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1. AU2002231970 - Mucoadhesive pharmaceutical formulations

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]
P: OPERIln\2002231970 r~es doc- 131)32007
THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:
1.    A cannabis-based pharmaceutical formulation which comprises both the cannabinoids cannbidiol (CBD) and tetrahydrocannabinol (THC), or the cannabinoids tetrahydrocannabinovarin (THCV) and cannabidivarin (CBDV), in a pre-defined ratio by weight wherein the formulation is in a liquid dosage form producing particles having a mean aerodynamic particle size between 15 and 45 microns.
2.    A pharmaceutical formulation according to claim 1 wherein the particle size is between 20 and 40 microns.
3.    A pharmaceutical formulation according to claim 1 wherein the average particle size is about 33 microns.
4.    A pharmaceutical formulation according to claim 1 which comprises both the cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC) in approximately equal amounts by weight.
A pharmaceutical formulation according to claim 1 which comprises both the cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC), wherein the THC is present in an amount by weight which is greater than the amount by weight of CBD.
6. A pharmaceutical formulation according to claim 1 which comprises both the cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC), wherein the CBD is present in an amount by weight which is greater than the amount by weight
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7.    A formulation according to claim 1 which is substantially free of cannabinoids other than CBD and THC.
8.    A formulation according to claim 1 which is substantially free of other cannabinoids found in Cannabis sp.
9.    A formulation according to claim 1 wherein said CBD and THC are in substantially pure form.
A formulation according to claim 1 which further comprises one or more other cannabinoids.
11.   A formulation according to claim 10 wherein the one or more other cannabinoids are tetrahydrocannabinovarin (THCV) and/or cannabidivarin (CBDV).
12.   A formulation according to claim 1 wherein the CBD and THC are derived from at least one extract from at least one Cannabis plant, said at least one extract comprising all the naturally occurring cannabinoids in said plant.
13.   A formulation according to claim 12 wherein the Cannabis plant is selected from Cannabis sativa, Cannabis indica, a genetic cross between them, a self-cross or a hybrid thereof.
14.   A formulation according to claim 13 wherein the Cannabis plant is Cannabis sativa, subspecies indica and is selected from var. indica and var. kafiristanica.
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A formulation as claimed in claim 12 which comprises extracts from two or more different Cannabis varieties.
16. A formulation according to claim 12 wherein said extract is prepared by supercritical or sub-critical fluid Cc extraction of dried Cannabis plant.
17. A method of preparing a Cannabis-based pharmaceutical formulation which comprises CBD and THC in a pre-defined ratio by weight or CBDV and THCV in a pre-defined ratio by weight which method comprises the steps of:
a) providing at least one dried Cannabis plant for which the amount of CBD and THC or CBDV and THCV by weight is known;
b) preparing an extract of said at least one Cannabis plant;
c) formulating a material from said extract or extracts prepared in step b) which exhibits said pre-defined ratio of CBD to THC or CBDV to THCV; and
d) further formulating the product of step c) into a pharmaceutical formulation in a liquid dosage form producing particles having a mean aerodynamic particle size between and 45 microns.
18. A method according to claim 17 wherein the extract of step b) is prepared using at least one of the following procedures:
i)    maceration  P OPERKmQ2002231970 r I.doc-1303/2007
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ii) percolation
iii) extraction with solvent such as C1-C5 alcohols, norflurane or HFA227
iv) subcritical or supercritical fluid extraction.
19.   A method according to claim 17 wherein prior to extraction said dried Cannabis is heated to a temperature of from about 600C to about 2250C, to decarboxylate the acid form of any cannabinoids present in the extract.
A method according to claim 19 wherein the Cannabis is heated to a temperature of from about 1000C to about 1500C.
21.   A method according to claim 17 which comprises extracting said at least one Cannabis plant with supercritical or subcritical CO2
22.   A method according to claim 21 wherein after extraction with said supercritical or subcritical fluid said extract is subjected to "winterisation" to remove waxes from the extract.
23.   A formulation according to claim 1 which allows delivery of at least 1.0 mg of cannabinoids per 0.1 ml of liquid formulation.
24. A formulation according to claim 12 which is a botanical drug product prepared from a botanical drug substance.
P:\OPERMKhn202231970 ral doe-I 3M07
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A formulation according to claim 12 wherein each extract is derived from a specific chemovar.
26.   A formulation according to claim 24 wherein the botanical drug substance has an HPLC profile with THC, CBD and CBN having retention times of 9.6-10.6 minutes, 5.4-5.9 minutes and 7.9-8.7 minutes respectively.
27. A formulation according to claim 26 wherein the extract comprises a CBD herbal drug extract having a chromatographic profile as shown below.
28.   A formulation according to claim 26 wherein the extract comprises a THC herbal drug extract having a chromatographic profile as shown below.
P \OPERKtbnl2002231970 r I doc-133/2007
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29. A pharmaceutical formulation according to claim 1 which comprises both the cannabinoids tetrahydrocannabinovarin (THCV) and cannabidivarin (CBDV) wherein the CBDV is present in an amount by weight which is greater than the amount by S 5 weight of THCV.
Cc-1 30. A formulation according to claim 29 which further Ocomprises CBD and/or THC.
(N
31. A formulation according to claim 29 which is substantially free from other cannabinoids found in Cannabis sp.
32. A formulation according to claim 29 wherein the CBDV and THCV form part of an extract from a Cannabis plant, said extract comprising all of the naturally occurring cannabinoids in said plant.
33. A formulation according to claim 32 wherein the Cannabis plant is selected from Cannabis sativa, Cannabis indica or a genetic cross between them, a self-cross or a hybrid thereof.
34. A formulation according to claim 29 which allows delivery of at least 1.0 mg of cannabinoids per 0.1 ml of liquid formulation.
A formulation according to claim 32 which is a botanical drug product prepared from a botanical drug substance.
S-87-S36. A formulation according to claim 32 wherein each
Sextract is derived from a specific chemovar.
37. A pharmaceutical formulation which comprises both the S 5 cannabinoids THC and THCV wherein the THCV is present in an amount by weight which is approximately equal to or greater C-i than the amount by weight of THC.
38. A pharmaceutical formulation according to claim 37 wherein the ratio by weight of THCV to THC is between 99:1 and 1.5:1.
39. A formulation according to claim 37 wherein the ratio by weight of THCV to THC is approximately 17:3.
A formulation according to claim 37 which also comprises CBD and/or CBDV at an amount by weight which is less than the amount by weight of THCV.
41. A formulation according to claim 37 wherein the THCV and THC form part of an extract from a Cannabis plant, said extract comprising all the naturally occurring cannabinoids in said plant.
42. A formulation according to claim 41 wherein said Cannabis plant is selected from Cannabis sativa, Cannabis indica or the result of a genetic cross between them, a self-cross or a hybrid thereof.
43. A method of preparing a Cannabis-based pharmaceutical formulation which comprises a pre-determined ratio by weight of THCV to THC which method comprises the steps of: a) providing at least one dried Cannabis plant for which the amount of THCV and THC by weight is known;
b) preparing an extract of said at least one Cannabis plant;
c) formulating a material from said extract or extracts prepared in step b) which exhibits said pre-defined ratio of THCV to THC; and
d) further formulating the product of step c) into a pharmaceutical formulation with a pharmaceutically acceptable carrier or diluent.
44.   A method according to claim 43 wherein the extract of step b) is prepared using at least one of the following procedures:
i) maceration
ii) percolation
iii) extraction with solvent such as Ci-C 5 alcohols, norflurane or HFA227
iv) subcritical or supercritical fluid extraction.
45.   A method according to claim 43 wherein prior to extraction said dried Cannabis is heated to a temperature of from about 600C to about 2250C to decarboxylate the acid form of any cannabinoids present in the extract.
46.   A method according to claim 45 wherein the Cannabis is heated to a temperature of from about 1000C to about 1500C.
P \OPERKlbm2002231970 r I doc- I 332007
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47.   A method according to claim 43 which comprises extracting said at least one Cannabis plant with supercritical or subcritical CO2
48.   A method according to claim 43 wherein after extraction with said supercritical or subcritical fluid said extract is subjected to "winterisation" to remove waxes from the extract.
49. A method of treating inflammatory disease or any disease or condition during the course of which oxidative stress plays a part comprising administering to a patient a Cannabis-based pharmaceutical formulation according to claim 1i.
A method of treating inflammatory disease as claimed in claim 49 wherein said administration is to the buccal cavity or sub-lingual mucosa.
51. A method of treating rheumatoid arthritis, or inflammatory bowel disease or Crohn's disease comprising administering to a patient a Cannabis-based pharmaceutical formulation according to claim 1.
52. A method of treating rheumatoid arthritis or inflammatory bowel disease or Crohn's disease as claimed in claim 51 wherein said administration is to the buccal cavity or sub-lingual mucosa.
53. A method of treating psychotic disorders, epilepsy, movement disorders, stroke, head injury, or diseases which P:\OPER'Kbm,202231970 r,.l doc- 133/2007
require appetite suppression comprising administering to a patient a Cannabis-based pharmaceutical formulation according to claim 1.
54.   A method of treating psychotic disorders, epilepsy, movement disorders, strokes, head injury or diseases which require appetite suppression as claimed in claim 53 wherein said administration is to the buccal cavity or sub-lingual mucosa.
A method of treating multiple sclerosis, spinal cord injury, peripheral neuropathy or other neurogenic pain comprising administering to a patient a Cannabis-based pharmaceutical formulation according to claim 1.
56. A method of treating multiple sclerosis, spinal cord injury, peripheral neuropathy or other neurogenic pain as claimed in claim 55 wherein said administration is to the buccal cavity or sub-lingual mucosa.
57. A method of treating cancer pain or migraine or for stimulation of appetite comprising administering to a patient a Cannabis-based pharmaceutical formulation according to claim 1.
58. A method of treating cancer pain or migraine or for stimulation of appetite as claimed in claim 57 wherein said administration is to the buccal cavity or sub-lingual mucosa.
59. The method of treating cancer pain, migraine, multiple sclerosis, spinal cord injury, peripheral neuropathy, other
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neurogenic pain, rheumatoid arthritis, inflammatory bowel disease, psychotic disorders (schizophrenia), epilepsy, movement disorders, stroke, disease modification in RA and other inflammatory conditions or for stimulation or suppression of the appetite by administering buccally or sublingually an effective amount of the Cannabis-based pharmaceutical formulation of claim 1.
A Cannabis-based pharmaceutical formulation which is obtained by the method of claim 17.
61.   A pump-action spray comprising a pharmaceutical formulation according to claim 1.
62.   A pump-action spray according to claim 61 wherein the formulation is delivered through a nozzle such that the mean aerodynamic diameter of the particles produced is between and 45 microns.
63.   A formulation according to claim 1 which is not in the form of a propellant-driven aerosol or a propellant-driven liquid spray.
64.   A formulation according to claim 1 which is in the form of a pump action spray.
Use of a formulation according to claim 1 in the manufacture of a medicament for the treatment of cancer pain, migraine, multiple sclerosis, spinal cord injury, peripheral neuropathy, other neurogenic pain, rheumatoid arthritis, inflammatory bowel disease, psychotic disorders (schizophrenia), epilepsy, movement disorders, stroke, P OPER\Kbml200223197 r0l doc-313)/2007
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disease modification in RA and other inflammatory conditions or for stimulation or suppression of the appetite.
66.   Use according to claim 65 wherein the medicament is formulated for buccal or sublingual administration.
67.   A formulation, method, pump-action spray or use according to any one of claims 1 to 66, substantially as hereinbefore described and/or exemplified.