LIQUID FORMULATION
An electronic cigarette liquid formulation (e-liquid) comprising cannabidiol, a stabiliser and a liquid carrier; wherein the liquid carrier comprises 60-100% v/v propylene glycol, 0-40% v/v glycerol, and 0-40% v/v of one or more triglyceride compounds; and the stabiliser comprises a head portion and a tail portion, wherein the head portion includes one or more reducing moieties and the tail portion comprises a C3-C20 straight or branched aliphatic chain, wherein the stabiliser is soluble or miscible with the liquid carrier.
The present invention relates to liquid formulations and in particular to liquid formulations containing cannabidiol. It also relates to e-cigarette liquids (vaping liquids or vaping formulations) containing cannabidiol.
Electronic cigarette (E-cigarette) liquids or formulations typically include nicotine in a liquid carrier comprising principally propylene glycol. However, it is proposed to replace some or all of the nicotine with cannabidiol.
Cannabidiol (2-[(1R, 6R)-6-isopropenyl-3-methylcyclohex-2-en-1yl]-5-pentylbenzene-1,3-diol) is one of at least 85 active cannabinoids found in cannabis. Cannabidiol (hereinafter referred to as “CBD”) is considered to be a safer alternative to tetrahydrocannabinol (THC) as it produces less or no short term memory impairment in subjects. It is also considered not to generate the feelings of anxiety often associated with the use of THC.
The structure of CBD is as follows:
It will be appreciated that the two hydroxyl groups on the benzene ring may be readily oxidised. It has been found that formulations of CBD in a liquid carrier comprising propylene glycol result in the discolouration of the liquid. Without wishing to be bound by theory, this is believed to be a result of the oxidation of at least one of the hydroxyl groups of the CBD molecule, likely by the propylene glycol component.
Furthermore, it is known that CBD is largely insoluble in water, but it is soluble in organic solvents, including propylene glycol.
According to a first aspect of the invention, there is provided an electronic cigarette liquid formulation (e-liquid) comprising cannabidiol, a stabiliser and a liquid carrier; wherein the liquid carrier comprises 60-100% v/v propylene glycol, 0-40% v/v glycerol, and 0-40% v/v of one or more triglyceride compounds; and the stabiliser comprises a head portion and a tail portion, wherein the head portion includes one or more reducing moieties and the tail portion comprises a C3-C20 straight or branched aliphatic chain, wherein the stabiliser is soluble or miscible with the liquid carrier.
Electronic cigarette liquid formulations may also be referred to as an e-cigarette liquid or simply an e-liquid. They are also sometime referred to as vaping liquids or vaping formulations.
It will be appreciated that the major component of the liquid carrier is propylene glycol, which comprises at least 60% by volume of the liquid carrier. Thus, reference to % v/v above refers to the percentage by volume of the liquid carrier. The liquid carrier may also contain glycerol and/or one or more triglyceride compounds. As triglyceride compounds tend to be derived from natural sources, they are typically provided in the form of a mixture of compounds. Further liquid components may be included in the liquid carrier.
The head portion of the stabiliser is typically a stronger reducing agent than CBD and thus is preferentially oxidised. The head portion of the stabiliser therefore acts as an anti-oxidant for the CBD formulation.
The tail portion of the stabiliser is required to ensure that the stabiliser is soluble or miscible in the formulation. The aliphatic group may be a branched or straight chain alkyl (alkane) group, a branched or straight chain alkene group or a branched or straight chain alkyne group. In embodiments in which the aliphatic chain is unsaturated, it may be mono unsaturated or polyunsaturated.
The head portion of the stabiliser may be a hydroxyl substituted 5- or 6-membered carbocyclic or heterocyclic ring. In embodiments in which the ring is a heterocyclic ring, it may contain one or more heteroatoms each independently selected from oxygen, nitrogen and sulphur. Suitably, the heteroatom is an oxygen atom.
Examples of suitable head portions include:
Ascorbic acid derivatives, such as:
Wherein R1 is a C3-C20 aliphatic tail portion, optionally coupled to the head portion via a linker moiety.
Hydroquinone derivatives, such as:
Wherein R2 and R3 are each independently selected from H, a C1-C6 alkyl group and a C3-C20 aliphatic tail portion optionally coupled to the head portion via a linker moiety, provided that at least one of R2 and R3 comprises an aliphatic tail portion.
Hydroxychromane derivatives, such as:
Wherein R4, R5, R6 and R7 are each independently selected from OH, H, and a C1-C3 alkyl group, wherein at least one of R4, R5, R6 and R7 is OH; and R8 is a C3-C20 aliphatic tail portion, optionally coupled to the head portion via a linker moiety.
Hydroxyanisole derivatives, such as:
Wherein R9 and R10 are each independently selected from H, a C1-C6 alkyl group and a C3-C20 aliphatic tail portion, optionally coupled to the head portion via a linker moiety, provided that at least one of R9 and R10 comprises an aliphatic tail portion.
Hydroxytoluene derivatives, such as:
Wherein R11 and R12 are each independently selected from H, a C1-C6 alkyl group and a C3-C20 aliphatic tail portion, optionally coupled to the head portion via a linker moiety, provided that at least one of R11 and R12 comprises an aliphatic tail portion.
Gallic acid derivatives, such as:
Wherein R13 is a C3-C20 aliphatic tail portion.
In the above examples, the linker group, where present, may be selected from —O—, —O(O)C—, —C(O)—, —N(H)C(O)— and —N(H)—. The aliphatic tail portion is suitably a branched or straight chain alkyl group containing 3 to 20, suitably 6 to 20, 7 to 20, 10 to 20 or 12 to 18 carbon atoms.
A suitable stabiliser comprises an ascorbic acid derivative as shown above, wherein R1 is a C6-C20 straight or branched aliphatic chain connected to the ascorbic acid head group via a —C(O)— linker group:
Wherein R14 is a C3-C20 aliphatic tail portion. R14 may be a C3-C20 branched or straight chain alkyl group, such as for example a C6-C20 alkyl group, a C10-C20 alkyl group or a C12-C20 alkyl group. Thus, the stabiliser may be an ascorbate ester of a long chain fatty acid having from 6 to 20 carbon atoms, 7 to 20 carbon atoms, 8 to 18 carbon atoms or 10 to 16 carbon atoms. The long chain fatty acid may be unsaturated, monounsaturated or polyunsaturated. For example, the stabiliser may be an ascorbyl ester of palmitic acid, which has a chain comprising 16 carbon atoms.
As the formulation is intended for human consumption, suitably in the form of an e-cigarette formulation, the stabiliser may already be approved for human consumption and/or as an approved food additive. For example, it may already have an “E” number.
One such example of an approved food additive is ascorbyl palmitate which is also known as E304 and is approved in the EU, the US, Australia and New Zealand.
Further examples include:
Tocopherols (E306) which have the following formula:
Wherein R4 and R6 are each independently H or CH3; R5 is OH; R7 is CH3; and R8 is a C16 branched chain alkyl group;
Propyl gallate (E310):
Wherein R13 is a propyl group;
Tertiary butylhydroquinone (E319):
Wherein R2 is a tertiary butyl group and R3 is H;
Butylated hydroxyanisole (E320):
Wherein R9 is a tertiary butyl group and R10 is H; and
Butylated hydroxytoluene (E321):
Wherein R11 and R12 are each independently a tertiary butyl group.
The CBD may be present in the formulation in an amount of 10 mg/ml to 300 mg/ml. The volume (ml) value refers to the volume of the liquid carrier. The lower limit on the amount of CBD in the formulation may be 15 mg/ml, 20 mg/ml, 25 mg/ml, 30 mg/ml, 35 mg/ml. 40 mg/ml, 45 mg/ml or 50 mg/ml. The upper limit on the amount of CBD present in the formulation may be 250 mg/ml, 200 mg/ml or 150 mg/ml.
The amount of the stabiliser present in the formulation may be 0.5% to 5% by weight of the CBD content. For example, the stabiliser may be present in an amount of 0.5% to 2% by weight or 0.5 to 1.5% by weight of the CBD present in the formulation.
In other words, the ratio (weight/ml) of CBD to stabiliser in the formulation may be 200:1 to 50:1. In certain embodiments of the invention, the stabiliser may be present in the formulation in an amount of 0.05 mg/ml to 5 mg/ml. Again, the volume (ml) refers to the volume of the liquid carrier.
As noted above, the liquid carrier may include glycerol and/or one or more glyceride compounds, suitably one or more plant-derived glyceride compounds. Glycerol and/or glyceride compounds are often present in E-cigarette liquid formulations and facilitate the formation of the vapour for inhalation when heated within the electronic cigarette.
The formulation may contain nicotine. In an embodiment of the invention, the CBD is intended to replace at least some of the nicotine. Accordingly, the formulation may contain less nicotine than would otherwise be present in an E-cigarette formulation.
Formulations according to the invention may be used to wean users away from nicotine. Accordingly, a number of different formulations may be available which contain a decreasing amount of nicotine. Thus, there may be provided a first formulation which contains CBD and a first amount of nicotine, and a second formulation which contains CBD and a second amount of nicotine, wherein the second amount of nicotine is less than the first amount of nicotine. Optionally, a third formulation may be provided, wherein the third formulation contains CBD and a third amount of nicotine, wherein the third amount of nicotine is less than the second amount of nicotine. Such formulations may be available separately or they may form part of a kit. Thus, an aspect of the invention provides a kit containing a first formulation which contains CBD and a first amount of nicotine and a second formulation which contains CBD and a second amount of nicotine, wherein the second amount of nicotine is less than the first amount of nicotine. In an embodiment of this aspect of the invention, there is provided a kit which further includes a third formulation which contains CBD and a third amount of nicotine, wherein and the third amount of nicotine is less than the second amount of nicotine. In this aspect of the invention, the formulations are as defined herein. The formulations discussed above are suitably formulations as defined in the first aspect of the invention, which also include nicotine. Accordingly, the first, second and optionally third formulations suitably comprise cannabidiol, nicotine, a stabiliser and a liquid carrier; wherein the liquid carrier comprises 60-100% v/v propylene glycol, 0-40% v/v glycerol, and 0-40% v/v of one or more triglyceride compounds; and the stabiliser comprises a head portion and a tail portion, wherein the head portion includes one or more reducing moieties and the tail portion comprises a C3-C20 straight or branched aliphatic chain, wherein the stabiliser is soluble or miscible with the liquid carrier. As noted above, the amount of nicotine in the first, second and third formulations decreases.
The amount of nicotine present in the formulations of the invention may be 0 to 50 mg/ml. Thus, no nicotine may be present in the formulation or, where present, it may be present in an amount of for example 5 to 40 mg/ml, such as 10 to 30 mg/ml.
The formulation may further comprise a flavouring agent. Such flavouring agents are common in the field of E-cigarette liquid formulations. Additionally or alternatively, the formulation may include a scent agent which releases a desired scent when the liquid is heated. In embodiments in which the flavouring component and/or the scent component are liquids, the flavouring component and/or the scent component may be considered to form a part of the liquid carrier. Thus, the liquid carrier may further comprise 0-5% v/v of a liquid flavouring component and 0-5% v/v of a scent component. Suitably the liquid carrier comprises 0-2% v/v of a liquid flavouring component and 0-2% v/v of a scent component.
On the basis that there are numerous legal restrictions associated with tetrahydrocannabinol (THC), the formulation is suitably substantially free from THC. By the term “substantially free”, it is meant that the formulation suitably includes less than 0.1 wt % THC, suitably less than 0.01 wt % or less than 0.001 wt % THC. Optionally, the term “substantially free” means that THC is not detectable in the formulation by HPLC.
A further aspect of the invention provides a cartridge containing an electronic cigarette liquid formulation as defined hereinabove. Such cartridges are suitably configured for location in an electronic cigarette.
A yet further aspect of the invention provides an electronic cigarette including an electronic cigarette liquid formulation as defined herein.
EXAMPLES Comparative Example 1A 20% w/v solution of CBD in propylene glycol with no stabiliser was prepared by dissolving 2 g of CBD in 8 ml of propylene glycol. The solution was placed in an open glass vial and monitored over a period of time. The colour of the solution was monitored during this time and the results are set out below:
It is believed that the colouration of the solution was due to the presence of an oxidised species of the CBD, wherein the CBD was being oxidised by the propylene glycol carrier. The oxidised species is thought to be a quinone derivative of CBD.
Comparative Example 2A 5% w/v solution of CBD was prepared having the following formula:
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- 2.5 ml of the 20% w/v CBD solution of Comparative Example 1
- 3 ml vegetable glycerine
- 4.1 ml propylene glycol
- 0.4 ml menthol solution (200 mg menthol in 1 ml propylene glycol)
The solution was placed in an open glass vial and monitored over a period of time. The colour of the solution was monitored during this time and the results are set out below:
A stabilised CBD solution was prepared by adding 0.2% w/v butylated hydroxyanisole (BHA) to the solution of Comparative Example 1 (2 g CBD and 20 mg BHA in 8 ml propylene glycol). The solution was placed in an open glass vial and monitored over a period of time. The colour of the solution was monitored during this time and the results are set out below:
As can be seen, the rate of oxidation of the CBD in solution is significantly slowed by the addition of the BHA.
Example 2A stabilised CBD solution was prepared by adding 0.05% w/v 6-O-palmitoyl-L-ascorbic acid (6-O-AP) to the solution of Comparative Example 1 (2 g CBD and 5 mg 6-O-AP in 8 ml propylene glycol).
The solution was placed in an open glass vial and monitored over a period of time. The colour of the solution was monitored during this time and the results are set out below:
A stabilised CBD solution was prepared by adding 0.2% w/v 6-O-palmitoyl-L-ascorbic acid (6-O-AP) to the solution of Comparative Example 1 (2 g CBD and 20 mg 6-O-AP in 8 ml propylene glycol). The solution was placed in an open glass vial and monitored over a period of time. The colour of the solution was monitored during this time and the results are set out below:
A stabilised CBD solution was prepared by adding 0.05% w/v 6-O-AP to the solution of Comparative Example 2 to provide a solution having the following formulation:
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- 2.5 ml of the 20% w/v CBD solution of Example 3 (2 g CBD and 20 mg 6-O-AP in 8 ml propylene glycol)
- 3 ml vegetable glycerine
- 4.1 ml propylene glycol
- 0.4 ml menthol solution (200 mg menthol in 1 ml propylene glycol)
The solution was placed in an open glass vial and monitored over a period of time. The colour of the solution was monitored during this time and the results are set out below:
It can be seen that the addition of a stabiliser as defined herein can reduce, slow down or prevent the oxidation of a solution of CBD in propylene glycol.
Claims
1. An electronic cigarette liquid formulation (e-liquid) comprising cannabidiol, a stabiliser and a liquid carrier; wherein the liquid carrier comprises 60-100% v/v propylene glycol, 0-40% v/v glycerol, and 0-40% v/v of one or more triglyceride compounds; and the stabiliser comprises a head portion and a tail portion, wherein the head portion includes one or more reducing moieties and the tail portion comprises a C3-C20 straight or branched aliphatic chain, wherein the stabiliser is soluble or miscible with the liquid carrier.
2. An electronic cigarette liquid formulation according to claim 1, wherein the head portion of the stabiliser includes a hydroxy substituted 5- or 6-membered carbocyclic or heterocyclic ring.
3. An electronic cigarette liquid formulation according to claim 2, wherein the head portion of the stabiliser is derived from ascorbic acid, hydroquinone, hydroxychromane, hydroxyanisole, hydroxytoluene or gallic acid.
4. An electronic cigarette liquid formulation according to an of claim 1, wherein the aliphatic tail of the stabiliser is directly bonded to the head portion or is bonded via a linker group selected from —O—, —O(O)C—, —C(O)—, —N(H)C(O)— and —N(H)—.
5. An electronic cigarette liquid formulation according to claim 1, wherein the stabiliser comprises a head group derived from ascorbic acid, a tail group which is a C6-C20 straight or branched aliphatic chain, and the tail group is connected to the head group via a carboxylate linker group.
6. An electronic cigarette liquid formulation according to claim 5, wherein the stabiliser is an ascorbate ester of a C7-C20 long chain acid.
7. An electronic cigarette liquid formulation according to claim 6, wherein the stabiliser is an ascorbate ester of palmitic acid.
8. An electronic cigarette liquid formulation according to claim 1, wherein the cannabidiol is present in the formulation in an amount of 10 mg/ml to 300 mg/ml.
9. An electronic cigarette liquid formulation according to claim 8, wherein the cannabidiol is present in an amount of 30 mg/ml to 250 mg/ml.
10. An electronic cigarette liquid formulation according to claim 9, wherein the cannabidiol is present in an amount of 50 mg/ml to 200 mg/ml.
11. An electronic cigarette liquid formulation according to claim 1, wherein the stabiliser is present in an amount of 0.05 mg/ml to 5 mg/ml.
12. An electronic cigarette liquid formulation according to claim 1, wherein the ratio of cannabidiol to stabiliser in the mixture is 200:1 to 50:1.
13. An electronic cigarette liquid formulation according to claim 1, wherein the or each triglyceride compound, where present, is derived from a plant source.
14. An electronic cigarette liquid formulation according to claim 1, wherein the formulation further includes nicotine.
15. An electronic cigarette liquid formulation according to claim 1, wherein the formulation further includes a flavouring agent and/or a scent agent.
16. An electronic cigarette liquid formulation according to claim 1, wherein the formulation is substantially free from tetrahydrocannabinol (THC).
Type: Application
Filed: Nov 11, 2016
Publication Date: Nov 15, 2018
Inventors: John Tiley (Herne Bay Kent), Michael Pacey (Herne Bay Kent)
Application Number: 15/775,995
