Compositions for treating lice infestations

Abstract

The present disclosure provides a pediculicidal formulation for treating or preventing lice infestation in a subject. In one embodiment, the pediculicidal formulation comprises a plant extract of Orig

Description

COMPOSITIONS FOR TREATING LICE INFESTATIONSFIELD

[0001] The present disclosure provides compositions or formulations and methods of using the same to treat or prevent lice infestations.BACKGROUND

[0002] Head lice are wingless, 2 mm to 4 mm long (adult louse), six legged, blood-sucking insects that live on the scalp of humans but not on pets such as dogs or cats. Infested children usually carry fewer than 20 mature head lice, each of which, if untreated, live for three to four weeks. Head lice stay close to the scalp for food, warmth, shelter and moisture. The head louse feeds every 3 h to 6 hours by sucking blood and simultaneously injecting saliva. After mating, the adult female louse can produce five to six eggs per day for 30 days, each in a shell (a nit) that is ‘glued’ to the hair shaft near the scalp. The eggs hatch 9 to 10 days later into nymphs that molt several times over the next 9 to 15 days to become adult head lice.

[0003] Lice occur worldwide and are remarkably widespread in children aged between 3 and 15 years old. An infestation with lice is called pediculosis. In a normal healthy child, an infestation usually involves less than 10 live lice. Infestations may be asymptomatic. Itching may occur if the individual becomes sensitized to antigenic components of louse saliva that is injected as the louse feeds. On the first infestation, sensitization may take four to six weeks. Some individuals can remain asymptomatic and never itch.

[0004] Pharmacologic treatment of head lice infestation is focused on three general mechanisms: neurotoxicity resulting in paralysis of the lice (insecticidal treatments), suffocation via “coating” the lice, or dissolution of the wax covering on the exoskeleton. Insecticidal agents that are neurotoxic to lice include permethrin, pyrethrins, malathion, spinosad, and ivermectin. Noninsecticidal agents that rely on suffocation or exoskeleton dissolution include benzyl alcohol, dimethicone, and isopropyl myristate.

[0005] A key for an effective treatment is the effectiveness of available treatments in destroying viable eggs. Malathion, spinosad, and topical ivermectin are considered ovicidal, and they will killboth live lice and eggs in one treatment. Nonovicidal agents (permethrin, pyrethrins, benzyl alcohol, dimethicone, oral ivermectin, and isopropyl myristate) typically require a repeat application for complete eradication. Timing for nonovicidal treatments is based on the life cycle of the louse. For example, an initial application followed by a second application seven to 10 days later.

[0006] Wet combing is a nonpharmacologic treatment of head lice that involves washing with ordinary shampoo, moistening the hair with commercially available leave-in conditioner, combing with a wide-tooth comb until detangled, and then systematically combing the hair from root to tip with a lice comb. The conditioner should then be rinsed out and the hair combed with a lice comb again. Wet combing alone does not have adverse effects and is often preferred by parents wanting to avoid a chemical treatment; however, it can be time-consuming and the cure rates vary considerably.

[0007] Strains of head lice have been identified worldwide which are resistant to available over- the-counter and prescription treatments for head lice infestation. These parasites have adapted to chemical treatments using pyrethrins, permethrins, lindane, and malathion. In the US, permethrin resistant lice have been found in Massachusetts, Idaho, Texas, California and Florida. Single and dual resistance to pyrethrins / permethrins and malathion has been broadly reported in Great Britain. Possible neural damage to human prevents raising the insecticide levels above the current threshold in an attempt to combat these newer treatment-resistant head lice.

[0008] Origanum dayi is an endemic subshrub of the Genus Origanum and the Family Lamiaceae, found in the Northern Negev and Judean deserts in Israel. The essential oils and extracts of the upper parts of O. dayi were identified, of which the major ones were 1,8-cineole, a-terpineol, (E)- sabinene hydrate, (E)-sabinene hydrate acetate, terpinen-4-ol and linalyl acetate (Dudai, N., Larkov, O., Chaimovitsh, D., Lewinsohn, E., Freiman, L., & Ravid, U. (2003). Essential oil compounds of Origanum dayi Post. Flavour and fragrance journal, 18(4-), 334-337; Amzallag, G. N., Larkov, O., Ben Hur, M., & Dudai, N. (2005). Soil microvariation as a source of variability in the wild: the case of secondary metabolism in Origanum dayi Post. Journal of chemical ecology, 31(6), 1235-1254).

[0009] There remains a need to develop improved formulations to treat and prevent lice infestations that are effective, safe, and easy to use.SUMMARY

[0010] In one aspect, the present invention is directed to a method of preventing or treating a lice infestation in a subject, comprising topically applying a pediculicidal formulation comprising a plant extract or a plant essential oil extract to the subject, wherein the plant is of the Family Lamiaceae.

[0011] In a related aspect, the lice infestation is a head lice infestation. In a related aspect, the lice infestation is a body lice infestation. In a related aspect, the lice infestation is a Pediculus humanus capitis lice infestation.

[0012] In a related aspect, the pediculicidal formulation is applied to the scalp of the subject.

[0013] In a related aspect, the plant is of the Genus Origanum. In a related aspect, the plant is Origanum dayi.

[0014] In a related aspect, the plant essential oil extract comprises 1,8-cineole, a-terpineol, (E)- sabinene hydrate, (E)-sabinene hydrate acetate, terpinen-4-ol, linalyl acetate, or any combination thereof. In a related aspect, the pediculicidal formulation further comprises one or more plant extracts or plant essential oil extracts.

[0015] In a related aspect, the pediculicidal formulation is applied at a dose of from about 0.5 ml to about 10 ml. In a related aspect, the dose is 5.0 ml.

[0016] In a related aspect, the pediculicidal formulation is applied for a period of time of from about 1 minute to about 60 minutes.

[0017] In a related aspect, the pediculicidal formulation is applied for about 3 minutes, about 5 minutes, or about 10 minutes. In a related aspect, the pediculicidal formulation is applied as a single dose. In a related aspect, the pediculicidal formulation is applied as an initial dose followed by one or two additional doses. In a related aspect, the pediculicidal formulation is applied daily.

[0018] In a related aspect, the pediculicidal formulation is formulated as shampoo, spray, aerosol, lotion, hair conditioner, gel, mousse or powder.

[0019] In a related aspect, the pediculicidal formulation further comprises one or more of a suspending agent, a solubilizing agent, a surfactant, and a preservative.

[0020] In another aspect, the present invention is directed to a pediculicidal formulation comprising a plant extract or a plant essential oil extract, wherein the plant is of the Family Lamiaceae. In a related aspect, the plant is of the Genus Origanum. In a related aspect, the plant is Origanum dayi.

[0021] In a related aspect, the plant essential oil extract comprises 1,8-cineole, a-terpineol, (E)- sabinene hydrate, (E)-sabinene hydrate acetate, terpinen-4-ol, linalyl acetate, or any combination thereof.

[0022] In a related aspect, the pediculicidal formulation further comprises one or more plant extracts or plant essential oil extracts.

[0023] In a related aspect, the pediculicidal formulation is formulated as shampoo, spray, aerosol, lotion, hair conditioner, gel, mousse or powder. In a related aspect, the pediculicidal formulation is formulated as washing solution, immersion solution, spray or powder for treatment of textiles, beddings, carpets or furniture.

[0024] In a related aspect, the composition further comprises one or more of a suspending agent, a solubilizing agent, a surfactant, and a preservative.

[0025] These and other aspects of the invention will be appreciated from the ensuing descriptions of the figures and detailed description of the invention.DETAILED DESCRIPTION

[0026] In one embodiment, the present invention relates to formulations or compositions useful as a pediculicidal agent in the treatment or prevention of an infestation of body lice. In one embodiment, the present invention relates to formulations or compositions useful as a pediculicidal agent in the treatment or prevention of an infestation of head lice. In one embodiment, the present invention relates to formulations or compositions useful as a pediculicidal agent in the treatment or prevention of an infestation of head lice. In some embodiments, the infested lice may be either a susceptible or treatment-resistant strain of Pediculus humanus capitis.

[0027] In one embodiment, the compositions disclosed herein address the emerging problem of treatment-resistant head lice strains by allowing use of a single product which is active in eliminating or preventing head lice infestations, whether the infestation represents a susceptible ortreatment-resistant strain of head lice.

[0028] In one embodiment, the present invention also relates to a method of treating or preventing a body lice infestation. In one embodiment, the present invention also relates to a method of treating or preventing a head lice infestation. In one embodiment, the present invention also relates to a method of treating or preventing a head lice infestation, whether the infestation be from a strain of head lice that remains susceptible to current over-the-counter (OTC) and prescription pediculicides (“a susceptible strain”) or from a strain that is resistant to one or more available OTC and / or prescription formulations (“a treatment-resistant” or “drug-resistant” strain). In one embodiment, the methodology comprises applying one dose or multiple doses (applications) of the compositions disclosed herein to the individual for a length of time to allow an effective amount of the active ingredients in the compositions to contact the infecting lice.

[0029] In another embodiment, there is provided a method for elimination of either susceptible or treatment-resistant head lice using the compositions disclosed herein as a shampoo-conditioner. In one embodiment, the shampoo-conditioner is used twice during about a seven day period (day 1 and day 7), left on the scalp for 1 to 60 minutes at each application, and then rinsed with warm water. The shampoo-conditioner is formulated to leave the hair in good condition while ridding the scalp of lice.

[0030] Another aspect of the present invention relates to the use of the compositions disclosed herein for treating or preventing a head lice infestation from a susceptible or treatment-resistant strain in a human patient.

[0031] In one embodiment, the present invention provides a method of preventing or treating a lice infestation in a subject, comprising topically applying a formulation comprising a plant extract or a plant essential oil extract to the subject.

[0032] In some embodiments, the formulations disclosed herein are pediculicidal formulations. One of ordinary skill in the art would appreciate that a "pediculicidal formulation” may encompass a formulation having the property or effect of killing lice.

[0033] In some embodiments, the lice infestation is a body lice infestation. In some embodiments, the lice infestation is a Pediculus humanus corporis infestation. In some embodiments, the lice infestation is a head lice infestation. In some embodiments, the lice infestation is a Pediculus humanus capitis infestation. In some embodiments, the lice infestation is a pubic lice infestation.In some embodiments, the lice infestation is a Phthirus pubis infestation.

[0034] In some embodiments, the formulations or compositions disclosed herein comprise a plant extract. In some embodiments, the formulations or compositions comprise a plant essential oil extract. In some embodiments, the formulations or compositions comprise a plant essential oil extract. In some embodiments, the plant is of the Family Lamiaceae. In some embodiments, the plant is of the Genus Origanum. In certain embodiments, the plant is Origanum dayi.

[0035] In one embodiment, the formulations or compositions disclosed herein comprise a plant extract of Origanum dayi. In one embodiment, the formulations or compositions comprise an oil extract of Origanum dayi. In one embodiment, the formulations or compositions comprise a plant extract of Origanum dayi. In one embodiment, the formulations or compositions comprise an essential oil extract of Origanum dayi.

[0036] In some embodiments, the formulations or compositions disclosed herein further comprise one or more plant extracts or plant essential oil extracts.

[0037] In some embodiments, the plant essential oil extract comprises 1,8-cineole, a-terpineol, (E)-sabinene hydrate, (E)-sabinene hydrate acetate, terpinen-4-ol, linalyl acetate, or any combination thereof. In some embodiments, the plant essential oil extract comprises 1,8-cineole. In some embodiments, the plant essential oil extract comprises a-terpineol. In some embodiments, the plant essential oil extract comprises (E)-sabinene hydrate. In some embodiments, the plant essential oil extract comprises (E)-sabinene hydrate acetate. In some embodiments, the plant essential oil extract comprises terpinene-4-ol. In some embodiments, the plant essential oil extract comprises linalyl acetate. As used herein, the term "applying" refers to bringing the formulation described herein into contact with a subject. In one embodiment, the formulation is applied locally. In another embodiment, the formulation is applied topically. In another embodiment, the formulation is applied to the scalp of a subject. In another embodiment, the formulation is applied to the skin of a subject.

[0038] According to any of the methods of the present invention and in one embodiment, a subject as described herein is human. In another embodiment, the subject is a mammal.

[0039] One of ordinary skill in the art would readily appreciate the proper dosing of the compositions disclosed to treat lice in a subject (e.g. a human). In one embodiment, the dosing canbe varied either by the altering the concentration, or by increasing the amount of the compositions applied to the subject.

[0040] In one embodiment, a single application (dose) of the formulations or compositions of the present invention would be in the range from about 0.01 ml to about 100 ml. In another embodiment, the dose ranges from about 0.1 ml to about 10 ml. In another embodiment, the dose ranges from about 0.1 ml to about 5 ml. In another embodiment, the dose ranges from about 0.5 ml to about 2.5 ml. In another embodiment, the dose ranges from about 0.5 ml to about 10 ml.

[0041] In another embodiment, the formulation is applied at a dose of about 0.5 ml. In another embodiment, the formulation is applied at a dose of about 0.6 ml. In another embodiment, the formulation is applied at a dose of about 0.7 ml. In another embodiment, the formulation is applied at a dose of about 0.8 ml. In another embodiment, the formulation is applied at a dose of about 1.0 ml. In another embodiment, the formulation is applied at a dose of about 2.0 ml. In another embodiment, the formulation is applied at a dose of about 3.0 ml. In another embodiment, the formulation is applied at a dose of about 4.0 ml. In another embodiment, the formulation is applied at a dose of about 5.0 ml. In another embodiment, the formulation is applied at a dose of about 6.0 ml. In another embodiment, the formulation is applied at a dose of about 7.0 ml. In another embodiment, the formulation is applied at a dose of about 8.0 ml.

[0042] In one embodiment, at least about 2.0 ml the composition is applied to totally saturate the roots and to effectively cover the entire scalp area. It is evident upon review of this specification that one of ordinary skill in the art may vary the concentration and / or volume of the composition to manipulate the effective amount of formulation to be applied to the patient's scalp.

[0043] In another embodiment, multiple doses / applications of the compositions of the present invention is applied in the treatment method. In one embodiment, multiple doses / applications will include at least one, two, three or four additional doses beyond the initial dose.

[0044] The initial dose is most likely in response to an infestation of lice, while the additional subsequent dose(s) are follow up applications to eradicate lice that hatch following the first dose or lice that have somehow survived the first dosing. Multiple dosing for a therapeutic regime provides an opportunity to deliver greater amounts of active ingredients spaced over a determined time frame.

[0045] In some embodiments, the compositions or formulations of the present invention are applied daily. In some embodiments, the compositions or formulations of the present invention are applied every other day. In some embodiments, the compositions or formulations of the present invention are applied every third day.

[0046] In some embodiments, the compositions or formulations of the present invention are applied in a treatment cycle or treatment schedule. In some embodiments, the compositions or formulations are applied to the subject over one or more treatment cycles. In some embodiments, the treatment cycle comprises at least two, at least three, at least four, at least five, at least six, at least 7, at least 14, at least 21, at least 28, at least 48, or at least 96 days or more. In some embodiments, a treatment cycle is 7 days. In some embodiments, a treatment cycle is 14 days. In some embodiments, a treatment cycle is 21 days. In some embodiments, a treatment cycle is 28 days.

[0047] In some embodiments, the treatment cycle comprises application once per week. In some embodiments, the treatment cycle comprises application once every two weeks. In some embodiments, the treatment cycle comprises application every day. In some embodiments, the treatment cycle comprises application every other day. In some embodiments, the treatment cycle comprises application every third day.

[0048] In one embodiment, the compositions disclosed herein are formulated as shampooconditioner. The shampoo-conditioner may be used twice during about a seven day period (e.g. day 1 and between about day 5 and day 9). In another embodiment, the shampoo-conditioner is applied on day 1 followed by a second, third or fourth application at intervals from about 5 days to about 9 days. At each dosing, the compositions remain in the scalp for about 1 minute to 60 minutes or from about 3 minutes to about 60 minutes, then rinsed with warm water.

[0049] Furthermore, the present invention relates to a method of preventing a lice infestation in a subject at risk of head lice infestation, comprising topically applying to the subject a formulation as disclosed herein by one dose or multiple doses. Such an at risk subject would be a human coming into close contact with an infested individual, such as a family member or possibly in response to an outbreak within a confined space such as school or the workplace. Either a single or multiple dosing regime will be effective, the course of a preventive treatment most likely is determined by the severity of the outbreak.

[0050] For the purposes of this disclosure, the following non-limiting definitions are used:

[0051] The term “active ingredient(s)”, when directed toward the present invention, refers to the active ingredients of a plant extract, for example, the plant extract of Origanum dayi, or the essential oil plant extract of Origanum dayi.

[0041] In some embodiments, “preventing” comprises preventative measures, wherein the object is to prevent or lessen the chances of contracting lice infestation. In some embodiments, “treating” may include directly repelling lice, preventing lice replication, and killing lice and eggs.

[0042] The terms “solubilizer” and / or “solubilizer phase” refers to compound or mixture of compounds in which the active ingredient(s) is initially dissolved. In one embodiment, the solubilizer phase is a mixture of water miscible organic compounds. By way of example, solubilizers may include the surfactants polysorbate 80 and cetyl acetate or other surfactants as more fully described herein.

[0043] The term “suspending agent(s)” refers to organic compounds that suspend the predissolved active ingredient(s) before being dispersed in water. Suspending agents include, without limitation, olive oil, shea butter, coco butter, vegetable oil, and the like.

[0044] The term “preservative(s)” refers to compounds that reduce the growth of fungus and other bacterial agents. In one embodiment, preservatives are selected from the compounds in the paraben family.

[0045] The term “non-ionic surfactant(s)” refers to compounds which act at the water-air and water-oil interfaces, thereby enhancing wetting ability, emulsion stabilization, foaming, rheology, antistatic, lubricity, and surface conditioning properties of a composition such as shampooconditioner.

[0046] The term “emollient(s)” refers to compounds that soften and makes the skin smooth by preventing skin from losing moisture.

[0047] The term “silicone compound” refers to hair conditioning agents that change the texture, feel, and appearance of human hair. In one embodiment, the silicone compound is cyclomethicone.

[0048] The term “susceptible” or “susceptible strain” refers to a strain of head lice which is susceptible to one or more available over-the-counter (OTC) and / or prescription pediculicides that contain one or more active ingredients such as pyrethrins, permethrins, lindane, and malathionwhere one or more of the active ingredients are at least at the pharmaceutically acceptable treatment concentration allowable for that respective pediculicide(s) and all or effectively all head lice are killed at that concentration. In other words, a susceptible strain is a strain which will be effectively controlled following treatment with a pharmaceutically acceptable concentration for that respective pediculicide.

[0049] The term “treatment-resistant” or “drug-resistant” or any such similar term refers to a strain of head lice which shows resistance to one or more available OTC and / or prescription pediculicides that contain one or more active ingredients such as pyrethrins, permethrin, lindane, and malathion, where one or more of the active ingredients are at least at the pharmaceutically acceptable treatment concentration recommended or allowed for that respective pediculicide(s) and at least some head lice survive at that concentration. Pyrethrins which are approved for use on humans are extracted from the chrysanthum flower, of which there are six active constituents which are esters of two carboxylic acids (chrysanthemic acid and pyrethric acid) and four cyclopentenoles (pyrethrolone, cinerolone, and jasmolone I and II). So, it is evident that a treatment-resistant strain of lice is a strain that shows a measurable level of resistance to killing by a specific pediculicide treatment regime as compared to a susceptible strain, where all or effectively all of the head lice will be killed. Such a measure may be made by any test generally known in the art.

[0050] In one embodiment, the composition disclosed herein is exemplified by, but in no way limited to, a topical formulation. This final formulation is in the consistency of a shampoocondition and at least comprises an effective amount of active ingredient(s), as well as a solubilising agent(s), water, a suspending agent(s), a surfactant(s), silicone compound(s), and a preservative(s), in any combination and / or concentration which may be contemplated by the artisan upon review of this specification.Solubilising Active Ingredient

[0051] In one embodiment, active ingredient(s) may be delivered to a head lice infested scalp by way of an emulsion based shampoo-conditioner. However, active ingredient(s) is hydrophobic and is poorly solvated by water. Thus, the active ingredient should be pre-dissolved in suitable surfactants to improve the stability of said active ingredients in water. In one embodiment, these surfactants are easily soluble in water or are water miscible.

[0052] In one embodiment, active ingredient(s) is pre-dissolved in a mixture containing the water miscible organic compounds, e.g. polysorbate 80, cetyl acetate, and acetylated lanolin alcohol. More specifically, active ingredient(s) is present at a level of about 0.05% to 5%, or alternatively from about 0.1% to 2% by weight, or alternatively from about 0.25% to 1% by weight. In one embodiment, polysorbate 80 is present at a level of about 5% to about 25% by weight, or alternatively from about 10% to 15% by weight (e.g. about 11.25% to 13.5% by weight). In one embodiment, cetyl acetate is present at a level of about 0.5% to 10% by weight, or alternatively from about 1% to 4% by weight (e.g. about 1.50% to 3.75% by weight). In one embodiment, acetylated lanolin alcohol is present at a level of about 0.10% to 3% by weight, or alternatively from about 0.5% to about 1% by weight (e.g, 0.15% to 0.75% by weight).

[0053] Having these surface active agents bound to the surfaces of active ingredient(s) will ensure that the active ingredient will be stable in the aqueous environment of the shampoo -conditioner. In one embodiment, active ingredient(s) may be stabilized by pharmaceutically accepted glycols present at a level below 30% by weight, such as, for example, below 25%, or below 20% or below 15% or below 10% or below 5%. In another embodiment, the composition disclosed herein does not include any glycols.Suspending Agents

[0054] Once the active ingredient is dissolved in a surfactant bath, active ingredient(s) is placed in suspending agents. In one embodiment, a combination of fatty oils and fats serve as suspending agents. Olive oil is a triacylglyceride, where three fatty acids are tethered to a glycerol backbone and shea butter is primarily made of palmitic, stearic, oleic, linoleic, and arachidic fatty acids. Although these fatty acids may be used as home remedies for removal of head lice from the scalp, they do not kill head lice. Both olive oil and shea butter are viscous materials that slow the movement of adult lice to better remove them. Also note that both fatty acids can act as skin moisturizers. In one embodiment, olive oil is present in the formula at a level of about 20% to 30% by weight, or alternatively from about 25% to 28% by weight (e.g., about 27.5% by weight). In one embodiment, shea butter is present in the formula at a level of about 1% to 5% by weight (e.g. about 2% by weight). Other known suspending agents which may be utilized in the formulations and related methods include, but are not limited to, coconut oil, palm oil, cottonseed oil, vegetable oil, soybean oil, olive oil, peanut oil, com oil, sunflower oil, safflower oil, jojoba oil, canola oil,shea butter, cocoa butter, milk fat, amaranth oil, apricot oil, argan oil, avocado oil, babassu oil, ben oil, algaroba oil, coriander seed oil, false flax oil, grape seed oil, hemp oil, kapok seed oil, meadowfoam seed oil, okra seed oil, perilla seed oil, poppyseed oil, prune kernel oil, pumpkin seed oil, qumoa oil ramtil oil, nee bran oil, camellia oil, thistle oil, wheat germ oil and combinations thereof.Surfactants

[0055] The formulation may be further stabilized by non-ionic surfactants. In one embodiment, a fatty alcohol or a mixture of fatty alcohols serve as surfactants. Apart from additional stabilization of active ingredient(s), the non-ionic surfactants have various purposes in the surface chemistry of the formula, where the formula is used in a final product comprising a shampoo -conditioner. In addition to their surface-active properties, fatty alcohols are emollients that make the skin smoother and act at the water-air and water-oil interfaces, thereby enhancing wetting ability, emulsion stabilization, foaming, rheology, antistatic, lubricity, and surface conditioning properties of the formula. Suitable non-ionic surfactants include, without limitations, oleyl alcohol, lanolin alcohol, sorbitan tristerate, bees wax, erucyl alcohol, ricinolyl alcohol, arachidyl alcohol, capryl alcohol, capric alcohol, behenyl alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, palmitoleyl alcohol, linoleyl alcohol, elaidyl alcohol, elaidolinoleyl alcohol, linolenyl alcohol, elaidolinolenyl alcohol, glycerine, glyceryl triacetate, sorbitol, xylitol, maltitol, polydextrose, quillaia, lactic acid, urea, and combinations thereof.

[0056] In one embodiment, the fatty alcohols are oleyl alcohol and lanolin alcohol with combined concentration of about 10% to 35%, or alternatively about 18% to about 24% by weight. More specifically, oleyl alcohol is present in the formula at a level of about 5% to 15% by weight (e.g. about 10% by weight). Lanolin alcohol is present in the formula at a level of about 3% to about 15% by weight, or alternatively from about 5% to 10% by weight (e.g. about 8% by weight).Silicone Compound

[0057] After active ingredient(s) has been pre-dissolved and stabilized by surfactants, a silicone compound may be added. In one embodiment, the silicone compound is a volatile silicones, for example, cyclomethicone. Cyclomethicone may act as a conditioner in the shampoo -conditioner. It gives a soft, silky feel to hair and evaporates quickly leaving little residue. In one embodiment, cyclomethicone is present in the formula at a level of about 1% to 5% by weight, e.g. about 3% byweight. Thus, conditioners which may be used include but are in no way limited to cyclomethicone, dimethicone, hexamethyldisiloxane, octamethyltrisiloxane, decamethyltetrasiloxane, dodecamethylpentasiloxane, polydimethylsiloxanes and combinations thereof.Preservatives

[0058] In yet another embodiment, the formula of the instant invention further contains a preservative, protecting the formula from fungus by chemicals. In one embodiment, the preservative is chosen from the paraben family. More specifically, the preservative is selected from methylparaben, propylparaben, or a combination thereof. In one embodiment, the concentration of the preservative is about 1 % by weight. More specifically, methylparaben is present in the formula at levels of about 0.01% to 2% by weight (e.g. 0.20% by weight). In one embodiment, propylparaben is present in the formula at levels of about 0.01% to 1.0%, or alternatively from about 0.01% to about 0.5% by weight (e.g., 0.05% by weight). Also note that representative preservatives may include, but are not limited to, methylparaben, propylparaben, ethylparaben, butylparaben, isobutylparaben, isopropylparaben, benzylparaben and their sodium salts thereo

[0059] In one embodiment, the present disclosure provides a method for treatment or preventing a head lice infestation in a subject, the method comprising applying a dose of a pediculicidal formulation to the subject’s scalp infested with lice for a period of time, wherein the formulation comprises a plant extract of Origanum dayi; and removing the pediculicidal formulation from the scalp, thereby treating head lice infestation in the subject. In one embodiment, the dose is from about 1 ml to about 100 ml. In one embodiment, the dose is 5.0 ml. In one embodiment, the pediculicidal formulation is applied to the scalp for about 1 minute to about 60 minutes. For example, the pediculicidal formulation is maintained on the scalp for about 3 minutes, about 5 minutes, or about 10 minutes.

[0060] In one embodiment, the pediculicidal formulation is applied as a single dose. In another embodiment, the pediculicidal formulation is applied as an initial dose followed by one or two additional doses.

[0061] In one embodiment, the pediculicidal formulation is adapted for application as a shampoo. The composition disclosed herein, however, can also be made in various formulations, including but are not limited to, mousse, gel, lotion, liquid, spray, aerosol, hair spray, paste, powder, hair conditioner or other compositional forms.

[0062] The pediculicidal formulation disclosed herein may further comprise one or more of a suspending agent, a solubilizing agent, a surfactant, and a preservative. Examples of suspending agents, solubilizing agents, surfactants, and preservatives have been described above.

[0063] In another embodiment, the present disclosure provides a composition for treating or preventing a lice infestation in a subject. The ingredients and formulations of the composition have been described above. For example, the composition can be formulated as shampoo, spray, aerosol, lotion, hair conditioner, gel, mousse or powder. In another embodiment, the composition of the present invention can be formulated in other formulations such as washing solution, spray or powder for treatment of textiles, beddings, carpets or furniture. In another embodiment, the composition of the present invention can be formulated as immersion solutions for lice combs that may be used successively for several individuals, or washing additives for lice eliminating treatments of clothing or bedding textiles.

[0064] The terms “comprise”, "comprises", "comprising", "includes", "including", “having” and their conjugates mean "including but not limited to".

[0065] As used herein, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise.

[0066] Throughout this application, various embodiments of the present disclosure may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0067] Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases “ranging / ranges between” a first indicate number and a second indicate number and “ranging / ranges from” a first indicate number “to” a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.

[0068] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting. Each literature reference or other citation referred to herein is incorporated herein by reference in its entirety.

[0069] Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In the description presented herein, each of the steps of the invention and variations thereof are described. This description is not intended to be limiting and changes in the components, sequence of steps, and other variations would be understood to be within the scope of the present invention.

[0070] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

[0071] In some embodiments disclosed herein is a pediculicidal formulation for use in preventing or treating a lice infestation in a subject.

[0001] Various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below find experimental support in the following examples.EXAMPLE 1Testing of Pediculicidal and Ovicidal Activity

[0072] Human body lice, Pediculus humanus humanus, were reared in the laboratory by feeding them every 24-48 hrs on rabbits. Lice were placed on the shaved abdomen of a white New Zealand rabbit and left until they fed to satiety. Between feedings, the lice were maintained at a temperatureof 30+l°C and 50-60% relative humidity. For each experiment, lice that had been fed 24 hrs previously were used.Bioassay

[0073] Fifty lice (10 males, 10 females and 30 nymphs) were placed on a 7-cm white filter paper disc and exposed to 1 ml or 1 gr of the test formulation. The lice were left in contact with the substance for a period. They were removed from the test solution and washed with normal shampoo (diluted 1:20) for 1 min and then with tap water for 1 min. In case of a shampoo formulation, the treatment with regular shampoo could be omitted. After treatment, lice were transferred to a fresh filter paper disc and incubated overnight at optimum temperature and humidity. Mortality was determined after 16-24 hrs.

[0074] Lice were placed on human hair every other day for 5 days and left for 24-48 hrs for oviposition. Fifty eggs, 2-6 days-old were treated as described above. The number of hatched and non-hatched eggs were counted after 10 days. As a negative control, lice and eggs, treated with regular shampoo (diluted 1:20) or 40% ethyl alcohol, were used. Each formulation was tested in triplicate.

[0075] The results of the tests are shown below:Pediculicidal and ovicidal activity after 15 min exposure to test formulationFormulation Mean percentage mortalityLice EggsTest Formulation 100 13.8Control 3.0 10.1EXAMPLE 2IN VIVO EFFICACY OF A PEDICULICIDAL FORMULATION

[0076] The aim of this example is to examine the in vivo efficacy and safety of a formulation for the treatment of pediculosis capitis in an open clinical study in school age children.

[0077] Four large schools with 300-400 pupils will be chosen. A letter will be send to all parents requesting the consent one of the parents to allow the examination of their child for lice in the school.

[0078] Approximately 1,000 children, 6-14 years old (first to the ninth grade) will be examined for head louse infestation after having received the consent of their parent(s) and approximately 150 infested children will be found. It is expected that only 1 / 3 of the parents whose child is infested with lice are ready to participate to a clinical trial.First Examination for Lice

[0079] In the school, the head master and the school nurse will help to organize the examination of the children in a separate room. For two days every week a team including a physician, three parasitologists and a secretary will visit the schools and examine daily ca. 200 children for infestation with head lice.

[0080] Each child will be examined separately, and care will be taken that only the people conducting the examination and writing the protocols will know the result of the examination.

[0081] The hair of each child will be briefly combed with a regular comb or brush to straighten the hair and then the entire scalp will be combed with a louse comb for a period of about 3-5 min or until the first louse is isolated. In cases where the child’s hair does not permit the use of a louse comb, the scalp will be examined by hand for a period of 5-7 min. These examination methods will also be used for the following examinations, e.g., 1 and 10 days after the beginning of the treatment.

[0082] Immediately after examination each child will receive a sealed letter for their parents explaining that their child was examined and was / was not infested with lice or had nits only. In the letter to parents whose child was found infested a form will be included, which should be send back to the investigators with an attached stamped envelope. The parents, who send back the form with their details (names, telephones, address), will be contacted and the family will be visited at home.First Parasitological and Medical Examination at Home

[0083] After having received their oral agreement, other family members of the infested child will be examined for lice. A pediculicide will be given to all those found infested as well and after having signed the consent form they will be included to the study. For all those who are less than 18 years, the consent of their parents will be requested. All those who are 13 years-old and above have to sign an additional consent form. In all cases, the treatment will be performed by the parents.

[0084] Every infested person who was enrolled in the study will be examined by the physician for any dermatological abnormalities e.g., excoriations, insect bites, lymphatic swelling, secondary infections, eczema, severe seborrheic dermatitis, as well as for conjunctivitis and other eye diseases. Only healthy children who had not been treated with an anti-louse product in the last 72 hrs will be included in the study. Criteria for exclusion of a child from the study will include: severe scalp dermatosis, secondary infections, open wounds, tinea of the scalp, eye irritation (conjunctivitis) and severe eye diseases (with the exception of myopathy).

[0085] A pediculicide and a louse comb will be given free of charge to each family member who consented to participate to the clinical trial. The parents will receive instructions as how to use the pediculicide.Second Parasitological and Medical Examination at Home

[0086] Treated people will be examined a second time the day following the treatment or the day thereafter to determine whether the pediculicide had killed all active stages of the lice. The physician will examine the treated people for any side-effects of the treatment on the skin and eyes, and will record their impressions about the smell, itching etc. during and after the treatment.

[0087] The treatment will be considered unsuccessful if the child was found to be infested with living lice during the second parasitological examination i.e., the tested pediculicide did not kill all the active stages of the louse (nymphs and adults). The parents of those children will receive another pediculicide, which is sold in Israel and will be requested to continue the treatment with this product.Third Parasitological Examination at Home

[0088] A third examination will take place 11-12 days after the beginning of the first treatment, i.e., 1-2 days after the second treatment, in order to determine whether the pediculicide had eliminated the entire lice population, including the lice which had meanwhile hatched from the eggs. Again, the treatment will be considered unsuccessful if lice were detected on the head of the child. Another pediculicide will be given to the parent of the child who will be also instructed to continue the treatment with this product.

[0089] While certain features of the invention have been illustrated and described herein, many modifications, substitutions, changes, and equivalents will now occur to those of ordinary skill in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention.

Claims

CLAIMS1. A method of preventing or treating a lice infestation in a subject, comprising topically applying a pediculicidal formulation comprising a plant extract or a plant essential oil extract to the subject, wherein the plant is of the Family Lamiaceae.

2. The method of claim 1, wherein the lice infestation is a head lice infestation.

3. The method of claim 1, wherein the lice infestation is a body lice infestation.

4. The method of claim 1 or 2, wherein the lice infestation is a Pediculus humanus capitis lice infestation.

5. The method of claim 1 or 2, wherein the pediculicidal formulation is applied to the scalp of the subject.

6. The method of any of claims 1-5, wherein the plant is of the Genus Origanum.

7. The method of any of claims 1-6, wherein the plant is Origanum dayi.

8. The method of any of claims 1-7, wherein the plant essential oil extract comprises 1,8- cineole, a-terpineol, (E)-sabinene hydrate, (E)-sabinene hydrate acetate, terpinen-4-ol, linalyl acetate, or any combination thereof.

9. The method of any of claims 1-8, wherein the pediculicidal formulation further comprises one or more plant extracts or plant essential oil extracts.

10. The method of any of claims 1-9, wherein the pediculicidal formulation is applied at a dose of from about 0.5 ml to about 10 ml.

11. The method of claim 10, wherein the dose is 5.0 ml.

12. The method of claim any of claims 1-11, wherein the pediculicidal formulation is applied for a period of time of from about 1 minute to about 60 minutes.

13. The method of claim 12, wherein the pediculicidal formulation is applied for about 3 minutes, about 5 minutes, or about 10 minutes.

14. The method of any of claims 1-13, wherein the pediculicidal formulation is applied as a single dose.

15. The method of any of claims 1-13, wherein the pediculicidal formulation is applied as an initial dose followed by one or two additional doses.

16. The method of any of claims 1-13, wherein the pediculicidal formulation is applied daily.

17. The method of any of claims 1-16, wherein the pediculicidal formulation is formulated as shampoo, spray, aerosol, lotion, hair conditioner, gel, mousse or powder.

18. The method of any of claims 1-17, wherein the pediculicidal formulation further comprises one or more of a suspending agent, a solubilizing agent, a surfactant, and a preservative.

19. A pediculicidal formulation comprising a plant extract or a plant essential oil extract, wherein the plant is of the Family Lamiaceae.

20. The pediculicidal formulation of claim 19, wherein the plant is of the Genus Origanum.

21. The pediculicidal formulation of claim 19 or 20, wherein the plant is Origanum dayi.

22. The pediculicidal formulation of any of claims 19-21, wherein the plant essential oil extract comprises 1,8-cineole, a-terpineol, (E)-sabinene hydrate, (E)-sabinene hydrate acetate, terpinen- 4-ol, linalyl acetate, or any combination thereof.

23. The pediculicidal formulation of any of claims 19-22, wherein the pediculicidal formulation further comprises one or more plant extracts or plant essential oil extracts.

24. The pediculicidal formulation of any of claims 19-23, formulated as shampoo, spray, aerosol, lotion, hair conditioner, gel, mousse or powder.

25. The pediculicidal formulation of any of claims 19-24, formulated as washing solution, immersion solution, spray or powder for treatment of textiles, beddings, carpets or furniture.

26. The pediculicidal formulation of any of claims 19-25, wherein the composition further comprises one or more of a suspending agent, a solubilizing agent, a surfactant, and a preservative.