INHALABLE CANNABINOID COMPOSITIONS AND USES

Abstract

An inhalable composition comprising: one or more cannabinoids or a pharmaceutically acceptable derivative or salt thereof; a propellant comprising HFA-152a; and a glycol and/or glycol ether.

Claims

1. An inhalable composition comprising: one or more cannabinoids or a pharmaceutically acceptable derivative or salt thereof; a propellant comprising HFA-152a; and at least one of a glycol and a glycol ether.

2. The inhalable composition of claim 1, wherein the composition comprises less than 1% w/w ethanol.

3. The inhalable composition of claim 1, wherein the composition comprises less than 0.5% w/w ethanol.

4. The inhalable composition according to claim 1, wherein the composition is free of ethanol.

5. The composition according to claim 1, wherein the one or more cannabinoids is selected from tetrahydrocannabinol (THC), preferably dronabinol, cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabivarin (THCV), cannabigerol (CBG), cannabidivarin (CBDV) and cannabichromene (CBC).

6. The composition according to claim 1, wherein the one or more cannabinoids is dronabinol.

7. The composition according to claim 1 comprising from 0.01 to 15% w/w of the one or more cannabinoids or pharmaceutically acceptable derivatives or salts thereof based on the total weight of the composition.

8. The composition according to claim 1, wherein the at least one of the glycol and the glycol ether is selected from the group consisting of propylene glycol, polypropylene glycol, polyethylene glycol (PEG), and combinations of two or more thereof.

9. The composition according to claim 1, wherein the at least one of the glycol and the glycol ether is propylene glycol and the composition comprises from 0.01 to 5% w/w propylene glycol, based on the total weight of the composition.

10. The composition according to claim 1, wherein the at least one of the glycol and the glycol ether is propylene glycol and the composition comprises from 0.1 to 2% w/w propylene glycol, based on the total weight of the composition.

11. The composition according to claim 1, wherein the composition further comprises a human TAS2R bitter taste receptor agonist.

12. The composition according claim 1, wherein the composition further comprises saccharin in an amount by weight from 0.001% w/w to 0.1% w/w.

13. The composition according claim 1 comprising at least 60% w/w propellant, based on the total weight of the composition.

14. The composition according claim 1 further comprising a flavour component, preferably selected from at least one of peppermint oil, aniseed, chocolate, coco, menthol, and vanillin.

15. The composition according to claim 14, wherein the composition comprises up to 0.1% w/w menthol, based on the total weight of the composition.

16. The inhalable composition of claim 1 for use as a medicament in the treatment of a subject wherein the composition is administered in the form of an aerosol having a fine particle fraction of 60% or more.

17. The composition for use according to claim 16, wherein the fine particle fraction is 70% or more.

18. The composition for use according to claim 16, wherein the fine particle fraction is 75% or more.

19. The composition for use according to claim 16, wherein the subject is suffering from a condition selected from: neuropathic pain, cannabis addiction, nausea, motion sickness, arthritis and neurodegenerative diseases such as Alzheimer's, Parkinson's and multiple sclerosis.

20. The composition for use according to claim 16, wherein the subject is a human.

21. An inhalable composition comprising: one or more cannabinoids or a pharmaceutically acceptable derivative or salt thereof; a propellant comprising HFA-152a; a monohydric alcohol; and at least one of a glycol and a glycol ether.

22. The inhalable composition of claim 21, wherein the ratio of monohydric or polyhydric alcohol to glycol or glycol ether by weight is from 6:1 to 1:1.

23. The composition according to claim 21, wherein the monohydric alcohol is ethanol.

24. The composition according to claim 23 wherein the composition comprises from 0.01 to 0.5% w/w ethanol, based on the total weight of the composition.

25. A cannabinoid inhaler comprising: a housing; a reservoir within the housing containing an inhalable composition, wherein the inhalable composition includes: one or more cannabinoids or a pharmaceutically acceptable derivative or salt thereof, a propellant comprising HFA-152a, and at least one of a glycol and s glycol ether; a composition flow path from the reservoir and out of a composition outlet at an inhaling end of the housing; and a non-metered breath operated outlet valve for controlling the flow of inhalable composition through the composition flow path.

26. The inhaler according to claim 25, wherein the breath operated inhaler further comprises an air flow path from an inlet spaced from the inhaling end of the inhaler to an air outlet at the inhaling end, the air flow path being configured such that suction on the inhaling end causes flow through the air flow path which causes the breath operated valve to open, the air outlet being positioned adjacent to the composition outlet, such that air from the air outlet impinges on the composition leaving the composition outlet.

27. The inhaler according to claim 26, wherein there is a respective air flow outlet on either side of the inhalable composition outlet.

28. The inhaler according to claim 27, wherein the air flow outlets are directed towards a composition plume emitted, in use, from the inhaler to break up the particle size of the composition plume.

29. The inhaler according to claim 25 wherein the outlet valve comprises: a flexible diaphragm within the housing and being positioned so as to be influenced by the air flowing through the air flow path; a valve element movable with the diaphragm and biased by a biasing force into a position in which it closes the composition flow path; wherein suction on the inhaling end causes a flow through the air flow path providing a pressure differential across the diaphragm thereby lifting the valve element against the biasing force to open the composition flow path; and wherein the biasing force is arranged to close the composition flow path once the suction ceases.

30. The inhaler according to claim 29, further comprising a first air flow path partly defined by one side of the diaphragm, a second air flow path partly defined by the opposite side of the diaphragm, each flow path having an opening at the outlet end, wherein the air flow paths are arranged such that suction at the outlet end results in a pressure differential across the diaphragm that moves the diaphragm and hence moves the valve element against the biasing force to open the composition flow path.

31. The inhaler according to claim 25, wherein at least a portion of the flow path is a deformable tube, and the outlet valve is provided by a clamping member which pinches the deformable tube closed when no suction force is applied to the inhaling end to close the composition flow path and releases the tube to open the composition flow path when suction is applied at the inhaling end.

32. The inhaler according to claim 25, wherein there is a single diaphragm and valve element.

33. The inhaler according to claim 25, further comprising tube having an internal bore leading from an inlet on a main axis of the housing a reservoir outlet.

34. The inhaler according to claim 33, wherein the inlet of the bore is in the vicinity of the centroid of the volume of the reservoir.

35. The inhaler according to claim 25, further comprising a refill valve in communication with the reservoir via which the reservoir may be refilled.

36. The inhaler according to claim 25, wherein the reservoir is pressurised, preferably wherein the inhalable composition further comprises a propellant.

37. The inhaler according to claim 36, wherein the size of the reservoir, the pressure within the reservoir, and the size of the composition flow path at its narrowest point are arranged so that, when the outlet valve is fully opened, the reservoir will discharge in less than 30 seconds.

38. The inhaler according to claim 25, wherein the inhaler is configured to eject the inhalable composition therefrom in the form of droplets, at least 99% vol of the droplets having a diameter of less than 10 microns.

39. A pressurised container containing a composition consisting of: one or more cannabinoids or a pharmaceutically acceptable derivative or salt thereof; a propellant comprising HFA-152a; and at least one of glycol and a glycol ether.

40. The pressurised container of claim 39 pressurised to a pressure of from 3×10.sup.5 Pa to 1.5×10.sup.7 Pa.

41. A method of manufacturing a composition, the method comprising: preparing a pre-mixture comprising a glycol or glycol ether, and at least one of a monohydric alcohol, a TAS2R taste receptor agonist, and flavouring component; adding one or more cannabinoids or pharmaceutically acceptable derivatives or salts thereof, to the pre-mixture to obtain a cannabinoid-containing mixture; and adding a propellant to the cannabinoid-containing mixture, wherein the propellant comprises HFA-152a.

42. The method according to claim 41, wherein the composition comprises at least one of the TAS2R taste receptor agonist and flavouring component, and wherein the glycol or glycol ether are combined before at least one of the TAS2R taste receptor agonist and flavouring component are added.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0099] FIG. 1 is an exploded perspective view of an inhaler;

[0100] FIG. 2 is a schematic axial cross-section through the outlet end of the inhaler in the plane containing an air flow path and with the vane removed for clarity;

[0101] FIG. 3 is a perspective view of the outlet end of the inhaler with the cover, vane and diaphragm removed to show the air flow paths;

[0102] FIG. 4 is a perspective view of the outlet end of the inhaler;

[0103] FIG. 5 is a plan view of the inhaler;

[0104] FIG. 6 is a full cross-section of the inhaler;

[0105] FIG. 6A is a cross-section through line 6A-6A in FIGS. 6; and

[0106] FIGS. 7-9 are cross-sectional views of an inhaler of a second example in various orientations.

[0107] To facilitate understanding, identical reference numerals have been used, where possible, to designate identical elements that are common to the figures. It is contemplated that elements and features of one embodiment may be beneficially incorporated in other embodiments without further recitation.

DETAILED DESCRIPTION

[0108] So that the manner in which the above recited features of the present disclosure can be understood in detail, a more particular description of the disclosure, briefly summarized above, may be had by reference to embodiments, some of which are illustrated in the appended drawings. It is to be noted, however, that the appended drawings illustrate only exemplary embodiments and are therefore not to be considered limiting of its scope, may admit to other equally effective embodiments.

[0109] The inhaler described below is based on that disclosed in WO 2010/073018. For further details of the device and its refill mechanism, reference is made to WO 2009/001078 and WO 2011/095781.

[0110] As shown in FIG. 1, the inhaler comprises a housing 1 which is broadly divided into two parts. The distal part is a reservoir 2 and the proximal part is the breath-activated valve mechanism 3. At the refill end 4 is a refill valve 5 allowing the reservoir to be filled. The reservoir may contain a wick 6 as shown in FIG. 6 and disclosed in WO 2011/107737. At the opposite end is the outlet end 7 which will be described in more detail below.

[0111] An elastomeric insert 10 (described in greater detail in GB 1305496.0) in the form of a tube open at both ends is inserted from the distal end. This insert 10 is normally pinched closed by a valve element 11 which is biased downwardly by a spring 12. This pinch closed valve mechanism is described in greater detail in WO 2011/015825.

[0112] The valve element 11 is part of a vane 13 which extends along most of the outlet end of the inhaler. The vane 13 is surrounded by a diaphragm 14 which extends across the entire lower face of the vane 13, with the exception of the orifice through which the valve element 11 projects. This valve element is sealed around its periphery to the surrounding housing. At the distal end of the diaphragm 14 is a kink 15 which provides some degree of freedom for the vane 13 to move up and down. The opposite end of the vane 13 is integral with a surrounding frame that is fitted into the housing such that there is a direct connection between the frame and vane to provide a hinge about which the vane pivots.

[0113] A mechanism for opening the valve element 11 against the action of the spring 12 will now be described.

[0114] This is achieved by first 16 and second 17 air flow paths as best shown in FIG. 2. The first flow path 16 is above the diaphragm 14 with the top of the flow path being formed by housing part 18 which is fixed to the housing 1 once the valve elements are in place. The first air flow path is essentially provided by a first air flow path outlet orifice 19 which leads into the space occupied by the vane 13 above the diaphragm 14. This flow path has no other orifices.

[0115] The second air flow path 17 is below the diaphragm 14 and is defined by a pair of second air flow path inlet orifices 20 (only one of which is shown in FIG. 2). In the present example, the second air flow path is actually defined by two separate paths which extend from the inlet orifices 20 along passages 17 which are defined by the housing 1 on the lower surface and the diaphragm 11 at its upper surface and which extends alongside the second portion 9 of the reservoir to the outlet end terminating at a pair of second air flow path outlet orifices 21 which are smaller than the corresponding inlet orifices 20 and are directed towards it to break up the particle size of the composition plume as described in greater detail in GB 1215282.3. The flow through the second air flow path is depicted by arrows in the lower part of FIG. 2 and in FIG. 3. Baffles 22 are provided along the second air flow path 17 to increase the flow resistance in this path.

[0116] As a user sucks on the outlet end 7, air is sucked out of the first flow path outlet orifice 19 thereby lowering the pressure in the first air flow path 16. At the same time, air is drawn in through the second flow path air inlet orifices 20. As these are larger than the second flow path outlet orifices 21, a choking effect aided by the baffles 22 effectively causes pressure to increase in the second air flow path. A combination of a reduced pressure above the vane and a raised pressure below the vane 13 causes the vane to be moved upwardly deforming the diaphragm 14 and raising the valve element against the action of the spring 12. When a user stops sucking on the outlet end 7, the pressure above and below the diaphragm 14 equalises and the spring 12 returns the valve element 11 to a position in which it pinches the insert 10 closed.

[0117] A second example of an inhaler is shown in FIGS. 7 to 9. This is described in greater detail in GB 1305494.5. In place of the wick 6, this example is provided with a tube 30 having an internal bore 31 leading to the insert 10 at the opposite end of tube 31.

[0118] At the inlet end 32 of the tube 30, the bore 31 has an inlet 33 which is supported by a support 34 so that the inlet end 32, and preferably the inlet 33 of the bore 31 is on the main axis X of the housing 1 as shown in FIG. 7.

[0119] It will be appreciated from the drawings that the shape of the reservoir is complex. The right hand portion has a generally cylindrical configuration occupying the majority of the diameter of the device while the left hand portion of the reservoir may just be the internal bore 31 of the tube, or there may be a portion of the reservoir on either side of this tube. Further, in the right hand portion, the volume of the reservoir is reduced by the inlet end portion of the tube 30, the support 34, and the refill valve assembly 5. Thus, while the volume of the reservoir 4 can be determined by measuring these components, it may be simpler to determine this experimentally.

[0120] The operation of the device will now be described with reference to FIGS. 7 to 9.

[0121] When a user sucks on the outlet end 7, the outlet valve 3 opens as previously described. Provided that the inlet 33 of the bore 31 is below the level L of the liquid in the reservoir, the liquid will travel along the bore 31 and will be atomised downstream of the outlet valve element 11 to create a plume for inhalation. FIGS. 7 to 9 show the centroid C of a body of liquid filling the reservoir 4. The inlet 33 of the bore 31 is in the vicinity of the centroid. In this specific example shown in FIG. 1, it is displaced by 1.3 mm from the centroid C towards the refill end 4. In the horizontal orientation shown in FIG. 1, all of the liquid above the level L which represents approximately 50% of the total liquid in the reservoir can be inhaled from the inhaler. When the inhaler is in the tip-down configuration shown in FIG. 2, as the inlet 33 is displaced from the centroid C as described above, slightly more liquid is available than it is in FIG. 1. Conversely, in the tip-up configuration, slightly less liquid is available for inhalation. In a different arrangement, the inlet 33 is at the centroid C, so that there is essentially no variation in dispensing between the three positions. The current preference is for a slight displacement of the inlet 33 towards the refill end from the centroid C as shown as this causes slightly more liquid to be dispensed in the more common tip-down orientation.

[0122] Once the cigarette reaches the liquid level position L shown in FIGS. 7 to 9 with the reservoir approximately half full, no further liquid can be inhaled and the inhaler then needs to be refilled via the refill valve 5.

[0123] The foregoing detailed description has been provided by way of explanation and illustration, and is not intended to limit the scope of the appended claims. Many variations in the presently preferred embodiments illustrated herein will be apparent to one of ordinary skill in the art and remain within the scope of the appended claims and their equivalents.