Cannabinoid-Containing Compositions and Methods for Their Use
This invention relates to cannabinoid-containing compositions, particularly cannabinoid-containing gel formulations and methods for the treatment of traumatic injury, e.g., strains, sprains and contusions, and disease conditions, e.g., arthritis, particularly osteoarthritis. The methods involve topically applying a cannabinoid or a cannabinoid-containing composition to a subject's skin near, or distant from, the area of the injury or the area affected by the disease condition, e.g., an arthritic joint. The cannabinoid-containing composition is preferably a pharmaceutically acceptable gel containing a therapeutically effective amount of a cannabinoid sufficient to alleviate the symptoms associate with the injury or disease condition.
1 . The use of a cannabinoid gel for the preparation of a medicament for the treatment of arthritis, wherein the cannabinoid gel is applied to the skin of a mammal and comprises:
a. a cannabinoid in an amount of about 1% to about 45% (wt/wt) of the composition;
b. a lower alcohol having between 1 and 6 carbon atoms present in an amount of about 15% to about 85% (wt/wt) of the composition;
c. a first penetration enhancer present in an amount of about 0.1% to about 15% (wt/wt) of the composition; and
d. water present in an amount of about 5% to about 45% (wt/wt) of the composition;
wherein, the cannabinoid is selected from the group consisting of: delta-9-tetrahydrocannabinol, delta-8-tetrahydrocannabinol, 6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol, 3-(1,1-dimethylheptyl)-6,6a,7,8,10,10a-hexahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo[b,d]pyran-9-one, (−)-(3S,4S)-7-hydroxy-delta-6-tetrahydrocannabinol-1,1-dimethylheptyl, (+)-(3S,4S)-7-hydroxy-delta-6-tetrahydrocannabinol-1,1-dimethylheptyl, 11-hydroxy-delta-9-tetrahydrocannabinol, delta-8-tetrahydrocannabinol-11-oic acid, (−)-(6S,6aR,9R,10aR)-5,6,6a,7,8,9,10,10a-octahydro-6-methyl-1-3-[(R)-1-methyl-4-phenylbutoxy]-1,9-phenanthridinediol 1-acetate, (R)-(+)-[2,3-dihydro-5-methyl-3-(−4-morpholinylmethyl)-pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenyl-methanone, 2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenedi-ol and 4-(1,1-dimethylheptyl)-2,3′-dihydroxy-6′ alpha-(3-hydroxypropyl)-1′,-2′,3′,4′,5′,6′-hexahydrobiphenyl, cannabinol, cannabidiol, nabilone, levonantradol, (−)-HU-210, (+)-HU-210,11-hydroxy-delta-9-tetrahydrocannabinol, delta-8-tetrahydrocannabinol-11-oic acid, CP 55,940, and R(+)-WIN 55, 212-2; and
wherein the first penetration enhancer is selected from the group consisting of: N-heptane, N-octane, N-nonane, N-decane, N-undecane, N-dodecane, N-tridecane, N-tetradecane, N-hexadecane, ethanol, propanol, butanol, 2-butanol, pentanol, 2-pentanol, hexanol, octanol, nonanol, decanol, benzyl alcohol, oleyl alcohol, caprylic alcohol, decyl alcohol, lauryl alcohol, 2-lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, linoleyl alcohol, linolenyl alcohol, propylene glycol, polyethylene glycol, ethylene glycol, diethylene glycol, triethylene glycol, dipropylene glycol, glycerol, propanediol, butanediol, pentanediol, hexanetriol, propylene glycol monolaurate, diethylene glycol monomethyl ether (transcutol) urea, dimethylacetamide, diethyltoluamide, dimethylormamide, dimethyloctamide, dimethyldecamide, biodegradable cyclic urea, 1-methyl-2-pyrrolidone, 2-pyrrolidone, 1-lauryl-2-pyrrolidone, 1-methyl-4-carboxy-2-pyrrolidone, 1-hexyl-4-carboxy-2-pyrrolidone, 1-lauryl-4-carboxy-2-pyrrolidone, 1-methyl-4-methoxycarbonyl-2-pyrrolidone, 1-hexyl-4-methoxycarbonyl-2-pyrrolidone, 1-lauryl-4-methoxycarbonyl-2-pyrrolidone, N-methyl-pyrrolidone, N-cyclohexylpyrrolidone, N-dimethylaminopropyl-pyrrolidone, N-cocoalkypyrrolidone, N-tallowalkypyrrolidone, esters of N-(2-hydroxyethyl)-2-pyrrolidone, 1-dodecylazacycloheptane-2-one, 1-geranylazacycloheptan-2-one, 1-farnesylazacycloheptan-2-one, 1-geranylgeranylazacycloheptan-2-one, 1-(3,7-dimethyloctyl)-azacycloheptan-2-one, 1-(3,7,11-trimethyldodecyl)azacyclohaptan-2-one, 1-geranylazacyclohexane-2-one, 1-geranylazacyclopentan-2,5-dione, 1-farnesylazacyclopentan-2-one, diethanolamine, triethanolamine, hexamethylenlauramide, octanoic acid, linoleic acid, valeric acid, heptanoic acid, pelagonic acid, caproic acid, capric acid, lauric acid, myristric acid, stearic acid, oleic acid, caprylic acid, isovaleric acid, neopentanoic acid, neoheptanoic acid, neonanoic acid, trimethyl hexaonic acid, neodecanoic acid, isostearic acid, ethyl oleate, isopropyl n-butyrate, isopropyl n-hexanoate, isopropyl n-decanoate, isopropyl myristate (“IPM”), isopropyl palmitate, octyldodecyl myristate, ethyl acetate, butyl acetate, methyl acetate, methylvalerate, methylpropionate, diethyl sebacate, ethyl oleate, butyl stearate, methyl laurate, sodium laurate, sodium lauryl sulfate, sodium octyl sulfate, cetyltrimethylammonium bromide, tetradecyltrimethylammonium, octyltrimethyl ammonium bromide, benzalkonium chloride, octadecyltrimethylammonium chloride, cetylpyridinium chloride, dodecyltrimethylammonium chloride, hexadecyltrimethylammonium chloride, hexadecyl trimethyl ammoniopropane sulfonate, oleyl betaine, cocamidopropyl hydroxysultaine, cocamidopropyl betaine, Polyxamer (231, 182, 184), Polysorbate (20, 60), Brij (30, 93, 96, 99), Span (20, 40, 60, 80, 85), Tween (20, 40, 60, 80), Myrj (45, 51, 52), Miglyol 840, sodium cholate, sodium salts of taurocholic acid, glycolic acids, desoxycholic acids, lecithin, d-limonene, alpha-pinene, beta-carene, alpha-terpineol, terpinen-4-ol, carvol, carvone, pulegone, piperitone, menthone, cyclohexene oxide, limonene oxide, alpha-pinene oxide, cyclopentene oxide, 1,8-cineole, ylang ylang oil, anise oil, chenopodium oil, eucalyptus oil, salicylic acid, salicylates, citric acid succinic acid, 2-hydroxypropyl-beta-cyclodextrin, 2,6-dimethyl-beta-cyclodextrin, alkyl-2-(N,N-disubstituted amino)-alkanoate ester, 2-(n-nonyl)-1,3-dioxolane, diisopropyl adipate, glyceryl monolaurate, tetrahydrofurfuryl alcohol, 2-(2-ethoxyethoxy)ethanol, alkylaryl ethers of polyethylene oxide, polyethylene oxide monomethyl ethers, polyethylene oxide dimethyl ethers, acetoacetic ester, oleoyl macrogolglyceride, caprylocaproyl macrogolylyceride, polyoxyethylene 6 caprylic triglyceride, polyoxyethylene glyceride, PPG-5 ceteth-20, lauroyl macroglyceride oleic acid.
2 . The use of claim 1 wherein the cannabinoid is cannabidiol.
3 . The use of claim 2 , wherein the cannabidiol is present in an amount of about 1% to about 10% (wt/wt) of the composition.
4 . The use of claim 2 , wherein the cannabidiol is present in an amount of about 1.5% to about 3.5% (wt/wt) of the composition.
5 . The use of claim 1 , wherein the first penetration enhancer is selected from the group comprises diethylene glycol monoethyl ether or oleyl alcohol.
6 . The use of claim 1 , wherein the first penetration enhancer is present in an amount of about 0.5% to about 10% (wt/wt) of the composition.
7 . The use of claim 1 , wherein the first penetration enhancer is diethylene glycol monoethyl ether and is present in an amount of about 7.5% (wt/wt) of the composition.
8 . The use of claim 1 , wherein the cannabinoid gel further comprises a second penetration enhancer in the amount of about 0.1% to about 5% (wt/wt) of the composition.
9 . The use of claim 8 , wherein the second penetration enhancer is present in the amount of about 0.1% to about 2% (wt/wt) of the composition.
10 . The use of claim 8 , wherein the second penetration enhancer is isopropyl myristate.
11 . The use of claim 1 , wherein the lower alcohol is ethanol or isopropyl alcohol.
12 . The use of claim 1 , wherein the lower alcohol is present in an amount of about 40% to about 70% (wt/wt) of the composition.
13 . The use of claim 1 , wherein the lower alcohol is present in an amount of about 45% to about 65% (wt/wt) of the composition.
14 . The use of claim 1 , wherein water is present in an amount of about 10% to about 40% (wt/wt) of the composition.
15 . The use of claim 1 , wherein water is present in an amount of about 20% to about 30% (wt/wt) of the composition.
16 . The use of claim 1 , wherein water is present in an amount of about 25% to about 30% (wt/wt) of the composition.
17 . The use of claim 1 , wherein the cannabinoid gel further comprises a thickening agent present in an amount of about 0.1% to about 5% (wt/wt) of the composition.
18 . The use of claim 17 , wherein the thickening agent is selected from the group consisting of: hydroxypropylcellulose, carboxypolymethylene, carboxymethylcellulose, acrylic acid polymer, or neutralized acrylic acid poylmer.
19 . The use of claim 17 , wherein the thickening agent is partially neutralized polyacrylic acid.
20 . The use of claim 17 , wherein the thickening agent is present in an amount of about 1% to about 3% (wt/wt) of the composition.
21 . The use of claim 1 , wherein the composition further comprises a neutralizing agent in an amount of about 0.001% to about 10% (wt/wt) of the composition.
22 . The use of claim 21 , wherein the neutralizing agent is selected from the group consisting of: triethanolamine, 0.1% aqueous sodium hydroxide solution and 1% aqueous sodium hydroxide solution.
23 . The use of claim 21 , wherein the neutralizing agent is triethanolamine and is present in amount of about 0.1% to about 0.2% (wt/wt of the composition.
24 . The use of claim 1 , wherein the cannabinoid gel further comprises a first antioxidant, present in the amount of about 0.01% to about 1% (wt/wt) of the composition.
25 . The use of claim 24 , wherein the first antioxidant is selected from the group consisting of: citric acid, butylated hydroxytoluene, ascorbic acid, glutathione, retinol, α-tocopherol, β-carotene, α-carotene, ubiquinone, butylated hydroxyanisole, ethylenediaminetetraacetic acid, selenium, zinc, lignan, uric acid, lipoic acid, and N-acetylcysteine.
26 . The use of claim 1 , wherein the cannabinoid gel further comprises a second antioxidant present in an amount of about 0.01% to about 1% (wt/wt) of the composition.
27 . The use of claim 26 , wherein the second antioxidant is selected from the group consisting of: citric acid, butylated hydroxytoluene, ascorbic acid, glutathione, retinol, α-tocopherol, β-carotene, α-carotene, ubiquinone, butylated hydroxyanisole, ethylenediaminetetraacetic acid, selenium, zinc, lignan, uric acid, lipoic acid, and N-acetylcysteine.
28 . The use of claim 1 , where in the cannabinoid gel further comprises propylene glycol present in an amount of about 1% to about 25% (wt/wt) of the composition.
29 . The use of claim 28 , wherein the propylene glycol is present in an amount of about 1% to about 20% (wt/wt) of the composition.