EP1020233A1 - Dosierungs- und Verteilungssystem - Google Patents

Dosierungs- und Verteilungssystem Download PDF

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Publication number
EP1020233A1
EP1020233A1 EP99870004A EP99870004A EP1020233A1 EP 1020233 A1 EP1020233 A1 EP 1020233A1 EP 99870004 A EP99870004 A EP 99870004A EP 99870004 A EP99870004 A EP 99870004A EP 1020233 A1 EP1020233 A1 EP 1020233A1
Authority
EP
European Patent Office
Prior art keywords
piston
valve
damper
reservoir
fluid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP99870004A
Other languages
English (en)
French (fr)
Inventor
David Victor Cann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Procter and Gamble Co
Original Assignee
Procter and Gamble Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Procter and Gamble Co filed Critical Procter and Gamble Co
Priority to EP99870004A priority Critical patent/EP1020233A1/de
Priority to NZ512600A priority patent/NZ512600A/xx
Priority to CN00802613A priority patent/CN1347346A/zh
Priority to CZ20012506A priority patent/CZ20012506A3/cs
Priority to AU25046/00A priority patent/AU748289B2/en
Priority to PE2000000022A priority patent/PE20001192A1/es
Priority to EG20000030A priority patent/EG22672A/xx
Priority to RU2001122593/12A priority patent/RU2198740C1/ru
Priority to KR1020017008745A priority patent/KR20020004944A/ko
Priority to CA002360411A priority patent/CA2360411A1/en
Priority to AT00903272T priority patent/ATE248030T1/de
Priority to US09/869,478 priority patent/US6471095B1/en
Priority to EP00903272A priority patent/EP1140368B1/de
Priority to HU0105057A priority patent/HUP0105057A3/hu
Priority to PCT/US2000/000834 priority patent/WO2000041816A1/en
Priority to CO00001231A priority patent/CO5231171A1/es
Priority to DE60004780T priority patent/DE60004780T2/de
Priority to PL00349767A priority patent/PL349767A1/xx
Priority to BR0007526-4A priority patent/BR0007526A/pt
Priority to JP2000593418A priority patent/JP4295437B2/ja
Priority to SK1006-2001A priority patent/SK10062001A3/sk
Priority to IL14409200A priority patent/IL144092A0/xx
Publication of EP1020233A1 publication Critical patent/EP1020233A1/de
Priority to ZA200105289A priority patent/ZA200105289B/en
Priority to MA26264A priority patent/MA25341A1/fr
Priority to NO20013508A priority patent/NO20013508L/no
Withdrawn legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
    • B05B11/02—Membranes or pistons acting on the contents inside the container, e.g. follower pistons
    • B05B11/028—Pistons separating the content remaining in the container from the atmospheric air to compensate underpressure inside the container
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
    • B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
    • B05B11/1001—Piston pumps
    • B05B11/1015—Piston pumps actuated without substantial movement of the nozzle in the direction of the pressure stroke
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
    • B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
    • B05B11/1042—Components or details
    • B05B11/1052—Actuation means
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
    • B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
    • B05B11/1094—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle having inlet or outlet valves not being actuated by pressure or having no inlet or outlet valve
    • 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
    • B05B5/16—Arrangements for supplying liquids or other fluent material
    • B05B5/1691—Apparatus to be carried on or by a person or with a container fixed to the discharge device

Definitions

  • the invention relates to a mechanical assembly for dosing and delivering a fluid.
  • Devices for dosing and delivering a fluid are widely used in consumer goods or in pharmaceutical industry. Such devices for dosing and delivering a fluid should allow a good control of the quantity of fluid dosed, as well as a good control of the delivery of this fluid dose. In particular in the pharmaceutical industry, accurate control of both the quantity and the delivery are critical. Furthermore, it is desired to produce such devices in a reproducible and economical manner. It is the object of this invention to provide accurate dosing and delivery of a fluid by means of an economical dosing and delivery device.
  • this object is accomplished in a dispensing device for a fluid, the dispensing device comprising a reservoir, a shaft, a back seal, a damper, a piston and a one-way valve, the back seal 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 and a closed position, the open 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
  • a device formed in accordance to the invention has a number of advantages. Since the devices comprises a piston having an opened position and a closed position allowing fluid communication between the valve and the reservoir, the quantity of fluid to dispense can be accurately controlled by displacing the desired quantity of fluid from the reservoir to the valve part by displacement of the piston from the closed to the opened position, the absence of a direct link between the reservoir and the valve avoiding uncontrolled emptying of the reservoir through the valve.
  • the displacement of the piston towards the opened position will necessitate the application of a force threshold sufficient to overcome or at least to balance the pressure reduction and internal system friction forces, so that undesired displacement of the piston is avoided.
  • the delivery of the dose is also accurately controlled via the combination of the use of the one way valve, of the piston, of the damper and of the back seal.
  • the one way valve will allow delivery of the fluid only when the piston is displaced forward towards the valve, the speed of displacement of the piston being regulated by the size of the connecting passage provided in the damper combined with the fluid viscosity and applied mechanism force (e.g. spring force), thus allowing control on the speed of the fluid delivery through the valve.
  • Figure 1 is a plan cross section view illustrating a dispensing device in accordance with the invention, the piston being in opened position.
  • Figure 2 is a plan cross section view illustrating a dispensing device in accordance with the invention, the piston being in closed position.
  • the invention relates to a dispensing device 1 or 2 for a fluid 10.
  • fluid it should be understood that it includes liquids having various viscosities.
  • Preferred fluids in a preferred embodiment of the invention are pharmaceutical fluids, but other applications are envisaged, such as air-freshening devices for example.
  • the dispensing device 1 or 2 comprising a reservoir 11.
  • the reservoir is typically a chamber in which the fluid 10 is to be found.
  • the reservoir is substantially gas tight, thus avoiding or limiting chemical evolution due to contact with O 2 or H 2 O vapour for example, or to retain air out of the device, in order to avoid discrepancies in the quantity of fluid to dose.
  • the dispensing device further comprises a shaft 12, the shaft typically being an elongated element having as a main axis the more elongated direction, the shaft also normally comprising a part having a constant cross section in a plane normal to the main axis for allowing translation of a back seal 13, or being for example threaded to allow helical displacement of the a back seal 13 along the shaft 12.
  • the device further comprises a back seal 13, the back seal 13 allowing sealing of the reservoir 11, substantially independently from the quantity of fluid 10 contained in the reservoir 11.
  • the back seal 13 has a substantially identical cross section, the back seal 13 cross section being preferably marginally larger than the constant cross section of the reservoir 11 in order to achieve sealing, so that displacement of the back seal 13 along the shaft 12 allows to seal the reservoir 11 along the constant cross section 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 varying volume.
  • the back seal 13 is made of a flexible and resilient material having an umbrella like shape, or even more preferably a double umbrella like shape, such that the seal is constantly pressing against the reservoir 11 on the cross section perimeter.
  • the device 1 or 2 further comprises a damper 14.
  • the damper is preferably a part made of a flexible material and having a umbrella like shape favouring collapsing during displacement in one direction and damping during 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 being 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 to the one of the piston 151 or 152 in order to allow good sealing.
  • the main axis of the piston 151 or 152 is parallel of even aligned with the main axis of the shaft 12.
  • the device further comprises a one-way valve 16.
  • valve 16 By a one way valve it should be understood that in normal use, the valve 16 will allow passage of the fluid in one direction only.
  • the valve 16 is a "self-seal" 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 back seal 13 is sealing a first end of the reservoir 11. This allows to use a gas tight reservoir 11, which is useful to allow stability of the fluid product 10 and is necessary to the functioning of the device as will be described below.
  • the back seal 13 should also be displaceable along the shaft 12, such displacement including linear or helical displacement for example.
  • the valve 16 is on the second end of the reservoir 11.
  • the reservoir is normally elongated along the main direction of the shaft, and comprises two end only, the first one being sealed by the back seal 13 and the other comprising the valve 16.
  • the piston 151 or 152 is fixed to one end of the shaft 12. Indeed, 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. In order to achieve this, the piston 151 or 152 being located between the valve 16 and the damper 14.
  • the damper 14 is also fixed to the shaft 12, the damper 14 being located between the piston 151 or 152 and the back seal 13. Indeed, the damper 14 is located in the part 110 of the reservoir 11 which is not containing a dose 100 ready to be dispensed.
  • the device 1 or 2 according to the invention is mainly intended for multiple use, so that the damper 14 stands in the part of the reservoir 11 which contains a plurality of doses which are not ready to be dispensed as they are not located between the piston and the valve. It should be noted that the device 1 or 2 could also be suitable for single use.
  • the piston 151 or 152 has an opened position 151 and a closed position 152, the open position 151 allowing fluid communication 153 between the valve 16 and the part of the reservoir 11 between the piston 151 and the back seal 13. This fluid communication 153 allows a dose of product 100 to be placed in between the piston 151 and the valve 16 prior to dispensing.
  • the displacement of the piston between the opened 151 and the closed 152 position is induced by a displacement of the shaft 12 along its own axis, which is the main axis.
  • the pressure in the area 100 comprised between the valve 16 and the piston reduces when the piston is moved from its closed position 152 towards its opened position 151, thus generating a part vacuum. This allows to "suck in” a dose 100 of product from the part of the reservoir 11 located between the piston an the back seal into the part 100 between the valve and the piston when the piston goes in opened position 151.
  • the damper 14 collapses when the piston is moved from its closed position 152 towards its opened position 151.
  • the piston has to move from its opened 151 towards its closed 152 position, thus moving the damper 14 as both the damper 14 and the piston are fixed to the shaft 12, the damper 14 moving through the fluid 10, thus creating a non-equilibrium in the sealed reservoir 11 between the part of the reservoir located between the damper 14 and the back seal 13 and the part of the reservoir 11 located between the damper 14 and the piston, this non-equilibrium being compensated by a flow in the connecting passage 140 situated in the damper 14, thus controlling the speed of ejection or delivery of the dose 100 ready to be dispensed through the valve 16 by control of the move of the piston.
  • the piston will have a maximum speed depending marginally on the compressibility and mainly on the viscosity of the fluid and on the geometrical and/or mechanical characteristics of the device. Indeed, for example, the larger the connecting passage 140 or the higher the applied forward force to the shaft 12 the higher the maximum speed.
  • the shaft is made out of a material conducting electricity, such as metal for example.
  • the fluid is electrically charged prior to being dispensed.
  • the device according to the invention is particularly suited for this application as charging of the fluid will be facilitated by the control on the flow. In particular, there is a maximum speed beyond which charging the fluid becomes difficult or impossible, so that a damped delivery allows good charging.
  • the charge rate is matched to the fluid flow rate to achieve efficient electro-hydrodynamic atomisation of the fluid.
  • the volume comprised between the piston in the opened position and the valve is of less than 100 ⁇ L.
  • control on delivery is such that the volume of fluid dispensed at each dispensing operation varies of less than 10% between each dispensing operation. Even more preferably, the variation is of less than 5%.
  • a compressed spring is located on the end of the shaft opposite to the one to which the piston is fixed, applying a force onto the shaft in a direction substantially parallel to the shaft axis.
  • the connecting passage is a single opening provided in the damper, even more preferably a circular opening.
  • a most preferred embodiment of the invention is obtained by integrating the device of the invention to the spray device as disclosed in the pending applications GB9806937.0 and GB9806939.6.
  • a spray device is particularly suited for treatment of maladies affecting the nasal region, such as hay fever or congestion due to colds.
  • the mucous membranes of the nasal cavity can be used as a convenient delivery site for drugs' targeted at other areas of the body. See for example WO 92/11049 which discloses a pen shaped device for nasal administration of, particularly, insulin.
  • a spray form is often convenient for such treatments. Treatment of the eyes can also conveniently be effected by a spray device.
  • Preferred volume doses for such applications are generally low, down to less than 10 ⁇ l.
  • the spray device is adapted to provide one or more unit doses of a fluid, each dose having a volume in the range from about 1 to about 100 ⁇ l, the device comprising an elastomeric, self-sealing valve having a fluid side and a delivery side, the valve opening to allow passage of the fluid when pressure is applied to fluid on the fluid side and sealing when the pressure is removed.
  • the spray device is an electrostatic spray device which charges the spray before entry into the nostrils.
  • 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, flavours, salts, surfactants and mixtures thereof.
  • the fluid optionally comprises other adjuvants dissolved or dispersed within it.
  • 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.
  • the fluid is an aqueous solution, dispersion or oil-in-water emulsion.
  • Suitable non-aqueous fluids comprise polyethylene glycols, glycerol, propylene glycol, dimethyl isosorbide, silicone oils, ketones, ethers and mixtures thereof.
  • the invention has particular application to low resistivity fluids, especially those having a bulk resistivity of less than 1 x 10 8 ohm.cm, preferably those having a resistivity of less than 1 x 10 4 ohm.cm, more preferably less than 1 x 10 3 ohm.cm.
  • the fluid may comprise a resistivity modifier, such as a pharmaceutically acceptable salt, in order to bring the bulk resistivity within the required range.
  • the fluid is preferably a pharmaceutically acceptable intranasal carrier.
  • the nasal composition is isotonic, i.e., it has the same osmotic pressure as blood and lacrimal fluid.
  • the desired isotonicity of the compositions of this invention may be accomplished 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 inorganic or organic solutes.
  • Sodium chloride is preferred particularly for buffers containing sodium ions. Further examples of sodium chloride equivalents are disclosed in Remington's Pharmaceutical Sciences pp. 1491-1497 (Alfonso Gennaro 18th ed. 1990), which is herein incorporated by reference.
  • the fluid can comprise a wide range of medicaments.
  • medicament 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 medicaments will depend on many factors including their potency, safety profile, solubility / ease of dispersion and intended effect.
  • the medicament when used, can be one which is intended to have an effect at the site of application, such as a decongestant, antihistamine or anti-inflammatory drug, or it may be intended for systemic absorption such as an antiviral, anti-depressant, anti-emetic, anti-pyretic medicament or a hormone or such-like.
  • the medicament can be soluble in the fluid or can be an insoluble, finely divided particulate liquid or solid 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.
  • oxymetazoline hydrochloride which is soluble in water.
  • 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 to the present invention include, but are not limited to, fast-acting, histamine H-1 receptor antagonists. Such H-1 receptor antihistamines may be selected from among the following groups of antihistamines: alkylamines, ethanolamines, ethylenediamines, piperazines, phenothiazines, piperidines.
  • Examples of useful fast acting antihistamines include acrivastine, carbinoxamine, diphenhydramine, chloropheniramine, brompheniramine, dexchloropheniramine, doxylamine, clemastine, promethazine, trimeprazine, methdilazine, hydroxyzine, pyrilamine, tripelennamine, meclizine, triprolidine, azatadine, cyproheptadine, rocastine, phenindamine or pharmaceutically acceptable salts and mixtures thereof.
  • antihistamines include terfenadine, azelastine, cetirizine, astemizole, ebastine, ketotifen, lodoxamide, loratadine, levocabastine, mequitazine, oxatomide, setastine, tazifylline, temelastine or pharmaceutically acceptable salts and mixtures thereof.
  • 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.
  • glucocorticoids selected from the group consisting of beclomethasone, flunisolide, fluticasone, memetasone, budesonide, pharmaceutically acceptable salts thereof and mixtures thereof.
  • 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%.
  • xanthine derivatives such as caffeine and methylxanthine and the like; antiallergics; mucolytics; anticholinergics; non-opiate analgesics such as acetaminophen, acetylsalicylic acid, ibuprofen, etodolac, fenbuprofen, fenoprofen, ketorolac, flurbiprofen, indomethacin, ketoprofen, naproxen, pharmaceutically acceptable salts thereof and mixtures thereof; opiate analgesics such as butorphanol; leukotriene receptor antagonists; mast cell stabilisers such as cromolyn sodium, nedocromil and lodoxamide; lipoxygenase inhibiting compounds; and nicotin, insulin and calcinotin.
  • suitable medicaments can be found in WO97/46243, EP-A-780127, US-A-5,124,315, US-A-5,
  • flavouring and/or aromatic components 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 fruit); 2-dodecenal (citrus, mandarin); and herbal components such as thyme, rosemary and sage oils.
  • Additional aromatic components suitable for use in the present invention include those described in U.S. Patent 4,136,163 to Watson et al., U.S. Patent 4,459,425 to Amano et al., and U.S. Patent 4.230,688 to Rowsell et al.; all of which are herein incorporated by reference. Mixtures of these aromatics can also be used.
  • the fluid can also comprise one or more pharmaceutically acceptable surfactants.
  • surfactants can be useful for dispersing or emulsifying medicaments or flavours, for enhancing absorption across the nasal membrane or as treatment agents in their own right, such as for softening earwax.
  • the surfactants can be anionic, nonionic, cationic or amphoteric, preferably they are nonionic.
  • Typical nonionic surfactants useful herein include: polyoxyethylene derivatives of fatty acid partial esters of sorbitol anhydrides such as polysorbate 80; polyoxyethylene derivatives of fatty acids such as polyoxyethylene 50 stearate, as well as oxyethylated tertiary octyl phenol formaldehyde polymer (available from Sterling Organics as Tyloxapol) or mixtures thereof.
  • concentration is from 0.1 % to 3% by weight.
  • the fluid can also comprise one or more pharmaceutically acceptable salts.
  • the salt can mineral salts such as e.g. sodium chloride, or salts of organic acids such as sodium citrate.
  • the fluid can further comprise other ingredients such as thickeners, humectants, suspending aids, encapsulating aids, chelating agents and preservatives.
  • the viscosity of the compositions may be maintained at a selected level using a pharmaceutically-acceptable thickening agent.
  • suitable thickening agents include, for example, xanthan gum, methyl cellulose, microcrystalline cellulose, carboxymethyl cellulose, chitosan, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, carboxyvinyl polymer, carbomer, and the like or pharmaceutically acceptable salts thereof. Mixtures of such thickening agents may also be used.
  • the preferred concentration of the thickener will depend upon the agent selected. The important point is to use an amount which will achieve the selected viscosity. Viscous compositions are normally prepared from solutions by the addition of such 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 to prevent irritation. Any of a variety of pharmaceutically-acceptable humectants can be employed including, for example sorbitol, propylene glycol, polyethylene glycol, glycerol or mixtures thereof. As with the 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 employed to increase the shelf life of the compositions of the present invention.
  • preservatives including, for example, benzyl alcohol, parabens, phenylethyl alcohol, thimerosal, chlorobutanol, chlorhexidine gluconate, or benzalkonium chloride can be employed.
  • the most preferred preservative system for use herein comprises a combination of benzalkonium chloride, chlorhexidine gluconate and disodium EDTA as a chelating agent.
  • a suitable concentration of the preservative will be from 0.001% to 2% based on the total weight, although there may be appreciable variation depending upon the agent selected.
  • the device is adapted to provide one or more unit fluid doses, preferably multiple fluid doses, each preferably with a volume in the range of from about 1 to about 100 ⁇ l, more preferably from about 1 to about 20, more preferably from about 5 to about 15 ⁇ l.
  • the dose volume is preferably pre-set but may be adjusted by the user to a desired volume.
  • the device is a refill unit which may be part of a larger device and which may be changed or replaced.
  • the device is preferably adapted to produce a spray having a fluid ligament, the ligament extending from the nosepiece and having a nosepiece end and a delivery end, the spray further comprising a spray cone diverging from the delivery end of the ligament.
  • nosepiece end is meant the point at which a plane (hereinafter the nosepiece plane) drawn perpendicular to the axis of the ligament and just touching the exterior of the nosepiece would intersect the centre of the ligament.
  • the ligament preferably has a length of from about 1 to about 20 mm, more preferably from about 1 to about 10 mm, yet more preferably from about 2 to about 8 mm, and especially from about 3 to about 6mm from the nosepiece end to the delivery end.
  • the spray cone has a cone angle of from about 10 to about 90°, preferably 20 to about 50°, more preferably from about 30 to about 40°.
  • the length of the ligament and the spray cone angle can be adjusted by varying the viscosity or surface tension of the fluid, by varying the fluid flow rate or exit velocity, or by changing the valve slit characteristics or valve material properties, or by varying the electrical field strength through applied voltage, potential gradient or by use of a field intensifying electrode.
  • the total length of the ligament can be, and preferably is, longer than the length from the nosepiece end to the delivery end since the ligament preferably originates from a point on the device side of the nosepiece plane, such as from an elastomeric, self-sealing valve as disclosed herein, and passes through a passage in the nosepiece.
  • the distance from the point of origin of the ligament to the nosepiece plane is in the range from about 2 mm to about 15 mm, preferably from about 3 to about 10 mm and more preferably from about 5 to about 9 mm.
  • the nosepiece can be employed as a field intensifier which helps to control the ligament length.
  • the nosepiece is preferably a non-conducting material such as a plastic which can be e.g. polypropylene but is preferably a soft thermoplastic elastomer which provides for greater comfort if held against the nose. Elastomers described herein for the self-sealing valve are also suitable for the nosepiece.
  • Electrostatic devices suitable for ligament mode spraying are described in WO 96/40441, in EP-A-501,725 and in co-pending application PCT/GB97/02746.
  • the present device is a device according to embodiments of EP-A-501,725 or PCT/GB97/02746 in which a jet is created by mechanical means and an applied high voltage leads to the jet or ligament breaking up into a spray cone.
  • Suitable jet velocities are from about 0.5 to about 8, preferably from about 1 to about 3 ms -1 .
  • a suitable high voltage is in the range from about 1 kV up to about 15 kV, preferably from about 2kV to about 10kV and more preferably from about 2kV to about 5kV.
  • the voltage can conveniently be applied, even within the constraints of a small hand-held device, from a low voltage (1.5V is sufficient) battery coupled to a step-up 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.
  • the switch includes a metal portion by means of which the user completes an earth return path to the high voltage circuit.
  • a suitable arrangement for the overall device construction is described in PCT/GB97/02746. In this way the user does not acquire a net charge. Alternate arrangements, whereby an alternating voltage is applied, can also be used to prevent charge build-up.
  • the device is preferably activated to deliver the spray.
  • the ligament of the spray extends through the nostril opening, into the vestibule and preferably to within a short distance of the nasal valve opening, before breaking up to form the spray cone.
  • the device preferably comprises an elastomeric, self-sealing exit valve having a fluid side and a delivery side, the valve opening to allow passage of the fluid when pressure is applied to fluid on the fluid side and sealing when the pressure is removed.
  • clean stop is achieved by having the piston ending its forward movement in a pressure relief chamber (wider diameter area) resulting in a immediate pressure drop and resulting valve closure.
  • exit valve is meant that the elastomeric valve is the final dispensing valve and that there are no other elements of the device which mechanically, restrict or modify the flow of the fluid on the downstream side of the valve.
  • the valve is a slit valve.
  • the valve can comprise a single slit or tow or more intersecting slits, to form a cross shape for example.
  • the valve comprises a single slit.
  • the valve can be flat it is preferably dome-shaped by which is meant a nonplanar valve having a recess such as with a hemispherical or frustoconical dome.
  • the valve is essentially in the form of a hemispherical dome having a flange along its perimeter so that a collar can be fitted to retain the valve in the device.
  • the diameter of the valve, including the flange is typically from about 2 to about 6 mm with the dome portion having a diameter of from about 1 to about 4 mm, typically about 2.5mm and a thickness from inside to out of from about 0.5 to about 1.5 mm, suitably about 1 mm.
  • the valve need not be of uniform thickness.
  • the valve dome's exterior surface is hemispherical whereas the internal surface is formed with a small flat at the top of the dome where the slit is formed.
  • Suitable slit widths are from about 50 to about 400 ⁇ m, preferably from about 150 to about 250 ⁇ m. It is to be understood that the slit width refers to the longest dimension of the slit when first created.
  • the term "elastomer” herein refers to a material which is both elastically compressible and elastically extensible. A wide range of elastomers can be used, including but not limited to polyurethanes; chloroprene, butyl, butadiene and styrene-butadiene rubbers, and silicone elastomers such as 2 part room temperature vulcanising (RTV) silicones. Preferred for use herein are the 2 part silicone RTVs.
  • Suitable silicone RTVs are available under the trademark NuSil and have a hardness of from about 30 to about 80 Shore A, preferably from about 40 to about 70 Shore A.
  • the elastomers can optionally be mixed with a suitable plasticiser or foaming agent to make them more compressible.
  • the elastomer may also have other materials dispersed within it in order to modify its properties, such as its conductivity. If elastomers of low tear strength are employed, the slit width may grow if the slit is held open for a prolonged period of time.
  • the slit valve can be formed by piercing an injection or compression moulded elastomeric seal, of the same dimensions and shape as the intended valve, with a pin having a sharpened tip.
  • the slit width is roughly proportional to the pin width.
  • the pin can be a flat blade or can have a polygonal or round cross-section.
  • the pin preferably has a polygonal or, especially, a round cross-section. It has been found that cone-shaped sharp-edged 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 may lead to unreliable or unpredictable spraying.
  • Suitable pin diameters are from about 100 to 350, more preferably from 150 to 250 ⁇ m in diameter. When silicone elastomers are used it is preferred that the piercing pin is withdrawn rapidly after forming the slit to avoid undesired slit growth.
  • the valve normally opens when pressure is applied to fluid on the fluid side and seals 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 rate through the valve is generally proportional to the pressure applied and is suitably in the range from about 5 to about 50, more preferably from about 5 to about 30 ⁇ ls -1 .
  • a straight fluid ligament with an exit velocity of from about 0.5 to about 8 preferably from about 1 to about 3 ms -1 is obtained.
  • the diameter of the issuing ligament is partly determined by the flow rate and is generally less than the width of the slit valve. Depending on the flow rate, ligament diameters of less than 50 ⁇ m can be achieved, even when a valve slit width of 200 ⁇ m is employed.
  • the ligament diameter strongly influences the particle size of the spray after break-up into the spray cone, the particle size being broadly similar to the ligament diameter. It is a feature of the ligament mode electrostatic spraying herein that a tightly distributed, almost mono-disperse spray is obtained.
  • the clean stop performance of the tip valve can be further improved by introducing a pressure relief feature behind the valve. This area will provide a sudden pressure drop when the piston enters this area near completing its forward stroke and enforce immediate and secure closure of the valve with no dripping at the end of the full dose.
  • the spray device herein is suitable for spraying into a body cavity, particularly into the nose, mouth or ears of a human.
  • the low volume and gentle spray also make it suitable for e.g. ophthalmic spraying.
  • the device is a nasal spray device.
  • a preferred method of administering 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.
  • without substantial penetration into the nostrils herein is meant that there is no insertion of a nozzle or such-like into the nasal vestibule.
  • the nosepiece of the device is preferably placed in contact with the nostril opening to obtain the full benefit of the field intensifying effect described herein in relation to the nosepiece. If pressure is applied by the user, for certainty of contact or to assist in orientation there may be some flaring of the nostril or overlap with the septum cartilage but nevertheless the nosepiece will not be completely surrounded by the nostril.

Landscapes

  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
  • Devices For Dispensing Beverages (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Loading And Unloading Of Fuel Tanks Or Ships (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
  • Vehicle Body Suspensions (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Devices For Use In Laboratory Experiments (AREA)
  • Reciprocating Pumps (AREA)
EP99870004A 1999-01-13 1999-01-13 Dosierungs- und Verteilungssystem Withdrawn EP1020233A1 (de)

Priority Applications (25)

Application Number Priority Date Filing Date Title
EP99870004A EP1020233A1 (de) 1999-01-13 1999-01-13 Dosierungs- und Verteilungssystem
HU0105057A HUP0105057A3 (en) 1999-01-13 2000-01-12 Dosing and delivering system
PCT/US2000/000834 WO2000041816A1 (en) 1999-01-13 2000-01-12 Dosing and delivering system
CN00802613A CN1347346A (zh) 1999-01-13 2000-01-12 定量和供给系统
CO00001231A CO5231171A1 (es) 1999-01-13 2000-01-12 Sistema de dosificacion y suministro de liquido en articulos de consumo o en la industria farmaceutica
PE2000000022A PE20001192A1 (es) 1999-01-13 2000-01-12 Sistema de dosificacion y suministro
EG20000030A EG22672A (en) 1999-01-13 2000-01-12 Dosing and delivering system
RU2001122593/12A RU2198740C1 (ru) 1999-01-13 2000-01-12 Устройство для дозирования и подачи
KR1020017008745A KR20020004944A (ko) 1999-01-13 2000-01-12 정량조절 및 배출 장치
CA002360411A CA2360411A1 (en) 1999-01-13 2000-01-12 Dosing and delivering system
AT00903272T ATE248030T1 (de) 1999-01-13 2000-01-12 System zur dosierung und abgabe einer flüssigkeit
US09/869,478 US6471095B1 (en) 1999-01-13 2000-01-12 Dosing and delivering system
EP00903272A EP1140368B1 (de) 1999-01-13 2000-01-12 System zur dosierung und abgabe einer flüssigkeit
NZ512600A NZ512600A (en) 1999-01-13 2000-01-12 Dosing and delivering system
CZ20012506A CZ20012506A3 (cs) 1999-01-13 2000-01-12 Zařízení pro dávkování a vydávání tekutiny
AU25046/00A AU748289B2 (en) 1999-01-13 2000-01-12 Dosing and delivering system
DE60004780T DE60004780T2 (de) 1999-01-13 2000-01-12 System zur dosierung und abgabe einer flüssigkeit
PL00349767A PL349767A1 (en) 1999-01-13 2000-01-12 Dosing and delivering system
BR0007526-4A BR0007526A (pt) 1999-01-13 2000-01-12 Sistema de dosagem e fornecimento
JP2000593418A JP4295437B2 (ja) 1999-01-13 2000-01-12 分量および送達システム
SK1006-2001A SK10062001A3 (sk) 1999-01-13 2000-01-12 Zariadenie na dávkovanie tekutiny
IL14409200A IL144092A0 (en) 1999-01-13 2000-01-12 Dosing and delivering system
ZA200105289A ZA200105289B (en) 1999-01-13 2001-06-27 Dosing and delivering system.
MA26264A MA25341A1 (fr) 1999-01-13 2001-07-11 Systeme de dosage et de liberation
NO20013508A NO20013508L (no) 1999-01-13 2001-07-13 Doserings- og forsyningssystem

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP99870004A EP1020233A1 (de) 1999-01-13 1999-01-13 Dosierungs- und Verteilungssystem

Publications (1)

Publication Number Publication Date
EP1020233A1 true EP1020233A1 (de) 2000-07-19

Family

ID=8243788

Family Applications (2)

Application Number Title Priority Date Filing Date
EP99870004A Withdrawn EP1020233A1 (de) 1999-01-13 1999-01-13 Dosierungs- und Verteilungssystem
EP00903272A Expired - Lifetime EP1140368B1 (de) 1999-01-13 2000-01-12 System zur dosierung und abgabe einer flüssigkeit

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP00903272A Expired - Lifetime EP1140368B1 (de) 1999-01-13 2000-01-12 System zur dosierung und abgabe einer flüssigkeit

Country Status (23)

Country Link
EP (2) EP1020233A1 (de)
JP (1) JP4295437B2 (de)
KR (1) KR20020004944A (de)
CN (1) CN1347346A (de)
AT (1) ATE248030T1 (de)
AU (1) AU748289B2 (de)
BR (1) BR0007526A (de)
CA (1) CA2360411A1 (de)
CO (1) CO5231171A1 (de)
CZ (1) CZ20012506A3 (de)
DE (1) DE60004780T2 (de)
EG (1) EG22672A (de)
HU (1) HUP0105057A3 (de)
IL (1) IL144092A0 (de)
MA (1) MA25341A1 (de)
NO (1) NO20013508L (de)
NZ (1) NZ512600A (de)
PE (1) PE20001192A1 (de)
PL (1) PL349767A1 (de)
RU (1) RU2198740C1 (de)
SK (1) SK10062001A3 (de)
WO (1) WO2000041816A1 (de)
ZA (1) ZA200105289B (de)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2893090A1 (fr) * 2005-11-09 2007-05-11 Claude Jaunay Ensemble de pompage et de distribution de fluide
WO2011043712A1 (en) * 2009-10-08 2011-04-14 Shl Group Ab Metered liquid droplet inhaler
US8020732B2 (en) 2006-01-24 2011-09-20 Rexam Airspray N.V. Squeeze foamer
US8833365B2 (en) 2008-12-23 2014-09-16 Sanofi-Aventis Deutschland Gmbh Dosing device for generating a gas flow with a finely dispersed active substance

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2389530B (en) 2002-06-14 2007-01-10 Cipla Ltd Pharmaceutical compositions
GB0602980D0 (en) * 2006-02-14 2006-03-29 Optinose As Delivery device and method
CA2740766C (en) * 2008-10-16 2016-02-02 Automatic Bar Controls, Inc. Apparatus and method and turntable for on-demand distributing of a food product
RU2452585C2 (ru) * 2009-06-03 2012-06-10 Макнейл Аб Карманное распределительное устройство
RU2529397C2 (ru) * 2012-10-04 2014-09-27 Ирина Леонидовна Лисовская Устройство для электрофореза лекарственного вещества в ткани глаза
GB2507313B (en) * 2012-10-25 2015-09-30 Tristel Plc Pump apparatus
JP5992321B2 (ja) * 2012-12-27 2016-09-14 株式会社吉野工業所 シリンジ型噴出容器
US11554229B2 (en) 2013-03-26 2023-01-17 OptiNose Inc. Nasal administration
DE102013013530A1 (de) * 2013-08-13 2015-03-12 Dürr Systems GmbH Applikationssystem mit seilgeführter Handhabungsvorrichtung zum Bewegen eines Applikationsgeräts
KR101498220B1 (ko) * 2013-08-30 2015-03-03 삼성중공업 주식회사 체결부 부식방지용 실링 장치
CN108578848A (zh) * 2015-05-16 2018-09-28 苏州汉方医药有限公司 由手动悬浮微颗粒发生器和板蓝根或板蓝根素组成的药盒
GB2553031B (en) 2017-06-27 2021-12-29 Kohler Mira Ltd Additive dispenser
DE102018121513B4 (de) 2018-09-04 2020-04-02 Prof. Reymond & Hetzel GbR (vertretungsberechtigter Gesellschafter: Alexander Hetzel, 78667 Villingendorf) Medizinisches Instrument zum gerichteten Einbringen einer Substanz in einen Hohlraum eines Körpers und Werkzeug dafür
US11666931B2 (en) 2019-05-14 2023-06-06 Kohler Co. Inline shower device

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR920943A (fr) * 1946-01-30 1947-04-22 éjecteur pour liquides
EP0160336A2 (de) 1984-04-27 1985-11-06 The Procter & Gamble Company Biegsamer Behälter mit einem selbstverschliessbaren Ventil zum automatischen Verschliessen und Dichthalten des umgekehrten Behälters
US4694977A (en) * 1983-10-28 1987-09-22 Ing. Erich Pfeiffer Gmbh & Co. Kg Fluid dispenser
EP0395380A2 (de) 1989-04-25 1990-10-31 Liquid Molding Systems, Inc. Ausgabepackung für Flüssigprodukte oder dergleichen
WO1992011049A1 (en) 1990-12-21 1992-07-09 Novo Nordisk A/S A pen shaped device for nasal administration of doses of a liquid medicine
EP0597601A1 (de) 1992-11-13 1994-05-18 National Semiconductor Corporation Speicherbusschnittstelle mit erwägter Breiteninstellung
US5511538A (en) * 1990-07-12 1996-04-30 Habley Medical Technology Corporation Super atomizing nonchlorinated fluorocarbon medication inhaler
EP0780127A1 (de) 1995-12-19 1997-06-25 The Procter & Gamble Company Nasenspray enthaltend einen Steroid und einen Antihistamin
WO1997046243A1 (en) 1996-06-04 1997-12-11 The Procter & Gamble Company A nasal spray containing an intranasal steroid and an antihistamine
WO1998012511A2 (en) * 1996-09-18 1998-03-26 The Boots Company Plc Fluid dispenser

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR920943A (fr) * 1946-01-30 1947-04-22 éjecteur pour liquides
US4694977A (en) * 1983-10-28 1987-09-22 Ing. Erich Pfeiffer Gmbh & Co. Kg Fluid dispenser
EP0160336A2 (de) 1984-04-27 1985-11-06 The Procter & Gamble Company Biegsamer Behälter mit einem selbstverschliessbaren Ventil zum automatischen Verschliessen und Dichthalten des umgekehrten Behälters
EP0395380A2 (de) 1989-04-25 1990-10-31 Liquid Molding Systems, Inc. Ausgabepackung für Flüssigprodukte oder dergleichen
US5511538A (en) * 1990-07-12 1996-04-30 Habley Medical Technology Corporation Super atomizing nonchlorinated fluorocarbon medication inhaler
WO1992011049A1 (en) 1990-12-21 1992-07-09 Novo Nordisk A/S A pen shaped device for nasal administration of doses of a liquid medicine
EP0597601A1 (de) 1992-11-13 1994-05-18 National Semiconductor Corporation Speicherbusschnittstelle mit erwägter Breiteninstellung
EP0780127A1 (de) 1995-12-19 1997-06-25 The Procter & Gamble Company Nasenspray enthaltend einen Steroid und einen Antihistamin
WO1997046243A1 (en) 1996-06-04 1997-12-11 The Procter & Gamble Company A nasal spray containing an intranasal steroid and an antihistamine
WO1998012511A2 (en) * 1996-09-18 1998-03-26 The Boots Company Plc Fluid dispenser

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2893090A1 (fr) * 2005-11-09 2007-05-11 Claude Jaunay Ensemble de pompage et de distribution de fluide
WO2007057543A1 (fr) * 2005-11-09 2007-05-24 Claude Jaunay Ensemble de pompage et de distribution de fluide
US8020732B2 (en) 2006-01-24 2011-09-20 Rexam Airspray N.V. Squeeze foamer
US8833365B2 (en) 2008-12-23 2014-09-16 Sanofi-Aventis Deutschland Gmbh Dosing device for generating a gas flow with a finely dispersed active substance
WO2011043712A1 (en) * 2009-10-08 2011-04-14 Shl Group Ab Metered liquid droplet inhaler
CN102639176A (zh) * 2009-10-08 2012-08-15 Shl集团有限责任公司 配量液体微滴吸入器
AU2010303985B2 (en) * 2009-10-08 2012-09-13 Shl Group Ab Metered liquid droplet inhaler
CN102639176B (zh) * 2009-10-08 2014-07-02 Shl集团有限责任公司 配量液体微滴吸入器
US9750900B2 (en) 2009-10-08 2017-09-05 Shl Group Ab Metered liquid droplet inhaler

Also Published As

Publication number Publication date
HUP0105057A2 (hu) 2002-04-29
CZ20012506A3 (cs) 2002-03-13
HUP0105057A3 (en) 2002-06-28
DE60004780D1 (de) 2003-10-02
DE60004780T2 (de) 2004-06-17
PL349767A1 (en) 2002-09-09
CO5231171A1 (es) 2002-12-27
EG22672A (en) 2003-06-30
EP1140368A1 (de) 2001-10-10
MA25341A1 (fr) 2001-12-31
CN1347346A (zh) 2002-05-01
ZA200105289B (en) 2002-03-06
NO20013508D0 (no) 2001-07-13
CA2360411A1 (en) 2000-07-20
RU2198740C1 (ru) 2003-02-20
AU2504600A (en) 2000-08-01
NO20013508L (no) 2001-07-13
ATE248030T1 (de) 2003-09-15
SK10062001A3 (sk) 2002-03-05
WO2000041816A1 (en) 2000-07-20
EP1140368B1 (de) 2003-08-27
AU748289B2 (en) 2002-05-30
PE20001192A1 (es) 2000-12-04
JP2002534331A (ja) 2002-10-15
NZ512600A (en) 2002-12-20
KR20020004944A (ko) 2002-01-16
BR0007526A (pt) 2001-11-27
IL144092A0 (en) 2002-05-23
JP4295437B2 (ja) 2009-07-15
RU2001122593A (ru) 2004-02-20

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