WO2010025505A1 - Analgesia by transmucosal administration - Google Patents

Analgesia by transmucosal administration Download PDF

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Publication number
WO2010025505A1
WO2010025505A1 PCT/AU2009/001143 AU2009001143W WO2010025505A1 WO 2010025505 A1 WO2010025505 A1 WO 2010025505A1 AU 2009001143 W AU2009001143 W AU 2009001143W WO 2010025505 A1 WO2010025505 A1 WO 2010025505A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
administration
administered
analgesia
transmucosal administration
Prior art date
Application number
PCT/AU2009/001143
Other languages
French (fr)
Inventor
Alexander James Kelly
Original Assignee
Phebra Pty Ltd
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 AU2008904595A external-priority patent/AU2008904595A0/en
Application filed by Phebra Pty Ltd filed Critical Phebra Pty Ltd
Publication of WO2010025505A1 publication Critical patent/WO2010025505A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/08—Ethers or acetals acyclic, e.g. paraformaldehyde
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the invention described herein relates generally to anesthesia and analgesia.
  • the invention is directed to transmucosal administration of halogenated ethers for the treatment of pain, although the scope of the invention is not necessarily limited thereto.
  • Anaesthetic agents are generally administered intravenously or by inhalation into the lungs.
  • Anaesthetics used as analgesics are generally administered by inhalation into the lungs.
  • Australian Patent Application No. 2002362844 discloses administration of vaporized halogenated ethers by inhalation into the lungs for conscious sedation.
  • WO 2007/033400 discloses a method of treating pain comprising administering an effective dose of methoxyfiurane via an inhaler means into the lungs.
  • Administration of these agents intravenously or by inhalation into the lungs can be disadvantageous as intravenous administration is difficult in emergency situations outside of a hospital setting, and inhalation administration into the lungs requires active participation by the patient. The latter two routes can also lead to addiction to these agents. Therefore, there would be an advantage if it were possible to provide a route of administration of anaesthetics for analgesia, which may overcome at least some of the above-mentioned disadvantages or provide a useful or commercial choice.
  • the invention provides compositions of anaesthetics for transmucosal administration with unexpected advantages over the administration routes disclosed in the prior art.
  • the invention provides a composition comprising a solution of at least one volatile anaesthetic, wherein the composition is administered transmucosally for treating pain.
  • the invention provides a method of treating pain in a subject, the method comprising transmucosal administration of a composition to the subject, the composition comprising a solution of at least one volatile anaesthetic.
  • transmucosal administration includes intranasal administration and intrabuccal administration, where the drug is administered directly into the nasal cavity or buccal cavity with no administration to the lungs.
  • the composition comprises any appropriate anaesthetic.
  • the composition comprises one or more halogenated ether anaesthetics, including but not limited to sevofiurane, methoxyflurane, isoflurane, enflurane and desflurane.
  • the concentration of anaesthetic alone or as a mixture of anaesthetics in the composition can be any practicable concentration but is preferably from 1% to 100% of the composition.
  • the composition can be included in a device for transmucosal administration wherein the device is configured for a single dose or multiple dose administration.
  • the composition intended for multiple dose administration can include a preservative such as benzyl alcohol, LiquaPar® Oil (ISP Corporation), benzalkonium chloride, EDTA, benzethonium chloride, chlorobutanol, parabens and phenoxyethanol.
  • the preservative is LiquaPar® Oil, parabens, benzyl alcohol or benzalkonium chloride.
  • the composition can further comprise a fragrance component, such as an ester or artificial scent.
  • a fragrance component such as an ester or artificial scent.
  • the transmucosal administration of the composition can be effected in any practicable manner which limits the administration to preferably the nasal or buccal cavity, including by swab, droplets, spray or aerosol.
  • the composition is preferably administered by spray, from a suitable spray device, ensuring application to the nasal or buccal cavity only.
  • the device can be of any appropriate configuration, and is preferably a device which delivers a spray volume of between 1 ⁇ l and 1 ml per actuation of the device.
  • An example of such a device is a Valois® VP7 pump, or the Valois FreepodTM system.
  • composition can be packed and stored in any practicable container, including but not limited to glass vial Type 1 clear or amber glass of volume between 1 mL and 20OmL.
  • the invention therefore provides a composition for the treatment of pain comprising an anaesthetic for intranasal delivery, which overcomes many disadvantages of current administration regimes for analgesics as discussed below.
  • Formulations of the invention are made in the following manner. All examples have a finished volume of 1OmL.
  • composition is packaged in a glass vial of Type 1 clear or amber glass of volume from 0.1 milliliter up to 100 milliliters of the type typically used for an injection pharmaceutical.
  • composition may also be packaged in a single use device of the type manufactured by Valois SAS or equivalent such as the Valois MonodoseTM or DolphinTM.
  • a single use device of the type manufactured by Valois SAS or equivalent such as the Valois MonodoseTM or DolphinTM.
  • volume of a single-use container is between 0.1 and 2 milliliters
  • Transmucosal administration of halogenated ethers is particularly suited to rapid relief of emergency pain, treatment and management. Transmucosal administration also allows for administration of the drug to an incapacitated patient, without risk of subsequent addiction to the drug.
  • Sevoflurane in a Valois® VP7 spray pump was also administered buccally. Onset of analgesia was rapid (less than one minute) and analgesia lasted more than 20 minutes. Both rapid onset and retention of effect are important in emergency settings.
  • the invention provides an improved administration route for anaesthetic agents used for analgesia.
  • the invention provides a method of administration, transmucosally, of anaesthetics, particularly halogenated ethers, with enhanced drug delivery and drug uptake, which necessitates lower doses of the active and consequent lower incidence of side effects.
  • Optional inclusion of a preservative allows for provision of a multi-dose formulation.

Abstract

The invention provides a composition comprising a solution of at least one volatile anaesthetic, wherein the composition is administered transmucosally for treating pain, and a method of treating pain comprising transmucosal administration of the composition.

Description

ANALGESIA BY TRANSMUCOSAL ADMINISTRATION TECHNICAL FIELD
The invention described herein relates generally to anesthesia and analgesia. In particular, the invention is directed to transmucosal administration of halogenated ethers for the treatment of pain, although the scope of the invention is not necessarily limited thereto.
BACKGROUND ART
Anaesthetic agents are generally administered intravenously or by inhalation into the lungs. Anaesthetics used as analgesics are generally administered by inhalation into the lungs. For example, Australian Patent Application No. 2002362844 discloses administration of vaporized halogenated ethers by inhalation into the lungs for conscious sedation.
Also, WO 2007/033400 discloses a method of treating pain comprising administering an effective dose of methoxyfiurane via an inhaler means into the lungs. Administration of these agents intravenously or by inhalation into the lungs can be disadvantageous as intravenous administration is difficult in emergency situations outside of a hospital setting, and inhalation administration into the lungs requires active participation by the patient. The latter two routes can also lead to addiction to these agents. Therefore, there would be an advantage if it were possible to provide a route of administration of anaesthetics for analgesia, which may overcome at least some of the above-mentioned disadvantages or provide a useful or commercial choice.
SUMMARY OF THE INVENTION
The invention provides compositions of anaesthetics for transmucosal administration with unexpected advantages over the administration routes disclosed in the prior art. In a first embodiment, the invention provides a composition comprising a solution of at least one volatile anaesthetic, wherein the composition is administered transmucosally for treating pain.
In a second embodiment, the invention provides a method of treating pain in a subject, the method comprising transmucosal administration of a composition to the subject, the composition comprising a solution of at least one volatile anaesthetic.
With regard to the first and second embodiment as defined above, transmucosal administration includes intranasal administration and intrabuccal administration, where the drug is administered directly into the nasal cavity or buccal cavity with no administration to the lungs.
The composition comprises any appropriate anaesthetic. Preferably the composition comprises one or more halogenated ether anaesthetics, including but not limited to sevofiurane, methoxyflurane, isoflurane, enflurane and desflurane.
The concentration of anaesthetic alone or as a mixture of anaesthetics in the composition can be any practicable concentration but is preferably from 1% to 100% of the composition.
The composition can be included in a device for transmucosal administration wherein the device is configured for a single dose or multiple dose administration. The composition intended for multiple dose administration can include a preservative such as benzyl alcohol, LiquaPar® Oil (ISP Corporation), benzalkonium chloride, EDTA, benzethonium chloride, chlorobutanol, parabens and phenoxyethanol. Preferably, the preservative is LiquaPar® Oil, parabens, benzyl alcohol or benzalkonium chloride.
The composition can further comprise a fragrance component, such as an ester or artificial scent. The addition of a fragrance ensures that a user of the transmucosal composition knows when it has been administered. In addition, the composition can then not be administered without subject knowledge, and patient compliance is improved due to a pleasant smell on administration of the composition.
The transmucosal administration of the composition can be effected in any practicable manner which limits the administration to preferably the nasal or buccal cavity, including by swab, droplets, spray or aerosol. The composition is preferably administered by spray, from a suitable spray device, ensuring application to the nasal or buccal cavity only. The device can be of any appropriate configuration, and is preferably a device which delivers a spray volume of between 1 μl and 1 ml per actuation of the device. An example of such a device is a Valois® VP7 pump, or the Valois Freepod™ system.
The composition can be packed and stored in any practicable container, including but not limited to glass vial Type 1 clear or amber glass of volume between 1 mL and 20OmL.
The invention therefore provides a composition for the treatment of pain comprising an anaesthetic for intranasal delivery, which overcomes many disadvantages of current administration regimes for analgesics as discussed below.
In order that the invention may be more readily understood and put into practice, one or more preferred embodiments thereof will now be described, by way of example only. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
Examples
Formulations of the invention are made in the following manner. All examples have a finished volume of 1OmL.
Example 1 : Sevoflurane 10.O mL
Example 2:
Sevoflurane 9.96 mL
LiquiPar Oil 0.04 mL
Example 3: Methoxyfiurane 10.O mL
Example 4:
Sevoflurane 7.5 mL
Water 2.5 mL - A -
The composition is packaged in a glass vial of Type 1 clear or amber glass of volume from 0.1 milliliter up to 100 milliliters of the type typically used for an injection pharmaceutical.
The composition may also be packaged in a single use device of the type manufactured by Valois SAS or equivalent such as the Valois Monodose™ or Dolphin™. Typically the volume of a single-use container is between 0.1 and 2 milliliters
Efficacy and Uses of Formulations
Animal data shows rapid occurring absorption of drugs via the nasal and buccal routes. The nasal and buccal routes are therefore suitable for use in patients requiring rapid relief of severe pain. General advantages of nasal application aiming at systemic effect are ease of self-administration, supporting a health-economic argument and the self-care concept. In addition, first pass liver metabolism and gastro-intestinal metabolism is avoided.
Transmucosal administration of halogenated ethers is particularly suited to rapid relief of emergency pain, treatment and management. Transmucosal administration also allows for administration of the drug to an incapacitated patient, without risk of subsequent addiction to the drug.
This is exemplified by administration of sevoflurane in a Valois® VP7 nasal spray pump to the nasal cavity of a number of subjects. The subjects reported significant analgesic effects in less than one minute.
Sevoflurane in a Valois® VP7 spray pump was also administered buccally. Onset of analgesia was rapid (less than one minute) and analgesia lasted more than 20 minutes. Both rapid onset and retention of effect are important in emergency settings.
It is clear from the foregoing that the invention provides an improved administration route for anaesthetic agents used for analgesia. The invention provides a method of administration, transmucosally, of anaesthetics, particularly halogenated ethers, with enhanced drug delivery and drug uptake, which necessitates lower doses of the active and consequent lower incidence of side effects. Optional inclusion of a preservative allows for provision of a multi-dose formulation. The foregoing embodiments are illustrative only of the principles of the invention, and various modifications and changes will readily occur to those skilled in the art. The invention is capable of being practiced and carried out in various ways and in other embodiments. It is also to be understood that the terminology employed herein is for the purpose of description and should not be regarded as limiting.
The term "comprise" and variants of the term such as "comprises" or "comprising" are used herein to denote the inclusion of a stated integer or stated integers but not to exclude any other integer or any other integers, unless in the context or usage an exclusive interpretation of the term is required. Any reference to publications cited in this specification is not an admission that the disclosures constitute common general knowledge in Australia.

Claims

Claims:
1. A composition comprising a solution of at least one volatile anaesthetic, wherein the composition is administered transmucosally for treating pain.
2. The composition of claim 1 wherein the composition is administered intranasally.
3. The composition of claim 1 wherein the composition is administered intrabuccally.
4. The composition of claim 1 wherein the volatile anaesthetic is a halogenated ether.
5. The composition of claim 5 wherein the halogenated ether is selected from the group consisting of sevoflurane, methoxyflurane, isoflurane, enfiurane and desflurane, or a combination.
6. The composition of claim 1 wherein the at least one volatile anaesthetic is 1% to 100% of the composition.
7. The composition of claim 1, further comprising a fragrance and/or preservative.
8. The composition of claim 1, wherein the composition is administered by swab, droplets, spray or aerosol.
9. A method of treating pain in a subject, the method comprising transmucosal administration of a composition to the subject, the composition comprising a solution of at least one volatile anaesthetic.
10. The method of claim 9 wherein the administration is intranasal.
11. The method of claim 9 wherein the administration is intrabuccal.
12. The method of claim 9 wherein the volatile anaesthetic is a halogenated ether.
13. The method of claim 9 wherein the halogenated ether is selected from the group consisting of sevoflurane, methoxyflurane, isoflurane, enfiurane and desflurane, or a combination.
14. The method of claim 9 wherein the at least one volatile anaesthetic is 1% to 100% of the composition.
15. The method of claim 9, wherein the composition further comprises a fragrance and/or preservative.
16. The method of claim 9, wherein administration is by swab, droplets, spray or aerosol.
PCT/AU2009/001143 2008-09-04 2009-09-02 Analgesia by transmucosal administration WO2010025505A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AU2008904595A AU2008904595A0 (en) 2008-09-04 Analgesia by Transmucosal Administration
AU2008904595 2008-09-04

Publications (1)

Publication Number Publication Date
WO2010025505A1 true WO2010025505A1 (en) 2010-03-11

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PCT/AU2009/001143 WO2010025505A1 (en) 2008-09-04 2009-09-02 Analgesia by transmucosal administration

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WO (1) WO2010025505A1 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017011865A1 (en) 2015-07-20 2017-01-26 Medical Developments International Limited Inhaler device for inhalable liquids
WO2017011866A1 (en) 2015-07-20 2017-01-26 Medical Developments International Limited Inhaler device for inhalable liquids
WO2017011867A1 (en) 2015-07-20 2017-01-26 Medical Developments International Limited Inhaler device for inhalable liquids
US11571526B2 (en) 2016-09-06 2023-02-07 Medical Developments International Limited Inhaler device for inhalable liquids

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002022116A1 (en) * 2000-09-14 2002-03-21 Messer Griesheim Gmbh Volatile anaesthetic with xenon
WO2007033400A1 (en) * 2005-07-29 2007-03-29 Medical Developments International Limited Method of treating pain in patients
WO2008036858A2 (en) * 2006-09-20 2008-03-27 The Board Of Regents Of The University Of Texas System Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief
WO2009094460A2 (en) * 2008-01-22 2009-07-30 Vapogenix, Inc. Volatile anesthetic compositions and methods of use
WO2009094459A1 (en) * 2008-01-22 2009-07-30 The Board Of Regents Of The University Of Texas System Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002022116A1 (en) * 2000-09-14 2002-03-21 Messer Griesheim Gmbh Volatile anaesthetic with xenon
WO2007033400A1 (en) * 2005-07-29 2007-03-29 Medical Developments International Limited Method of treating pain in patients
WO2008036858A2 (en) * 2006-09-20 2008-03-27 The Board Of Regents Of The University Of Texas System Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief
WO2009094460A2 (en) * 2008-01-22 2009-07-30 Vapogenix, Inc. Volatile anesthetic compositions and methods of use
WO2009094459A1 (en) * 2008-01-22 2009-07-30 The Board Of Regents Of The University Of Texas System Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Alternative Routes of Drug Administration", PEDIATRICS., vol. 100, no. 1, 1997, pages 143 - 152 *
STANLEY, TH.: "Anesthesia for the 21st Century", BUMC PROCEEDINGS., vol. 13, 2000, pages 7 - 10 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017011865A1 (en) 2015-07-20 2017-01-26 Medical Developments International Limited Inhaler device for inhalable liquids
WO2017011866A1 (en) 2015-07-20 2017-01-26 Medical Developments International Limited Inhaler device for inhalable liquids
WO2017011867A1 (en) 2015-07-20 2017-01-26 Medical Developments International Limited Inhaler device for inhalable liquids
US11672925B2 (en) 2015-07-20 2023-06-13 Medical Developments International Limited Inhaler device for inhalable liquids
US11571526B2 (en) 2016-09-06 2023-02-07 Medical Developments International Limited Inhaler device for inhalable liquids

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Publication number Publication date
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