WO2014188214A1

WO2014188214A1 - Topical composition with ginger

Info

Publication number: WO2014188214A1
Application number: PCT/GB2014/051596
Authority: WO
Inventors: Susan Jane Branch
Original assignee: Susan Jane Branch
Priority date: 2013-05-24
Filing date: 2014-05-23
Publication date: 2014-11-27
Also published as: GB201309406D0; GB2514417A

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 is described, wherein the composition 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.

Description

TOPICAL COMPOSITION WITH GINGER

Field of the Invention The 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 give rise to reduced mobility and reduced flexibility. Examples include spondylitis, spinal stenosis, sciatica, arthritic bone spurs, Dupuytren's contracture, 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 steroidal 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. Ginger has a long history of use in traditions of herbal medicine, for instance in the

Ayurvedic and Traditional Chinese Medicine (TCM) systems. It is the aromatic rhizome of the plant Zingiber officinale Roscoe, which is a member of the 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 ottensii, Zingiber citriodorum 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 Dec; 39(4): 342-8 (Snvastava K.C. et al) 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 randomised cross-over study comparing ginger extract with placebo and

Ibuprofen is reported in Osteoarthritis Cartilage, 2000 Jan; 8(1):9-12 (Bliddal H. et al). This shows that ginger extract and Ibuprofen 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 characterised 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. In the context of the present invention the term "swelling" includes lumps in soft tissue, such as nodules and ganglions, and lipomas.

Accordingly, the present invention provides 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, 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, stiffness, loss of mobility, loss of flexibility and swelling in a part or region of the 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 (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.

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 oil of 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 of principal 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 granules 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 case 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 C0₂.

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 (-)-zingiberene 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-l-(4-hydroxy-3-methoxyphenyl)-3-decanone ([6]-gingerol);

(,S)-5-Hydroxy-l-(4-hydroxy-3-methoxyphenyl)-3-dodecanone ([8]-gingerol);

(S)-5-Hydroxy- 1 -(4-hydroxy-3 -methoxyphenyl)-3 -tetradecanone ([ 10]-gingerol);

(£)-l-(4-Hydroxy-3- methoxyphenyl)dec-4-en-3-one ([6]-shogaol);

4-(4-hydroxy-3-methoxyphenyl)-2-butanone (zingerone);

l,3,3-Trimethyl-2-oxabicyclo[2,2,2]octane (1,8-cineole); and

2-Methyl-5-(6-methylhept-5-en-2-yl)cyclohexa-l,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 sesquiterpenoids, for instance (-)-zingiberene. 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 of a 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 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 may be 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 further 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. In some aspects of the invention the composition is warmed prior to application to the skin. The composition may thus be formulated so as to have a spreadable consistency after being warmed to above room temperature or to above body temperature, for instance to a temperature of around 40°C.

The viscosity-enhancing agent may comprise one or more of the following: xanthan gum, kuzu root starch, glucomannan gums, galactomannan gums, alginic acid and salts thereof, carageenan, gellan, gelatin, pectin, locust bean gum, glucomannan, gellan, bentonite, carbomers, cellulose, carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, magnesium aluminum silicate, methylcellulose, poloxamers, polyvinyl alcohol and tragacanth. 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 deacetylated 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 polysaccharide produced by the bio-fermentation of Xanthamonas campestris 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 using any suitable method of agitation. Suitable methods may include, for instance, blending, folding, high-speed mixing and 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 further 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 useful as skin penetration enhancers include alcohols, amides, esters, glycols, glycol ethers, fatty acids, pyrrolidones, sulphoxides 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 glycol monoethyl ether, oleic 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 for 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 (cl) 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 (cl) 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. Carrageenan 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, stiffness, 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, for instance from 0.5 - 15% or from 1 - 10% by volume of ginger oil. The appropriate concentration of ginger oil in the composition may depend on the use of the composition and on the context in which it is used. For example, a composition for use in a clinical environment might contain a higher concentration of ginger oil than a composition formulated or packaged for home use or a composition intended for repeated administration. Furthermore, the concentration may need to be selected on the basis of factors such as patient sensitivity to ginger or regulatory standards. An appropriate amount of ginger oil may, for instance, be in the range of from 0.5 - 10%, for example from 1 - 5%, or from 2 - 3%, or from 1.5 - 2.5% by volume.

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. When xanthan gum is used as the viscosity-enhancing agent it is typically present in the range of from 0.3%) - 2% by mass, for instance from 0.5 - 2.5% by mass. 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 are 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, perfuming 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 may be, 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:

(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 presented separately from it in the kit. For instance, 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.

In another embodiment, the composition of the invention may be packaged in a form that can be safely heated by the end user. For instance, it may be presented in a sealed tube suitable for immersion in a cup or other container of hot or boiling water, or it may be presented in a package or container that can be safely heated in a microwave oven.

Any kit of the invention may comprise the composition in a presentational format that delivers the composition in suitable measured, or metered, 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 been found that topical pharmaceutical compositions of the invention are effective 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, stiffness, loss of mobility, loss of flexibility and swelling in a part or region of the 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 stiffness are thereby reduced or alleviated. Mobility and flexibility are thereby improved; in many cases they are restored to a normal range.

A common factor associated with the symptoms being relieved is thought to be 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 defined as "tissue hardened by deposition of lime salts" and "abnormal hardening or thickening of tissue". The American Heritage Science Dictionary © 2005, Houghton Mifflin Company, defines calcification as follows: "The 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 instance 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 often results in hardening of the tissue. In one aspect of the invention, the composition serves to mobilise and soften soft tissue such as muscle, fascia, lipoma and scar tissue. In the case of scar tissue, application of the composition of the invention transforms the scar from the red/wide/rigid/shiny state observed in keloidal (hypertrophic) scarring to a normal, pale, flexible scar. This typically happens within a few minutes of applying the composition. The normalisation of the scar is thought to be due to a softening or reducing effect on the excess collagen produced in the hypertrophic state.

A topical composition of the invention may be used on or over any body region or body part affected by a clinical symptom selected from rigidity, stiffness, swelling, loss of mobility and loss of flexibility. For instance, it may be used to treat a bone, joint, ligament, tendon, muscle, fascia, connective tissue, soft tissue or blood vessel. It may also be used to treat skin, scar tissue or lipoma. It can shrink lipomas, including those that are not calcified. 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.e. by cutaneous administration. It is suitable for administration to both human and animal subjects and thus has both pharmaceutical and veterinary application.

A human or animal subject 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. Said clinical symptom may be reduced, diminished, removed and/or normalised as a result. The condition of the subject is thereby improved or ameliorated. In some situations the composition of the invention has a palliative effect. In those cases it reduces, or reduces the severity of, the symptom being treated. In other situations the composition of the invention has a curative effect, meaning that it cures, removes or normalises the symptom being treated. The subject being treated may then be in remission, typically complete remission. In some aspects of the invention a curative effect is achieved after a single application of the composition, or a single course of treatment. The subject being treated may then be in remission, typically complete remission, from the clinical symptom in question.

A single application of the composition may sufficiently reduce, diminish, remove or normalise the clinical symptom being treated that repeat applications are not necessary. The need for multiple or repeated treatments over time is thus avoided in many cases. It may be appropriate in some cases to administer the composition as a single dose on a one- off basis. In trials carried out on 138 persons, over 168 regions of the body and for a wide variety of conditions, after 1 treatment course (mean 2.1 treatments) 70 % of cases had remission of the condition such that they required no reapplication over a 2-year follow up period. 30% required reapplication and only 14% of these required more than one re- application in total over the 2 years.

The clinical symptom to be treated by a composition of the invention may be caused by, or associated with, any of the following: a sports injury, ankyolosing spondilitis, calcified lipoma, lipoedema, Peyronie's disease, breast calcification, heterotopic ossification, otosclerosis (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, heel pain, lumbar invertebral 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. The clinical symptom may also be one that is caused by, or associated with, any of the following: non-calcified lipoma, Dupuytren's contracture, tendinitis, deafness, dystrophic calcification and/or calcinosis, hypertrophic calcification and/or calcinosis, scleroderma, fibrosis, (hyper)lordosis and scoliosis.

The application to a subject of a composition of the invention may have a beneficial effect on pain associated with, or arising from, the clinical symptom being treated. For instance, when the clinical symptom is one that occurs in soft tissue, there may be associated pain arising from scarring in that soft tissue. The softening effect on the scar tissue, achieved by a composition of the invention, therefore has the additional benefit of reducing or eliminating the associated pain. The pain in question may be acute or chronic. In use, the composition of the invention is applied to, adjacent 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 an extended area around the affected part or region of the body, for instance laterally to said part or region. If the part or region being treated 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 the 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. In other situations repeated application of the composition is not needed because, as discussed above, the condition or symptom being treated is cured or sufficiently improved after a single application.

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 - 4FC , 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 5ml (approx 3g) of essential oil of ginger with 110 ml of white vinegar. Powdered xanthan gum (1.5ml, approx. lg) was added to the resulting emulsion, with agitation. The resulting composition was a semi- opaque/translucent gel-like 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, heterotopic ossification, otosclerosis, bunion, tendinosis, adhesive capsulitis, 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 = 1.25ml (approx. lg)

white vinegar = 110ml

ginger oil = 5ml

Formulation 2: Kuzu = 5ml

white vinegar = 60ml

ginger oil = 2.5ml

Patient Treatment

Formulation 1 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 immediately lateral to the spine to allow absorption throughout the back and sides of the inter vertebral spaces. For the knee, the composition was applied over "eyes of knee" (lateral and medial to lower border of patella) and also above upper border of patella.

The composition was applied in a layer of from 2-8 mm thick, usually 3-4 mm thick. The exact thickness chosen in each case 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 overlying 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 first administration (sometimes accompanied by very mild 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 relevant 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 15 minutes. Following treatment there was a process of continued effect which in most trial cases 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: Home Use of the Composition

A narrow 10ml glass bottle half-full of a composition of Example 1 (denoted "Gel") was placed upright in a mug half- full of boiling water. The bottle remained in the mug for 5 minutes until the Gel had reached about 41.5 °C . (In a clinical setting a water bath at a constant temperature could be used to keep the Gel at an appropriate temperature).

The affected area was pre-warmed with a hot-water bottle having a surface temperature of 45 °C. The hot-water bottle was wrapped around the region in question until the area felt quite hand-hot, i.e. for about 10 minutes. 1.75 ml (¼ teaspoon) of warm Gel was then applied to the affected area (e.g. hand or knee) using disposable gloves to protect the hands. 10-15 minutes after application the Gel was washed off with a moist tissue. Example 4: Individual Case Histories

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

Case History Showing Effects on Disc Damage /Compression of Sciatic Nerve

Treatment: Gel & TDP Heat Lamp

Age 63, Female

Duration of condition: 16 months

Occupation: Housewife/ DIY

Description of condition: Sciatic nerve trapped on left , refers to hip. MRI shows

torn/compressed 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: T11, 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 of condition: 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 T9 Dates: 07/12/11 after this back freer /arms steadier

Area Applied: C3 to T6 Dates: 14/12/11 after this much less tremor , what remains is almost imperceptible

Area Applied: C3 to T6 Dates: 15/02/12 improved but some remaining pain at base of neck

Area Applied: C3 to C5 Dates: 28/03/12 generally very good

Area Applied: C3 to C5 Dates: 16/05/12 generally very good, top up

Area Applied: C3 to T5 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 Effects 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: 08/02/12 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 Effects 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 of condition: More painful 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 Otosclerosis at 18 years accompanied by loud "marching termites like Tom and Jerry" drumming tinnitus 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 History Showing Effects on Osteoarthritis in a Horse

Treatment: Gel & Click to Heat Salt Gel Pads

Age 25, Mare

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 Click 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 taped 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.

Results: 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%

Case History 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 "S" 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: Tl- 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: Tl- L5 Dates: 07/03/13 Post Gel treatment very gentle

realignment at C3, C4, C5 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 - T8 still slightly rigid. Post gel application gentle easing of L2 , T3 and T7.

Results: Normal child

% Improvement: 90%

8. Case History Showing Effects 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, 1 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%

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 carpals 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. Other joints 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:

21/03/12 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 Effects 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 of condition: Pain C2-T9, L2-L5, Sacroiliac (especially left affecting leg mobility); Headaches Occipital to front over eye; Chronic fatigue.

Number of treatments: 1

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%

Case History Showing Effects on Scar tissue and Chronic 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 415^th 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 tissue) 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 NHS but no further

improvement in leg pain.

Area Applied: On scar 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%

Case History 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 4^th 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 inner 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%

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 2013

Results: Plantar fasciitis resolved.

% Improvement: 100%

Case History Showing Effects on Foot Tendinitis

Treatment: Gel & TDP Heat Lamp

Age 48, Female

Duration of condition: 5 years

Occupation: Chef

Description of condition: Seen multiple Orthopaedic Specialists and diagnosis of inflamed foot tendons (tendon scans show no ruptures). 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 5^th 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 1 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.

75: Case History Showing Effects on Hearing in Person suffering Age Onset Deafness

Age: 63, Male

Duration of condition: Gradual onset over several years worsened over last 2 years Occupation: Proprietor of Small Manufacturing Business / Shop

Description of condition: Age related hearing loss at the stage requiring bilateral

hearings aids for some years, latterly hearing worse even with properly calibrated hearing aids. Expecting to soon lose hearing entirely. On palpation mastoid was swollen by between 0.4 and 10 mm with a hard, lumpy texture.

Number of treatments 2

Area Applied: Mastoid bilaterally : Dates: 07/11/13, 12/11/13

Results: Patient states "Hearing better now without hearing aids than ever before even when using the Hearing Aids."

On 26/11/13 "The right ear no longer needs a hearing aid and the radio has been turned down to only slightly above that required by normal hearing persons" Further applications Mastoid bilaterally : Dates: 26/11/13, 11/12/13, 13/02/14 Results: 16/04/14 Reported that his "ears were stable and only one hearing aid (left) required at the moment."

% Improvement: 70%

16. Case History Showing Effects on Hearing in Person suffering Age Childhood infection early onset Deafness from 2 years old

Age 13, Female

Duration of condition: First diagnosed at 2 years , one hearing aid (left) at 4 years old and at 7 years significant permanent bilateral hearing loss and fitted with bilateral hearing aids.

Occupation: Child

Description of condition: Bilateral hearing loss diagnosed as permanent and requiring hearing aids. Still leaves her with significant loss. Very swollen , enlarged mastoids.

Number of treatments 2

Area Applied: Mastoids Dates: 01/04/14, 06/05/14

Results: Patient stated at the start of her second treatment that her

"hearing has definitely improved with hearing now including a higher pitch, finding that she can hear and understand women's voices and that hearing in situations with background noise is also much easier."

% Improvement: 60%

17. Case History Showing Effects on Sacral Lipomas causing muscle spasm and low back/hip pain

Age 34, Male

Duration of condition: Lipomas formed following activity 3S 3 5-3- side goalkeeper up until 5 years ago, now associated with pain and muscle tension in lumbo-sacral/buttock region.

Occupation: Manager of large store for large multinational fast food

outlet Description of condition: Multiple small (eg 1-1.5 cm) sacral lipomas over the whole sacrum.

Number of treatments 1

Area Applied: Sacrum at site of lipomas

Results: Lipomas gone - no longer palpable, Hip/back pain improved and much more stable

% Improvement: 90%

18. Case History Showing Effects on Bunions

Age 54, Female

Duration of condition: 10 years

Occupation: Guest house owner

Description of condition: Distorted joints in feet dictating comfort footwear and

causing chronic pain.

Number of treatments 1

Area Applied: Bilaterally -Over bunions, inside foot arch and over lateral metatarsals where arthritic rigidity had occurred.

Results: Significant reduction in bunion size and swelling. Feet so good that she has not felt it necessary to have any follow up in an 11 month period.

% Improvement: 80%

Claims

1. 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, wherein the composition comprises (a) a ginger ingredient, (b) vinegar or a physiologically acceptable acid, and (c) a viscosity-enhancing agent.

2. A composition for use according to claim 1, 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 hydration enhancing agent.

3. A composition for use according to claim 1 or 2 wherein the viscosity enhancing agent is selected from xanthan gum, kuzu root starch, glucomannan 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 one of the preceding claims wherein the ginger ingredient is or comprises at least one compound selected from:

(,S)-5-hydroxy-l-(4-hydroxy-3-methoxyphenyl)-3-decanone ([6]-gingerol);

(,S)-5-Hydroxy-l-(4-hydroxy-3-methoxyphenyl)-3-dodecanone ([8]-gingerol);

(£)-l-(4-Hydroxy-3- methoxyphenyl)dec-4-en-3-one ([6]-shogaol);

4-(4-hy droxy-3 -methoxyphenyl)-2-butanone (zingerone);

l,3,3-Trimethyl-2-oxabicyclo[2,2,2]octane (1,8-cineole); and 2-Methyl-5-(6-methylhept-5-en-2-yl)cyclohexa-l,3-diene ( (-)-zingiberene).

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 wherein the pathological calcification occurs in a bone, joint, ligament, tendon, connective tissue, soft tissue, blood vessel or skin.

11. A composition for use according to any one of the preceding claims, wherein the use comprises the cutaneous administration of the composition to, or adjacent to, the site of said clinical symptom and the application of heat to said site.

12. A composition for use 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 of the preceding claims wherein the clinical symptom is caused by, or associated with, any of the following: a sports injury, ankyolosing spondilitis, calcified lipoma, non-calcified lipoma, lipoedema, Peyronie's disease, breast calcification, heterotopic ossification, otosclerosis (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, heel pain, lumbar invertebral 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, fibromyalgia,

Dupuytren's contracture, tendinitis, deafness, dystrophic calcification and calcinosis, hypertrophic calcification and calcinosis, scleroderma, fibrosis, (hyper)lordosis or scoliosis .

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 active 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:

(S)-5-hydroxy-l-(4-hydroxy-3-methoxyphenyl)-3-decanone ([6]-gingerol);

(S)-5-Hydroxy-l-(4-hydroxy-3-methoxyphenyl)-3-dodecanone ([8]-gingerol);

(S)-5 -Hydroxy- 1 -(4-hy droxy-3 -methoxyphenyl)-3 -tetradecanone ([ 10] -gingerol);

(E)-l-(4-Hydroxy-3- methoxyphenyl)dec-4-en-3-one ([6]-shogaol);

4-(4-hy droxy-3 -methoxyphenyl)-2-butanone (zingerone); l,3,3-Trimethyl-2-oxabicyclo[2,2,2]octane (1,8-cineole); and

2-Methyl-5-(6-methylhept-5-en-2-yl)cyclohexa-l,3-diene ( (-)-zingiberene).

19. A composition according to any one of claims 14 to 18 which further comprises one or more pharmaceutically acceptable carriers, diluents, excipients or additives.

20. A kit comprising:

(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, stiffness, 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 further comprises instructions 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.