AU2021106893A4 - Topical Compositions - Google Patents

Abstract

This invention defines a composition comprising menthol in an amount from about 30-60 mg/g, and capsaicin in an amount from about 0.07-0.11 mg/g for topical application to treat aches and pain.

Description

DCC-24/08/2021

TOPICAL COMPOSITIONS FIELD

The present disclosure relates generally to topical compositions, methods for their production and use of said compositions.

BACKGROUND

The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

Numerous topical products are marketed for the treatment or relief of muscle aches, pain and soreness (such as lower back pain, neck pain, and soreness and pain associated with strains and injuries), neuropathic pain, as well as the relief of joint pain associated with mild arthritis. While some products contain active ingredients with anti-inflammatory properties, e.g., NSAIDs such as diclofenac, other products provide relief through active ingredients that act as counter-irritants (agents that create localised irritation or inflammation to alter pain perception in another location). These counter-irritants act on transient receptor potential (TRP) receptors, a group of thermosensitive ion channels expressed in primary sensory neurons and other tissues, manifesting as warming and/or cooling sensations on the skin. Examples of counter-irritants commonly used in topical pain relief products include: warming agents, such as capsaicin (8-methyl-N-vanillyl-trans-6-noneamide), wintergreen oil (containing methyl salicylate), and clove oil (containing eugenol); and cooling agents, such as camphor oil, eucalyptus oil (containing eucalyptol, or 1,8-cineol), peppermint oil (containing menthol) and amica montana extract. However, the use of these agents can also result in unpleasant and uncomfortable side effects, such as erythema, burning, stinging, or itching sensations at the site of application

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Capsaicin is the main active ingredient in chillies and capsicums that is responsible for the heat and burning sensations experienced when it comes in contact skin or mucous membranes, and is used in a number of preparations to provide longer term relief of pain. Its pain relieving action comes about through selective agonism of the heat- TRPV1 calcium channel, with prolonged activation of TRPV1 resulting in desensitization of the receptor. Activation by capsaicin results in the opening of the channel at a temperature lower than its threshold (37-46°C), resulting in the sensation of warmth.

However, topical administration of pain relieving or warming doses must be carefully managed to minimize unpleasant side effects that are commonly reported: typically anywhere from mild to severe stinging or burning sensation, erythema, itching and swelling at the site of application that may last several hours. For example, administration in patch form (8% capsaicin) is performed by a medical professional, usually under local anaesthetic. Even over the counter cream formulations for home use by the patient, typically containing lower concentrations of capsaicin (0.025, 0.075 or 0.1% capsaicin), can result in the unpleasant side effects, particularly with the higher potency formulations (0.075% and 0.1%), and leads to poor patient compliance. Due to the heat sensitivity of the TRPM1 receptor, additional applied heat, such as covering the affected body part with clothing, bandaging or bedcovers, bathing in warm water, high ambient temperature and/or humidity, or body temperature increases, such as during physical activity or during sleep, can exacerbate or reactivate the unpleasant side effects.

Menthol also has counter-irritant properties providing a cooling sensation through its selective activation of TRPM8. TRPM8 is activated by temperatures below 26°C, and thus its activation imparts a cooling effect. Menthol acts as a counter-irritant local analgesic by imparting a cooling effect and by initially stimulating nociceptors and then desensitizing them, altering pain perception.

A number of commercially available topical compositions comprising both capsaicin and menthol are intended to provide both immediate warming and cooling effects, however, many such preparations still have unpleasant side effects or do not provide adequate

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warming and/or cooling effects, or pain relief, or the effects only last a short period of time (such as only about 30 or 60 minutes).

There remains the need for topical compositions for use in the relief of muscle and joint pain, aches, and/or discomfort.

SUMMARY

The present disclosure relates to topical compositions that, in one or more embodiments, may provide relief from one or more types of pain or discomfort, for example, muscle aches/pains/soreness, mild joints aches and pains, mild joint inflammations, mild nerve/neuralgia, symptoms associated with muscle sprain/strain and injuries and symptoms associated with mild arthritis/osteoarthritis. In one or more embodiments, the composition may reduce, ameliorate, or otherwise fully or partially overcome one or more of the disadvantages associated with topical formulations containing counter-irritant active agents.

Advantageously, the compositions of the present disclosure provide an initial cooling effect upon topical application to the skin, and a latent warming effect that is activated by physical activity or exercise.

The compositions comprise capsaicin and a cooling agent, wherein the capsaicin in present in an amount such that the warming effect is activated by physical activity or exercise, and the cooling agent is present in an amount sufficient to provide an initial cooling effect to the skin. In addition to providing a cooling sensation to the skin upon application, the cooling agent may also attenuate any undesirable or excessive capsaicin heating effects

In one or more embodiments, there is provided a topical composition comprising menthol in an amount from about 30-60 mg/g, and capsaicin in an amount from about 0.07-0.11 mg/g.

In some embodiments, the menthol is present in an amount from about 35-55 mg/g, preferably about 40-50 mg/g.

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In some embodiments, the capsaicin is present in an amount of from about 0.75-0.10 mg/g, preferably about 0.08-0.09 mg/g (0.008-.009%). In some further embodiments, the capsaicin is present in the form of capsaicin oleoresin (capsicum fruit oleoresin). In further embodiments, the capsaicin oleoresin contains about 1-5 wt% capsaicin, such as about 2, 3 or 4 wt% (for example 2.5-3.5 wt% capsaicin). In some embodiments, the capsaicin oleoresin has a Scoville Heat Unit rating of about 400,000-600,000, such as about 500,000 SHU. In some embodiments, the composition contains about 3 mg/g of caspsaicin oleoresin having a capsaicin content of about 2.5-3.5 wt%..

In some embodiments, including any of the embodiments described above, the composition further includes beeswax.

In some embodiments, including any of the embodiments described above, the composition further includes olive oil.

In some embodiments, including any of the embodiments described above, the composition further includes one or more additional cooling and/or pain relieving agents. In still further embodiments, an additional agent is arnica montana extract. In still further embodiments, the compositions comprise clove oil (e.g. clove bud oil).

The composition may optionally further include one or more pharmaceutically acceptable excipients, such as carriers, humectants, preservatives, film formers, viscosity agents, and/or one or more additional therapeutic agents.

In some embodiments, the disclosure provides a topical composition comprising: capsaicin in an amount of about 0.09 mg/g (0.009 wt%); menthol in an amount of about 50 mg (5.0 wt%).

In one or more embodiments, the compositions may start to provide a cooling effect within 5 minutes of application, preferably within 2 or 1 minute of application.

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In some embodiments, the warming effect may be reactivated at least once or twice, and may be experienced for up to 5, 12, 15, 18, 20, 24, 30, 36 or 48 hours after application.

In some embodiments, there is provided a topical composition comprising: amica montana flower extract dry concentrate in an amount equivalent to about 50 mg/g (5 wt%) arnica montana (dry), e.g. about 5 mg/g arnica montana flower extract dry concentrate; menthol in an amount of about 50 mg/g (5 wt%); clove oil, in an amount of about 30 mg/g (3 wt%); and olive oil, in an amount of about 20 mg/g (2 wt%). capsaicin oleoresin, in an amount equivalent to about 0.09 mg/g (0.009 wt %) capsaicin.

In some further embodiments the compositions described herein further comprises beeswax. In some embodiments, the beeswax is white beeswax. In still further embodiments, the beeswax is present in an amount of about 5-50 mg/g (0.5-5 wt%).

In another aspect, there is provided a method for treating pain or discomfort, such as muscle aches/pain/soreness, mild joint aches and pains, mild joint inflammation, mild nerve/ neuralgia and symptoms associated with muscle sprain/strain and injuries and symptoms associated with mild arthritis/osteoarthritis, in a subject in need thereof, comprising topically applying a composition of the disclosure to said subject.

Another aspect provides a topical composition of the disclosure for use in treating pain or discomfort, such as muscle aches/pain/soreness, mild joint aches and pains, mild joint inflammation, mild nerve/ neuralgia and symptoms associated with muscle sprain/strain and injuries and symptoms associated with mild arthritis/osteoarthritis.

DESCRIPTION

Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise" and variations such as "comprises" and "comprising" will

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be understood to imply the inclusion of a stated integer or step or group of integers but not the exclusion of any other integer or step or group of integers or steps.

Throughout this specification and the claims which follow, unless the context requires otherwise, the phrase "consisting essentially of', and variations such as "consists essentially of' will be understood to indicate that the recited element(s) is/are essential i.e. necessary elements of the invention. The phrase allows for the presence of other non-recited elements which do not materially affect the characteristics of the invention but excludes additional unspecified elements which would affect the basic and novel characteristics of the invention defined.

The singular forms "a", "an" and "the" include plural aspects unless the context clearly dictates otherwise.

The term "invention" includes all aspects, embodiments and examples as described herein.

As used herein, "about" refers to a quantity, value or parameter that may vary by as much as 10%, 5%, 2%, or 1 % of the stated quantity, value or parameter, and includes at least tolerances accepted within the art. When prefacing a recited range of values, it is intended to apply to both upper and lower limits of the range. Similarly, when preceding a list of values, unless the context indicates otherwise, "about may apply to each stated value. For example, in some embodiments, when prefacing an amount or range expressed in terms of wt% or mg/g, "about" includes a variation of 5, 4, 3, 2 or1 wt%, or mg/g respectively.

The compositions of the present invention provide an initial cooling effect when applied to the skin, but the warming effect is only substantially felt with further physical activity. The initial cooling effect facilitates warm-up or stretching exercises. This activity generates heat during which blood circulation increases, warming the skin and thus activating the warming effect. The compositions of the disclosure contain a cooling agent in an amount sufficient to provide an initial or immediate cooling effect upon application to the skin. In advantageous embodiments, the cooling agent may also attenuate or moderate any side

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effects due to capsaicin. The compositions also contain capsaicin in an amount such that no substantial warming effect is felt upon initial application to the skin, but is generated with subsequent activity. Thus, the ensuing warming effect also serves as an indicator to the subject that the muscles or area of interest (e.g. pain/discomfort/injury) is warmed up and is ready or primed for further intense activity, lessening the likelihood of strain or injury. This contrasts with compositions containing higher concentrations of capsaicin, which provide an immediate warming effect, but may also provide false comfort that the muscles are adequately warmed up, and therefore increasing the risk of injury or strain if intense activity is commenced before the muscles are actually warmed up.

In some embodiments the cooling effect may be felt for up to one hour, and the cooling effect of the cooling agent (e.g. menthol) may help to attenuate any unpleasant side effect sensations (burning, redness, itching) associated with the topical application of capsaicin.

The compositions of the disclosure advantageously allow for lower amounts of capsaicin compared to commercial over the counter products (i.e. less than 0.025 wt%). Unlike some commercial preparations with higher concentrations of capsaicin, in some embodiments, once physical activity has stopped, the warming effect subsides. However, it can be reactivated when the subject restarts physical activity, such as warming up or stretching, again. For example, an athlete could decide to rest or stop, or spends a period of time on the bench, or rests between quarters, halves or sets, during which the warming effect will subside, but when activity recommences, the warming effect is reactivated. In this manner the warming effect may be experienced continuously or intermittently during a sporting activity, and may be suitable for long or high intensity sports or high intensity interval training. On the other hand, where the activity over a longer period, for example, physical labour or gardening, a continuous warming effect can be felt during the activity period.

For the compositions described herein, capsaicin may be used in any appropriate form, for example, crystalline (e.g. synthetic or extracted from naturally occurring sources), capsaicin oleoresin, neat or diluted chilli or capsicum oil (e.g. cayenne pepper oil) or other extract obtained from chilli or capsicum. In some embodiments the capsaicin is provided in the

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form of capsaicin (capsicum fruit) oleoresin. In further embodiments, the capsaicin oleoresin contains about 1.0-5.0 wt% capsaicin, such as about 2.0-4.0 wt% capsaicin, such as about 2.5-3.5 wt%, for example about 2.6, 2.7, 2.8, 2,9, 3.0, 3.1, 3.2, 3.3 or 3.4 wt% capsaicin. In some embodiments, the capsaicin oleoresin has a Scoville Heat Unit rating of about 400,000-to about 600,000, such as about 450,000-550,000 SHU, for example about 500,000 SHU. In some embodiments the capsaicin is included in the composition in the form of capsaicin oleoresin in an amount of about 3mg/g (comprising about 2.5-3.5 wt

% capsaicin, such as 2.9-3.1 wt% capsaicin equating to about 0.0087-0.0093 wt% capsaicin in the composition (approximately 500,OOSHU).

The compositions contain one or more cooling agents in an amount that provide cooling effect when the composition is applied to the skin and/or counteract or attenuate excessive heat side effects from the capsaicin. Cooling agents for use in the compositions may include one or more of menthol, menthol stereoisomers and menthol derivatives (e.g. (+)/(-) isomenthol, (+)/(-)-neomenthol, (+)/(-)-neoisomenthol, menthyl ethers and esters, such as 3 (1-menthoxy)propane-1,2-diol, 3-(1-menthoxy)-2-methylpropane-1,2-diol, menthyl lactate), camphor oil, eucalyptus oil, eucalyptol (1,8-cineol), peppermint oil and arnica montana extract.

In some embodiments, the compositions contain menthol. The menthol may be used in any appropriate form, for example crystalline, flaked or powdered menthol (e.g. L or (-) menthol, D or (+)- menthol, or mixtures thereof). The menthol may be naturally derived (e.g. from peppermint oil) or synthetic menthol. The main form of naturally occurring menthol is L ( )-menthol. In further embodiments, the composition contains menthol (e.g. (L)-menthol) in an amount of about 30-60 mg/g.

As used herein, an immediate cooling effect refers to a cooling sensation on the skin within 5 minutes of application, preferably within 4, 3, 2 or 1 minutes of application.

The compositions according to the disclosure may further include one or more additional therapeutic agents/oils as described below.

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Arnica Montana extract, is extracted from the Arnica Montana flower. Arnica Montana extract is credited with pain relieving and anti-inflammatory properties and is used to relieve muscle aches/pain/soreness, mild joint aches and pains, mild joint inflammation, mild nerve/neuralgia and symptoms associated with muscle sprain/strain and injuries and symptoms associated with mild arthritis/osteoarthritis. Arnica montana may also have a mild cooling effect. Thus the addition of Arnica Montana extract may provide an additional cooling effect upon initial application to the skin, and/or a pain relieving effect, which may facilitate warm-up and stretching exercises prior to commencing more vigorous activity. The compositions of the disclosure may include amica montana extract added in a therapeutically effective amount, i.e. to provide additional initial cooling effect and/or pain relief, for example, equivalent to about 20-80 mg/g arnica flower (dry), e.g. about 2-8 mg /g amica extract (dry). In further embodiments, the compositions may include arnica montana extract added in an a amount, equivalent to about 40-60 mg/g arnica flower (dry), e.g. about 4-6 mg /g arnica extract (dry), such as about 50 mg/g arnica flower (dry), e.g. about 5 mg /g arnica extract (dry). .Arnica Montana extract may be added in the form of a powder, oil or tincture.

Eugenol is found in clove, nutmeg, cinnamon, basil and bay leaf oil, but is present in significant amounts (typically 80-90%) in clove (leaf, stem or bud) oil, with clove bud oil typically containing the largest concentration, and provides an initial warming effect, that unlike capsaicin, is not reactivated by physical activity. Eugenol may be added to the composition in a therapeutically effective amount, in any suitable form. In some embodiments eugenol is added to the composition in the form of clove oil, such as clove bud oil in an amount from 10-60 mg/g, such as about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 or 60

mg/g.

In some advantageous embodiments, the compositions of the disclosure comprise arnica montana extract and/or clove oil.

Camphor and eucalyptol (1,8-cineole) are counter-irritants that have a cooling effect

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(camphor may also have a warming effect), and both are used for topical pain relief and treatment of inflammation. Camphor oil is obtained from Cinnamonun Camphora, Eucalyptol is found in significant quantities in eucalyptus oil (typically at least about 60 70%). In some embodiments, the composition further comprises camphor and/or eucalyptol. One or both oils may optionally be added in a therapeutically effective amount, e.g. a cooling effective amount, for example, each may independently be added in an amount from about 1 mg/g to about 80 mg/g, such as about 5-60 mg/g, or about 10-50 mg/g or about 20-40

mg/g.

Rosemary oil contains significant amounts of eucalyptol (about 25%) and camphor (about 20%), as well as alpha- and beta-pinene and camphene, and in some embodiments, the composition may comprise rosemary oil. In still further embodiments, the rosemary oil is Spanish type. Rosemary oil may be added in a therapeutically effective amount, from about 1 mg/g to about 80 mg/g, such as about 5-60 mg/g, or about 10-50 mg/g or about 20-40 mg/g.

One or more other essential oils /extracts having pain relieving or other beneficial (e.g. anti inflammatory) properties may also be optionally added to the composition in a therapeutically effective amount, for example, teatree oil, helichrysum oil, marjoram oil, lavender oil, Roman or German chamomile oil, yarrow oil, ginger oil, cypress oil, sandalwood oil, black pepper oil, clary sage oil, juniper oil, laurel leaf oil , saro oil ,

ravintsara oil, frankinscence oil, wintergreen oil, peppermint oil, vetiver oil, thyme oil, copaiba oil, turmeric oil, cajaput oil, birch oil, calendula oil, hypericum perforatum, (St Johns Wort) oil, jacoba oil, and pine oil pumilio, .

In some embodiments, the composition optionally comprises one or more plant-derived oils (e.g. from the fruit and/or seeds), such as olive oil, grape oil, vegetable oil, canola oil, sunflower oil, coconut oil, argan oil, soybean oil, almond oil, safflower oil, jojoba oil, avocado oil, apricot kernel oil, moringa oil, castor oil, evening primrose oil, hempseed oil, flaxseed oil, rice bran oil, and macadamia nut oil. The addition of one or more oils may also provide moisturizing and/or soothing properties to the composition, and may provide some

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attenuation of undesirable capsaicin side effects. In some embodiments the oil is a cold pressed oil. The oil(s) may be added in any suitable amount, such as from about 1 mg/g to about 800 mg/g, such as from about 2, 5, 10, 20, 30, 40,50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 400, 500, 600 or 750 mg/g. In further embodiments, the composition comprises olive oil in an amount of about 10-50 mg/g (1-5 wt%), such as 20, 30 or 40 mg/g.

The compositions may optionally comprise a wax, or mixture of two or more waxes. In some embodiments, the presence of wax may add one or more of the following properties to the composition: humectant and skin softening properties, adjust viscosity/texture of the composition, or adjust the melting point of the composition. Waxes used herein may be natural (including beeswax and plant-derived waxes), semi-synthetic or synthetic, and may include: beeswax, candelilla wax, green tea wax, rice bran wax, soy wax, carnauba wax, bayberry wax, sunflower wax, myrica wax, laurel wax, ceresine wax, synthetic beeswax paraffin wax, microcrystalline wax, emulsifying wax, ceresine wax In some embodiments, composition comprises a natural wax. In some embodiments the composition contains beeswax. The beeswax may be yellow beeswax or white beeswax. In some embodiments, beeswax may impart one or more therapeutically beneficial properties such as skin softening or moisturizing, anti-inflammatory and/or reducing pain, or joint stiffness. In some embodiments, wax, such as beeswax, may be added in an amount up to about 5-50 mg/g (0.5-5.0 wt %), such as about 10, 15, 20, 25, 30, 35, 40, or 45 mg/g.

In some embodiments, the compositions comprise both olive oil and beeswax. In some embodiments the combination of both beeswax and olive oil may provide soothing, moisturizing and emollient properties to the composition, and aid in counteracting or attenuating any undesirable side effects, due to the capsaicin.

In some embodiments, the compositions may optionally contain one or more additional pharmaceutically acceptable carriers, additives or excipients. For example, although one or more components of the composition may possess preservative activity, such as anti-oxidant or anti-microbial activity (e.g. antibacterial or antifungal), the composition may contain one or more further agents, including antioxidants (such as vitamin E, tocopherols (-,, y- 6-

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),tocotrienols (da-, dp-, dy- d-)), parabens and their salts (methyl- ethyl-, propyl-, butyl isobutyl-), sorbic acid, potassium sorbate, lactic acid, phenoxy ethanol, benzyl alcohol, salicylic acid). Other ingredients may include water, colouring agents, fragrances, humectants (e.g. glycerine, glycols, hyaluronic acid) and emollients (e.g. cocoa butter, shea butter, kokum butter, mango butter, avocado butter), emulsifiers and surfactants, (e.g., polyethylene glycols, polysorbates, film formers, thickeners (e.g. gums, such as xanthan gum, acacia gum, carob gum, alginate derivatives, pectin and carbomer; polymethylmethacrylate,polymethylmethacrylates,polyacryamides, cellulose derivatives such as methyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropylmethyl,cellulose, sorbitol) , viscosity builders and binders. An additional ingredient may perform one or more functions. The additional ingredient(s) may be natural (e.g. derived or obtainable from natural sources) or synthetic. In some embodiments the additional agent is derived or obtainable from natural sources.

In some embodiments, the composition may include one, more than one, or all of: paraffins or paraffin waxes, (e.g. C13-14 isoparaffin), stearyl alcohols, (e.g. cetostearyl alcohol), glycerols (e.g. glycerol, ethylhexylglycerin, glyceryl monostearate), purified water, stearic acid, phenoxy ethanol, film formers (e.g. polyacrylamide), emulsifiers and surfactants (e.g. laureth-7), gums, (e.g. xanthan gum), oils (such as described herein, e.g. olive oil, sunflower oil)

The composition may be in any suitable format, for example, ointment, cream, lotion, emulsion (oil-in-water or water-in-oil), mousse, jelly or gel, or stick formulation. Depending on the format, the composition may be packaged and presented for use in tubes, tubs, jars, sachets, vials, bottles and roll-on or stick devices.

In some embodiments, the composition is free of (i.e. does not contain), or is substantially free of (i.e. contains less than about 5%, or 4%, or 3%, or 2% or 1% by weight), a topical NSAID, e.g. diclofenac, methyl salicylate, ibuprofen, ketoprofen, indomethacin benzydamine, etofenamate, felbinac, fentiazac, flunoxaprophen, flurbiprofen, ketorolac, lysine cloxinate, meclofenamic acid, naproxen, niflumic acid and piroxicam.

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In some embodiments, the composition comprises: menthol - about 30-60 mg/g, such as about 35, 40, 45, 50, 55 or 60 mg/g; capsaicin about 0.07-0.11 mg/g capsaicin, such as about 0.07, 0.075, 0.08, 0.085, 0.09, 0.095, 0.1, 0.105, 0.11 mg/g, optionally in the form of capsaicin oleoresin; clove oil about 20-40 mg/g, such as about 20, 25, 30, 35 or 40 mg/g; amica montana extract, equivalent to about 40-60 mg/g arnica flower (dry), such about 40, 45, 50, 55, or 60 mg arnica flower (dry) beeswax about 5-50 mg/g, such as about 10, 15, 20, 25, 30, 35 or 40 mg/g; and olive oil about 10-30 mg/g, such as about 10, 15, 20, 25, or 30 mg/g.

In some further embodiments, the composition comprises: menthol about 50mg/g; capsaicin about 0.09 mg/g, preferably in the form of capsaicin oleoresin; clove oil about 30 mg/g; amica montana extract about 5/mg/g (equivalent to about 50 mg/g arnica flower (dry) beeswax about 20 mg/g; and olive oil about 20 mg/g.

The compositions may be prepared by heating and mixing the components (available from commercial suppliers) to ensure homogeneity. In advantageous embodiments, the mixture components are not heated beyond about 85°C, preferably not beyond about 65 or 70, 75 or 80°C. The heating temperature may depend on the of the components used. For example, solid components (e.g. crystalline menthol, beeswax, and, if used, arnica montana powder) may be gently heated (e.g. up to about 65-70°C) to ensure the solid components liquefy in the carrier oil. Depending on the volatility of any further ingredients added, the mixture may be cooled before additional ingredients are added, and mixed to homogeneity. In other embodiments, water miscible/soluble ingredients and oil miscible/soluble ingredients may be separately mixed to provide an aqueous phase and an oil phase, and the oil and water phases then mixed together, optionally with one or more binders, emulsifiers or surfactants. The resulting mixture can then be optionally further cooled and then decanted or transferred

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or packaged into appropriate containers.

In some embodiments, the compositions described herein are suitable for topical use on humans. In other embodiments, the compositions may be suitable for veterinary use i.e. for topical use on non-human animals, including domestic companion animals (e.g. dogs, cats, rabbits, guinea pigs, rats, mice), livestock animals (e.g. cows, horses, sheep, pigs and goats) or non-domesticated or captive wild animals.

As used herein, treatment or treating may include one or more of alleviating pain (e.g. a reduction in intensity or absence of pain, for example as measured on a scale of 1-10, 10 being the highest level of pain reduction), delay in onset or re-emergence of pain, or an increase in physical mobility or joint movement. As used herein, "relief' may include a reduction of intensity or absence of pain, delay in onset or re-emergence of pain, or an increase in physical mobility or joint movement. In one or more embodiments, the compositions may start to treat (e.g. alleviate pain) in as little as 5, 10, 20 or 30 minutes after application. In some embodiments, relief from a single application (dosage) may be experienced for up to 2-4, 5-7, 10-12, 15-20 or 24 hours after application. In some embodiments, 2-3 applications for 1, 2, 3, 4, 5, 6 or 7 days may provide at least from about 5, 7, 10, 12, 14 or-21 days of relief.

In some embodiments, the warming effect of the composition may be reactivated one or more times by intermittent physical activity, e.g. one, two or three times.

A therapeutically, or treatment effective amount includes an amount that imparts a therapeutic property to the composition or contributes to a therapeutic property, such as pain alleviation, anti-inflammatory effect, reducing swelling, reducing symptoms of muscle sprain/strain etc.

A treatment effective amount is intended to include an amount of composition which, when administered according to the desired dosing regimen, at least partially attains the desired therapeutic effect, including one or more of: alleviating, eliminating or reducing the

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frequency of one or more symptoms, e.g. pain or soreness. The amount of composition used will depend on the area requiring treatment, but some exemplary dosage amounts are in the range of about 50 mg to about 5 g of composition. In further embodiments, the dosage amounts are in the order of about 100 or 250 mg to about 1-3 grams, such as about 500 mg or 750 mg to about 1, 1.5 or 2.0 g per dosage. The composition may be applied as often as required to achieve a level of pain relief and warming, such as hourly, every two or three or four hours, or once, twice or three times daily. In some embodiments, the composition is applied once daily, twice daily or 3 times daily. In some embodiments, the composition is applied no more than 3 times daily. The pain may be acute or chronic, and therefore treatment may occur as long as required, and may extend for 1, 2 or 3 days, 5-7 days, 10-14 days, 1-2 weeks, 3-4 weeks, 2-3 months, 6-12 months or longer. Dosing periods may be interspersed with non-dosing periods, for example 2-3 applications per day for 1, 2 or 3 days, followed by a non- dosing period of 2-3 days 1 week, 10 days or 2 weeks. The compositions may be applied to the relevant area experiencing pain or discomfort (e.g. neck, shoulders, lower back, hips, legs, knees, ankles, feet, toes, arms, hands, wrists, elbows, fingers), and can be rubbed or massaged into the skin.

Suitable dosage amounts and dosing regimens may depend on the origin of the pain being treated, the location and severity of the pain as well as the general age, health and weight of the subject.

In one or more embodiments, compositions of the disclosure may be useful in treating acute pain or discomfort, or chronic pain or discomfort, such as associated with one or more of: injury, trauma or disease. For example, in some embodiments, the compositions may be useful in treating pain associated with one or more of: overuse or unaccustomed use of muscles (e.g. muscle strain or sprain) due to unaccustomed or vigorous exercise or activity (such as sporting activities or exercise, gardening, manual labour, repeated load-bearing activity, such as moving or lifting heavy objects);muscle aches/pain/soreness, mild joint aches and pains, mild joint inflammation, mild nerve/ neuralgia and symptoms associated with muscle sprain/strain and injuries and symptoms associated with mild arthritis/osteoarthritis. The pain may be acute or chronic. The pain may present anywhere

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on the body, such as any one or more of the back, neck, shoulders, arms, elbows, wrists, hands, fingers, thumb, hips, buttocks, thighs, knees, calves, ankles, feet, or toes.

In some embodiments, compositions of the disclosure may be usefully applied prior to physical activity, such as fitness, sport and training activities, leisure activities such as walking, hiking and gardening; and physical labour.

In some embodiments, the compositions may be applied around the painful/injured area and massaged in until the skin absorbs the composition, 3 times a day for 7 days. In other embodiments, the composition may be applied 3 times in succession within one hour, 3 times a day on the site of the injury/pain, and repeated the following day.

During sport training or competition, the composition may be applied to the skin approximately 30 minutes before activity. Optionally the relevant painful or injured area may be covered by a bandage, support wrap. brace or clothing to increase the warming effect experienced.

The following examples illustrate some embodiments of the disclosure. These are included for the purpose of illustration and are not to be construed as limiting the generality hereinbefore described.

EXAMPLES

Example 1 - Preparation of an exemplary composition

In an exemplary process, aqueous and oil phases were separately prepared them combined together, to which was added PEHG and Sepigel 305 to afford the composition.

Manufacturing process (100g Net)

Phase 1:

DCC-24/08/2021

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The following ingredients were mixed in a glass receptacle for 10 to 12 min, not exceeding 80°C. Prolonged heating should be avoided to prevent loss by evaporation.

1. Arnica powder (arnica monatana flower extract dry concentrate) 2. Purified water 3. Xanthan gun 4. Glycerol

Phase 2:

The following ingredients were mixed in a glass receptacle approximately for 15 mins at 65°C.

5. Olive oil 6. Beeswax 7. Cetostearyl alcohol 8. Glyceryl monostearate 9. Menthol crystal (CAS 2216-51-5, (IR, 2S, 5R)-5-Methyl-2-(1 methylethyl)cyclohexanol) 10. Stearic acid 11. Capsicum oleoresin (3.1 wt% capsaicin), blended with sunflower oil 12. Clove bud oil (CAS 8000-34-8, 84961-50-2)

Phase 3:

The following ingredients were added to the cream formulation after mixing the above oil and water phases.

13. Sepigel 305 (a mixture of, C13-14 isoparaffin, Laureth-7 ,

Polyacrylramide)

14. PEHG (a mixture of phenoxyethanol and ethyhexylglycerin.

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The resulting composition comprised:

Capsaicin Arnica flower extract (dry), Clove (Eugenia Carophyllus) bud oil, Menthol Olive oil Beeswax (white) C13-14 isoparaffin cetostearyl alcohol ethyhexylglycerin glycerol glyceryl monostearate laureth-7 phenoxyethanol polyacrylramide purified water stearic acid sunflower oil xanthan gum

Example 2 - Patient results using the composition of Example 1.

The composition of Example 1 was evaluated by 10 subjects (Si-S10) presenting with a variety of muscle/joint pain experienced in in the areas of legs, arms back, hip, shoulder and knee.. The composition was applied by rubbing into the skin before sporting or physical activity at a dosing rate of approximately 500 mg to about 1 g of composition, depending on the area to be treated. Each subject completed an evaluation survey. The results are presented below in Table 1.

o

* c/i c/i -~ o *- cJ~ A ~

o~ c/~ .~ 0

0

0 -~ 0 ~ Cl

0 I.- -~ 0 H Cl Cl Cl

0 c/i

'-~ 0 ~ 0 _ 0 C/~ C/~ ~ Cl

Id~) -~ -~ 0 Cl Cl

0

Id-) 0 0 Cl

0

~'

0 ~ 0 -~ -~ 0 Cl

0 0 -~ 0 Cl Cl Cl

0 0 -~ 0 Cl Cl Cl

:e~ :e~ ~ ~ 0 ~ ~

t - . ~ 0 ~ C~0

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*S3 and S10 applied the cream at home before work. This is the time between applying the composition and warming muscles at work by physical activities.

Claims (5)

DCC-24/08/2021 - 21 CLAIMS

1. A topical composition comprising menthol in an amount from about 30-60 mg/g, and capsaicin in an amount from about 0.07-0.11 mg/g, together with one or more pharmaceutical carriers, additives or excipients.

2. The composition according to claim 1 wherein the capsaicin is present in an amount from about 0.075 to about 0.09 mg/g.

3. The composition according to claim 1 or 2 further comprising beeswax and olive oil.

4. The composition according to any one of claims 1-3 further comprising arnica montana flower extract and/or clove oil.

5. The composition according to claim 1 comprising. (L)-menthol - about 30-60 mg/g; capsaicin about 0.07-0.11 mg/g capsaicin, optionally in the form of capsaicin oleoresin; clove bud oil about 20-40 mg/g; amica montana extract powder, equivalent to about 20-80 mg/g arnica flower (dry); beeswax about 5-50 mg/g; and olive oil about 10-30 mg/g.