WO2024047351A1 - Dispositif d'administration de médicament en poudre sèche - Google Patents

Dispositif d'administration de médicament en poudre sèche Download PDF

Info

Publication number
WO2024047351A1
WO2024047351A1 PCT/GB2023/052249 GB2023052249W WO2024047351A1 WO 2024047351 A1 WO2024047351 A1 WO 2024047351A1 GB 2023052249 W GB2023052249 W GB 2023052249W WO 2024047351 A1 WO2024047351 A1 WO 2024047351A1
Authority
WO
WIPO (PCT)
Prior art keywords
naso
pulmonary
adaptor
dry powder
delivery device
Prior art date
Application number
PCT/GB2023/052249
Other languages
English (en)
Inventor
Elliot GOODMAN
Louise RAWCLIFFE
Christopher Townsend
Original Assignee
Therakind Limited
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
Priority claimed from GBGB2212729.4A external-priority patent/GB202212729D0/en
Priority claimed from GBGB2311305.3A external-priority patent/GB202311305D0/en
Application filed by Therakind Limited filed Critical Therakind Limited
Publication of WO2024047351A1 publication Critical patent/WO2024047351A1/fr

Links

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
    • A61M15/08—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
    • A61M11/02—Sprayers or atomisers specially adapted for therapeutic purposes operated by air or other gas pressure applied to the liquid or other product to be sprayed or atomised
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • A61M15/0001—Details of inhalators; Constructional features thereof
    • A61M15/0013—Details of inhalators; Constructional features thereof with inhalation check valves
    • A61M15/0015—Details of inhalators; Constructional features thereof with inhalation check valves located upstream of the dispenser, i.e. not traversed by the product
    • 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
    • A61M15/0001—Details of inhalators; Constructional features thereof
    • A61M15/002—Details of inhalators; Constructional features thereof with air flow regulating means
    • 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
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
    • A61M15/0043—Non-destructive separation of the package, e.g. peeling
    • 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
    • A61M15/0086—Inhalation chambers
    • 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
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/06—Solids
    • A61M2202/064—Powder
    • 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
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/30—Vaccines
    • 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
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/07—General characteristics of the apparatus having air pumping means
    • A61M2205/071—General characteristics of the apparatus having air pumping means hand operated
    • A61M2205/073—Syringe, piston 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
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/07—General characteristics of the apparatus having air pumping means
    • A61M2205/071—General characteristics of the apparatus having air pumping means hand operated
    • A61M2205/075—Bulb 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
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/12—General characteristics of the apparatus with interchangeable cassettes forming partially or totally the fluid circuit
    • A61M2205/123—General characteristics of the apparatus with interchangeable cassettes forming partially or totally the fluid circuit with incorporated reservoirs
    • 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
    • A61M2209/00—Ancillary equipment
    • A61M2209/06—Packaging for specific medical equipment
    • 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
    • A61M2209/00—Ancillary equipment
    • A61M2209/08—Supports for equipment
    • A61M2209/084—Supporting bases, stands for equipment

Definitions

  • the present invention relates to novel dry powder medicament delivery device and uses thereof.
  • the invention relates to novel dry powder medicament delivery device which is suitable for use as, for example, a naso-pulmonary medicament delivery device for the delivery of medicaments, e.g. for the treatment of a respiratory disorder; especially for delivering a vaccine or a hormone, such as, glucagon, in dry powder form; or the treatment of pulmonary disorders, such as asthma, COPD, cystic fibrosis and lung cancers.
  • a naso-pulmonary medicament delivery device for the delivery of medicaments, e.g. for the treatment of a respiratory disorder; especially for delivering a vaccine or a hormone, such as, glucagon, in dry powder form; or the treatment of pulmonary disorders, such as asthma, COPD, cystic fibrosis and lung cancers.
  • the naso-pulmonary delivery device is especially suitable for the delivery of small doses and is therefore useful for use with infants, including neonates, or small animals.
  • the delivery device is therefore useful for use, inter alia, in animal models, e.g. in pre-clinical studies.
  • drug formulations have been developed in dry powder form, e.g. for delivery by inhalation, or by admixing in a solution for delivery by intravenous infusion.
  • dry powder formulations include existing compounds reformulated into dry powder form and newly developed compounds, used in the treatment of many conditions and diseases.
  • Oral (pulmonary) or nasal delivery of a medicament using a dry powder medicament delivery device is a particularly attractive method of drug administration as such devices can be relatively easy for an individual to use.
  • dry powder medicament delivery devices have more recently also be used to deliver drugs to the bloodstream via the lungs or nasal passages, thereby avoiding, for example, the need for injections; and for delivery direct to the brain via the olfactory region.
  • Nasal drug delivery is well known for the treatment of common ailments such as cold, cough, hay fever, rhinitis, etc.
  • a large number of problems are associated with oral, parenteral, rectal, injectable and other routes of drug administration. Therefore, there has been an increase in interest in intranasal delivery of various drugs for systemic use including peptides, proteins, vaccines and the like.
  • Nasal delivery offers many benefits over traditional approaches to vaccine administration. These include ease of administration without needles that reduces issues associated with needle injuries and disposal, reduces the need for advance training in administration and assists with self-administration. Furthermore, recently dry powder intranasal vaccines have been developed. There are a number of advantages to intranasal delivery of drugs, in particular in dry powder form. Intranasal drug delivery offers rapid uptake into the blood stream by absorption through the nasal mucus, the potential to reduce or eliminate cold chain management of vaccines during storage and transportation, and the elimination of needles and the potential for needle stick injuries.
  • Intranasal vaccination represents an attractive non-invasive alternative to needlebased injection and provides superior protection at mucosal surfaces.
  • new formulations and delivery devices are needed to improve efficacy and reduce the refrigerated storage and distribution requirements associated with standard liquid vaccines.
  • Vaccines and other pharmaceutically active agents, formulated as liquids can be subject to chemical degradation, e.g., aggregation, denaturation, hydrolysis, and oxidation that can result in their inactivation.
  • Liquid vaccine formulations can also be sensitive to temperature: high temperatures can increase inactivation, and freezing temperatures can result in ice that can damage antigen in the vaccine. Thus, to prevent inactivation, liquid vaccines often must be stored at a temperature range of from 2-8°C.
  • the mode of administration of a vaccine can play a role in its efficacy.
  • One mode of administration non-parental administration (e.g., nasal) can induce and promote mucosal and systemic immune responses.
  • nasal mucosa can help bind a virus or other pathogen at the mucosal surface, preventing access of the pathogen to deeper tissues and/or decreasing the likelihood of full-blown infection.
  • the volume of a mouse’s nasal cavity is only a quarter the size of that of a rat which itself presents several issues with delivery.
  • the force and volume of air exiting the device can be potentially lethal for murinae.
  • air pulses should not exceed of 2ml per pulse.
  • a dry powder insufflator device was made commercially available by Penn-Century Inc., the Penn-Century Dry Powder InsufflatorTM -DP-4. The main application for this insufflator device was for delivery to the lungs, but it was also advertised as being suitable for intranasal delivery. However, the Penn-Century device was withdrawn from sale and has not been available for several years.
  • a PADA (Powder Administration Device for Animals) starter kit is available from Aptar Pharma. The kit is designed to enable intra-tracheal administration of a powder directly to the lungs of mice.
  • the present invention seeks to provide a dry powder medicament delivery device that overcomes or substantially alleviates the problems with conventional inhalation devices.
  • a holding chamber is capable of reducing the force and volume of air exiting a nasal inhalation device.
  • a dry powder medicament naso-pulmonary delivery device comprising: a medicament container, e.g. a cartridge, containing a unit dose of dry powder medicament; a main body, optionally provided with an air source; and a medicament dispensing assembly, said medicament dispensing assembly comprising: a dispensing nozzle; a holding chamber; and a naso-pulmonary adaptor.
  • the dispensing nozzle will generally comprise an airway, e.g. with an inlet end and an outlet end.
  • the inlet end of the dispensing nozzle is adapted to be attached to the main body of the naso-pulmonary delivery device.
  • the outlet end of the dispensing nozzle is adapted to be attached to the holding chamber.
  • the naso- pulmonary adaptor may be provided with an integral holding chamber, in which case the outlet end of the dispensing nozzle may be adapted to be attached to the naso- pulmonary adaptor.
  • a naso-pulmonary adaptor provided with an integral holding chamber is a preferred embodiment of the present invention.
  • the naso-pulmonary adaptor is a nasal adaptor.
  • the naso-pulmonary adaptor is a pulmonary adaptor.
  • the holding chamber is provided at one end with an inlet to receive a dispensed dry powder and an outlet to transmit the dry powder into the naso-pulmonary adaptor.
  • the inlet end of the holding chamber is adapted to be attached to the outlet end of the dispensing nozzle and the outlet end of the holding chamber is adapted to be attached to the inlet end of the naso-pulmonary adaptor.
  • the holding chamber is integral to the naso- pulmonary adaptor.
  • the naso-pulmonary adaptor is provided at one end with an inlet to receive a dispensed dry powder and an outlet to transmit the dry powder into the nasal cavity or the lungs of an individual upon administration.
  • the inlet end of the naso-pulmonary adaptor is adapted to be attached to the outlet end of the holding chamber.
  • the holding chamber is integral to the naso-pulmonary adaptor in which case the naso-pulmonary adaptor is adapted to be attached to the outlet end of the dispensing nozzle. It is preferred for the holding chamber to be integral to the naso-pulmonary adaptor.
  • the medicament container comprises a cartridge provided with a well cavity adapted to holding a medicament, usually in the form of a dry powder.
  • the cartridge may be provided with a protective sleeve, said sleeve being adapted to be retracted. In a first position the protective sleeve covers and protects the dry powder medicament, but when the protective sleeve is retracted it renders the cartridge in an open position and exposes the well cavity and the dry powder medicament therein.
  • the cartridge is provided with an abutment, e.g. an integral abutment or a pair of integral abutments.
  • an abutment e.g. an integral abutment or a pair of integral abutments.
  • a pair of abutments aids in providing a seal around the cartridge.
  • a dry powder medicament naso-pulmonary delivery device comprising: a medicament container, e.g. a cartridge, containing a unit dose of dry powder medicament; a main body, optionally provided with an air source; and a medicament dispensing assembly, said medicament dispensing assembly comprising: a dispensing nozzle; and a naso-pulmonary adaptor, wherein said naso-pulmonary adaptor includes an integral holding chamber.
  • the naso-pulmonary adaptor is a nasal adaptor.
  • the naso-pulmonary adaptor is a pulmonary adaptor.
  • a pulmonary adaptor may optionally be provided with a cannula to facilitate delivery of a dry powder medicament to the lungs of an individual.
  • the outlet of the naso-pulmonary adaptor will generally comprise a conduit with an orifice at an outlet end.
  • the shape and dimensions of the outlet orifice may vary depending upon, inter alia, the nature of the individual being treated and dry powder being delivered.
  • the outlet orifice is desirably sized and shaped to be suitable for placing inside the nostril of an individual (infant, murinae or other small animals, such as, rabbits, guinea pigs and the like).
  • the outlet orifice may have an external diameter of from about 0.5mm to about 2mm.
  • the outlet orifice external diameter may be about 1.6mm or with mice the external diameter may be about 0.5mm.
  • the outlet will be about the size of a hypodermic needle, e.g. a Gauge (Birmingham Gauge) 10 to 25 hypodermic needle, for example, for use with rats the outlet orifice external diameter may be about 16 gauge or with mice about a 25 gauge. It will be understood by a person skilled in the art that for use with infants, including neonates, the outlet orifice may have a generally larger external diameter or be of a larger gauge.
  • an air flow restrictor may optionally be included, dependent upon the, inter alia, the exit orifice diameter of the naso- pulmonary adaptor attached to the device.
  • Such an air flow restrictor when present, may be incorporated in the naso-pulmonary delivery device of the invention between the air source, e.g. a syringe, and the main body of the naso-pulmonary adaptor.
  • an air flow restrictor may be advantageous in that, inter alia, it improves performance of the naso-pulmonary delivery device, for example, by adjusting the ratio of the outlet nozzle of the tip to the diameter of the restrictor hole the pickup of powder from the medicament container can be significantly improved.
  • the medicament dispensing assembly may be provided with a valve situated between the air source and the medicament dispensing assembly, such that, if the valve is in the closed position upon actuation of the air source, a pocket of pressurised air will be created; and opening of the valve will provide a burst of pressurised air to medicament dispensing assembly.
  • a valve is a stopcock, e.g. a two-way manual stopcock, which is adapted to be manually switched from a closed to an open position.
  • valve may be utilised instead of an air flow restrictor, it is within the scope of the present invention for the medicament dispensing assembly to be provided with an air flow restrictor and a valve.
  • a valve e.g. a stopcock, may be advantageous, since it assists in clearing the dry powder medicament from the dispensing assembly. It has been found that, with the use of a valve, about 25% w/w more of the dry powder medicament is cleared from the dispensing assembly and delivered to the nasal cavity or lungs of an individual.
  • the dry powder medicament delivery device may be mounted on a moveable plate.
  • the moveable plate may desirably be provided with a releasable locking mechanism.
  • a locking mechanism comprises a retractable plate provided with a tongue adapted to fit a groove in the moveable plate on which the syringe sits. The moveable plate may be locked with the tongue sitting in the groove. By retracting the plate the tongue can be withdrawn from the groove, allowing the moveable plate to freely move and allowing the syringe plunger to prime the delivery device with air.
  • the medicament container may optionally be clamped to the main body of the device. Any conventionally known clamping mechanism may be used, but in one aspect of the invention the clamp may comprise a thumb screw clamp.
  • the size of the dose delivered may be varied, for example, by altering the size of the medicament container.
  • the holding chamber may comprise a conical, frusto conical or tapered chamber.
  • the holding chamber may be provided with an inner conduit, e.g. a longitudinal conduit, which is an airway with a first end adjacent the connection with the dispensing nozzle and a second end which protrudes into the holding chamber.
  • the inner conduit may have an external diameter of from about 0.1mm to about 2.0mm. The use of the holding chamber and the inner conduit is advantageous in that, inter alia, the force of the air flow is reduced.
  • the naso-pulmonary adaptor comprises a frusto conical or tapered holding chamber.
  • a frusto conical or tapered holding chamber is generally better for delivery of the medicament.
  • the use of a frusto conical or tapered holding chamber provides additional distance to reduce the pressure build up within the holding chamber.
  • the naso-pulmonary adaptor may be in the form of a pipette tip.
  • the naso-pulmonary adaptor may comprise a bifurcated adaptor.
  • a bifurcated adaptor may suitably be adapted to fit the nozzle; alternatively a bifurcated adaptor may be adapted to fit on the end of the naso- pulmonary adaptor herein described.
  • Use of a bifurcated adaptor is especially advantageous in nasal delivery of a dry powder medicament, since it enables the dry powder medicament to be delivered simultaneously to each nostril of an individual. Luer Lock
  • Means for attaching the naso-pulmonary adaptor and/or the holding chamber to the dispensing nozzle may comprise a snap-fit, screw fit, bayonet fit, Luer-lock or Luer- taper and the like.
  • the releasable attachment comprises a Luer-lock or Luer-taper connection, that is, the means for attaching the naso-pulmonary adaptor and/or the holding chamber to the dispensing nozzle may comprise a tabbed female hub on the dispensing nozzle and a slotted or threaded male hub on the naso-pulmonary adaptor or the holding chamber.
  • the dry powder medicament delivery device includes an air source.
  • the medicament dispensing assembly of the invention generally comprises a body and a nozzle. More particularly, the medicament dispensing assembly comprises a body, a nozzle and an airway, e.g. one or two airways, an inlet and an outlet.
  • the nozzle may desirably be sized and shaped to be suitable for placing inside the nostril of an individual.
  • the medicament dispensing assembly is provided with a naso-pulmonary adaptor, such that the adaptor is placed inside the nostril of an individual. This is especially the case when the medicament dispensing assembly is for use in administering a medicament to an infant or murinae.
  • the medicament dispensing assembly may also be designed so as to be suitable for oral delivery, such as an insufflator for delivery to the lungs (respiratory tract).
  • the air source may comprise a delivery pump e.g. it may comprise a syringe.
  • a syringe may, for example, comprise a conventionally known propriety syringe, e.g.
  • a disposable syringe or may comprise a conventionally known means for ejecting an air stream, for example, an insufflator or other such apparatus suitable for blowing air or gas upon activation, such as a cylinder and piston, bellows, a squeezable bulb or a compressed air or gas source such as a compressed air canister or from a compressed air system fitted with suitable volume and pressure control apparatus.
  • an insufflator or other such apparatus suitable for blowing air or gas upon activation such as a cylinder and piston, bellows, a squeezable bulb or a compressed air or gas source such as a compressed air canister or from a compressed air system fitted with suitable volume and pressure control apparatus.
  • a method of producing an aerosol of a dry powder for naso-pulmonary administration comprising positioning a dispersible dry powder material, e.g. a medicament material, downstream of a naso- pulmonary adaptor; wherein said naso-pulmonary adaptor includes an optionally integral holding chamber; and wherein said naso-pulmonary adaptor is attached to a dispensing nozzle of a dry powder medicament naso-pulmonary delivery device as herein described.
  • the method according to this aspect of the invention is especially useful for the delivery of a dry powder medicament material to infants, including neonates, and/or murinae.
  • the dry powder medicament delivery device may be suitable for delivery of a variety of medicaments and may be suitable for use in the treatment of a variety of disorders.
  • medicaments for use as an insufflator, e.g. an insufflator for oral drug delivery, or a naso-pulmonary dry powder medicament delivery device, e.g. a naso-pulmonary insufflator, a variety of medicaments may be administered.
  • Such medicaments are generally suitable for the treatment of asthma, COPD and respiratory infections.
  • Such medicaments include, but are not limited to [beta] 2-agonists, e.g.
  • fenoterol formoterol, pirbuterol, reproterol, rimiterol, salbutamol, salmeterol and terbutaline; non-selective beta-stimulants such as isoprenaline; xanthine bronchodilators, e.g. theophylline, aminophylline and choline theophyllinate; anticholinergics, e.g. ipratropium bromide; mast cell stabilisers, e.g. sodium cromoglycate and ketotifen; bronchial anti-inflammatory agents, e.g. nedocromil sodium; and steroids, e.g. beclomethasone dipropionate, fluticasone, budesonide, flunisolide and ciclesonide, and isomers and/or salts or derivatives thereof.
  • non-selective beta-stimulants such as isoprenaline
  • xanthine bronchodilators
  • Specific combinations of medicaments which may be mentioned include combinations of steroids, such as, beclomethasone dipropionate and formoterol; beclomethasone dipropionate and salmeterol; fluticasone and formoterol; fluticasone and salmeterol; budesonide and formoterol; budesonide and salmeterol; flunisolide and formoterol; and flunisolide and salmeterol. It is also within the scope of this invention to include combinations of one or more of the aforementioned steroids with one or more of the aforementioned P2-agonists.
  • steroids such as, beclomethasone dipropionate and formoterol; beclomethasone dipropionate and salmeterol; fluticasone and formoterol; fluticasone and salmeterol; budesonide and formoterol; budesonide and salmeterol; flunisolide and formoterol; and flunisolide and salmeterol.
  • steroids such as
  • medicaments include systemically active materials, such as, proteinaceous compounds and/or macromolecules, for example, hormones and mediators, such as insulin, glucagon, human growth hormone, leuprolide and alpha interferon, growth factors, anticoagulants, immunomodulators, cytokines and nucleic acids.
  • systemically active materials such as, proteinaceous compounds and/or macromolecules, for example, hormones and mediators, such as insulin, glucagon, human growth hormone, leuprolide and alpha interferon, growth factors, anticoagulants, immunomodulators, cytokines and nucleic acids.
  • medicaments which may be mentioned are those for the treatment of neurological disorders, such as Parkinsonism, such as, levodopa, carbidopa, benserazide, selegiline, tolcapone, entacapone, bromocriptine, lysuride, pergolide, ropinirole and cabergoline; or migraine, such as divalroex sodium, ergotamine, methysergide, metoprolol, propranolol, zolmitriptan, vigabatrine, clonidine, ganaxolone, lysine acetylsalicylate, sumatriptan, naratriptan, timolol, almotriptan, cyproheptadine, rizatriptan, timotol, dotarizine, dihydroergotamine, metysergide, pizotifen, eletriptan, prochlorperazine,
  • medicaments for the treatment of sexual dysfunction may be mentioned.
  • disorders include erectile dysfunction where treatments include administration of phosphodiesterase type-5 (PDTE5) inhibitors, such as tadalafil, vardenafil and sildenafil; and premature ejaculation, where treatments include administration of selective serotonin reuptake inhibitors, such as dapoxetine.
  • PDTE5 phosphodiesterase type-5
  • compositions suitable for controlled or targeted release of the medicament may comprise compositions suitable for controlled or targeted release of the medicament.
  • the compositions are may be designed to be provide slow, delayed or positioned release of the medicament. Delayed release may be achieved by a coating that is simply slow to disintegrate.
  • Suitable compositions for delayed or positioned release include film coated formulations wherein the coating may be water resistant, pH sensitive or sloughed off at a slow but regular rate when moistened.
  • Suitable coating materials include, but are not limited to, hydroxypropyl methylcellulose, ethyl cellulose, cellulose acetate phthalate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose phthalate, polymers of methacrylic acid and its esters, and combinations thereof.
  • Suitable excipients may include, but shall not be limited to, excipients obtained by interesterification of hydrogenated palm oil and palm kernel oil (Cg-Cis triglycerides), esterification of glycerol and specific fatty acids, or polyglycosylated glycerides; stabilizing agents, thickeners and emulsifiers like carboxymethylcellulose and salts thereof, polyacrylic acid and salts thereof, carboxyvinyl polymers and salts thereof, alginic acid and salts thereof, propylene glycol alginate, chitosan, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxy ethylcellulose, ethylcellulose, methylcellulose, polyvinyl alcohol, polyvinyl pyrrolidone, N- vinylacetamide polymer, polyvinyl methacrylate, polyethylene glycol, pluronic, gelatin, methyl vinyl ether-maleic anhydride copolymer, soluble starch, pullulan and a
  • one particular aspect of the present invention provides the dry powder medicament delivery device as herein described as a naso-pulmonary dry powder medicament delivery device.
  • a naso-pulmonary dry powder medicament delivery device according to this aspect of the invention may be suitable for the delivery of any of the medicaments herein described.
  • the intranasal or intravenous route of drug delivery can afford rapid absorption of drugs into the blood circulation.
  • the intranasal route can also offer a less invasive route of drug administration compared with some other routes such intravenous or intramuscular injection.
  • Such rapid and effective drug delivery can be useful in the treatment of crisis situations such as pain, convulsions, serious hypoglycaemic reaction, etc.
  • the delivery device of the present invention is found to be especially advantageous in the delivery of a medicament in an emergency situation, for example, where the patient is unconscious.
  • the naso-pulmonary delivery device of the invention is especially useful in a situation where medical staff are not available.
  • One specific such therapy is the intranasal administration of a therapeutically effective amount of glucagon to a diabetic who is experiencing a serious hypoglycaemic reaction.
  • Glucagon is a hormone that causes the liver to release glucose into the blood and is used to quickly increase blood sugar levels in diabetics with hypoglycaemia (low blood sugar).
  • Glucagon is usually provided in powder form and given as an injection either into a vein, an arm or leg muscle or under the skin as directed, usually to an unconscious patient.
  • the glucagon powder must first be dissolved in a diluting fluid and must be used immediately after it has been mixed.
  • a method of delivering glucagon to an individual which comprises the use of a medicament delivery device as herein described, especially the use of a dry powder naso-pulmonary dry powder medicament delivery device.
  • the delivery device of the present invention as an intranasal drug delivery device may be beneficial.
  • the medicament delivery device as herein described may suitably be used for the delivery of one or more dry powder vaccines.
  • Dry powder vaccine compositions for intranasal delivery are described in International Patent application No. WO 2011/129120. Therefore, a dry powder vaccine for use in association with a medicament delivery device, such as a naso- pulmonary dry powder medicament delivery device, of the present invention, can be useful for the prevention and/or treatment of infection by any virus.
  • the dry powder medicament delivery device comprises a device described in International Patent application No. WO 2011/129120; provided with a naso-pulmonary adaptor with an integral holding chamber.
  • the invention further provides a method of delivering a medicament, e.g. a dry powder medicament, to an individual, such as an infant or murina, said method comprises the use of a dry powder medicament delivery device as herein described.
  • a medicament e.g. a dry powder medicament
  • the invention further provides a method of treatment of an individual with a disorder which comprises the administration of a medicament using a medicament delivery device as herein described.
  • the method of treatment according to this aspect of the invention may comprise the administration of any one or more of the therapeutically active agents described herein.
  • an emergency therapy such as, glucagon, or a vaccine, e.g. a dry powder vaccine to an individual.
  • the invention provides a method of treating an individual which comprises the administration of a therapeutically effective amount of glucagon to a diabetic experiencing a hypoglycaemic reaction or in which a hypoglycaemic reaction has been induced using the dry powder medicament naso-pulmonary delivery device herein described.
  • a method of delivering a therapy for the treatment of pulmonary disorders such as asthma, COPD, cystic fibrosis and lung cancers.
  • a naso-pulmonary adaptor provided with an integral holding chamber is novel per se. Therefore, according to a further aspect of the present invention there is provided a naso-pulmonary adaptor for use with a dry powder medicament delivery device wherein the naso-pulmonary adaptor is provided with an integral holding chamber. More specifically, there is provided a naso-pulmonary adaptor provided with an integral holding chamber for use in conjunction with a dry powder medicament naso- pulmonary delivery device; especially for use in conjunction with a dry powder medicament naso-pulmonary delivery device herein described.
  • the assembly and/or the naso-pulmonary adaptor may comprise a variety of suitable materials and may be made by a variety of methods, and the member and sleeve may optionally comprise the same material e.g. a plastics material.
  • the assembly comprises a suitable first plastics material and the naso- pulmonary adaptor comprises an alternative second plastics material.
  • the preferred device i.e. comprising first and second plastics materials may be manufactured by a variety of methods, including, preferably a method known as two shot moulding.
  • the two shot moulding method is a process of moulding that allows the combined components, i.e. the member (first plastics material) and sleeve (second plastics material) to be produced in a single machine cycle with no subsequent assembly. Such a method produces clear savings on economy.
  • the dry powder medicament naso-pulmonary delivery device as herein described is advantageous in that, inter alia, it permits the naso-pulmonary delivery of low dosages of a dry powder, which is especially suitable for use with infants, including neonates, and small animals, such as murinae. Furthermore, the dry powder medicament naso-pulmonary delivery device may be reusable by changing the dispensing nozzle and inserting a new pre- filled medicament container.
  • a dry powder medicament naso-pulmonary delivery device kit comprising: a dry powder medicament naso-pulmonary delivery device as herein described, which includes a dispensing nozzle; a holding chamber; a naso-pulmonary adaptor; optionally, at least one unit dose of a dry powder medicament.
  • the kit includes a naso-pulmonary adaptor which includes an integral holding chamber.
  • the kit includes an air source.
  • the air source of the kit as herein described may comprise a delivery pump, such as a syringe or a bellows, etc.
  • the kit may be suitable for the administration of any one or more of the therapeutically active agents described herein.
  • an emergency therapy such as, glucagon, or a vaccine, e.g. a dry powder vaccine to an individual.
  • Figure 1 is a side view of a medicament delivery device of the invention comprising a medicament dispensing assembly and a naso-pulmonary adaptor;
  • Figures 2(a) and 2(b) are side views of a medicament container, e.g. a cartridge, containing a unit dose of dry powder medicament with a protective sleeve retracted (Fig 2(a)) and in situ (Fig 2(b));
  • Figure 3 is a side view of a medicament delivery device of the invention with a medicament container being placed in position;
  • Figure 4 is a side view of a medicament delivery device of the invention, provided with a naso-pulmonary adaptor, the medicament delivery device is being actuated;
  • Figure 5 is a cross-sectional view of a naso-pulmonary adaptor
  • Figure 6 is a cross-sectional view of an alternative tapered naso-pulmonary adaptor
  • Figures 7(a) and (b) are perspective views of an air flow restrictor
  • Figure 8 is a disassembled view of a medicament delivery device of the invention with an air flow restrictor included;
  • FIG. 9(a) and (b) illustrate alternative medicament containers
  • Figure 10 illustrates a bifurcated adaptor
  • Figures 11(a) and (b) illustrate a dry powder medicament delivery device with the syringe extended (a) and the syringe depressed (b);
  • Figure 12 illustrates a dry powder medicament delivery device mounted on a base
  • Figures 13(a) and (b) illustrate a dry powder medicament delivery device being primed
  • Figures 14(a) and (b) illustrates a locking assembly.
  • a dry powder medicament delivery device 1 comprises a medicament dispensing assembly 2 and a syringe 3, provided with plunger 4.
  • the syringe 3 and plunger 4 act as an air source.
  • the dispensing assembly 2 comprises a body 5, a dispensing nozzle 6, and an airway (not shown) provided with an inlet end 7 and an outlet end 8.
  • the dispensing assembly 2 is provided with means 9 for housing and engaging with a medicament container (not shown).
  • a naso-pulmonary adaptor 10 is adapted to be located at the outlet end 8 of the dispensing nozzle 6.
  • the naso-pulmonary adaptor 10 comprises an inlet end 11 and an outlet end 12.
  • the inlet end 11 is adapted to be located on the outlet end 8 of the dispensing nozzle 6.
  • the inlet end 11 is provided with a Luer-lock fixing 13 to cooperate with the outlet end 8 of the dispensing nozzle 6.
  • the outlet end 12 of the naso-pulmonary adaptor 10 is provided with a conduit 14 about the size of a hypodermic needle.
  • a medicament container 15 comprises a cartridge 16 provided with a well cavity 17 for holding a medicament 18, usually in the form of a powder and a protective sleeve 19.
  • the protective sleeve 19 is retracted, rendering the cartridge 16 in an open position and the well cavity 17 is exposed.
  • the protective sleeve 19 is in a closed position, and the well cavity 17 is covered and protected.
  • the medicament dispensing assembly 2 comprises a body 5, a dispensing nozzle 6, and an airway (not shown) provided with an inlet end 7 and an outlet end 8.
  • the dispensing assembly 2 is provided with a housing 9 adapted to engage with a medicament container 15.
  • the protective sleeve 19 of the medicament container 15 is in the closed position.
  • the air source comprises bellows 16 attached to the inlet end 7 dispensing assembly 2.
  • a naso-pulmonary adaptor 10 is located at the outlet end 8 dispensing assembly 2.
  • the medicament container 15 is located in the housing 9 of the dispensing assembly 2. As the medicament container 15 is pushed into the housing 9, the protective sleeve 19 of the medicament container 15 is retracted (not shown) exposing the well cavity (not shown) and the medicament.
  • a user depresses the bellows 16 forcing air through the medicament dispensing assembly 2 and entraining the dry powder medicament (not shown) in the airway (not shown).
  • the entrained dry powder medicament 17 is dispensed from the conduit 14 at the outlet end 12 of the naso-pulmonary adaptor 10.
  • a naso-pulmonary adaptor 10 suitable for use with a mouse model is shown.
  • the naso-pulmonary adaptor 10 comprises a body 18, the body comprises a frusto conical or tapered holding chamber 19 with an inlet end 20 and an outlet end 21.
  • the inlet end 20 of the naso-pulmonary adaptor body 18 is provided with a conduit 22 which extends from the inlet end 20 and protrudes into the holding chamber 19.
  • An external portion of the inlet end 20 is provided a Luer-lock fitment enabling the naso-pulmonary adaptor 10 to be securely located onto the outlet end 8 of the dispensing assembly 2.
  • the outlet end 21 of the holding chamber 19 is provided with a conduit 14 through which the dry powder medicament (not shown) is dispensed.
  • naso-pulmonary adaptor 22 suitable for use with a rat model is shown.
  • the naso-pulmonary adaptor 22 comprises a body 23, the body comprises a frusto conical or tapered holding chamber 24 with an inlet end 25 and an outlet end 26.
  • the inlet end 25 of the naso-pulmonary adaptor body 23 is provided with a conduit 27 which extends from the inlet end 25 and protrudes into the holding chamber 24.
  • An external portion of the inlet end 25 is provided a Luer-lock fitment enabling the naso-pulmonary adaptor 22 to be securely located onto the outlet end 8 of the dispensing assembly 2.
  • the inlet end 25 of the naso-pulmonary adaptor body 23 is also provided with external support ribs 28.
  • the outlet end 26 of the holding chamber 24 is provided with a conduit 29 through which the dry powder medicament (not shown) is dispensed.
  • an air flow restrictor 30 comprises a body 31 provided with a longitudinal conduit 32.
  • the body 31 comprises a first end 33 and a second end 34.
  • the first end 33 is provided with means 35 for connecting, e.g. a snap-fit, with a medicament dispensing assembly body (not shown).
  • the second end 34 comprises means 36 for connecting, e.g. a screw thread, with a dispensing nozzle (not shown).
  • the longitudinal conduit 32 is generally of narrower diameter than the connecting orifice at the end of the medicament dispensing assembly body (not shown).
  • a dry powder medicament delivery device 37 comprises a medicament dispensing assembly 38 and a syringe 39, provided with plunger 40.
  • the syringe 39 and plunger 40 act as an air source.
  • the dispensing assembly 38 comprises a body 41, an air flow restrictor 42, a dispensing nozzle 43, and an airway (not shown) provided with an inlet end 44 and an outlet end 45.
  • a medicament container 15 comprises a cartridge 16 provided with a well cavity 17 (reference Figure 2(a)).
  • a medicament container 15 comprises a cartridge 16 wherein the cartridge 15 is provided with a pair of integral abutments 46 and 47 e.g. in the form of “wings” around the cartridge 16. The abutments 46 and 47 create a stop 48 and 49 respectively when the delivery device (not shown) is actuated.
  • the medicament container 15 is provided with a protective sleeve 19.
  • a bifurcated adaptor 50 comprises a connector 51 adapted to connect the bifurcated adaptor 50 to the outlet end of a dispensing nozzle 6 (not shown), the connector 51 sits adjacent a bifurcation chamber 52 and a pair of outlet conduits 53 and 54 extend from the bifurcation chamber 51.
  • a dry powder medicament delivery device 1 comprises a medicament dispensing assembly 2 and a syringe 3, provided with plunger 4.
  • the syringe 3 and plunger 4 act as an air source.
  • the syringe 3 is provided with a syringe stop (55).
  • the dispensing assembly 2 comprises a body 5, a dispensing nozzle 6, and an airway (not shown) provided with an inlet end 7 and an outlet end 8.
  • the dispensing assembly 2 is provided with means 9 for housing and engaging with a medicament container 15, said medicament container 15 being provided with abutments 46 and 47.
  • a stopcock 54 is provided between the syringe 3 and the dispensing assembly 2.
  • a dry powder medicament delivery device 1 is mounted on a base 55, said base 55 being provided with a plunger holder 56 and a locking plate 57.
  • a locking plate 57 comprises a retractable plate 58 provided with a tongue 59 adapted to fit a groove 60 in a moveable plate 61 on which the syringe 3 sits.
  • the moveable plate 61 is locked with the tongue 59 sitting in the groove 60.
  • the retractable plate 58 is retracted and the tongue 59 withdrawn from the groove 60, allowing the moveable plate 61 to freely move and allowing the syringe plunger 4 to prime the delivery device 1 with air.
  • the clearance of the body and dispensing nozzle of the delivery device was measured using the following methodology: 1.
  • the dispensing nozzle (a lOpL pipette tip, as shown in Figure 6) was cleaned with compressed air and weighed on a tared scale; the result was recorded.
  • the main body of the device was cleaned with compressed air and weighed on a tared scale; the result was recorded.
  • the drug (medicament) cartridge and protective sleeve were separated and cleaned with compressed air.
  • the protective sleeve was placed over the open end of the cartridge and weighed on a tared scale; the result was recorded.
  • the drug used was a spray dried placebo formulation.
  • the drug cartridge was filled with a powdered medicament and tapped three (3) times to level.
  • the protective sleeve was moved into position to cover the well cavity and covered cartridge was cleaned with compressed air to remove any excess powder.
  • the filled and covered cartridge was placed on a tared scale; the result was recorded.
  • the delivery device was assembled, primed and fired.
  • the dispensing nozzle was removed and weighed on a tared scale; the result was recorded.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Pulmonology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Otolaryngology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un dispositif d'administration de médicament en poudre sèche par voie nasopulmonaire, comprenant : un récipient pour médicament, par exemple une cartouche, contenant une dose unitaire de médicament en poudre sèche ; un corps principal, éventuellement pourvu d'une source d'air ; et un ensemble de distribution de médicament, ledit ensemble de distribution de médicament comprenant : une buse de distribution ; une chambre de maintien ; et un adaptateur nasopulmonaire.
PCT/GB2023/052249 2022-09-01 2023-08-31 Dispositif d'administration de médicament en poudre sèche WO2024047351A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB2212729.4 2022-09-01
GBGB2212729.4A GB202212729D0 (en) 2022-09-01 2022-09-01 Nasal delivery device
GB2311305.3 2023-07-24
GBGB2311305.3A GB202311305D0 (en) 2023-07-24 2023-07-24 Dry powder medicament delivery device

Publications (1)

Publication Number Publication Date
WO2024047351A1 true WO2024047351A1 (fr) 2024-03-07

Family

ID=88241284

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2023/052249 WO2024047351A1 (fr) 2022-09-01 2023-08-31 Dispositif d'administration de médicament en poudre sèche

Country Status (1)

Country Link
WO (1) WO2024047351A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011129120A1 (fr) 2010-04-15 2011-10-20 Shin Nippon Biomedical Laboratories, Ltd. Procédés et compositions pour administration intranasale
WO2013088112A2 (fr) 2011-12-16 2013-06-20 Indosys Limited Cartouche de dose unitaire de médicament et dispositif d'administration
WO2021150878A1 (fr) * 2020-01-22 2021-07-29 Virginia Commonwealth University Inhalateurs de poudre sèche et interfaces pour une administration d'aérosol améliorée à des enfants
WO2021150883A1 (fr) * 2020-01-22 2021-07-29 Virginia Commonwealth University Inhalateur à poudre sèche à jet d'air pour administration rapide d'aérosols pharmaceutiques aux nourrissons

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011129120A1 (fr) 2010-04-15 2011-10-20 Shin Nippon Biomedical Laboratories, Ltd. Procédés et compositions pour administration intranasale
WO2013088112A2 (fr) 2011-12-16 2013-06-20 Indosys Limited Cartouche de dose unitaire de médicament et dispositif d'administration
WO2021150878A1 (fr) * 2020-01-22 2021-07-29 Virginia Commonwealth University Inhalateurs de poudre sèche et interfaces pour une administration d'aérosol améliorée à des enfants
WO2021150883A1 (fr) * 2020-01-22 2021-07-29 Virginia Commonwealth University Inhalateur à poudre sèche à jet d'air pour administration rapide d'aérosols pharmaceutiques aux nourrissons

Similar Documents

Publication Publication Date Title
CA2858997C (fr) Cartouche de dose unitaire de medicament et dispositif d'administration
JP6785767B2 (ja) 吸入式の薬剤送達装置
EP2214649A1 (fr) Compositions pour le traitement de la maladie de parkinson
JP2006527046A (ja) 粉末エアロゾル用送給装置
EA003405B1 (ru) Способ и устройство для введения действующего вещества в виде аэрозоля в легкие пациента
JP2010057950A (ja) 吸入療法に使用するためのエアロゾル形成装置
US20180056022A1 (en) Hand-actuated dry powder inhaler and its use
JP2002504833A (ja) 総吸入容積を制御することによる制御された用量でインスリンを投与するための装置
WO2016187120A1 (fr) Générateur d'aérosol actionné à la main et son utilisation
KR20210019604A (ko) 열 에어로졸 응축 공정을 위한 에어웨이에서 대전방지 소재의 용도
TW201249442A (en) Administration of iloprost as aerosol bolus
CN113876748A (zh) 一种用于治疗肺动脉高压的曲前列尼尔气溶胶吸入剂的雾化方法
WO2024047351A1 (fr) Dispositif d'administration de médicament en poudre sèche
JP2022517172A (ja) 乾燥粉末吸入器
JP7258854B2 (ja) 複数回投与薬剤送達装置
WO2011110970A1 (fr) Inhalateur de poudre sèche à dose unique
US20030150462A1 (en) Aerosol delivery apparatus-ventilator connector with adapter (VCA) and medicament dispenser and adapter (MDA)
MXPA06006284A (en) Portable gas operating inhaler
WO2008128280A1 (fr) Procédé et système pour l'administration transdermique d'un agent actif volatil

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23783491

Country of ref document: EP

Kind code of ref document: A1