TOBACCO EXTRACTION METHODS AND FORMULATIONS

FIELD OF THE INVENTION

The present invention is concerned with processes for extracting tobacco and compositions containing tobacco. In particular, the invention relates to gel based compositions and methods for producing same for use as a cigarette replacement product (CRP) .

BACKGROUND TO THE INVENTION

The use of tobacco has existed for recreational purposes in society for more than six thousand years, whilst the origins of the cigarette date back to about the time of the Crimean war. Tobacco, the dried leaf product of Nicotianna spp, in recent years, when smoked has been shown to cause a broad range of diseases. However, amongst the two thousand or so chemicals the plant contains, several have been shown to be of significant benefit in small amounts, for example nicotine and cotinine. During the last ten years or so a group of medicines known as Nicotine Replacement Therapies (NRTs) have been introduced into the market for use in weaning smokers off smoking. The market for these products has been shown to be small compared to the market for tobacco, ca $10bn to >$350bn.

The globally accepted definition of a tobacco product is one that is derived from the leaves of Nicotiana spp for smoking, chewing or inhaling. Given the widespread trend in society to restrict smoking to fewer and fewer areas by . banning it in most places, it follows that there is a need for a cigarette replacement for those that do not wish to quit smoking. Cigarette replacement should not be confused

with NRTs : these are a range of medicines which contain purified nicotine for use solely to assist in the weaning of a smoker from smoking.

There are no true alternatives to cigarettes currently other than this invention; there are low tar or lower smoke (smokeless) versions and also dummy cigarettes designed solely for putting in one's mouth.

SUMMARY OF THE INVENTION

The present invention sets out a new and novel use for tobacco that circumvents many of the health issues associated with smoking, chewing or inhaling tobacco, but offers all of the benefits of tobacco and as such the present invention is termed a cigarette replacement.

The present invention is simply described, but not limited by, as a tobacco gel for application to the skin, facilitating movement of all the compounds present in tobacco across the skin and, into the bloodstream.

The present invention is completely novel in that it provides a the first cigarette replacement, maintaining the physiological condition of the smoker and thus preventing the craving for cigarettes associated with "cold turkey" .

The current invention is a simple and novel means of delivering a complete tobacco product across the skin in a non-greasy, non-staining aqueous gel and presents a complete alternative to cigarettes, i.e. a cigarette replacement, without the health risks of smoking.

The present invention is a formulation and manufacturing process for a tobacco aqueous gel that is non-staining, non- greasy, allows rapid increase of the active ingredients, is rapidly absorbed and contains all the necessary ancillary ingredients to be stable both chemically and microbiologicalIy.

Accordingly, in a first aspect of the invention there is provided a composition containing tobacco for application to skin. The composition thus contains the compounds present in tobacco in appropriate amounts . The composition is absorbed through the skin to deliver the tobacco compounds to the bloodstream. Importantly, using complete tobacco, that is to say a tobacco based product that mirrors the natural composition of the tobacco plant, provides a much greater beneficial effect in users than use of solely nicotine based compositions.

The composition may take any suitable form for application to the skin. The most preferred composition takes the form of a gel. In one aspect the invention provides a composition containing a tobacco extract which is in the form of a gel . The tobacco extract may be any suitable extract derived from a tobacco plant. The tobacco extract provides a beneficial effect in terms of replicating in the user the physiological condition associated with smoking.

Thus, the invention provides the product arising from the complete extract of tobacco, made into a gel. This is preferably for use as a cigarette replacement, but may be used as an NRT. As discussed herein, the extract of tobacco

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may be derived from the plant stem/leaves/buds/roots. In one embodiment, the quantity of tobacco used pro rata in the final gel volume is equivalent to 50mg to 1Og per application of the gel. More preferred is a quantity of 55mg to Ig of tobacco, even more preferred as 55mg to 500mg and most preferably 55mg to 250mg.

In one embodiment of the invention, a concentrate, syrup, or dried powder is made for the purpose of being used in the manufacture of a cigarette replacement gel or gel to aid quit smoking. Thus, the tobacco extract may take any suitable form.

Where the composition is in the form of a gel it is most preferably an aqueous gel. The gel may, however, be a nonaqueous gel . ■ The gel used to carry the tobacco extract preferably contains a glycol, more preferably a glycol ether and most preferably contains diethylene glycol monoethyl ether. The glycol is present in the final gel composition in an appropriate amount. Preferred is a range between 10 and 50% v/v such as at least 20% v/v, for example 20 to 40% v/v and most preferably around 40% v/v. However, the glycol, in particular diethylene glycol monoethyl ether, may be substituted in part or completely by one or more chemicals which aid the ingress of the tobacco extract across the skin.

In a further embodiment of the invention, the extract from tobacco is not complete but contains both nicotine and cotinine or their salts or derivatives at any (suitable) concentration. In a specific embodiment, the extract from tobacco only contains cotinine or its salts or derivatives .

Similarly, the extract from tobacco may only contain nicotine or its salts or derivatives.

In a preferred formulation, the gel is made using one other or both of xanthan gum or its derivatives and guar gum or its derivatives. In a preferred embodiment xanthan gum is present in the gel composition at 1.5 to 2% w/v, preferably around 1.8% w/v and guar gum is present in the composition at 1.7 to 2.3% w/v, preferably around 2% w/v. However, these gel agents may be substituted in part or completely by other chemicals which result in aqueous gel formation. As mentioned above, in alternative embodiments a non-aqueous gel is formed.

The gel may be provided in any suitable container. For example, the gel may be provided in containers of various volumes . The container may then carry appropriate instructions to indicate to the user the desired volume of gel which should be used in each application. An alternative construction is to pre'sent the gel , in single use packaging, such that a single dosage of the composition is provided in each packaged unit. A preferred dosage is such that it provides the user with approximately the same physiological response as smoking a cigarette. Of course, the exact preferred dosage may be readily determined by an individual user on a case by case basis .

The term "gel" is intended to encompass all semi-solid tobacco containing compositions. Thus, appropriate composition types include all compositions which are suitable for use on the skin and which allow the compounds present in tobacco to be absorbed through the skin into the

bloodstream. In embodiments of the invention, the composition may more specifically take the form of an aerosol, a cream, a lotion, a wax, a liquid, a powder, a foam, a mousse or a shampoo. Thus, the tobacco may be formulated with a suitable carrier and optionally a preservative/stabiliser to allow storage in a suitable container. Other additives may be added as appropriate, such as fragrances, emulsifiers and emollients. From this container, the composition may be easily applied to the skin. For example, in the case of an aerosol, the tobacco may be provided in suspension in a suitable solvent, which is preferably an aqueous solution. Examples of solvents include alcohol and ether based solvents. The aerosol may be applied via a pump spray or via use of a suitable propellant for example. Creams, lotions, waxes etc. may be based upon suitable carriers such as lanolin and paraffin for example. Processes producing liquid tobacco compositions are described in detail below, any extraction using a suitable solvent will produce a composition which can be directly applied to the skin. Preferred liquid compositions are water based compositions. Alcohols may be added as appropriated, including volatile alcohols such as ethanol and propanol and mixtures thereof . A liquid based composition may be used in a roll-on applicator for example. Foam and mousse compositions may incorporate suitable surfactants to allow a composition of the appropriate consistency to be formed.

The concentration of the tobacco in the composition is such that a cigarette equivalent is provided in a suitable volume of the composition. This allows both the compositions of the invention to be provided in suitably proportioned

packaging and more importantly facilitates convenient and effective application of the composition to the skin by the end user. In a specific embodiment, the final cigarette equivalent gel volume is 1 micro litre to 5 ml . A preferred equivalent volume is 0.1 to 2ml, more preferably 0.1 to ImI and most preferably 0.1 to 0.5ml. A particularly preferred application volume is 0.8ml .

The compositions of the invention are primarily intended for use as a cigarette replacement. This is especially relevant in circumstances where an individual is not permitted to smoke, for example on public transport, in particular on aeroplanes and in public places such as restaurants, bars and public houses. However, additional uses of the compositions of the invention may be envisaged and include, inter alia, use as a nicotine replacement therapy to encourage reduction or cessation of smoking by a user.

Thus, in one specific embodiment, a tobacco extract is used to augment the function of any other tobacco replacement product. Likewise, the tobacco extract may be used in a non-tobacco product. The tobacco extract may be in any suitable form, as discussed in greater detail herein.

Previous compositions used in nicotine replacement therapy tend to have been produced using ammonia based extraction from tobacco stems . Additional nicotine is then added to the compositions as required. The compositions thus do not provide a tobacco extract which mirrors the natural composition of tobacco. It has been found that extraction of tobacco in heated aqueous solution, such as boiling water, produces an extract which incorporates the

representative molecules from the tobacco plant and that these "complete" extracts are much improved over nicotine based compositions as a cigarette replacement. Accordingly, in a further aspect of the invention there is provided a process for extracting tobacco from a tobacco plant comprising placing at least part of a tobacco plant in aqueous solution at elevated temperature/a heated aqueous solution.

Extraction of tobacco may begin with any suitable part of the tobacco plant, or indeed using the whole plant. Preferably, the at least part of the tobacco plant is kibbled prior to extraction. In one embodiment, the at least part of a tobacco plant comprises the stem/leaves/buds/roots.

Preferably, the aqueous solution is boiling water since this produces particularly useful results. In one embodiment, the tobacco is extracted in aqueous solution at greater than 80 ⁰ C, preferably at least 85°C.

The time for extraction of tobacco is preferably in the range of 1 minute to 5 hours, more preferably between 5 minutes and 1 hour.

During the extraction process, the mixture may be agitated. In a further embodiment, the tobacco may be added to the heated aqueous solution in a suitably perforated packaging, such as a polypropylene sachet for example.

In a more specific embodiment of this aspect of the invention there is provided a process for preparing a

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tobacco extract for use in the preparation of a tobacco containing composition for application to the skin comprising; a) placing at least part of a tobacco plant in aqueous solution at elevated temperature; b) filtration of plant extract from the aqueous extract; c) addition of a glycol; d) addition of purified water; and e) extraction of the resulting precipitates.

In one specific embodiment the at least part of a tobacco plant is placed in boiling water for a period of not more than 5 minutes. In an alternative embodiment, where the aqueous solution is at a temperature of greater than 80 ⁰ C, preferably at least 85°C, the at least part of the tobacco plant is kept in the solution for a longer period which is preferably at least 30 minutes and more preferably around 1 hour.

In one specific embodiment, 90 kg of the at least part of a tobacco plant is used per 1000 L of aqueous solution.

In step c) any suitable glycol, such as a glycol ether may utilised. In one embodiment, the glycol is diethyl glycol monoethyl ether. The glycol ether may be added in any suitable volume to give an appropriate concentration. In one embodiment, in step c) the glycol is added to 20% v/v. In a preferred embodiment, the glycol is added to be present in the final composition at 10 to 50% v/v, in particular 20 to 40% v/v and most preferably around 40% v/v.

The invention also relates, in a further aspect, to a tobacco extract produced according to the processes of the invention as described in greater detail herein. As aforementioned, use of aqueous based extraction produces complete tobacco extracts which are particularly useful in the compositions of the invention. Such a tobacco extract may display a unique GCMS profile, as shown in figure 1 for example. Thus, the tobacco extracts of the invention may also be defined by their GCMS profile and/or a characterisation of the peaks there from. Thus, for example, a tobacco extract of the invention may incorporate at least nicotine to include its salts and other derivatives and, cotinine including its salts and other derivatives and optionally carbitol. Additionally, the extract may include any one or more, up to all of methanol, acetone, acetic acid, SO ₂ , lactones (in particular beta angelica lactone) , carbitol, myosmine (3- ( 1-pyrroline-2-yl) pyridine) , furfural and 2 , 3-dihydro-3 , 5-dihydroxy-6-methyl~4H-pyran-4-one . The compositions of the invention may incorporate any of these tobacco extracts of the invention. The tobacco extracts thus contain preferably at least 5 compounds from tobacco, more preferably at least 10, 20, 50 or 100 compounds and even more preferably at least 150 compounds from tobacco.

In a still further aspect, the invention also provides a process for preparing a tobacco containing composition for application to the skin comprising (complete) extraction of tobacco from at least part of a tobacco plant to produce a (complete) tobacco extract followed by formulation of the tobacco extract into a composition for application to the skin. The tobacco extract thus formulated contains the

compounds from tobacco in the appropriate (relative) amounts .

As aforementioned, the preferred composition which is thus formulated is a gel. Thus, in one embodiment of the invention there is provided a process for preparing a tobacco containing composition for application to the skin comprising extraction of tobacco from at least part of a tobacco plant to produce a tobacco extract followed by formulation of the tobacco extract into a gel.

The tobacco may be formulated into any suitable composition type for application to the skin. Therefore, the discussion herein in respect of the compositions of the invention applies mutatis mutandis to this aspect of the invention.

The extraction of tobacco from at least part of a tobacco plant may, in a preferred embodiment, be carried out according to the processes of the invention for tobacco extraction since this produces particularly useful tobacco compositions .

In one specific embodiment, formulation of the extract into a gel comprises; a) adding glycol to a suitable vessel; b) adding the extract and stirring of the mixture; c) addition of a gum,- and d) continued stirring to produce a gel .

In a more specific embodiment, formulation of the extract into a gel comprises; a) to a vessel containing a glycol adding the extract;

b) making up the volume with an aqueous solution; c) rapid stirring of the solution; d) addition of a gum; e) addition of a preservative; and f) continued stirring to produce a gel.

Preferably in step b) the aqueous solution is (ambient) water. In step a) the vessel preferably contains a final quantity of 10% to 50% v/v of glycol, more preferably at least 20% v/v such as 20 to 40% v/v of the glycol and most preferably 40% v/v. The glycol is preferably a glycol ether and even more preferably diethyl glycol monoethyl ether. In one embodiment, in step a) the extract is added at ambient temperature. In a further embodiment, in step a) the extract is added at a volume of 62.5% of the total vessel volume. Preferably, in step d) the gum is a combination of xanthan and guar gum, or derivatives thereof, and is most preferably a 1:1 pre-blended mixture of xanthan and guar gum, or derivatives thereof. In one embodiment, in step d) the final combined concentration of xanthan and guar gum is

2.5% w/v. In an embodiment of the invention xanthan gum is present in the final composition at 1.5 to 2% w/v, preferably around 1.8% w/v and guar gum is present at 1.7 to 2.3% w/v, most preferably around 2% w/v.

In a further specific embodiment, the preservative used is sodium metabisulphite although any suitable preservative may be added in the process . The preservative may be added to any acceptable concentration for example between 100 and 300 ppm. Preferably, the preservative is added to a final concentration of 200 ppm.

In one embodiment, in step f) the continued stirring is for 2 to 5 minutes although any suitable period of stirring may ^¬ be employed as would be readily determined by a skilled person by routine experiments .

In a further embodiment, formulation of the extract into a gel comprises; a) adding glycol to a suitable vessel containing a glycol; b) stirring the glycol; c) adding the extract; d) addition of a gum; e) addition of a combination of extract and water,- and f) continued stirring to produce a gel.

Preferably the glycol is a glycol ether and most preferably contains diethylene .glycol monoethyl ether. However, the diethylene glycol monoethyl ether may be substituted in part or completely by one or more alternative chemicals which aid the ingress of the tobacco extract across the skin. As aforementioned, the glycol may be present in the final gel at 10 to 50% v/v, more preferably at least 20% v/v such as 20 to 40% v/v and most preferably around 40% v/v.

Stirring may be at any suitable speed but is preferably at 1 to 5 rpm and more preferably at 2 to 3 rpm.

In a preferred embodiment, the gel is made using one other or both of xanthan gum or its derivatives and guar gum or its derivatives. However, these gel agents may be substituted in part or completely by other chemicals which result in aqueous gel formation. In a particularly preferred embodiment, in step d) guar gum is added followed

by xanthan gum. Preferred ratios are 2 kg guar gum per 1.8 kg of xanthan gum. In an embodiment of the invention xanthan gum is present in the final composition at 1.5 to 2% w/v, preferably around 1.8% w/v and guar gum is present at 1.7 to 2.3% w/v, most preferably around 2% w/v. As mentioned above, in alternative embodiments a non-aqueous gel is formed and this may require use of alternatives as would be appreciated by a skilled person.

The combination of extract and water in step e) is preferably added in a 1:1 ratio. This leads to particularly impressive results in terms of rapid gel formation.

The processes above result in rapid and homogenous gel formation as described in the experimental section below.

In all extraction processes of the invention, the at least part of a tobacco plant used to form the extract comprises the stem/leaves/buds/roots. Preferably, the at least part of the tobacco plant is kibbled prior to extraction.

The invention also relates to compositions which are produced according to any of the processes of the invention as described herein.

BRIEF DESCRIPTION OF THE DRAWING

Figure 1 is a representative gas chromatography mass spectrometry (GCMS) profile of a tobacco extract of the invention, as produced according to a tobacco extraction process of the invention. The peaks are assigned on the profile and the relative proportions of the component parts are also indicated.

DESCRIPTION OF THE INVENTION The invention is the product resulting from the process and base formulation that allows the low cost and rapid preparation of a tobacco gel for use as a cigarette replacement . The examples provided are in respect of a specific aqueous gel formulation for convenience although the tobacco extracts may be formulated into other types of composition as discussed herein.

Process 1

The process involves the following steps: a) An aqueous extraction of kibbled tobacco stems in boiling water for a period of not more than 5 minutes, using 90kg of tobacco per IOOOL of water b) The filtration of plant extract from the aqueous extract c) The addition of diethylene glycol monoethyl ether to 20% v/v d) The addition of purified water e) The extraction of resulting precipitates f) Steps a-e represent the manufacture of a tobacco concentrate and result in a typical GCMS profile as shown in

Figure 1.

The GCMS profile reveals the following components of the tobacco extract (with the first number being the time of release as plotted on the x axis) :

Approx . 3.30 methanol (1.215%)

Acetone (0.394%)

5.20 acetic acid (1.629%)

6.67 acetol (0.256%)

10.00 furfural (0.168%)

21.08 beta-angelica lactone (0.160%)

26.95 carbitol (6.432%)

37.85 not assigned

38.45 2 , 3-dihydro-3 , 5-dihydroxy-6-methyl-4H-pyran

4-one (1.751%)

53.38 nicotine (86.782%)

60.00 myosmine

65.00 dipyridyl

71.48 not assigned

75.04 cotinine (0.41%)

76.48 not assigned some SO ₂ is also believed to be present.

g) To a vessel containing a final quantity of 20% v/v diethylene glycol monoethyl ether add 62.5% of this volume of tobacco concentrate at ambient temperature h) Make up the volume with ambient water i) Beginning rapid stirring of the solution j) Add a 1:1 pre-blended mixture of xanthan and guar gum such that their final combined concentration is 2.5% w/v k) Add sodium metabisulphite to a final concentration of 20Oppm

1) Continue stirring for 2-5 minutes; the resulting mixture will have numerous flexes of gum evenly distributed throughout it, however it can be packed off immediately as the gum disperses quickly and evenly over a short period of time (typically less than 4 hours) m) The resulting gel delivers a cigarette replacement dose in ImI of gel n) Application of the gel is by dispensing ImI into the palm of one's hands and rubbing in to both palms in a similar manner to either soaping one's hands or administering hand lotion. Within 45 seconds the gel has completely disappears leaving no residue or odour. The effects of the tobacco are felt by the user within 1 minute of applying the gel

Process 2

1) 7.5litres of kibbled tobacco are placed in perforated polypropylene sachets. In groups of two 125 litres of water at 85 C is added. These are agitated lightly for 60 minutes. At the end of 60 minutes the extract is set aside.

2) in the gelling vessel (250 litre capacity) 80 litres of glycol is added

3) stirring at 2-3 rpm commences

4) 40 Litres of extract is added

5) 2kg of Guar Gum is then added quickly and then 1.8kg of Xanthan Gum

6) 80 litres of 1:1 extract and water is then added with continued stirring. The gel forms instantly and entirely homogeneously.