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.