AU2006233158A1 - Pediculicidal and ovacidal treatment compositions and methods for killing head lice and their eggs - Google Patents

Description

-1-

AUSTRALIA

PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT

ORIGINAL

Name of Applicant/s: Actual Inventor/s: Johnson Johnson Consumer Companies, Inc.

Herwig Janssen and Glenn A. Nystrand and Dexter Williams and C.

Scott Lamb and Kie Ho Address for Service is: SHELSTON IP Margaret Street SYDNEY NSW 2000 CCN: 3710000352 Telephone No: Facsimile No.

(02) 9777 1111 (02) 9241 4666 Attorney Code: SW Invention Title: PEDICULICIDAL AND OVACIDAL TREATMENT COMPOSITIONS AND METHODS FOR KILLING HEAD LICE AND THEIR EGGS Details of Original Application No. 34397/02 dated 18 Apr 2002 The following statement is a full description of this invention, including the best method of performing it known to me/us:- File: 35113AUP01 501003928 1.DOC/5844 la PEDICULICIDAL AND OVACIDAL TREATMENT COMPOSITIONS AND O METHODS FOR KILLING HEAD LICE AND THEIR EGGS

O

Ci FIELD OF THE INVENTION 00 The present invention relates to compositions and methods for controlling and treating adult lice and nits (or ova) of species of the order of Anoplura, including but not limited to C Pediculus capitis, Pediculus humanus and Pthiris pubis, by applying a composition of pediculicides and ovacides in solution to skin and hair, including but not limited to human skin and hair. The compositions comprise effective pediculicidal agents and ovacidal agents that are solubilized to promote penetration of the ova. More particularly, the effective pediculicidal agents and ovacidal agents are spinosad, spinosyn A, spinosyn D, or combinations thereof.

BACKGROUND OF THE INVENTION Lice present a source of serious health problems worldwide for man and animals. Not only do lice carry a variety of bacteria on their outer surfaces, but in their fecal matter as well.

Lice transmit the bacteria to their hosts through puncture wounds that are inflicted during feeding, since lice must feed from their host's blood. Ailments ranging from skin infections to typhus can be traced back to lice infestation.

Lice belong to the order Anoplura. Specific species that affect human beings include Pediculus capitis (head lice), Pediculus humanus (body lice) and Pthiris pubis (pubic lice).

Lice are capable of spreading rapidly. A fertilized female lays about six to eight eggs, or nits, every twenty-four hours. It has been estimated that a single female louse and her daughters could have 112,778 offspring in a period of forty-eight days.

Pediculus capitis clings to the hair shaft when feeding, mating, and laying eggs.

Removal of nits is particularly difficult, as each nit is cemented to a shaft of hair by a glycoprotein glue, acting as a binding cement. Lice eggs themselves are covered by a chitinous sheath that surrounds both the nit and the attached hair shaft.

Various methods and compositions have been used to remove lice, for example mechanical removal with combs and chemical removal with insecticides (known as pediculicides). Pediculicides, such as lindane and various permethrins, have been used in 0 -2conjunction with shampoos for killing and rinsing out lice. However, as noted in the prior U art, the use of these methods and compositions is not entirely effective in controlling head lice, as some lice often survive the treatment. Indeed, the National Pediculosis Association C has reported that twenty to eighty percent of nits survive initial pediculicide treatment, resulting in reinfestation.

00 00 In the prior art, pyrethrum, permethrin, and lindane pesticides, all work as central nervous system toxins on lice. Their effectiveness depends on their ability to reach the i functioning central nervous system on lice. Unfortunately, nits do not develop a functioning IN central nervous system until they are between three and four days old, during an average incubation period of approximately ten days. As a result, only sixty to seventy percent of nits treated can be killed upon application of one of these pediculicides.

Moreover, recently, lice may have begun to develop resistance to current pediculicides. For example, resistance has already been documented in Europe, United States and Israel. Thus, a new active to kill lice and their eggs is desirable.

It has been discovered that spinosyn A and spinosyn D, compounds that have been used as insecticides for turf building and ornamental plants may be used for killing lice.

Spinosyn A and spinosyn D are components of a fermentation product derived from the bacterium species Saccharopolyspora spinosa. The bacteria decompose much of the organic matter in soil and the most active metabolites from this fermentation were identified as spinosyn A and D. The combination of spinosyn A and spinosyn D is known as spinosad.

The chemical structure of spinosyn contains two sugar molecules, one located at each end. A tetracyclic ring structure joins the two sugars. This structure is one of a class of compounds called macrolides. The chemical structure of spinosyns has the general formula of: 0 o °zN 0 IN- 3- R is defined as any chemical group which provides pediculicidal and ovacidal o properties, most preferably H and CH 3 0 It is known that spinosyn A and spinosyn D are useful as insecticides against

C

Lepidoptera and Diptera species. Spinosyns have been used in a pediculicidal shampoo. The prior art does not teach the use of spinosyns in solution.

00 00 Known pediculicides have been noted to be ineffective on killing ova. Thus, the use ,of these pediculicides results in a reinfestation of the hair or skin as soon as the ova hatch, since the treatment was ineffective in controlling and killing the ova. A need has arisen to develop an effective treatment for both adult lice and their ova in a cosmetically elegant form.

SUMMARY OF THE INVENTION The present invention includes a composition comprising an effective amount of one or more agents having pediculicidal and ovacidal properties for adult lice and nits of the species of order Anoplura in solution.

Another embodiment of the invention comprises pediculicidal agents and ovacidal agents in solution for adult lice and nits having the chemical structure of:

HH

.0 H H 0 0 R In another embodiment, the present invention includes a composition comprising a mixture of spinosyn A and spinosyn D in an approximate weight ratio of 85:15,water, methyl vinyl ether/maleic anhydride crosslinked with 1,9-decadiene, propylene glycol, a mixture of cetyl and stearyl alcohols, ceteareth-20, stearalkonium chloride, benzyl alcohol, pentylene glycol, isopropyl alcohol, BHT and sodium hydroxide.

The present invention includes a method of controlling adults and ova of the species 4 r, of order Anoplura by topically applying to one or more of skin and hair a composition -4-4 O comprising an effective amount of one or more agents having pediculicidal and ovacidal

O

properties for adult lice and nits of the species of order Anoplura in solution. The C1 pediculicidal and ovacidal properties include the abilities to control adult lice and lice ova (or nits).

00 00 The present invention includes a method of controlling adults and ova of the species of order Anoplura by topically applying to one or more of skin and hair a composition c comprising an effective amount of one or more agents having pediculicidal and ovacidal 0 properties for adult lice and nits of the species of order Anoplura in solution, which agents have the chemical structure of: I o0 *N 0 0 0 O0 H H .0 The present invention includes a method of controlling adults and ova of the species of order Anoplura by topically applying to one or more of skin and hair a composition comprising a mixture of spinosyn A and spinosyn D in an approximate weight ratio of 80:20, water, methyl vinyl ether/maleic anhydride crosslinked with 1,9 decadiene, propylene glycol, a mixture of cetyl and stearyl alcohols, ceteareth-20, stearalkonium chloride, benzyl alcohol, pentylene glycol, isopropyl alcohol, BHT and sodium hydroxide.

Another embodiment of the present invention includes a method of controlling adults and ova of the species of order Anoplura by topically applying to one or more of skin and hair a composition comprising about 1 to about 2.2% of spinosyn A and D in an approximate weight ratio of 85:15, about 44% deionized water, about 1.1% Stabileze QM PVM/MA decadiene crosspolymer, about 3% propylene glycol, about 3% cetostearyl alcohol, about 0.9% ceteareth-20, about 4.17% stearalkonium chloride (or Ammonyx 4 about NO c K, benzyl alcohol, about 6% hexylene glycol, about 4% pentylene glycol, about 20% isoproyl o alcohol, about 0.1% BHT and about 1.2 to about 1.9% sodium hydroxide (10% solution).

O

A further separate embodiment of the present invention is a method for solubilizing C1 agents having pediculicidal and ovacidal properties comprising combining one or more solvents and an effective amount of one or more agents having pediculicidal and ovacidal 00 properties; wherein the agents have the chemical structure of: I o S 0 0

R

HH H .0 "o 0 o o DETAILED DESCRIPTION OF THE INVENTION All cited references in this application are herein incorporated by reference. All percentages in this disclosure are weight percentages.

The present invention relates to a composition comprising an effective amount of agents with pediculicidal and- ovacidal properties in a cosmetically elegant solution or emulsion, including but not limited to imidacloprid, spinosad, a spinosyn, spinosyn A, spinosyn D, any component produced from the Saccharopolyspora spinosa species or combinations. Additionally, the present invention includes the method of applying a pediculicide and ovacide composition in solution to hair or skin for the control of adults and nits of the species of the order Anoplura.

Spinosyn A and Spinosyn D are also known as A83543A and A83543D respectively.

Both Spinosyn A and spinosyn D are the major components of a fermentation product known as A83543. This fermentation product, A83543, is produced by the species Saccharopolyspora spinosa.

What is meant by "an effective amount" refers to an amount of imidacloprid, spinosad, spinosyn, spinosyn A, spinosyn D or a combination thereof sufficient to decrease -6the number of live lice and viable nits, i.e. eggs. The effective amount can typically range 0 from greater than about 0% to about 10%, preferably, about 0.5% to about All percentages in this disclosure are weight percentages.

SWhen "effective amount" refers to solvents, solubilizing agents or solutions, the term means that the solvents solubilize the pediculicidal agents and ovacidal agents and also that 00 0t the solution has a concentration that effectively controls the lice and ova.

SWhat is meant by "skin" refers to that of an animal, preferably a mammal, most preferably a human. Skin that would be commonly prone to nits includes that of the scalp, ,O body, and pubic areas.

What is meant by "to control" is to reduce the number of viable nits and live lice. The extent of reduction accomplished by the composition depends upon the application rate of the composition, the choice of imidacloprid, spinosad, spinosyn, spinosyn A, spinosyn D, any component produced from the Saccharopolyspora spinosa species and a combination thereof, and the species of Anoplura targeted.

The order Anoplura includes the following families: echniophtiriidae, enderleinellidae, haematopinidae, linognathidae, pecaroecidae, pediculidae, polyplacidae, and pthiridae. Examples of species in the order Anoplura include, but are not limited to Pediculus humanus, Pediculus capitis, and Pthiris pubis. These three species are known more commonly as the body louse, head louse, and pubic louse.

What is meant by "solubilizing agent" or "solvent" refers to solvents capable of solubilizing the pediculicides and ovacides, preferably in the minimum amount required to solubilize the pediculicides and ovacides, preferably about 3% propylene glycol, about benzyl alcohol, about 6% hexylene glycol, about 4% pentylene glycol, and about isopropyl alcohol. Examples of solubilizing agents include, but are not limited to, glycols, for example, propylene glycol, polyethylene glycol, dipropylene glycol, pentylene glycol, and methoxypolyethylene glycol, hexylene glycol, butylene glycol; benzyl alcohol; isopropyl alcohol; preferably penetylene glycol; combinations of pentylene glycol, benzyl alcohol and isopropyl alcohol, either with or without one of the following: hexylene glycol, butylene glycol, dipropylene glycol, methoxypolyethylene glycol or propylene glycol; or combinations of hexylene glycol, butylene glycol, benzyl alcohol and isopropyl alcohol ("Solvent Matrices"). These Solvent Matrices are capable of solubilizing poorly soluble drugs, including but not limited to imidacloprid, spinosad, spinosyn, spinosyn A, spinosyn D, any O -7component produced by the Saccharopolyspora spinosa species and a combination thereof.

O These Solvent Matrices have the additional function of aiding in the penetration of the ova of the louse.

SThe compositions of this invention comprise an effective amount of pediculicidal agents and ovacidal agents in solution, used for controlling lice and its ova. The solvents are 00 t beneficial because they solubilize the pediculicidal agents and ovacidal agents, and also c promote the penetration of the ova so that the ovacidal agents are highly effective. Without being bound by a mechanism, the present invention is believed to better penetrate lice and its N ova. Additionally, the compositions of this invention are cosmetically elegant. The preferred solvents are benzyl alcohol, pentylene glycol, isopropyl alcohol, hexylene glycol, butylene glycol, dipropylene glycol and combinations thereof. More particularly, the pediculicidal agents and ovacidal agents may be, including but not limited to imidacloprid, spinosad, spinosyn, spinosyn A, spinosyn D, any component produced from the Saccharopolyspora spinosa species or a combination thereof. The preferred pediculicidal agent and ovacidal agent is a combination of spinosyn A and spinosyn D in a weight ratio of 85:15 to 80:20.

The compositions disclosed in this patent have an improved solubility of pediculicides and ovacides, including but not limited to imidacloprid, spinosad, spinosyn, spinosyn A, spinosyn D, any component produced from the Saccharopolyspora spinosa species or a combination thereof, which yields a more effective pediculicide and ovacide for the specie of the order of Anoplura. Specific species that affect human beings include Pediculus capitis (head lice), Pediculus humanus (body lice) and Pthiris pubic (pubic lice).

More particularly, the pediculicides and ovacides are present in a composition with solvents and stabilizers. The solvents may help promote the penetration of the composition into the ova in order to act like a ovacide, in addition to being a pediculicide.

In one embodiment, the invention features a composition comprising an effective amount of one or more pediculicidal and ovacidal properties, which may include but is not limited to imidacloprid, spinosad, spinosyn, spinosyn A, spinosyn D, any component produced from the Saccharopolyspora spinosa species or a combination thereof; water; benzyl alcohol; hexylene glycol; pentylene glycol; butylene glycol; dipropylene glycol; isopropyl alcohol; and a non-acrylic stabilizer, for example, a co-polymer of methyl vinyl ether/maleic anhydride cross-linked with 1,9-decadiene. This composition is beneficial because it is capable of solubilizing the pediculicidal and/or ovacidal agents, which results in 8 high mortality of adult lice and their ova.

O In one embodiment, the solubilizing agents of the composition may include glycols, for example, propylene glycol, polyethylene glycol, dipropylene glycol, pentylene glycol, and methoxypolyethylene glycol, hexylene glycol, butylene glycol; benzyl alcohol; isopropyl alcohol; preferably penetylene glycol; combinations of pentylene glycol, benzyl alcohol and 00 isopropyl alcohol, either with or without one of the following: hexylene glycol, butylene Sglycol, dipropylene glycol, methoxypolyethylene glycol or propylene glycol; or combinations M, of hexylene glycol, butylene glycol, benzyl alcohol and isopropyl alcohol.

I, The present invention also relates to a composition comprising an effective amount of one or more pediculicides and ovacides for nits and adult lice (collectively "Lice") of the species of the order Anoplura and a solubilizing agent. The pediculicides and ovacides are ingredients which control the Lice, including but not limited to any component produced by the Saccharopolyspora spinosa species, imidacloprid (also known as NTN 33893, which is a proprietary chemical of Bayer AG), spinosad, spinosyn, spinosyn A and spinosyn D, and a combination thereof, preferably a mixture of spinosyn A and spinosyn D in an approximate weight ratio of 80:20. The preferable amount of stabilizers is between about 0.5% to about What is meant by "cleansing surfactant" is one or more compounds used for skin and/or hair cleaning, and the cleansing surfactant is used in an amount which produces the desired function provided that the amount does not affect the stability of the solution. These compounds can also serve as cosmetic emulsifiers. Classes of compounds include soaps and fatty acids/alkali combinations. Examples include, but are not limited to, ammonium lauryl sulfate, ammonium laureth sulfate, sodium lauryl sulfate, sodium laureth sulfate. For a more complete listing of cleansing surfactants, herein incorporated by reference, see Wenniger and McEwen, eds., 2 International Cosmetic Ingredient Dictionary and Handbook 1764 (2000 ed.) (hereinafter "CFTA Dictionary"), 1789-1795.

What is meant by "emulsifying surfactant" is one or more compounds that reduce surface tension and the emulsifying surfactants are used in an amount which produces the desired function provided that the amount does not effect the stability of the solution. They create barriers around droplets to prevent them from coalescing. Emulsifiers could be, but are not limited to oil-in-water emulsifiers, water-in-oil emulsifiers, water-in-oil-in-water emulsifiers, oil-in-water-in-oil emulsifiers, silicone-in-water emulsifiers, and water-in- IND-9silicone emulsifiers. Examples include, but are not limited to, glyceryl trioleate, acetylated O sucrose distearate, sorbitan trioleate, polyoxyethylene monostearate, glycerol monooleate, sucrose distearate, polyethylene glycol (50) monostearate, octyl phenoxypoly (ethyleneoxy) Sethanol, deacylerin penta-isostearate, sorbitan sesquioleate, hydroxylated lanolin, lanolin, triglyceryl diisostearate, polyoxyethylene oleyl ether, calcium stearoyl-2-lactylate, cetearyl 00 tn glucoside, methyl glucoside sesquistearate, sorbitan monopalmitate, methoxy polyethylene c glycol-22/dodecyl glycol copolymer, polyethylene glycol-45/dodecyl glycol copolymer, M polyethylene glycol 400 distearate and glyceryl stearate, cetyl phosphate, potassium cetyl Sphosphate. See also CTFA Dictionary 1796-1803.

What is meant by "foam-boosting surfactants" is one or more compounds that have the ability to either generate or stabilize foams and the foam-boosting surfactants are used in an amount which produces the desired function provided that the amount does not effect the stability of the solution. They generally increase the surface viscosity of the vehicle surrounding the bubbles. Examples of foam-boosting surfactants include, but are not limited to, cocamidoethyl betaine, cetyl betaine, disodium cetearyl sulfosuccinate, disodium oleoamphodipropionate, lauramide DEA, lauramidopropyl betaine. See also CTFA Dictionary, 1803-1804.

What is meant by "emollient skin conditioning agent" is one or more compounds that soften and smooth the skin and the emollient skin conditioning agent is used in an amount that produces the desired function provided that the amount does not affect the stability of the solution. These compounds achieve this effect lubricating the skin surface, encouraging skin water retention, and altering product textures. Examples include, but are not limited to, octyl hydroxystearate, lanolin, capric/caprylic triglyceride, cetyl palmitate, cetyl alcohol, isopropyl isostearate, glyceryl dilaurate, isopropyl myristate, palm alcohol, and sucrose cocoate. See also CTFA Dictionary, 1768-1773.

What is meant by "humectant" is one or more compounds that prevents the skin from losing moisture and the humectant is used in an amount that produces the desired function provided that the amount does not affect the stability of the solution. Examples include, but are not limited to, glycerin, glucose, honey, lactic acid, polyethylene glycol, propylene glycol, sorbitol, sucrose, and trehalose. See also CTFA Dictionary, 1773-1774.

What is meant by "buffering agents" is one or more compounds that can maintain a desired pH in an aqueous environment and the buffering agent is used in an amount that S- 10 -10 c produces the desired function provided that the amount does not -affect the stability of the U solution. Examples include, but are not limited to, boric acid, citric acid, lactic acid, fumaric

O

acid, phosphoric acid, and salts thereof. See also CTFA Dictionary, 1733-1734.

What is meant by "chelating agents" is one or more compounds that can complex and subsequently inactivate ions in the formulation and the chelating agent is used in an amount 00 00 which produces the desired function provided that the amount does not affect the stability of the solution. Examples include, citric acid, disodium edetate, pentapotassium triphosphate, and phytic acid. See also CTFA Dictionary, 1734-1735.

SWhat is meant by "preservatives" is one or more compounds that prevents or reduces or slows down microbial growth and the preservative is used in an amount that produces the desired function provided that the amount does not affect the stability of the solution.

Examples include, but are not limited to, benzoic acid, butylparaben, ethylparaben, propylparaben, methylparaben, sorbic acid, phenoxyethanol, and triclosan. See CTFA Dictionary, 1765-1766.

"pH Adjuster" are acids or bases that can be used to adjust the pH of the finished product to the desired level. "pH Adjusters" may also be present in some embodiments of the invention and the pH Adjusters are used in an amount that produces the desired function provided that the amount does not affect the stability of the solution. Examples include, but are not limited to, acetic acid, ammonia, citric acid, ethanolamine, formic acid, oxalic acid, potassium hydroxide, sodium hydroxide, and triethanolamine. See also CFTA Dictionary, 1764.

Further an embodiment of the invention may include one or more moisturizers, preferably propylene glycol and the moisturizer is used in an amount that produces the desired function provided that the amount does not affect the stability of the solution. Additionally, emulsifying agents may be desirable, preferably ceteareth-20, manufactured by Promateen Chemicals Inc., which is a polyethylene glycol ether of cetearyl alcohol. Ceteareth-20 has moles of ethylene oxide that is added to the non-ionic surfactant to increase its water solubility. In the event that an emulsion stabilizer is used, the preferred one is a mixture of cetyl and stearyl alcohols, sold by Croda Inc. under the name Cetearyl Alcohol.

In order to prevent the degradation caused by oxidation, antioxidants may be included in the formulation and the antioxidants are used in an amount which produces the desired function provided that the amount does not effect the stability of the solution. Antioxidants 11

O

include, but are not limited to free radical scavengers and reducing agents such as, acetyl U cysteine, ascorbic acid, butylated hydroxytoluene, green tea extract, caffeic acid, cysteine, 0 tocopherol, ubiquinone, and propyl gallate, preferably butylated hydroxytoluene C See CFTA Dictionary, 1727.

What is meant by "hair conditioning agents" or "conditioning agents" are compounds 00 00 that can alter the texture, appearance, styling, or feel of the hair and the conditioning agents Sare used in an amount which produces the desired function provided that the amount does not effect the stability of the solution. Examples include, but are not limited to, alanine, arginine,

N

O biotin, calcium panthothenate, dimethicone, cyclomethicone, hydrolyzed plant protein, and S 10 polyquatemiums, preferably stearalkonium chloride, sold under the name Ammonyx-4 by Stepan Company. See CFTA Dictionary, 1752-1759.

In other embodiments, in addition to the pediculicides, ovacides and Solvent Matrices, these compositions can further comprise adjuvants and the adjuvants are used in an amount which produces the desired function provided that the amount does not effect the stability of the solution. Examples of adjuvants include, but are not limited to vehicles, stabilizers, moisturizers, cleansing surfactants, emulsifying surfactants, emulsifying stabilizers, foamboosting surfactants, emollient skin conditioning agents, humectants, hair conditioning agents, buffering agents, pH adjusters, chelating agents, antioxidants, preservatives, botanical extracts, fragrances, and dyes.

In another embodiment, the composition includes one or more pediculicide and ovacide, the Solvent Matrices, and one or more stabilizers to prevent physical separation of the formulation ("Stabilizers"). Non-acrylic decadiene crosspolymers, including but not limited to Stabileze QM and Stabileze 06 (preferably Stabileze QM) manufactured by Intemational Specialty Products may be employed to stabilize and optionally to thicken the formulations. Stabileze QM and Stabileze 06 are benzene-free copolymers of methyl vinyl ether/maleic anhydride crosslinked with 1,9-decadiene. The INCI name for Stabileze 06 and Stabileze QM is PVM/MA Decadiene crosspolymers. Stabileze 06 has a particle size of 850 li. Stabileze QM has a particle size of< 75 p. Since Stabileze QM has a smaller particle size, it may be dispersed faster than Stabileze 06 and may be more rapidly converted to a gel.

In some embodiments, a neutralizer of the stabilizer may be required to neutralize the formulation to an approximate pH of 5.5 in order to allow thickening of the formulation. A preferred neutralizer is sodium hydroxide.

12 Stabilizers may also include but are not limited to acrylates/aminoacrylates C 10 30 Alkyl PEG-20 Itaconate copolymer, long chain acyl derivatives (including but not limited to ethylene glycol distearate and ethylene glycol monostearate), alkanoamides (including but not C limited to cocamide MEA), esters of long chain fatty acids (including but not limited to stearyl stearate), alkyl dimethylamine oxides, methylcellulose, hydroxybutyl methylcellulose, 00 I hydroxypropylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, distearyl phthalic amide Stepan SAB-2), di(hydrogenated) tallow phthalic amide Stepan C TAB-2), primary amines with a fatty alkyl moiety of at least 16 carbons (including but not N limited to palmitate amine or stearamine), polyacrylic acids, polysaccharide gums (including but not limited to xanthan gum), colloidal clays (including but not limited to benzyl dimethyl hydrogenated tallow ammonium montmorillonite) and colloidal silica.

One of the preferred embodiments is in the form of a conditioner or cream rinse for human hair or animal hair. Hair conditioning agents may be included in the formulation.

The compositions can be administered topically to an animal, by the direct laying on or spreading of the composition on the skin or hair, preferably of a mammal, most preferably of a human. The compositions useful in the subject invention involve formulations suitable for topical application to mammalian skin or hair. Additionally, the compositions may be made into a wide variety of product types. These include, but are not limited to solutions, aerosols, lotions, creams, gels, sticks, ointments, pastes, cream rinses, shampoos, and body washes. The preferred embodiments are cream rinses, conditioners and shampoos.

Vehicles include but are not limited to water, propylene glycol, butylene glycol, ethanol, isopropanol, silicones. Preferably, the vehicle is water.

The invention will be clarified further by a consideration of the following examples.

Example 1 Testing of Spinosyn A and Spinosyn D on Pediculis Captitis Eggs Both spinosyn A and spinosyn D are sold together as the active ingredient for Conserve SC. Conserve SC is a commercial product from DowElanco used for insect control of turf and ornamental plants. The combination of spinosyn A and spinosyn D is known as spinosad. Conserve SC contains 11.60%, by weight, of the spinosad. Spinosad contains approximately 80% spinosyn A and 20% spinosyn D. Three dilutions of the Conserve SC were created: 13 Dilution 1 contained 8.62% Conserve SC, 15% isopropanol, 10% propylene carbonate, and 53.45% deionized water. Dilution 1 resulted in a 1% spinosad concentration.

Dilution 2 contained 21.55% Conserve SC, 15% isopropanol, 10% propylene carbonate, and 66.38% deionized water. Dilution 2 resulted in a 2.5% spinosad concentration.

00 SDilution 3 contained 43.10% Conserve SC, 15% isopropanol, 10% propylene Cc carbonate, and 31.9% deionized water. Dilution 3 resulted in a 5% spinosad concentration.

An in vitro test of Dilutions 1, 2, and 3 was conducted using fresh specimens of IND Pediculus capitis eggs. Specimens were collected from volunteers who had abundant nits.

Collected eggs were examined for viability. A viable egg is shiny, plump, with an intact operculum, and in more developed eggs, an eye spot. Eggs that were dry, shrunken, indented or otherwise damaged were rejected, as were any eggs containing air pockets.

The ovacidal assay was conducted at ambient room temperature (250 to 35C) and humidity (70-90% RH). Ten hairs with viable eggs were sandwiched between small adhesive labels, allowing 2 cm of the hairs to protrude, with the eggs aligned at the distal end.

Immediately prior to testing, the dilutions were shaken thoroughly and dispensed into clean glass vials. The eggs were completely immersed in the formulations for ten minutes.

Following immersion, the hair and eggs were rinsed in a gentle stream of filtered water from a squeeze bottle to simulate natural shower conditions. They were allowed to air dry for minutes before being placed in capped vials for incubation at 280 to 32 0 C, RH 70-90%.

Ten batches of ten eggs were tested for each dilution for a total of one hundred eggs for each dilution. One hundred untreated eggs and one hundred eggs immersed in water were used as controls.

Another set of ten batches of ten eggs each (for a total of 100 eggs) were tested on three successive days. After immersion and rinsing, these eggs were allowed to air dry, and then stored in separate, glass vials. The same eggs were tested on three consecutive days and then left to incubate for two weeks.

Ovacidal activity was recorded as number of eggs tested, number of eggs hatched, number of eggs not hatched, and number of eggs stillborn. What was meant by "stillborn" referred to the nymphs that reach maturity, are able to lift the operculum, or cap of the egg, but are unable to fully emerge. These stillborn eggs were considered non-viable.

All three dilutions demonstrated good ovacidal activity. No significant difference in IN 14 the activity of the dilutions was observed. There was no significant difference between a U single treatment of 10 minutes followed by rinsing and a 10-minute treatment on three consecutive days 3 treatments). The high hatch rates (96% to 98%) of the eggs treated r with water in the identical manner as the dilutions indicate that every aspect of the conduct of the test was optimal, including the selection of eggs by the collecting teams, protection of the 00 eggs from heat, lack of contamination by toxic agents on the hands of the collectors and the investigators, and the incubation conditions. Table 1 shows the ovacidal activity for the Cc single 10-minute immersion followed by a water rinse and two week incubation. Table 2 IND shows the ovacidal activity for 10-minute immersion on three successive days followed by two-week incubation. lo two-week incubation.

C.)

0O 0

(N

O

0~ 15 Table 1 Dilution of Eggs of Eggs of Eggs of Eggs of Eggs Tested Hatched Not Hatched Stillborn Hatched Dilution 1 100 1 96 3 1% (1% Spinosad) Dilution 2 100 0 96 4 0% Spinosad) Dilution 3 100 2 92 6 2% Spinosad) Water 100 96 4 0 96% Untreated 110 105 5 0 Table 2 Dilution of Eggs of Eggs of Eggs of Eggs of Eggs Tested Hatched Not Hatched Stillborn Hatched Dilution 1 100 0 100 0 0% Spinosad) Dilution 2 100 0 98 2 0% Spinosad) Dilution 3 100 0 99 1 0% Spinosad) Water 100 98 2 0 98% Example 2 In-vitro Ovacidal Testing In vitro tests were conducted on human head lice with six formulations in order to study the pediculicidal and ovacidal activity of the formulations. No human subjects were used. The ovacidal results were as follows: 16 Table 3 Description Active Ingredient Single Exposure Double Exposure Ovacidal Rate Ovacidal Rate Cream Rinse A 1% Spinosad 80% 100% Cream Rinse Al 2% Spinosad 95% 100% Cream Rinse B 1% Spinosad 85% 84% Cream Rinse C 1% Spinosad 76% 94% Nix® (control) 1% Permnethrin 76%58 Deionized Water 11% 8 Note that the 76% ovacidal rate for Nix® afler single exposure is an outlier versus the prior testing which was usually 50-60% ovacidal rate after single exposure.

Table 4 Trade Name INCI Name Cream Cream Cream Crea Rinse A Rinse Al Rinse B Rinse C Deionized Water 44.8 44.25 44.8 44.81 Stabileze QM PVMIMA 1.1 1.1 1.1 1.1 Decadiene Crosspolyrner Propylene Propylene 3 3 3 3 Glycol Glycol Cetostearyl Cetearyl alcohol 3 3 3 3 Alcohol NF Ceteareth-20 0.9 0.9 0.9 0.9 Amnmonyx 4 Stearalkoniumn 4.17 4.17 4.17 4.1 7 Chloride Benzyl Alcohol Benzy] Alcohol 10 10 10 Hexylene Hexylene Glycol 6 6 Glycol Butylene Glycol Butylene Glycol 5 Dipropylene Dipropylene Glycol Glycol Pentylene 4 4 5 Glycol Isopropyl Isopropyl 20 20 20 alcohol alcohol Spinosad Spinosyn A D 1.095 2.19 1.095 1.095

O

0 o 17 BHT Butylated 0.1 0.1 0.1 0.1 Hydroxytoluene Sodium Sodium 1.83 1.29 1.81 1.82 Hydroxide (10% Hydroxide soln.) 100 100 100 100 In this test, Single Exposure means that the ova were exposed to the formulation for minutes on Day 1. Double Exposure means that the ova were exposed to the formulation for 10 minutes on Day 1 and Day 4. Ovacidal Rate means the percent of louse ova unhatched after a 14-day incubation period.

Therefore, all of the cream rinses effectively deliver spinosad into the louse ova resulting in strong ovacidal activity. Double exposures of Cream Rinse A and Cream Rinse Al are most effective with 100% mortality rates of the ova in-vitro, while double exposures of any level of spinosad increases ovacidal effectiveness. Finally, spinosad 1% and 2% formulations are superior to Nix". Nix" is the prior art lice treatment currently marketed to treat lice infestation.

Example 3 In-Vitro Pediculicidal Testing The following are results taken for the same formulations as Example 3 as tested on adult lice for the pediculicidal rates.

O

0 0O

O

'1

O

18 Table Formulation Active Single Exposure Single Exposure Ingredient 1-Minute Immersion 10-Minute Immersion Dead Dead Moribund Alive Moribund Alive Well Well A2 0.5% 77% 23% 100% Spinosad A 1% 92% 8% 100% Spinosad Al 2% 82% 18% 100% Spinosad B 1% 92% 8% 97% 3% Spinosad C 1% 87% 13% 100% Spinosad Nix® 1% 92% 8% 92% 8% Permethrin Deionized 3% 97% 2% 98% Water All measurements on this chart were taken at 4 hours after exposure. Moribund means that the lice were in terminal stages of life, from which they can never recover any useful function. In this phase, the lice may show signs of central nervous system or peripheral nerve toxicity, such as tremors, convulsions or twitching of a leg or antenna.

From this study, one can conclude that 1% and 2% spinosad deliver excellent pediculicidal activity at 1-minute and 10-minute exposure times. Formulations A, Al and A2 have superior pediculicidal activity to Nix® after a 10-minute immersion time.

O

0 -q- 19 Table 6 Trade Name INCI Name Cream Rinse A2 Placebo Deionized Water 45.022 46.046 Stabileze QM PVM/MA Decadiene 1.1 1.1 Crosspolymer Propylene GlycolPrene Gne Glycol 3 3 Cetostearyl Alcohol NF Cetearyl alcohol 3 3 Ceteareth-20 0.9 0.9 Ammonyx 4(18%) Stearalkonium Chloride 4.17 4.17 Benzyl Alcohol Benzyl Alcohol 10 Hexylene Glycol Hexylene Glycol 6 6 Butylene Glycol Butylene Glycol-- Dipropylene Glycol Dipropylene Glycol Pentylene Glycol 4 4 Isopropyl alcohol Isopropyl alcohol 20 Spinosad Spinosyn A D 0.548 BHT Butylated Hydroxytoluene 0.1 0.1 Sodium Hydroxide (10% Sodium Hydroxide 2.16 1.684 soln.) Since it is critical that the compositions of this invention are not irritants to human skin, we performed a Draize sensitization study (repeat insult patch test) using a placebo (described in the table above) for one of the vehicles. 100 human subjects were involved for weeks. No subject showed sensitization when the vehicle was applied to the skin.

It is understood that while the invention has been described in conjunction with the detailed description thereof, that the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are evident from a review of the following claims.

Claims (16)

1. A composition comprising: an effective amount of at least one agent having pediculicidal and ovacidal properties for adult lice and nits of the species of order Anoplura in solution; wherein the agents comprise a chemical structure of: H H

2. The composition of claim 1, further comprising at least one stabilizer.

3. The composition of claim 1, wherein said agent is at least one material selected from the group consisting of imidacloprid, spinosad, spinosyn A, spinosyn D, and any component produced by the Saccharopolyspora spinosa species.

4. The composition of claim 1, wherein R is H. The composition of claim 1, wherein R is CH3.

6. The composition of claim 1, wherein R is a radical selected from the group consisting of H and CH3. !0

7. The composition of claim 6, wherein the weight ratio said H to said CH 3 is of about 85:15.

8. The composition of claim 1, wherein said agent is present at a level of greater than about 0 to about 10 percent of the composition. ID 0 21 c) 9. The composition of claim 1, wherein said agent is present at a level of about 0.5 to about 5 percent of the composition.

10. The composition of claim 2, wherein said stabilizer is selected from the group 00 00 consisting of PVM/MA decadiene crosspolymers, acrylates/aminoacrylates, Cl 0 3 0 alkyl PEG-20 itaconate copolymer, long chain acyl derivatives, alkanolamides, esters of long chain of fatty acids, alkyl dimethylamine oxides, methylcellulose, IN hydroxybutyl methylcellulose, hydroxypropylcellulose, hydroxypropyl S 10 methylcellulose, hydroxethyl cellulose, distearyl phthalic amide, di(hydrogenated) tallow phthalic amide, primary amines with a fatty alkyl moiety of at least 16 carbons, polyacrylic acids, polysaccharide gums, colloidal clays and colloidal silica.

11. The composition of claim 2, wherein said stabilizer is PVM/MA decadiene crosspolymer.

12. The composition of claim 2, wherein said stabilizer is present at a level of about to about 1.5 percent of the composition.

13. The composition of claim 2, wherein said stabilizer has a particle size of less than

14. The composition of claim 1, wherein said solution further comprises a solvent selected from the group consisting of benzyl alcohol, pentylene glycol, isopropyl alcohol, hexylene glycol, butylene glycol and dipropylene glycol. The composition of claim 1, further comprising at least one additive selected from the group consisting of stabilizer, moisturizer, emulsion stabilizer, emulsifying agent, conditioning agent, antioxidant and pH adjuster.

16. A method of controlling adults and ova of the species of order Anoplura, comprising the step of: 22 topically applying to one or more of skin and hair a composition comprising an effective amount of at least one agent having pediculicidal and ovacidal properties in solution; wherein said agent has the chemical structure of: 0' H H

17. A method for solubilizing agents having pediculicidal and ovacidal properties, comprising the step of: combining at least one solvent and an effective amount of at least one agent having pediculicidal and ovacidal properties; wherein said agent has the chemical structure of: IN fl 0~~ 0 NO N 23- O 18. A composition comprising at least one agent having pediculicidal and ovacidal properties for adult lice and nits of the species of order Anoplura, substantially as herein described with reference to any one of the embodiments of the invention illustrated in the accompanying drawings and/or examples. 00 n

19. A method of controlling adults and ova of the species of order Anoplura, substantially as herein described with reference to any one of the embodiments I N O of the invention illustrated in the accompanying drawings and/or examples. O

20. A method for solubilizing agents having pediculicidal and ovacidal properties, substantially as herein described with reference to any one of the embodiments of the invention illustrated in the accompanying drawings and/or examples. DATED this 24 t h Day of October 2006 Shelston IP Attorneys for, Johnson Johnson Consumer Companies, Inc.