GB2514417A

GB2514417A - Topical composition

Info

Publication number: GB2514417A
Application number: GB1309406.5A
Authority: GB
Inventors: Susan Jane Branch
Original assignee: Individual
Current assignee: Individual
Priority date: 2013-05-24
Filing date: 2013-05-24
Publication date: 2014-11-26
Also published as: GB201309406D0; WO2014188214A1

Abstract

A topical pharmaceutical composition for use in alleviating or reversing a clinical symptom selected from rigidity, stiffness, loss of mobility, loss of flexibility and swelling in a part or region of the body comprises (a) a ginger ingredient, (b) vinegar or a physiologically acceptable acid, and (c) a viscosity-enhancing agent. The ginger ingredient may be essential oil of ginger, ginger extract or tincture, fresh ginger, powdered ginger or a constituent compound of ginger. Examples of the viscosity-enhancing agent include xanthan gum, kuzu and glucomannan gums, and combinations thereof. The viscosity-enhancing agent may further be a skin penetration enhancing or skin hydration enhancing agent or the composition may additionally comprise a skin penetration enhancing or skin hydration enhancing agent.

Description

TOPICAL COMPOSITION

Field of the Invention

Thc present invention relates to a topical pharmaceutical composition comprising ginger, which is useful in alleviating clinical symptoms in the body such as rigidity, pain, swelling and decreased mobility.

Background of the Invention

Many clinical conditions and disorders involve increased rigidity or stiffness in the body.

They may be associated with inflammation or swelling and may giye rise to reduced mobility and reduced flexibility. Examples includc spondylitis, spinal stcnosis, sciatica, arthritic bone spurs, Dupion's coiltracture, osteoarthritis and rheumatoid arthritis. Many such conditions are considered irreversible without surgical intervention, and surgery is not suitable or feasible in all cases.

As these conditions and disorders often involve pain they are typically managed in the clinic with pain medication such as NSAIDs or steroida! drugs. However, such medication is not suitable for all patients. It can cause unwanted side-effects and may become less effective when used continually on a long-term basis. Physical therapy supervised by a physiotherapist may be appropriate for some patients, but this can take many months to deliver results and even then may be of limited or short-term benefit.

Gingcr has a long history ofuse in traditions of hcrbal medicinc, for illstancc in the Ayurvedic and Traditional Chinese Medicine (TCM) systems. It is the aromatic rhizome of thc plant Zin giber officinale Roscoc, which is a mcmbcr of thc family Zingiberaceae.

Zingiber offIcinale is widely grown as a commercial crop in south and southeast Asia, tropical Africa, Latin America, the Caribbean and Australia. Other species of the genus Zingiber include Zingiber ottensli, Zin giber citrioc/oruin and Zingiber spectabile.

Ginger has been used to treat a variety of ailments including rheumatism and inflammation.

Studies into the use of ginger in this context are also reported in contemporary scientific literature. For instance, Med. Hypotheses 1992 Dcc; 39(4): 342-8 (Srivastava K.C. eta!) describes a study in which powdered ginger was administered to patients suffering from osteoarthritis and rheumatoid arthritis and was found to bring about some symptomatic relief A randomiscd cross-over study comparing ginger extract with placebo and Ibuprofen is reported in Osteoarthritis Cartilage, 2000 Jan; 8(1):9-12 (BliddaiR. eta!).

This shows that ginger extract and lbuprofcn were both better than placebo in the treatment period before cross-over, although no significant difference between placebo and ginger extract was observed in the study as a whole.

Summary of the Invention

It has been found that a range of clinical conditions and disorders charactcrised by rigidity, stiffness, loss of mobility, loss of flexibility and/or swelling can be improved by the cutaneous administration of a combination of a ginger ingredient and vinegar or an acid.

Accordingly, the present invention provides a topical pharmaceutical composition for use in alleviating or reversing a clinical symptom selected from rigidity, stififiess, loss of mobility, loss of flexibility and swelling in a part or region of the body, wherein the composition comprises (a) a ginger ingredient, (b) vinegar or a physiologically acceptable acid, and (c) a viscosity-enhancing agent.

The present invention further provides, as a novel product, a topical pharmaceutical composition which comprises (a) a ginger ingredient, b) vinegar or a physiologically acceptable acid, and (c) a viscosity-enhancing agent; wherein the viscosity enhancing agent is also a skin penetration enhancing or skin hydrating agent, or the composition further comprises a skin penetration enhancing or skin hydrating agent. The viscosity enhancing agent is typically selected from xanthan gum, kuzu root starch, glucomannan gums and combinations thereof In one embodiment of the composition, no additional pharmaceutically active agent is present.

Further aspects of the invention include: -Use of (a) a ginger ingredient, (b) vinegar or an aqueous solution of a physiologically acceptable acid, and (c) a viscosity-enhancing agent in the manufacture of a medicament for cutaneous administration in alleviating or reversing a clinical symptom selected from rigidity, stifthess, loss of mobility, loss of flexibility and sweHing in a part or region ofthe body.

-A method of alleviating or reversing a clinical symptom selected from rigidity, stiffness, loss of mobility, loss of flexibility and swelling in a part or region of the body of a human or animal subject, which method comprises cutaneously administering to the subject a topical composition comprising (a) a ginger ingredient, (b) vinegar or an aqueous solution of a physiologically acceptable acid, and (c) a viscosity-enhancing agent.

-A kit comprising: (a) a topical pharmaceutical composition comprising U) a ginger ingredient, (ii) vinegar or a physiologically acceptable acid, and (iii) a viscosity-enhancing agent; wherein the viscosity enhancing agent is also a skin penetration enhancing or skin hydrating agent or the composition further comprises a skin penetration enhancing or skin hydrating agent; and (b) a source of heat or a heating means.

-A kit for use in alleviating or reversing a clinical symptom selected from rigidity, stiffness, loss of mobility, loss of flexibility and swelling in a part or region of the body, comprising: (a) a topical pharmaceutical composition comprising (i) a ginger ingredient, (ii) vinegar or a physiologically acceptable acid, and (iii) a viscosity-enhancing or gelling agent; and (b) instructions for use.

Detailed Description of the Invention

Composition Ingredients Compositions of the invention include a ginger ingredient. The term "ginger ingredient" means an ingredient which is ginger, which comprises ginger, which is present in ginger, or which is obtained from ginger. It may be, for instance, fresh ginger, dried ginger, powdered ginger, ginger extract, ginger tincture, essential oil of ginger or a constituent compound of ginger. Essential oilof ginger is particularly suitable. When it is a constituent compound of ginger, i.e. a compound that occurs naturally in ginger, it may be obtained from ginger or produced synthetically. The constituent compounds ofprincipal interest are available commercially.

Fresh ginger, dried ginger, ginger extract, ginger tincture and essential oil of ginger are also available commercially. Ginger extract and ginger tincture may be prepared from ginger by solvent extraction using conventional extraction techniques. For instance, ginger extract may be prepared by reducing dried ginger to wanules or powder and treating the granules or powder with a suitable solvent. The resulting crude extract solution may be used as is or the solvent may be evaporated to leave a dry crude extract. In either ease the crude extract may be purified using conventional techniques to form pure extract. Suitable solvents for ginger extraction include organic solvents such as alcohols (e.g. ethanol or isopropanol), acetone and ethyl acetate. Solvent mixtures may also be used, such as mixtures of water and an organic solvent and mixtures of alcohols.

Essential oil of ginger may be prepared by the steam distillation or solvent distillation of the ginger rhizome. Alternatively, oil of ginger may be obtained by supercritical fluid extraction of ginger using CO2.

Over 400 compounds have been identified in ginger, including zingerone, shogaoLs and gingerols. The major components are [6]-gingerol, [8]-gingerol, zingerone, [6]-shogaol and 1.8-cineole (Int. Journal of ChemTech Research, vol. 2, no. 1, pp 700-705, Jan-Mar 2010). Ginger contains up to three percent of a fragrant essential oil whose main constituents are sesquiterpenoids, with (-)-zingibcrcne as the main component. One or more of any of the compounds present in ginger (the ginger rhizome) may be used as the ginger ingredient in the present invention. For instance, the ginger ingredient is or comprises at least one compound selected from: (S)-5-hydroxy-1 -(4-hydroxy-3-methoxyphenyl)-3-decanone ([6]-gingerol); (S)-5-Flydroxy-I -(4-hydroxy-3-mcthoxyphcnyl)-3-dodecanone ([8]-gingcrol); (S)-5-Uydroxy-I -(4-hydroxy-3-methoxyphenyl)-3-tetradecanone ([1 O]-gingerol); (F)-1 -(4-Hydroxy-3-methoxyphenyl)dee-4-en-3-one ([6]-shogaol); 4-(4-hydroxy-3-methoxyphenyl)-2-butanone (zingerone); I,3,3-Trimethyl-2-oxabieyclo[2,2,2oetane (1,8-eineole); and 2-Methyl-5-(6-methylhept-5-en-2-yl)cyelohexa-1,3-diene ((-)-zingiberene).

In one embodiment of the invention, the ginger ingredient is essential oil of ginger. In another embodiment the ginger ingredient is selected from fresh ginger, dried ginger, ginger extract, ginger tincture and the constituent compounds of ginger, and the composition further includes a pharmaceutically acceptable oil. In this embodiment the ginger ingredient is, for instance, selected from the hydrophobic compounds of ginger such as the scsquitcrpenoids, for instance (-)-zingibcrcnc. Suitable oils in this context are those that are non-allergenic and may therefore be safely applied to the skin. Examples include grapeseed oil, almond oil, tea tree oil, lavender oil, citrus oil (for instance, lemon), frankincense and mineral oils.

Compositions of the invention include vinegar or an aqueous solution ofa physiologically acceptable acid. Vinegar itself comprises an aqueous solution of acetic acid. Any type of vinegar may be used, although white vinegar is particularly suitable. The physiologically acceptable acid must be an acid that is suitable for application to the skin of a human or animal subject. Suitable acids include acetic acid, citric acid and tartaric acid.

Compositions of the invention further include a viscosity-enhancing agent. This forms a gel or gel-like formulation in a solvent, typically water, and thereby provides a carrier for the other components of the composition. The presence of a separate carrier is therefore

S

optional rather than essential in compositions of the invention. The viscosity-enhancing agent also imparts the desired consistency and texture to the composition of the invention.

It is desirable for a skin penetration enhancing or skin hydrating agent to be included in compositions of the invention. This maybe the viscosity-enhancing agent itself. For instance, xanthan gum is known to have skin hydrating properties. Alternatively or additionally a separate skin penetration enhancing or skin hydrating agent may be included in the composition. Skin penetration enhancing agents are discussed fhrther below.

The gel or gel-like formulation is desirably spreadable. The term "spreadable" in this context means that the formulation flows at low strain; it can thus be readily administered to the skin of a human or animal subject. It should nonetheless be rigid enough to remain in place on the skin once it has been administered. In some contexts a more rigid formulation is required to start with, for instance in veterinary applications, although the formulation should not be so rigid as to fracture significantly if subjected to strain in the form of rubbing.

The viscosity-eithaneing agent may comprise one or more of the following: xanthan gum, kuzu root starch, glucomannan gums, galactomannan gums, alginie acid and salts thereof earageenan, gellan, gelatin, pectin, locust bean gum, glueomannan, gellan, bentonite, carbomers, cellulose, carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, magnesium aluminum silicate, methylcellulose, poloxamers, polyvinyl alcohol and tragaeanth. Suitable salts of alginic acid include sodium alginate, calcium alginate, potassium alginate and ammonium alginate.

Generally the viscosity-enhancing agent is selected from xanthan gum, kuzu root starch, glucomannan gums (for instance, konjac mannan), galactomannan gums (for instance, locust bean gum, tara gum or cassia gum, alginic acid and salts thereof carageenan, gellan, gelatin, pectin, and combinations thereof More typically it is selected from xanthan gum, kuzu root starch, glucomannan gums and combinations thereof In one embodiment of the invention the viscosity-enhancing agent is or comprises xanthan gum. The xanthan may be used in native or deaectylatcd form. Xanthan gum may be used on its own or combined with one or more other ingredients, particularly when a modification in the consistency of the resulting formulation is required. For instance, a combination of xanthan gum with a glucomannan (e.g. konjac-mannan) gives a gel-like formulation that is more rigid, i.e. less spreadable, than a formulation obtained using xanthan gum alone.

Xanthan gum is a polysaecharide produced by the bio-fermentation ofXanthwnonas cwnpestris and sucrose or glucose. It is available in the form of a powder that readily swells in water to create a gel-like formulation. Industry guidelines recommend using from 0.05% -3% by mass of xanthan gum in water, for instance 0.3% -2%. The dry xanthan gum is mixed with the water at high shear, for instance by whisking.

Xanthan gum is known to have skin hydration properties. This fact may contribute to the ability of a composition of the invention to absorb effectively into the skin once it has been applied. However, absorption of the active components of the composition into the skin may be farther improved by including in the composition a separate skin penetration enhancer. A skin penetration enhancer is also desirable when the composition of the invention includes a viscosity-enhancing agent that does not possess intrinsic skin hydrating or skin penetration enhancing properties.

A skin penetration enhancing agent is a compound that can permeate the stratum corneum, thereby allowing active agents to be transported into or across the skin. Skin penetration enhancers are reviewed by M.E. Lane in International Journal of Pharmaceutics 447 (2013) 12-21. Classes of compound useftil as skin penetration enhancers include alcohols, amides, esters, glycols, glycol ethers, fatty acids, pyrrolidones, sulphoxidcs and fatty acids.

Specific examples of penetration enhancers used in commercial formulations include urea, ethanol, isopropyl alcohol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, diethylene glyeol monoethyl ether, oleie acid, methyl oleate, ethyl oleate, oleyl oleate, sorbitan monooleate, isopropyl myristate, glycerol monolaurate, lauryl lactate, octyl salicylate, isopropyl palmitate, pentadecalactone, octyl dodecanol, diethyltoluamide and triacetin.

One example of a composition of the invention is a topical composition comprising essential oil of ginger, white vinegar and a viscosity enhancing agent comprising xanthan, kuzu root starch or a combination thereof: Typically a composition of the invention comprises no additional pharmaceutically active agents. This distinguishes it from ginger-containing compositions used in Traditional Chinese Medicine (TCM), which contain multiple different active ingredients. It is not unusual fbr TCM compositions to contain ten or more different active agents. In one embodiment of the invention, the composition contains no ingredients other than those specified.

For instance, a composition of the invention may consist of(a) essential oil of ginger, (b) vinegar or a physiologically acceptable acid, and either (ci) a viscosity-enhancing agent that is also a skin penetration enhancing (or skin hydrating) agent, or (c2) a viscosity-enhancing agent and a skin penetration enhancing (or skin hydrating) agent. Alternatively it may consist of(a) a ginger ingredient selected from fresh ginger, dried ginger, ginger extract, ginger tincture and the constituent compounds of ginger (b) vinegar or a physiologically acceptable acid; either (cI) a viscosity-enhancing agent that is also a skin penetration enhancing (or skin hydrating) agent, or (c2) a viscosity-enhancing agent and a skin penetration enhancing (or skin hydrating) agent; and (d) a physiologically acceptable oiL Preparation of the Composition A topical pharmaceutical composition of the invention may be prepared by combining the specified constituents in suitable proportions in any order using conventional techniques.

For instance, the ginger ingredient and the vinegar or acid are combined and then the viscosity-enhancing agent is added to the resulting mixture, typically with agitation.

When xanthan gum is the viscosity-enhancing agent it is typically mixed with the other ingredients of the composition by being sprinkled finely with whisking until the mixture thickens. Kuzu root starch is typically dissolved in aqueous ingredients and then the mixture is stirred continuously with heating until it thickens and turns translucent.

Cellulose is typically mixed with water at 40°C -50°C and then whisked steadily until it thickens. Carragccnan is whisked steadily into warm water while heating the water to boiling point, when thickening occurs.

The composition is formulated using amounts of the ginger ingredient and vinegar or acid that are effective to achieve the desired reduction in rigidity, stifthess, loss of mobility, loss of flexibility or swelling without causing irritation to the skin of the patient. Typically the composition comprises from 0.5 -97% by volume of vinegar or of an aqueous solution of the acid. When the ginger ingredient is essential oil of ginger, the composition typically comprises from 0.5 -25% by volume of the ginger ingredient. The viscosity-enhancing agent is used in the amount required to achieve the thickness and/or consistency desired in the resulting composition of the invention.

If desired, the composition of the invention may further comprise one or more further pharmaceutically acceptable carriers, diluents, excipients or additives. A typical formulation is prepared by mixing a composition of the present invention and a carrier, diluent or excipient. Suitable carriers, diluents and excipients arc well known in the art and include materials such as polysaccharides, waxes, water soluble and/or swellable polymers, hydrophilic or hydrophobic materials, gelatin, oils, solvents, water and the like.

In general, safe solvents are non-toxic aqueous solvents such as water and other non-toxic solvents that are soluble or miscible in water. Suitable aqueous solvents include water, ethanol, propylene glycol, polyethylene glycols and mixtures thereof.

Suitable additives include buffers, stabilizing agents, pertliming agents, surfactants, wetting agents, lubricating agents, emulsifiers, suspending agents, preservatives, antioxidants, opaquing agents, glidants, processing aids, colorants and other known additives. The purpose of such additives may be to provide a desired presentation of the composition of the invention or to aid in its manufacture.

In one embodiment, the invention provides a kit comprising a container which comprises a topical pharmaceutical composition of the invention. The container maybe, for instance, a bottle, vial, bag or plastic package. It may be an airtight container. The kit may further comprise a label or package insert on or associated with the container, providing information or instructions relating to the use of the composition in treating, alleviating or relieving stiffness, rigidity, lack of mobility, lack of flexibility and/or swelling in a body part or body region.

In one aspect of the invention a kit comprises: (a) a topical pharmaceutical composition comprising (i) a ginger ingredient, (ii) vinegar or a physiologically acceptable acid, and (iii) a viscosity-enhancing agent; wherein the viscosity enhancing agent is also a skin penetration enhancing or skin hydrating agent or the composition further comprises a skin penetration enhancing or skin hydrating agent; and (b) a source of heat or a heating means.

The source of heat or the heating means may be combined with the composition in the kit, or presentcd scparately from it in the kit. For instancc, the source of heat or the heating means may be an infra-red lamp which is packaged for sale with the topical composition.

It may alternatively be a thermal pad or patch, a heat salt gel pad or a heated mitten or glove. Heat sources and heating means are discussed further below.

The pad, patch, mitten or glove may be coated or impregnated with the composition, or it may be presented separately from the composition such that it can be applied or used as appropriate in combination with the composition by a clinical technician or practitioner, or the end user. The pad or patch may be provided with attachment means that are suitable for the part or region of the body and the particular subject (human or animal) being treated. The pad or patch may be tailored to the location, size and/or other characteristic of the part or region of the body being treated.

Any kit of the invention may comprise the composition in a presentational format that dclivcrs thc composition in suitabic measurcd, or mctercd, amounts. This enhances convenience and compliance for the end user, as well as facilitating the administration of the composition to a patient by a clinical technician.

Use of the Composition It has bccn found that topical pharmaccutical compositions of thc invcntion arc cffcctivc in relieving the stiffness, rigidity, lack of mobility, lack of flexibility and swelling associated with a wide range of clinical conditions. A clinical symptom selected from rigidity, stiffncss, loss of mobility, loss of ficxibility and swclling in a part or rcgion ofthc body of a human or animal subject may thus be alleviated or reversed by the cutaneous administration of a composition of the invention to a subject. Rigidity and stifthess are thcrcby rcduccd or allcviatcd. Mobility and flcxibility arc thcrcby improvcd; in many cases they are restored to a normal range.

A common factor associatcd with thc symptoms bcing rclicvcd is thought to bc underlying pathological calcification. Accordingly, in one embodiment the clinical symptom being alleviated or reversed by a composition of the invention is associated with, or caused by, pathological calcification in the body which commonly follows inflammatory processes.

Calcification is variously dcfincd as "tissue hardcncd by dcposition of limc salts" and "abnormal hardening or thickening of tissue". The American Heritage Science Dictionary © 2005, Houghton Mifflin Company, dcfincs calcification as follows: "Thc accumulation of calcium or calcium salts in a body tissue. Calcification normally occurs in the formation of bone, but can be deposited abnormally, as in the lungs." Bone calcification results from calcium deposit build-up in the joints, for iiistance as a result of arthritis or injury. Calcium deposits commonly build up in areas where body cells are damaged, such as in breast tissue, joints or artery walls. As noted above, calcification oflen results in hardcning of thc tissue.

A topical composition of thc invcntion may bc uscd on or ovcr any body rcgion or body part affected by a clinical symptom selected from rigidity, stifthess, swelling, loss of mobility and loss of tlcxibility. For instanec, it may bc uscd to trcat a bonc, joint, ligament, tendon, muscle, fascia, connective tissue, soft tissue or blood vessel. It may be applied to the head, neck, shoulder, arm, elbow, wrist, hand, finger, thumb, spine (cervical, thoracic or lumbar), sacrum, hip, leg, knee, ankle, heel, foot or toe. It is administered to the skin, i.c. by cutancous administration. It is suitablc for administration to both human and animal subjccts and thus has both pharmaccutical and vctcrinary application.

A human or animal subjcct suffering from any clinical condition, disorder or disease characterised by a clinical symptom selected from rigidity, stiffness, swelling, loss of mobility and loss of flexibility may benefit from treatment with a composition of the invention. For instance, the clinical symptom may be caused by, or associated with, any of thc following: a sports injury, ankyolosing spondilitis, calcificd lipoma, lipoedcma, Peyronie's disease, breast calcification, heterotopic ossification, otoscierosis (ossification of ear ossicles), bunion, tendinosis, frozen shoulder (adhesive capsulitis, omarthritis), osteoarthritis, Achilles Tendinitis, calcaneal spur (heel spur), osteophyte, plantar fasciitis, cervical spondylosis, spinal stenosis, disc calcification, kyphosis, dystrophic calcification (carpal tunnel syndrome), prolapse of lumbar intervertebral disc, hyperosteogeny, rheumatic osteoarthrosis, osteoarthropathy, swelling, inflammation, pain, osteoproliferation, musculoskeletal or joint-related conditions, rheumatism, muscular atrophy, heci pain, lumbar invcrtebral disc pain, cramp in the leg or foot, rheumatic pain, rheumatoid arthritis, muscle fatigue, bone hyperplasia, bruises/haematoma, arthroncus (joint swelling), arthralgia, scapulohumeral periarthritis, ischial neuralgia (sciatic nerve pain), lumbar muscle degeneration, salivary calculi, inflammation or fibromyalgia.

In use, the composition of the invention is applied to, on or over the affected part or region of the body, for instance using a spatula, and is spread out into a layer of the desired thickness. Once applied, the layer absorbs into the skin. Typically the layer is from 2- 10mm thick, for instance 2 -8mm thick, or 3 -4mm thick. The exact thickness will depend on a number of factors including, for instance, the location and severity of the symptom being treated, the depth and density of the tissue being targeted and the amount of body fat overlying the area or region being treated.

The composition may be applied over a extended area around the affected part or region of thc body, for instancc laterally to said part or rcgion. If the part or region bcing treatcd includes bone, for instance a joint, it is important for the composition to be applied such that it can penetrate into less bony areas. For example, when the composition is used to treat the spine it is generally applied both on the dorsal surface and immediately lateral to the spine to allow absorption through the back and sides of the intervertebral spaces.

Repeated application of thc composition may be required, either immediately or after a period of time, depending on the severity of the condition or symptom being treated. For instance, the composition may be applied on a given occasion and then reapplied on one or more subsequent occasions separated by intervals of several days, typically 4 or more days.

The efficacy of the composition of the invention is generally improved with heat. In one embodiment the composition of the invention is itself warmed prior to application to the skin of the subject being treated. Another variant involves warming or heating the area or region of the body being treated. The invention therefore includes the administration of the composition to the skin of the human or animal subject in combination with the application of heat to the site of said administration. Said application of heat takes place prior to, after or simultaneously with the administration of the composition.

Any suitable heat source or means of heating may be used to warm the area or region of the body, either before or after application of the composition of the invention. An appropriate choice can be made by the practitioner. The heat source may, for example, provide direct heat, radiant heat or hot air. The body part or region needs to be warmed sufficiently to promote absorption of the composition into the skin but not so much as to dry the composition too rapidly.

Examples of suitable heat sources include a hairdryer, infrared lamp, any source of radiant heat, a chemical heating pad such as a heat salt gel pad, a trans-dermal heat patch, an electrical heating pad, a Moxa Stick (used in Traditional Chinese Medicine for moxibustion) or electrical Moxa simulator (Moxa Pen), a hot wax bath, a hot water bottle, a heat pad, a hot water bath, and far infrared heating devices such as TDP (Teding Diancibo Pu, or infrared electromagnetic heat) lamps. Where appropriate, any of the abovementioned heat sources and heating means may be included in a kit of the invention as described above.

The area of skin to which the composition of the invention is (or has been) applied is warmed to a temperature that depends on various factors such as the sensitivity of the individual to heat, the thickness of gel applied, room temperature and individual body temperature. Warming typically continues until the skin surface temperature is in the range of from 37°C -41°C,usually from 38°C -40°C.

The invention will be further illustrated in the following Examples.

Example 1: Preparation of Composition A composition was prepared by combining Sml (approx 3g) of essential oil of ginger with ml of white vinegar. Powdered xanthan gum (1. 5m1, approx. I g) was added to the resuhing emulsion, with agitation. The resulting composition was a semi-opaque/translucent gel-I ike formulation.

Example 2: Testing in the Clinic Test subjects A total of 100 patients were recruited, each one suffering from at least one of the following: a sports injury, ankyolosing spondilitis, calcified lipoma, breast scarring or calcification, heterotopie ossification, otoselerosis, bunion, tendinosis, adhesive eapsulitis, osteoarthritis, Achilles Tendinitis, calcaneal spur (heel spur), osteophyte, plantar fasciitis, cervical spondylosis, spinal stenosis, disc calcification, kyphosis, dystrophic calcification (carpal tunnel syndrome), prolapse of lumbar intervertebral disc, hyperosteogeny, rheumatic osteoarthrosis, osteoarthropathy, swelling, inflammation, pain, osteoproliferation, musculoskeletal or joint-related conditions, rheumatism, muscular atrophy, heel pain, lumbar invertebral disc pain, cramp in the leg or foot, rheumatic pain, rheumatoid arthritis, omarthritis, muscle fatigue, bone hyperplasia, bruises/haematoma, arthroncus (joint swelling), arthralgia, scapulohumeral periarthritis, ishioneuralgia (sciatic nerve pain), lumbar muscle degeneration, salivary calculi, inflammation or fibromyalgia.

In total, there were 210 different regions needing treatment (i.e. some subjects presented with symptoms in more than one region of the body, for instance knee and lumbar spine).

Test compositions The following two compositions of the invention were prepared, using the technique described in Example 1. In the case of Formulation 2, the kuzu was blended into the vinegar and ginger oil emulsion with heating.

Formulation 1: Xanthan powder = 1.25m1 (approx. lg) white vinegar = 11 OmI ginger oil = 5m1 Formulation 2: Kuzu = 3m! white vinegar = 6Oml ginger oil = 2.5m1 Patient Treatment Formulation I or 2 was applied over the affected area(s) of each patient and, if appropriate, lateral to the region to increase 3D adsorption. For the spine, application was to the dorsal surface and also immediate!y!ateral to the spine to allow absorption throughout the back and sides of the inter vertebra! spaces. For the knee, the composition was app!ied over "eyes of knee" (lateral and medial to lower border ofpatella) and also above upper border ofpatella.

The composition was applied in a layer of from 2-8 mm thick, usually 3-4 mm thick. The exact thickness chosen in each ease depended upon the severity of the symptom being treated, the depth and density of scar/calcified tissue to be treated and on the amount of body fat over!ying the area or region being treated.

In severe cases application of the composition was repeated, either in one session or on a subsequent occasion 4 or more days later. This is because there continues to be change for 3-4 days after the fir st administration (sometimes accompanied by very mi!d inflammation) which results in further improvement. Patients were encouraged to mobilise the area after completed treatments. Sometimes crepitation could be felt, which rapidly resolved upon 2 to 6 repetitions of the re!evant joint movement.

For some of the patients, application of the composition was preceded, accompanied or followed by heating of the body part being treated. Heat was applied by various methods, most commonly using a TDP heat lamp. The skin surface temperature when patients reported feeling very hot varied from 37-41°C, most commonly from 38-39°C.

Results In 85% of patients an improvement occurred almost immediately, i.e. after approximately minutes.

Following treatment there was a process of continued effect which in most trial eases was noted to last up to 72 hours. Only about 40% of those treated notice this effect and a small proportion (approximately 20%) were aware of a low grade continued inflammatory response which resolved over 4 days. This typically involved slight tenderness and redness which no one expressed concern about. Those patients who experienced this effect reported greater continued improvement post-application.

In the trial overall, a significant improvement in symptoms was seen in 96% of the patients treated.

Example 3: Individual Case Histories In each case history described below, a composition of Example 1 (denoted "Gel") was used.

1. Case History Showing Effects on Disc Damage /Compression oJSciatic Nerve Treatment: Gel & TDP Heat Lamp Age 63, Female Duration of condition: 16 months Occupation: Housewife! DIY Description of condition: Seiatie nerve trapped on left, refers to hip. MRI shows torn!eomprcsscd L5!S1 disc with other disc compression Number of treatments: 3 Area Applied: L3 to S4 Dates: 07/02/13, 19/02/13, 26/02/13 Area Applied: 111, L2-L3 Dates: 26/02/13 Results: Patient states "No pain at all in hip which is a miracle-even when driving" % Improvement: 90% 2. Case History Showing Effects on Severe Cervical Arthritis/Spinal Stenosis Tremor Treatment: Gel & TDP Heat Lamp Age 81, Female Duration of condition: 10 years following bad fall Occupation: Retired Coffee Shop Manager Description ofeondition: Constant Head and bilateral hand/arm tremor so severe that she cannot get a cup to her mouth with any liquid remaining in it.

Number of treatments 7 Area Applied: C3 to 19 Dates: 07/12/11 after this back freer /arms steadier Area Applied: C3 to 16 Dates: 14/12/11 after this much less tremor, what remains is almost imperceptible Area Applied: C3 to 16 Dates: 15/02/12 improved but some remaining pain at base of neck Area Applied: C3 to CS Dates: 28/03/12 generally very good Area Applied: C3 to CS Dates: 16/05/12 generally very good, top up Area Applied: C3 toTS Dates: 11/07/12 shaking not returned some elbow soreness inner R Area Applied: C3 to L2 Dates: 27/02/13 shaking not returned, a little stiffer Results: Patient very pleased and full mobility achieved % Improvement: 85% 3. Case History Showing EtJCcts on Ankylosing Spondylitis Treatment: Gel & TDP Heat Lamp Age 43, Female Duration of condition: 21 years Occupation: Doctor in Medical Scientific Research Description of condition: Comes and goes, flares making back and neck sore and rigid and remits but chronic slow deterioration Number of treatments: 3 Area Applied: Sacroiliac Dates: 08/02112 Much improved flexibility on forward bend and lifting feet for socks. Eg could only reach fingers to knees pre treatment but could reach her ankles immediately afterwards.

Area Applied: C3 to T3 Dates: 15/02/12 Improvement stable Area Applied: C3 to C7 sides of cervical spine Dates: 29/02/12 Headaches at base of skull at C2/3. Hence treatment applied to this region today. Lateral neck movement still a little restricted especially at C4/5/6.

Results: Range of movement better -reversed into a parking space by turning her head, which hasn't been possible for years! % Improvement 85%; no further treatment required to date.

4. Case History Showing Ff7 ects on Knee Arthritis Treatment: Gel & TDP Heat Lamp Age 70, Male Duration of condition: Right knee cartilage removed 1970. Left knee cartilage shaved 1986. Bakers cyst comes and goes on right knee.

Occupation: Builder/Roofer Description ofcondition: More painftii now than ever.

Number of treatments: 3 Area Applied: Anterior aspect of knees Dates: 04/04/13 Immediately after this treatment he had no pain and could lift his legs and put on his trousers by bending his knees which he hasn't been able to do for more than 10 years. Crepitation much reduced on bending and rapidly dissipated on repetition.

Area Applied: Anterior aspect of knees Dates: 11/04/13 Wife said "he was walking instead of shuffling" after the first treatment.

Continued improvement.

Area Applied: Anterior aspect of knees Dates: 9/05/13 On his knees at work a lot this week. Still greatly increased range of movement.

Pain still hugely improved but comes and goes with some occasional pain under knee caps.

Results: Pain relief and normal mobility % Improvement: 80% 5. Case History Showing Effects on Tinnitus following Otosclerosis Treatment: Gel & TDP Heat Lamp Age 41, Female Duration of condition: 23 years.

Occupation: Factory Worker Description of condition: Deaf in right ear since Otoselerosis at 18 years accompanied by loud "marching termites like Tom and Jerry" drumming tinrntus continuous.

Number of treatments: 3 Area Applied: Posterior to ear and below mastoid. Dates: 06/10/11 Immediately after this treatment she had no tinnitus.

Area Applied: Posterior to ear and below mastoid. Dates: 08/12/11 No tinnitus, no marching ants even with nasal congestion.

Noticing sound more as too loud at work so perhaps a beneficial effect on deafness.

Area Applied: Posterior to ear and below mastoid. Dates: 25/01/12 Tinnitus remained resolved despite a cold Results: As at May 2013 still no tinnitus.

% Improvement: 70% 6. Case Histoty Showing Effects on Osteoarthritis in a Horse Treatment: Gel & Click to Heat Salt Gel Pads Agc 25, Marc Duration of condition: 10 years.

Description of condition: Retired due to arthritis in knees, now so severe in left knee that barely able to walk, very static in field despite veterinary medication so about to be put down.

Number of treatments: 2 Area Applied: Over whole of left knee (heat applied by (lick to Heat Salt Gel Pads taped around joint over medicated gel) Dates: 14/10/12 Immediately after this treatment knee joint reduced from 43 cm circumference to 35.5 cm. Horse was moving more freely.

Area Applied: Over whole of left knee (heat applied by Click to Heat Salt Gel Pads' tapcd around joint over medicated gel)

Dates: 20/10/12 Horse was 200 yards down the field

cantered! trotted to the field gate. Still limping a little. Knee reduced to 33 cm. Knee was no longer hot! inflamed to touch.

Resuhs: As at May 2013 improvement still maintained although limping a little more. N.B. Fur on horse didn't impede effectiveness of product and animal which is rather tetchy appeared to enjoy the process, standing still and complying well. Video/Photos available.

% Improvement: 65% 7. Case Histoty Showing Effects on Kyphosis in a Child Treatment: Gel & TDP Heat Lamp Age 7, Female Duration of condition: 2-3 years.

Occupation: Child Description of condition: Back badly misaligned and rigid in this position. Lumbar region straight with no natural curve, Thoracic region deep dorsal curvature and curving in an "5" laterally. Low energy, poor apetite, bursts of energy yet easily exhausted.

Muscle/joint aches, very emotional, struggling at school.

Number of treatments: 3 Area Applied: TI-L5 Dates: 21/02/13 Immediately after this treatment her back became softer and less rigid. Given simple spinal stretching exercise to do for 15 seconds twice a day (Previous physiotherapy has not helped). Mother reported that she was brighter in herself and better for I week then alternating between energetic and exhausted.

Area Applied: Ti-L5 Dates: 07/03/13 Post Gel treatment very gentle realignment at C3, C4, CS all easy as back now very flexible.

Continue stretches at home. After this treatment Mother reported that she was a different child at home and school reported that her work quality has immeasurably improved.

Area Applied: T12 -L3; C3 -T8 Dates: 28/03/13 Back almost fully aligned with a much more flexible spine. T12 -L3; C3 -18 still slightly rigid. Post gel application gentle easing of L2, T3 and T7.

Results: Normal child % Improvement: 90% 8. Case History Showing Effi?cts on Reactive Arthritis Finger Joints Treatment: Gel Alone (No Heat) Age 55, Female Duration of condition: 3 weeks Occupation: Health worker Description of condition: Sudden onset of enlarged finger joints already lasting 3 weeks and increasing in a reactive arthritis sufferer. Previous attacks have taken months to resolve. 2 joints on right index, 1 on right middle, 1 on right ring, I on left index Fingers.

Number of treatments: 14 Area Applied: Over affected joints, unheated night and morning for 14 days. Dates: 07/12 Results: First 2 days more inflamed and sore then steady improvement until resolved after 2 weeks. Smaller & less affected joints recovered quicker % Improvement: 100% 9. Case History Showing Effects on Multi-joint Arthritis Treatment: Gel & TDP Heat Lamp Age 64, Male Duration of condition: 10 years; worsened 1 year ago Occupation: Retired Builder Description of condition: Pain chronic and most days but worsened a year ago. Since then, often cannot go out, right leg collapses. Intolerable pain. Joints can swell to 4 times normal size, will hardly bend and are hot /painful. Worst in damp weather. Shoulders both "frozen" with limited range of movement,left hand calcified and swollen 2" gap short of forming a fist.

Number of treatments: 6 Area Applied: Shoulder -applied over the whole joint bilaterally, whole left hand inner and outer aspect from earpals to phalanges. Also Carpals on right. Dates: 20/10/11 immediately after treatment pain reduced and range of movement near normal in all joints, able to form a fist for first time in ages.

Area Applied: L4-S4 Dates: 28/02/12 After last treatment joints are excellent and twinges after working come to nothing so returned to see if back will respond in the same way.

Area Applied: Coccyx (over old operation scar which has adhered) -T3 Dates: 07/03/12 More mobile but not fully mobile in back yet. Otherjoints play up a bit after excessive use e.g. heavy gardening but recover rapidly.

Area Applied: Coccyx -sacral scar (now half softened and released) Dates: 2 1/03/12 Walking and feeling a lot better, upright but L5 disc deterioration is main remaining problem.

Area Applied: Sacroiliac Dates: 05/04/12 Back much better, very good, tiny remaining pain but dismissed as nothing. In the past a head cold would set off the back and joints within 5 days but

now all is stable.

Area Applied: Knees Dates: 21/03/12 Returned for top up for knees which grumble a little but generally well despite very damp weather which used to be a trigger.

Results: Transformed, very active, very mobile, little pain % Improvement: 95% 10. Case History Showing Efjicts on Neck/Back pain and Fatigue Treatment: Gel & TDP Heat Lamp Age 36, Female Duration of condition: 16 years following car accident, worsened 5 years ago after another car accident.

Occupation: Teaching Assistant Description ofeondition: Pain C2-T9, L2-L5, Sacroiliac (especially left affecting leg mobility); Headaches Occipital to front over eye; Chronic fatigue.

Number of treatments: Area Applied: Sacrum Dates: 06/03/13 Immediately after this treatment she could lift her left leg and place it across her right knee (similar to Lotus Position),and could lift her left knee and lower leg up so that the knee was level with chest.

Results: Subject was amazed as she had relied upon raising this leg manually with her hands for years.

% Improvement: 90% II. Case Histoty Showing Etjècts on Scar tissue and Chmnic Constant Pain in Lower Leg Treatment: Gel & TDP Heat Lamp Age 71, Male Duration of condition: 15 years Occupation: Retired from Printing; Builder; Plumber Description of condition: Constant pain (very severe at night) below left knee laterally and on foot in line with 4151h toes onset 15 years ago as an itch finally diagnosed as Morton's Neuroma and surgically removed 2 years ago which has left adhered scar tissue and calcified joints. Also virtually immovable right big toe. Also low back pain following fall off ladder 30 years ago onto and damaging back leaving sacrum with a layer of solidity (calcified scar tissuc) 4 cm thick. Has to do 30 pelvic lifts to be able to get out of bed.

Number of treatments 4 Area Applied: Sacrum Dates: 16/02/12 After treatment reduced solidity and tension in low back by 50% and by 23/02 the solidity had reduced to 1 cm.

Area Applied: Sacrum Dates: 23/02/12 After treatment back pain much better, foot pain remains. MRI scan and NI-IS but no further improvement in leg pain.

Area Applied: On sear tissue 1 cm up from distal point of scar on left foot.

On lateral side of right big toe at the base. Then mobilise now less rigid big toe. Dates: 22/11/12 Big toe much more mobile just slightly stiff at middle joint.

Area Applied: On lateral side and also at middle joint of right big toe at the base. Dates: 06/12/12 Scar tissue on left foot almost completely healed and flexible with good range of movement Results: On 19/12/12 Toe movement now amazing'. Sleeping much better despite nerve pain in leg not completely eradicated but massively reduced. Circulation (can be gouty) improved in both feet. Now off painkillers such as Gabapentin.

% Improvement 80% /2. Case Histo;y Showing Effects on Trigger Finger Treatment: Gel & TDP Heat Lamp Age 70, Male Duration of condition: 2 Years Occupation: Carpenter Description of condition: Trigger finger on right hand at proximal joint 4th of metacarpal and also occasionally catching on same position on left hand. Carpal tunnels also tight.

Number of treatments: 2 Area Applied: Over affected hand palms and inner wrists over carpal tunnel. Dates: 30/10/12 Area Applied: Over affected hand palms and iimer wrists over carpal tunnel. Dates: 08/11/12 Much better after first treatment but fingers still catching slightly.

Results: Satisfied with improvement following two treatments and

stable.

% Improvement: 90% 13. Case History Showing Effects on Plantar Fasciitis Treatment: Gel & TDP Heat Lamp Age 61, Female Duration of condition: 8 months (10 years previous on/off foot problems) Occupation: Teacher Description of condition: Plantar Fasciitis severe incapacitating in right foot.

Number of treatments: 3 Area Applied: Sacrum. Dates: 19/07/12 Area Applied: Sacrum. Dates: 02/08/12 Improved after first treatment for 1 day Area Applied: Over outer edge right heel in painful area Dates: 11/09/12 Much better after 11/09 treatment foot has hardly twinged.

Area Applied: Over outer edge right heel in painful area Dates: 18/09/12 No pain after this session and still stable! pain free as at May Results: Plantar fasciitis resolved.

% Improvement: 100% 14. Case Histoty Showing Effects on Foot Tendinitis Treatment: Gel & TDP Heat Lamp Age 48, Female Duration of condition: 5 years Occupation: Chef Description ofcondition: Seen multiple Orthopaedic Specialists and diagnosis of inflamed foot tendons (tendon scans show no ruptures). 5 1⁄4 years ago reached point where unable to depress clutch to change gear. Foot pain is especially between the cuneiform and the medial calcaneus and between the lateral tuberosity of the 5th metatarsal and the lateral maleolus.

Number of treatments 2 Area Applied: On painful sites of feet (see above) Dates: 08/05/13 Improved flexibility of feet.

Area Applied: On painful sites of feet (see above) Dates: 15/05/13 Not now in constant pain.

Results: Huge improvement, near normal now. Pain killers reduced from 8-10 per day to 0-1. Now not always taking I and previously couldn't even get out of bed without 1.

% Improvement 80% Treatment continues as can be on her feet 14 hours/day in busy summer period and necessary to ensure that improvement is robust enough to maintain in these circumstances.

Claims

CLAIMSA topical pharmaceutical composition for use in alleviating or reversing a clinical symptom selected from rigidity, stiffliess, loss of mobility, loss of flexibility and swelling in a part or region of thc body, whcrein the composition compriscs (a) a ginger ingrcdient, (b) vinegar or a physiologically acceptable acid, and (c) a viscosity-enhancing agent.
2. A composition for usc according to claim I, wherein the viscosity enhancing agent is also a skin penetration enhancing or skin hydration enhancing agent, or the composition further comprises a skin penetration enhancing or skin hydratioll enhancrng agent.
3. A composition for use according to claim I or 2 wherein the viscosity enhancing agent is sclcctcd from xanthan gum, kuzu root starch, glucomailnan gums, galactomannan gums, alginic acid and salts thereof; carageenan, gellan, gelatin, pectin, and combinations thereof.
4. A composition for use according to any one of the preceding claims wherein the viscosity enhancing agent is selected from xanthan gum, kuzu root starch, glucomannan gums and combinations thereof
5. A composition for use according to any one of the preceding claims wherein the ginger ingredient is selected from fresh ginger, powdered ginger, essential oil of ginger, ginger extract and compounds present in the ginger rhizome.
6. A composition for use according to any onc of the preceding claims whercin the ginger ingredient is or comprises at least one compound selected from: (S)-5-hydroxy-1 -(4-hydroxy-3-mcthoxyphenyl)-3-dccanonc ([6]-gingcrol); (S)-5-Hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-dodecanone ([8]-gingerol); (S)-5-Hydroxy-1 -(4-hydroxy-3-methoxyphenyl)-3-tetradecanone ([1 O]-gingerol); (E)-1 -(4-Hydroxy-3-methoxyphenyl)dec-4-en-3-one ([6]-shogaol); 4-(4-hydroxy-3-methoxyphenyl)-2-butanone (zingeronc); 1,3,3-Trimethyl-2-oxabicyclo[2,2,2loctane (1,8-cineole); and 2-Mcthyl-5-(6-mcthylhcpt-5-cn-2-yl)cyclohcxa-I,3-dicnc ((-)-zingibcrcnc).
7. A composition for use according to any one of the preceding claims which comprises one or more skin penetration enhancing agents.
8. A composition for use according to any one of the preceding claims which further comprises one or more pharmaceutically acceptable carriers, diluents, excipients or additives.
9. A composition for use according to any one of the preceding claims wherein the clinical symptom is associated with, or caused by, pathological calcification in the body.
10. A composition for use according to claim 9 whcrcin thc pathological calcification occurs in a bone, joint, ligament, tendon, connective tissue, soft tissue or blood vessel.
11. A composition for use according to any one of the preceding claims, wherein the use comprises the cutaneous administration of the composition to the site of said clinical symptom and the application of heat to said site.
12. A composition for usc according to claim 11 wherein the application of heat takes place prior to, after or simultaneously with the administration of the composition.
13. A composition for use according to any one ofthe preceding claims wherein the clinical symptom is caused by, or associated with, any of the following: a sports injury, ankyolosing spondilitis, calcified lipoma, lipocdcma, Pcyronic's discasc, breast calcification, heterotopic ossification, otoselerosis (ossification of ear ossicles), bunion, tendinosis, frozen shoulder (adhesive eapsulitis, omarthritis), osteoarthritis, Achilles Tendinitis, calcaneal spur (heel spur), osteophyte, plantar fasciitis, cervical spondylosis, spinal stenosis, disc calcification, kyphosis, dystrophic calcification (earpal tunnel syndrome), prolapse of lumbar intervertebral disc, hyperosteogeny, rheumatic osteoarthrosis, ostcoarthropathy, swelling, inflammation, pain, osteoproliferation, musculoskeletal or joint-related conditions, rheumatism, muscular atrophy, heel pain, lumbar invertcbral disc pain, cramp in the leg or foot, rheumatic pain, rheumatoid arthritis, muscle fatigue, bone hyperplasia, bruises/haematoma, artbroncus (Joint swelling), arthralgia, scapulohumeral periarthritis, ischial neuralgia (sciatic nerve pain), lumbar muscle degeneration, salivary calculi, inflammation or fibromyalgia.
14. A topical pharmaceutical composition which comprises (a) a ginger ingredient, (b) vinegar or a physiologically acceptable acid, and (c) a viscosity-enhancing agent; wherein the viscosity enhancing agent is also a skin penetration enhancing or skin hydrating agent, or the composition further comprises a skin penetration enhancing or skin hydrating agent.
15. A composition according to claim 14 wherein no additional pharmaceutically actiye agent is present.
16. A composition according to claim 14 wherein the viscosity-enhancing agent is selected from xanthan gum, kuzu root starch, glucomannan gums and combinations thereof;.
17. A composition according to claim 14, 15 or 16 wherein the ginger ingredient is selected from fresh ginger, powdered ginger, essential oil of ginger, ginger extract and compounds present in the ginger rhizome.
18. A composition according to any one of claims 14 to 17 wherein the ginger ingredient is or comprises at least one compound selected from: (5)-5-hydroxy-I -(4-hydroxy-3-methoxypheny-3-decanone ([6]-gingero I); (S)-5-Hydroxy-1 -(4-hydroxy-3-mcthoxyphcnyl)-3-dodecanonc ([8]-gingcrol); (S)-5-Hydroxy-1 -(4-hydroxy-3-methoxyphenyl)-3-tetradecanone ([1 O]-gingerol); (F)-1 -(4-Hydroxy-3-mcthoxyphcnyl)dcc-4-cn-3-onc ([6]-shogaol); 4-(4-hydroxy-3-methoxyphenyl)-2-butanone (zingerone); 1,3,3-Trimethyl-2-oxabicyclo[2,2,2]octane (1,8-cineo1e; and 2-Methyl-5-(6-methylhept-5-en-2-yl)cyclohexa-1,3-diene ((-)-zingiberene).
19. A composition according toy one of claims 14 to 18 which further comprises one or more pharmaceutically acceptable carriers, diluents, excipients or additives.
20. A kit coiipiising: (a) a topical pharmaceutical composition comprising (9 a ginger ingredient, (ii) vinegar or a physiologically acceptable acid, and (iii) a viscosity-enhancing agent; wherein the viscosity enhancing agent is also a skin penetration enhancing or skin hydrating agent or thc composition further comprises a skin penetration enhancing or skin hydrating agent; and (b) a source of heat or a heating means.
21. A kit according to claim 20 which takes the form of a thermal pad or patch (dermal heat patch) or a mitten or glove.
22. A kit according to claim 20 or 21 which is for use in alleviating or reversing a clinical symptom selected from rigidity, stilThess, loss of mobility, loss of flexibility and swelling in a part or region of the body.
23. A kit according to claim 20 or 21 which father comprises instructions for use in alleviating or reversing a clinical symptom selected from rigidity, stifthess, loss of mobility, loss of flexibility and swelling in a part or region of the body.