GB2462526A

GB2462526A - A composition for the control of ectoparasites

Info

Publication number: GB2462526A
Application number: GB0913595A
Authority: GB
Inventors: Nigel Cooper
Original assignee: Thornton and Ross Ltd
Current assignee: Thornton and Ross Ltd
Priority date: 2008-08-12
Filing date: 2009-08-05
Publication date: 2010-02-17
Also published as: EP2315529A1; DE112009001947T5; WO2010018360A1; GB0913595D0; GB0814713D0

Abstract

An ectoparasiticidal composition is provided that comprises a mixture of a carrier and an active. The carrier comprises a mixture of a volatile siloxane and an essential oil and/or a derivative of an essential oil in an amount such that it is incapable of adding any significant insecticidal activity to the composition over that of the active. Preferably, the essential oil and/or the derivative of an essential oil comprises a terpene, in particilar nerolidol, or a phenylpropanoid derivative. These impart significant penetration enhancement of the active or actives of the ectoparasiticidal composition. The volatile siloxane may be an alkylsubstituted cyclic or linear siloxane wherein methyl groups predominate. The essential oil may be a terpene or a phenylpropanoid derivative and is preferably nerolidol. The composition may be used to treat head lice.

Description

A METHOD AND COMPOSITION FOR

THE CONTROL OF ECTOPARASITES

The present invention relates to ectoparasiticidal compositions and to a method of controlling ectoparasites, in particular head lice and their ova.

The control of head lice infestations has traditionally been performed using conventional insecticides. However, many of these substances have an unpleasant odour and may cause allergic reactions. Organic insecticides such as hexachlorocyclohexane, malathion and pyrethrins can cause toxic responses in humans such as nerve damage. Such responses are consideraMy more dangerous than the head lice infestations which they are used to treat.

Recently, other problems have also arisen as head lice can mutate and have developed resistance to several insecticides. The desire to find alternative therapy has prompted many consumers to experiment and to resort to untested methods that may be dangerous.

In view of the foregoing, non-toxic products which are found to be safe to use and clinically effective have become very important in the control of head lice. Such products are also more acceptable to consumers who are concerned about the use of toxic pediculicides, in particular use on young children.

Compositions for the control of ectoparasites, in particular head lice, are known that comprise a mixture of a carrier in the form of a volatile silicone and an active, for example in the form of a non-volatile siloxane. In use, when the composition is applied to the hair, the volatile silicone acts to spread the active over the scalp and hair and then evaporates leaving the active as a deposit coating the hair and any lice and ova that are present.

One of the objects of the present invention is to provide an ectoparasiticidal composition with a carrier that improves the efficacy of the active. In particular, it is an object of the invention to provide an ectoparasiticidal composition that is effective against louse ova as well as against the insects themselves. Such a composition would have the considerable advantage that the number of treatments required for eradication of a louse infestation could he significantly reduced, in particular in the most effective compositions to a single treatment.

According to a first aspect of the present invention there is provided an ectoparasiticidal composition comprising a carrier and an active, the carrier comprising a mixture of a volatile siloxane and an essential oil and/or a derivative of an essential oil in an amount such that it is incapable of adding any significant insecticidal activity to the composition over that of the active.

It should be understood both herein and in the claims that the terms essential oil" and "derivative of an essential oil" are to be interpreted broadly to include compounds that have been isolated from naturally derived substances, that are synthetic or that are a combination of such compounds.

Siloxanes may be volatile or non-volatile. It will be appreciated that there is no absolute definition of the term "volatile" but its meaning in the context of the present invention will be apparent to those skilled in the art and for the purposes of this application the term "volatile" is taken to mean that the siloxane has a measurable vapour pressure, i.e. a vapor pressure of at least 2 mm of rnercuiy at 200 C. Typically, this means that the volatile siloxane will have a viscosity of 0.5 to 25 centistokes at 25° C. By "amount such that it is incapable of adding any significant insecticidal activity to the composition" is meant that the quantity of essential oil and/or derivative of an essential oil added. to the composition is such that it produces no increase in insecticidal activity of the composition over that of the same composition used without the addition of the essential oil and/or the derivative of the essential oil. This could be confirmed by a significant number of ectoparasites surviving exposure to the essential oil and/or the derivative of an essential oil when mixed with an appropriate solvent such as isopropanol or ethanol in the same concentration as in the composition of the invention, Alternatively, it could be confirmed by tests with a formulation in accordance with the invention plus or minus the added essential oil and/or derivative of an essential oil.

Preferably, the essential oil and/or the derivative of an essential oil comprises a terpene or a phenylpropanoid derivative.

Preferably also, the terpene is a linear terpene. Advantageously, it comprises neroildoL The essential oil and/or the derivative of an essential oil may comprise up to qo% of the carrier dependent upon its insecticidal properties but preferably comprises less than 50 % and most preferably between o5 to 10 % of the composition.

Suitable volatile siloxanes for use in the invention include cyclic silicones, linear silicones and mixtures thereof. In some embodiments the volatile siloxane comprises a low viscosity linear polysiloxane having a viscosity less than 10 centistokes. In other embodiments the volatile siloxane advantageously comprises cyclomethicone.

In a second aspect the present invention provides the use of a composition in a method of treatment or prophylaxis of a human or animal wherein the composition comprises a carrier and an active, the carrier comprising a mixture of a volatile siloxane and an essential oil and/or a derivative of an essential oil in an amount such that it is incapable of adding any significant insecticidal activity to the composition over that of the active.

In a third aspect the present invention provides a method of controlling an ectoparasitical infestation which comprises applying to said ectoparasite or its ovum a composition comprising a carrier and an active, the carrier comprising a mixture of a volatile siloxane and an essential oil and/or a derivative of an essential oil in an amount such that it is incapable of adding any significant insecticidal activity to the composition over that of the active.

Preferably in all of the aspects of the invention, both the carrier and the active comprise non-toxic products such that the composition is both non-irritating and non-sensitizing to the eyes and skin when tested in compliance with Iso 10993-10:2002. This ISO standard is the standard that must be reached by compositions in order for them to be classified as medical devices'.

In a first embodiment of the invention, the active comprises a non-vollatile siloxane. In other embodiments of the invention, the active may comprise a fatty acid ester, for example isopropyl myristate or a mixture of a fatty acid ester and a non-volatile siloxane.

Whilst volatile siloxanes are excellent at delivering actives to kill adult lice, lice ova have proved to be more difficult to kill. The louse egg cuticle is hydrophobic and almost impenetrable in contrast to the louse cuticle and gaseous exchange occurs via one small group of pores (aeropyles). rmese aeropyles have a very narrow entrance which creates surface tension and bridging, preveiiting penetration of aqueous solutions, and the hydrophilic inner structure of the pore lining is a barrier to organic solvents. The siloxane compositions are hydrophobic and while they are very low in surface tension and can penetrate most orifices without surface tension bridges, they are repelled by hydrophilic agents.

By adding an essential oil and/or a derivative of an essential oil, in particular a terpene or a phenylpropanoid derivative to a carrier comprising a volatile siloxane, the applicant has found that whilst having no inherent insecticidal properties the surfactant physicochemical properties of the carrier are improved and that a degree of hydrophillicity is added to the overall composition. This improves the penetrating properties of the composition and permits tile active to penetrate the aeropyles of the ova in addition to the spiracles of the insects, thereby improving the overall effectiveness of the composition as a whole.

Other features and advantages of the present invention will be apparent to those skilled in the art from the following further description of various examples and preferred embodiments of the invention.

A carrier in a composition according to the invention comprises a volatile siloxane as defined above. Such siloxanes may be either linear or cyclic siloxanes, or a combination of both.

Cyclic volatile siloxanes may be selected from those consisting of the general formula

R (I)

where each R is independently selected from an alkyl group consisting of 1 to carbon atoms and an aryl group consisting of 6 to 10 carbon atom; and x has the value of 3 to 7. The preferred cyclic silicones of the instant invention are those where R predominantly comprises the group -CH3 and x is 4, 5 or 6 or a mixture thereof. In particular, the volatile siloxane comprises cyclopentasiloxane D5.

Linear volatile siloxanes may be selected from the group consisting of the general formulas

R R and

R

R R R

R K

where R is as described above and y has the value of 1 to 5. The preferred linear volatile siloxanes are those of formula (II) where R is predominantly the group -CH3.

Advantageously, the carrier comprises a cyclomethicone. Preferably, the cyclomethicone is cyclopentasiloxane or a mixture of cyclopentasiloxane and cyclohexasiloxane.

Compositions comprising a mixture of a cyclomethicone and an active in the form of a dimeticone or a dimeticonol have been shown to be highly effective against head lice. The active may comprise a non-volatile siloxane and/or a fatty acid ester in an amount up to 90% by volume of the composition but preferably comprises up to o% and most preferably comprises between o.i% and i% by volume of the composition. In particular, the present applicant has conducted experiments using formulations wherein the volatile silicone comprises between 97.5% and 95.5% and the non-volatile silicone comprises between 2.5% and 4.5% of the formulation. Specifically, the formulation comprises cyclomethicone in admixture with dimeticone, wherein the cyclomethicone comprises between 94.5% and 97.5% and the dimeticone comprises between 2.5% and.o%.

In these experiments live adult head lice were collected from healthy volunteers and treated by coating in the formulation and by leaving them overnight at room temperature. Treated and untreated lice were then viewed by scanning electron microscopy and the chemical elements found in the spiracles of the lice were determined by cutting the surrounding tissues away using a focused ion beam and X-ray microanalysis to find the chemical element silicon, which is present in dimeticone but not in lice. X-ray analysis showed silicon present over the whole surface of treated lice but absent on untreated lice. The silicone had formed a plug or a thin coating on the inside of the spiracles of treated lice. Ion beam cutting in the scanning electron microscope created a cross section of an abdominal spiracle. X-ray spectral analysis of the sectioned area highlighted the distribution of silicon from the dimeticone.

Human head lice have a unique strategy of water management. They do not produce urine, but eliminate excess water by respiratory transpiration via the trachea and spiracles. Blockage of the spiracles was shown to prevent or reduce water excretion, often leading to death by gut rupture. When the head lice were immersed in the formulation their locomotion ceased within 30 seconds with no further movements of appendages, although slight gut movements could be seen in some lice. When lice were treated after taking a blood meal they initially lost weight at a similar rate to untreated lice but, from about 30 minutes after treatment, the rate of water excretion was reduced, so that after 4 hours the treated group had lost only 15% of the weight of the blood meal compared with 45% in the untreated group. This indicates a blockage of the louse transpiration process. Some insects experienced gut rupture several hours after treatment believed to be due to a reverse osmotic effect. It should be noted that gut rupture has only been observed in fed lice with a blood filled gut. This is highly visible and an extreme mechanism of death. However unfed lice also died as a result of immobility, which is in effect death from starvation. The water vapour barrier efficacy of silicones is a complex relationship between the structure, molecular weight, and thickness of the silicone oil film -the higher the molecular weight, the better its barrier properties. Lice treated with the formulation always entered a moribund state and were never noticed to recover. The exact mechanism of death is debatable and although asphyxiation cannot be ruled out as one mechanism, it is believed that the major cause is the prolonged immobility reflex associated with osmotic disruption and gut rupture or starvation.

Whilst compositions comprising solely a mixture of volatile and non-volatile siloxanes are highly effective against head lice, they are not so effective against their ova.

Terpenoids and phenylpropanoids are compounds that form the major active ingredients in essential oils and may be synthetic or isolated from naturally derived substances. Individual terpenoids and phenylpropanoids contained within different essential oils have widely differing effects on the insects and their ova. However, the applicant has found that certain ones improve the penetrating characteristics of volatile siloxane carriers in ectoparasiticidal compositions without having licicidal properties per Se. In particular, those having one or more hydroxyl groups and preferably those that are also linear were found to be highly effective at improving the penetrating characteristics of volatile siloxane carriers.

It is known that essential oils including terpenoids and phenylpropanoids generally should not be applied directly to the skin in an undiluted or "neat" form. Some can cause severe irritation, or provoke an allergic reaction.

Others may sensitize the skin to other factors, for example some are photosensitizers and make the skin vulnerable to sunburn. Yet others are cytotoxic. The terpenoid and/or phenylpropanoid used in the invention must preferably combine safety of use with efficacy for the intended purpose.

Nerolidol is a linear terpenoid with a single hydroxyl group. It is non-toxic and is not known to cause allergic reactions or to sensitize the skin. It has been found that compositions containing even relatively small quantities of nerolidol in combination with a carrier comprising a volatile siloxane and active comprising a non-volatile siloxane consistently produce close to 100% insect and ova kill rates, which is a significantly higher kill rate, particularly against the ova, than using compositions that do not contain the nerolidol.

The following tests illustrate the invention.

Materials and Methods The efficacy of four formulations against louse eggs with an overnight exposure was measured. The formulations used in the tests each comprise an active base mixture of 4% dimeticone (ioo,ooo centistokes) and up to 100% cyclopentasiloxane to which 0, 1.5% or 2.0% nerolidol had been added.

Water was used as the control.

Insects used in the tests Louse eggs were obtained by providing actively laying adult lice with a close meshed nylon gauze substrate, in place of a cotton corduroy substrate, over a 48 hour period. At the end of this time the insects were removed and the gauze substrate was cut into appropriately sized smaller pieces. The small gauze pieces were randomly allocated to plastic Petri dishes in advance of the test.

For the test procedure an aliquot of approximately 5-10 millilitres of the appropriate formulation was poured into the base of a clean millimetre plastic Petri dish. The gauze bearing the eggs were immersed in the fluid for seconds, during which time the gauze was turned at least twice to ensure removal of air bubbles. After removal from the fluid the gauze and eggs were lightly blotted to remove excess fluid and returned to their marked Petri dish. The same procedure was repeated for the other replicate gauze squares in that batch.

The gauze squares bearing eggs were incubated under normal maintenance conditions (300 � 2° Celsius and o% � i% relative humidity) for the remainder of the test period. At the end of the exposure period the insects and gauze were washed using a bland toiletry shampoo diluted one part shampoo with fourteen parts water (FWS 1:15) after which they were rinsed using 500 millilitres of warm (° Celsius) tap water poured through and over the gauze squares. They were then blotted dry using medical wipe -10 -tissue and incubated under normal maintenance conditions in clean plastic Petri dishes of the appropriate size until the results were recorded. The results of tests against eggs were read after the entire control batch had completed emergence a minimum of ten days after treatment.

Results Activity against eggs The activity of insecticides against louse eggs requires classification of the effect according to the degree of penetration of the insecticide.

"Hatched" describes louse eggs that have not been penetrated by the insecticide so that the embryo inside develops normally and hatches normally.

"Half-hatched" describes those eggs in which either a small amount of insecticide may have penetrated, but insufficient to kill the emerging louse before it has started the emergence process, or else the emerging insect picks up enough insecticide from the outside of the eggshell to kill it but only after it has partially emerged from the shell.

"Dead" describes those eggs in which the embryo has apparently completed its development but which has not emerged from the eggshell. In some cases this description also applies to eggs in which sufficient insecticide becomes lodged in the outer layers of the eggshell, between the chorionic membranes that surround the embryo and the eggshell cap, that the young louse is killed during the emergence process but before it is capable of lifting the lid from the eggshell.

"Undeveloped" is a description that is applied to all those eggs that fail to develop correctly or at all. This can be identified because at the time of testing the young embryos appear amorphous inside the transparent eggshell. When the developing embryo is about 48 hours old it starts to develop a small pigmented spot at the cap end of the shell. This spot will -11 -develop to become the eye of the louse and is referred to as the "eyespot". If a material is capable of cutting off the oxygen supply to the egg by entering and blocking the aeropyles it can kill the young embryo before it has developed to the point of showing the eyespot. In some cases the embryo may develop only to the point of showing an eyespot but in these cases the spot is misshapen or may even be at the wrong end of the eggshell. All such cases are classified as "Undeveloped".

Table 1 below shows the results of the tests against louse eggs with an overnight exposure.

Table 1

Half Mortality Composition Replicate Total Hatehed Hatched Dead Undeveloped % Control 1 142 129 1 7 5 ___________ _____________ 2 128 114 1 7 6 ___________ __________ Total 270 243 2 14 11 10% Active base +1.5% nerolidol 1 84 1 0 4 79 __________ ____________ 2 70 1 1 13 55 ___________ __________ Total 154 2 1 17 134 98.70% Active base +2.0% iierolidol 1 8o 0 0 6 74 __________ ____________ 2 94 0 1 1 92 __________ __________ Total 174 0 1 7 i66 100% Active base alone i 63 32 0 10 21 __________ _____________ 2 49 26 1 2 20 ___________ __________ Total 112 8 1 12 41 48.21% These results show that an overnight exposure with the active base alone produced a mortality of 48.21% followed by 98.70% for the active base with 1.5% added nerolidol and 100% for the active base with 2% added nerolidol.

The formulations with the added nerolidol resulted in a higher percentages of undeveloped eggs which indicates that these compositions are capable of cutting off the oxygen supply to the egg, by entering and blocking the aeropyles.

-12 -Overall the composition containing 2% nerolidol was found to be the most effective formulation against louse eggs with an overnight exposure. Further tests were carried out using this composition with a view to establishing the exposure time which is most effective against louse eggs. The exposure times tested were 1 hour, 2 hours, 3 hours, 4 hours and overnight.

Using the same materials and methods as above but using only the active base indicate above with 2% nerolidol added for the specified periods of time produced the results shown in the following Table 2.

Table 2

Replicate Total Hatched Half Dead Undeveloped Mortality ___________ _______ _________ Hatched ______ _______________ % Overnight ________ __________ __________ ______ ________________ __________ 1 147 4 3 i8 122 __________ 2 156 12 3 11 130 __________ 3 115 5 0 19 91 __________ Total 418 21 6 48 343 94.97% 4 Hours ________ __________ __________ ______ _______________ _________ 1 128 0 0 11 117 __________ 2 120 20 2 17 83 __________ 3 130 9 1 10 110 __________ Total 378 29 3 38 310 92.85% 3 Hours ________ __________ __________ ______ ________________ __________ 1 49 7 1 i6 25 __________ 2 117 26 2 22 67 __________ 3 141 78 4 i8 41 __________ Total 307 111 7 6 133 63.84% 2 Hours __________ ______ _______________ _________ 1 121 8 3 22 88 __________ 2 139 25 1 23 90 __________ 3 90 57 1 13 19 __________ Total 350 90 5 8 197 74.28% 1 Hour __________ ______ _______________ _________ 1 96 46 1 23 26 __________ 2 71 43 2 10 i6 __________ 3 102 23 3 19 57 __________ Total 269 112 6 52 99 58.36% Gontrol _____________ ________ ____________________ ____________ 1 64 6i 0 1 2 __________ 2 83 76 0 4 3 __________ 3 iiG 107 2 4 3 _________ Total 263 244 2 ______ 8 7.22% -13 -The results shown in Table 2 demonstrate that the most effective exposure time for 2% nerolidol formulation is overnight. However, the four hour exposure produced very high levels of mortality at 92.85% compared to the overnight exposure which was 94.97%. This shows that there is very little difference in the efficacy with a longer exposure time after four hours. An exposure time of three hours or below produces much lower levels of efficacy against the louse eggs.

The results of all the tests are interesting because they indicate that the addition of only small quantities of nerolidol to a composition comprising a mixture of volatile and non-volatile siloxanes significantly improves the ovicidal activity of the composition. As indicated above, the aeropyles of the louse ovum have a narrow entrance and a hydrophilic inner pore lining.

Nerolidol has no licicidal activity, indicating that it has no pharmacological activity, but it does have weak surfactant physicochemical properties, by virtue of a single -OH group at or near one end of a long aliphatic portion.

This will, therefore add a degree of hydrophillicity to the overall composition.

Lice eggs aeropyles treated with the compositions detailed above were scanned in a scanning electron microscope by X ray spectroscopy. It was found that the aeropyles in those treated with an active base composition alone contain some silicon but those treated with the 2% nerolidol formulation typically had double the response, as illustrated in the following Traces 1 and 2.

Trace 1 is an X ray spectrograph of an aeropyle treated with the active base composition alone.

Trace 2 is an X ray spectrograph of an aeropyle treated with the active base composition plus 2% nerolidol.

Lice eggs require oxygen/carbon dioxide gaseous exchange through the aeropyle openings, to develop. Blocking this structure will prevent the eggs from developing. Whilst the carrier in the active base composition comprises -14 -an excellent penetrating oil it has limited gas barrier properties, which are proportional to the thickness of the layer. The active base composition alone has been shown to have some efficacy at killing eggs (40-60%), which indicates some efficacy at blocking the aeropyles, but it is not totally effective. However, by adding nerolidol, its ovicidal efficacy is boosted to virtually 100% efficacy.

Trace 2 shows there to be twice as much silicone present in those treated with the active base plus 2% nerolidol composition as those treated with the active base composition alone, as shown in Trace 1. Thus it can be concluded that the nerolidol increases the penetration of the active base thus increasing its gas barrier properties. Organic oils are also significantly better gas barriers than silicon oils, thus the presence of nerolidol itself will add to this effect. This has been hypothesized to be due to the nerolidol adding a degree of surfactancy to the fluid. This hypothesis is also supported by the fact that in a further test where more hydrophobic oils, for example paraffin oil, were added (at 2% to the active base composition) its efficacy against eggs reduced by up to 50%.

The applicant believes that phenylpropanoid derivatives will also act in a similar way to nerolidol and impart significant penetration enhancement of the active or actives of an ectoparasiticidal composition into the aeropyles of the target insects' ova.

-15 -Trace 1 Si tkS3) IS) Trace 2 Si

-

tie iso

Claims

-16 -CLAIMS1. An ectoparasiticidal composition comprising a carrier and an active, the carrier comprising a mixture of a volatile siloxane and an essential oil and/or a derivative of an essential oil in an amount such that it is incapable of adding any significant insecticidal activity to the composition over that of the active.
2. A composition as claimed in Claim 1, wherein the essential oil and/or the derivative of an essential oil comprises a terpene or a phenylpropanoid derivative.
3. A composition as claimed in Claim 2, wherein the terpene is a linear terpene.
4. A composition as claimed in Claim 2 or Claim 3, wherein the terpene comprises nerolidoL
5. A composition as claimed in any of Claims 1 to 4, wherein the volatile siloxane comprises a linear polysiloxane having a viscosity less than centistokes or cyclomethicone.
6. A composition as claimed in Claim 5, wherein the cyclomethicone is cyclopentasiloxane or a mixture of cyclopentasiloxane and cyclohexasiloxane.
7. A composition as claimed in any of Claims 1 to 6, wherein the essential oil and/or the derivative of an essential oil comprises up to 90% of the carrier.-17 -
8. A composition as claimed in any of Claims 1 to 6, wherein the essential oil and/or the derivative of an essential oil derivative comprises up to 50% of the carrier.
9. A composition as claimed in any of Claims 1 to 8, wherein the essential oil and/or the derivative of an essential oil comprises up to 2.5% of the carrier.
10. A composition as claimed in any of Claims 1 to 9, wherein the active comprises a non-volatile siloxane and/or a fatty acid ester.
ii. A composition as claimed in any of Claims 1 to 10, wherein the active comprises a non-volatile siloxane and/or a fatty acid ester in an amount up to 90% by volume of the composition.
12. A composition as claimed in any of Claims 1 to 10, wherein the active comprises a non-volatile siloxane and/or a fatty acid ester in an amount up to o% by volume of the composition.
13. A composition as claimed in any of Claims 1 to 10, wherein the active comprises a non-volatile siloxane and/or a fatty acid ester in an amount between o.i% and 15% by volume of the composition.
14. A composition as claimed in any of Claims 1 to 10, wherein the non-volatile siloxane comprises between 2.5 % and.o% by volume of the composition.
15. A composition as claimed in any of Claims 1 to 14, wherein the non-volatile siloxane is a dimeticone or a dimeticonol.
i6. A composition as claimed in any of Claims 1 to 15, wherein the active comprises a fatty acid ester in an amount between % and 70% w/w of the composition.-18 -
17. A composition as claimed in Claim i6, wherein the fatty acid ester comprises isopropyl myristate.
18. A composition as claimed in any of Claims 1 to 17, that is both non-irritating and non-sensitizing to the eyes and skin when tested in compliance with Iso 10993-10:2002.
19. Use of a composition in a method of treatment or prophylaxis of a human or animal wherein the composition comprises a carrier and an active, the carrier comprising a mixture of a volatile siloxane and an essential oil and/or a derivative of an essential oil in an amount such that it is incapable of adding any significant insecticidal activity to the composition over that of the active.
20. Use of a composition as claimed in Claim 19, wherein the essential oil and/or the derivative of an essential oil comprises a terpene or a phenylpropanoid derivative.
21. Use as claimed in Claim 20, wherein the terpene comprises nerolidol.
22. Use as claimed in any of Claims 19 to 21 in which the method is for the treatment or prophylaxis of a head lice infestation.
23. A method of controlling an ectoparasitical infestation which comprises applying to said ectoparasite or its ovum a composition as claimed in any of Claims 1 to i8.