Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M15/00—Inhalators
  • A61M15/0065—Inhalators with dosage or measuring devices
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M15/00—Inhalators
  • A61M15/08—Inhaling devices inserted into the nose
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
  • A61M11/06—Sprayers or atomisers specially adapted for therapeutic purposes of the injector type
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M15/00—Inhalators
  • A61M15/0065—Inhalators with dosage or measuring devices
  • A61M15/0068—Indicating or counting the number of dispensed doses or of remaining doses
  • A61M15/007—Mechanical counters
  • A61M15/0071—Mechanical counters having a display or indicator
  • A61M15/0073—Mechanical counters having a display or indicator on a ring
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body

Definitions

• the present invention relates to a device for administering, in particular but not exclusively, opioid analgesics for the relief and treatment of pain.
• the invention is particularly concerned with administration in the form of a spray such as in the intranasal, buccal or sublingual administration of drugs, or more particularly the intranasal administration of opioid analgesics.
• Opioid analgesics are currently the most pharmacologically effective means of alleviating severe pain. Examples include morphine, diamorphine, codeine, hydromorphone, oxymorphone, oxycodone, meperidine, fentanyl, sufentanil, remifentanil and alfentanil.
• intranasal administration of opioid analgesics is especially advantageous since it provides the potential for very rapid treatment of acute pain since the drug molecule will rapidly pass from the nasal passages into the systemic circulation.
• opioid analgesics For many therapeutic applications it is necessary to administer opioid analgesics several times throughout a day.
• a device for administering a predefined number (N) of predefined volume unit doses (Vu) of an opioid analgesic solution including a closed container containing a predetermined fill volume (Vf) of the opioid analgesic solution and a dispenser connected to the container, the dispenser being operable to administer an individual one volume unit dose (Vu) repeatedly said predefined number of times (N), both the dispenser being adapted and the concentration of said opioid analgesic in said solution being chosen such that said volume unit dose is in the range 0.05 to 0.15ml.
• volume unit dose is 0.1ml.
• the concentration of the opioid analgesic in liquid form is in the range of 0.005 to 1000 mg/ml.
• the opioid analgesic is a solution of fentanyl, the concentration of the fentanyl in the solution being in the range 0.1 to 20 mg/ml.
• the opioid drug solution is a solution of fentanyl citrate, the concentration of fentanyl citrate in the solution being in the range of about 0.16 to 31.4 mg/ml.
• the choice of the opioid solution as defined above which is dispensed in a volume unit dose in the range 0.05 to 0.15ml enables the device to be used to administer say one or maybe two volume unit doses at any one time to provide effective treatment.
• the dispenser includes counting means operable to count the number of one volume unit doses administered and further includes dispenser deactivating means which is operated by the counting means to prevent further administration of the drug by the dispenser when the counting means has counted said predefined number of times
• N This number (N) is chosen (bearing in mind the fill volume (Vf) of the solution contained in the container before any doses have been administered) in order to ensure that (N) full doses are administered, i.e. the deactivation means operates to prevent further discharge of solution from the device before the tail off phenomenon is reached.
• the predefined number (N) of volume unit doses is chosen to be in the range of 2 to 30, more preferably in the range 3-20, and most preferably the predefined number (N) is in the range 4 to 8.
• Figure 1 is a schematic side view of a device according to a first embodiment of the present invention
• Figures 2A and 2B are, respectively, schematic side views of devices according to the first and second embodiments shown in a tipped condition;
• Figures 3A, 3B, and 3C are, respectively, schematic side views of devices according to second, third and forth embodiments of the present invention.
• Figure 4 is a schematic side view of a device according to a fifth embodiment of the invention.
• a nasal dispensing device 10 which includes a closed container 12 and a dispenser 14.
• An analgesic solution 15 is contained within the container 12.
• the dispenser 14 is preferably a dispenser of the type disclosed in US patent 4565302 (the full disclosure being incorporated herein by reference).
• the dispenser 14 thereby includes a spray head 16 which is reciprocally mounted on a mounting body 18.
• the mounting body 18 is fixedly secured to the container 12 to prevent its removal; accordingly access to the solution 15 is not permitted unless it is dispensed via the dispenser 14.
• the body 18 may be attached to the container 12 by a crimp and snap fitting or a one-way screw fitting in which a ratchet on the body 18 engages with lugs on the container such that the body 18 can only be screwed in one direction only.
• An example of such a container can be purchased from Saint Gobain
• the dispenser 14 further includes a pump 20 mounted on the mounting body 18.
• the pump 20 has an inlet (not shown) communicating with a dip tube 22.
• the dip tube 22 depends from the pump 20 towards the bottom of the container 12 such that its terminal end 23 is located beneath the surface of the solution 15. Accordingly on operation of the pump 20, solution is drawn along the tube 22 into the inlet of the pump 20.
• the pump 20 further includes an outlet (not shown) which communicates with a spray nozzle 26 formed on the spray head 16. Accordingly on operation of the pump 20 solution is discharged through the spray nozzle 26 to form a spray 30.
• the pump 20 is preferably of the two stroke reciprocating type having a priming chamber in which a pump piston reciprocates; the reciprocal motion of the piston in one direction, i.e. a first stroke of the piston, causing solution contained in the priming chamber to be discharged through the spray nozzle 26 and reciprocal motion of the piston in the opposite direction, i.e. a second stroke of the piston, causing solution to be drawn from the container 12 and into the priming chamber in readiness for the next discharging first stroke.
• the volume of solution discharged through the nozzle 26 is determined by the volume of the priming chamber.
• This .volume is preferably chosen to be in the range 0.05ml to 0.15ml for the reasons previously mentioned and defines the volume unit dose (Vu) to be dispensed by the device 10.
• the volume unit dose (Vu) is 0.1 ml.
• the pump 20 is operably connected to the spray head 16 such that downward depression of the head 16 in the direction of arrows 'O' in Figure 1 causes the pump 20 to discharge the volume unit dose (Vu) of the solution in the form of spray 30.
• the dispenser 14 includes a counting means which is operated each time the pump 20 is operated to dispense a volume unit dose of solution 15.
• the counting means operates a visual display 34 which indicates to the operative (i.e. the patient or carer) the number of volume unit doses which have been administered from the device 10.
• the device 10 includes dispenser inactivation means which operates to prevent further discharge of the solution 15 after the predefined number (N) of volume unit doses have been dispensed.
• N the number of volume unit doses have been dispensed.
• the number (N) is preferably chosen to ensure that only full volume unit doses of solution are discharged from the device 10 in order to avoid the tail- off phenomenon. This number (N) needs to be chosen bearing in mind the fill volume (Vf) and also the residual volume (Vr) of the solution.
• Vf the minimum fill volume of the solution contained in container 12
• Vf ( Vu x N ) + P + Vr
• Vu is the volume unit dose
• N is the predefined number of volume unit doses to be administered by the device
• P is the volume of solution required to initially prime the pump and fill the dip tube
• Vr is the residual amount of solution remaining in the container 12 after N full volume unit doses have been dispensed from the container 12.
• Vr is chosen to be sufficiently great to maintain the terminal end 23 of the dip tube 22 submerged beneath the surface of the solution 15 after dispensing a volume unit dose for the Nth time.
• Vr should be kept to a minimum in order to avoid unnecessary waste and preferably the volume (Vr) is less than 1ml, more preferably less than 0.8ml and most preferably less than 0.6ml.
• the shape of the container 12 is adapted to reduce the volume (Vr) required to ensure that a full final Nth volume unit dose of solution is administered, particularly when bearing in mind that the container 12 is typically angled at about 30 degrees from the vertical when used.
• FIG. 3A, 3B, and 3C Various designs of container 12 according to the present invention are illustrated by way of example in Figures 3A, 3B, and 3C; these containers share the common aim of providing a container having a relatively large external volume to provide stability for the container 12 when placed upon a surface, e.g. table top, whilst providing a reduced internal volume for retaining the solution 15 and thereby reduce volume Vr.
• the reduced internal volume is achieved by increasing the thickness of the side walls 12a of the container 12.
• the side walls 12a are also thickened to define an internal volume which is of inverted conical shape. This provides an internal bottom for the container 12a which is only slightly wider than the width of the dip tube 22 and so requires a small volume of solution to submerge the terminal end 23 of the tube 22.
• the internal volume of the container 12 is defined by a narrow closed tube insert 12b.
• the internal diameter of the tube insert 12b is slightly greater than the external diameter of the dip tube 22 and so again requires only a small volume Vr to submerge the tip 23 of the dip tube 22.
• These preferred shapes of container 12 may be expressed in terms of the 'volume ratio ' of the internal volume to the external volume, i.e. if the container has an interna! volume of 6ml and external volume of 10ml, then the container would have a volume ration of 0.6.
• the internal volume of the container 12 is most conveniently measured by determining the weight of water required to fill the container to the brim and then, using the known density of water, calculating the volume.
• the external volume of the container may be determined by measuring the external dimensions of the container and calculating the volume from the measured dimensions, or by measuring the weight of water displaced when the container is fully immersed in water and then using the known density of water to calculate the volume.
• the volume ratio is in the range 0.15 to 0.9, more preferably 0.2 to 0.9, and most preferably 0.25 to 0.7.
• the container 12 may be made from glass, plastics or a combination of both, for example a glass bottle with a plastics insert.
• the preferred plastic is a cyclic olefin copolymer.
• the solution 15 contained within the container 12 is preferably an opioid solution which contains as an active component an opioid analgesic in a sufficient concentration to provide the desired therapeutic relief per volume unit dose (Vu).
• volume unit dose typically in the range of 1 to 50 mg whereas for a more potent analgesic such as sufentanil the amount present by weight in a volume unit dose (Vu) is 1 to 200 micrograms.
• An especially preferred opioid analgesic for use in the compositions of this invention is fentanyl.
• Fentanyl N-(1-phenethyl-4-piperidyl)propionanilide
• fentanyl is a potent opioid analgesic agent used in the treatment of severe acute and chronic pain.
• fentanyl we include its salts.
• Fentanyl is generally used in the form of the citrate salt.
• the preferred intranasal dose of fentanyl, expressed as base, for treating a single episode of acute pain is in the range 10 to 2000 micrograms, more preferably 15 to 1500 micrograms, and most preferably 20 to 1000 micrograms.
• the preferred amount of fentanyl by weight, expressed as base, present in a volume unit dose (Vu) is in the range of 5 to 2000 micrograms.
• Drug solution The solution is preferably predominantly aqueous and contains 0.1 to 20 mg/ml fentanyl, preferably in the form of the citrate salt, wherein 0.1 mg/ml and 20 mg/ml fentanyl are equivalent to approximately 0.16 mg/ml and 31.4 mg/ml fentanyl citrate, respectively.
• the drug solution may optionally contain additives well known to one skilled in the art, such as preservatives, agents to adjust tonicity and acids or bases to adjust pH. Viscosity-modifying or gel-forming polymers, such as pectin, chitosan, celluloses or poloxamers may also be included. Examples of fentanyl intranasal compositions suitable for use in this invention may be found in WO 04/062561 and WO 02/09707.
• volume unit dose (Vu) The volume of each dose spray delivered by actuation of the spray pump is preferably 0.05 ml or 0.1 ml.
• the container preferably has a volume ratio, as defined earlier, in the range 0.3 to 0.7.
• Number of volume unit doses (N): The number of dose sprays is preferably in the range 2 to 30, more preferably in the range 3 to 20, and most preferably in the range 3 to 16, for example 4 to 8.
• the dispensing device 12 described above and illustrated in the accompanying drawings is particularly adapted for intranasal administration of the solution 15. It is however appreciated that the device may be adapted by adopting a suitably shaped nozzle instead of spray nozzle 26 to administer opioid analgesics by other routes, such as the oral cavity for buccal or sublingual absorption.

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• Medical Preparation Storing Or Oral Administration Devices (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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• 2008
  • 2008-10-08 GB GB0818396A patent/GB2464282A/en not_active Withdrawn
• 2009
  • 2009-09-28 AU AU2009300898A patent/AU2009300898B2/en active Active
  • 2009-09-28 CA CA2738735A patent/CA2738735C/en not_active Expired - Fee Related
  • 2009-09-28 HR HRP20210968TT patent/HRP20210968T1/hr unknown
  • 2009-09-28 CN CN2009801403613A patent/CN102176942A/zh active Pending
  • 2009-09-28 NZ NZ591915A patent/NZ591915A/xx unknown
  • 2009-09-28 EP EP09740918.9A patent/EP2340072B1/en active Active
  • 2009-09-28 MX MX2011003516A patent/MX2011003516A/es active IP Right Grant
  • 2009-09-28 DK DK09740918.9T patent/DK2340072T3/da active
  • 2009-09-28 PT PT97409189T patent/PT2340072T/pt unknown
  • 2009-09-28 PL PL09740918T patent/PL2340072T3/pl unknown
  • 2009-09-28 LT LTEPPCT/GB2009/002288T patent/LT2340072T/lt unknown
  • 2009-09-28 JP JP2011530545A patent/JP5709755B2/ja active Active
  • 2009-09-28 HU HUE09740918A patent/HUE056261T2/hu unknown
  • 2009-09-28 US US13/122,332 patent/US20110257632A1/en not_active Abandoned
  • 2009-09-28 WO PCT/GB2009/002288 patent/WO2010040979A1/en not_active Ceased
  • 2009-09-28 SI SI200932130T patent/SI2340072T1/sl unknown
  • 2009-09-28 BR BRPI0920313A patent/BRPI0920313A2/pt not_active Application Discontinuation
  • 2009-09-28 KR KR1020117010470A patent/KR101632764B1/ko active Active
  • 2009-09-28 ES ES09740918T patent/ES2875015T3/es active Active
  • 2009-09-29 TW TW098132858A patent/TWI569822B/zh active
• 2011
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