WO2002024182A1

WO2002024182A1 - Ectoparasite formulation

Info

Publication number: WO2002024182A1
Application number: PCT/AU2001/001183
Authority: WO
Inventors: William Victor Greig; Wendy Louise Free
Original assignee: Hair Advisory Centre Pty Ltd T/A Queensland Cosmetic Laboratories
Priority date: 2000-09-21
Filing date: 2001-09-20
Publication date: 2002-03-28
Also published as: AUPR028000A0

Abstract

An ectoparasite formulation, which is non-toxic and effective in use, comprising 20-87% w/w of a lower alkanol containing 1-4 carbon atoms and 0.1-2.0% w/w of a thickening agent. There also may be utilised 0.05-20.0% w/w of a conditioning or anti-static agent or emulsion binding or stabilising agent. A preferred formulation is 50-70% isopropanol, 1.0-5.0% of the thickening agent and 0.1-5.0% of the conditioning agent or anti-static agent or emulsion binding or stabilising agent.

Description

TITLE OF INVENTION ECTOPARASITE FORMULATION FIELD OF THE INVENTION THIS INVENTION relates to an ectoparasite formulation for treatment of headlice and other parasitic infections which may be utilised in susceptible human and animal species. A primary active component of the formulation is a C,-^ lower alkanol which may be selected from ethanol or isopropanol.

BACKGROUND OF THE INVENTION Reference may be made to International Publication WO

95/255544 which refers to a gel composition for treatment of skin diseases and for disinfection of the skin which comprises more than 90% of ethanol based on the weight of the gel composition and less than 10% of water based on the weight of the gel composition. There is also provided between 0.1 and 10% by weight of a high molecular weight polymer gelling agent. The gel composition utilised in this reference was of use in treatment of open wounds such as skin abrasions and also skin eruptions caused by viral infections, especially herpes infections. The composition could be applied to the mucous membranes and could also be utilised for controlling parasitic organisms inclusive of ectoparasites such as scabies, chigger and headlice.

The active component in the abovementioned gel composition was the ethanol which disinfected the infected area and protected the infected area against reinfection via a "plaster effect" obtained by the dried gel, until the wound had healed. The disinfectant action of the ethanol would only be obtained when used in a concentrated form i.e. more than 90% because the use of the ethanol in lower concentrations such as 60% provided a distinct pain reaction which made it inappropriate for use, especially in application to the mucous membranes. The water could only be used in concentrations less than 10% because of the necessity of the gel composition to be hygroscopic.

It will be appreciated that use of a disinfectant composition with ethanol as a primary active component for treatment of ectoparasites inclusive of headlice was to be preferred when compared to headlice killing compositions as described in US Patent 5783202 which described the use of toxic active components such as pesticides, inclusive of pyrethrins, which also have a further disadvantage in that they are often regarded as being non-ovicidal in use. An additional disadvantage of pyrethrins as described in US

Patent 5783202 was that they do not kill lice consistently when used in shampoos.

However, as reported in the Merck Index Eleventh Edition (1989), the major disadvantage of pyrethrins is that they can cause severe allergic dermatitis and systemic allergic reactions. Large amounts may cause nausea, vomiting, tinnitus, headache and other disturbances related to the central nervous system (CNS).

It will also be appreciated that conventional ectoparasitic treatments inclusive of chlorophenothane (DDT) and gamma benzene hexachloride (marketed under the "Kwell" trade mark), benzyl benzoate, pyrethrins, malathion (i.e. a combination of tetrahydronapthalene and cupric oleate), isobornyl thiocyanoacetate, sulphur and sulphurated lime have been questioned as being satisfactory in use in relation to the necessity for precautions and also potential adverse responses and/or effectiveness as described in

Goodman and Gilman, The Pharmacological Basis of Therapeutics, Fifth Edition pp 1012-1015 (1975).

Reference also may be made to US Patent 4447423 which described a lice treatment or pediculicide composition comprising :-

(i) a surface wetting agent which is preferably sodium or calcium dioctyl sulphosuccinate;

(ii) benzyl salicylate; and

(iii) a lower C C₄ alkanol which is preferably isopropanol. The alcohol component in US Patent 4447423 is stated to act as a solvent and vehicle for components (i) and (ii). The mechanism behind the pediculicide composition is that there appears to be a synergistic effect between components (i) and (ii).

Thus a summary of the prior art reveals that while various conventional ectoparasite treatment formulations have been proposed, it seems that major disadvantages of such conventional formulations is that they are toxic or ineffective in use. The use of a lower alkanol such as isopropanol or ethanol as an active component has not generally been proposed with the exception of WO 95/255544. However, the primary thrust of that reference is that only a concentrated solution of alcohol (i.e. greater than 90%) can be used to avoid causing excessive pain when the formulation is applied topically.

SUMMARY OF THE INVENTION The object of the invention is to provide an ectoparasite treatment formulation which is non toxic and effective in use.

The treatment formulation of the invention comprises from 20-87% w/w of a lower alcohol having 1 -4 carbon atoms and 0.1 -20.0% of a thickening agent. Preferably there is also included 0.05-20.0% w/w of a conditioning or anti-static agent or emulsion binding and/or stabilising agent. The lower alcohol used in the formulation of the invention to most preferably isopropanol although ethanol can be utilised if desired. Methanol or butanol may be used, although they are less preferred as they may be toxic in some circumstances. The thickening agent used in the formulation of the invention may be any substance that increases the viscosity of the formulation and which is also alcohol compatible. Thus the viscosity of the formulation, after inclusion of the thickening agent, may be from 100 to 100,000 centistokes. The thickening agent may be used singly or a combination of thickening agents may be utilised. The thickening agent may be a polymer which can be linear, branched or cross linked and may be naturally derived, or may be synthetic. Any of the gelling or thickening agents may be used that are described in WO 95/255544, which is totally incorporated herein by reference. Such polymers are mostly cellulose derivatives, naturally derived polysaccharides and synthetic polymers inclusive of polyethylene glycols, polyethylene oxides, polyvinyl pyrrolidones and polyacrylic acid.

Alternatively, suitable thickening agents may be those described in "International Cosmetic Ingredient Dictionary and Handbook" published by The Cosmetic, Toiletry and Fragrance

Association, Washington, DC, United States of America which publication is also totally incorporated herein by reference. Such thickening agents may be selected from viscosity increasing agents that thicken or have a gelling effect on the aqueous or alcoholic components of cosmetic or therapeutic products. Their ability to perform this function is related to their water and alcohol solubility or hydrophilic nature and includes acrylamide copolymers, cross polymers or copolymers having an acrylate component, alginic acid or alginates, carbomers, carboxymethyl polymers, betaines, tallowamides, stearamides, gums, cocamides, gelatins, kelp, polythylene glycols and polymers containing polyethylene glycol, clays including bentonite, hyaluronic acid, lauramides, oleamides, palmamides, kemelamides and the like.

The conditioning or anti-static agents are primarily cationic or anionic surfactants, amines, betaines, protein derivatives, amino acids and quaternary ammonium compounds that alter the electrical properties of the formulation after application to skin or scalp by reducing their tendency to acquire an electrical charge. Examples of such conditioning agents or anti-static agents are described in the publication "International Cosmetic Ingredient Dictionary and Handbook" discussed above.

Examples of such conditioning agents may include polyquaternium species, polyethylene glycol amides, polyethylene glycol amines, quaternium species, polyethylene glycol tallow amines, isostearamidopropyl compounds, steramidopropyl compounds and the like.

The formulation of the invention may also include an emulsion stabiliser that may assist in the formation and stabilisation of emulsions. Such emulsion stabilisers may be used in lieu of the antistatic or conditioning agent or used in combination with the anti-static or conditioning agent. The emulsion stabilisers may also be utilised as a thickening agent. Emulsion stabilisers do not function as primary emulsifiers but prevent or reduce the coalescence of emulsified droplets by modifying the continuous or disperse phase of the emulsion. The stabilisation may result from electrical repulsion from changes in viscosity or from film formation on the droplet surface.

Examples of appropriate emulsion stabilisers are referred to in the publication "International Cosmetic Ingredient Dictionary and Handbook" discussed above and include aluminium salts of long chain fatty acids, C_9-11 alcohols, C₁₂.₁₈ alcohols, C₂₀_₄₀ alcohols, C_1-5 alkyl galactomannan, C_18-38 alkyl hydroxystearoyl stearate, C_14-30 glycols, lanolin and the like.

The formulation of the invention may also include emollients or skin conditioning agents also described in the publication "International Cosmetic Ingredient Dictionary and Handbook" described above. Examples of suitable emollients are canola sterols, avocado sterols, brain lipids, algae extract and the like. The formulation of the invention may also include humectants which are skin conditioning agents that increase the water content of the top layers of the skin. Examples of humectants are described in the "International Cosmetic Ingredient Dictionary and Handbook" publication described above and include agarose, honey, lactose, sea salt, urea and the like.

The formulation of the invention may also include occlusive skin conditioning agents that retard the evaporation of water from the skin surface. Such skin conditioning agents are described in the "International Cosmetic Ingredient Dictionary and Handbook" publication referred to above and are generally lipids that remain on the skin surface. Examples are kernel oils, castor oils, waxes, beeswax, methicone compounds and the like.

There also may be included colourants as desired which are listed in the "International Cosmetic Ingredient Dictionary and

Handbook" publication. Examples are the various ACID or BASIC Blues, Blacks, Reds, Pigment reds, Pigment Yellows and the various CI prefixed colourants referred to in the "International Cosmetic Ingredient Dictionary and Handbook" publication. There also may be included various fragrances for inclusion in the formulation which are listed in the "International Cosmetic Ingredient Dictionary and Handbook" publication. Examples include aroma chemicals, essential oils, natural extracts, distillates and isolates as is known in the art. Examples are camphor, carvone, citral eucalyptol, oleic acid, coumarin methyl lactate and the like.

Preferred formulations of the invention include from 50- 70% lower alkanol, from 1 -5% of the thickening agent and 0.1 -5% of the conditioning and/or anti-static agent and/or emulsion stabilising agent with or without secondary active components. Suitably the balance of the formulation is water. An especially preferred formulation is 64% lower alkanol 0.2% conditioning agent and 1 .0% thickening agent.

If it is desired to use humectants, emollients and/or occlusive skin conditioning agents, these may be in a concentration of 0.1 -0.5%. Colourants and/or fragrances may be used in a concentration of 0.05-0.2%.

The formulation of the invention may be applied to a suitable subject for a period of from 1 -10 minutes. More preferably this period is from 2-5 minutes.

EXPERIMENTAL Example 1

A 12 year old female patient was diagnosed as having a severe headlice infection and live eggs and some nymphs were identified in the hair of the patient. The formulation of the invention comprising 64.0% isopropanol, 0.2% quaternary ammonium salt in the form of Ceteareth-12 and 1 .0% gel in the form of Carbomer 940 was applied topically to the hair for 6 minutes and subsequently the hair was combed thoroughly. Thereafter about 100 dead nymphs were identified which were removed. The quantity of lice or nymphs were assessed by combing the hair about 2cm from the scalp to the hair tips and the eggs were allowed to remain. On a follow up visit within seven days, 50 eggs were identified and tested and found to be all dead i.e. they did not snap. Thus in a complete comb through the hair, zero nymphs and zero lice were found. It was also confirmed that no additional treatment had occurred in the interim period.

Example 2

A 1 2 year old female was diagnosed with five eggs and some nymphs. This headlice infection had been treated with four different products which were various combinations of Neem Oil, Tea Tree Oil, Permethrin and Maldison over the last 2-3 months. Upon application of the formulation used in Example 1 to the hair for 10 minutes and after the hair was combed through, it was ascertained that there were approximately 2000 dead nymphs and lice which were removed. The removal step was carried out by combining through within 2cm from the scalp to the hair tips allowing the eggs within 2cm of the scalp to remain. A follow up visit 7 days later ascertained that no lice were present.

Example 3

A five year old female patient was diagnosed as having a headlice infection with live eggs and some nymphs. The patient had been treated with four different headlice treatments involving active ingredients including pyrethrins, tea tree oil and Maldison over the past 2-3 weeks. After application of the formulation referred to in Example 1 for 5 minutes a subsequent comb through of the hair resulted in approximately 400 dead nymphs and lice being removed. The removal step comprised combing the hair approximately 2cm from the scalp to the tips allowing the eggs within 2cm of the scalp to remain. On a follow up visit 7 days later, it was ascertained that no lice were present.

Example 4

The aim of this example was to collect a single population of adult lice from an infestation and subject the lice to a number of different commercially available head lice treatment products. As part of screening for lice in a kindergarten environment, subjects who have significant infestations were sought. None were found with more than 9 adult lice (no nymphs were present as the patients had been treated the previous week with the formulation of Example 1 and it was anticipated that the population selected was due to a re-infestation).

Lice were collected individually and counted into a closed container. Hair fibres from the same patient were included to prevent "grounding" of the lice.

Approximately 5-20ml of product was dispensed into four separate containers and then two lice dipped into each of the products, so that the lice were submerged but hair shafts protruded from the product, allowing the lice movement. The lice were monitored continuously for 20 minutes and scored for movement indicating product effectiveness. A score of 5 indicated full and unimpaired movement, thus resistance, a score of 1 indicated no movement detected at all, thus an effective treatment.

Ten minutes into the trial the lice were "nudged" with the tail of a comb to attempt to promote movement. Responses were also scored and the results tabulated as per Table 2. Where the columns are split the first relates to the uninterrupted treatment and the second to the response noted from the nudge.

The products tested reflect those treatments most likely to be effective:

• Permethrin has been regarded as an effective treatment for some time although resistant populations are known to exist.

• Herbal products are gaining popularity and indeed Lice Blaster is being upheld by popular research as the product of choice.

• Foams are considered to be the most effective at penetrating the insect (and eggs).

• Products containing Maldison (Malathion) were not used because of concerns regarding the safety of the product, given the high potential for the presence of development of toxic breakdown products.

• Products containing Neem Oil were not tested because this active is not recognised by the Therapeutic Goods Administration of Australia (TGA) as being an active ingredient.

Follow Up:

The control, and Permethrin subjected lice were randomly subjected to either Example 1 Formulation or Tea Tree Lice Foam that resulted in immediate cessation of movement.

Interpretation of Results:

The results shown that the population harvested were almost certainly "Permethrin resistant". The lice in both the water control and the Permethrin based product moved freely and easily climbed out of the "product", even after repeat dipping, dousing and submerging. It can be noted that the Orange Medic Plus also listed Tea Tree Oil as a fragrance ingredient. Although the quantity is not stated, Tea Tree Oil is acknowledged as an active ingredient by the Therapeutic Goods Administration of Australia. It may be that the delivery method of the Tea tree Oil is important given the resistance of the lice to Orange Medic Plus and their sensitivity to the Meditree Product.

The Lice Blaster product was highly effective and the lice were almost certainly fatally dosed, responding only weakly when provoked.

Both the formulation of the invention and the Meditree Tea Tree Lice Foam resulted in total impairment over the entire 20 minutes of observation.

Summary:

The test confirms that the formulations of the invention immobilise lice on contact, and that such formulations compare favourably with popular commercially available products. The test demonstrates that the formulation and presentation of the formulation of Example 1 is equally as effective as the Lice foam in totally immobilising lice. The test also demonstrates that the immobilisation is irreversible over the time period measured.

Because the lice treated are completely impaired and because of the mode of action of the formulation of the invention, it is anticipated that resistance will not be able to develop.

Example 5:

Over an approximate 3 month period, volunteers were sought from school and pre-school communities. Written descriptions of the product and the purpose of the trial were prepared and circulated to parents and written consent obtained on each occasion.

Additionally, verbal and written information regarding current management techniques was provided to each household utilised. No refusals to participate were noted.

The treatment regime was essentially unchanged for each person screened and real time written records prepared. Individuals contacted the office and initial discussions determined the willingness of the families to participate. Home visits were arranged at mutually convenient times and all family members (present) were screened used the "conditioner and comb" technique. Treatment was applied to the hair and scalp beginning at the fringe and working to the nape of the neck, saturating all hair and scalp. Assessment of the kill was made using a thorough comb through using a lice-meister (or like) comb. Counts and/or estimates of climbers and nymphs were recorded. For the purpose of evaluating nit kill, nits were (on most occasions) allowed to remain within 2cm of the scalp and were not removed using the comb. Participates were asked not to use additional chemical treatments during the screening period. Follow up calls 7-10 days later counted nits, nymphs and climbers (when possible). Participants were asked if they had used any additional treatments between visits. The presence of climbers was taken to be an indication of re-infestation, as all had been thoroughly treated and combed out on the initial visit. The presence of nymphs and climbers would indicate a re-infestation and possibly, failure to treat the nits. The presence of nymphs alone was considered to represent a failure to dose nits (The possibility of nymph only re-infestation was neither considered nor determined). The presence of nits alone, was assessed as live or dead.

In the school-based trial 29 individuals were assessed, representing 8 family groups. Of the individuals screened, 24 had active, positively identified infestations at some stage during the screening program. Only 8 people within the families screened showed no signs of infestation at any stage. Several younger participants were not fully screened. Within the pre-school based program, 21 individuals were screened, representing 17 family groups. Of those screened, 5 had active infestations and an additional 2 showed signs of previous infestation. The remaining 14 showed no signs of infestation. The results are shown in Tables 3 and 4, wherein Table 3 records the summary of the initial field trials and Table 4 shows the re-screening of participants 7-10 days later. A total of 45 separate treatments were documented. A family group associated with a single participant indirectly reported an additional 15 treatments. Despite comments being sought, no adverse reactions of any type were noted by any of the participants. All treatments showed a score of fatally dosed or dead. Results:

On 17 occasions re-infestation occurred as evidence by the presence of climbers; 4 participants could not be re-assessed. 23 treatments resulted in a zero count of nymphs at the 7 to 10 day inspection, indicating that the method were effective in killing nits

(eggs). 5 treatments, notably using the lower concentrations of the key ingredient, had apparent insufficient dosing of the eggs to elucidate an ovicidal claim. On one occasion a younger patient skipped an inspection and treatment with the family and was subsequently scored as having "nymphs only", the following week. A full comb through to determine the accuracy of this result (i.e. excluding climbers) was not possible.

The results demonstrate that the formulation of the invention has been effective in both killing the lice and nits in a single treatment when re-infestation did not occur. The product was neither expected to, nor showed any evidence of deterring re-infestation.

Although these results indicate that a single treatment may be effective, discretion would indicate that there may be circumstances where thorough initial saturation is impractical or not adequately achieved. Additionally, it is extremely difficult to ensure a thorough investigation of particularly long hair. In order to provide a balanced and comprehensive treatment regime, two doses, spaced 7 to 10 days apart are advisable.

General Conclusions:

It will also be appreciated that the formulation of the invention can be used in conjunction with 0.01 -10% and more preferably 0.2-2.0% and most preferably 0.5-1.0% of other secondary active components to increase the knock down rate and thus improve the efficacy of the formulation in use. Suitable secondary active components are essential oils, inclusive of tea tree oil and rosemary oil, natural and synthetic pyrethroids, organophosphates and the like.

From the foregoing it will therefore be appreciated that the ectoparasitic formulation of the invention is effective in use and does not involve the use of toxic components. The formulation of the invention may be used in treatment of acute and chronic external parasitic infections. The therapeutic action of the isopropanol which is the preferred lower alkanol is a function of its intrinsic de-fatting solvency and its volatile nature that results in an azeotropic dehydration activity. The action of alcoholic evaporation is exothermic, drawing heat from the body and thereby providing a cooling effect. Both the cooling effect and the dehydration reaction are prolonged by the adherence of the thickened formulation to the scalp.

The addition of the thickening agent has the following effect;

(i) to promote maximisation of therapeutic action per dose;

(ii) easy and safety of use;

(iii) control dosage form;

(iv) enhanced distribution across the treatment surfaces;

(v) reduced flammability, (partially retard evaporative loss); and

(vi) reduced risk of the potential of adverse eye contact.

The addition of the anti-static and/or hair/skin conditioning agents minimises detrimental loss of "condition", through static build up and moisture loss, both of which could be expected to occur as a result of the de-fatting and dehydrating action of the alcohol. The addition of the emulsion binding and/or stabilising agent is to facilitate shelf life and stability of the compounded alcohol formulation. If desired, there also may be provided form 0.1 -0.5% of a local anaesthetic or anti-inflammatory agent at therapeutically active concentrations which act independently or in conjunction with the alcohol to relieve the symptoms of the ectoparasitic infection. The pH of the ectoparasite formulation of the invention may be from 4.5-8.5 and more suitably about 5.5-7.5. The dosage is dependant on hair length, but may range from 20-500mls of the formulation.

It will also be appreciated that because the formulation of the invention contains a lower C C₄ alcohol that the formulation will have a fluid base, which is preferably translucent and non-aqueous, while still being a mobile liquid or semi-solid gel that facilitates the distribution of both active and excipient or non-active components across the treatment area.

TABLE 1

Products used in Example 4

TABLE 2

NOTE: Key to Results 5 - Complete Movement 4 - Some what Impaired 3 - Impaired 2 - Significantly Impaired 1 - No detectable Movement

TABLE 3

Summary Results Field Trials - Lice Treatments

H 03

TABLE 4

u.

Claims

1 . A treatment formulation for ectoparasites, comprising 20-87% w/w of a lower alcohol having 1 -4 carbon atoms and 0.1 -20% w/w of a thickening agent, together with a pharmaceutically acceptable vehicle.

2. A treatment formulation as claimed in claim 1 , wherein there is also included 0.05-20.0% w/w of a conditioning or anti-static agent or emulsion binding and/or stabilising agent.

3. A treatment formulation as claimed in claim 1 , comprising 50-70% w/w of the lower alcohol.

4. A treatment formulation as claimed in any preceding claim, wherein the lower alcohol is isopropanol.

5. A treatment formulation as claimed in any preceding claim, wherein there is provided from 1 .0-5.0% w/w of the thickening agent.

6. A treatment formulation as claimed in claim 5, wherein the thickening agent is selected from the group consisting of linear polymers, branched polymers, cross linked polymers, naturally derived polymers and synthetic polymers.

7. A treatment formulation as claimed in claim 6, wherein the polymers are selected from cellulose derivatives, naturally derived polysaccharides and synthetic polymers, inclusive of polyethylene glycols, polyethylene oxides, polyvinyl pyrrolidones and polyacrylic acid.

8. A treatment formulation as claimed in claim 5, wherein the thickening agent is selected from the group consisting of acrylamide co-polymers, cross polymers or co-polymers, having an acrylate component, alginic acid or alginates, carbomers, carboxymethyl polymers, betaines, tallow amides, stearamides, gums, cocamides, gelatins, kelp, polyethylene glycols, polymers containing polyethylene glycol, clays including bentonite, hyaluronic acid, lauramides, oleamides, palmamides and kernel amides.

9. A treatment formulation as claimed in claim 8, wherein the thickening agent is a carbomer.

10. A treatment formulation as claimed in claim 8, wherein the thickening agent is selected from the group consisting of acrylamide co-polymers, cross polymers containing an acrylate component and co-polymers containing an acrylate component.

1 1 . A treatment formulation as claimed in any one of claims 2-1 0, wherein there is provided from 0.1 -5.0% w/w of the conditioning or anti-static agent or emulsion binding and/or stabilising agent.

1 2. A treatment formulation as claimed in claim 1 1 , wherein the conditioning or anti-static agents are selected from the group consisting of cationic surfactants, anionic surfactants, amines, betaines, protein derivatives, amino acids and quaternary ammonium compounds.

1 3. A treatment formulation as claimed in claim 1 1 , wherein the conditioning or anti-static agent is selected from the group consisting of polyquaternium species, polyethylene glycol amines, polyethylene glycol amides, quaternium tallow amines, isostearamidopropyl compounds and stearamindopropyl compounds.

14. A treatment formulation as claimed in claim 1 2, wherein the conditioning anti-static agent is a quaternary ammonium compound.

1 5. A treatment formulation as claimed in claim 1 1 , wherein the emulsion stabiliser is selected from the group consisting of aluminium salts of long chain fatty acids, long chain fatty acids, C_{9-1 1} alcohols, C_12-18 alcohols, C_20-40 alcohols, C_{1 -5} alkyl galactomannans, C₁₈.₃₈ alkyl hydroxystearoyl stearate, C^14"30 glycols and lanolin.

1 6. A treatment formulation as claimed in claim 1 5, wherein the emulsion stabiliser is a C12-18 alcohol.

17. A treatment formulation as claimed in any one of claims 2-16, comprising 64% lower alkanol, 0.2% conditioning agent and 1 .0% thickening agent.

18. A treatment formulation as claimed in any preceding claim, wherein the pH of the formulation is 4.5-8.5.

19. A treatment formulation as claimed in claim 18, wherein the pH is 5.5-7.5.

20. A treatment formulation as claimed in any preceding claim, also including 0.01 -10% of a secondary active component selected from the group consisting of essential oils, inclusive of tea tree oil and rosemary oil, natural and synthetic pyrethroids and organophosphates.

21 . A treatment formulation as claimed in claim 20, including 0.2-2.0% of the secondary active component.

22. A treatment formulation as claimed in claim 20, including 0.5-1 .0% of the secondary active component.

23. A treatment formulation as claimed in any preceding claim, wherein the pharmaceutically acceptable carrier is water.

24. A method of treatment of ectoparasite infection, which includes the step of topical application of the treatment formulation of any preceding claim to an infected area of a patient.

25. A method as claimed in claim 24, wherein the dosage of the formulation utilised in the treatment step is 20-500 mis.