US 20080069779A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0069779 A1 Tamarkin et al. (43) Pub. Date: Mar. 20, 2008 (54) FOAMABLE VEHICLE AND VITAMIN AND (60) Provisional application No. 60/843,140, filed on Sep. FLAVONOID PHARMACEUTICAL 8, 2006. Provisional application No. 60/784,793, filed COMPOSITIONS THEREOF on Mar. 21, 2006. Provisional application No. 60/679, 020, filed on May 9, 2005. Provisional application (75) Inventors: Dov Tamarkin, Maccabim (IL); Doron No. 60/530,015, filed on Dec. 16, 2003. Provisional Friedman, Karmei Yosef (IL); Meir application No. 60/492.385, filed on Aug. 4, 2003. Eini, Ness Ziona (IL); Tal Berman, Rishon LeZiyyon (IL); David Schuz, Publication Classification Moshav Gimzu (IL) (51) Int. Cl. Correspondence Address: A6IR 9/12 (2006.01) WILMERHALEABOSTON A6IP 37/00 (2006.01) 6O STATE STREET (52) U.S. Cl. ................................................................ 424/45 BOSTON, MA 02109 (US) (73) Assignee: Foamix Ltd., Ness Ziona (IL) (57) ABSTRACT (21) Appl. No.: 11/900,072 Vitamin and flavonoid containing compositions are provided (22) Filed: Sep. 10, 2007 that are stable to degradation. Stabilized compositions include one or more features including a hygroscopic Sol Related U.S. Application Data vent at a sufficient concentration to provide an Aw value of the hygroscopic Vitamin and or flavonoid containing com (63) Continuation-in-part of application No. 11/430,599, position of less than 0.9, antioxidant flavonoids that are filed on May 9, 2006, and which is a continuation preferentially oxidized before the vitamin, preservatives, in-part of application No. 10/835,505, filed on Apr. and hydrocarbon propellants selected to reduce the oxidation 28, 2004. potential of the composition. US 2008/0069779 A1 Mar. 20, 2008 FOAMABLE VEHICLE AND VITAMIN AND left following their topical application onto the skin, FLAVONOID PHARMACEUTICAL mucosal membranes and wounds. COMPOSITIONS THEREOF 0004 Foams and, in particular, foams that are substan CROSS REFERENCE TO RELATED tially based on non-aqueous solvents are complicated sys tems which do not form under all circumstances. Whilst APPLICATIONS aqueous foam formulations are better known, they are also 0001) This application claims the benefit under 35 U.S.C. complicated and similarly do not form under all circum S119(e) of U.S. Provisional Patent Application No. 60/843, StanceS. 140, filed on Sep. 8, 2006, and U.S. Provisional Patent Application No. TBA, filed on Sep. 4, 2007, each of which 0005 Antioxidants can be protective. Flavonoids are said is entitled "Foamable Vehicle and Vitamin Pharmaceutical to have high antioxidant activity and many health promoting Compositions Thereof.” This application is also a continu effects, including anti-inflammatory and anti-allergic effects ation-in-part application of co-pending U.S. patent applica as well as reducing the risk of cancer and pulmonary disease, tion Ser. No. 11/430,599 filed on May 9, 2006, which claims improved cardiovascular health and prevention of damage the benefit under 35 U.S.C. S 119(e) of U.S. Provisional from free radicals. The use of flavonoids for protecting Patent Application No. 60/679,020, filed on May 9, 2005, ascorbic acid and ascorbyl compounds has been proposed in entitled Hygroscopic Anti-Infective Compositions, and U.S. respect of lotions creams and gels Provisional Patent Application No. 60/784,793, filed on 0006 By using specialized delivery systems like micro Mar. 21, 2006, entitled Polyol Foamable Vehicle and Phar sponges it may be possible to incorporate hydrophobic maceutical Compositions Thereof, and which is also a active ingredients within the microSponges, which active continuation-in-part application of co-pending U.S. patent ingredients are released when the microSponges come into application Ser. No. 10/835,505, filed on Apr. 28, 2004, mechanical contact with the skin. which claims the benefit of priority under 35 U.S.C. S 119(e) to U.S. Provisional Patent Application No. 60/.530,015, filed SUMMARY on Dec. 16, 2003, and U.S. Provisional Patent Application 0007 Compositions containing vitamins and/or fla No. 60/492.385, filed on Aug. 4, 2003, all entitled “Oleagi vonoids or derivative thereof using non-aqueous and aque nous Pharmaceutical Foam; all of which are hereby incor ous carriers and foamable compositions containing them and porated in their entirety by reference. methods of treatment are described. 0008 Hygroscopic and aqueous stable vitamin contain BACKGROUND ing compositions and foamable therapeutic vitamin compo 0002 Vitamins are an essential component of the bodies sitions with and without additional active agents may be daily requirements and they are needed in various metabolic used for treatment of dermal and mucosal tissues are stable. pathways and to maintain good health. Some vitamins are They are non irritating, facilitate penetration at a target, are believed to support, facilitate, improve or optimize the presentable in an easily applicable stable form, can be function and effect of other vitamins and or active agents. handled with ease thereby facilitating compliance and either Compositions which can be applied to the skin, a body minimize or eliminate the amount of free water and in cavity, a mucosal Surface, the nose, the mouth, the eye, the consequence, the potential breakdown of vitamin by oxida ear canal, the respiratory system, the vagina and the rectum tion/hydrolysis, or provide an aqueous environment where that contain an effective amount of one or more vitamins they can resist or are protected from said potential break would be useful. Some vitamins are susceptible to oxidation down. and breakdown in Solution. Vitamins may for example 0009. In one or more embodiments, topical and body breakdown in the presence of water and may not be stable cavity foam formulations containing flavonoids on their own in compositions for Sufficiently long periods of time to and in combination with one or more vitamins are described. facilitate satisfactorily cosmetic and pharmaceutical uses. 0010. In one or more embodiments, topical and body Vitamin absorption is on the other hand also retarded by cavity foam formulations containing microSponges compris Substances like paraffin's and by certain pharmaceuticals. ing one or more active ingredients are provided. In particu 0003 External topical administration is an important lar, the microSponges comprise one or more vitamins or one route for the administration of drugs in disease treatment. or more flavonoids alone or in combination and also with Many groups of drugs, including, for example, antibiotic, other active ingredients. anti-fungal, anti-inflammatory, anesthetic, analgesic, anti allergic, corticosteroid, retinoid and anti-proliferative medi 0011. In other embodiments, the use of flavonoids on cations are preferably administered in hydrophobic media, their own, Synergistically, and in combination with other namely ointment. However, ointments often form an imper active agents is disclosed. meable barrier, so that metabolic products and excreta from 0012. In one or more aspects there is provided a hygro the wounds to which they are applied are not easily removed scopic Vitamin and or flavonoid containing composition or drained away. Furthermore, it is difficult for the active comprising: drug dissolved in the carrier to pass through the white petrolatum barrier layer into the wound tissue, so the effi 0013 a. at least one agent selected from the group cacy of the drug is reduced. In addition, ointments and consisting of Vitamins and flavonoids; creams often do not create an environment for promoting 0014) b. at least one hygroscopic solvent at a sufficient respiration of the wound tissue and it is not favorable to the concentration to provide an AW value of the hygroscopic normal respiration of the skin. An additional disadvantage of Vitamin and or flavonoid containing composition of less than petroleum jelly-based products relates to the greasy feeling 0.9; US 2008/0069779 A1 Mar. 20, 2008 0.015 c. a foam stabilizer selected from the group con 0.01% to about 5% by weight of at least one polymeric agent sisting of at least one surface-active agent; at least one selected from a bioadhesive agent, a gelling agent, a film polymeric agent selected from the group consisting of a forming agent and a phase change agent; and a Surface bioadhesive agent, a gelling agent, a film forming agent and active agent. a phase change agent and mixtures thereof, and 0033. In one or more embodiments, the hygroscopic 0016 d. a propellant at a concentration of about 3% to Substance is selected from the group consisting of polyeth about 25% by weight of the total composition, ylene glycols (PEGs), Surfactants comprising PEG, polyols, 0017 wherein the composition is contained in a pressur monosaccharides, disaccharides, oligosaccharides and Sugar ized container, is substantially flowable and provides a foam alcohols in an amount to provide hygroscopic properties, upon release. and honey. 0018. In one or more aspects there is provided a foamable 0034. In one or more embodiments there is provided a hygroscopic vitamin and or flavonoid containing composi foamable composition comprising a stabilized-vitamin, tion comprising: comprising: 0019 a. at least one agent selected from the group 0035) a water-unstable vitamin; consisting of Vitamins and flavonoids; 0036) an optional flavonoid; and 0020 b. at least one hygroscopic solvent at a sufficient 0037) a foamable carrier comprising: concentration to provide an AW value of the hygro 0038 i. water; Scopic Vitamin and or flavonoid containing composi 0039) ii. a foam stabilizer selected from the group tion of less than 0.9; consisting of at least one surface-active agent; at least 0021 c. a foam stabilizer selected from the group one polymeric agent selected from the group consisting consisting of at least one surface-active agent; and at of a bioadhesive agent, a gelling agent, a film forming least one polymeric agent selected from the group agent and a phase change agent and mixtures thereof; consisting of a bioadhesive agent, a gelling agent, a 0040 iii.