutically acceptable humectants can be used which include, for example, sorbitol, propylene glycol, polyethylene glycol. glycerol, or mixtures thereof. As in the case of thickeners, the concentration will vary with the selected agent, although the presence or absence of these agents, or their concentration, is not an essential feature of the invention. A pharmaceutically acceptable preservative is generally used to increase the shelf life of the compositions of the present invention. A variety of preservatives can be used which include, for example, benzyl alcohol, parabens, phenyl ethyl alcohol, thimerosal, chlorobutanol, chlorhexidine gluconate or benzalkonium chloride. The most preferred preservative system for use herein comprises a combination of benzalkonium chloride, chlorhexidine gluconate and disodium EDTA as the chelating agent. An adequate concentration of the preservative will be from 0.001% to 2%, based on the total weight, although there may be an appreciable variation, depending on the agent selected. The device is adapted to provide one or more unit dosages of fluid, preferably multiple fluid dosages, each preferably with a volume on the scale of from about 1 to about 100 μl, more preferably from about 1 to about 20, most preferably from about 5 to about 15 μl. The volume of the dose is preferably pre-adjusted, but can be adjusted by the user to a desired volume. Preferably, the device is a refillable unit, but can be part of a larger device, and which can be changed or replaced.

The device is preferably adapted to produce a spray having a fluid ligation, the ligation extending from the nasal piece and having a nose piece end and a supply end, the spray also comprising a spray cone that diverges from the end of the nose. supply of the ligament. By "end of nasal piece" is meant the point at which a recess (in the consecutive recess of a nasal piece) traced perpendicular to the axis of the ligament and just touching the outside of the nasal piece, would interconnect the center of the ligament. The weave preferably has a length of from about 1 to about 20 mm, more preferably from about 1 to about 10 mm, even more preferably from about 2 to about 8 mm, and especially from about 3 to about 6 mm from the end of the nasal piece to the supply end. In preferred embodiments, the spray cone has a cone angle of from about 10 to about 90 °, preferably from about 20 to about 50 °, more preferably from about 30 to about 40 °. In electrostatic devices, the length of the ligament and the angle of the spray cone can be adjusted by varying the viscosity or surface tension of the fluid, by varying the flow velocity or the exit velocity of the fluid, or by modifying the characteristics of the groove of the fluid. the valve or the material properties of the valve, or by varying the intensity of the electric field through the applied voltage, potential gradient or through the use of a field intensifying electrode.

The total length of the ligament can be, and is preferably, greater than the length of the end of the nose piece towards the delivery end, since the ligament originates preferably from a point on the device side of the part recess nasal, such as from a self-sealing elastomeric valve as described herein, and passes through a passage in the nasal piece. Suitably, the distance from the point of origin of the ligament to the recess of the nose piece is on the scale of about 2 mm to about 15 mm, preferably about 3 to about 10 mm, and more preferably about 5 to about 9 mm. In this way, the nasal piece can be used as a field enhancer that helps control the length of the ligament. For this purpose, the nasal piece is preferably a non-conductive material such as a plastic which may be, for example, polypropylene, but is preferably a soft thermoplastic elastomer which provides greater comfort if held against the nose. Elastomers described herein for the self-sealing valve are also suitable for the nasal piece. Electrostatic devices suitable for spraying by sheaf mode are described in WO 96/40441, EP-A-501, 725 and in copending application PCT / GB97 / 02746. Preferably, the present device is a device in accordance with the embodiments of EP-A-501, 725 or PCT / GB97 / 02746, in which a jet is created by mechanical means and a high applied voltage makes the jet or ligament is divided into the spray cone. Suitable jet speeds are from about 0.5 to about 8, preferably from about 1 to about 3 msec. 1. A suitable high voltage is in the range of about 1 kV to about 15 kV, preferably about 2 kV. at about 10kV, and more preferably about 2kV to about 5kV.The voltage can be conveniently applied, even within the constraints of a small handheld device, from a low voltage battery (1.5V is sufficient) coupled to a multiplier transformer. The battery is preferably of the long life type, and can be rechargeable The generator can be activated by the user by means of an external switch, which can also be used to mechanically prime the pump. Preferably, the switch includes a portion of metal by means of which the user concludes a return path to ground for the high-voltage circuit. A suitable arrangement for the general construction of the device is described in PCT / GB97 / 02746. In this way, the user does not acquire a net charge. Alternate arrangements, by which an alternate voltage is applied, can also be used to prevent the accumulation of charge. The device is preferably actuated to supply the spray. The spraying ligament extends through the nostril opening in the vestibule and preferably within a short distance of the opening of the nasal valve, before dividing to form the spray cone. To provide clean closure at low unit volumes, the device preferably comprises a self-sealing elastomeric outlet valve having a fluid side and a supply side, the valve opening to allow fluid passage when pressure is applied to the fluid on the side of the fluid, and sealing when the pressure is removed. Preferably, a clean seal is achieved by terminating the piston moving forward in a pressure relief chamber (wider diameter area), resulting in an immediate decrease in pressure and closing of the valve. By "outlet valve" is meant that the elastomeric valve is the final supply valve, and that there are no other elements of the device that restrict or mechanically modify the flow of fluid on the downstream side of the valve. In highly preferred embodiments of the present, the valve is a slot valve. The valve may comprise a single groove or two or more intersecting grooves, to form a cross shape, for example. Preferably, however, the valve comprises a single slot. Although the valve may be flat, it is preferably in the form of a dome, by which is meant a non-planar valve having a depression such as with a hemispherical or frusto-conical dome. In preferred embodiments, the valve is essentially in the form of a hemispherical dome having a flange along its perimeter, so that a collar can be adjusted to retain the valve in the device. The diameter of the valve, including the flange, is typically from about 2 to about 6 mm, wherein the dome portion has a diameter of about 1 to about 4 mm, typically about 2.5 mm, and a thickness of inside out about 0.5 to about 1.5 mm, conveniently about 1 mm. The valve does not need to be of a uniform thickness. In preferred embodiments, the outer surface of the valve dome is hemispherical, while the inner surface is formed of a small recess in the upper part of the dome, where the slot is formed. Suitable widths of the slot are from about 50 to about 400 μm, preferably from about 150 to about 250 μm. It will be understood that the width of the slot refers to the longest dimension of the slot when it is created first. The term "elastomer" refers herein to a material which is elastically compressible and elastically stretchable. A wide range of elastomers can be used including, but not limited to, polyurethanes, styrene-butadiene rubbers and butadiene, butyl and chloroprene, and silicone elastomers such as 2-part room temperature vulcanized silicones (RTV). Preferred for use herein are 2-part silicone RTVs. Suitable silicone RTVs are available under the trademark NuSil, and have a Shore A hardness of from about 30 to about 80, preferably Shore A from about 40 to about 70. The elastomers can optionally be mixed with a foaming agent or suitable plasticizer to make them more compressible. The elastomer may also have other materials dispersed therein to modify its properties, such as its conductivity. If elastomers of low tear strength are used, the width of the groove may increase if the groove is kept open for a prolonged period. The groove valve can be formed by piercing an elastomeric stamp by injection or compression, of the same dimensions and shape of the desired valve, with a pin having a sharp tip. The width of the slot is almost proportional to the width of the pin. The pin may be a flat sheet or may have a polygonal or round cross section. The pin preferably has a polygonal cross section or, especially, a round cross section. It has been found that the sharp cone shaped pins create a cut which behaves in use as a flap rather than a hole. This can lead to a jet which is not straight, or even to the creation of two or more jets which can lead to unreliable or unpredictable spraying. Suitable pin diameters are from about 100 to 350, more preferably from 150 to 250 μm in diameter. When silicone elastomers are used, it is preferred that the piercing pin be removed quickly after forming the groove to prevent unwanted increase of the groove. It has further been found that the geometry of the elastomeric seal and the perforation method have a significant effect on the efficiency and reproducibility of the groove formation. A more reliable formation of the groove is achieved if the seal is drilled from inside the dome, rather than from the outside.

The valve normally opens when pressure is applied to the fluid on the fluid side, and is sealed when the pressure is removed. The applied pressure is suitably in the range from about 200 to about 5000 mbar (20 to 500 kPa), preferably from about 500 to about 3000 mbar (50 to 300 kPa). The flow velocity through the valve is generally proportional to the applied pressure, and is suitably in the range of about 5 to about 50, more preferably about 5 to about 30 μls. "At those pressures and with the type of valve and the described slot dimensions, a straight fluid weave is obtained with an exit velocity of about 0.5 to about 8, preferably about 1 to about 3 msec. "1. The diameter of the ligament is determined in part by the flow velocity, and is generally smaller than the width of the groove valve. Depending on the flow velocity, ligament diameters of less than 50 μm can be achieved, even when a valve groove width of 200 μm is used. The diameter of the ligament greatly influences the size of the spray particle after it is divided into the spray cone, the particle size being broadly similar to the diameter of the ligament. It is a characteristic of the electrostatic spraying mode by ligament of the present, that a closely distributed and almost monodisperse spray is obtained. In this way, it is possible to achieve a spray with an average particle size of from 20 to about 80, preferably from about 30 to about 70 μm, more preferably from about 40 to about 60 μm, the particle size distribution having generally one standard deviation less than 5, typically less than 2 μm, and preferably less than 1 μm. It is commonly understood that, for nasal spray, a particle size of 10 μm or less is not desirable, so that the particles are not carried through the lungs. However, it is thought that having an electrostatic charge on the spray particles is much less likely to be carried beyond the nose, since the charged particles tend to find a grounded surface rather quickly. The clean closing performance of the valve tip can also be improved by introducing a pressure relief feature behind the valve. This area will provide a sudden decrease in pressure when the piston enters this area shortly before the end of its forward stroke, and requires immediate and safe valve closure without dripping at the end of the full dose.

Methods The spray device herein is suitable for spraying in a body cavity, particularly in the nose, mouth or ear of a human. The low volume and the soft spray also make it suitable, for example, for ophthalmic spraying. Preferably, the device is a nasal spray device. A preferred method for delivering a fluid to the nasal cavity from the spray device comprises spraying the fluid into the nasal cavity without substantial penetration of the device into the nostrils. By "without substantial penetration in the nostrils", it is understood herein that there is no insertion of a nozzle or its similar in the nasal vestibule. During use, the nasal piece of the device is preferably placed in contact with the nostril opening to obtain the full benefit of the field enhancing effect described herein in relation to the nasal piece. If the user applies pressure, to be certain that there is contact or to facilitate orientation, there may be some widening of the nostrilo or overlap with the cartilage of the nasal septum, but nevertheless the nasal piece will not be completely surrounded by the nostrilo.

Claims (8)

NOVELTY OF THE INVENTION CLAIMS

1. - A dispensing device (1, 2) for a fluid (10), the dispensing device (1, 2) comprising a reservoir (11), an arrow (12), a rear seal (13), a gate (14), a piston (151, 152) and a unidirectional valve (16), the rear seal (13) sealing a first end of the reservoir (11) and being displaceable along the arrow (12), the valve (16) being in the second end of the reservoir (11), the piston (151, 152) being fixed to one end of the arrow (12), the piston (151, 152) being located between the valve (16) and the gate, the gate ( 14) being also fixed to the arrow (12), the gate (14) being located between the piston and the rear seal (13), whereby the piston (151, 152) has an open position (151) and a position closed (152), the open position allowing fluid communication between the valve (16) and the tank part (11) between the piston (151, 152) and the rear seal (13), the displacement of the piston (151, 152) between the open position and the closed position being induced by a displacement of the arrow (12) along its own axis, the pressure in the area between the valve (16) and the piston (151, 152) decreasing when the piston moves from its closed position to its open position, the gate (14) crushing when the piston moves from its closed position to its open position, the only fluid flow from the reservoir part (11) located between the gate (14) and the rear seal (13) and the part of the tank (11) located on the other side of the gate (14), being a connection passage (140) located in the gate ( 14) when the piston (151, 152) moves from its open position to its closed position.

2. The dispensing device according to claim 1, further characterized in that the arrow (12) is made of a material that conducts electricity.

3. The dispensing device according to claim 2, further characterized in that the fluid is electrically charged before being dispensed.

4. The dispensing device according to claim 1, further characterized in that the volume comprised between the piston in the open position and the valve (16) is less than 100 μl.

5. The dispensing device according to claim 1, further characterized in that the volume of fluid dispensed in each assortment operation varies from less than 10% between each assortment operation.

6. The dispensing device according to claim 1, further characterized in that a compressed spring is located at the end of the arrow (12) opposite the end to which the piston (151, 152) is fixed, applying a force on the arrow (12) in a direction substantially parallel to the axis of the arrow (12).

7. - The dispensing device according to claim 1, further characterized in that the unidirectional valve (16) is a self-sealing valve (16).

8. The dispensing device according to claim 1, further characterized in that the connection passage (140) is a single opening provided in the gate (14). SUMMARY OF THE INVENTION The present invention relates to a dispensing device 1 for a fluid 10, the dispensing device 1 comprising a reservoir 11, an arrow 12, a rear seal 13, a gate 14, a piston 151 and a unidirectional valve 16, the rear seal 13 by sealing a first end of the reservoir and being displaceable along the arrow, the valve being at the second end of the reservoir, the piston being fixed to one end of the shaft, the piston being located between the valve and the gate, the gate also being fixed to the arrow, the gate being located between the piston and the rear seal, whereby the piston has an open position 151 and a closed position 152, the open position allowing fluid communication between the valve and the part of the tank between the piston and the rear seal, the displacement of the piston between the open position and the closed position being induced by a displacement of the arrow along its own axis, the pressure in the area between the valve and the piston decreasing as the piston moves from its closed position to its open position, the gate collapsing when the piston moves from its closed position to its open position, the only flow of fluid from the part of the reservoir located between the gate and the rear seal and the part of the reservoir located on the other side of the gate, a connecting passage 140 being located in the gate 14 when the piston moves from its open position towards its closed position. P01 / 1019F