USOO921 1237B2

(12) United States Patent (10) Patent No.: US 9.211,237 B2 Huggins et al. (45) Date of Patent: *Dec. 15, 2015

(54) FILM FOAMING HYDROALCOHOLIC FOAM 5,208,011 A 5/1993 Vaughan 5,985,294. A * 1 1/1999 Peffly ...... 424/401 (71) Applicant: STIEFEL RESEARCHAUSTRALIA glas f ck 22999 et al ...... 424,59 PTY LTD, Rowville, Victoria (AU) 7.5, 5 57 E." 2002/0182234 A1 12/2002 Riedel et al. (72) Inventors: Joan Kathleen Huggins, Wheelers Hill 2006/0193789 A1 8/2006 Tamarkin et al. (AU); Robert James Houlden, Kilsyth (AU) FOREIGN PATENT DOCUMENTS (73) Assignee: STIEFEL RESEARCHAUSTRALIA A g s: ki 3.286 PTY LTD, Rowville, Victoria (AU) CA 2444 533 C 4/2002 DE 198 OS 432 C1 3, 1999 (*) Notice: Subject to any disclaimer, the term of this GB 1557 580 A 12, 1979 patent is extended or adjusted under 35 GB 2345 636 A T 2000 U.S.C. 154(b) by 0 days. JP 63-230622 A 9, 1988 JP 08-119831 A 5, 1996 This patent is Subject to a terminal dis- JP 11-505254 T 5, 1999 claimer. JP 2000516571 A 12/2000 JP 2002534453. A 10, 2002 JP 2003O11200 1, 2003 (21) Appl. No.: 14/028,981 WO 96/36322 A1 11, 1996 WO 97.03559 A1 2, 1997 (22) Filed: Sep. 17, 2013 WO 97,42933 A1 11, 1997 WO 01.05366 A1 1, 2001 (65) Prior Publication Data WO O3,O11238 A2 2/2003 US 2014/OO1717.6 A1 Jan. 16, 2014 OTHER PUBLICATIONS Related U.S. Application Data Supplementary European Search Report, Application No. EP 0471 (63) Continuation of application No. 1 1/187.217, filed on 0305, mailed Feb. 13, 2012, five (5) pages. Jul. 22, 2005, now Pat. No. 8,562,959, which is a “Personal Care Polymers: Speciality Products from National Starch continuation of application No. and Chemical Company. DERMACRYL Skin Care Formulating PCT/AU2004/000170, filed on Feb. 12, 2004. Guide, 1993, pp. 1-7. National Starch and Chemical Company, Bridgewater, New Jersey, USA. (60) Provisional application No. 60/447,445, filed on Feb. Battistini, G., “Un moderno tensio—attivo non ionico', Rivista Ital 12, 2003. ian Essenze, Profumi, Piante Officinali. Aromi, Saponi, Cosmetici. Aerosol. v. 98, n. 7, p. 422-427, 1966 (English Summary of article (51) Int. Cl. appears on pp. 426-427). A6 IK 8/04 (2006.01) Brazilian Office Action prepared Nov. 19, 2013, for counterpart A61O 1704 (2006.01) Brazilian application PIO407373-8. A6 IK 8/35 (2006.01) A6 IK S/37 (2006.01) * cited by examiner A6 IK 8/8 (2006.01) (52) CPC.U.S. Cl. A61K 8,046 (2013.01); A61K 8/35 (2013.01); Primary Examiner-Janet Epps-Smith A61K 8/37 (2013.01); A61K 8/8158 (2013.01); Assistant Examiner — Courtney Brown A61O 1704 (2013.01) (74) Attorney, Agent, or Firm Nath, Goldberg & Meyer; (58) Field of Classification Search Joshua B. Goldberg; Tanya E. Harkins CPC ...... A61K 8/046; A61K 8/35; A61K 8/37; A61K 8/8158: A61Q 17/04 USPC ...... 424/43 (57) ABSTRACT See application file for complete search history. The present invention provides a foam composition compris (56) References Cited ing an active agent. In particular, the foam composition pro duces a water resistant, preferably very water resistant, film U.S. PATENT DOCUMENTS upon application. 4,567,038 A 1, 1986 Ciaudelli et al. 5,204,090 A 4, 1993 Han 14 Claims, No Drawings US 9,211,237 B2 1. 2 FILMI FOAMINGHYDROALCOHOLIC FOAM invention provides a composition in a pressurized container for forming a hydroalcoholic foam, wherein the composition CROSS-REFERENCE TO RELATED comprises: APPLICATIONS at least one active agent; a water insoluble film-forming polymer; The present application is a Continuation Application of a hydroalcoholic foaming agent; and U.S. application Ser. No. 11/187.217 filed Jul. 22, 2005, an aerosol propellant. which was a Continuation Application of PCT/AU04/00170 In one particular embodiment, the active agent is a Sun filed Feb. 12, 2004, and claims priority to U.S. Provisional screen component. Preferably, the Sunscreen component Patent Application No. 60/447,445, filed Feb. 12, 2003, the 10 comprises at least one UVB Sunscreen and/or at least one disclosure of which hereby incorporated by reference in its UVA sunscreen. entirety for all purposes. When applied to the skin, the water insoluble polymer forms a thin film of a water resistant, preferably very water BACKGROUND OF THE INVENTION 15 resistant, barrier. In this manner, the active agent remains within the applied skin area even when wet. Topical delivery of active compounds is well known. In another aspect, the present invention provides a hydroal Unfortunately, many topical delivery formulations are not coholic foaming agent which comprises a C-C alcohol, waterproof or water resistant. Thus, when these active agents water, wax and a surfactant. Preferably, the amount of water are applied to the skin and exposed to moisture, most of the present in the composition is greater than the amount of C-C, active agents are often washed away from the skin thereby alcohol. reducing their effectiveness. These and other objects, embodiments and advantages will There are many challenges in the topical application of become more apparent with reference to the detailed descrip active agents. For example, application of active agents tion which follows. should be easy and Smooth. Moreover, in some instances the 25 composition should remain within the applied area for a pro DETAILED DESCRIPTION OF THE INVENTION longed period even when exposed to moisture to provide a relatively constant amount of the active agent within the I. Definitions applied area. Water resistant or very water resistant formulations of topi 30 Unless the context requires otherwise, the terms “active cal delivery systems are especially desirable because they agent”, “active compound' and “active component are used eliminate the need for reapplication after exposure of the interchangeably herein and refer to a substance having a applied area to water, Such as after Swimming, bathing or cosmetic, pharmaceutical, pharmacological or therapeutic excessive perspiration. This is particularly true for Sunscreen effect. products. 35 Unless indicated otherwise, a “water resistant composi Sunscreen products provide protection for the human skin tion includes a “very water resistant composition. against damages of ultraviolet light. Products with various Unless otherwise indicated, all percentages recited herein sun protection factor (SPF) values are available, thus allow are weight percentages, based upon total composition weight ing consumers to choose the amount of protection desired. excluding the propellant. While a variety of sunscreen products are available, “water 40 Unless otherwise indicated “comprises'/'comprising and resistant” or “very water resistant sunscreens are especially grammatical variations thereof when used in this specifica desirable because they eliminate the need for reapplication tion are to be taken to specify the presence of stated features, after Swimming, bathing or excessive perspiration. Generally integers, steps or components or groups thereof, but do not “water resistant Sunscreenformulations can undergo at least preclude the presence or addition of one or more other fea about 40 minutes of water immersion without significant SPF 45 tures, integers, steps, components or groups thereof. loss, whereas “very water resistant sunscreen formulations All disclosures referred to herein are hereby incorporated can undergo at least about 80 minutes of water immersion by reference. without significant SPF loss. Ideally, Sunscreen products should be stable and easy to II. General apply, and provide acceptable consistency and skin-feel. The 50 foregoing factors, which are important to achieving consis The present invention provides various topical delivery tent distribution on the skin, even Sun protection, along with foam compositions for active agents. In particular, composi consumer acceptance and commercial viability, are largely tions of the present invention are directed to water resistant, functions of the vehicle which carries the Sunscreen agents. preferably very water resistant, topical delivery foam compo For the above reasons, it is clearly desirable to formulate a 55 sitions comprising active agents. A water resistant property of topical vehicle that is capable of providing acceptable con the active agent is achieved by applying the foam composition sistency, skin feel and stability, and is easy to use and apply to a desired topical area, e.g., skin, which then forms a thin Sunscreen agents, and, thereby, achieve both water resistant film of a water resistant layer. The compositions of the present character and high-SPF values. The present invention fulfills invention are contained in a pressurized container. When the Such needs. 60 composition is dispensed from the container, it forms a foam structure. The rubbing or shearing action of foam application SUMMARY OF THE INVENTION breaks down the foam structure leaving behind a water resis tant film of active agent. The present invention provides a hydroalcoholic foam that In particular, the composition that is contained within the comprises an active agent. Advantageously, the hydroalco 65 pressurized container comprises: at least one active agent; a holic foam of the present invention is useful for topical appli water insoluble film-forming polymer; a hydroalcoholic cation as it is easy to apply. As such, in one aspect, the present foaming agent; and an aerosol propellant. The amount of each US 9,211,237 B2 3 4 of these components can vary depending on a wide variety of In certain preferred aspects, the active agent is a light factors, such as the desired foam characteristics, the degree of sensitive drug Such as an antibiotic (e.g., amikacin, augmen water resistance, and the like. tin amoxicillin, amplicillin, cefazolin, cefoxitin, ceftazidime, Typically, the pressurized container is any container that ceftiofur, cephalothin, enrofloxacin, florfenicol, gentamicin, has a Sufficient mechanical strength to withstand the pressure. imipenem, kanamycin, Sarafloxicin, tetracycline, ticarcillin, The container is generally fitted with a valve, e.g., an upright and tilmicosin) an antifungal or other light sensitive pharma or inverted valve, and a conventional foam spout actuator. ceutical actives Such as tretinoin, isotretinoin, sodium Sulfac In addition, the present invention provides various aspects etamide, calcipotriene and hydroquinone. Those of skill in related to Such compositions, including methods for protect the art will know of other light sensitive active agents suitable ing the skin of a subject from ultraviolet light and the use of 10 for use in the present invention. the compositions in protecting skin against the negative Other Suitable pharmaceutical agents are well known to effects of ultraviolet light. In certain preferred embodiments, the compositions of the one skilled in the art. See, for example, The Merck Index, 13' present invention are emulsions. In these instances, oil is Ed., 2001, Merck & Co., Inc., Whitehouse Station, N.J., pp. preferably the dispersed liquid (the discontinuous phase) and 15 THER-1 to THER-31, which is incorporated herein by refer the hydroalcoholic solution is the continuous phase. Typi ence in its entirety. The compositions of the present invention cally oil in hydroalcoholic emulsions are difficult to stabilize. can comprise a mixture of two or more cosmetic agents and/or Therefore, one advantage of this invention is a stable hydroal pharmaceutically active agents. In this manner, a wide com coholic film Such as a hydroethanolic foam, and more pref bination of active agents can be used simultaneously. For erably a stable hydroalcoholic film forming foam. example, the active agent can be a mixture of a Sunscreen component and a light sensitive pharmaceutical agent, e.g., an III. Active Agents antibiotic compound. The Sunscreen component protects the light sensitive pharmaceutical agent from Sun light. More The active agent can be any cosmetic agent or pharmaceu over, the water resistant property allows the Subject to pursue tically active agent, including Sunscreen components, antibi 25 active outdoor activities, e.g., Swimming and other physical otics, antifungal agents, antiviral compounds, nicotine, as activities, which can cause perspiration, without having the well as other pharmaceutical or therapeutically active agents active agent being washed away. that are capable of being used topically. Exemplary antifungal In one particular embodiment of the present invention, the agents that are Suitable in compositions of the present inven active agent is a Sunscreen component. The term "sunscreen tion include, but are not limited to, diols, allylamines (includ 30 component as used herein includes commonly used ultra ing naftifine and terbinafine), polyene macrollide antibiotics (including amphotericin and nystatin), triazole derivatives violet ray-blocking compounds. Preferably, the Sunscreen (such as fluconazole), fatty acids (such as caprylic and pro component comprises at least one UVB Sunscreen and/or at pionic acid), amorolfine, ciclopiroX, lamine, benzoic acid, least one UVA sunscreen. More preferably, the sunscreen flucytosine, haloprogin, tolnaftate, undecenoic acid and its 35 component comprises at least one UVB Sunscreen and at least salts, griseofulvin and imidazole compounds (such as keto one UVA sunscreen. As expected, the combination of UVB conazole and chlorphenesin (3-(4-Chlorphenoxy)propane-1, and UVA sunscreens provide a broad spectrum UV protec 2-diol)). tion. A more detailed discussion of Sunscreen agents useful in The terms “antibiotic' and “antimicrobial are used herein this invention is provided by Roelandts et al., “A Survey of interchangeably to refer to a compound that inhibits the 40 Ultraviolet Absorbers in Commercially Available Sun Prod growth of inhibits the virulence of, or kills bacterial cells. ucts”, Int. J. Dermatol., Vol. 22, pp. 247-255 (May, 1983). Antibiotics include, e.g., Substances produced by various spe In another embodiment, the Sunscreen component is pref cies of microorganisms (e.g., bacteria, fungi, and actino erably selected from the group of Aminobenzoic acid mycetes), variants thereof, and synthetic antibacterial agents. (4-Aminobenzoic acid); AVobenzone (4-tert-butyl-4-meth A complete list of antibiotics is too long to be included herein, 45 oxydibenzoylmethane); Benzophenone-2 (Bis(2,4-Dihy and those of skill in the art are aware of the multitude of droxyphenyl)Methanone); Benzophenone-3 (Oxybenzone); antibiotics that can be used in the present invention. See, e.g., BenZophenone-4 (Sulisobenzone); Benzophenone-5 Chambers and Sande, Antimicrobial Agents. General Con (Sulisobenzone sodium); BenZophenone-8 (Dioxybenzone); siderations in Goodman & Gilman's The Pharmacological Benzylidene Camphor (3-(4-Methylbenzylidene)-d-1 cam Basis of Therapeutics, Hardman and Limbard eds., (1996); 50 phor); Cinoxate; Ecamsule (Terephthalylidenedicamphor and Kucers, et al., The Use of Antibiotics: A Clinical Review sulfonic acid); Ethoxylated ethyl 4-aminobenzoic acid of Antibacterial, Antifiungal, and Antiviral Drugs Oxford (PEG25 PABA); (Homomethyl salicylate); Univ. Press (1997). Suitable antibiotic agents include, but are Isoamylmethoxycinnamate (Isopentenyl-4-methoxycin not limited to, clindamycin, erythromycin, tetracycline, namate); Isopropylbenzyl salicylate; Menthyl anthranilate minocycline, doxycycline, penicillin, amplicillin, carbenicil 55 (Methyl 2-aminobenzoate); Mexoryl XL (phenol.2-(2H-ben lin, methicillin, cephalosporins, Vancomycin, and bacitracin, Zotriazol-2-yl)-4-methyl-62-methyl-3-1,3,3,3-tetramethyl streptomycin, gentamycin, chloramphenicol, fusidic acid, 1- (trimethylsilyl)oxydisiloxanylpropyl)Octyl dimethyl ciprofloxin and other quinolones, Sulfonamides, trimethop PABA; Octinoxate (Octyl methoxycinnamate); Octyl salicy rim, dapsone, isoniazid, teicoplanin, avoparcin, synercid, Vir late (2-Ethylhexyl Salicylate); Octocrylene (2-cyano-3,3- giniamycin, cefotaxime, ceftriaxone, piperacillin, ticarcillin, 60 diphenyl acrylic acid.2-ethylhexyl ester); Octyl triazone (2.4. cefepime, cefpirome, rifampicin, pyrazinamide, ciprofloxa 6-Trianalino-(p-Carbo-2'-ethylhexyl-1'oxy)1,3,5-Triazine); cin, levofloxacin, enrofloxacin, amikacin, netilmycin, imi Padimate O (2-Ethylhexyl 4-dimethylaminobenzoate); Phe penem, meropenem, inezolid, pharmaceutically acceptable nylbenzimidazole sulfonic acid (2-Phenylbenzimidazole-5- salts thereof, and prodrugs thereof. Preferably, the antibiotic Sulfonic acid) and its potassium, Sodium and triethanolamine agent is clindamycin, erythromycin, tetracycline, minocy 65 salts; N.N.N-Trimethyl-4-(oxoborn-3-ylidenemethyl) cline, doxycycline, pharmaceutically acceptable salts anilinium methylsulfate; salts (potassium, So thereof, or prodrugs thereof. dium and triethanolamine); Tinosorb M. (2,2'-Methylene US 9,211,237 B2 5 6 bis-6-(2H-benzotriazol-2yl)-4-(tetramethyl-butyl)-1,1,3,3- 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, phenol); Titanium dioxide; Triethanolamine salicylate; Zinc 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29% and 30%. oxide; and mixtures thereof. The carboxylic acid functional groups can be neutralized The nature and the amount of Sunscreen component using a basic compound. Such as an inorganic base. Such as present in the composition generally affects the Sun protec Sodium hydroxide, sodium benzoate or potassium hydroxide, tion factor (SPF) of the composition. Thus, a wide SPF range, or an amino-alcohol selected for example from 2-amino-2- is possible in compositions of the present invention. Typi methyl-1-propanol (AMP), triethanolamine, triisopropanola cally, however, the amount of a particular Sunscreen used is mine (TIPA), monoethanolamine, diethanolamine, tris(2-hy determined by the desired SPF. As such, SPF as low as two (2) droxy-1-propylamine, 2-amino-2-methyl-1,3-propanediol and as high as 45 or greater can be achieved by adjusting the 10 (AMPD), alkaline salts of ethylene diamine tetraacetic acid Such as tetrasodium ethylene diamine tetra acetic acid amount of Sunscreen present in the composition. Generally, (NaEDTA), or 2-amino-2-hydroxymethyl-1,3-propanediol. however, sunscreens having SPF of about 15 or about 30 are Lysine, arginine or cystine can also be used as neutralizing most commonly used. However, it should be appreciated that agents, or combinations of the foregoing. Preferably, the car the Sunscreen compositions of the present invention are not 15 boxylated acrylic copolymer is neutralized using Sodium ben limited to any particular SPF values. Zoate and/or tetrasodium EDTA. The Sunscreen component can also be used as an agent to Generally, compositions of the present invention have protect light sensitive drugs. Therefore, in one embodiment, about 0.01 to about 15 weight percent of a carboxylated the present invention provides a combination of a light sen acrylic copolymer. The range is preferably from about 0.1% sitive active agent and a Sunscreen active agent. to about 10%, with about 0.5% to about 5% being especially As Stated above, the amount of Sunscreen component preferred. present in compositions of the present invention vary depend It is known that these polymers become water dispersible/ ing on the particular Sunscreen component(s) chosen and the soluble via neutralization of their carboxyl (i.e., carboxylic SPF desired. Typically, however, compositions of the present acid) groups with a base, e.g., an alkaline material. Thus, in invention comprise from about 1 to about 30% by weight of 25 Some embodiments of the present invention, a portion of the the total composition in the container, including the propel carboxyl groups in the carboxylated acrylic copolymer is lant. Preferably, the amount of Sunscreen component present neutralized with a base. In this manner, the amount of organic in compositions of the present invention is from about 5 to solvent, e.g., C-C alcohol, used in the composition can be about 40%. Alternatively, at least about 5%, preferably at least reduced significantly. about 10%, of the Sunscreen component is present in compo 30 sitions of the present invention. The amount of Sunscreen V. Hydroalcoholic Foaming Agent referred to herein refers to the total amount of all sunscreen components that are present in compositions of the present The hydroalcoholic foaming agent comprises a C-C alco invention. As such, for a composition comprising a mixture of hol, water, wax and a surfactant. Sunscreen components, the amount of each Sunscreen com 35 A. Alcohols ponent can vary significantly depending on the desired physi Suitable C-C alcohols include methanol, , pro cal and chemical properties as well as the SPF desired. panol, butanol, pentanol, hexanol and their isomers. How ever, since methanol is poisonous, for safety reasons ethanol IV. Water Insoluble Film-Forming Polymer n-propanol or isopropanol are preferred. With ethanol being 40 particularly preferred, such as “SD Alcohol 40” or “SDA40”. Typically, the water insoluble film-forming polymer is In one particular embodiment, the amount of water in the preferably a carboxylated acrylic copolymer. Water insoluble hydroalcoholic foaming agent is higher than the amount of carboxylated acrylic copolymers including those sold by alcoholic solvent, e.g., C-C alcohol. Preferably, the amount National Starch and Chemical Corporation under the trade of C-C alcohol present in the composition is less than about names “Dermacryl', Amphomer' and “Versacryl” (acry 45 50% by weight of the total composition, more preferably less lates/octylacrylamide copolymer) (CFTA), are known to be than about 40% and most preferably, less than about 30%. useful in this invention. Particularly preferred carboxylated Alternatively, the amount of C-C alcohol present in the acrylic copolymer is a solid copolymer sold under the trade composition of the present invention ranges from about 5% to name “Dermacryl-79, which provides satisfactory water about 40% by weight, preferably from about 10% to about resistant and/or very water resistant properties. In addition, 50 30% and more preferably from about 15% to about 25%, such Amphomer,” or “octylacrylamide/acrylate/butylaminoethyl as 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, and methacrylate copolymer, a polymer formed from octylacry fractions thereof. lamide, t-butylaminoethyl methacrylate and two or more B. Water monomers of acrylic acid, methacrylic acid or any of their Typically at least about 40% of the composition is com simple esters, can also be employed. Dermacryl 79 CAS 55 prised of water, preferably at least about 45% and more pref Number 129702-02-9 is a hydrophobic, high molecular erably at least about 50%. Alternatively, the amount of water weight carboxylated acrylic copolymer. present in the compositions of the present invention generally Advantageously, the carboxylic acid functional groups of ranges from about 35 to about 65%, preferably from about 40 the film-forming polymers are at least partially neutralized in to about 60% and more preferably from about 50 to about order to obtain good dispersion of the film-forming polymer 60 55%. Thus, unlike other conventional water resistant compo in the aqueous medium. In certain aspects, a percentage of the sitions, compositions of the present invention have a signifi carboxylic acid groups present in the water insoluble car cantly higher amount of water than the amount of C-C, boxylated acrylic copolymer are neutralized. Preferably, the alcohol. percentage that is neutralized is between 0% to about 40%. C. Wax Preferably, the percentage that is neutralized is between about 65 Various waxes are suitable for use in the present invention. 3% to about 35%, more preferably about 7% to about 33%, These include for example, non-ionic self-emulsifying and most preferably about 10% to about 30%, such as 10%, waxes. For example, Polawax GP200 (cetearyl alcohol and US 9,211,237 B2 7 8 PEG-20 stearate) (Croda Surfactants) is a non-ionic self a) Sunscreen Component emulsifying wax that is used in oil-in-water emulsions. The Parsol MCX (octinoxate) is a highly effective, oil soluble waxy material was used to impart structural Support to the UV-B absorber with maximum absorption at 308 nm. In foam and to improve the film-forming properties and water addition, Parsol MCX is an excellent solvent for Uvinul M40. resistance of the emulsion on the skin. Other waxes suitable A concentration of 7.5% w/w was chosen based on the mono for use in the present invention include, but are not limited to, natural waxes such as animal waxes such as carnauba and graph requirements. beeswax, vegetable waxes, mineral waxes such as petroleum Uvinul M40 (oxybenzone) is an oil soluble UV-A and waxes, and synthetic waxes. UV-B absorber offering maximum absorption in the short D. Surfactants wave UV-B and UV-A spectra. Uvinul M40 is usually Compositions of the present invention can also include a 10 employed as a coabsorber in combination with a specific Surfactant system. The presence of Surfactant allows emulsi UV-B absorber (such as Parsol MCX). Uvinul M40 requires fication of one or more components that may be otherwise sufficient solubility in emulsions to ensure that re-crystalli insoluble within the composition. The surfactant system of Zation does not occur. the invention can comprise a polyoxyalkylene ester of a Parsol 1789 (butyl methoxydibenzolymethane) is a highly straight or branched chain fatty acid, polysorbate or mixtures 15 thereof. Preferred polyoxyalkylenes include polypropylene effective oil-soluble UV-A filter. It is often used in conjunc glycol and polyethylene glycol, with the latter being espe tion with UV-B filters to provide full-spectrum UV protec cially preferred. tion. The maximum absorption of Parsol 1789 is at or near Useful polyoxyalkylene esters offatty acid include, but are 360 nm. not limited to, the fatty acid esters of polyoxyethylene glycol b) Excipients sold as a "Cithrol' (Croda) and “Myr 52 (Uniqema). Useful Polawax GP200 (cetearyl alcohol and PEG-20 stearate) polysorbate includes Polysorbate 85 sold as “Crillet 45.” (Croda Surfactants) is a non-ionic self-emulsifying wax that (Croda). The Surfactant system can also include combinations is used in oil-in-water emulsions. The waxy material was used of one or more Surfactants disclosed herein. to impart structural Support to the foam and to improve the Generally, the total amount of surfactant(s) present in com 25 film-forming properties and water resistance of the emulsion positions of the present invention ranges from about 0.1 to on the skin. about 20% by weight. The preferred range is from about 0.5% DermacrylR 79 (acrylates/octylacrylamide copolymer) to about 15%, with about 2% to about 10% being highly (National Starch & Chemical) is a hydrophobic, high molecu preferred. lar weight, polymer. It was used at a level of about 1.5-2.5% VI. Optional Components 30 wfw in the formulation. It forms a water resistant or water proof film when applied. Its highly water resistant property The compositions of the invention can also include suitable was used to produce a water resistant sunscreen product. amounts of cosmetically and pharmaceutically acceptable MyrS2 (PEG-40 Stearate) (Uniqema) is a non-ionic emul additives, i.e., excipients and/or chemically active adjuvants, sifier that was used in conjunction with Crillet 45 to obtain a including chelating agents, such as EDTA and its salts, and 35 desired HLB (hydrophobic lipophilic balance) system for the corrosion protecting agents, such as sodium benzoate, or preservatives. formulation. MyrS2 is preferred to other emulsifiers because In addition, other additives such as colorants, thickeners, it is a solid waxy material. A concentration of 1.5-2.5% was perfumes, fillers, diluents, carriers, plasticizers, stabilizers, used based on a HLB screening (using different ratios of Myr gelling agents, preservatives, Supplemental emollients/sol 52 and Crillet 45), and as a result of foam quality optimiza vents and the like can also be added. 40 tion. Crillet 45 (Polysorbate 85) (Croda Surfactants) is an oil VII. Use in-water emulsifier. It was usedata concentration of 0.5-1.2% in association with Myri 52 to achieve a desired HLB. When dispensed from the container, the compositions of Sodium Benzoate is a commonly used corrosion inhibitor the present invention form a foam structure. When the foam is 45 and about 0.10-0.30% was added to the system to prevent can applied to a desired area, it dries relatively quickly to leave a corrosion during storage. water resistant or very water resistant active agent film on the Disodium EDTA (BASF) is a chelating agent that was skin. added to the system at 0.05-0.20%. It is known to one skilled The melting point of the hydroalcoholic foam that is pro in the art that Parsol 1789 reacts with metals, particularly duced from compositions of the present invention is about 35° 50 Fe", during manufacture or storage and develops a red com C. or higher. Preferably, the foam melting temperature is plex that discolors the formulation. about 40°C. or higher. An especially preferred foam melting The Sunscreen foam formulation is a non-greasy, water temperature is about 45° C. or higher. The term “foam melting resistant, SPF 15 foam product that can be used on the head, temperature” refers to the temperature at which the foam face and body. One particular Sunscreen component formu structure breaks down without any application of force, e.g., 55 lation is shown below. rubbing. Parsol MCX 7.5% w/w (in the absence of propellant) Additional objects, advantages, and novel features of this Uvinul M40 4.0% w/w (in the absence of propellant) invention will become apparent to those skilled in the artupon Parsol 1789—2.0% w/w (in the absence of propellant) examination of the following examples thereof, which are not The foam melting temperature of the formulation was found intended to be limiting. 60 to be about 40° C. VIII. Examples c) Water Resistance Dermacryl requires neutralization and heating to be incor 1. Example 1 porated into standard creams. In one embodiment, the present invention utilizes a new manufacturing method, whereby dis This example illustrates various preferred components to 65 Solving the Dermacrylin the ethanol first, then combining this formulate a stable Sunscreen foam for use on the scalp, face with the warm oil phase (40-45°C.) before forming the emul and body. sion has the advantage of not having to heat the ethanol, thus US 9,211,237 B2 9 10 providing a safer method of manufacture than traditional TABLE 2 techniques where a hot oil/ethanol phase is added to a hot water phase. SPF 15 Foan The acrylic copolymer with carboxyl groups such as Der Trade Name % w/w (No propellant) % w/w (with propellant) macryl 79, is insoluble in water, thereby imparting wash Ethanol SDA 40-2 24.96 23.71 resistance in a formulation. If the carboxyl groups are fully Dermacryl 79 2.OO 1.90 neutralized, the acrylic copolymer would be water soluble, Polawax GP200 3.00 2.85 hence impart no wash resistance. A partially neutralized Parsol. MCX 7.50 7.13 copolymer (for example, 29% neutralization), has been sur Uwinul M40 4.OO 3.80 10 Parsol 1789 2.OO 1.90 prising found to show enhanced water Solubility over an Myri 52 1.2O 1.14 un-neutralised formulation, and improved wash resistance Purified Water 54.24 51.53 over a fully neutralized formulation. An example of a fully Sodium Benzoate O.2O O.19 (100%) neutralized formula is given below: An example of a di-sodium EDTA O.10 O.095 fully (100%) neutralized formula is given below in Table 1: Crillet 1 O.8O O.76 15 Propellant P70 O S.OO TABLE 1. Item No. Ingredient % ww TABLE 3

1 Purified Water S2.11 SPF 15 Foan 2 Sodium Benzoate O.19 3 EDTA di-Sodium O.10 % w/w (No. 9% w/w (with 4 Polawax GP200 2.85 Trade Name propellent) propellant) Function 5 Parsol. MCX 7.13 6 Uwinul M40 3.80 Deionized Water 56.30 53.49 Solvent 7 Parsol 1789 1.90 Alcohol SDA 40-2 21.90 20.81 Solvent 8 Crillet 45 O.83 25 Parsol. MCX 7.50 7.13 Sunscreen-UVB 9 Ethiomeen C25 3.92 Propellant P45 O.OO S.OO Propellant 10 Dermacryl-79 1.90 Uwinul M-40 4.OO 3.80 Sunscreen-UVA 11 Ethanol SDA 40-2 20.27 Polawax GP200 3.00 2.85 Emulsifier Myri 52 2.13 2.02 Emollient TOTAL 95.00 Parsol 1789 2.00 1.90 Sunscreen-UVA 30 Dermacryl-79 2.00 1.90 Film Former Crillet 45 O.87 O.83 Emulsifier Sodium Benzoate O.2O O.19 Anti-corrosion plus propellant at 5% w/w. protection The effect of partially neutralized and fully neutralized di-sodium EDTA O.10 O.10 Chelating agent Dermacryl-79 in the formulation was investigated. SPF results of the formulations are shown below: 100% neutral 35 ized Dermacryl 79—SPF 3.9 (40-minutes wash resistance) 2. Example 2 Table 1.29% neutralized Dermacryl 79 SPF 16.1 (40-min utes wash resistance) (Table 3). This example illustrates a method of manufacturing the d) Neutralization of Dermacryl 40 compositions of the present invention. Dermacryl 79 is carboxylated and is normally neutralized The sunscreen formulations of the present invention can be with a suitable alkaline material in formulation. The formu produced using the following procedure. The particle size and lator can use materials such as triethanolamine, 2-amino-2- emulsion appearance were assessed using an Olympus BX50 methyl-1-propanol, ammonium or potassium hydroxides, or microscope. The ambient manufacturing method of manufac long chain amines. The amount of base required to neutralize 45 ture is set out below: the carboxyl groups in DERMACRYL 79 can be determined a) Water Phase: by the following relationship: 1. Weigh purified water into a vessel. Heat to 45-50° C. 2. While stirring add Myri 52, continue to stir until the Myr 52 has dissolved. W x 2.4 xN XE 50 3. While stirring, add Sodium Benzoate, stir until dissolved. 1000 4. While continuing to stir the product, add bisodium EDTA, stir until dissolved. Where: B-weight (grams) of base needed; W= weight 5. Stir cool to 20-30° C. (grams) of DERMACRYL 79 used; N=% neutralization 6. Correct for any loss of water. required (decimal); and E-equivalent weight of base (eq/g). 55 b) Ethanol Phase: A specific example of 100% neutralization of 100 grams of 7. Weigh Ethanol into a separate tank. DERMACRYL 79 with triethanolamine is as follows: 8. While stirring, slowly add Dermacryl 79, continue to stir until dissolved. EXAMPLE: W=100 grams: N=1.00; E=149.2: Oil Phase: 60 9. Weigh Parsol MCX into a separate vessel and heat to B 100x2.4x100x149.2 50-55o C. 1000 = 35.8 grams TEA. 10. While stirring, add Crillet 45, Uvinul M40, Parsol 1789 and Polawax GP200, continue to stir until all components have dissolved. Tables 2 and 3 show different SPF 15 foam compositions of 65 11. Stir cool to 40-45° C. the present invention. The partially neutralized formula is set 12. While stirring, slowly add the oil phase to the ethanol forth below (Table 3). phase and continue to stir until dissolved. US 9,211,237 B2 11 12 13. Correct for any loss of Ethanol. The results indicate that at 0% neutralization and at 25% 14. Maintain at 20-30° C. neutralization of the Dermacryl, the water resistance of the c) Emulsion Formation: film was higher than the 100% neutralized film. While the 15. While stirring the water phase, slowly add the Ethanol/Oil partial neutralization of the Dermacryl allowed it to be solu phase into the Vortex. 5 bilised in the formulation, the formulation still provided good 16. Homogenise batch until the particle size is within speci water resistance. From this, it can further be expected that the fication. partially neutralized Dermacryl formulation would provide 17. Slow stir to allow the batch to de-aerate. better SPF than the 100% neutralized Dermacryl formulation post immersion in water. 3. Example 3 10 This example shows percent neutralization can have an effect on water resistance. TABLE 4

Product:

Sunscreen Foam Sunscreen Foam Sunscreen Foam F210,04f OS F210,04f13 F210,04f18 E210,04f OS E210,04f13 E210,04f18 30% EtOH 10%. Ethanol 10%. Ethanol 25% Neutralization 0% Neutralization 100% Neutralization

1 2 1 2 1 2 Wt of microscope slide 16.8371 7.2195 6.7635 16.7936 17.5840 17.1021 (T): Wt of microscope slide 18.1036 8.368O 7.7508 17.8898 186974 18.1176 plus product: *Wt of product applied 1.2665 1.1485 O.9873 1.0962 1.1134 1.015S to microscope slide: After 15 hrs at 25°C. 17.0993 7.4681 6.9861 17.0297 17.8473 17.3413 5 mins at ambient After 60 mins at 17.0953 7.4641 6.9861 17.0264 17.8445 17.3392 50° C.f5 mins at ambient After 135 mins at 50° C. 17.0939 17.0258 17.8442 17.3390 5 mins at ambient After 180 mins at 50° C. 7.4628 6.9860 5 mins at ambient After 210 mins at 50° C. 5 mins at ambient (MF1) 17.0939 7.4628 6.9860 17.0258 17.8442 17.3390 Immerse in static waterbath at 25°C. for 20 mins 60 mins at 50° C.5 7.4OOO mins at ambient 90 mins at 50° C.5 17.0281 mins at ambient 140 mins at 50° C.f5 17.0169 mins at ambient 170 mins at 50° C.f5 17.01.19 mins at ambient After 62 hrs at 25°C.5 16.9976 mins at ambient 120 mins at 50° C.f5 16.9964 mins at ambient (MF2) 16.9964 17.3833 16.92O1 16.9461 17.6531 17.1623 Washability (in water) - 62 67 70 66 27 25 % Weight Loss AVERAGE WATER 65 68 26 RESISTANCE

As shown below in Table 4, 0% and 25% neutralization The foregoing discussion of the invention has been pre show exceptional water resistance capabilities. sented for purposes of illustration and description. The fore The in vitro water resistance testing involves applying an going is not intended to limit the invention to the form or accurately weighed mass of Sunscreen foam formulation to an 60 forms disclosed herein. Although the description of the inven accurately weighed substrate (ie glass microscope slide). The tion has included description of one or more embodiments product is placed in an incubator and allowed to dry to a film. and certain variations and modifications, other variations and The substrate with the dried film is placed into a waterbath modifications are within the scope of the invention, e.g., as with shaking, after which it is returned to an incubator and may be within the skill and knowledge of those in the art, after redried. 65 understanding the present disclosure. It is intended to obtain The water resistance of each film is calculated as the per rights which include alternative embodiments to the extent centage of film remaining on the Substrate. permitted, including alternate, interchangeable and/or US 9,211,237 B2 13 14 equivalent structures, functions, ranges or steps to those (2-Ethylhexyl Salicylate); Octocrylene (2-cyano-3,3- claimed, whether or not such alternate, interchangeable and/ diphenyl acrylic acid, 2-ethylhexyl ester); Octyl triaz or equivalent structures, functions, ranges or steps are dis one (2.4.6-Trianalino-(p-Carbo-2-ethylhexyl-1'oxy) closed herein, and without intending to publicly dedicate any 1,3,5-Triazine); Padimate O (2-Ethylhexyl 4-dimethy patentable subject matter. laminobenzoate); Phenylbenzimidazole sulfonic acid The invention claimed is: (2-Phenylbenzimidazole-5-sulfonic acid) and its potas 1. A composition in a pressurized container for forming a sium, sodium and triethanolamine salts; N.N.N-Trim hydroalcoholic foam, said composition comprising: ethyl-4-(oxoborn-3-ylidenemethyl) anilinium methyl a Sunscreen component; Sulfate; Salicylic acid salts (potassium, sodium and a water insoluble film-forming polymer which is a water 10 triethanolamine); Tinosorb M (2,2'-Methylene-bis-6- insoluble carboxylated acrylic copolymer; (2H-benzotriazol-2yl)-4-(tetramethyl-butyl)-1,1,3,3- a hydroalcoholic foaming agent comprising a C1-C6 alco phenol); Titanium dioxide; Triethanolamine salicylate: hol present in an amount from about 5% to about 40% by Zinc oxide; and a mixture thereof. weight based on the total weight of the composition, 4. The composition of claim 3, wherein said sunscreen water, wax and surfactant; and 15 component is selected from the group consisting of octinox an aerosol propellant; ate, oxybenzone, avobenzone, and a mixture thereof. and wherein said composition forms a foam when released 5. The composition of claim 1, wherein the total amount of from the container, and said foam, in use, forms a water said sunscreen component is from about 1% to about 30% by resistant film on skin, and weight based on the total weight of the composition. wherein a percentage of the carboxylic acid groups that are 6. The composition of claim 1, wherein said water present in the water insoluble carboxylated acrylic insoluble carboxylated acrylic copolymer is selected from the copolymer are neutralized and the percentage neutral group consisting of acrylate?t-octylpropenamide, octylacry ization is between about 3% to about 35%. lamide/acrylate/butylaminoethyl methacrylate copolymer, 2. The composition of claim 1, wherein said sunscreen acrylates/octylacrylamide copolymer, and a mixture thereof. component comprises at least one UVB sunscreen and/or at 25 7. The composition of claim 6, wherein said water least one UVA sunscreen. insoluble carboxylated acrylic copolymer is acrylates/octy 3. The composition of claim 2, wherein said sunscreen lacrylamide copolymer. component is selected from the group consisting of Ami 8. The composition of claim 1, wherein said percentage nobenzoic acid (4-Aminobenzoic acid); neutralization is between about 7% to about 33%. AVobenzone (4-tert-butyl-4-methoxydibenzoylmethane); 30 Benzophenone-2 (Bis(2,4-Dihydroxyphenyl) Metha 9. The composition of claim 1, wherein said carboxylated none); BenZophenone-3 (Oxybenzone); Benzophe acrylic copolymer is neutralized using sodium benzoate. none-4 (Sulisobenzone); Benzophenone-5 (Sulisoben 10. The composition of claim 1, wherein the total amount Zone sodium); BenZophenone-8 (Dioxybenzone); of said carboxylated acrylic copolymer is about 0.1% to about Benzylidene Camphor (3-(4-Methylbenzylidene)-d-1 35 10% by weight based on the total weight of the composition. camphor); Cinoxate; Ecamsule (Terephthalylidene 11. The composition of claim 1, wherein the amount of said dicamphor sulfonic acid); Ethoxylated ethyl 4-ami C1-C6 alcohol is from about 10% to about 30% by weight nobenzoic acid (PEG25 PABA); Homosalate (Homom based on the total weight of the composition. ethyl salicylate); Isoamylmethoxycinnamate (Isopente 12. The composition of claim 1, further comprising a nyl-4-methoxycinnamate); Isopropylbenzyl salicylate: 40 chelating agent. Menthyl anthranilate (Methyl 2-aminobenzoate): 13. The composition of claim 2, further comprising a cor Mexoryl XL (phenol.2-(2H-benzotriazol-2-yl)-4-me rosion protection agent. thyl-62-methyl-3-1,3,3,3-tetramethyl-1-(trimethylsi 14. The composition of claim 1, wherein said foam, in use, lyl)oxydisiloxanylpropyl); Octyl dimethyl PABA: forms a very water resistant film on the skin. Octinoxate (Octyl methoxycinnamate);