IE60936B1

IE60936B1 - A topical lousicidal composition for controlling lice or their ova

Info

Publication number: IE60936B1
Application number: IE137088A
Authority: IE
Original assignee: Euro Celtique Sa
Priority date: 1987-05-07
Filing date: 1988-05-06
Publication date: 1994-09-07
Also published as: GB2204243B; GB2204243A; GB8810161D0; GB8710784D0; IE881370L

Abstract

A method for controlling lice or their ova on human subjects without irritating the skin consists of applying a topical composition containing a lousicide and a C2-C4 alkyl ester of a C10-C20 fatty acid dissolved in an alcoholic solution. Preferably the lousicide is carbaryl, malathion or phenothrin, the alkyl ester is isopropyl myristate and the alcoholic solution is isopropanol.

Description

The present invention relates to a topical lousicidal composition for controlling lice or their ova on human subjects without irritating the skin of said subjects.

According to the present invention, there is provided a topical lousicidal composition for controlling lice or their ova on human subjects without irritating the skin of said subjects comprising a lousici dally effective amount of at least one lousicide and at least one C2-C4 alkyl ester of a Ciq-C2q fatty acid dissolved in an alcoholic solution.

Preferably the topical composition is a pour-on composition such as a lotion. The at least one lousicide must be soluble in the alcoholic solution and must be compatible with the fatty acid ester. It may be, for example, permethrin or a siloxane, but is preferably, carbaryl malalthion or phenothrin.

The at least one fatty acid ester must also be soluble in the alcoholic solution and must be compatible with the lousicide. It may be, for example, ethyl laurate but is preferably a C3-C4 ester of a C^-C^q fatty acid, such as butyl stearate, isobutyl stearate, butyl oleate or, which is especially preferred, isopropyl myristate.

The alcoholic solution must dissolve both the at least one lousicide and the at least one fatty acid ester. Together with the at least one lousicide and the at least one fatty acid ester, it must be substantially non-irritant to human skin.

Preferably, the alcoholic solution comprises at least one C2-C4, especially C3-C4, alkanol such as n-propanol, tert.butyl alcohol or, which is especially preferred, isopropanol.

The alcoholic solution may also contain a certain proportion, generally up to about 40%(v/v), of water.

In addition to the above ingredients, the present topical, composition may also contain further constituents, provided they are pharmaceutically acceptable, .compatible with the at least one lousicide and the at least one fatty acid ester and soluble in the alcoholic solution. Suitable materials, such as perfumes, will be known to those skilled in the pharmaceutical art.

The amount of the at least one lousicide in the present lousicidaT composition must be sufficient, in use, to control lice or their ova on human subjects. In the present specification, an amount sufficient to control lice or their ova is that amount which will cause at least 50% of the lice exposed in the two minute immersion tests described below to die within 24 hours, in the case of adult lice, and within 2 weeks, in the case of their ova. for the preferred lousicides, the preferred concentrations (g/lOOml of solution) in the present composition are Permethri n Carbaryl Siloxane Malathion Phenothrin 0.1 - 1.0%, especially 0.1 - 0.5% 0.25 - 1.25%, especially 0.5 - 1.0% 5 - 25%, especially 10 - 20% 0.25 - 1.25%, especially 0.5 - 1.0% 0.1 - 0.5%, especially 0.2 - 0.4% The two minute immersion tests referred to above is carried out as follows: Lousicial activity A 50ml beaker is filled with tap water and allowed to come to room temperature (about 20°C). Ten young adult male and ten young adult female lice (Pediculus humanus corporis) of the same age group and from the same stock colony are placed on a 2 x 2cm coarse mesh patch. The sample to be tested, maintained at room temperature, is shaken and placed into a 50ml beaker. Tne mesh patch is placed into the sample immediately after pouring, allowed to submerge, and after two minutes is removed and immediately plunged into the beaker containing tap water. The patch is vigorously agitated every ten secounds and after one minute the patch is removed and placed on paper toweling. The lice are then transferred to a 4 x 4cm black corduroy cloth patch and this point of time is considered zero hours. Thereafter, the corduroy patch is placed in a petri dish which is covered and stored in a 30°C holding chamber.

Ovicidal activity adult, 5 to 10 day old, female lice (Pediculus humanus corporis) are placed on a 2 x 2cm nylon mesh patch which is placed on a petri dish, covered and maintained in an incubator at. 30eC for 24 hours. The adult lice are then removed and the number of plump viable eggs and shrive lied non-fertile eggs on the patch are recorded. The sample to be tested, maintained at room temperature, is shaken and poured into a 50ml beaker. Immediately after the pouring, the mesh patch is placed into the beaker, allowed to submerge, and after two minutes is removed and immediately plunged into a 50ml beaker containing tap water at room temperature (about 24°C). Tne patch is vigorously agitated every ten seconds, and after one minute, the patch is removed and placed on paper toweling for one minute. The patch is then placed in a petri dish which is ' covered and stored in the 3O°C incubator.

/ Fourteen days following treatment, the number of hatched eggs and the number of shrivelled or unhatched eggs is noted.

In both two minute immersion tests, controls are run in identical manner to that described with room temperature (24°C) tap water substituted for the sample to be tested.

The amount of the at least one fatty acid ester in the present composition will depend, amongst other factors, on the fatty’ acid ester used, and the choice of lousicide and alcoholic solution. Preferably, the composition contains between 5 and % (v/v), especially between 5 and 15% (v/v), of the fatty acid ester.

The amount of the alcoholic solution in the present composition must be sufficient to dissolve both the at least one lousicide and the at least one fatty acid ester.

Preferably, the composition contains between 70 and 95% (v/v), especially between 80 and 95% (v/v) of the alcoholic solution.

The present topical, lousicidal composition must be substantially non-irritant to human skin. In the present specification, the phrases without irritating the skin of said (human) subjects and substantially non-irritant to human skin means that more than 80, preferably more than 90, patients out of every 100 patients show no reaction to the topical, lousicidal composition.

The present composition is used to control lice or their ova in humans, by applying the composition to a site of infestation or io a site believed to be infested.

Alternatively, the composition may be used prophylactically to prevent infestation.

In a further aspect of the present invention, there is provided a topical, lousicidal composition for controlling lice or their ova comprising a lousicidally effective amount of at least one lousicide selected from carbaryl, malathion or phenothrin and 5 to 20% (v/v) of at least one C2-C4 alkyl ester of a C10-C20 fatt^ acid dissolved in 70-95% (v/v) of an alcoholic solution, the composition being substantially non-irritant to human skin.

In a still further aspect of the present invention there is provided a process for the preparation of a topical, lousicidal composition that is substantially non-irritant to human skin comprising dissolving a lousicidally effective amount of at least one lousicide selected from carbaryl, malathion cr phenothrin and 5 to 20% (v/v) of at least one C2-C4 alkyl ester of a C10-C20 fatty acid in 70-95% (v/v) of an alcoholic solution.

The present topical, lousicidal composition and processes for its preparation will now be described by way of Example only.

Example 1 (Malathion Lotion) A solution was prepared by mixing isopropyl myristate (100ml), golden delicious perfume P15498 (PFW Ltd., Greenford, Middlesex) (5ml) and isopropanol (678ml). To this solution was added malathion (5.0gm) and the whole was mixed until homogeneous. A further aliquot of isopropanol was then added to bring the volume of the composition to 1000ml and the whole was again mixed until homogeneous. - 6 Example 2 (Phenothrin Lotion) The procedure of Example 1 was followed except that phenothrin (2.0gm) replaced malathion and herbal green bouquet (PFW Ltd., Greenford, Middlesex) (5.0ml) replaced golden delicious perfume P15498. f fc Comparative Example (Malathion Lotion) A lotion having the following formulation was prepared, Malathion Terpineol Di pentene Perfume 07676* Isopropanol 0.525% (w/v) 11.0 (v/v) 10.0 (v/v) 0.25 (v/v) to 100.0 (v/v) * PFW Ltd, Greenford, Middlesex Irritancy Test Malathion lotions (Example 1 and Comparative Example) were tested using a routine repeat insult schedule of applications with assessment over a 24 day period. j The procedure was as follows: Day 1 Day 3 Day 5 Day 8 Day 10 Day 12 Day 15 Day 22 Day 24 Apply materials Remove, wait 15 Remove, wait 15 Remove, wait 15 Remove, wait 15 Remove, wait 15 Remove, wait 15 Apply materials Remove, wait 15 under occlusion minutes, assess, re-apply minutes, assess, re-apply minutes, assess, re-apply minutes, assess, re-apply minutes, assess, re-apply minutes, assess under occlusion minutes, assess re-application This technique of repeat insult supplied a maximal cutaneous stimulus which was designed to reveal low order of irritancy and sensitisation potential.

At each assessment time the sites were graded on a 0-6 scale, as follows: = No reaction = Slight erythema = Moderate erythema = Strong erythema with some swelling = Erythema, swelling and vesiculation = Marked erythema, spreading outside patch = Severe reaction with erosion All repeat applications were of the same materials to the same sites, but no re-application was made to any site showing a reaction at any time that was graded 2 or more on the above scale of assessment.

After the sixth grading (day 15) the sites were left untreated for a seven day period. On day 22 the materials were re-applied to new sites, occluded as before, and a final assessment was made on day 24 to check for any delayed hypersensitivity.

Fifty-two patients were treated with Comparative Example lotion and 100 patients were treated with the Example 1 lotion.

A summary of the results is presented in the following table.

| Lotion | Irritancy scores 0 1 I Sensitisation 1 scores | 0 1 1 2 1 1 1 2 I 1 | Comparative | Example | 50 0 2 1 1 - | | Example 1 | 1 0 99 1 1 2 J 5 93 | - Product not re-applied in these subjects Efficacy Trial A study was conducted using phenothrin lotion (Example 2} in 23 patients.

Patient's scalps were examined for evidence of the live lice and/or viable eggs (Visit 1). This was recorded together with details of the patient's age and sex. Each patient was issued with a bottle of phenothrin lotion (Example 2).

Instructions were issued that the lotion should be applied on one occasion to all parts of the hair and scalp, and that it should be left on the hair for 2 hours. Patients were requested to return for re-inspection after 24 hours (Visit 2). Ai this second visit a record was again made of any live lice and/or viable eggs.

Patients returned three weeks after treatment (Visit 3), when a final inspection for live or viable eggs was carried out.

RESULTS (i) Patients A total of 23 patients were entered into the study, 7 male and 16 female. (ii) Infestation prior to treatment (Visit 1) All 23 patients had evidence of live lice, viable eggs or both on entry to the study. (iii) Infestation following treatment (Visit 2) Patients were requested to attend for re-inspection approximately 24 hours following treatment. At this second visit, no patients had evidence of live lice, although 6 had viable eggs. (iv) Infestation at final follow-up (Visit 3) Patients were requested to return for final inspection 3 weeks following treatment. At this final inspection, no patients showed any evidence of live lice or viable eggs.

Details of head infestation over the study period are given in the Table.

Claims

1. A topical, lousicidal composition for controlling lice or their ova comprising a lousicidally effective amount of at least one lousicide and at least one C 2 -C 4 alkyl ester of a Cjq-C 2 q fatty acid dissolved in an alcoholic solution.

2. A composition according to claim 1 wherein the at least one lousicide comprises carbaryl, malathion or phenothrin.

3. A composition according to claim 2 wherein the at least one lousicide comprises 0.25% to 1.25% (g/lOOml of solution) carbaryl, 0.25% - 1.25% (g/lOOml of solution) malathion or 0.1% - 0.5% (g/lOOml of solution) phenothrin.

4. A composition according to claim 3 wherein the at least one lousicide comprises 0.5% - 1.0% (g/lOOml of solution) carbaryl, 0.5% - 1.0% (g/lOOml of solution) malathion or 0.2% - 0.4% (g/lOOml of solution) phenothrin.

5. A composition according to any one of claims 1 to 4 wherein the at least one alkyl ester comprises a C 3 -C 4 alkyl ester of a C 14 -C 18 fatty acid.

6. A composition according to claim 5 wherein the at least one alkyl ester comprises butyl stearate, isobutyl stearate, butyl oleate or ispropyl myristate.

7. A composition according to claim 6 wherein the at least one alkyl ester comprises isopropyl myristate.

8. A composition according to any one of claims 1 to 7 comprising 5 - 20% (v/v) of the at least one alkyl ester. 12

9. A composition according to claim 8 comprising 6 - 15% (v/v) of the at least one alkyl ester. r

10. A composition according to any one of claims 1 to 9 5 wherein the alcoholic solution comprises at least one ~ C 2 -C 4 alkanol.

11. A composition according to claim 10 wherein the alcoholic solution comprises at least one C 3 -C 4 alkanol.

12. A composition according to claim 11 wherein the alcoholic solution comprises n-propanol, isopropanol or tert.butyl alcohol. 15

13. A composition according to claim 12 wherein the alcoholic solution comprises isopropanol.

14. A composition according to claim 13 comprising 70 - 95% (v/v) of the alcoholic solution.

15. A composition according to claim 14 comprising 80 - 95% (v/v) of the alcoholic solution.

16. A composition according to claim 1 comprising a 25 lousicidally effective amount of at least one ilousicide selected from carbaryl, malathion or phenothrio and 5 - 20% (v/v) of at least one C 2 -C 4 alkyl ester of a θ10θ20 fatt * ac id dissolved in 70-95% (v/z) of an alcoholic solution, the composition being substantially , n non-irritant to human skin. -13

17. A composition according to claim 16 wherein the at least one lousicide comprises 0.5% - 1.0% (g/lOOml of solution) carbaryl, 0.5% -. 1.0% (g/lOOml of solution) malathion or 0.2% - 0.4% (g/lOOml of solution) phenothrin.

18. A composition according to either claim 16 or claim 17 wherein the alkyl ester comprises isopropyl myristate.

19. A composition according to any one of claims 16 to 18 wherein the alcoholic solution comprises isopropanol.

20. A topical, lousicidal composition for controlling lice or their ova according to claim 16 substantially as hereinbefore described with particular reference to either Example 1 or Example 2.

21. A process for the preparation of a topical, lousicidal composition that is substantially non-irritant to human skin comprising dissolving a lousicidally effective amount of at least one lousicide selected from carbaryl, malathion or phenothrin and 5 - 20% (v/v) of at least one C2C 4 alkyl ester of a Cjq^q fatty acid in 70 - 95% (v/v) of an alcoholic solution.

22. A process for the preparation of a topical, lousicidal composition according to claim 21 substantially as hereinbefore described with particular reference to either Example 1 or Example 2.

23. A topical lousicidal composition whenever prepared by a process as claimed in claim 21 or claim 22.