US 2008.0063607A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0063607 A1 Tamarkin et al. (43) Pub. Date: Mar. 13, 2008 (54) OLEAGINOUS PHARMACEUTICAL AND (60) Provisional application No. 60/492.385, filed on Aug. COSMETC FOAM 4, 2003. Provisional application No. 60/492.385, filed on Aug. 4, 2003. Provisional application No. 60/.530, (75) Inventors: Dov Tamarkin, Maccabim (IL); Doron 015, filed on Dec. 16, 2003. Provisional application Friedman, Karmei Yosef (IL); Meir No. 60/679,020, filed on May 9, 2005. Provisional Eini, Ness Ziona (IL); Alex Besonov, application No. 60/784,793, filed on Mar. 21, 2006. Rehovot (IL); Jorge Danziger, Rishom LeZion (IL); David Schuz. Moshav Gimzu (IL); Tal Berman, Rishon Publication Classification LeZiyyon (IL) (51) Int. Cl. Correspondence Address: A6IR 9/12 (2006.01) WILMERHALEABOSTON A6II 47/00 (2006.01) 6O STATE STREET A6IP 7/00 (2006.01) BOSTON, MA 02109 (US) (52) U.S. Cl. .............................................. 424/43; 514/789 (73) Assignee: FOAMIX LTD (57) ABSTRACT (21) Appl. No.: 11/894,798 (22) Filed: Aug. 20, 2007 The invention relates to stable pharmaceutical or cosmetic foam compositions containing certain active agents, having Related U.S. Application Data unique therapeutic properties and methods of treatment using Such compositions. The foamable composition (63) Continuation of application No. 1 1/653,205, filed on includes at least one solvent comprising polyethylene glycol Jan. 12, 2007. (PEG) or PEG derivative and mixtures thereof, or compris Continuation-in-part of application No. 10/911,367, ing propylene glycol, wherein the solvent is present at a filed on Aug. 4, 2004. concentration of about 70% to about 96.5% by weight of the Continuation-in-part of application No. 11/430,599, total composition, at least a non-ionic Surface-active agent at filed on May 9, 2006, which is a continuation-in-part a concentration of about 0.1% to less than about 10% by of application No. 10/835,505, filed on Apr. 28, 2004. weight of the total composition. US 2008/0063607 A1 Mar. 13, 2008 OLEAGNOUS PHARMACEUTICAL AND 0008 U.S. Pat. No. 6,524,594 describes a gelled oil COSMETC FOAM composition containing an emulsifier, a gelling agent, an oil. and a Surfactant which, when applied to the skin in the RELATED APPLICATIONS presence of water, produces a significant amount of foam. The surfactant is used in an amount from about 10% to about 0001. This application claims the benefit of priority under 20%, and more preferably, from about 15% to about 20%. 35 U.S.C. S 120 to co-pending U.S. application Ser. No. 1 1/653,205, filed Jan. 12, 2007, entitled “Oleaginous Phar 0009 U.S. Pat. No. 6,121,210 discloses foamable, sili maceutical and Cosmetic Foam, which is a continuation-in cone oil compositions and methods of lubricating Surfaces part application of co-pending U.S. patent application Ser. with Such compositions. The compositions are oil-in-water No. 10/911,367, filed on Aug. 4, 2004, which claims the emulsions comprising silicone oil-in-water emulsion, a liq benefit of priority under 35 U.S.C. S 119(e) to U.S. Patent uid propellant and a foam builder comprising a solid, Application Ser. No. 60/492.385, filed on Aug. 4, 2003, both non-ionic lipophilic Surfactant having an HLB value of entitled "Foam Carrier Containing Amphiphilic Copolymer about 3 to about 8. Foam stabilizers including long claim Gelling Agent” and both hereby incorporated in their fatty alcohols are included. A propellant is included to create entirety by reference. a foamable composition. 0002 This application is a continuation-in-part applica 0010. In general, the foamable compositions of the art are tion of co-pending U.S. patent application Ser. No. 10/835, based on oil-in-water emulsions. Furthermore, they often 505, filed on Apr. 28, 2004, which claims the benefit of include a high content level of Surfactants and foaming priority under 35 U.S.C. S 119(e) to U.S. Patent Application agents required to form acceptable foams which are stable Ser. No. 60/.530,015, filed on Dec. 16, 2003, both entitled and possess low specific gravity. Such surfactants, and “Oleaginous Pharmaceutical Foam and both hereby incor particularly ionic Surfactants, such as anionic Surfactants porated in their entirety by reference. (e.g. sodium lauryl sulfate (SDS)), may have adverse affects on certain patients, including concentration-dependent skin FIELD OF THE INVENTION irritation. 0003. The invention relates to foam compositions includ 0011. There remains an unmet need for improved, stable ing cosmetic or therapeutic active agents, and methods of and non-irritating foam formulations and oleaginous foam topical treatment using the compositions. formulations, intended for dermal and mucosal delivery of pharmaceutical and cosmetic, with unique therapeutic and BACKGROUND OF THE INVENTION cosmetic properties. 0004 Certain foam products for topical application of SUMMARY OF THE INVENTION therapeutical agents and cosmetics have been prepared as oil-in-water emulsions. Foams and, in particular, foam com 0012. The invention relates to stable pharmaceutical or positions having a high oil content are complicated systems cosmetic foam compositions containing certain active that do not form under all circumstances. Slight shifts in agents, having unique therapeutic properties and methods of foam composition, Such as the addition of an active ingre treatment using such compositions. The foamable compo dient, may destabilize the foam. It is known in the art that sition includes at least one solvent comprising polyethylene hydrophobic solvents are difficult to formulate into a foam glycol (PEG) or PEG derivative and mixtures thereof, or producing product. Addition of conventional hydrophobic comprising propylene glycol, wherein the solvent is present solvents interferes with the foam forming ability of the at a concentration of about 70% to about 96.5% by weight Surfactant, and thus, in the few foam products containing of the total composition, at least a non-ionic Surface-active high-oil concentrations that have been reported, high Sur agent at a concentration of about 0.1% to less than about factant concentrations are used, which may cause undesir 10% by weight of the total composition. able irritancy on one hand, and costly raw material usage on 0013 The present invention provides stable foam-form the other hand are used. ing compositions, and stable oleaginous foam-forming com 0005 Oleaginous formulations for the preparation of positions including at least one active agent for dermal and cosmetic and therapeutic compositions are known in the art. mucosal delivery. The composition is dispensed as a foam providing a stable product that is pleasant and easy to 0006 U.S. Pat. No. 6,620,773 relates to a foaming oil spread, resulting in high patient compliance. The invention composition, which includes a Surfactant mixture and an oil more particularly relates to a foamable pharmaceutical or component, the Surfactant mixture containing an anionic or cosmetic composition, comprising: Zwitterionic Surfactant, a nonionic Surfactant and at least one ethoxylated alkyl phosphate ester component. The Surfactant 0014 a solvent comprising polyethylene glycol (PEG) or mixture ranges from about 15% to about 50% of the total PEG derivative and mixtures thereof, wherein the PEG or composition, and that of the oil component ranges from PEG derivative is present at a concentration of about 70% to about 50% to about 85%. about 96.5% by weight of the total composition; 0007 U.S. Pat. Nos. 5,700,396 and 5,589,515 disclose a 00.15 a surface-active agent at a concentration of about cosmetic emulsion composition containing 1 to 99 wt % oily 0.1% to less than about 10% by weight of the total compo component (balance aqueous component). The oily compo sition; and nent includes 85% or more weight% of cis A9-octadecanoic acid or derivatives thereof, which serves as a surfactant in 0016 a therapeutically effective amount of at least one the formulation. active agent. US 2008/0063607 A1 Mar. 13, 2008 0017. The invention also relates to a foamable pharma 0034. The invention still further relates to a foamable ceutical or cosmetic carrier composition for dermatological pharmaceutical or cosmetic carrier composition for derma use, comprising: tological use, comprising: 0018 a solvent comprising polyethylene glycol (PEG) or 0035 a solvent comprising propylene glycol, wherein the PEG derivative and mixtures thereof, wherein the PEG or propylene glycol is present at a concentration of about 70% PEG derivative is present at a concentration of about 70% to to about 96.5% by weight of the total composition; and about 96.5% by weight of the total composition; and 0036) a surface-active agent at a concentration of about 0.019 a surface-active agent at a concentration of about 0.1% to less than about 10% by weight of the total compo 0.1% to less than about 10% by weight of the total compo sition. sition. 0037 at least one gelling agent at a concentration of 0020 at least one gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition. about 0.1% to about 5% by weight of the total composition. 0038 at least one liquefied or compressed gas propellant, 0021 at least one liquefied or compressed gas propellant, at a concentration of about 3% to about 25% by weight of at a concentration of about 3% to about 25% by weight of the total composition the total composition wherein the composition is stored in an aerosol container wherein the composition is stored in an aerosol container and upon release expands to form a breakable foam. and upon release expands to form a breakable foam.