NZ605317B - A Formulation for Topical Administration And A Method Of Its Use - Google Patents

Abstract

No. 605317 Disclosed herein is a topical formulation comprising - by weight – a diluent (preferably deionised water), 25-60% of an emollient that is glycerol (glycerine, glycerine), 5-20% sodium chloride as an antimicrobial active ingredient and additionally aloe vera extract. Further disclosed is the formulations use as a teat dip for treating damage or infection to the teats of dairy cows or other milk producing animals, including mastitis. is the formulations use as a teat dip for treating damage or infection to the teats of dairy cows or other milk producing animals, including mastitis.

Description

James & Wells ref: 133330/47 A FORMULATION FOR TOPICAL ADMINISTRATION AND A METHOD OF ITS USE TECHNICAL FIELD The present invention relates to a formulation for topical administration. The invention has particular application to the preparation and use of a topical formulation to be applied as a spray to the skin for treatment or maintenance.

BACKGROUND ART Dairying is a significant primary industry in New Zealand, and significant investment is made in ensuring the health and wellbeing of dairy cows. The health of a cow can affect its productivity.

One common issue that arises in the management of dairy cows is the condition of the skin of the teats of the dairy cow. The skin acts as a barrier to moisture and pathogens.

The skin barrier protects the internal environment of the body from excessive absorption of water and other solutes that may be found in the environment.

The skin of the teats of dairy cows can become damaged as a result of machine milking.

The use of pulsating teat cups in machine milking can result in some minor skin trauma such as abrasions, grazes and blisters. Such trauma, if left untreated, can result in ischaemia and ulceration of the skin.

Furthermore, in the field, the teats are often exposed to moisture and other pathogens.

This is particularly the case during the wet spring months of the milking season.

Prolonged exposure to moisture and detritus on the teats can result in the loss of natural secretions, such as glycerol, which are expressed from the sebaceous glands of hair follicles onto the skin. Glycerol assists in the hydration of the skin which is important to its function as a barrier.

The loss of such secretions can disrupt the function of the moisture barrier of the skin, leading to an increased susceptibility to infection.

James & Wells ref: 133330/47 To help care for the teats of dairy cows, some dairy farmers will wash and clean the teats on a regular basis. However, excess washing and cleaning particularly with detergents and soaps, can strip the skin of the udder and teats of its natural emollients.

This subsequently can lead to cracking and scarring of the skin surface, which in turn can potentially lead to bacterial infection.

The cracking of the skin of the teats can also have detrimental effects on milk production. The milking action on teats having cracked skin can lead to pain-avoidance behaviours, such as retaining milk.

As an alternative to the use of detergents and soaps, teats sprays may be used by dairy farmers to help maintain healthy skin on the teats of dairy cows. The spray can also assist in the repair of minor injuries to the teats as well as help prevent and/or control of mastitis and other bacterial infections that may develop in the teats and udders of dairy cows.

Conventional teat sprays generally use inorganic chemicals as their active antimicrobial agent. Such chemicals include iodine or chlorhexidine. An example of one such teat spray is TeatX , manufactured and distributed by Deosan (www.deosan.co.nz).

Iodine and chlorhexidine are relatively expensive actives, and therefore the manufacture of teat sprays can represent a significant financial investment. There is also a subsequent impact on the retail price per unit for such teat sprays. Conventional teat sprays are often provided as concentrates which have to be diluted for safe use. Using iodine at too high a level can result in burns. Furthermore, because of the expense involved, care must be taken when diluting the concentrate. However, it should not be diluted too much as the teat spray may have reduced efficacy.

The use of chemicals as actives can also create toxicity and environmental issues.

Many active agents used in teat sprays are not generally recognised as safe (GRAS).

Furthermore, conventional teat sprays can represent a food safety or residue threat to James & Wells ref: 133330/47 people consuming milk or dairy products derived from cows treated with conventional teat sprays.

There is an increasing awareness amongst the public for the need for environmentally friendly conduct by industries and businesses. Dairy farming is no exception, and there is a growing shift way from the use of potentially harmful chemicals, such as those used in many veterinary products, which may enter the food chain in a variety of ways.

Thus, in New Zealand there are increasing numbers of dairy farms that are being managed in such a way to obtain organic certification by recognised bodies such as AsureQuality (http://www.organiccertification.co.nz/). To achieve this certification the use of non-organic chemicals, such as teat sprays including iodine or chlorhexidine, is not desirable. All constituents of a formulation must be approved before organic certification of a particular product can be allowed.

However, this then limits the organic dairy farmer in their choice of available products for management of the teat condition of their cows. Such products are preferably animal- friendly while also being as environmentally sensitive as practical.

It is an object of the present invention to address the foregoing problems or at least to provide the public with a useful choice.

Further aspects and advantages of the present invention will become apparent from the ensuing description which is given by way of example only.

All references, including any patents or patent applications cited in this specification are hereby incorporated by reference. No admission is made that any reference constitutes prior art. The discussion of the references states what their authors assert, and the applicants reserve the right to challenge the accuracy and pertinency of the cited documents. It will be clearly understood that, although a number of prior art publications are referred to herein, this reference does not constitute an admission that any of these documents form part of the common general knowledge in the art, in New Zealand or in any other country.

James & Wells ref: 133330/47 Throughout this specification, the word "comprise", or variations thereof such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

DISCLOSURE OF THE INVENTION According to one aspect of the present invention there is provided a topical formulation, wherein the formulation includes: a diluent, and an emollient, and an organic antimicrobial active characterised in that the organic antimicrobial active is sodium chloride.

According to another aspect of the present invention there is provided a preparation for a topical formulation, wherein the formulation includes: a diluent, and an emollient, and an antimicrobial organic active characterised in that the organic antimicrobial active is sodium chloride, and wherein the formulation also includes a herbal extract.

According to another aspect of the present invention, there is provided a method of treating a condition of the skin of a mammal with a topical formulation, wherein the James & Wells ref: 133330/47 formulation includes a diluent, emollient, and an organic antimicrobial active, wherein the organic antimicrobial active is sodium chloride, the method characterised by the step of: a) applying the formulation to the skin of a mammal.

According to another aspect of the present invention, there is provided a method of treating a condition of the skin of a mammal with a topical formulation substantially as described above, the method including the additional step prior to applying the formulation to the skin of the mammal of: b) diluting the formulation with water by a factor of between approximately 3:1 (2 parts water to 1 part formulation) and 10:1.

The present invention relates to a topical formulation intended for application to the skin of a mammal.

The mammal may be any mammal that may require treatment of the skin. For example, the mammal may be a human, dog, a cow or the like. Reference shall now be made throughout the remainder of the specification to the mammal being a cow, although this is not meant to be limiting. Cows are valued as dairy animals, and dairying is a significant primary industry in many countries. However, it will be appreciated that goats and sheep are also valued dairy animals, and the present invention may readily be used with these animals as well.

The formulation may be applied to any area of the skin which may have a condition requiring treatment.

The condition may be any condition in which the skin becomes damaged or dehydrated.

For example, the condition may be cracking, chafing, windburn or sunburn of the skin.

Other examples of conditions to be treated with the present invention may be conditions in which pathogens such as bacteria, fungi or viruses play a role, either causing skin James & Wells ref: 133330/47 damage or dehydration of the skin or causing more serious conditions of damaged or dehydrated areas of the skin, such as infection. Examples of such conditions include acne, athlete’s foot, psoriasis or dermatitis. The stated examples of skin conditions are not meant to be limiting and persons skilled in the art will readily appreciate a variety of skin conditions may be treated with the present invention.

The formulation is to be applied to the area of skin requiring treatment or preventative maintenance. For example, the formulation may be applied to the ears, nose or in skin folds.

In preferred embodiments of the present invention, the formulation is applied to the teats of cow, and reference shall now be made to the use of the present invention on the teats of a cow.

The teats of a cow can become damaged as a result of machine milking or through contact with the ground or objects in the path of the teats as the cow moves. Another source of trauma to the teats can be excessive moisture, which can lead to the skin of the teats becoming cracked. Such cracks then become points of entry for pathogens.

The present invention is ideal for use to treat or prevent damage to the skin of the teat.

The formulation may be applied to the skin in a number of ways, for example as a paste or ointment. In preferred embodiments of the present invention, the formulation is applied to the teats as a spray. Reference shall now be made throughout the remainder of the specification to the formulation being used as a teat spray. An important aspect of the present invention is that the constituents of the formulation are organic and Generally Recognised As Safe (GRAS).

The use of organic in the context of the present invention should be understood to mean that the formulation of the present invention does not include synthetic compounds.

GRAS is an acronym used by the United States Food and Drug Administration (FDA) to refer to any substance that is approved by the FDA for intentional addition to food as a James & Wells ref: 133330/47 food additive, unless the substance is generally recognised, by qualified experts, as having already been sufficiently proven to be safe for its intended use.

The formulation may be provided as a concentrate which needs to be diluted with water before application. Such an approach may be preferred by bulk users such as larger scale dairy farms. Alternatively, the formulation may be provided to the consumer as a working solution, ready for immediate use with no dilution step. Small scale users, such as lifestylers, may prefer such products for being easy to use.

The constituents of the formulation are now discussed, and unless otherwise indicated are expressed as a percentage of a concentrate which would need to be diluted by a factor of approximately 5 parts to 10 parts water to 1 part concentrate.

The formulation includes a diluent or thinner.

A diluent should be understood to mean a diluting agent, and reduces the viscosity of the remaining constituents of the formulation.

The diluent may be any suitable substance which is chemically inert, and persons skilled in the art will readily recognise which liquids or substances would be suitable for use as a diluent, depending on whether the formulation is to be applied to the cow as a paste or spray.

For example, when the formulation is being applied to the animal as a spray, the diluent may be water (formula H O).

In preferred embodiments of the present invention, the diluent is deionised water.

Deionised water is water from which any mineral ions have been removed. This ensures the water is as pure as possible.

The amount of deionised water present in the formulation will depend on the amount of emollient and microbial organic active that is also present, but in preferred embodiments of the present invention, the formulation contains from 30 to 60% by weight of deionised water.

James & Wells ref: 133330/47 In preferred embodiments of the present invention, the formulation contains from 30 to 40% by weight of deionised water, this being the appropriate amount of diluent required for full dissolution of the organic antimicrobial active.

The formulation includes an emollient. An emollient should be understood to be a moisturiser which acts to reduce evaporation of water in the skin, thereby increasing the skin’s hydration.

In preferred embodiments of the present invention, the emollient has bacteriostatic or antimicrobial properties.

In preferred embodiments of the present invention, the emollient is glycerin (also known as glycerine or glycerol). This is not meant to be limiting and persons skilled in the art will appreciate that other emollients may be suitable for use with the present invention.

Reference shall now be made throughout the remainder of this specification to the emollient being glycerin.

The inventors prefer the use of glycerin in the present formulation for a number of reasons. Firstly, the use of glycerin (formula C H O ) as an emollient is well known and 3 8 3 it plays an important part in the maintenance of a healthy skin barrier.

Glycerin is also known for its bacteriostatic properties. Bacteriostatic should be understood to mean an agent that stops or inhibits bacteria from reproducing as opposed to killing them, as is the case with a bactericide.

Glycerin may be cheaply and easily sourced, making it an ideal and cost efficient emollient for the purpose of the present invention.

Furthermore, as it is GRAS, glycerin is commonly used in foods. This will facilitate organic certification of the present invention.

A factor that affects the amount of glycerin that may be present in the formulation is its limited ability to dilute the organic active. There must be a certain amount of diluent James & Wells ref: 133330/47 present in the formulation as well in order to achieve the full dissolution of the organic antimicrobial active.

In preferred embodiments of the present invention, the formulation contains from 25 to 60% by weight of glycerin. In a particularly preferred embodiment, the formulation contains from 45% to 55% by weight of glycerin.

In an even more preferred embodiment, the formulation contains from 48% to 52% by weight of glycerin.

The formulation also includes an antimicrobial organic agent. This should be understood to mean that the organic agent has properties that inhibit, kill or otherwise detrimentally affects bacteria, fungi, viruses and/or other pathogens.

In the present invention, the antimicrobial organic agent is sodium chloride.

Sodium chloride (formula NaCl), which throughout the remainder of this specification shall be referred to as salt, although in some embodiments of the present invention, iodised salt may be used, is known to have antibacterial properties. It is a natural desiccant which may disrupt the metabolic processes of many pathogens.

The salt constituent of the formulation is its key active, and is particularly advantageous for a number of reasons. These include:  readily available;  low cost;  readily soluble in water;  is approved in some countries for inclusion in organic formulations;  does not react with other ingredients.

James & Wells ref: 133330/47 The antimicrobial property of salt also supplements the bacteriostatic action of the glycerin component of the formulation. The inventors have found when used as a teat spray, the combination of salt and glycerin works surprisingly well in improving the teat condition of cows treated with the teat spray. The glycerin acts to counter the desiccant property of salt, ensuring the skin remains as hydrated as possible.

Additionally, the combined bacteriostatic nature of glycerin and the antimicrobial effect of salt increases the efficacy of the formulation.

Furthermore, as it is GRAS, salt is commonly used as a food preservative. This will facilitate organic certification of the present invention.

Salt is also hypertonic, and may act to reduce swelling and oedema in damaged teats or teats affected by swelling associated with mastitis infections by drawing water away from the swollen or damaged area.

However, salt is also a desiccant.

Thus the amount of salt present in the formulation needs to be an appropriate amount to avoid excessive dehydration for which the emollient present is insufficient, while still allowing a small degree of water loss to assist in reducing swelling associated with trauma and infections.

In preferred embodiments of the present invention, the formulation contains salt in a therapeutically effective amount by weight.

In preferred embodiments of the present invention, the formation includes from 5 to 20% by weight of sodium chloride.

In a particularly preferred embodiment, the formulation contains from 12 to 13% by weight of sodium chloride.

James & Wells ref: 133330/47 In preferred embodiments the formulation also includes a herbal extract which when used on skin has therapeutic properties. In preferred embodiments of the present invention, the herbal extract is aloe vera, although this is not meant to be limiting.

Persons skilled in the art will appreciate that other organic herbal extracts may also be used according to the preference of the user.

For example, other organically certified extracts which are known to have beneficial properties may be used as a constituent in the present invention. Such examples of such extracts may be garlic, cumin and turmeric.

Aloe vera is well known for its soothing and restorative properties when used on the skin.

In preferred embodiments of the present invention, the formation includes from 1 to 5% by weight of aloe vera powder.

In some embodiments of the present invention, the formulation may include additional constituents.

For example, when used as a teat spray, the formulation may include a dye. This is useful when applying the teat spray as may indicate to the user the extent of the coverage of the teat spray when applying it to the skin of the udder and teats.

The dye may be any suitable dye which is GRAS.

The inventors prefer Indigo Carmine supra food grade dye (CAS Number 8600) and/or Erythrosine supra food grade dye (CAS Number 164230). Both dyes have been approved by the FDA and the Food Safety Agency of the United Kingdom (FSA).

These dyes result in the formulation having a visibly detectable reddish colouring.

However, the disclosed examples are not meant to be limiting and persons skilled in the art will appreciate that dyes for any colour may be used with the present invention so long as they are recognised as being GRAS.

James & Wells ref: 133330/47 In preferred embodiments of the present invention, the formation includes from 0.1 to 2% by weight of dye.

Other optional constituents may include additional emollients and/or actives, so long as such constituents are organic.

In a particularly preferred embodiment, the formulation, in its concentrate form, includes the constituents as expressed in table 1: Ingredient name (common or chemical) CAS Number Quantity Function (g/kg) Deionised water 77325 372.3 Diluent Glycerine BP 565 504 Emollient Sodium Chloride Solar Salt (Grade 27) 76475 122.5 Organic antimicrobial active Erythrosine supra Food grade dye 164230 0.1 Food grade Indigo carmine supra food grade dye 8600 0.1 Food grade Aloe Vera powder 200:1 1000847 3 Herbal extract Table 1: Constituents of the concentrate (prior to dilution to a working solution) formulation (as g/kg) with an indication of the function of each constituent.

An example of a method of preparing the formulation shall now be described.

To a main tank of 100 litres, 32.03 kilograms of deionised water is added. The tank is then heated to 45 to 50° Celsius.

While being heated, sodium chloride, 12.25 kilograms is added to the main tank, together with 0.3 kilograms of aloe vera powder (200:1). The contents of the main tank is mixed with a Silverson mixer for 15 minutes until the solution is clear and the powders are dissolved.

Once the solution is clear, 50.4 kilograms of Glycerine BP is added, and mixed into the solution.

James & Wells ref: 133330/47 A separate formulation is prepared for the dye. To a 10 litre tank containing 5 kilograms of deionised water, 0.01 kilograms of Erythosine Supra FG dye is added together with 0.01 kilograms of Indigo Carmine Supra FG dye. The mixture is mixed to ensure even dispersion, and is then added to the main tank.

The resulting solution is mixed for a further 10 minutes, with deionised water (0.3 kilograms) being added to bring the formulation up to 100 litres.

The formulation may then diluted by a factor of approximately 3 to 10 into a diluent (water) for a working solution.

The inventors prefer a dilution factor of approximately 5:1 (four parts water to one part concentrate). This dilution factor is consistent with conventional teat sprays making it easier for the present invention to gain market acceptance.

However, this is not meant to be limiting, and good results have been achieved with the preferred concentrate formulation being diluted by a factor of approximately 7:1.

Higher dilution factors, such as 7:1 or even 10:1, may be used if the herd is milked twice daily as this represents an opportunity for the present invention to be applied twice a day.

This may justify the use of higher dilution factors, as the twice daily application may offset the reduced efficacy of the higher dilution. This may also allow prolonged use of the concentrate.

The present invention offers a number of advantages, including:  a teat spray which may be produced in a cost effective manner;  a teat spray in which all its constituents are GRAS;  a teat spray in which all its constituents are organic, such that the teat spray may be organically certified; James & Wells ref: 133330/47  a teat spray that has a efficacy comparable or superior to conventional teat sprays;  at the very least, the present invention offers the public a useful choice.

BEST MODES FOR CARRYING OUT THE INVENTION The following experimentation is given by way of example, and is not meant to be limiting.

Objective The objective of the inventors was to develop an organic teat spray suitable for use on dairy cows. The various formulations were trialed on a farm in the Northland region of New Zealand. The dairy herd was milked once daily, and thus there were approximately 24 hours between each milking event.

Climatically, the season during which the formulations were trialed was consistent with the previous season, in which conventional teat sprays were used.

Experiment Formulation 1 A first formulation (F1) was developed in which the working solution (dilution factor 7 parts water to 1 part concentrate (the list of constituents of F1 tabulated below in table 2) included salt at approximately 59.16 g/kg and glycerin at approximately 27.38 g/kg, the balance of the formulation made up of a diluent in the form of distilled water.

Dyes were added to provide an indication of coverage, these being Country Mile Red Marker dye (Rhodamine) and FIL Done That dye (Indigo Carmine) but only in trace amounts.

James & Wells ref: 133330/47 Ingredient name (common or chemical) Quantity Function (g/kg) Deionised water 394 Diluent Glycerine BP 191 Emollient Sodium Chloride Solar Salt 414 Organic antimicrobial active Erythrosine supra Food grade dye 0.004 Food grade Indigo carmine supra food grade dye 0.004 Food grade Table 2: Constituents of the concentrate (prior to dilution) of F1 (as g/kg) with an indication of the function of each constituent.

Results The working solution was applied to the teats using a conventional hand held spray gun, following the removal of the teat cups after each milking event.

After several days of use, it was observed that F1 appeared to result in excessive drying of the teat. It was speculated that there was insufficient glycerin in the formulation to counter the hypertonicity of the salt.

Formulation 2 A second formulation (F2) was prepared in which the salt content in the working solution was decreased to approximately 53.36 g/kg and glycerin increased to approximately 41.41 g/kg.

As with F1, the working solution had been diluted from the concentrate by a factor of 7:1.

The dyes used were also increased but only in marginal amounts. This was to improve the visibility of the residual colour of the F2 on the teats following application as a spray.

James & Wells ref: 133330/47 Results The trial with F2 (and the third formulation) took place during the wettest part of the season, when ground condition is at its poorest. Historically, this is when cracking of the skin of the teats is at its worst.

It was observed that after ten days of trial with F2 that the teat condition improved somewhat. The skin of the teat felt softer to the touch, and cracking was reduced from what would have otherwise been expected for the time of the season.

However, the visibility of F2 following application to the teats remained inconsistent.

Visibility is an important factor when using teat sprays as it is preferable to be as efficient as possible with coverage of the spray.

Formulation 3 A third formulation (F3) was then trialed. The glycerin content was increased substantially to 92.80 g/kg while the salt content remained unchanged at approximately 53.36 g/kg. In an attempt to provide a more visible spray, the amount of dye used was increased, from 0.00008 g/kg in the second formulation, to 0.001 g/kg for each of the two dyes used in the third formulation. As with the previous formulations, the working solution had been diluted by a factor of 7:1.

Results Superior results were observed using F3 than seen when using F2. Teat condition improved considerably and the cracking was significantly reduced.

It was later found that the manufacturer specifications for the salt were incorrect, and the specific density was double from what was expected. Thus, F3, as well as the previous formulations trialed, had a salt concentration twice what was intended.

James & Wells ref: 133330/47 Formulation 4 As a result of the issue with the salt concentration issue identified following the trial of formulation 3, the new formulation (F4) was revised such that the working solution included salt at approximately 28.42 g/kg, with glycerin being increased to approximately 117.2 g/kg. The concentration of each of the two dyes was increased to 0.00145 g/kg, with the balance being 854 g/kg being diluent in the form of distilled water.

Results The teats of treated cows showed a noticeable improvement, which was believed to be as a result of the increase in glycerin. It was particularly noticeable that cows that had ongoing problems with cracked teats began to show improved condition.

At the same time, somatic cell count (SCC) was generally reduced when compared to animals being treated with conventional teat sprays in previous seasons.

Furthermore, subclinical mastitis in the treated herd was reduced, as measured by SCC, was reduced by about 20% compared to the previous season, as tabulated in Table 3 below.

Date Previous season Current season 2/8 317 254 12/8 284 225 21/8 217 176 1/9 210 190 11/9 244 173 21/9 261 206 1/10 237 188 James & Wells ref: 133330/47 11/10 223 187 21/10 305 No data 1/11 267 232 Table 3: SCC (x 1000) of across a three month period of the previous season compared to the current season in which formulations 1 to 4 were tested.

The incidence rate of mastitis also dropped by approximately 60% from the previous season.

As the farm on which the formulations were trialed milked once daily, it is likely that superior results may been seen on farms being milked twice daily, assuming the dilution factor remained consistent with what had been trialed. It is possible that the concentrate could be diluted further on farms operating herds milked twice a day; the reduced efficacy of a single application could be compensated for by being applied twice, after each milking event.

Further variations of the formulation were trialed in the following season to ensure the results observed the previous season were not due to other factors.

When aloe vera, a certified organic herbal extract, was added to the formulation in an amount of approximately 0.696 g/kg, further improvement in the condition of the skin of the teats was observed.

At the same time, the dye was changed. It was found that the Rhodamine based dye as used to date was not GRAS. As a result, the dyes were replaced with food grade dyes, these being Indigo Carmine and Erythosine. Both were included in concentrations of approximately 0.023 g/kg.

Additionally, it was decided to lower the dilution factor from 7:1 to 5:1 to make the dilution factor consistent with conventional sprays. It was thought that this may assist in the product gaining market acceptance once it enters the market.

James & Wells ref: 133330/47 Conclusion When salt is used in a therapeutically effective amount in conjunction with an appropriate amount glycerin to counteract the hypertonic effect of salt, positive changes in the skin of the teats of the treated animals was observed.

Furthermore incidences of bacterial infections, i.e. mastitis, were reduced with a subsequent positive effect on milk production of the treated herd when compared to herds treated with conventional products.

Aspects of the present invention have been described by way of example only and it should be appreciated that modifications and additions may be made thereto without departing from the scope thereof as defined in the appended claims.

James & Wells ref: 133330/47

Claims (8)

WHAT WE CLAIM IS:

1. A topical formulation, wherein the formulation contains: a diluent, and an emollient in an amount from 25% to 60% by weight, and an organic antimicrobial active in an amount from 5% to 20% by weight, characterised in that the organic antimicrobial active is sodium chloride, and wherein the emollient is glycerin, the formulation also including a herbal extract, wherein the herbal extract is aloe vera in an amount from 1 to 5% by weight.

2. The topical formulation of claim 1 wherein the formulation contains from 10% to 15% by weight of sodium chloride.

3. The topical formulation of claim 2 wherein in the formulation contains from 12% to 13% by weight of sodium chloride.

4. The topical formulation of any one of claims 1 to 3 wherein the formulation contains from 45 to 55% by weight of glycerin.

5. The topical formulation of any one of claims 1 to 4 wherein the diluent is water.

6. The topical formulation of claim 5 wherein the diluent is deionised water.

7. The topical formulation of any one of claims 1 to 6 wherein the formulation includes a dye.

8. The topical formulation of claim 7 wherein the dye is indigo carmine supra food grade dye. James & Wells ref: