US 2011 0052506A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/005250.6 A1 Abel et al. (43) Pub. Date: Mar. 3, 2011

(54) STABLE AEROSOL TOPICAL FOAMS Publication Classification COMPRISINGA HYPOCHLORITE SALT (51) Int. Cl. (75) Inventors: Douglas Abel, Sudbury, MA (US); st 94;O CR Ronald M. Gurge, Franklin, MA ( .01) (US); Mark W. Trumbore, A6IP3L/00 (2006.01) Westford, MA (US) (52) U.S. Cl...... 424/45 (73) Assignee: Collegium Pharmaceutical, Inc., (57) ABSTRACT Cumberland, RI (US) Described herein are compositions useful in the treatment of atopic dermatitis and other skin conditions, which composi (21) Appl. No.: 12/872,566 tions exhibit enhanced stability. The compositions contain a 1-1. hypochlorite salt, useful for its antimicrobial properties, and (22) Filed: Aug. 31, 2010 are non-irritating when applied to the skin. The compositions O O also provide enhanced moisturizing properties. The compo Related U.S. Application Data sitions can be formulated into a topical aerosol foam with (60) Provisional application No. 61/238,439, filed on Aug. inert, non-flammable propellants, such as hydrofluoroal 31, 2009. kanes, and may be used in cosmetics or pharmaceuticals. US 2011/005250.6 A1 Mar. 3, 2011

STABLE AEROSOL TOPCAL FOAMS itch associated with atopic dermatitis; however, they can COMPRISINGA HYPOCHLORITE SALT cause sleepiness and may not help in all cases of atopic dermatitis. RELATED APPLICATION 0007 For mild cases of atopic dermatitis, an over-the counterformulation of coal taris often used. Coaltar has long 0001. This application claims benefit under 35 U.S.C. 119 been a treatment for a variety of skin conditions. Shampoos (e) of U.S. Provisional Application No. 61/238,439, filed on and Soaps containing coal tar can help with mild cases of Aug. 31, 2009, the entire content of which is incorporated atopic dermatitis. Coal tar tends to work better on thickened herein by reference. skin that is not scaly and the early symptoms of itching. However, coal tar can be irritating to already inflamed skin. BACKGROUND Coal tar is used for mild cases of atopic dermatitis only. 0008 For more severe flares of atopic dermatitis—for 0002 Atopic dermatitis (AD) is a disease characterized by example if the rash covers a large part of the body or face— dry, cracked, itchy, and inflamed skin, often presenting on oral corticosteroids, Such as prednisone, prednisolone, and greater than 10% of the body surface area. In accounts for medrol, may be used. Long-term use of oral steroids has 10-20% of all visits to a dermatologist and affects approxi numerous side effects, including weight gain, thinning of the mately 3% of the US population, most of whom are children. bones, and Suppression of the immune system; consequently, The condition is characterized by intense pruritus (itch) and a though they may clear atopic dermatitis well, the side effects course marked by exacerbations and remissions. Higher tran are too risky to warrant using them as a first-line treatment. To sepidermal water loss (TEWL) has also been noted in dry skin avoid these side effects, but still benefit from the medication, atopic patients; TEWL is indicative of a disturbed barrier oral steroids are often prescribed for a short course (e.g., five function, and it has been correlated to pruritus intensity in days) to calm the rash. Topical steroids can then be used on the patients. Furthermore, the compromised skin barrier allows remaining rash. excessive water loss through the epidermal layer of the skin 0009. As discussed above, atopic dermatitis reduces the and the potential penetration of allergens. skin's natural defenses, making it easier for skin to become 0003 Environmental factors, such as psychological stress, infected. If the skin becomes infected, antibiotics are often climate (e.g., low humidity caused by cold winters and central prescribed. Antibiotics, such as cefadroxil or cephalexin, are heating), and exposure to irritants and allergens determine the often prescribed at the first sign of infection. course of the disease. The defective barrier function associ 0010 Transient immersion of affected skin in a low con ated with AD can also make atopic patients more prone to centration chlorine bleach bath (i.e., aqueous Sodium irritant contact dermatitis, since ordinary Soaps and deter hypochlorite) has been shown to decrease the microbial bur gents often irritate the skin. Exposure to hard water, espe den associated with atopic dermatitis, resulting in an cially to calcium salts in domestic water, has been found to be improvement in Symptoms. Skin and wound cleansers con associated with a higher prevalence of atopic eczema in pri taining bleach have also been shown to reduce microbial skin mary-school children. contamination. To date, all bleach containing products for 0004 Another potential triggering factor for AD is the topical use are intended fortransient skin contact, no leave-on colonization of the skin with microorganisms, such as Sta products such as creams, lotions or topical foams intended for phylococcus aureus and Malassezia. S. aureus can release long term skin contact and containing bleach exist. Incorpo Superantigenic exotoxins, which produce a massive release of ration of bleach into leave-on products intended for long term cytokines Staphylococcus enterotoxin B also induces eczema skin contact allows for the potential to provide additional when applied to uninvolved atopic and normal skin, while the long-term treatment benefits such as improved moisturization severity of AD has been reported to correlate linearly with S. and control of transepidermal water loss not possible with a tirett.S COuntS. products intended for transient skin contact. 0011 Hypochlorite salts are inherently unstable in aque 0005. A doctor has three main goals in designing a treat ous solution. The decomposition rate of hypochlorite in water ment regime for the patient: healing the skin and keeping it is dependent on concentration, temperature, and pH. High healthy, preventing flare ups, and treating symptoms when temperatures and acidic pHs greatly accelerate the rate of they do occur. Proper skin care and moisturizing ointments decomposition, as does the presence of metal ions. The nor are the mainstays of topical treatment. Moisturizers which mal shelf-life of bleach solutions is approximately six months improve barrier function have been reported which reduce the at a pH of between 12 and 13.5. Additionally, due to the high prevalence of AD and can reduce the associated symptoms. pH and oxidative potential of bleach, bleach solutions are 0006. In addition to moisturizers, a variety of medications frequently irritating to the skin. may be prescribed to help manage the condition. Topical 0012. There exists a need for a stable, non-irritating topi steroids are the first-line treatment for atopic dermatitis flares cal formulation containing bleach Suitable for the long-term because they are effective at reducing the inflammation application in the treatment of atopic dermatitis. caused by this disease. Immunomodulators (calcineurin inhibitors, such as tacrolimus and pimecrolimus) may also be SUMMARY OF THE INVENTION prescribed. Immunomodulators change Some of the functions of the immune system that cause atopic dermatitis without 0013. In certain embodiments, the invention relates to a Suppressing the whole immune system. Other immune-Sup composition containing monovalent or divalent salts of pressing medications being investigated as a treatment for hypochlorite, wherein the concentration of hypochlorite does atopic dermatitis include: cyclosporine, interferon, methotr not appreciably change with time. In certain embodiments, exate, and azothiaprine. Another mechanism of treatment the composition is packaged into an aerosol can and pressur includes the use of oral antihistamines, such as diphenhy ized with a hydrofluorocarbon propellant. In certain embodi dramine or hydroxyZine. Oral antihistamines are used to treat ments, when the can is actuated, a foam is dispensed. In US 2011/005250.6 A1 Mar. 3, 2011

certain embodiments, the dispensed foam is time- and tem tion, thus overcoming the expected and well-known stability perature-stable, exhibits robust antimicrobial activity, mois issues associated with these chemicals. turizes the skin, and is non-irritating. 0020. In one embodiment, the compositions are formu lated such that the chemical instability is reduced. For DETAILED DESCRIPTION OF THE INVENTION example, compositions were formulated with the addition of antioxidants to the concentrate. In one embodiment, the air in 0014. In certain embodiments, the invention relates to a the container headspace may be replaced with an inert gas thickened aerosol foam composition containing a monova (argon). Compositions formulated in this way may exhibit lent or divalent hypochlorite salt that is stable. In certain improved stability in the presence of HFA propellants (e.g., embodiments, when applied to the skin a composition of the HFA-134a and HFA-227). invention reduces the number of skin-associated bacteria, yeasts, and fungi, improves skin moisture levels, and is non Moisturization and Irritation irritating and non-drying. In certain embodiments, the inven tion relates to a composition that is suitable for the treatment 0021 Topical formulations of hypochlorite salts are of atopic dermatitis. known to be generally irritating and lack the ability to hydrate 0015. In one embodiment, the compositions do not con skin. These two negative attributes can lead to reduced patient tain volatile lower alcohols. In certain embodiments, the compliance with its concomitant impact on therapeutic invention relates to a composition that does not comprise response. In one embodiment, the inventive aerosol foam steroids. formulations of hypochlorite salts are no more irritating than 0016. In one embodiment, the compositions comprise an vehicle control. In one embodiment, the inventive aerosol aerosol propellant. In one embodiment, the aerosol propellant foam formulations of hypochlorite salts demonstrate similar is a hydrofluoroalkane (HFA) propellant. levels of erythema as intact untreated skin. In one embodi 0017. In one embodiment, a composition produces a foam ment, the inventive aerosol foam formulations have the ability upon actuation of an aerosol container charged with the com to moisturize skin. position. In one embodiment, the foams are relatively stable against collapse. In one embodiment, the foams rub in Exemplary Compositions quickly without a greasy, oily, or sticky residue. In one 0022. In certain embodiments, the composition has a embodiment, the foam is moisturizing. In one embodiment, humectant concentration of about 5% to about 15% (by the foam is non-irritating. Application of the foam to the weight of the concentrate), a water concentration of about affected areas of a Subject reduces the number of skin-asso 60% to about 80% (by weight of the concentrate), a bleach ciated bacteria, yeasts, and fungi, and improves skin moisture concentration of about 0.0001% to about 1.5% (by weight of levels. In one embodiment, the composition rapidly and effi the concentrate), and a stabilizer concentration of about 0.5% ciently releases active ingredients. to about 5.0% (by weight of the concentrate). 0023. In one embodiment, the invention relates to a com Propellants position, comprising a concentrate and a propellant, wherein 0018. There are a number of conceivable choices of pro 0024 the concentrate comprises pellants for a hypochlorite aerosol foam, including, but not 0.025 an amount of a hypochlorite salt, wherein the limited to, CFCs, hydrocarbons, compressed gases, and amount of the hypochlorite salt is about 0.0001% to hydrofluoroalkanes (HFAs). The Montreal Protocol has about 1.5% by weight of the concentrate; banned the use of CFCs (chlorofluorocarbons) due to their 0026 an amount of a humectant, wherein the amount of ability to deplete the ozone layer. Montreal Protocol on Sub the humectant is about 15% to about 35% by weight of stances that Deplete the Ozone Layer, United Nations Envi the concentrate; ronmental Programme, 1987. Alternatively, hydrocarbon 0027 an amount of water, wherein the amount of water propellants demonstrate very low reactivity and good resis is about 60% to about 80% by weight of the concentrate; tance to free-radical attack. However, hydrocarbon propel and lants are highly flammable and it would be undesirable and hazardous to combine these propellants with hypochlorite 0028 an amount of a stabilizer, wherein the amount of salts, strong oxidizers, in anaerosol foam system. The chemi the stabilizer is about 0.5% to about 5.0% by weight of cal classes of “oxidizer” and “flammable' are known to be the concentrate; and incompatible. Finally, compressed inert gases, such as nitro 0029 the propellant is a hydrofluoroalkane propellant. gen and carbon dioxide, can be used as an aerosol propellant. 0030. In one embodiment, the invention relates to a com While offering good chemical stability due to their non-reac position, consisting essentially of a concentrate and a propel tivity, they are unable to deliver consistent product delivery lant, wherein throughout the life of the aerosol can due to their high vapor 0.031 the concentrate comprises pressures. Another option is HFAs. These propellants are 0.032 an amount of a hypochlorite salt, wherein the pharmaceutically acceptable, generally non-reactive, and amount of the hypochlorite salt is about 0.0001% to ozone-friendly. about 1.5% by weight of the concentrate; 0033 an amount of a humectant, wherein the amount of Stabilization of Exemplary Compositions of the Invention the humectant is about 15% to about 35% by weight of 0019 Remarkably, we have developed a stable aerosol the concentrate; foam formulation containing a hypochlorite salt and a fluori 0034 an amount of water, wherein the amount of water nated propellant. In one embodiment, the invention relates to is about 60% to about 80% by weight of the concentrate; the formation of a stable hypochlorite aerosol foam formula and US 2011/005250.6 A1 Mar. 3, 2011

0035 an amount of a stabilizer, wherein the amount of 0.001%, about 0.005%, about 0.01%, about 0.05%, about the stabilizer is about 0.5% to about 5.0% by weight of 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, the concentrate; and about 0.6%, about 0.7%, about 0.8%, about 0.9%, or about 0036 the propellant is a hydrofluoroalkane propellant. 1.5% by weight of the concentrate. 0037. In one embodiment, the invention relates to a com 0055. In one embodiment, the invention relates to any one position, consisting of a concentrate and a propellant, of the above-mentioned compositions, wherein the hypochlo wherein rite salt is sodium hypochlorite, potassium hypochlorite, cal 0038 the concentrate comprises cium hypochlorite, magnesium hypochlorite, lithium 0039 an amount of a hypochlorite salt, wherein the hypochlorite, or copper(I) or copper(II) hypochlorite. In one amount of the hypochlorite salt is about 0.0001% to embodiment, the invention relates to any one of the above about 1.5% by weight of the concentrate; mentioned compositions, wherein the hypochlorite salt is 0040 an amount of a humectant, wherein the amount of Sodium hypochlorite or calcium hypochlorite. the humectant is about 15% to about 35% by weight of 0056. In one embodiment, the invention relates to any one the concentrate; of the above-mentioned compositions, wherein water is 0041 an amount of water, wherein the amount of water present in an amount from about 60% to about 80% by weight is about 60% to about 80% by weight of the concentrate; of the concentrate. In one embodiment, the invention relates and to any one of the above-mentioned compositions, wherein 0042 an amount of a stabilizer, wherein the amount of water is present in an amount from about 65% to about 75% the stabilizer is about 0.5% to about 5.0% by weight of by weight of the concentrate. In one embodiment, the inven the concentrate; and tion relates to any one of the above-mentioned compositions, 0043 the propellant is a hydrofluoroalkane propellant. wherein water is present in an amount from about 68% to 0044. In one embodiment, the invention relates to a com about 72% by weight of the concentrate. In one embodiment, position, comprising a concentrate and a propellant, wherein the invention relates to any one of the above-mentioned com 0045 the concentrate comprises positions, wherein water is present in about 60%, about 65%, 0046) an amount of a hypochlorite salt, wherein the about 70%, about 75%, or about 80% by weight of the con amount of the hypochlorite salt is about 0.0001% to centrate. In one embodiment, the invention relates to any one about 1.5% by weight of the concentrate; of the above-mentioned compositions, wherein water is 0047 an amount of a viscosity modifier, wherein the present in an amount from about 80% to about 99% by weight amount of the viscosity modifier is about 0.1% to about of the concentrate. 6% by weight of the concentrate; 0057. In one embodiment, the invention relates to any one 0048 an amount of a surfactant, wherein the amount of of the above-mentioned compositions, wherein the stabilizer the surfactant is about 0.01% to about 1% by weight of is selected from the group consisting of DL-alpha tocopheryl the concentrate; acetate, imidazolidinyl urea, diazolidinyl urea, phenoxyetha 0049 an amount of water, wherein the amount of water nol, Sodium methyl paraben, methylparaben, ethylparaben, is about 80% to about 99% by weight of the concentrate; propylparaben, potassium Sorbate, Sodium benzoate, Sodium and chloride, Sorbic acid, benzoic acid, formaldehyde, citric acid, 0050 an amount of a stabilizer, wherein the amount of Sodium citrate, chlorine dioxide, benzalkonium chloride, the stabilizer is about 0.01% to about 1.0% by weight of benzethonium chloride, cetrimide, dequalinium chloride, the concentrate; and cetylpyridinium chloride, phenylmercuric nitrate, phenylm 0051 the propellant is a hydrofluoroalkane propellant. ercuric acetate, thimerosal, chlorobutanol, dichlorobenzyl 0052. In one embodiment, the invention relates to any one alcohol, phenylethyl alcohol, benzyl alcohol, ascorbic acid, of the above-mentioned compositions, wherein the hydrof sodium bisulfite, butylated hydroxytoluene, butylated luoroalkane propellant is 1,1,1,2-tetrafluoroethane, 1.1.1.2.3, hydroxyanisole, C-tocopherol, Sodium ascorbate, ascorbyl 3.3-heptafluoropropane, or a mixture thereof. palmitate, propyl gallate, disodium EDTA, and mixtures 0053. In one embodiment, the invention relates to any one thereof. of the above-mentioned compositions, wherein the hydrof 0058. In one embodiment, the invention relates to any one luoroalkane propellant is 1,1,1,2-tetrafluoroethane. of the above-mentioned compositions, wherein the stabilizer 0054. In one embodiment, the invention relates to any one is DL-alpha tocopheryl acetate, methylparaben, propylpara of the above-mentioned compositions, wherein the hypochlo ben, disodium EDTA, or a mixture thereof. In one embodi rite salt is present in an amount from about 0.0001% to about ment, the invention relates to any one of the above-mentioned 1.5% by weight of the concentrate. In one embodiment, the compositions, wherein the stabilizer is sodium chloride. invention relates to any one of the above-mentioned compo 0059. In one embodiment, the invention relates to any one sitions, wherein the hypochlorite salt is present in an amount of the above-mentioned compositions, wherein the stabilizer from about 0.001% to about 0.8% by weight of the concen is present in an amount from about 0.01% to about 1.0% by trate. In one embodiment, the invention relates to any one of weight of the concentrate. In one embodiment, the invention the above-mentioned compositions, wherein the hypochlorite relates to any one of the above-mentioned compositions, salt is present in an amount from about 0.01% to about 0.5% wherein the stabilizer is present in an amount from about by weight of the concentrate. In one embodiment, the inven 0.8% to about 4.0% by weight of the concentrate. In one tion relates to any one of the above-mentioned compositions, embodiment, the invention relates to any one of the above wherein the hypochlorite salt is present in an amount from mentioned compositions, wherein the stabilizer is present in about 0.1% to about 0.25% by weight of the concentrate. In an amount from about 1.0% to about 3.0% by weight of the one embodiment, the invention relates to any one of the concentrate. In one embodiment, the invention relates to any above-mentioned compositions, wherein the hypochlorite one of the above-mentioned compositions, wherein the sta salt is present in about 0.0001%, about 0.0005%, about bilizer is present in about 0.5%, about 0.8%, about 1.0%, US 2011/005250.6 A1 Mar. 3, 2011

about 1.5%, about 2.0%, about 2.5%, about 3.0%, about hexadecyl ether phosphate, polyoxyethylene monooctadecyl 3.5%, about 4.0%, about 4.5%, or about 5.0% by weight of ether, cetostearyl alcohol, or a mixture thereof. the concentrate. 0066. In one embodiment, the invention relates to any one 0060. In one embodiment, the invention relates to any one of the above-mentioned compositions, wherein the emulsifier of the above-mentioned compositions, wherein the humec or the surfactant is present in an amount from about 0.01% to tant is selected from the group consisting of 2-ethylhexyl about 1% by weight of the concentrate. In one embodiment, palmitate, sodium hyaluronate, glycerol, PPG-15 stearyl the invention relates to any one of the above-mentioned com ether, lanolin alcohol, lanolin, cholesterol, petrolatum, isos positions, wherein the emulsifier or the Surfactant is present in tearyl neopentanoate, octyl Stearate, mineral oil, isocetyl an amount from about 2% to about 10% by weight of the Stearate, myristyl myristate, octyl dodecanol, dimethicone, concentrate. In one embodiment, the invention relates to any phenyl trimethicone, cyclomethicone, C-C alkyl ben one of the above-mentioned compositions, wherein the emul Zoates, dimethiconol, propylene glycol, lactic acid, butylene sifier or the surfactant is present in an amount from about 3% glycol, sodium PCA, carbowax 200, carbowax 400, carbowax to about 9% by weight of the concentrate. In one embodiment, 800, and mixtures thereof. the invention relates to any one of the above-mentioned com 0061. In one embodiment, the invention relates to the positions, wherein the emulsifier or the Surfactant is present in above-mentioned composition, wherein the humectant is an amount from about 4% to about 8% by weight of the 2-ethylhexyl palmitate, Sodium hyaluronate, glycerol, petro concentrate. In one embodiment, the invention relates to any latum, dimethicone, propylene glycol, or a mixture thereof. one of the above-mentioned compositions, wherein the emul 0062. In one embodiment, the invention relates to any one sifier or the surfactant is present in an amount from about 3% of the above-mentioned compositions, wherein the humec to about 7% by weight of the concentrate. In one embodiment, tant is present in an amount from about 18% to about 32% by the invention relates to any one of the above-mentioned com weight of the concentrate. In one embodiment, the invention positions, wherein the emulsifier or the Surfactant is present in relates to any one of the above-mentioned compositions, about 4%, about 5%, about 6%, about 7%, or about 8% by wherein the humectant is present in an amount from about weight of the concentrate. 20% to about 30% by weight of the concentrate. In one 0067. In one embodiment, the invention relates to any one embodiment, the invention relates to any one of the above of the above-mentioned compositions, wherein the concen mentioned compositions, wherein the humectant is present in trate further comprises a pH adjusting agent. In one embodi an amount from about 22% to about 28% by weight of the ment, the invention relates to any one of the above-mentioned concentrate. In one embodiment, the invention relates to any compositions, wherein the pH adjusting agent is sodium one of the above-mentioned compositions, wherein the hydroxide. In various embodiments, the invention relates to humectant is present in about 15%, about 16%, about 17%, any one of the above-mentioned compositions, wherein the about 18%, about 19%, about 20%, about 22%, about 25%, pH adjusting agent is monobasic sodium phosphate, dibasic about 28%, about 30%, about 32%, or about 35% by weight Sodium phosphate, or a combination of monobasic sodium of the concentrate. In one embodiment, the humectant is phosphate and dibasic sodium phosphate. present in an amount from about 5% to about 15% by weight 0068. In one embodiment, the invention relates to any one of the concentrate. of the above-mentioned compositions, wherein the concen 0063. In one embodiment, the invention relates to any one trate further comprises a natural extract. In one embodiment, of the above-mentioned compositions, wherein the concen the natural extract is a fat or glycidic oil from Theobroma trate further comprises an emulsifier or a surfactant. grandiflorum. 0064. In one embodiment, the invention relates to any one 0069. In one embodiment, the invention relates to any one of the above-mentioned compositions, wherein the emulsifier of the above-mentioned compositions, wherein the composi or the Surfactant is selected from the group consisting of tion is colorless. In one embodiment, the invention relates to dicetyl phosphate, polyethylene glycol hexadecyl ether phos any one of the above-mentioned compositions, wherein the phate, polyoxyethylene monooctadecyl ether, polysorbate composition is off-white. 20, polysorbate 40, polysorbate 60, polysorbate 80, steareth 0070. In one embodiment, the invention relates to any one 10, sodium dodecyl sulfate, lauryl dimethyl amine oxide, of the above-mentioned compositions, wherein the composi cetyltrimethylammonium bromide (CTAB), polyoxyethyl tion is low odor. In one embodiment, the invention relates to ene sorbitan, octoxynol, N,N-dimethyldodecylamine-N-ox any one of the above-mentioned compositions, wherein the ide, hexadecyltrimethylammonium bromide (HTAB), poly composition is fragrance-free. oxyl 10 lauryl ether, sodium deoxycholate, sodium cholate, 0071. In one embodiment, the invention relates to any one polyoxyl castor oil, nonylphenol ethoxylate, cyclodextrins, of the above-mentioned compositions, wherein the composi lecithin, dimethicone copolyol, lauramide DEA, cocamide tion has a pH of from about 4.5 to about 7. In one embodi DEA, cocamide MEA, oleyl betaine, cocamidopropyl ment, the invention relates to any one of the above-mentioned betaine, cocamidopropyl phosphatidyl PG-dimonium chlo compositions, wherein the composition has a pH of from ride, methylbenzethonium chloride, behentrimonium metho about 4.5 to about 6. In one embodiment, the invention relates Sulfate-cetearyl alcohol, emulsifying wax, polyoxyethylene to any one of the above-mentioned compositions, wherein the oleyl ether, PEG-40 stearate, cetostearyl alcohol, ceteareth composition has a pH of about 4.5, about 5.0, about 5.5, or 12, ceteareth-20, ceteareth-30, ceteareth alcohol, glyceryl about 6.0. stearate, PEG-100 stearate, glyceryl Stearate, PEG-100 stear 0072. In one embodiment, the invention relates to any one ate, Steareth-2, Steareth-20, Stearamidopropyl dimethy of the above-mentioned compositions, wherein the concen lamine, behentrimonium methosulfate, and mixtures thereof. trate has a pH of from about 4.5 to about 7. In one embodi 0065. In one embodiment, the invention relates to any one ment, the invention relates to any one of the above-mentioned of the above-mentioned compositions, wherein the emulsifier compositions, wherein the concentrate has a pH of from about or the Surfactant is dicetyl phosphate, polyethylene glycol 4.5 to about 6. In one embodiment, the invention relates to any US 2011/005250.6 A1 Mar. 3, 2011

one of the above-mentioned compositions, wherein the con I0082 In one embodiment, the invention relates to any one centrate has a pH of about 4.5, about 5.0, about 5.5, or about of the above-mentioned compositions, wherein the foam is 6.O. moisturizing over a period of at least 8 hours when applied to 0073. In one embodiment, the invention relates to any one the skin of a subject. I0083. In one embodiment, the invention relates to any one of the above-mentioned compositions, wherein the composi of the above-mentioned compositions, wherein the composi tion is in an aerosol container. tion does not comprise methanol, ethanol, propanols, or 0074. In one embodiment, the invention relates to any one butanols. of the above-mentioned compositions, wherein the composi I0084. In one embodiment, the invention relates to any one tion is in anaerosol container, thereby forming aheadspace of of the above-mentioned compositions, wherein the composi the aerosol container, and the headspace of the aerosol con tion does not comprise methane, ethane, propane, butane, tainer is substantially free of oxygen. pentane, or hexane. 0075. In one embodiment, the invention relates to any one I0085. In one embodiment, the invention relates to any one of the above-mentioned compositions, thereby forming a of the above-mentioned compositions, wherein the composi headspace of the aerosol container, and the headspace of the tion is non-irritating when applied to the skin. aerosol container consists essentially of argon. I0086. In one embodiment, the invention relates to any one of the above-mentioned compositions, wherein the composi 0076. In one embodiment, the invention relates to any one tion is moisturizing when applied to the skin. In one embodi of the above-mentioned compositions, wherein when the ment, when applied to the skin, the composition is moistur aerosol container is actuated, the composition is expelled as a izing over a period of at least 4, at least 6, at least 8, at least 10, foam. or at least 12 hours. In one embodiment, when applied to the 0077. In one embodiment, the invention relates to any one skin, the composition is moisturizing over a period of up to of the above-mentioned compositions, wherein the composi about 24 hours. In one embodiment, when applied to the skin, tion is in an aerosol container. In one embodiment, the inven the composition is moisturizing over a period of up to about tion relates to any one of the above-mentioned compositions, 48 hours. In one embodiment, when applied to the skin, the wherein the composition is about 4% to about 50% propel composition is moisturizing over a period of at least 8 hours. lant, by weight of the composition. In one embodiment, the I0087. In one embodiment, the invention relates to any one invention relates to any one of the above-mentioned compo of the above-mentioned compositions, wherein the composi sitions, wherein the composition is about 5% to about 40% tion is non-sterile. In one embodiment, the invention relates to propellant, by weight of the composition. In one embodiment, any one of the above-mentioned compositions, wherein the the invention relates to any one of the above-mentioned com composition is sterile. positions, wherein the composition is about 6% to about 30% propellant, by weight of the composition. In one embodiment, Exemplary Methods of Use the invention relates to any one of the above-mentioned com I0088. In one embodiment, the present invention relates to positions, wherein the composition is about 6% to about 18% a method of treating a condition of a Subject in need thereof, propellant, by weight of the composition. In one embodiment, comprising the steps of the invention relates to any one of the above-mentioned com I0089 applying to an affected area of the subject an effec positions, wherein the composition is about 6%, about 7%. tive amount of a foam prepared from any one of the above about 8%, about 9%, about 10%, about 11%, about 12%, mentioned compositions. about 13%, about 14%, about 15%, about 20%, about 25%, or 0090. In one embodiment, the present invention relates to about 30% propellant, by weight of the composition. In one any one of the above-mentioned methods, further comprising embodiment, the invention relates to any one of the above the step of: mentioned compositions, wherein the composition is about 0091 expelling from an aerosol container any one of the 12% propellant, by weight of the composition. In one above-mentioned compositions, thereby preparing a foam. embodiment, the invention relates to any one of the above 0092. In one embodiment, the present invention relates to mentioned compositions, wherein about 6%, about 7%, about a method of treating a condition of a Subject in need thereof, 8%, about 9%, about 10%, about 11%, about 12%, about comprising the steps of 13%, about 14%, about 15%, about 20%, about 25%, or about 0093 applying to an affected area of the subject an effec 30% propellant, by weight of the composition, is required to tive amount of a foam prepared from any one of the above deliver the concentrate as a stable foam. mentioned compositions, thereby simultaneously treating and moisturizing the affected area. 0078. In one embodiment, the invention relates to any one 0094. In one embodiment, the present invention relates to of the above-mentioned compositions, wherein the composi a method of treating a condition of a Subject in need thereof, tion is in the form of a foam. comprising the steps of 0079. In one embodiment, the invention relates to any one 0.095 applying to an affected area of the subject an effec of the above-mentioned compositions, wherein the composi tive amount of a foam prepared from any one of the above tion produces a foam. mentioned compositions, thereby simultaneously treating 0080. In one embodiment, the invention relates to any one and hydrating the affected area. of the above-mentioned compositions, wherein the foam is 0096. In one embodiment, the present invention relates to produced by actuation of an aerosol container comprising the the above-mentioned method, wherein the condition is atopic composition. dermatitis, contact dermatitis, Xerotic eczema, Seborrhoeic 0081. In one embodiment, the invention relates to any one dermatitis, psoriasis, dyshidrosis, discoid eczema, Venous of the above-mentioned compositions, wherein the foam is eczema, dermatitis herpetiformis, neurodermatitis, autoecze non-irritating when applied to the skin of a Subject. matization, herpes simplex I, other topical herpes or viral US 2011/005250.6 A1 Mar. 3, 2011

infections, common cold Sores and fever blisters, ringworm, approved or may become approved for medical use are Suit impetigo, or other viral, fungal, or bacterial infections of the able. Hydrocarbon as well as chlorofluorocarbon (CFC) pro skin. In one embodiment, the condition is a heavily contami pellants can also be used in the present invention. nated or infected wound. In one embodiment, a heavily con taminated wound is understood by those of ordinary skill in 2. Hypochlorite Salts the art to mean a wound that is heavily contaminated by 0106 A variety of salts of hypochlorous acid (HOCl), both micro-organisms, but not clinically infected. Such wounds monovalent and divalent, may be present in a composition. are often characterized by a prolonged period of inflamma These include sodium hypochlorite, potassium hypochlorite, tion, as well as a delay in wound healing or repair. In one calcium hypochlorite, magnesium hypochlorite, lithium embodiment, heavily infected wounds are understood by hypochlorite, and copper(I) or copper(II)hypochlorite. those of ordinary skill in the art to mean wounds with a bioburden greater than 10 micro-organisms per gram of tis SC. 3. Other Active Agents 0097. In one embodiment, the present invention relates to 0107. One or more additional active agents may be present any one of the above-mentioned methods, wherein the con in the composition. These include any material that has a dition is eczema. desired effect when applied topically to a mammal, particu 0098. In one embodiment, the present invention relates to larly a human. Suitable classes of active agents include, but any one of the above-mentioned methods, wherein the con are not limited to, antibiotic agents, antimicrobial agents, dition is atopic dermatitis. In one embodiment, the present anti-acne agents, antibacterial agents, antifungal agents, anti invention relates to any one of the above-mentioned methods, viral agents, Steroidal anti-inflammatory agents, non-steroi wherein the condition is atopic dermatitis with more than dal anti-inflammatory agents, anesthetic agents, antiprurigi about 10% body surface area (BSA) involvement. In one nous agents, antiprotozoal agents, anti-oxidants, embodiment, the present invention relates to any one of the antihistamines, vitamins, and hormones. above-mentioned methods, wherein the condition is atopic dermatitis with up to about 80% body surface area (BSA) 3.1 Antibiotics involvement. 0.108 Representative antibiotics include, without limita 0099. In one embodiment, the present invention relates to tion, octopiroX, erythromycin, Zinc, tetracyclin, triclosan, any one of the above-mentioned methods, wherein the subject aZelaic acid and its derivatives, phenoxyethanol and phenoxy is human. proponol, ethyl acetate, clindamycin and meclocycline; 0100. In one embodiment, the present invention relates to Sebostats such as flavinoids; alpha and beta hydroxy acids; the above-mentioned method, wherein the affected area of the and bile salts, such as Scymnol Sulfate and its derivatives, Subject is the face, earlobes, neck, Scalp, genitals, eyelids, deoxycholate and cholate. The antibiotic can be an antifungal palms, fingers, feet, exural (inner) Surfaces of joints, extensor agent. Suitable antifungal agents include, but are not limited aspects of joints, or any combination thereof. In one embodi to, clotrimazole, econazole, ketoconazole, itraconazole, ment, the present invention relates to the above-mentioned miconazole, oxiconazole, Sulconazole, butenafine, naftifine, method, wherein the affected area of the subject is the face. In terbinafine, undecylinic acid, tolnaftate, and nystatin. one embodiment, the present invention relates to the above mentioned method, wherein the affected area of the subject is 3.2 Non-Steroidal Anti-Inflammatory Agents the exural surfaces of elbows or knees. In one embodiment, the present invention relates to the above-mentioned method, 0109 Representative examples of non-steroidal anti-in wherein the affected area of the subject is the extensor aspects flammatory agents include, without limitation, oxicams. Such of wrists, elbows, ankles, or knees. as piroxicam, isoxicam, tenoxicam, Sudoxicam, Salicylates, 0101. In one embodiment, the present invention relates to Such as aspirin, disalcid, benorylate, trilisate, Safapryn, Sol any one of the above-mentioned methods, wherein the com prin, diflunisal, and fendosal; acetic acid derivatives, such as position is applied once daily. diclofenac, fenclofenac, indomethacin, Sulindac, tolmetin, 0102. In one embodiment, the present invention relates to isoxepac, furofenac, tiopinac, Zidometacin, acematacin, fen any one of the above-mentioned methods, wherein the com tiazac, Zomepirac, clindanac, oxepinac, felbinac, and ketoro position is applied twice daily. lac, fenamates, such as mefenamic, meclofenamic, flufe namic, niflumic, and tolfenamic acids; propionic acid 0103. In one embodiment, the invention relates to a derivatives, such as ibuprofen, naproxen, benoxaprofen, flur method of disinfecting an intact skin site prior to a Surgical or biprofen, ketoprofen, fenoprofen, fenbufen, indopropfen, pir invasive procedure. profen, carprofen, oxaprozin, pranoprofen, miroprofen, tioX Exemplary Constituents of Compositions of the Present aprofen, Suprofen, alminoprofen, and tiaprofenic; pyrazoles, Invention Such as phenylbutaZone, oxyphenbutaZone, feprazone, aza propaZone, and trimethaZone. Mixtures of these non-steroidal 0104 Exemplary identities of various constituents of the anti-inflammatory agents may also be employed, as well as compositions of the present invention are described below. the dermatologically acceptable salts and esters of these agents. 1. Propellants 3.3 Steroidal Anti-Inflammatory Agents 0105. In one embodiment, the propellant is a HFA or a mixture of one or more hydrofluorocarbons. Suitable hydrof 0110 Representative examples of steroidal anti-inflam luorocarbons include 1,1,1,2-tetrafluoroethane (HFA-134a): matory drugs include, without limitation, corticosteroids 1,1,1,2,3,3,3-heptafluoropropane (HFA-227); and mixtures Such as hydrocortisone, hydroxyl-triamcinolone, alpha-me and admixtures of these and other HFAs that are currently thyl dexamethasone, dexamethasone-phosphate, beclom US 2011/005250.6 A1 Mar. 3, 2011

ethasone dipropionates, clobetasol Valerate, desonide, des ride, methenamine hippurate, methenamine mandelate, oxymethasone, desoxycorticosterone acetate, minocycline hydrochloride, neomycin Sulfate, netilmicin Sul dexamethasone, dichlorisone, diflorasone diacetate, diflucor fate, paromomycin Sulfate, Streptomycin Sulfate, tobramycin tolone Valerate, fluadrenolone, fluclorolone acetonide, Sulfate, miconazole hydrochloride, amanfadine hydrochlo fludrocortisone, flumethasone pivalate, fluosinolone ride, amanfadine Sulfate, triclosan, octopirox, nystatin, acetonide, fluocinonide, flucortine butylesters, fluocortolone, tolnaftate, clotrimazole, anidulafungin, micafungin, Vori fluprednidene (fluprednylidene) acetate, flurandrenolone, conazole, lanoconazole, ciclopiroX and mixtures thereof. halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cor 3.6 Keratolytic Agents tisone, cortodoxone, flucetonide, fludrocortisone, difluo 0114 Suitable keratolytic agents include, but are not lim rosone diacetate, fluradrenolone, fludrocortisone, difluroSone ited to, urea, salicylic acid, papain, Sulfur, glycolic acid, pyru diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone and the balance of its esters, chlo Vic acid, resorcinol, N-acetylcysteine, retinoids such as ret roprednisone, chlorprednisone acetate, clocortelone, clesci inoic acid and its derivatives (e.g., cis and trans, esters), alpha nolone, dichlorisone, diflurprednate, flucloronide, hydroxy acids, betahydroxy acids, coal tar, and combinations flunisolide, fluoromethalone, fluperolone, fluprednisolone, thereof. hydrocortisone Valerate, hydrocortisone cyclopentylpropi onate, hydrocortamate, meprednisone, paramethasone, pred 3.7 Other Agents nisolone, prednisone, beclomethasone dipropionate, triamci 0115 Suitable other agents include, but are not limited to, nolone, and mixtures thereof. skin soothing agents, deodorant agents, antiperspirants, Sun 0111. In certain embodiments, steroids may be excluded Screening agents, Sunless tanning agents, Vitamins, hair con from the compositions of the invention. ditioning agents, anti-irritants, anti-aging agents, and combi nations thereof. 3.4 Anesthetics 0116 Examples of skin soothing agents include, but are not limited to, allantoin, aloe, avocado oil, green tea extract, 0112 Suitable anesthetics include the aminoacylanilide hops extract, chamomile extract, colloidal oatmeal, calamine, compounds such as lidocaine, prilocaine, bupivacaine, levo cucumber extract, and combinations thereof. bupivacaine, ropivacaine, mepivacaine and related local anes 0117 Examples of vitamins include, but are not limited to, thetic compounds having various Substituents on the ring Vitamins A, D, E, K, and combinations thereof. system or amine nitrogen; the aminoalkyl benzoate com 0118. Examples of sunscreens include, but are not limited pounds, Such as procaine, chloroprocaine, propoxycaine, to, p-aminobenzoic acid, AVobenzone, Cinoxate, Dioxyben hexylcaine, tetracaine, cyclomethycaine, benoximate, Zone, Homosalate, Menthyl anthranilate, Octocrylene, Octyl butacaine, proparacaine, butamben, and related local anes methoxycinnamate, Octyl salicylate, Oxybenzone, Padimate thetic compounds; cocaine and related local anesthetic com O. Phenylbenzimidazole sulfonic acid, Sulisobenzone, Tita pounds; amino carbonate compounds such as diperodon and nium dioxide, Trolamine salicylate, Zinc oxide, 4-methyl related local anesthetic compounds; N-phenylamidine com benzylidene camphor, Methylene Bis-Benzotriazolyl Tet pounds such as phenacaine and related anesthetic com ramethylbutylphenol, Bis-Ethylhexyloxyphenol pounds; N-aminoalkyl amide compounds such as dibucaine Methoxyphenyl Triazine, Terephthalylidene Dicamphor Sul and related local anesthetic compounds; aminoketone com fonic Acid, Drometrizole Trisiloxane, Disodium Phenyl pounds such as fallicaine, dyclonine and related local anes Dibenzimidazole Tetrasulfonate, Diethylamino Hydroxy thetic compounds; and amino ether compounds such as benzoyl Hexyl Benzoate, Octyl Triazone, Diethylhexyl Buta pramoxine, dimethisoquien, and related local anesthetic com mido Triazone, Polysilicone-15, and combinations thereof. pounds; and para-amino benzoic acid esters such as ben Zocaine. Other Suitable local anesthetics include ketocaine, 4. Stabilizers dibucaine, amethocaine, propanacaine, and propipocaine. 0119 The composition may further include components 3.5 Antimicrobial Agents adapted to improve the stability or effectiveness of the applied formulation. These include, but are not limited to, preserva 0113 Suitable antimicrobial agents include, but are not tives, buffers, antioxidants, and chelators. limited to, antibacterial, antifungal, antiprotozoal and antivi I0120 Suitable preservatives for use in the present inven ral agents, such as beta-lactam drugs, quinolone drugs, cipro tion include, but are not limited to: ureas, such as imidazo floxacin, norfloxacin, tetracycline, erythromycin, amikacin, lidinyl urea and diazolidinyl urea; phenoxyethanol; sodium triclosan, doxycycline, capreomycin, chlorhexidine, chlortet methyl paraben, methylparaben, ethylparaben, and propylpa racycline, oxytetracycline, clindamycin, ethambutol, metron raben; potassium Sorbate; sodium benzoate: Sorbic acid; ben idazole, pentamidine, gentamicin, kanamycin, lineomycin, Zoic acid; formaldehyde; citric acid; sodium citrate; chlorine methacycline, methenamine, minocycline, neomycin, dioxide; quaternary ammonium compounds, such as benza netilmicin, Streptomycin, tobramycin, and miconazole. Also Ikonium chloride, benzethonium chloride, cetrimide, dequal included are tetracycline hydrochloride, famesol, erythromy inium chloride, and cetylpyridinium chloride; mercurial cineStolate, erythromycin Stearate (salt), amikacin Sulfate, agents. Such as phenylmercuric nitrate, phenylmercuric doxycycline hydrochloride, chlorhexidine gluconate, chlo acetate, and thimerosal; and alcoholic agents, for example, rhexidine hydrochloride, chlortetracycline hydrochloride, chlorobutanol, dichlorobenzyl alcohol, phenylethyl alcohol, oxytetracycline hydrochloride, clindamycin hydrochloride, and benzyl alcohol. ethambutol hydrochloride, metronidazole hydrochloride, 0121 Suitable antioxidants include, but are not limited to, pentamidine hydrochloride, gentamicin Sulfate, kanamycin ascorbic acid and its esters, sodium bisulfite, butylated sulfate, lineomycin hydrochloride, methacycline hydrochlo hydroxytoluene, butylated hydroxyanisole, tocopherols US 2011/005250.6 A1 Mar. 3, 2011

(such as C-tocopherol), DL-alpha tocopheryl acetate, sodium ether, PEG-40 stearate, cetostearyl alcohol (C-C alcohol), ascorbate/ascorbic acid, ascorbyl palmitate, propyl gallate, ceteareth-12, ceteareth-20, ceteareth-30, ceteareth alcohol, and chelating agents like ethylenediaminetetraacetic acid glyceryl Stearate, PEG-100 stearate, glyceryl Stearate and (EDTA, e.g., disodium EDTA), citric acid, and sodium cit PEG-100 stearate, steareth-2, steareth-20, and polyoxyethyl rate. ene monooctadecyl ether, or combinations/mixtures thereof, 0122. In addition, combinations or mixtures of these pre as well as cationic emulsifiers like Stearamidopropyl dim servatives or anti-oxidants may also be used in the formula ethylamine and behentrimonium methosulfate, or combina tions of the present invention. tions/mixtures thereof. 5. Surfactants and Emulsifiers 6. Vehicles 0123 Many topical formulations contain chemical emul I0127 Suitable topical vehicles and vehicle components sions which use Surface active ingredients (emulsifiers) to for use with the formulations of the invention are well known disperse dissimilar chemicals in a particular solvent system. in the cosmetic and pharmaceutical arts, and include Such For example, most lipid-like (oily or fatty) or lipophilic ingre vehicles (or vehicle components) as water, organic solvents dients do not uniformly disperse in aqueous solvents unless Such as alcohols (particularly lower alcohols readily capable they are first combined with emulsifiers which form micro ofevaporating from the skin Such as ethanol), glycols (such as scopic aqueous soluble micelles that contain a lipid-soluble propylene glycol, butylene glycol, and glycerol), aliphatic interior and an aqueous-soluble exterior, resulting in an oil alcohols (Such as lanolin); mixtures of water and organic in-water emulsion. In order to be soluble in aqueous media, a Solvents (such as water and alcohol), and mixtures of organic molecule must be polar or charged so as to favorably interact Solvents such as alcohol and glycerol (optionally also with with water molecules which are also polar. Similarly, to dis water); lipid-based materials such as fatty acids, acylglycer Solve an aqueous-soluble polar or charged ingredient in a ols (including oils, such as mineral oil, and fats of natural or largely lipid or oil-based solvent, an emulsifier is typically synthetic origin), phosphoglycerides, sphingolipids and used which forms stable micelles that contain the aqueous waxes; protein-based materials such as collagen and gelatin: soluble components in the micelle interior while the exterior silicone-based materials (both non-volatile and volatile) such of the micelle is lipophilic so that it can dissolve in the as cyclomethicone, demethiconol and dimethicone copolyol; lipophilic solvent to form a water-in-oil emulsion. It is well hydrocarbon-based materials such as petrolatum and known that such emulsions can be destabilized by the addi squalane; and other vehicles and vehicle components that are tion of salts or other charged ingredients which can interact suitable for administration to the skin, as well as mixtures of with the polar or charged portions of the emulsifier within an topical vehicle components as identified above or otherwise emulsion micelle. Emulsion destabilization results in the known to the art. aqueous and lipophilic ingredients separating into two layers, I0128. In one embodiment, the compositions of the present potentially destroying the commercial value of a topical prod invention are oil-in-water emulsions. Liquids Suitable for use uct. in formulating compositions of the present invention include 0.124 Surfactants suitable for use in the present invention water, and water-miscible solvents such as glycols (e.g., eth may be ionic or non-ionic. These include, but are not limited ylene glycol, butylene glycol, isoprene glycol, propylene gly to: dicetyl phosphate (1-hexadecanol, hydrogen phosphate), col), glycerol, liquid polyols, dimethylsulfoxide, and isopro ceteth-10 phosphate (polyethylene glycol hexadecyl ether pyl alcohol. One or more aqueous vehicles may be present. phosphate), polysorbates (Polysorbate 20, Polysorbate 40, 0129. In one embodiment, formulations without metha Polysorbate 60, Polysorbate 80), steareth-10, sodium dodecyl nol, ethanol, propanols, or butanols are desirable. Sulfate (sodium lauryl Sulfate), lauryl dimethylamine oxide, cetyltrimethylammonium bromide (CTAB), polyethoxylated 7. Moisturizers and Humectants alcohols, polyoxyethylene sorbitan, octoxynol, N,N-dimeth yldodecylamine-N-oxide, hexadecyltrimethylammonium 0.130. One of the most important aspects of topical prod bromide (HTAB), polyoxyl 10 lauryl ether, bile salts (such as ucts in general, and cosmetic products in particular, is the Sodium deoxycholate or Sodium cholate), polyoxyl castor oil, consumer's perception of the aesthetic qualities of a product. nonylphenol ethoxylate, cyclodextrins, lecithin, dimethicone For example, while petrolatum is an excellent moisturizer and copolyol, lauramide DEA, cocamide DEA, cocamide MEA, skin product, it is rarely used alone, especially on the face, oleyl betaine, cocamidopropyl betaine, cocamidopropyl because it is greasy, sticky, does not rub easily into the skin phosphatidyl PG-dimonium chloride, methylbenzethonium and may soil clothing. Consumers highly value products chloride, alkyl polyglucoside, e.g., TritonTM CG-110 (Dow which are aesthetically elegant and have an acceptable tactile Chemical Co.), ammonium lauroyl sarcosinate, e.g., Per feel and performance on their skin. lastan R AL-30 (Struktol, Stow, Ohio), sodium lauroyl sarco 0131 Suitable moisturizers or humectants for use in the sinate, e.g., Perlastan.R. L-30 (Struktol, Stow, Ohio), and formulations of the present invention include, but are not ammonium myristoyl sarcosinate, e.g., Perlastan.R. M-30 limited to, lactic acid and other hydroxy acids and their salts, (Struktol, Stow, Ohio). Appropriate combinations or mixtures glycerol, propylene glycol, butylene glycol, Sodium PCA, of such surfactants may also be used according to the present sodium hyaluronate, hyaluronic acid, Carbowax 200, Carbo invention. wax 400, and Carbowax 800. 0.125 Many of these surfactants may also serve as emul (0132 Suitable humectants for use in the formulations of sifiers in formulations of the present invention. the present invention include, but are not limited to, 2-ethyl 0126. Other suitable emulsifiers for use in the formula hexyl palmitate (hexadecanoic acid, 2-ethylhexyl ester), tions of the present invention include, but are not limited to, glycerol, PPG-15 stearyl ether, lanolin alcohol, lanolin, lano behentrimonium methosulfate-cetearyl alcohol, non-ionic lin derivatives, cholesterol, petrolatum, isostearyl neopen emulsifiers like emulsifying wax, polyoxyethylene oleyl tanoate, octyl Stearate, mineral oil, isocetyl Stearate, myristyl US 2011/005250.6 A1 Mar. 3, 2011

myristate, octyl dodecanol, dimethicone, phenyl trimethi 0143. The indefinite articles“a” and “an as used herein in cone, cyclomethicone, C-C alkyl benzoates, dimethi the specification and in the claims, unless clearly indicated to conol, propylene glycol, and dicaprylate/dicaprate. the contrary, should be understood to mean “at least one.” 0133. In addition, appropriate combinations and mixtures 0144. The phrase “and/or as used herein in the specifica of any of these moisturizing agents or humectants may be tion and in the claims, should be understood to mean “either used in accordance with the present invention. or both of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present 8. Viscosity Modifiers in other cases. Multiple elements listed with “and/or should 0134 Suitable viscosity adjusting agents (i.e., thickening be construed in the same fashion, i.e., "one or more' of the and thinning agents) for use in the formulations of the present elements so conjoined. Other elements may optionally be invention include, but are not limited to, protective colloids or present other than the elements specifically identified by the non-ionic gums such as hydroxyethylcellulose, Xanthan gum, “and/or clause, whether related or unrelated to those ele and Sclerotium gum, as well as magnesium aluminum sili ments specifically identified. Thus, as a non-limiting cate, silica, microcrystalline wax, beeswax, paraffin, and example, a reference to A and/or B, when used in conjunc cetyl palmitate. In addition, appropriate combinations or mix tion with open-ended language such as "comprising can tures of these viscosity adjusters may be utilized according to refer, in one embodiment, to A only (optionally including the present invention. elements other than B); in another embodiment, to B only 0135) In one embodiment the viscosity modifier is (optionally including elements other than A); in yet another hydrous sodium lithium magnesium silicate, e.g., Laponite R embodiment, to both A and B (optionally including other (Rockwood Additives Limited, Cheshire, UK). elements); etc. 0136. In one embodiment the viscosity modifier is present 0145 The phrase “or,” as used herein in the specification in a composition of the invention in an amount from about and in the claims, should be understood to mean “either or 0.1% to about 6.0% by weight of the concentrate. both of the elements so conjoined, i.e., elements that are 9. Additional Constituents conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with "or should be 0.137 Additional constituents suitable for incorporation construed in the same fashion, i.e., "one or more' of the into the emulsions of the present invention include, but are not elements so conjoined. Other elements may optionally be limited to: skin protectants, adsorbents, demulcents, moistur present other than the elements specifically identified by the izers, buffering agents, Sustained release materials, solubiliz “or clause, whether related or unrelated to those elements ing agents, skin-penetration agents, abrasives, absorbents, specifically identified. Thus, as a non-limiting example, a anti-caking agents, anti-static agents, astringents (e.g., witch reference to “A or B, when used in conjunction with open hazel, alcohol, and herbal extracts such as chamomile ended language such as "comprising can refer, in one extract), binders/excipients, buffering agents, chelating embodiment, to A only (optionally including elements other agents, film forming agents, conditioning agents, opacifying than B); in another embodiment, to B only (optionally includ agents, and pH adjusters (e.g., citric acid, Sodium hydroxide, ing elements other than A); in yet another embodiment, to and sodium phosphate). both A and B (optionally including other elements); etc. 0138 Natural fats and oils, other than those listed above, 0146. As used herein in the specification and in the claims, may also be beneficial constituents of the inventive compo the phrase “at least one.” in reference to a list of one or more sitions. For example, fats and glyceridic oils from plants, such elements, should be understood to mean at least one element as Theobroma grandiflorum, may be added. selected from any one or more of the elements in the list of 0139 Suitable fragrances and colors may be used in the elements, but not necessarily including at least one of each formulations of the present invention. Examples of fra and every element specifically listed within the list of ele grances and colors Suitable for use in topical products are ments and not excluding any combinations of elements in the known in the art. list of elements. This definition also allows that elements may 0140. Often, one constituent of a composition may accom optionally be present other than the elements specifically plish several functions. In one embodiment, the present identified within the list of elements to which the phrase “at invention relates to constituents that may act as a lubricant or least one' refers, whether related or unrelated to those ele a skin-penetrating agent. In one embodiment, the multi-func ments specifically identified. Thus, as a non-limiting tional constituent is Socetyl Stearate, isopropyl isostearate, example, “at least one of A and B (or, equivalently, “at least isopropyl palmitate, or isopropyl myristate. one of A or B.’ or, equivalently “at least one of A and/or B) can refer, in one embodiment, to at least one, optionally 10. Purging Gases including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to 0141. In one embodiment, the air in the container charged at least one, optionally including more than one, B, with no A with the composition is replaced by an inert gas. In certain present (and optionally including elements other than A); in embodiments, the inert gas is selected from the group con yet another embodiment, to at least one, optionally including sisting of argon, nitrogen, and mixtures thereof. more than one, A, and at least one, optionally including more Definitions than one, B (and optionally including other elements); etc. 0.147. It should also be understood that, unless clearly 0142 For convenience, certain terms employed in the indicated to the contrary, in any methods claimed herein that specification and appended claims are collected here. These include more than one step or act, the order of the steps or acts definitions should be read in light of the entire disclosure and of the method is not necessarily limited to the order in which understood as by a person of skill in the art. the steps or acts of the method are recited. US 2011/005250.6 A1 Mar. 3, 2011

0148. In the claims, as well as in the specification, all transitional phrases Such as "comprising.” “including. "car TABLE 1-continued rying,” “having.” “containing,” “involving,” “holding.” “composed of and the like are to be understood to be open Formulations of four concentrates ended, i.e., to mean including but not limited to. Only the NB435- NB435 NB435- NB489 transitional phrases "consisting of and "consisting essentially Ingredient (%) 74/75 77/98 99.100 1.2 of shall be closed or semi-closed transitional phrases, respec Sodium Phosphate, O.O2 O.O2 O.O2 O.O2 tively, as set forth in the United States Patent Office Manual of Dibasic Patent Examining Procedures, Section 2111.03. Alkyl O.S 014.9 The invention now being generally described, it will Polyglucoside? Ammonium Lauroyl O.S be more readily understood by reference to the following Sarcosinate examples, which are included merely for purposes of illus Sodium Lauroyl O.S tration of certain aspects and embodiments of the present Sarcosinate' Ammonium Myristoyl O.S invention, and are not intended to limit the invention. Sarcosinate Examples Total 1OOOOOO 10O.OOOO 10O.OOOO 100.OOOO Laponite R Example 1 2Triton TM CG-110 Perlastan (R AL-30 Formulation Perlastan (RL-30 Perlastan (RM-30 0150. Four concentrates according to the invention were formulated as indicated in Table 1. Each column refers to two Example 2 preparations; for example NB435-74/75 refers to NB435-77 Stability and to NB435-75. Values shown are weight percentages of the 0151. The formulations described in Example 1 were total concentrate for each formulation. An HFA propellant in packed in aerosol containers and evaluated for stability of the the form of HFA-134a was included in each formulation in an hypochlorite in each over a period of up to two and a half amount corresponding to 12.5% of the weight of the compo weeks at 25°C., 30°C., and 40°C. Aerosol containers were sition. typical 1-inch aluminum can/aluminum valve aerosol con figuration or 20 mm glass aerosol bottle/valve combination. Results are shown in Tables 2-4. TABLE 1.

Formulations of four concentrates TABLE 2 NB435- NB435- NB435- NB489 Stability at 25 C. Ingredient (%) 74/75 77/98 99.100 1.2 25o C. Water 96.3434 96.3434 96.3434 94.8434 Hydrous Sodium Lithium 3 3 3 4.5 NB43S-75 NB43S-98 NB435-100 NB489-2 Magnesium Silicate' Sodium Hypochlorite O.11 O.11 O.11 O.11 Zero Time O.OO940 O.O1OOO O.OO911 O.O1022 Sodium Chloride O.OO66 O.OO66 O.OO66 O.OO66 2.5 wic O.OO213 O.OO424 O.004OO No Bleach Sodium Phosphate, O.O2 O.O2 O.O2 O.O2 Monobasic typical 1-inch aluminum can aluminum valve aerosol configuration

TABLE 3

Stability at 30° C.

30° C.

NB435-74 NB435-77 NB435-99 NB489-1

Zero Time 0.00958 O.O1043 O.OO924 O.O1421 1 wk 0.00339 (pH 9.4) 0.00584 (pH 9.7) 0.00536 (pH 9.8) 0.00069 (pH 10.1) 2 wik Not Tested 0.00458 (pH 10.0) 0.00448 (pH 10.0) Not Tested 2 wk 0.00171 (pH 9.2) 0.00492 (pH 9.7) 0.00455 (pH 10.0) Not Tested

typical 1-inch aluminum can aluminum valve aerosol configuration 20 mm glass aerosol bottle valve combination US 2011/005250.6 A1 Mar. 3, 2011

TABLE 4 Stability at 40 C.

40° C.

NB435-75 NB43S-98 NB435-100 NB489-2 Zero Time 0.00940 O.O1OOO O.OO911 O.01022 1 wk 0.00143 (pH 9.6) 0.00421 (pH 9.6) 0.00336 (pH 10.0) No Bleach (pH 9.8) 2 wik Not Tested 0.00129 (pH 9.7) 0.00130 (pH 10.0) Not Tested 2 wk Not Tested 0.00280 (pH 9.1) 0.00180 (pH 9.6) Not Tested typical 1-inch aluminum can aluminum valve aerosol configuration 20 mm glass aerosol bottlefvalve combination

Equivalents herpes simplex I, other topical herpes or viral infections, common cold Sores and fever blisters, ringworm, impetigo, 0152 Those skilled in the art will recognize, or be able to and other viral, fungal, or bacterial infections of the skin. ascertain using no more than routine experimentation, many 10. The method of claim 9, wherein the condition is atopic equivalents to the specific embodiments of the invention dermatitis. described herein. Such equivalents are intended to be encom 11. The method of claim 9, wherein the subject is human. passed by the following claims. 12. The method of claim 4 or 5, wherein the composition is We claim: applied once daily or twice daily. 1. A composition, comprising a concentrate and a propel 13. A composition, comprising a concentrate and a propel lant, wherein lant, wherein the concentrate comprises the concentrate comprises an amount of a hypochlorite salt, wherein the amount of an amount of a hypochlorite salt, wherein the amount of the hypochlorite salt is about 0.0001% to about 1.5% the hypochlorite salt is about 0.0001% to about 1.5% by weight of the concentrate; by weight of the concentrate; an amount of a viscosity modifier, wherein the amount of an amount of a humectant, wherein the amount of the the viscosity modifier is about 0.1% to about 6% by humectant is about 15% to about 35% by weight of the weight of the concentrate; an amount of a Surfactant, wherein the amount of the concentrate; surfactant is about 0.01% to about 1% by weight of an amount of water, wherein the amount of water is the concentrate; about 60% to about 80% by weight of the concentrate; an amount of water, wherein the amount of water is and about 80% to about 99% by weight of the concentrate; an amount of a stabilizer, wherein the amount of the and stabilizer is about 0.5% to about 5.0% by weight of the an amount of a stabilizer, wherein the amount of the concentrate; and stabilizer is about 0.01% to about 1.0% by weight of the propellant is a hydrofluoroalkane propellant. the concentrate; and 2. The composition of claim 1, wherein the composition is the propellant is a hydrofluoroalkane propellant. in an aerosol container. 14. The composition of claim 13, wherein the composition is in an aerosol container. 3. The composition of claim 2, wherein when the aerosol 15. The composition of claim 14, wherein when the aerosol container is actuated, the composition is expelled as a foam. container is actuated, the composition is expelled as a foam. 4. A method of treating a condition of a subject in need 16. A method of treating a condition of a Subject in need thereof, comprising thereof, comprising applying to an affected area of the Subject an effective applying to an affected area of the Subject an effective amount of a foam prepared from a composition of claim amount of a foam prepared from a composition of claim 1. 13. 5. The method of claim 4, further comprising 17. The method of claim 16, wherein the affected area of expelling from an aerosol containera composition of claim the Subject is selected from the group consisting of the face, 1, thereby preparing a foam. earlobes, neck, Scalp, genitals, eyelids, palms, fingers, feet, 6. The method of claim 4 or 5, wherein the subject is exural Surfaces of joints, extensor aspects of joints, and any human. combination thereof. 7. The method of claim 6, wherein the affected area of the 18. The method of claim 16, wherein the condition is Subject is selected from the group consisting of the face, selected from the group consisting of atopic dermatitis, con earlobes, neck, Scalp, genitals, eyelids, palms, fingers, feet, tact dermatitis, Xerotic eczema, Seborrhoeic dermatitis, pso riasis, dyshidrosis, discoid eczema, Venous eczema, dermati exural Surfaces of joints, extensor aspects of joints, and any tis herpetiformis, neurodermatitis, autoeczematization, combination thereof herpes simplex I, other topical herpes or viral infections, 8. The method of claim 6, wherein the affected area of the common cold Sores and fever blisters, ringworm, impetigo, subject is the face. and other viral, fungal, or bacterial infections of the skin. 9. The method of claim 4 or 5, wherein the condition is 19. The method of claim 18, wherein the subject is human. selected from the group consisting of atopic dermatitis, con 20. The method of claim 16, wherein the composition is tact dermatitis, Xerotic eczema, Seborrhoeic dermatitis, pso applied once daily or twice daily. riasis, dyshidrosis, discoid eczema, Venous eczema, dermati tis herpetiformis, neurodermatitis, autoeczematization, c c c c c