GB2628149A

GB2628149A - Nasal spray for performing sphenopalatine ganglion block

Info

Publication number: GB2628149A
Application number: GB2303839.1A
Authority: GB
Inventors: Nathaniel-Wurie Lee
Original assignee: Individual
Current assignee: Individual
Priority date: 2023-03-16
Filing date: 2023-03-16
Publication date: 2024-09-18
Also published as: WO2024189189A1

Abstract

A composition for use in treating a disease or disorder by sphenopalatine ganglion block, wherein the composition comprises a local anaesthetic formulated for administration as a nasal spray, is provided. Preferably the disease or disorder is a post dural puncture headache sequelae to spinal anaesthesia or epidural catheterisation. The disease or disorder may be a cluster headache or migraine headache. The local anaesthetic may comprise an amino amide local anaesthetic, preferably bupivacaine and/or ropivacaine, particularly levo-bupivacaine. The amino amide local anaesthetic may comprise lidocaine. The composition may be administered with a nasal decongestant. A nasal spray device 100 comprising: a reservoir 110 holding a composition; an applicator 150 coupled to the reservoir 110, the applicator 150 being configured for insertion into the nose of the patient; and a pump 120 for driving the composition from the reservoir 110 through the applicator 150 and into the nose of the patient; wherein the composition comprises a local anaesthetic and a nasal decongestant in a pharmaceutically acceptable fluid carrier, the nasal decongestant being a vasoconstrictor, is also outlined. A kit comprising: a local anaesthetic; and a nasal decongestant, wherein the nasal decongestant is a vasoconstrictor is also provided.

Description

Nasal spray for performing sphenopalatine ganglion block

Background

[0001] The dura mater is a membrane which surrounds the brain and spinal cord. This membrane may be punctured during certain medical procedures, either intentionally (e.g., to relieve hydrocephalus or during a lumbar puncture) or unintentionally (e.g., during the administration of epidural anaesthesia).

[0002] Puncture of the dura mater may lead to a post dural puncture headache, PDPH, sometimes referred to as a post lumbar puncture (LP) headache. The headache is usually positional (worse when the patient is upright, better when the patient is lying flat) and is often accompanied by neck stiffness, photophobia, nausea, or subjective hearing symptoms.

[0003] The precise aetiology of headache after dural puncture is unclear. It is theorised that leakage of cerebrospinal fluid, CSF, through the dural hole can lead to low CSF pressure. However, not all patients with PDPH have low CSF pressure, and not all patients with significant CSF leak develop a headache.

[0004] Mild cases of PDPH can be treated by bed rest and a brief course of an oral analgesic such as paracetamol or a nonsteroidal anti-inflammatory drug, NSAID.

[0005] Moderate to severe cases of PDPH can be debilitating, leaving the patient unable to tolerate sitting or standing, or unable to perform activities of daily living. The gold standard treatment for moderate to severe cases of PDPH is an epidural blood patch, EBP. EBP is performed by injecting the patient's blood through an epidural needle into the epidural space.

EBP usually provides immediate relief, and has a success rate of between 65 and 98 %.

Summary

[0006] In one aspect, the present invention provides a composition for use in treating a disease or disorder by sphenopalatine ganglion block. The composition comprises a local anaesthetic formulated for administration as a nasal spray. By administering a local anaesthetic as a nasal spray, sphenopalatine ganglion block may be achieved in a non-invasive way. Sphenopalatine ganglion block is effective for relieving post dural puncture headaches, as well as various other conditions, such as migraine.

[0007] Diseases or disorders which may be treated by sphenopalatine ganglion block include headaches and facial pain of variable pathology. Examples include post dural puncture headache, cluster headache, migraine, trigeminal neuralgia, herpes zoster neuralgia, paroxysmal hemicrania, pain associated with cancer of the head or neck; atypical facial pain; complex regional pain syndrome ("CRPS"), temporomandibular disorder, nasal contact point headache, and vasomotor rhinitis. As used herein, the term "treatment" encompasses palliative treatment.

[0008] In particular, the disease or disorder may be a post dural puncture headache. The post dural puncture headache may be a sequela to spinal anaesthesia or attempted or successful epidural catheterisation.

[0009] The composition may be administered to a patient for whom an epidural blood patch is contraindicated. Examples of such patients include those who are suffering from one or more of obesity, scoliosis, a coagulopathy, a systemic infection, a localised infection at a lumbar puncture site.

[0010] Alternatively, the headache may be a migraine headache or a cluster headache.

[0011] The local anaesthetic may comprise a long-acting local anaesthetic. Long-acting local anaesthetics may allow the composition to be dosed at reduced frequency.

[0012] The local anaesthetic may comprise an amino amide local anaesthetic. The amino amide class of local anaesthetics may be less allergenic than amino amide ester local anaesthetics.

[0013] The amino amide local anaesthetic may comprise bupivacaine and/or ropivacaine. Bupivacaine and ropivacaine have long durations of action. This may allow the composition to be administered less frequently when compared with other local anaesthetics.

[0014] In particular, the amino amide local anaesthetic may comprise bupivacaine.

Bupivacaine may be more cost-effective than ropivacaine. The bupivacaine may be in the form of levo-bupivacaine. For example, at least 90 % of the bupivacaine by weight may be the levo isomer. The levo isomer of bupivacaine has lower toxicity than the dextro isomer.

[0015] The amino amide local anaesthetic may comprise lidocaine. Lidocaine provides rapid blockade of nerve conduction.

[0016] The local anaesthetic may comprise a combination of a rapid onset local anaesthetic (e.g., lidocaine) and a long duration rapid anaesthetic (e.g., bupivacaine and/or ropivacaine).

This combination may allow for rapid relief of symptoms with a reduced frequency of dosage.

[0017] The composition may further comprise a nasal decongestant, the nasal decongestant being a vasoconstrictor. The vasoconstrictor synergises with the local anaesthetic. By reducing swelling of tissue in the nasal cavity, the vasoconstrictor may increase the effective surface area for uptake of the local anaesthetic. By reducing blood flow at the delivery site, the vasoconstrictor may improve the duration of the analgesia, by reducing absorption of the local anaesthetic into the blood stream. Further, reducing blood flow may reduce systemic toxicity. Systemic toxicity may occur when peak plasma concentration of the local anaesthetic is too high. The peak plasma concentration is a function of speed of systemic absorption as opposed to purely dose of administration, [0018] The nasal decongestant may be an adrenergic agonist. Adrenergic agonists are effective as vasoconstrictors. In particular, the adrenergic agonist may be an alphaadrenergic agonist. Alpha-adrenergic agonists may have fewer side-effects than non-specific adrenergic agonists. A preferred alpha-adrenergic agonist is xylometazoline. Xylometazoline is a well-characterised drug with a good safety profile.

[0019] The composition may further comprise a pH buffering agent. An example pH buffering agent is bicarbonate. Many local anaesthetics and nasal decongestants are ionisable compounds. Generally, unionised compounds are taken up more rapidly than ionised compounds. The buffer may adjust the pH composition such that a greater proportion of the local anaesthetic and/or nasal decongestant is in the unionised form.

[0020] In use, the composition is administered as a nasal spray. The composition may be administered to a patient in a supine position. When the patient is supine, the composition may remain at the back of the patient's nasal cavity for a longer duration. This may improve uptake of the local anaesthetic by the sphenopalatine ganglion.

[0021] In another aspect, the present invention provides a kit comprising a local anaesthetic and a nasal decongestant. The nasal decongestant is a vasoconstrictor.

[0022] The kit is useful for preparing a composition as discussed herein. It will be appreciated that optional features described in relation to the medical use aspect are equally applicable to the kit.

[0023] For example, the local anaesthetic may comprise any of the local anaesthetics discussed above, such as an amino amide local anaesthetic. The nasal decongestant may comprise any of the nasal decongestants discussed above, and may comprise an adrenergic agonist.

[0024] Another related aspect provides a composition comprising a local anaesthetic and a nasal decongestant, the nasal decongestant being a vasoconstrictor. The composition may further comprise a pharmaceutically-acceptable fluid carrier, suitable for a nasal spray.

[0025] The composition may be prepared using the kit. As will be appreciated, all compositional features discussed with reference to the medical use aspect are equally applicable to the composition aspect.

[0026] Still another aspect provides a nasal spray device. The nasal spray device comprises a reservoir holding a composition; an applicator coupled to the reservoir, the applicator being configured for insertion into a nose of a patient; and an actuator for driving the composition from the reservoir through the applicator and into the nose of the patient. The composition comprises a local anaesthetic and a nasal decongestant in a pharmaceutically-acceptable fluid carrier, the nasal decongestant being a vasoconstrictor.

[0027] The nasal spray device is useful for administering a composition as provided herein. It will be appreciated that the composition included in the nasal spray device may be as discussed with reference to the medical use aspect.

[0028] The applicator may be formed of a pliable material. An example pliable material is poly(vinyl chloride), PVC. This may allow the applicator to be inserted into the nose of the patient atraumatically, i.e. without damaging the soft tissues of the nose.

[0029] The applicator may have a length in the range 6 to 10 cm, optionally 7 to 9 cm. The sphenopalatine ganglion is located in the posterior nasopharynx. Delivering the composition to, or slightly in front of, the posterior nasopharynx may maximize the efficacy of the composition. In most patients, the distance from the opening of the nose to the posterior nasopharynx is in the range 6 to 10 cm. The nasal spray device may be configured to be operated in an inverted orientation. This may allow for easier delivery of the composition to a patient who is in a supine position.

Brief Description of the Drawings

[0030] To assist understanding of embodiments of the present disclosure and to show how such embodiments may be put into effect, reference is made, by way of example only, to the accompanying drawings in which: Fig. 1 is a schematic cross-sectional diagram of an example nasal spray device.

Detailed Description

[0031] Directional terms such as "top", "bottom", "left", "right", "above", "below", "horizontal" and "vertical" are used herein for convenience of description. For the avoidance of any doubt, this terminology is not intended to limit orientation in an external frame of reference.

[0032] The terms "short-acting", "medium-acting", and "long-acting" are widely used in the field of local anaesthesia, and have well-recognized meanings amongst practitioners. By way of illustration, a "short-acting" local anaesthetic may have a duration of action of up to 2 hours, a medium-acting local anaesthetic may have a duration of action of between 2 and 4 hours, and a long-acting local anaesthetic may have a duration of action of 4 or more hours.

[0033] It will be appreciated that some of the compounds disclosed herein may be ionisable, i.e. some compounds may be weak acids, weak bases, or ampholytes. Any ionisable compound discussed herein may be supplied in its free form or as a pharmaceutically-acceptable salt.

[0034] The compositions provided herein are most preferably for use in treating human patients. Veterinary use in non-human animals is also contemplated.

[0035] Though epidural blood patch, EBP, is an effective treatment for post dural puncture headache, it has several limitations. EBP is an in-patient treatment which must be delivered by an experienced practitioner and which unavoidably carries the risk of causing a further dural puncture. The risks associated with EBP limit it use to only the most severe cases.

[0036] Further, EBP is not suitable for all patients, such as those who have challenging anatomies (e.g., obesity or scoliosis); a coagulopathy; a systemic infection such as HIV; or a localised infection at a site for epidural needle placement.

[0037] Transnasal sphenopalatine ganglion block, SPGB, has been proposed as an alternative to EBP. In transnasal SPGB, the patient is positioned supine or semi-sitting, and a cotton tip applicator saturated with 2 to 5 % lidocaine is inserted through each nostril until it contacts the posterior pharynx. The applicators are left in place for at least 10 minutes before removal. This procedure is less invasive than EBP and provides 4 to 6 hours of relief of symptoms. However, this procedure must still be delivered by a professional as an in-patient treatment, and provides only short-term relief.

[0038] Provided herein is a composition for use in treating headache by sphenopalatine ganglion block which addresses drawbacks of the existing methods.

[0039] The present invention provides a composition for use in treating headache by sphenopalatine ganglion block, which composition comprises a local anaesthetic formulated for administration as a nasal spray. Administering the composition in the form of a nasal spray may allow the composition to be delivered as an out-patient treatment.

[0040] The composition includes an effective amount of a local anaesthetic. By way of illustration, the local anaesthetic may be present in an amount of at least 0.1 % by weight based on the total weight of the composition.

[0041] The nature of the local anaesthetic is not particularly limited, and may be selected as 20 appropriate.

[0042] Many local anaesthetics have a general structure as shown in Formula 1: R2 AK 'IR 'R Formula 1 [0043] Ar is a lipophilic aromatic group, such as an optionally-substituted phenyl group. The substituent(s), if present, may be selected from NH2, halides, and C1 to C6 alkyl groups. In particular, Ar may be a phenyl group or a para-amino phenyl group.

[0044] Lisa linker selected from an ester and an amide group.

[0045] R1 to R3 may be independently selected to provide a hydrophilic group. R1 to R3 are often selected from optionally substituted alkyl groups, e.g. C1 to C6 alkyl groups.

[0046] The structure of Formula 1 includes a tertiary amine group. As such, many local anaesthetics are ionisable. The local anaesthetic may be in free base form, or may be provided as a pharmaceutically-acceptable salt (e.g., a hydrochloride salt).

[0047] Local anaesthetics in which the linker Lis an ester are referred to as amino ester local anaesthetics:

RAN

Formula 2 [0048] Examples of amino ester local anaesthetics include amoproxan, amylocaine, benzocaine, butacaine, butamben, chloroprocaine, cyclomethylcaine, dimethocaine, eucaine, p-eucaine, 4-fluorotropacocaine, hexylcaine, isobucaine, meprylcaine, metabutethamine, metabutoxycaine, nitracaine, orthocaine, piperocaine, piridocaine, procaine (commonly referred to using the trade names Novocain or Novocaine), propoxycaine, proxymetacaine, tetracaine and risocaine. Cocaine is a further example of an amino ester local anaesthetic, but is a controlled substance in many jurisdictions. Preferred examples of amino ester local anaesthetics include procaine, chlorprocaine, and tetracaine.

[0049] Local anaesthetics in which the linker L is an amide are referred to as amino amide local anaesthetics: NH R1 R2 O F3 Formula 3 [0050] Examples of amino amide local anaesthetics include articaine; bupivacaine, optionally levobupivacaine; butanilicaine, carticaine, cinchocaine (also referred to as dibucaine), etidocaine, lidocaine, mepivacaine, prilocaine, ropivacaine; and trimecaine.

[0051] Of these two classes, the amino amide local anaesthetics are preferred since amino amide local anaesthetics are less likely to provoke an allergic reaction.

[0052] The local anaesthetic may in particular be selected from bupivacaine and ropivacaine: CH3 CH3 ° CH3.NHS H H3C CH30 CH3 bupivacaine ropivacaine [0053] Bupivacaine and ropivacaine each have long durations of action. This may allow for the less frequent administration of the composition.

[0054] Bupivacaine and ropivacaine are chiral compounds and may be provided as a racemic mixture, or as their S-enantiomers.

[0055] The S-enantiomer of bupivacaine may be referred to as levo-bupivacaine or Lbupivacaine: levo-bupivacaine CH3 [0056] L-bupivacaine may have lower systemic toxicity than R-bupivacaine. Where bupivacaine is present, at least 75 mol%, optionally at least 90 mol%, further optionally at least 99 mol% of the bupivacaine may be L-bupivacaine. The difference in toxicity is small, and a racemic mixture of L-and R-bupivacaine may be used.

[0057] The composition may comprise a combination of two or more different local anaesthetics. In particular, the composition may comprise a combination of a short-or medium-duration local anaesthetic and a long-duration local anaesthetic.

[0058] Short-or medium-duration local anaesthetics provide a rapid onset of anaesthesia, allowing for the rapid relief of symptoms. The effects of short-or medium-duration local anaesthetics may wear off relatively quickly (e.g., within 1 to 4 hours). Long-duration local anaesthetics provide relief of symptoms for extended periods of time (e.g., 4 to 8 hours), but can be slow to take effect. Combining a short-or medium-duration local anaesthetic with a long-duration local anaesthetic may allow for both the rapid relief of symptoms and infrequent dosing.

[0059] Examples of short-and medium-duration local anaesthetics include procaine, chloroprocaine, lidocaine, mepivacaine, and prilocaine.

[0060] Examples of long-duration local anaesthetics include tetracaine, bupivacaine, and ropivacaine.

[0061] In particular, the local anaesthetic may comprise lidocaine in combination with either bupivacaine or ropivacaine.

[0062] The local anaesthetic may be co-administered with a nasal decongestant. The nasal decongestant may more specifically be a vasoconstrictor. The combined administration of the local anaesthetic with the nasal decongestant may improve the efficacy and/or safety of the local anaesthetic.

[0063] Vasoconstriction reduces blood flow to the site of delivery of the local anaesthetic. This reduces absorption of the local anaesthetic into the bloodstream. The risk of serious systemic side-effects, those which effect the heart or central nervous system, increases as a function of the concentration of local anaesthetic in the blood. Reducing uptake of the local anaesthetic into the blood therefore reduces the risk of systemic toxicity.

[0064] By the same token, vasoconstriction increases the targeted effect site dosage: a greater proportion of the local anaesthetic remains at the site of the delivery. This increases efficacy for a given dosage.

[0065] Further, the decongestant effect may improve local absorption of the local anaesthetic. The local anaesthetic reaches the sphenopalatine ganglion via the nasal turbinates: narrow passages within the nose which are lined with soft tissue. The nasal decongestant increases the diameter of these passages, allowing a greater proportion of the local anaesthetic to arrive at the target area.

[0066] The nasal decongestant may be administered immediately before the local anaesthetic. For example, the local anaesthetic may be administered within 10 minutes, and optionally within 5 minutes, of administering the nasal decongestant.

[0067] Most conveniently, the nasal decongestant and the local anaesthetic may be administered simultaneously, as components of the same nasal spray. This may ensure that both the nasal decongestant and the local anaesthetic are delivered to the same target site.

[0068] The nature of the nasal decongestant is not particularly limited, provided that the nasal decongestant is a vasoconstrictor. Many suitable nasal decongestants are known in the art.

[0069] The nasal decongestant may be an adrenergic agonist. Adrenergic agonists are effective as vasoconstrictors.

[0070] In particular, the adrenergic agonist may be an alpha-adrenergic agonist. Alphaadrenergic agonists may have fewer side-effects than non-specific adrenergic agonists. For example, non-specific adrenergic agonists such as adrenaline can create a sense of impending doom.

[0071] Examples of alpha-adrenergic agonists include (R)-3-nitrobiphenyline, amidephrine, amitraz, apraclonidine, cirazoline, epinephrine, ergotamine, etilefrine, fadolmidine, guanabenz, guanethidine, guanfacine, guanoxabenz, indanidine, lofexidine, medetomidine, mephentermine, metaraminol, methoxamine, methoxamine, methyldopa, methylnorepinephrine, midodrine, mivazerol, naphazoline, norepinephrine, norfenefrine, octopamine, oxymetazoline, phenylephrine, phenylpropanolamine, propylhexedrine, rilmenidine, romifidine, synephrine, talipexole, tizanidine, xylazine, and xylometazoline.

[0072] In particular, the alpha-adrenergic agonist may be an agonist of both alpha-1 and alpha-2 adrenergic receptors. Examples of such compounds include apraclonidine, cirazoline, epinephrine, oxymetazoline, and xylometazoline. In particular, the alpha-adrenergic agonist may be oxymetazoline or xylometazoline. Oxymetazoline and xylometazoline are well-characterised drugs with good safety profiles, as well as being relatively inexpensive.

[0073] In particular, the composition may comprise a local anaesthetic selected from bupivacaine and ropivacaine; and xylometazoline or oxymetazoline as a vasoconstrictor. The local anaesthetic may in particular be bupivacaine, optionally levobupivacaine. The composition may optionally further comprise a short-or medium-duration local anaesthetic such as lidocaine.

[0074] The dosage of the nasal decongestant is not particularly limited, provided that an effective amount is used. The dosage may be selected as appropriate based on the nature of the nasal decongestant chosen. By way of illustration, the composition may comprise the nasal decongestant in an amount of at least 0.1 % by weight, based on the total weight of the composition.

[0075] The composition may optionally further comprise an analgesic. The analgesic may be a non-steroidal anti-inflammatory drug, NSAID. Examples of useful NSAIDs include diclofenac and ketoprofen. An opioid analgesic may in principle be used.

[0076] The composition further comprises a pharmaceutically-acceptable fluid carrier. The nature of the carrier is not particularly limited, provided that the carrier is suitable for use as a nasal spray.

[0077] The carrier typically comprises water, optionally in combination with a co-solvent.

Example co-solvents include ethanol and benzyl alcohol. The use of non-aqueous carriers is also contemplated.

[0078] The local anaesthetic and the nasal decongestant (if present) are distributed in the carrier. The local anaesthetic may be dissolved, suspended, or emulsified in the carrier. The nasal decongestant may be dissolved, suspended, or emulsified in the carrier.

[0079] The composition may optionally include one or more excipients selected from a pH buffer, a salt, an antioxidant, a surfactant, a humectant, a preservative, a rheology modifier, a flavour, and a sweetener.

[0080] In particular, the composition may further comprise a pH buffer. In many implementations, the local anaesthetic and/or nasal decongestant is an ionisable compound. In particular, the tertiary amine group of the compounds of Formula 1 will often be ionisable.

[0081] Compounds in unionised form are more rapidly absorbed. The proportion of the compound which is unionised is dependent upon the plc of the compound and the pH of the composition. By adjusting the pH, the fraction of the local anaesthetic which is unionised can be varied.

[0082] Further, to minimize nasal irritation, it is desirable for the pH of the composition to be in the range 4.5 to 6.5.

[0083] Any pharmaceutically-acceptable buffer may be used to control the pH. One illustrative example is a bicarbonate buffer.

[0084] The composition may include a salt for adjusting the osmolality of the composition.

An example salt is sodium chloride. When the composition is isotonic, i.e. has an osmolality in the range 280 to 300 mOsm/kg, local irritation may be reduced.

[0085] When the composition comprises an emulsion of the local anaesthetic and/or nasal decongestant, the composition further comprises a surfactants and/or emulsifier. The nature of the surfactant and/or emulsifier is not particularly limited, provided that the surfactant and/or emulsifier is pharmaceutically-acceptable and is compatible with the species to be emulsified.

[0086] The composition may include a rheology modifier. The rheology modifier may comprise a pharmaceutically-acceptable thickener or gel. The rheology modifier may increase the viscosity of the composition. Increasing the viscosity of the composition may reduce the rate of loss of the composition from the nasopharyngeal space, thereby allowing for improved bioavailability of the active components. For example, the rheology modifier may be selected such that the composition has viscosity approximating that of nasal mucus, e.g. a steady-shear viscosity in the range 5 to 100 cps when measured at a shear frequency of rad/s and a temperature of 37°C.

[0087] A humectant, a flavour, and/or a sweetener may be included in the composition. These components may improve patient compliance. A humectant may prevent nasal dehydration and reduce irritation. Flavours and sweeteners may mask the taste and smell of the other components of the formulation.

[0088] In use, the composition is delivered as a nasal spray to a patient in need of sphenopalatine ganglion block. In particular, the composition may be for use in the treatment of headache.

[0089] The headache may be a post dural puncture headache. The composition may be delivered to a patient who has undergone a procedure selected from lumbar puncture or epidural drug delivery.

[0090] The lumbar puncture may be a diagnostic lumbar puncture or a therapeutic lumbar puncture.

[0091] For example, the patient may have undergone a lumbar puncture for the diagnosis of a neurological disease, in particular an infectious disease of the central nervous system such as meningitis, encephalitis or syphilis. EBP is contraindicated in patients having systemic infectious diseases.

[0092] An example of a therapeutic lumbar puncture is a lumbar puncture to relieve hydrocephalus.

[0093] The composition may be delivered to a patient who has undergone spinal or epidural drug delivery, such as spinal anaesthesia. For example, the patient may be a post-partum woman who has undergone spinal anaesthesia for caesarean section.

[0094] The composition may be useful for the treatment of post dural puncture headaches in patients for whom EBP is contraindicated. Examples include patients with challenging anatomy (e.g., those suffering from obesity or scoliosis); patients suffering from a coagulopathy (e.g., haemophilia or thrombocytopenia); patients undergoing anticoagulant therapy (e.g. treatment with warfarin or heparin); patients suffering from systemic infections (e.g., HIV, meningitis, encephalitis, syphilis); and patients suffering from a localised infection at a lumbar puncture site or epidural drug delivery site.

[0095] The composition is useful for the treatment of other conditions by sphenopalatine ganglion block, such as cluster headache or a migraine headache.

[0096] In use, the composition is delivered as a nasal spray. As will be appreciated, delivering the composition as a nasal spray does not involve inserting a swab into the patient's nasal cavity.

[0097] Optionally, the nasal spray is delivered with the patient in a supine position. The sphenopalatine ganglion is located at the back of the nasal cavity. Delivering the nasal spray with the patient in a supine position may aid delivery of the composition to the location of the sphenopalatine ganglion.

[0098] The frequency of administration may be selected as appropriate based on the duration of action of the local anaesthetic chosen. For example, bupivacaine and ropivacaine each have a duration of action of 8 to 10 hours, and may be administered two to three times daily. Shorter-acting local anaesthetics may be administered more frequently.

[0099] Delivery of the composition as a nasal spray is non-invasive, and may be performed by the patient themselves. Local anaesthetics and nasal decongestants have good safety profiles. Therefore, the composition may be provided as an out-patient prescription. Use of the composition is thus less labour-intensive than existing methods for sphenopalatine ganglion block.

[0100] In comparison to EBP, which is reserved for use in only severe cases of post dural puncture headache due to its inherent risks, the composition provided herein may be used to treat any post dural puncture headache, regardless of severity.

[0101] An example nasal spray device 100 useful for delivering the composition to a human patient will now be described with reference to Fig. 1.

[0102] The nasal spray device 100 includes a reservoir 110, a pump mechanism 120, a dip tube 130, an actuator 140, and an applicator 150.

[0103] Reservoir 110 stores a composition as provided herein. The configuration of reservoir 110 is not particularly limited. Reservoir 110 is typically a hermetically-sealed chamber, for maintaining the composition in a sterile state prior to use. Reservoir 110 may be a pressurised chamber. To facilitate release of the composition from a pressurized chamber, the composition provided herein may include a pharmaceutically-acceptable propellant.

[0104] Pump mechanism 120 is configured to draw composition from the reservoir 110 via dip tube 130, and to deliver a spray of the composition from orifice 152 of the applicator 150. Any suitable pump mechanism may be used. To allow control over dosage, the pump mechanism is most preferably a metered pump mechanism, such that the nasal spray is configured to deliver a predetermined amount of composition upon actuation.

[0105] The dip tube 130 is coupled to the pump mechanism 120 and extends into the reservoir 110. The configuration of dip tube 130 is not particularly limited, provided that the dip tube allows the composition to be drawn from the reservoir.

[0106] To improve delivery of the composition to the patient's posterior nasopharynx, the patient may be supine or semi-recumbent when the composition is administered. To this end, the nasal spray 110 may be configured to allow delivery of the composition with the spray in an inverted orientation with respect to gravity g, as illustrated in Fig. 1.

[0107] In the illustrated example, the dip tube 130 is configured such that intake 132 of the dip tube 130 is proximal to the top of reservoir 110. This may ensure that intake 132 remains submerged in the composition when the nasal spray is used in the inverted orientation. Further, wastage of the composition may be reduced since the intake 132 may remain submerged even when the reservoir is not completely filled.

[0108] The pump mechanism 120 is configured to discharge the composition as a spray via orifice 152 of applicator 150. Applicator 150 is in the form of a tube. The tube may be a pliable tube, capable of supporting its own weight when no external forces are applied but sufficiently flexible as to allow the tube to be inserted into the nose without damaging the patient's soft tissues. Many suitable materials are known in the field of medical tubing. In particular, materials useful for ventilator tubing have a suitable degree of flexibility. One example material is PVC.

[0109] Since the composition is most preferably delivered to or slightly in front of the posterior nasopharynx, the applicator 150 may have a length L in the range 6 to 10 cm, optionally 7 to 9 cm. In most patients, the distance from the opening of the nose to the posterior nasopharynx is in the range 6 to 10 cm, with the average distance being about 8 cm.

Longer applications could in principle be used, however increasingthe length of the applicator above 10 cm may increase the difficult of inserting the applicator, to no particular benefit.

[0110] Length L refers to the exposed length of the applicator, available for insertion into the nose of the patient. In this example, length L is measured from orifice 152 along the path the of the applicator 150 to the top surface of actuator 140.

[0111] The illustrated example further includes an actuator 140. Actuator 140 is illustrated as a cap which extends over reservoir. The actuator 140 of this example is configured such that pressing the actuator actuates the pump mechanism 120 and causes the pump mechanism to discharge a dose of the composition.

[0112] It will be appreciated that the above embodiments have been described by way of example only.

[0113] Other variants or use cases of the disclosed techniques may become apparent to the person skilled in the art once given the disclosure herein. The scope of the disclosure is not limited by the described embodiments but only by the accompanying claims.

Claims

Claims 1. A composition for use in treating a disease or disorder by sphenopalatine ganglion block, which composition comprises a local anaesthetic formulated for administration as a nasal spray.
2. The composition for use according to claim 1, wherein the disease or disorder is a post dural puncture headache.
3. The composition for use according to claim 2, wherein the post dural puncture headache is a sequela to spinal anaesthesia or epidural catheterisation.
4. The composition for use according to claim 2 or claim 3, which is to be administered to a patient for whom an epidural blood patch is contraindicated.
5. The composition for use according to claim 4, wherein the patient is suffering from at least one of: obesity, scoliosis, a coagulopathy, a systemic infection, a localised infection at a lumbar puncture site.
6. The composition for use according to claim 1, wherein the disease or disorder is a cluster headache or a migraine headache.
7. The composition for use according to any preceding claim, wherein the local anaesthetic comprises an amino amide local anaesthetic.
8. The composition for use according to claim 7, wherein the amino amide local anaesthetic comprises bupivacaine and/or ropivacaine.
9. The composition for use according to claim 8, wherein the amino amide local anaesthetic comprises levo-bupivacaine.
10. The composition for use according to any of claims 4 to 6, wherein the amino amide local anaesthetic comprises lidocaine.
11. The composition for use according to any preceding claim, which is to be co-administered with a nasal decongestant, the nasal decongestant being a vasoconstrictor.
12. The composition for use according to any of claims 1 to 10, further comprising a nasal decongestant, the nasal decongestant being a vasoconstrictor.
13. The composition for use according to claim 11 or claim 12, wherein the nasal decongestant is an adrenergic agonist.
14. The composition for use according to claim 13, wherein the nasal decongestant is an alpha-adrenergic agonist.
15. The composition for use according to claim 14, wherein the alpha-adrenergic agonist comprises xylometazoline and/or oxymetazoline.
16. The composition for use according to any preceding claim, further comprising a pH buffering agent.
17. The composition for use according to any preceding claim, which is to be administered to a patient in a supine position.
18. A kit comprising: a local anaesthetic; and a nasal decongestant, wherein the nasal decongestant is a vasoconstrictor.
19. The kit according to claim 18, wherein the local anaesthetic comprises an amino amide local anaesthetic.
20. The kit according to claim 18 or claim 19, wherein the nasal decongestant is an adrenergic agonist.
21. A nasal spray device, comprising: a reservoir holding a composition; an applicator coupled to the reservoir, the applicator being configured for insertion into a nose of a patient; and a pump for driving the composition from the reservoir through the applicator and into the nose of the patient; wherein the composition comprises a local anaesthetic and a nasal decongestant in a pharmaceutically-acceptable fluid carrier, the nasal decongestant being a vasoconstrictor.
22. The nasal spray device according to claim 21, wherein the applicator is formed of a pliable material and is suitable for atraumatic insertion into the nose of the patient.
23. The nasal spray device according to claim 19 or claim 20, wherein the applicator has a length in the range 6 to 10 cm.
24. The nasal spray device according to any of claims 19 to 21, which is configured to be operated in an inverted orientation.