GB1604857A - Use of higher alcohols as toxicants against lice - Google Patents

Abstract

The ectoparasiticidal or ovicidal composition is based on a monoalcohol, for which the logarithm of the partition coefficient between n-octanol and water is greater than 0.61, mixed with a pharmaceutically acceptable inert carrier. The radical of the monoalcohol is an alkyl, optionally substituted by aryl, aryloxy, halogen or the like, and preferably comprises 4 to 24 carbon atoms. This composition is applicable to man and to animals for the destruction of ectoparasites such as lice and acarians. The composition contains the said monoalcohol as sole active ingredient or as adjuvant.

Description

(54) USE OF HIGHER ALCOHOLS AS TOXICANTS AGAINST LICE (71) We, STAFFORD-MILLER LIMITED, of 166 Great North Road, Hatfield, Hertfordshire, a British Company, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described, in and by the following statement: This invention relates to ectoparasiticidal toxicants and a method of controlling ectoparasites. More particularly, the invention relates to the use of certain higher alcohols as toxicants for lice.

There are only a relatively few pediculicides which are commercially available today. The most popular pediculicidal toxicants are Lindane (gamma benzene hexachloride), Malathion [(S- 1 ,2-dicarbethoxyethyl)-0,0-dimethylhosphorodithioate], synergized pyrethrins and Cuprex (a combination of tetrahydronapthalene, copper oleate and acetone, the acetone not asserted to be active). Because of increased concern about the overall safety of some of the known ectoparasitic toxicants, the search for new, safe and effective pediculicides has intensified recently.

In addition to killing insects, a good ectoparasiticide should also destroy ova to avoid a resurgence of the infestation. Surviving ova may hatch days or weeks after the initial treatment. Lacking ovicidal activity, a pediculicide safe to the host usually must be re-applied until control is achieved.

It is the object of this invention to provide a new, safe and effective method for controlling lice.

According to the present invention there is provided a method of controlling lice which comprises applying to a substrate at least one of the monohydric alcohols specified hereinbelow. The invention can be performed using an ectoparasiticidal toxicant composition for use in the method and comprising an active toxicant active against lice and an inert pharmaceutically acceptable carrier therefor, the active toxicant being at least one of the specified monohydric alcohols.

The invention can also be performed using an ectoparasiticidal toxicant composition comprising an active toxicant active against lice and an inert pharmaceutically acceptable carrier therefor, at least one of the specified monohydric alcohols being incorporated as an adjuvant toxicant in an effective toxic amount. This composition can be used in another method of controlling lice provided by the invention and which involves applying a toxicant with an adjuvant toxicant which is one of the specified a monohydric alcohols.

It has been found that certain higher alcohols which have a logarithm of their partition coefficient between n-octanol and water of at least 0.61 exhibit pediculicidal activity. These alcohols are known materials and have been incorporated into many pharmaceutical and cosmetic preparations. For example, cetyl alcohol constitutes 15% of a published hair groom gel and 61% of a floating bath oil, and lauryl or isocetyl or dodecyl alcohol constitute about 30% of a mineral oil gel. Cetyl alcohol and lauryl alcohol are also listed under the United States Food & Drug Administration's approved Synthetic Flavor Substituents and Adjuvants list (21 CFR 1.1.1164). Cetyl alcohol has been used in compositions applied to the skin (U.S. 3,226,295 and 3,943,234) and lauryl alcohol derivatives have been used in parasiticides (U.S. 2,030,093).

The toxicants employed for the instant invention are the specified monohydric alcohols, ROH, in which R is a particular alkyl or aralkyl group, and the logarithm of the partition coefficient (hereinafter log P) for the compound ROH between n-octanol and water is at least 0.61. Log P values can be obtained by consulting Leo et al, Chemical Review, 71, 525 (1971) or calculated by the method therein described. It is preferred that the alcohols be unsubstituted alkyl alcohols having log P values of 1.16-7.13. For accompanying ovicidal activity, it is preferred to employ an unsubstituted alkyl alcohol having log P values of 2.13-5.1.

The "specified monohydric alcohols" for this invention are iso-pentanol, n-pentanol, n-hexanol, n-octanol, hexadecyl alcohol, and 2-phenylethanol.

One or more of the specified toxic alcohols can be incorporated into an active toxicant composition which can be in the form of a liquid, powder, lotion, cream, gel, aerosol spray, or foam as the result of formulation with inert pharmaceutically acceptable carriers by procedures well known in the art. Any pharmaceutically acceptable carrier, whether aqueous or not aqueous, which is inert to the active ingredient can be employed. By inert is meant that the carrier does not have a substantial detrimental effect on the pediculicidal toxicant activity of the active ingredient.

The active alcohol is incorporated into the toxicant composition used to treat the substrate (human or animal) in need of such treatment, believed to be in need of such treatment, or desired to be prophylactically protected in an effective toxicant amount. By such amount is meant the amount which will cause at least 75% of the lice exposed in the two minute immersion tests described below to die within 24 hours. The minimum concentration of alcohol in the composition required to provide an effective toxic amount varies considerably depending on the particular alcohol, the particular inert pharmaceutically acceptable carrier being employed and any other ingredients which are present. Thus, in one case a 10% concentration may suffice, while in other cases, concentrations as high as 30 to 40% may be required to obtain an effective toxic dose. The alcohols can also be employed as an adjuvant toxicant in a preparation which otherwise exhibits pediculicidal activity. In such preparations, the term "effective toxic dose" means that amount which will increase the mortality rate by about 20% in the standard immersion test.

The two minute immersion test referred to above is carried out as follows: Pediculicidal activity: A 50 ml beaker is filled with tap water and allowed to come to room temperature (about 24"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 2x2 cm coarse mesh patch. The sample to be tested, maintained at room temperature, is shaken until homogeneous and placed into a 50 ml beaker. The 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 the tap water. The patch is vigorously agitated every ten seconds and after one minute the patch is removed and placed on paper toweling. The lice are then transferred to a 4x4 cm 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.

In the pediculicidal two minute immersion tests, controls are run in identical manners to that described with room temperature (24"C) tap water substituted for the sample to be tested. The results of the tests reported are net results.

In the following table, the results of pediculicidal testing for various alcohols of this invention and other alcohols are set forth. The alcohols were tested in undiluted form (100% alcohol), as a 25% solution in water, and in a solution containing 15% of the alcohol, 25% isopropanol and 60% water ("15/25/60"). The results are set forth in terms of percent mortality.

Table 1 Pediculicidal Rating 100% 25% Alcohol Log P Alcohol Solution 15/25160 Methanol -0.66 0 0 0 Ethanol -0.32 45 0 0 iso-Propanol -0.12* 65 0 0 n-Propanol 0.34 70 0 0 tert-Butanol 0.37 80 0 0 sec-Butanol 0.61 95 0 35 iso-Butanol 0.65 95 40 0 N-Butanol 0.88 100 20 0 Benzyl Alcohol 1.10 90 0 5 iso-Pentanol 1.16 100 55 80 2-Phenoxy ethanol 1.16 100 5 5 Cyclohexanol 1.23 100 0 20 4-Chloro butanol 1.27* 100 0 20 2-Phenyl ethanol 1.36 100 0 80 n-Pentanol 1.40 100 10 75 n-Hexanol 2.03 100 5 85 n-Octanol 3.15 100 10 85 n-Decanol 4.15* 100 20 95 n-Dodecanol 5.13 100 10 100 Hexadecyl Alchol < 7.13* 100 40 90 Oleyl Alcohol 7.47* 100 0 40 The log P values set forth in the foregoing table I are those set forth in the aforementioned Leo et al article except for the values starred which were calculated using standard methods. The log P value for hexadecyl alcohol is a calculated value and the actual figure is dependent on the degree of branching of the alkyl moiety.

As noted above, various end use formulations can be prepared. Some typical formulations are set forth below and the amounts recited are percentages by welght: Lotion Isopropyl alchol 25 Hexadecyl alchol 15 Carboxypolymethylene 0.1 Triethanolamine 0.1 Water 59.8 Cream Isopropyl alcohol 25.0 Isopentanol 15.0 Glyceryl monostearat 22.5 Sorbitan monostearate 1.5 Polysorbate 60 3.5 Xanthan gum 0.2 Water 32.3 Quick Breaking Aerosol Foam Mono and diglycerides from the glycerides of edible fats 8 n-Octanol 15 Isopropanol 25 Glycerine 3 Isobutane 8 Water 41 An illustrative example will now be given of the use of the compounds with adjunctive toxicants. There is given the formulation and activity of a composition of the invention with and without adjuvant, and then of a comparison composition based on the adjuvant.

Isopropanol 25 90 29 Hexadecyl alcohol 15 Water 60 Isopropanol 25 100 100 Hexadecyl alcohol 15 N.(2-Hydroxyprnpyl)- lauramide 10 Water 50 Isopropanol 25 15 100 N-(2-Hydroxypropyl) lauramide 15 Water 60 Various changes and modifications can be made: the various embodiments disclosed herein are for the purpose of further illustrating the invention but are not intended as limiting. Throughout this specification and claims, all temperatures are in degrees Centigrade and all parts and percentages are by weight unless otherwise indicated.

WHAT WE CLAIM IS: 1. A method of controlling lice which comprises applying to a substrate at least one monohydric alcohol which is pentanol, 2-phenylethanol, n-pentanol, n-hexanol, n-octanol or hexadecyl alcohol.

2. A method according to Claim 1 wherein the alcohol is an alkanol having a log P of 2.3-5.13.

3. A method according to claim 2 wherein the alcohol is n-octanol, or hexadecyl alcohol.

4. A method according to any on preceding claim wherein the alcohol is employed in combination with an inert pharmaceutically acceptable carrier.

5. A method according to Claim 4 wherein the carrier is aqueous.

6. A method of controlling lice by applying a toxicant, which method comprises applying with said toxicant an adjuvant toxicant which is isopentanol 2-phenylethanol, n-pentanol, n-hexanol, n-octanol, or hexadecyl alcohol.

7. A method according to claim 6 wherein the alcohol is an alkanol having a log P of 2.3-5.13.

8. A method according to Claim 6 wherein the alcohol is n-octanol or hexadecyl alcohol.

9. A method of controlling lice or their ova substantially as herein described and which employs one of the specified alcohols.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (9)

**WARNING** start of CLMS field may overlap end of DESC **. Glycerine 3 Isobutane 8 Water 41 An illustrative example will now be given of the use of the compounds with adjunctive toxicants. There is given the formulation and activity of a composition of the invention with and without adjuvant, and then of a comparison composition based on the adjuvant. Isopropanol 25 90 29 Hexadecyl alcohol 15 Water 60 Isopropanol 25 100 100 Hexadecyl alcohol 15 N.(2-Hydroxyprnpyl)- lauramide 10 Water 50 Isopropanol 25 15 100 N-(2-Hydroxypropyl) lauramide 15 Water 60 Various changes and modifications can be made: the various embodiments disclosed herein are for the purpose of further illustrating the invention but are not intended as limiting. Throughout this specification and claims, all temperatures are in degrees Centigrade and all parts and percentages are by weight unless otherwise indicated. WHAT WE CLAIM IS:

1. A method of controlling lice which comprises applying to a substrate at least one monohydric alcohol which is pentanol, 2-phenylethanol, n-pentanol, n-hexanol, n-octanol or hexadecyl alcohol.

2. A method according to Claim 1 wherein the alcohol is an alkanol having a log P of 2.3-5.13.

3. A method according to claim 2 wherein the alcohol is n-octanol, or hexadecyl alcohol.

4. A method according to any on preceding claim wherein the alcohol is employed in combination with an inert pharmaceutically acceptable carrier.

5. A method according to Claim 4 wherein the carrier is aqueous.

6. A method of controlling lice by applying a toxicant, which method comprises applying with said toxicant an adjuvant toxicant which is isopentanol 2-phenylethanol, n-pentanol, n-hexanol, n-octanol, or hexadecyl alcohol.

7. A method according to claim 6 wherein the alcohol is an alkanol having a log P of 2.3-5.13.

8. A method according to Claim 6 wherein the alcohol is n-octanol or hexadecyl alcohol.

9. A method of controlling lice or their ova substantially as herein described and which employs one of the specified alcohols.