US 200602694.85A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0269485 A1 Friedman et al. (43) Pub. Date: Nov.30, 2006

(54) ANTIBIOTIC KIT AND COMPOSITION AND (60) Provisional application No. 60/492.385, filed on Aug. USES THEREOF 4, 2003. Provisional application No. 60/429.546, filed on Nov. 29, 2002. Provisional application No. 60/688, (75) Inventors: Doron Friedman, Karmei Yosef (IL); 244, filed on Jun. 7, 2005. Alex Besonov, Rehovot (IL); Dov Tamarkin, Maccabim (IL); Meir Eini, Publication Classification Ness Ziona (IL) (51) Int. Cl. Correspondence Address: A6IL 9/04 (2006.01) WILMER CUTLER PICKERING HALE AND (52) U.S. Cl...... 424/45 DORR LLP 6O STATE STREET (57) ABSTRACT BOSTON, MA 02109 (US) The present invention relates to a therapeutic kit to provide a safe and effective dosage of an antibiotic agent, including an aerosol packaging assembly including: a container (73) Assignee: Foamix Ltd., Rehovot (IL) accommodating a pressurized product; and an outlet capable of releasing the pressurized product as a foam, wherein the (21) Appl. No.: 11/448,490 pressurized product comprises a foamable composition (22) Filed: Jun. 7, 2006 including: an antibiotic agent; at least one organic carrier selected from the group consisting of a hydrophobic organic Related U.S. Application Data carrier, an organic polar solvent, an emollient and mixtures thereof, at a concentration of about 2% to about 50% by (63) Continuation-in-part of application No. 10/911.367. weight, a surface-active agent, about 0.01% to about 5% by filed on Aug. 4, 2004. weight of at least one polymeric additive selected from the Continuation-in-part of application No. 10/532,618, group consisting of a bioadhesive agent, a gelling agent, a filed on Dec. 22, 2005, filed as 371 of international film forming agent and a phase change agent, water; and application No. PCT/IB03/05527, filed on Oct. 24, liquefied or compressed gas propellant at a concentration of 2003. about 3% to about 25% by weight of the total composition. Patent Application Publication Nov.30, 2006 US 2006/026948S A1

AEROSOL VALVE VALVESTEM 132 100 N VALVE CUP 110 NNER GASKET 136

120 s

OUTER GASKET

21 130 SPRING134 a VALVE HOUSING

140 DIP TUBE

FIG. 1 US 2006/02694.85 A1 Nov.30, 2006

ANTIBOTC KIT AND COMPOSITION AND USES water and insoluble in both water and the occlusive agent, THEREOF and wherein there is sufficient occlusive agent to form an occlusive layer on the skin. CROSS REFERENCE TO RELATED 0008 U.S. Published Application No. 2004/0151671 pro APPLICATIONS vides pharmaceutical compositions in a pressurized con 0001. This application is a continuation-in-part applica tainer, comprising a quick breaking alcoholic foaming agent. tion of co-pending U.S. patent application Ser. No. 10/532, 618, filed Apr. 25, 2005, which is a national stage application SUMMARY OF THE INVENTION of International Patent Application No. IB03/005527, des 0009. The present invention relates to a therapeutic kit to ignating the United States and filed on Oct. 24, 2003, which provide a safe and effective dosage of an antibiotic agent, claims the benefit of priority under 35 U.S.C. S119(e) to U.S. including an aerosol packaging assembly including: Patent Application Ser. No. 60/429,546, filed on Nov. 29, 2002, both entitled “Cosmetic and Pharmaceutical Foam,” 0010) a) a container accommodating a pressurized and which claims the benefit of priority under 35 U.S.C. product; and S119(a) to Israeli Patent Application No. 152486, filed Oct. 0011 b) an outlet capable of releasing the pressurized 25, 2002, all of which are hereby incorporated in their product as a foam; entirety by reference. 0012 wherein the pressurized product comprises a 0002 This application is a continuation-in-part applica foamable composition including: tion of co-pending U.S. patent application Ser. No. 10/911, 367, filed on Aug. 4, 2004, which claims the benefit of 0013) i. an antibiotic agent; priority under 35 U.S.C. S 119(e) to U.S. Patent Application 0014 ii. at least one organic carrier selected from Ser. No. 60/492.385, filed on Aug. 4, 2003, both entitled the group consisting of a hydrophobic organic car “Foam Carrier Containing Amphiphilic Copolymer Gelling rier, an organic polar solvent, an emollient and Agent” and both hereby incorporated in their entirety by mixtures thereof, at a concentration of about 2% to reference. about 50% by weight; 0003. This application claims the benefit of priority under 0015 iii. a surface-active agent; 35 U.S.C. S119(e) to U.S. Patent Application Ser. No. 60/688,244, filed on Jun. 7, 2005, entitled “Antibiotic Kit 0016 iv. about 0.01% to about 5% by weight of at and Composition and Uses Thereof and hereby incorpo least one polymeric additive selected from the group rated in its entirety by reference. consisting of a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent; BACKGROUND OF THE INVENTION 0017 v. water; and 0004 Antibiotic agents have been used to relieve various 0018 vi. liquefied or compressed gas propellant at a systemic and Superficial disorders. Classical treatment appli concentration of about 3% to about 25% by weight cations include skin infections, vaginal infections, and other of the total composition. disorders that involve a bacterial infection in their etiologi cal factors. 0019. In one or more embodiments, the composition is selected from the group consisting of an oil-in-water emul 0005 Antibiotic agents are available in topical dosage sion and a water-in-oil emulsion. form. Compositions containing antibiotic agents for topical treatment of dermatological disorders are available prima 0020. In one or more embodiments the kit contains a rily in cream, lotion gel and ointment forms. Rubbing valve, which is optionally attached to metered dose device. creams or ointments into the skin is inherently inefficient and 0021. In one or more embodiments the kit further difficult to achieve a constant and balanced application over includes a therapeutically active foam adjuvant is selected large area of skin. Therefore, while semi-solid compositions, from the group consisting of a fatty alcohol having 15 or Such as creams, lotions, gels and ointments are commonly more carbons in their carbon chain; a fatty acid having 16 or used by consumers, new forms are desirable in order to more carbons in their carbon chain; fatty alcohols, derived achieve better control of the application, while maintaining from beeswax and including a mixture of alcohols, a major or bestowing the skin beneficial properties of Such products. ity of which has at least 20 carbon atoms in their carbon Hence, the development of new compositions, having break chain; a fatty alcohol having at least one double bond; a fatty able foam consistency when released from a container and acid having at least one double bond; a branched fatty liquid properties when applied onto the skin is advanta alcohol; a branched fatty acid and a fatty acid substituted geous. with a hydroxyl group. 0006 Foams and, in particular, foam emulsions are com 0022. In one or more embodiments, the composition plicated systems which do not form under all circumstances. further contains a penetration enhancer. Changes in foam emulsion composition, Such as by the 0023 The kit according to the present invention can addition of active ingredients, may destabilize the foam. optionally further contain at least one additional therapeutic 0007 PCT/AU99/00735 teaches a pharmaceutical foam agent selected from the group consisting of a steroidal composition including (a) an active ingredient; (b) an occlu anti-inflammatory agent, an immunosuppressive agent, an sive agent; (c) an aqueous solvent; and (d) an organic immunomodulator, an immunoregulating agent, a hormonal cosolvent, in which the active ingredient is insoluble in agent, an antifungal agent, an antiviral agent, an antiparasitic US 2006/02694.85 A1 Nov.30, 2006

agent, vitamin A, a vitamin A derivative, vitamin B, a salpingitis, oophoritis, genital cancer, cancer of the cervix, vitamin B derivative, vitamin C, a vitamin C derivative, cancer of the Vulva, cancer of the vagina, Vaginal dryness, vitamin D, a vitamin D derivative, vitamin E, a vitamin E dyspareunia, anal and rectal disease, anal abscess/fistula, derivative, vitamin F, a vitamin F derivative, vitamin K, a anal cancer, anal fissure, anal warts, Crohn's disease, hem Vitamin K derivative, a wound healing agent, a disinfectant, orrhoids, anal itch, pruritus ani, fecal incontinence, consti an anesthetic, an antiallergic agent, an alpha hydroxyl acid, pation, polyps of the colon and rectum; lactic acid, glycolic acid, a beta-hydroxy acid, a protein, a peptide, a neuropeptide, a allergen, an immunogenic Sub BRIEF DESCRIPTION OF THE DRAWING stance, a haptene, an oxidizing agent, an antioxidant, a dicarboxylic acid, azelaic acid, sebacic acid, adipic acid, 0.031) The invention is described with reference to the fumaric acid, a retinoid, an antiproliferative agent, an anti figure which is presented for the purpose of illustration and cancer agent, a photodynamic therapy agent, benzoyl chlo are not intended to be limiting of the invention. ride, calcium hypochlorite, magnesium hypochlorite, an 0032 FIG. 1 is a schematic illustration of an aerosol anti-wrinkle agent, a radical scavenger, a metal, silver, a valve Suitable for use in the aerosol packaging assembly metal oxide, titanium dioxide, Zinc oxide, Zirconium oxide, according to in one or more embodiments of the invention. iron oxide, silicone oxide, talc, carbon, an anti wrinkle agent, a skin whitening agent, a skin protective agent, a masking agent, an anti-wart agent, a refatting agent, a DETAILED DESCRIPTION OF THE lubricating agent and mixtures thereof. INVENTION 0024. In further embodiments, the present invention pro 0033. The present invention provides a therapeutic kit vides a method of treating, alleviating or preventing disor including an antibiotic agent. The kit includes an aerosol ders of the skin, body cavity or mucosal surface, wherein the packaging assembly having a container accommodating a disorder involves inflammation as one of its etiological pressurized product and an outlet capable of releasing the factors, including administering topically to a Subject having pressurized product as a foam. the disorder, a foamed composition including: Aerosol Packaging Assembly 0025 (1) an antibiotic agent; 0034. The aerosol packaging assembly typically includes a container Suitable for accommodating a pressurized prod 0026 (2) at least one organic carrier selected from a uct and an outlet capable of releasing a foam. The outlet is hydrophobic organic carrier, a polar solvent, an emol typically a valve. FIG. 1 illustrates a typical aerosol valve lient and mixtures thereof, at a concentration of about 100. The valve is made up of the valve cup 110 typically 2% to about 50% by weight; constructed from tinplated Steel, or aluminum, an outer 0027 (3) about 0.1% to about 5% by weight of a gasket 120, which is the seal between the valve cup and the Surface-active agent; aerosol can (not shown), a valve housing 130, which con tains the valve stem 132, spring 134 and inner gasket 136, 0028 (4) about 0.01% to about 5% by weight of a and a dip tube 140, which allows the liquid to enter valve. polymeric additive selected from a bioadhesive agent, The valve stem is the tap through which the product flows. a gelling agent, a film forming agent and a phase The inner gasket 136 covers the aperture 150 (hole) in the change agent; and valve stem. The valve spring 134 is usually made of stainless 0029 (5) water, steel. wherein the antibiotic agent is administered in a thera 0035) The valve stem is fitted with small apertures 150 peutically effective amount. (also termed "orifices' and “holes'), through which the product flows. Valves may contain one, two, three, four or 0030. In one or more embodiments, the disorder to be more apertures, depending on the nature of the product to be treated is selected from the group consisting of a dermatose, dispensed. In the closed position, the aperture(s) is covered a dermatitis, a vaginal disorder, a Vulvar disorder, an anal by the inner gasket. When the actuator is depressed it pushes disorder, a disorder of a body cavity, an ear disorder, a the valve stem through the inner gasket, and the aperture(s) disorder of the nose, a disorder of the respiratory system, a is uncovered, allowing liquid to pass through the valve and bacterial infection, fungal infection, viral infection, derma into the actuator. tosis, dermatitis, parasitic infections, disorders of hair fol licles and sebaceous glands, Scaling papular diseases, benign 0036) The valve can have a stem with 1 to 4 apertures, or tumors, malignant tumors, reactions to Sunlight, bullous 1 to 2 apertures. Each aperture can have a diameter of about diseases, pigmentation disorders, disorders of cornification, 0.2 mm to about 1 mm, or a diameter of about 0.3 mm to pressure Sores, disorders of Sweating, inflammatory reac about 0.8 mm. The total aperture area, i.e., the Sum of areas tions, Xerosis, ichthyosis, allergy, burn, wound, cut, chlamy of all apertures in a given stem, is between about 0.01 mm dia infection, gonorrhea infection, hepatitis B, herpes, HIV/ and 1 mm or the total aperture area is between about 0.04 AIDS, human papillomavirus (HPV), genital warts, bacterial mm and 0.5 mm. vaginosis, candidiasis, chancroid, granuloma Inguinale, 0037. In order to provide proper therapy, precise dosing lymphogranloma Venereum, mucopurulent cerviciitis is desired. According to one or more embodiments, the valve (MPC), molluscum contagiosum, nongonococcal urethritis is attached, directly, or through a tube, to a metered dose (NGU), trichomoniasis, Vulvar disorders, vulvodynia, Vulvar device, which for dispensing an accurate dose of drug in the pain, yeast infection, Vulvar dystrophy, Vulvar intraepithelial form of a foam. The metered dose valve is selected to release neoplasia (VIN), contact dermatitis, osteoarthritis, joint a foam in a Volume that provides an adequate therapeutic pain, hormonal disorder, pelvic inflammation, endometritis, dose to the target site of the skin, a body Surface, a body US 2006/02694.85 A1 Nov.30, 2006

cavity or mucosal Surface, e.g., the mucosa of the nose, substantially alcohol-free and includes less than about 5% mouth, eye, ear, respiratory system, vagina or rectum. final concentration of lower alcohols, preferably less than 0038. In one or more embodiments, the meter dose valve about 2%, more preferably less than about 1%. provides a unit dose of between about 10 uL and about 1000 0048. In one or more embodiments, the foam composi LL. Assuming a representative foam density (specific grav tion is formulated as an oil-in-water emulsion or oil-in-water ity) of 0.06 g/mL, a 10 LL valve provides a volume of about microemulsion, yet, in additional embodiments, the foam 0.17 mL of foam, and a 1000 uL metered dose valve composition is formulated as an water-in-oil emulsion or provides about 17 mL of foam. Thus, by selecting a specific water-in-oil microemulsion. metered dosing valve and adjusting the foam density by fine tuning formulation parameters and adjusting the ratio 0049. In one or more embodiments, the concentration of between the liquid components of the composition and the surface-active agent about 0.1% to about 5%, or from about propellant, one can design an adequate dosage form accord 0.2% to about 2%. ing to the specific target site. Exemplary metered dose 0050. In the context of the present invention, an antibiotic devices may be found in co-pending application Ser. No. agent is a Substance that has the capacity to inhibit the 11/406,133, entitled “Apparatus and Method for Releasing a growth of or to destroy bacteria and other microorganisms. Measured Amount of Content from a Container, filed Apr. 0051. In one or more embodiments, the antibiotic agent is 18, 2006, which is hereby incorporated in its entirety by selected from the classes consisting of beta-lactam antibi reference. otics, aminoglycosides, ansa-type antibiotics, anthraquino Pharmaceutical Composition nes, antibiotic azoles, antibiotic glycopeptides, macrollides, antibiotic nucleosides, antibiotic peptides, antibiotic poly 0.039 All % values are provided on a weight (w/w) basis. enes, antibiotic polyethers, quinolones, antibiotic steroids, 0040 According to one or more embodiments of the Sulfonamides, tetracycline, dicarboxylic acids, antibiotic present invention, the foamable therapeutic composition for metals, oxidizing agents, Substances that release free radi administration to the skin, a body Surface, a body cavity, a cals and/or active oxygen, cationic antimicrobial agents, mucosal Surface, the nose, the mouth, the eye, the ear canal, quaternary ammonium compounds, biguanides, triguanides, the respiratory system, the vagina and the rectum (severally bisbiguanides and analogs and polymers thereof and natu and interchangeably termed herein “target site') includes: rally occurring antibiotic compounds. 0041 (1) an antibiotic agent, wherein the antibiotic 0.052 Beta-lactam antibiotics include, but are not limited agent is effective in the treatment of a disorder of the to, 2-(3-alanyl)clavam, 2-hydroxymethylclavam, 8-epi-thie target site; namycin, acetyl-thienamycin, amoxicillin, amoxicillin Sodium, amoxicillin trihydrate, amoxicillin-potassium cla 0042 (2) at least one organic carrier selected from a Vulanate combination, amplicillin, amplicillin sodium, ampi hydrophobic organic carrier, a polar solvent, an emol cillin trihydrate, amplicillin-Sulbactam, apalcillin, aspoxicil lient and mixtures thereof, at a concentration of about lin, azidocillin, azlocillin, aztreonam, bacampicillin, 2% to about 5%, or about 5% to about 10%; or about biapenem, carbenicillin, carbenicillin disodium, carfecillin, 10% to about 20%; or about 20% to about 50% by carindacillin, carpetimycin, cefacetril, cefaclor, cefadroxil, weight; cefalexin, cefaloridine, cefalotin, cefamandole, cefaman 0.043 (3) about 0.1% to about 5% by weight of a dole, cefapirin, cefatrizine, cefatrizine propylene glycol, Surface-active agent; cefazedone, cefazolin, cefbuperaZone, cefcapene, cefcapene pivoxil hydrochloride, cefdinir, cefditoren, cefditoren piv 0044) (4) about 0.01% to about 5% by weight of at oxil, cefepime, cefetamet, cefetamet pivoxil, cefixime, least one polymeric agent selected from a bioadhesive cefinenoXime, cefinetazole, cefiminox, cefiminox, cef agent, a gelling agent, a film forming agent and a phase molexin, cefodizime, cefonicid, cefoperaZone, ceforanide, change agent; and cefoselis, cefotaxime, cefotetan, cefotiam, cefoxitin, cefo 0045 (5) a liquefied or compressed gas propellant at a Zopran, cefpiramide, ce?pirome, cefpodoxime, cefpodoxime concentration of about 3% to about 25% by weight of proxetil, cefprozil, cefiguinome, cefradine, cefroxadine, cef the total composition. Sulodin, ceftazidime, cefteram, cefteram pivoxil, ceftezole, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime, 0046) Water and optional ingredients are added to com cefuroxime axetil, cephalosporin, cephamycin, chitinovorin, plete the total mass to 100%. Upon release from an aerosol ciclacillin, clavulanic acid, clometocillin, cloxacillin, container, the foamable composition forms an expanded cycloserine, deoxy pluracidomycin, dicloxacillin, dihydro foam Suitable for topical administration. pluracidomycin, epicillin, epithienamycin, ertapenem, faro 0047 According to one or more embodiments, the foam penem, flomoxef flucloxacillin, hetacillin, imipenem, lena able composition is substantially alcohol-free, i.e., free of mpicillin, loracarbef mecillinam, meropenem, metampicil short chain alcohols. Short chain alcohols, having up to 5 lin, meticillin, meZlocillin, moxalactam, nafcillin, carbon atoms in their carbon chain skeleton and one northienamycin, oxacillin, panipenem, penamecillin, peni hydroxyl group. Such as ethanol, propanol, isopropanol, cillin, phenethicillin, piperacillin, taZobactam, pivampicil butanol, iso-butanol, t-butanol and pentanol, are considered lin, pivoefalexin, pivmecillinam, pivmecillinam hydrochlo less desirable solvents or polar solvents due to their skin ride, pluracidomycin, propicillin, Sarmoxicillin, Sulbactam, irritating effect. This disadvantage is particularly meaningful Sulbenicillin, talampicillin, temocillin, terconazole, thiena in the case of an antibiotic treatment, which is often directed mycin, ticarcillin and analogs, salts and derivatives thereof. to open wounds and damaged skin and mucosal tissues. 0053 Aminoglycosides include, but are not limited to, Thus, in one or more embodiments, the composition is 1,2'-N-DL-isoseryl-3',4'-dideoxykanamycin B, 1,2'-N-DL US 2006/02694.85 A1 Nov.30, 2006 isoseryl-kanamycin B, 1,2'-N-(S)-4-amino-2-hydroxybu mycin, nebramycin, neomycin, netilmicin, oligostatin, tyryl-3',4'-dideoxykanamycin B, 1,2'-N-(S)-4-amino-2-hy paromomycin, quintomycin, ribostamycin, Saccharocin, sel droxybutyryl-kanamycin B, 1-N-(2-Aminobutanesulfonyl) domycin, sisomicin, Sorbistin, spectinomycin, Streptomycin, kanamycin A, 1-N-(2-aminoethanesulfonyl)3',4'-dideoxyri tobramycin, trehaloSmaine, trestatin, validamycin, Verdamy bostamycin, 1-N-(2-Aminoethanesulfonyl)3'-deoxyribosta cin, Xylostasin, Zygomycin and analogs, salts and derivatives mycin, 1-N-(2-aminoethanesulfonyl)3'4'-dideoxykanamy thereof. cin B, 1-N-(2-aminoethanesulfonyl)kanamycin A, 1-N-(2- 0054 Ansa-type antibiotics include, but are not limited aminoethanesulfonyl)kanamycin B, 1-N-(2- to, 21-hydroxy-25-demethyl-25-methylthioprotostreptova aminoethanesulfonyl)ribostamycin, 1-N-(2- ricin, 3-methylth iorifamycin, ansamitocin, atropisostrepto aminopropanesulfonyl)3'-deoxykanamycin B, 1-N-(2- Varicin, awamycin, halomicin, maytansine, naphthomycin, aminopropanesulfonyl)3'4'-dideoxykanamycin B, 1-N-(2- rifabutin, rifamide, rifampicin, rifamycin, rifapentine, rifaxi aminopropanesulfonyl)kanamycin A, 1-N-(2- min, rubradirin, Streptovaricin, tolypomycin and analogs, aminopropanesulfonyl)kanamycin B, 1-N-(L-4-amino-2- salts and derivatives thereof. hydroxy-butyryl)2,3'-dideoxy-2'-fluorokanamycin A, 1-N- 0055 Antibiotic anthraquinones include, but are not lim (L-4-amino-2-hydroxy-propionyl)2,3'-dideoxy-2'- ited to, auramycin, cinerubin, ditrisarubicin, ditrisarubicin fluorokanamycin A, 1-N-DL-3',4'-dideoxy C. figaroic acid fragilomycin, minomycin, rabelomycin, isoserylkanamycin B, 1-N-DL-isoserylkanamycin, 1-N-DL isoserylkanamycin B, 1-N-L-(-)-(alpha-hydroxy-gamma rudolfomycin, Sulfurmycin and analogs, salts and deriva aminobutyryl)-XK-62-2,2',3'-dideoxy-2'-fluorokanamycin tives thereof. A.2-hydroxygentamycin A3.2-hydroxygentamycin B, 2-hy 0056 Antibiotic azoles include, but are not limited to, droxygentamycin B1, 2-hydroxygentamycin JI-20A 2-hy aZanidazole, bifonazole, butoconazol, chlormidazole, chlo droxygentamycin JI-20B, 3"-N-methyl-4"-C-methyl-3',4'- rmidazole hydrochloride, cloconazole, cloconazole mono dodeoxy kanamycin A, 3"-N-methyl-4"-C-methyl-3',4'- hydrochloride, clotrimaZol, dimetridazole, econazole, dodeoxy kanamycin B, 3"-N-methyl-4"-C-methyl-3',4'- econazole nitrate, enilconazole, fenticonazole, fenticonazole dodeoxy-6'-methyl kanamycin B, 3',4'-Dideoxy-3'-eno nitrate, fezatione, fluconazole, flutrimazole, isoconazole, ribostamycin.3',4'-dideoxyneamine.3',4'- isoconazole nitrate, itraconazole, ketoconazole, lanocona dideoxyribostamycin, 3'-deoxy-6'-N-methyl-kanamycin Zole, metronidazole, metronidazole benzoate, miconazole, B.3'-deoxyneamine.3'-deoxyribostamycin, 3'-oxysaccharo miconazole nitrate, neticonazole, nimorazole, niridazole, cin.3,3'-nepotrehalosadiamine, 3-demethoxy-2"-N-formim omoconazol, ornidazole, oxiconazole, Oxiconazole nitrate, idoylistamycin B disulfate tetrahydrate, 3-demethoxyista propenidazole, secnidazol, Sertaconazole, Sertaconazole mycin B.3-O-demethyl-2-N-formimidoylistamycin B, 3-O- nitrate, Sulconazole, Sulconazole nitrate, tinidazole, tiocona demethylistamycin B,3-trehalosamine,4",6"- Zole, Voriconazol and analogs, salts and derivatives thereof. dideoxydibekacin, 4-N-glycyl-KA-6606VI, 5"-Amino-3',4', 0057 Antibiotic glycopeptides include, but are not lim 5'-trideoxy-butirosin A, 6'-deoxydibekacin,6'-epifortimicin ited to, acanthomycin, actaplanin, avoparcin, balhimycin, A. 6-deoxy-neomycin (structure 6-deoxy-neomycin B),6- bleomycin B (copper bleomycin), chloroorienticin, chlo deoxy-neomycin B, 6-deoxy-neomycin C, 6-deoxy-paromo ropolysporin, demethylvancomycin, enduracidin, galacar mycin, acmimycin, AHB-3',4'-dideoxyribostamycin, AHB din, guanidylfungin, hachimycin, demethylvancomycin, 3'-deoxykanamycin B, AHB-3'-deoxyneamine, AHB-3'- N-nonanoyl-teicoplanin, phleomycin, platomycin, ristoce deoxyribostamycin, AHB-4'-6"-dideoxydibekacin, AHB tin, staphylocidin, talisomycin, teicoplanin, Vancomycin, 6'-deoxydibekacin, AHB-dideoxyneamine, AHB Victomycin, Xylocandin, Zorbamycin and analogs, salts and kanamycin B, AHB-methyl-3'-deoxykanamycin B, derivatives thereof. amikacin, amikacin Sulfate, apramycin, arbekacin, astromi cin, astromicin Sulfate, bekanamycin, bluenSomycin, bohol 0058 Macrollides include, but are not limited to, mycin, butirosin, butirosin B, catenulin, coumamidine acetylleucomycin, acetylkitasamycin, angolamycin, azithro gammal, coumamidine gamma2.D.L-1-N-(alpha-hydroxy mycin, bafilomycin, brefeldin, carbomycin, chalcomycin, beta-aminopropionyl)-XK-62-2, dactimicin, de-O-methyl cirramycin, clarithromycin, concanamycin, deisovaleryl 4-N-glycyl-KA-6606VI, de-O-methyl-KA-6606I, de-O-me niddamycin, demycinosyl-mycinamycin, Di-O-methylti thyl-KA-7038I, destomycin A, destomycin B, di-N6'O3 acumicidin, dirithromycin, erythromycin, erythromycin demethylistamycin A, dibekacin, dibekacin Sulfate, estolate, erythromycin ethyl Succinate, erythromycin lacto dihydrostreptomycin, dihydrostreptomycin Sulfate, epi-for bionate, erythromycin Stearate, flurithromycin, focusin, mamidoylglycidylfortimicin B, epihygromycin, formim foromacidin, haterumalide, haterumalide, josamycin, josa idoyl-istamycin A, formimidoyl-istamycin B, fortimicin B, mycin ropionate, juvenimycin, juvenimycin, kitasamycin, fortimicin C, fortimicin D, fortimicin KE, fortimicin KF, ketotiacumicin, lankavacidin, lankavamycin, leucomycin, fortimicin KG, fortimicin KG 1 (stereoisomer KG1/KG2), machecin, maridomycin, megalomicin, methyleucomycin, fortimicin KG2 (stereoisomer KG1/KG2), fortimicin KG3, methymycin, midecamycin, miocamycin, mycaminosylty framycetin, framycetin Sulphate, gentamicin, gentamycin lactone, mycinomycin, neutramycin, niddamycin, nonactin, Sulfate, globeomycin, hybrimycin A1, hybrimycin A2, oleandomycin, phenylacetylideltamycin, pamamycin, picro hybrimycin B1, hybrimycin B2, hybrimycin C1, hybrimycin mycin, rokitamycin, rosaramicin, roXithromycin, sedecamy C2, hydroxyStreptomycin, hygromycin, hygromycin B, cin, shincomycin, spiramycin, Swalpamycin, tacrolimus, isepamicin, isepamicin Sulfate, istamycin, kanamycin, kana telithromycin, tiacumicin, tilmicosin, treponemycin, trole mycin Sulphate, kasugamycin, lividomycin, marcomycin, andomycin, tylosin, Venturicidin and analogs, salts and micronomicin, micronomicin Sulfate, mutamicin, myomy derivatives thereof. cin, N-demethyl-7-O-demethylcelesticetin, demethylceles 0059 Antibiotic nucleosides include, but are not limited ticetin, methanesulfonic acid derivative of istamycin, nebra to, amicetin, angustmycin, azathymidine, blasticidin S. US 2006/02694.85 A1 Nov.30, 2006 epiroprim, flucytosine, gougerotin, mildiomycin, nikkomy enrofloxacin, fleroxacin, flumequine, gatifloxacin, gemi cin, nucleocidin, oxanosine, oxanosine, puromycin, pyrazo floxacin, grepafloxacin, levofloxacin, lomefloxacin, lom mycin, showdomycin, sinefungin, sparsogenin, Spicamycin, efloxacin, hydrochloride, miloxacin, moxifloxacin, nadi tunicamycin, uracil polyoxin, Vengicide and analogs, salts floxacin, nalidixic acid, nifuroquine, norfloxacin, ofloxacin, and derivatives thereof. orbifloxacin, oxolinic acid, paZufloxacine, pefloxacin, 0060 Antibiotic peptides include, but are not limited to, pefloxacin mesylate, pipemidic acid, piromidic acid, prema actinomycin, aculeacin, alaZopeptin, amfomycin, amythia floxacin, roSoxacin, rufloxacin, sparfloxacin, temafloxacin, mycin, antifungal from Zalerion arboricola, antrimycin, to Sufloxacin, trovafloxacin and analogs, salts and derivatives apid, apidaecin, aspartocin, auromomycin, bacileucin, bacil thereof. lomycin, bacillopeptin, bacitracin, bagacidin, beminamycin, 0065 Antibiotic steroids include, but are not limited to, beta-alanyl-L-tyrosine, bottromycin, capreomycin, caspo aminosterol, ascosteroside, cladosporide A, dihydrofusidic fungine, cepacidine, cerexin, cillofungin, circulin, colistin, acid, dehydro-dihydrofusidic acid, dehydrofusidic acid, cyclodepsipeptide, cytophagin, dactinomycin, daptomycin, fusidic acid, squalamine and analogs, salts and derivatives decapeptide, desoxymulundocandin, echanomycin, echi thereof. nocandin B, echinomycin, ecomycin, enniatin, etamycin, fabatin, ferrimycin, ferrimycin, ficellomycin, fluorono 0066 Sulfonamides include, but are not limited to, cathiacin, fusaricidin, gardimycin, gatavalin, globopeptin, chloramine, dapsone, mafenide, phthalylsulfathiazole. Suc glyphomycin, gramicidin, herbicolin, iomycin, iturin, iyo cinylsulfathiazole, Sulfabenzamide, Sulfacetamide, Sul mycin, iZupeptin, janiemycin, janthinocin, jolipeptin, fachlorpyridazine, Sulfadiazine, Sulfadiazine silver, Sulfadi katanosin, killertoxin, lipopeptide antibiotic, lipopeptide cramide, Sulfadimethoxine, Sulfadoxine, Sulfaguanidine, from Zalerion sp., lysobactin, lysozyme, macromomycin, Sulfalene, SulfamaZone, Sulfamerazine, Sulfamethazine, Sul magainin, melittin, mersacidin, mikamycin, mureidomycin, famethizole, Sulfamethoxazole, Sulfamethoxypyridazine, mycoplanecin, mycosubtilin, neopeptifluorin, neovirido Sulfamonomethoxine, SulfamoXol, Sulfanilamide, Sulfa grisein, netropsin, nisin, nocathiacin, nocathiacin 6-deoxyg perine, Sulfaphenazol, Sulfapyridine, Sulfaquinoxaline, Sul lycoside, nosiheptide, octapeptin, pacidamycin, pentade fasuccinamide, Sulfathiazole, Sulfathiourea, Sulfatolamide, capeptide, peptifluorin, permetin, phytoactin, phytostreptin, Sulfatriazin, Sulfisomidine, Sulfisoxazole, Sulfisoxazole planothiocin, plusbacin, polcillin, polymyxin antibiotic acetyl, Sulfacarbamide and analogs, salts and derivatives complex, polymyxin B, polymyxin B1, polymyxin F. pre thereof. neocarzinostatin, quinomycin, quinupristin-dalfopristin, 0067 Tetracyclines include, but are not limited to, dihy safracin, Salmycin, salmycin, salmycin, sandramycin, Sara drosteflimycin, demethyltetracycline, aclacinomycin, mycetin, siomycin, sperabillin, sporamycin, a streptomyces akrobomycin, baumycin, bromotetracycline, cetocyclin, compound, Subtilin, teicoplanin aglycone, telomycin, ther chlortetracycline, clomocycline, daunorubicin, demeclocy mothiocin, thiopeptin, thiostrepton, tridecaptin, tsushimy cline, doxorubicin, doxorubicin hydrochloride, doxycycline, cin, tuberactinomycin, tuberactinomycin, tyrothricin, Vali lymecyclin, marcellomycin, meclocycline, meclocycline nomycin, viomycin, Virginiamycin, Zervacin and analogs, Sulfosalicylate, methacycline, minocycline, minocycline salts and derivatives thereof. hydrochloride, musettamycin, oxytetracycline, rhodirubin, 0061. In one or more embodiments, the antibiotic peptide rolitetracycline, rubomycin, serirubicin, Steflimycin, tetra is a naturally-occurring peptide that possesses an antibacte cycline and analogs, salts and derivatives thereof. rial and/or an antifungal activity. Such peptide can be obtained from a herbal or a vertebrate source. 0068 Dicarboxylic acids, having between about 6 and about 14 carbon atoms in their carbon atom skeleton are 0062 Polyenes include, but are not limited to, amphot particularly useful in the treatment of disorders of the skin ericin, amphotericin, aureofungin, ayfactin, azalomycin, and mucosal membranes that involve microbial. Suitable blasticidin, candicidin, candicidin methyl ester, candimycin, dicarboxylic acid moieties include, but are not limited to, candimycin methyl ester, chinopricin, filipin, flavofungin, adipic acid, pimelic acid, Suberic acid, azelaic acid, sebacic fradicin, hamycin, hydropricin, levorin, lucensomycin, luc acid, 1,11-undecanedioic acid, 1,12-dodecanedioic acid, knomycin, mediocidin, mediocidin methyl ester, mepartri 1,13-tridecanedioic acid and 1,14-tetradecanedioic acid. cin, methylamphotericin, natamycin, niphimycin, nystatin, Thus, in one or more embodiments of the present invention, nystatin methyl ester, oxypricin, partricin, pentamycin, peri dicarboxylic acids, having between about 6 and about 14 mycin, pimaricin, primycin, proticin, rimocidin, sistomy carbon atoms in their carbon atom skeleton, as well as their cosin, Sorangicin, trichomycin and analogs, salts and deriva salts and derivatives (e.g., esters, amides, mercapto-deriva tives thereof. tives, anhydraides), are useful immunomodulators in the 0063 Polyethers include, but are not limited to, treatment of disorders of the skin and mucosal membranes 20-deoxy-epi-narasin, 20-deoxysalinomycin, carriomycin, that involve inflammation. AZelaic acid and its salts and dianemycin, dihydrolonomycin, etheromycin, ionomycin, derivatives are preferred. It has antibacterial effects on both aerobic and anaerobic organisms, particularly propionibac iso-lasalocid, lasalocid, lenoremycin, lonomycin, lysocellin, terium acnes and Staphylococcus epidermidis, normalizes monensin, narasin, oxolonomycin, a polycyclic ether anti keratinization, and has a cytotoxic effect on malignant or biotic, salinomycin and analogs, salts and derivatives hyperactive melanocytes. In a preferred embodiment, the thereof. dicarboxylic acid is azelaic acid in a concentration greater 0064 Quinolones include, but are not limited to, an than 10%. Preferably, the concentration of azelaic acid is alkyl-methylendioxy-4-(1H)-oxocinnoline-3-carboxylic between about 10% and about 25%. In such concentrates, acid, alatrofloxacin, cinoxacin, ciprofloxacin, ciprofloxacin azelaic acid is suitable for the treatment of a variety of skin hydrochloride, danofloxacin, dermofongin A, enoxacin, disorders, such as acne, rosacea and hyperpigmentation. US 2006/02694.85 A1 Nov.30, 2006

0069. In one or more embodiments, the antibiotic agent is 0075. In one or more embodiments, the antibiotic agent is an antibiotic metal. A number of metals ions been shown to selected from the group of biguanides, triguanides, bisbigu possess antibiotic activity, including silver, copper, Zinc, anides and analogs thereof. mercury, tin, lead, bismutin, cadmium, chromium and ions thereof. It has been theorized that these antibiotic metal ions 0076 Guanides, biguanides, biguanidines and exert their effects by disrupting respiration and electron triguanides are unsaturated nitrogen containing molecules transport systems upon absorption into bacterial or fungal that readily obtain one or more positive charges, which make cells. Anti-microbial metal ions of silver, copper, Zinc, and them effective antimicrobial agents. The basic structures a gold, in particular, are considered safe for in vivo use. guanide, a biguanide, a biguanidine and a triguanide are Anti-microbial silver and silver ions are particularly useful provided below. due to the fact that they are not substantially absorbed into the body. 4 2 2 HN NH NH 0070 Thus, in one or more embodiment, the antibiotic 4 6 metal consists of an elemental metal, selected from the group consisting of silver, copper, Zinc, mercury, tin, lead, HNul HNus NH2 H2Nus HN --- i. 3 bismutin, cadmium, chromium and gold, which is suspended Biguanide NH in the composition as particles, microparticles, nanoparticles 5 or colloidal particles. The antibiotic metal can further be Biguanidine intercalated in a chelating Substrate. 6 4 2 0071. In further embodiments, the antibiotic metal is NH NH NH ionic. The ionic antibiotic metal can be presented as an 7 ls 5 l 3 l inorganic or organic salt (coupled with a counterion), an HN HN HN NH organometallic complex or an intercalate. Non binding Triguanide examples of counter inorganic and organic ions are sulfa diazine, acetate, benzoate, carbonate, iodate, iodide, lactate, laurate, nitrate, oxide, palmitate, a negatively charged pro 0077. In one or more preferred embodiments, the tein. In preferred embodiments, the antibiotic metal salt is a guanide, biguanide, biguanidine or triguanide, provide bi silver salt, Such as silver acetate, silver benzoate, silver polar configurations of cationic and hydrophobic domains carbonate, silver iodate, silver iodide, silver lactate, silver within a single molecule. laurate, silver nitrate, silver oxide, silver palmitate, silver protein, and silver Sulfadiazine. 0078 Examples of guanides, biguanides, biguanidines and triguanides that are currently been used as antibacterial 0072. In one or more embodiments, the antibiotic metal agents include chlorhexidine and chlorohexidine salts, ana or metalion is embedded into a Substrate. Such as a polymer, logs and derivatives, such as chlorhexidine acetate, chlo a mineral (such as Zeolite, clay and silica). rhexidine gluconate and chlorhexidine hydrochloride, 0073. Oxidizing agents and substances that release free picloxydine, alexidine and polihexanide. Other examples of radicals and/or active oxygen. In one or more embodiments, guanides, biguanides, biguanidines and triguanides that can the antibiotic agent comprises strong oxidants and free conceivably be used according to the present invention are radical liberating compounds, such as oxygen, hydrogen chlorproguanil hydrochloride, proguanil hydrochloride (cur peroxide, benzoyl peroxide, elemental halogen species, as rently used as antimalarial agents), meformin hydrochlo well as Oxygenated halogen species, bleaching agents (e.g., ride, phenformin and buformin hydrochloride (currently Sodium, calcium or magnesium hypochloride and the like), perchlorite species, iodine, iodate, and benzoyl peroxide. used as antidiabetic agents). Organic oxidizing agents are also included in the definition 0079. In one or more embodiments, the cationic antimi of “oxidizing agent according to the present invention, Such crobial agent is a polymer. as quinones. Such agents possess a potent broad-spectrum 0080 Cationic antimicrobial polymers include, for activity example, guanide polymers, biguanide polymers, or poly 0074. In one or more embodiments the antibiotic agent is mers having side chains containing biguanide moieties or a cationic antimicrobial agent. The outermost surface of other cationic functional groups. Such as benzalkonium bacterial cells universally carries a net negative charge, groups or quarternium groups (e.g., quaternary amine making them sensitive to cationic Substances. Examples of groups). It is understood that the term “polymer as used cationic antibiotic agents include: quaternary ammonium herein includes any organic material comprising three or compounds (QAC’s)—QAC's are surfactants, generally more repeating units, and includes oligomers, polymers, containing one quaternary nitrogen associated with at least copolymers, block copolymers, terpolymers, etc. The poly one major hydrophobic moiety; alkyltrimethyl ammonium merbackbone may be, for example a polyethylene, ploypro bromides are mixtures of where the alkyl group is between pylene or polysilane polymer. 8 and 18 carbons long, such as cetrimide (tetradecyltrim ethylammonium bromide); benzalkonium chloride, which is 0081. In one or more embodiments, the cationic antimi a mixture of n-alkyldimethylbenzyl ammonium chloride crobial polymer is a polymeric biguanide compound. When where the alkyl groups (the hydrophobic moiety) can be of applied to a Substrate. Such a polymer is known to form a variable length; dialkylmethyl ammonium halides; dialkyl barrier film that can engage and disrupt a microorganism. An benzyl ammonium halides; and QAC dimmers, which bear exemplary polymeric biguanide compound is polyhexam bi-polar positive charges in conjunction with interstitial ethylene biguanide (PHMB) salts. Other exemplary bigu hydrophobic regions. anide polymers include, but are not limited to poly(hexam US 2006/02694.85 A1 Nov.30, 2006 ethylenebiguanide), poly(hexamethylenebiguanide) cin, prop-2-enylmonate, protomycin, pseudomonas antibi hydrochloride, poly(hexamethylenebiguanide) gluconate, otic, pseudomonic acid, purpuromycin, pyrinodemin, pyr poly(hexamethylenebiguanide) Stearate, or a derivative rolnitrin, pyrrolomycin, amino, chloro pentenedioic acid, thereof. In one or more embodiments, the antimicrobial rapamycin, rebeccamycin, resistomycin, reuterin, reveromy material is substantially water-insoluble. cin, rhizocticin, roridin, rubiflavin, naphthyridinomycin, saframycin, Saphenamycin, Sarkomycin, Sarkomycin, sclo 0082 Yet, in one or more embodiment, the antibiotic is a pularin, selenomycin, siccanin, Spartanamicin, spectinomy non-classified antibiotic agent, including, without limitation, cin, Spongistatin, Stravidin, streptolydigin, streptomyces are aabomycin, acetomycin, acetoxycycloheximide, acetylnan nae antibiotic complex, Streptonigrin, streptothricins, aomycin, an actinoplanes sp. Compound, actinopyrone, afl streptovitacin, streptozotocine, a strobilurin derivative, astatin, albacarcin, albacarcin, albofungin, albofungin, alisa stubomycin, Sulfamethoxazol-trimethoprim, Sakamycin, mycin, alpha-R.S.-methoxycarbonylbenzylmonate, teeramycin, terpentecin, tetrocarcin, thermorubin, ther altromycin, amicetin, amycin, amycin demanoyl compound, moZymocidin, thiamphenicol, thioaurin, thiolutin, thiomar amycine, amycomycin, anandimycin, anisomycin, anthra inol, thiomarinol, tirandamycin, tolytoxin, trichodermin, mycin, anti-Syphilis imune Substance, anti-tuberculosis trienomycin, trimethoprim, trioxacarcin, tyrissamycin, imune Substance, antibiotic from Eschericia coli, antibiotics umbrinomycin, unphenelfamycin, urauchimycin, usnic acid, from Streptomyces refitineus, anticapsin, antimycin, aplas uredolysin, variotin, Vermisporin, Verrucarin and analogs, momycin, aranorosin, aranorosinol, arugomycin, ascofura none, ascomycin, ascosin, Aspergillus flavus antibiotic, salts and derivatives thereof. asukamycin, aurantinin, an Aureolic acid antibiotic Sub 0083. In one or more embodiments, the antibiotic agent is stance, aurodox, avilamycin, azidamfenicol, azidimycin, a naturally occurring antibiotic compound. As used herein, bacillaene, a Bacillus larvae antibiotic, bactobolin, benano the term “naturally-occurring antibiotic agent” includes all mycin, benzanthrin, benzylmonate, bicoZamycin, bravomi antibiotic that are obtained, derived or extracted from plant cin, brodimoprim, butalactin, calcimycin, calvatic acid, can or vertebrate sources. Non-limiting examples of families of diplanecin, carumonam, carzinophilin, celesticetin, cepacin, naturally-occurring antibiotic agents include phenol, resor cerulenin, cervinomycin, chartreusin, chloramphenicol, cinol, antibiotic aminoglycosides, anamycin, quinines, chloramphenicol palmitate, chloramphenicol Succinate anthraquinones, antibiotic glycopeptides, azoles, mac Sodium, chlorflavonin, chlorobiocin, chlorocarcin, chromo rolides, avilamycin, agropyrene, cnicin, aucubin antibiotic mycin, ciclopiroX, ciclopiroX olamine, citreamicin, cla saponin fractions, berberine (isoquinoline alkaloid), arc dosporin, claZamycin, clecarmycin, clindamycin, tiopicrin (sesquiterpene lactone), lupulone, humulone (bitter coliformin, collinomycin, copiamycin, corallopyronin, acids), allicin, hyperforin, echinacoside, coniosetin, tetramic corynecandin, coumermycin, culpin, cuprimyxin, cyclami acid, imanine and novoimanine. domycin, cycloheximide, dactylomycin, danomycin, danubomycin, delaminomycin, demethoxyrapamycin, dem 0084 Ciclopirox and ciclopiroxolamine possess fungi ethylscytophycin, dermadin, desdamethine, dexylosyl-bena cidal, fungistatic and sporicidal activity. They are active nomycin, pseudoaglycone, dihydromocimycin, dihydronan against a broad spectrum of dermatophytes, yeasts, moulds cimycin, diumycin, dnacin, dorrigocin, dynemycin, and other fungi. Such as trichophyton species, microsporum dynemycin triacetate, ecteinascidin, efrotomycin, endomy species, epidermophyton species and yeasts (candida albi cin, ensanchomycin, equisetin, ericamycin, esperamicin, cans, candida glabrata, other candida species and crypto ethylmonate, everninomicin, feldamycin, flambamycin, fla coccus neoformans). Some aspergillus species are sensitive vensomycin, florfenicol, fluvomycin, fosfomycin, fos to ciclopiroX as are some penicillium. Likewise, ciclopiroX fonochlorin, fredericamycin, frenolicin, fumagillin, fumi is effective against many gram-positive and gram-negative fungin, funginon, fusacandin, fusafungin, gelbecidine, bacteria (e.g., escherichia coli, proteus mirabilis, pseudomo glidobactin, grahamimycin, granaticin, griseofulvin, nas aeruginosa, Staphylococcus and Streptococcus species). griseoviridin, grisonomycin, hayumicin, hayumicin, hazy as well as mycoplasma species, trichomonas vaginalis and micin, hedamycin, heneicomycin, heptelicid acid, holomy actinomyces. cin, humidin, isohematinic acid, karnatakin, kazusamycin, 0085 Plant oils and extracts which contain antibiotic kristenin, L-dihydrophenylalanine, a L-isoleucyl-L-2- agents are also useful. Non limiting examples of plants that amino-4-(4-amino-2',5'-cyclohexadienyl) derivative, lano contain agents include thyme, perilla, lavender, tea tree, mycin, leinamycin, leptomycin, libanomycin, lincomycin, terfezia clayeryi, Micromonospora, putterlickia verrucosa, lomofungin, lysolipin, magnesidin, manumycin, melanomy putterlickia pyracantha putterlickia retroSpinosa, Maytenus cin, methoxycarbonylmethylmonate, methoxycarbonyleth ilicifolia, maytenus evonymoides., maytenus aquifolia, fae ylmonate, methoxycarbonylphenylmonate, methyl nia interjecta, cordyceps sinensis, couchgrass, holy thistle, pseudomonate, methylmonate, microcin, mitomalcin, moci plantain, burdock, hops, echinacea, buchu, chaparral, myrrh, mycin, moenomycin, monoacetyl cladosporin, monomethyl red clover and yellow dock, garlic and St. John's wort. cladosporin, mupirocin, mupirocin calcium, mycobacidin, myriocin, myxopyronin, pseudoaglycone, nanaomycin, nan 0086 Mixtures of these antibiotic agents may also be cimycin, nargenicin, neocarcinostatin, neoenactin, neothra employed according to the present invention. mycin, nifurtoinol, nocardicin, nogalamycin, novobiocin, octylmonate, olivomycin, orthosomycin, oudemansin, 0087 Solubility of the antibiotic agent is an important oxirapentyn, oxoglaucine methiodide, pactacin, pactamycin, factor in the development of a stable foamable composition papulacandin, paulomycin, phaeoramularia fungicide, according to the present invention. phenelfamycin, phenyl, cerulenin, phenylmonate, pholipo 0088 For definition purposes, in the context of the mycin, pirlimycin, pleuromutilin, a polylactone derivative, present invention, the descriptive terminology for solubility polynitroXin, polyoxin, porfiromycin, pradimicin, prenomy according to the US Pharmacopoeia (USP 23, 1995, p. 10), US 2006/02694.85 A1 Nov.30, 2006 the European Pharmacopoeia (EP, 5" Edition (2004), page 0094. The antibiotic agent is included in the composition 7) and several other textbooks used in the art of pharma of the present invention in a concentration that provides a ceutical sciences (see for example, Martindale, The Extra desirable ratio between the efficacy and safety. Typically, Pharmacopoeia, 30" Edition (1993), page xiv. of the Preface: antibiotic agents are included in the composition in a con and Remington's Pharmaceutical Sciences, 18" Edition centration between about 0.005% and about 12%. However, (1990), page 208) is adapted: in some embodiments, the concentration of between about 0.005% and about 0.5%, in other embodiment between about 0.5% and about 2%, and in additional embodiments between about 2% and about 5% or between about 5% and Parts of Solvent Required for 1 about 12%. Descriptive Term Part of Solute Very soluble Less than 1 0095. In one or more embodiments, the antibiotic agent is Freely soluble From 1 to 10 encapsulated in particles, microparticles, nanoparticles, Soluble From 10 to 30 microcapsules, spheres, microsphres, nanocapsules, nano Sparingly soluble From 30 to 100 spheres, liposomes, niosomes, polymer matrix, nanocrystals Slightly soluble From 100 to 1,000 or microSponges. Very slightly soluble From 1,000 to 10,000 Practically insoluble or Insoluble 10,000 and over 0096. In one or more embodiments, the antibiotic agent is an antibiotic agent precursor present at a concentration 0089. Thus, in one or more embodiments, the antibiotic between about 0.05% and about 12%. agent is “soluble”, “freely soluble' or “very soluble” (as 0097. In one or more embodiments, the antibiotic agent is defined above) in the aqueous phase of the emulsion. In a compound that is positively identified using a laboratory other embodiments, where the agent possesses hydrophobic method, Suitable of detecting an antibiotic agent. characteristics, the antibiotic agent is “soluble”, “freely soluble' or “very soluble' in the oil phase of the emulsion. 0098. In one or more embodiments, the antibiotic agent is In other cases, the antibiotic agent is “very slightly soluble'. a Substance that is positively identified using a competitive “slightly soluble' or “sparingly soluble' in either the water nuclear retinoic acid receptor-binding assay. phase or oil phase of the emulsion. 0099. Several disorders of the target site (such as the skin, 0090. In other embodiments, the antibiotic agent is a body Surface, a body cavity, a mucosal Surface, the nose, insoluble i.e., “requires 10,000 parts or more of a solvent to the mouth, the eye, the ear canal, the respiratory system, the be solubilized, in either the water phase of the composition, vagina and the rectum), involve a combination of etiological or the oil phase of the composition, but not in both. factors, Some of which are related to a microbiological infection (that can be affected by an antibiotic agent); and 0091. In yet other embodiments, the antibiotic agent is other etiological factors that require an additional therapeu not fully dissolved in both the aqueous phase of the oil phase tic modality. For example, impetigo involves bacterial infec of the emulsion concurrently, and thus, it is suspended in the tion as well as inflammation, and therefore combined treat emulsion (i.e., at least a portion of the antibiotic agent ment with an antibiotic agent and an anti-inflammatory portion remains in Solid state in the final composition). In agent would be beneficial. Likewise, chronic ulcers involve Such a case, the polymeric agents that are listed herein serve poor blood Supply and potential bacterial, fungal and viral as Suspension-stabilizing agents to stabilize the composition. infections, which warrants a beneficial effect of a combina 0092. In certain embodiments of the present invention, tion of an antibiotic agent and a vasoactive agent. the composition and properties of the aqueous phase of the emulsion (e.g., pH, electrolyte concentration and chelating 0.100 Additional non-limiting examples of combinations agents) and/or the composition of the oil phase of the of an antibiotic agent and an additional active agent are emulsion are adjusted to attain a desirable solubility profile provided in the following table: of the active agent. 0093 Antibiotic agents are useful for the treatment of skin infections and infections of other target sites, such as Disorder Exemplary Additional Active Agent the vagina and rectum. The pH of the composition is 80l. At least one agent selected from the group consisting of adjusted for optimal efficacy, according to the specific a retinoid; a keratolytic acid, an alpha-hydroxy acid and infection and in light of the specific target site. In certain derivatives thereof, a beta-hydroxy acid and derivatives embodiments, the pH of the composition is between 3.5 and thereof, a skin-drying agent, an anti-seborrhea agent, a 8.5, and more preferably between about 4.5 and about 7.0, corticosteroid and a non-steroidal anti-inflammatory agent. . . Rosacea At least one agent selected from the group consisting which is preferable for skin therapy. Yet, in other exemplary of a retinoid; a keratolytic acid, an alpha-hydroxy acid, embodiments, the pH of the composition is between about 3 a beta-hydroxy acid and derivatives thereof. and about 4.5, which is suitable for vaginal therapy. In Otitis At least one agent selected from the group of an certain embodiments, the pH of the composition can be antifungal agent, a local anesthetic agent, a corticosteroid and a non-steroidal anti-inflammatory agent. lower than 3. Two exemplary antibiotic agents that are being Psoriasis At least one agent selected from the group consisting used both in skin therapy and vaginal therapy are metron of a corticosteroid, coal tar, anthralin and a photodynamic idazole and clindamycin. For both agents, the pH of the therapy agent foamable composition is adjusted between about 4.5 and about 7.0 for skin treatment and about 3 and about 4.5 for vaginal treatment. The adjustment of the pH can performed, Hence, in many cases, the inclusion of an additional thera as needed by the addition of an acid, a base or a buffering peutic agent in the foamable composition of the present agent. invention, contributes to the clinical activity of the antibiotic US 2006/02694.85 A1 Nov.30, 2006

agent. Thus, in one or more embodiments, the foamable rials suitable for use as a hydrophobic carrier in the foamable composition further includes at least one additional thera compositions described herein. peutic agent, in a therapeutically effective concentration. 0105. In one or more embodiments, the hydrophobic 0101. In one or more embodiments, the at least one organic carrier is an oil. Such as mineral oil. Mineral oil additional therapeutic agent is selected from the group (Chemical Abstracts Service Registry number 8012-95-1) is consisting of a steroidal anti-inflammatory agent, a nonste a mixture of aliphatic, naphthalenic, and aromatic liquid roidal anti-inflammatory drug, an immunosuppressive agent, hydrocarbons that derive from petroleum. It is typically an immunomodulator, an immunoregulating agent, a hor liquid; its viscosity is in the range of between about 35 CST monal agent, an antifungal agent, an antiviral agent, an and about 100 CST (at 40°C.), and its pour point (the lowest antiparasitic agent, a vasoactive agent, a vasoconstrictor, a temperature at which an oil can be handled without exces vasodilator, vitamin A, a vitamin A derivative, vitamin B, a sive amounts of wax crystals forming so preventing flow) is vitamin B derivative, vitamin C, a vitamin C derivative, below 0° C. The hydrophobic organic carrier does not vitamin D, a vitamin D derivative, vitamin E, a vitamin E include thick or semi-solid materials, such as white petro derivative, vitamin F, a vitamin F derivative, vitamin K, a latum, also termed “Vaseline', which, in certain composi Vitamin K derivative, a wound healing agent, a disinfectant, tions is disadvantageous due to its waxy nature and semi an anesthetic, an antiallergic agent, an alpha hydroxyl acid, solid texture. lactic acid, glycolic acid, a beta-hydroxy acid, a protein, a 0106 According to one or more embodiments, hydro peptide, a neuropeptide, a allergen, an immunogenic Sub phobic solvents are liquid oils originating from vegetable, stance, a haptene, an oxidizing agent, an antioxidant, a marine or animal sources. Suitable liquid oil includes satu dicarboxylic acid, azelaic acid, sebacic acid, adipic acid, rated, unsaturated or polyunsaturated oils. By way of fumaric acid, an antibiotic agent, an antiproliferative agent, example, the unsaturated oil may be olive oil, corn oil, an anticancer agent, a photodynamic therapy agent, an Soybean oil, canola oil, cottonseed oil, coconut oil, Sesame anti-wrinkle agent, a radical scavenger, a metal oxide (e.g., oil, Sunflower oil, borage seed oil, SyZigium aromaticum oil, titanium dioxide, Zinc oxide, Zirconium oxide, iron oxide), hempseed oil, herring oil, cod-liver oil, salmon oil, flaxseed silicone oxide, an anti wrinkle agent, a skin whitening agent, oil, wheat germ oil, evening primrose oils or mixtures a skin protective agent, a masking agent, an anti-wart agent, thereof, in any proportion. a refatting agent, a lubricating agent and mixtures thereof. 0.107 Suitable hydrophobic solvents also include poly 0102. In certain cases, the disorder to be treated involves unsaturated oils containing poly-unsaturated fatty acids. In unaesthetic lesions that need to be masked. For example, one or more embodiments, the unsaturated fatty acids are rosacea involves papules and pustules, which can be treated selected from the group of omega-3 and omega-6 fatty acids. with an antibiotic agent, as well as erythema, telangiectasia Examples of Such polyunsaturated fatty acids are linoleic and redness, which partially respond to treatment with an and linolenic acid, gamma-linoleic acid (GLA), eicosapen antibiotic agent. Thus, in one or more embodiments, the taenoic acid (EPA) and docosahexaenoic acid (DHA). Such additional active agent is a masking agent, i.e., a pigment. unsaturated fatty acids are known for their skin-conditioning Non limiting examples of Suitable pigments include brown, effect, which contribute to the therapeutic benefit of the yellow or red iron oxide or hydroxides, chromium oxides or present foamable composition. Thus, the hydrophobic sol hydroxides, titanium oxides or hydroxides, Zinc oxide, vent can include at least 6% of an oil selected from omega-3 FD&C Blue No. 1 aluminum lake, FD&C Blue No. 2 oil, omega-6 oil, and mixtures thereof. In the context of the aluminum lake and FD&C Yellow No. 6 aluminum lake. present invention, oils that possess therapeutically beneficial 0103) The foamable composition of the present invention properties are termed “therapeutically active oil'. can be an emulsion, or microemulsion, including an aqueous 0108) Another class of hydrophobic solvents is the essen phase and an organic carrier phase. The organic carrier is tial oils, which are also considered therapeutically active oil, selected from a hydrophobic organic carrier (also termed which contain active biologically occurring molecules and, herein “hydrophobic solvent'), an emollient, a polar solvent, upon topical application, exert a therapeutic effect, which is and a mixture thereof. The identification of a “solvent, as conceivably synergistic to the beneficial effect of the anti used herein, is not intended to characterize the solubilization biotic agent in the composition. capabilities of the solvent for any specific active agent or any 0109) Another class of therapeutically active oils other component of the foamable composition. Rather, Such includes liquid hydrophobic plant-derived oils, which are information is provided to aid in the identification of mate known to possess therapeutic benefits when applied topi rials suitable for use as a carrier in the foamable composi cally. tions described herein. 0110 Silicone oils also may be used and are desirable due 0104. A “hydrophobic organic carrier as used herein to their known skin protective and occlusive properties. refers to a material having solubility in distilled water at Suitable silicone oils include non-volatile silicones, such as ambient temperature of less than about 1 gm per 100 mL. polyalkyl siloxanes, polyaryl siloxanes, polyalkylaryl silox more preferable less than about 0.5gm per 100 mL, and anes and polyether siloxane copolymers, polydimethylsilox most preferably less than about 0.1 gm per 100 mL. It is anes (dimethicones) and poly(dimethylsiloxane)-(diphenyl liquid at ambient temperature. The identification of a hydro siloxane) copolymers. These are chosen from cyclic or linear phobic organic carrier or “hydrophobic solvent, as used polydimethylsiloxanes containing from about 3 to about 9, herein, is not intended to characterize the solubilization preferably from about 4 to about 5, silicon atoms. Volatile capabilities of the solvent for any specific active agent or any silicones such as cyclomethicones can also be used. Silicone other component of the foamable composition. Rather, Such oils are also considered therapeutically active oil, due to information is provided to aid in the identification of mate their barrier retaining and protective properties. US 2006/02694.85 A1 Nov.30, 2006

0111. In one or more embodiments, the hydrophobic 0.117) According to one or more embodiments, the polar carrier includes at least 2% by weight silicone oil or at least solvent is a polyethylene glycol (PEG) or PEG derivative 5% by weight. that is liquid at ambient temperature, including PEG200 (MW (molecular weight) about 190-210 kD), PEG300 (MW 0112 The solvent may be a mixture of two or more of the about 285-315 kD), PEG400 (MW about 380-420 kD), above hydrophobic solvents in any proportion. PEG600 (MW about 570-630 kD) and higher MW PEGs 0113. A further class of solvents includes “emollients' such as PEG 4000, PEG 6000 and PEG 10000 and mixtures that have a softening or soothing effect, especially when thereof. applied to body areas, such as the skin and mucosal Surfaces. Emollients are not necessarily hydrophobic. Examples of 0118. The polymeric agent serves to stabilize the foam Suitable emollients include hexyleneglycol, propylene gly composition and to control drug residence in the target col, isostearic acid derivatives, isopropyl palmitate, isopro organ. Exemplary polymeric agents are classified below in a pyl isostearate, diisopropyl adipate, diisopropyl dimerate, non-limiting manner. In certain cases, a given polymer can maleated Soybean oil, octyl palmitate, cetyl lactate, cetyl belong to more than one of the classes provided below. ricinoleate, tocopheryl acetate, acetylated lanolin alcohol, 0119). In one or more embodiments, the composition of cetyl acetate, phenyl trimethicone, glyceryl oleate, toco the present invention includes at least one gelling agent. A pheryl linoleate, wheat germ glycerides, arachidyl propi gelling agent controls the residence of a therapeutic com onate, myristyl lactate, decyl oleate, propylene glycol rici position in the target site of treatment by increasing the noleate, isopropyl lanolate, pentaerythrity1 tetrastearate, viscosity of the composition, thereby limiting the rate of its neopentylglycol dicaprylate/dicaprate, isononyl clearance from the site. Many gelling agents are known in isononanoate, isotridecyl isononanoate, myristyl myristate, the art to possess mucoadhesive properties. triisocetyl citrate, octyl dodecanol. Sucrose esters of fatty 0.120. The gelling agent can be a natural gelling agent, a acids, octyl hydroxy Stearate and mixtures thereof. Synthetic gelling agent and an inorganic gelling agent. 0114. An additional class of emollients, suitable accord Exemplary gelling agents that can be used in accordance ing to the present invention consists of polypropylene glycol with one or more embodiments of the present invention (PPG) alkyl ethers, such as PPG stearyl ethers and PPG include, for example, naturally-occurring polymeric mate Butyl Ether, which are polypropylene ethers of stearyl ether rials, such as locust bean gum, Sodium alginate, Sodium that function as skin-conditioning agent in pharmaceutical caseinate, egg albumin, gelatin agar, carrageenin gum, and cosmetic formulations. PPG alkyl ethers can be incor Sodium alginate, Xanthan gum, quince Seed extract, traga porated in the foamable composition of the present invention canth gum, guar gum, starch, chemically modified Starches in a concentration between about 1% and about 20%. The and the like, semi-synthetic polymeric materials such as sensory properties of foams containing PPG alkyl ethers are cellulose ethers (e.g. hydroxyethyl cellulose, methyl cellu favorable, as revealed by consumer panel tests. Surprisingly, lose, carboxymethyl cellulose, hydroxy propylmethyl cellu it has been discovered that foams comprising PPG alkyl lose), guar gum, hydroxypropyl guar gum, Soluble starch, ethers are non-flammable, as shown in a test according to cationic celluloses, cationic guars, and the like, and Syn European Standard prEN 14851, titled “Aerosol contain thetic polymeric materials, such as carboxyvinyl polymers, ers—Aerosol foam flammability test', while foams contain polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid ing other oils are inflammable. polymers, polymethacrylic acid polymers, polyvinyl acetate polymers, polyvinyl chloride polymers, polyvinylidene 0115 According to one or more embodiments of the chloride polymers and the like. Mixtures of the above present invention, the hydrophobic organic carrier includes compounds are contemplated. a mixture of a hydrophobic solvent and an emollient. According to one or more embodiments, the foamable 0121 Further exemplary gelling agents include the composition is a mixture of mineral oil and an emollient in acrylic acid/ethyl acrylate copolymers and the carboxyvinyl a ratio between 2:8 and 8:2 on a weight basis. polymers sold, for example, by the B.F. Goodrich Company 0116. A “polar solvent' is an organic solvent, typically under the trademark of CarbopolR) resins. These resins soluble in both water and oil. Examples of polar solvents consist essentially of a colloidal water-soluble polyalkenyl include polyols, such as glycerol (glycerin), propylene gly polyether crosslinked polymer of acrylic acid crosslinked col, hexylene glycol, diethylene glycol, propylene glycol with from 0.75% to 2% of a crosslinking agent such as n-alkanols, terpenes, di-terpenes, tri-terpenes, terpen-ols, polyallyl Sucrose or polyallyl pentaerythritol. Examples limonene, terpene-ol. 1-menthol, dioxolane, ethylene glycol, include Carbopol R. 934, Carbopol R 940, Carbopol R 950, other glycols, Sulfoxides, such as dimethylsulfoxide Carbopol R, 980, Carbopol R 951 and Carbopol R 981. Car (DMSO), dimethylformanide, methyl dodecyl sulfoxide, bopol R 934 is a water-soluble polymer of acrylic acid dimethylacetamide, monooleate of ethoxylated glycerides crosslinked with about 1% of a polyallyl ether of sucrose (with 8 to 10 ethylene oxide units), azone (1-dodecylazacy having an average of about 5.8 allyl groups for each Sucrose cloheptan-2-one), 2-(n-nonyl)-1,3-dioxolane, esters, such as molecule. isopropyl myristate/palmitate, ethyl acetate, butyl acetate, 0122) In one or more embodiment, the composition of the methyl proprionate, capric/caprylic triglycerides, present invention includes at least one polymeric agent, octylmyristate, dodecyl-myristate; myristyl alcohol, lauryl which is a water-soluble cellulose ether. Preferably, the alcohol, lauric acid, lauryl lactate ketones; amides, such as water-soluble cellulose ether is selected from the group acetamide oleates such as triolein; various alkanoic acids consisting of methylcellulose, hydroxypropyl cellulose, Such as caprylic acid; lactam compounds, such as aZone; hydroxypropyl methylcellulose (Methocel), hydroxyethyl alkanols, such as dialkylamino acetates, and admixtures cellulose, methylhydroxyethylcellulose, methylhydroxypro thereof. pylcellulose, hydroxyethylcarboxymethylcellulose, car US 2006/02694.85 A1 Nov.30, 2006 boxymethylcellulose and carboxymethylhydroxyethylcel 0129. The foam composition may contain a film-forming lulose. More preferably, the water-soluble cellulose ether is component. The film-forming component may include at selected from the group consisting of methylcellulose, least one water-insoluble alkyl cellulose or hydroxyalkyl hydroxypropyl cellulose and hydroxypropyl methylcellu cellulose. Exemplary alkyl cellulose or hydroxyalkyl cellu lose (Methocel). In one or more embodiments, the compo lose polymers include ethyl cellulose, propyl cellulose, butyl sition includes a combination of a water-soluble cellulose cellulose, cellulose acetate, hydroxypropyl cellulose, ether; and a naturally occurring polymeric materials, hydroxybutyl cellulose, and ethylhydroxyethyl cellulose, selected from the group including Xanthan gum, guar gum, alone or in combination. In addition, a plasticizer or a carrageenan gum, locust bean gum and tragacanth gum. cross-linking agent may be used to modify the polymers characteristics. For example, esters such as dibutyl or diethyl 0123 Yet, in other embodiments, the gelling agent phthalate, amides Such as diethyldiphenyl urea, vegetable includes inorganic gelling agents, such as silicone dioxide oils, fatty acids and alcohols such as oleic and myristyl acid (fumed silica). may be used in combination with the cellulose derivative. 0124 Mucoadhesive/bioadhesion has been defined as the attachment of synthetic or biological macromolecules to a 0.130. In one or more embodiments, the composition of biological tissue. Mucoadhesive agents are a class of poly the present invention includes a phase change polymer, meric biomaterials that exhibit the basic characteristic of a which alters the composition behavior from fluid-like prior hydrogel, i.e. Swell by absorbing water and interacting by to administration to Solid-like upon contact with the target means of adhesion with the mucous that covers epithelia. mucosal Surface. Such phase change results from external Compositions of the present invention may contain a stimuli. Such as changes in temperature or pH and exposure mucoadhesive macromolecule or polymer in an amount to specific ions (e.g., Ca"). Non-limiting examples of phase sufficient to confer bioadhesive properties. The bioadhesive change polymers include poly(N-isopropylamide) and macromolecule enhances the delivery of biologically active Poloxamer 407(R). agents on or through the target Surface. The mucoadhesive 0131 The polymeric agent is present in an amount in the macromolecule may be selected from acidic synthetic poly range of about 0.01% to about 5.0% by weight of the foam mers, preferably having at least one acidic group per four composition. In one or more embodiments, it is typically repeating or monomeric Subunit moieties, such as poly less than about 1 wt % of the foamable composition. (acrylic)- and/or poly(methacrylic) acid (e.g., Carbopol R, Carbomer(R), poly(methylvinyl ether/maleic anhydride) 0132) Surface-active agents (also termed “surfactants”) copolymer, and their mixtures and copolymers; acidic syn include any agent linking oil and water in the composition, thetically modified natural polymers, such as carboxymeth in the form of emulsion. A surfactants hydrophilic/lipo ylcellulose (CMC); neutral synthetically modified natural philic balance (HLB) describes the emulsifiers affinity polymers, such as (hydroxypropyl)methylcellulose; basic toward water or oil. The HLB scale ranges from 1 (totally amine-bearing polymers such as chitosan; acidic polymers lipophilic) to 20 (totally hydrophilic), with 10 representing obtainable from natural Sources. Such as alginic acid, hyalu an equal balance of both characteristics. Lipophilic emulsi ronic acid, pectin, gum tragacanth, and karaya gum, and fiers form water-in-oil (w/o) emulsions: hydrophilic surfac neutral synthetic polymers, such as polyvinyl alcohol or tants form oil-in-water (ofw) emulsions. The HLB of a blend their mixtures. An additional group of mucoadhesive poly of two emulsifiers equals the weight fraction of emulsifier A mers includes natural and chemically modified cyclodextrin, times its HLB value plus the weight fraction of emulsifier B especially hydroxypropyl-3-cyclodextrin. Such polymers times its HLB value (weighted average). may be present as free acids, bases, or salts, usually in a final 0.133 According to one or more embodiments of the concentration of about 0.01% to about 0.5% by weight. present invention, the Surface-active agent has a hydrophilic 0125 A suitable bioadhesive macromolecule is the fam lipophilic balance (HLB) between about 9 and about 14, ily of acrylic acid polymers and copolymers, (e.g., Car which is the required HLB (the HLB required to stabilize an bopolR). These polymers contain the general structure O/W, emulsion of a given oil) of most oils and hydrophobic —CH2—CH(COOH)—l. Hyaluronic acid and other bio Solvents. Thus, in one or more embodiments, the composi logically-derived polymers may be used. tion contains a single Surface active agent having an HLB value between about 9 and 14, and in one or more embodi 0126 Exemplary bioadhesive or mucoadhesive macro ments, the composition contains more than one surface molecules have a molecular weight of at least 50 kDa, or at active agent and the weighted average of their HLB values least 300 kDa, or at least 1,000 kDa. Favored polymeric is between about 9 and about 14. Yet, in other embodiments, ionizable macromolecules have not less than 2 mole percent when a water in oil emulsion is desirable, the composition acidic groups (e.g., COOH, SOH) or basic groups (NH2, contains one or more Surface active agents, having an HLB NRH, NR), relative to the number of monomeric units. The value between about 2 and about 9. acidic or basic groups can constitute at least 5 mole percent, or at least 10 mole percent, or at least 25, at least 50 more 0.134. The surface-active agent is selected from anionic, percent, or even up to 100 mole percent relative to the cationic, nonionic, Zwitterionic, amphoteric and ampholytic number of monomeric units of the macromolecule. Surfactants, as well as mixtures of these Surfactants. Such surfactants are well known to those skilled in the therapeutic 0127. Yet, another group of mucoadhesive agent includes and cosmetic formulation art. Nonlimiting examples of inorganic gelling agents such as silicon dioxide (fumed possible surfactants include polysorbates, such as polyoxy silica), including but not limited to, AEROSIL 200 ethylene (20) sorbitan monostearate (Tween 60) and poly (DEGUSSA). (oxyethylene) (20) sorbitan monooleate (Tween 80); poly 0128 Many mucoadhesive agents are known in the art to (oxyethylene) (POE) fatty acid esters, such as Myri 45, Myr also possess gelling properties. 49, Myri 52 and Myr 59: poly(oxyethylene) alkylyl ethers, US 2006/02694.85 A1 Nov.30, 2006

Such as poly(Oxyethylene) cetyl ether, poly(oxyethylene) invention to increase the foaming capacity of Surfactants palmityl ether, polyethylene oxide hexadecyl ether, polyeth and/or to stabilize the foam. In one or more embodiments of ylene glycol cetyl ether, brij 38, brij 52, brij 56 and brij W1; the present invention, the foam adjuvantagent includes fatty Sucrose esters, partial esters of Sorbitol and its anhydrides, alcohols having 15 or more carbons in their carbon chain, Such as Sorbitan monolaurate and Sorbitan monolaurate; Such as cetyl alcohol and Stearyl alcohol (or mixtures mono or diglycerides, isoceteth-20, Sodium methyl cocoyl thereof). Other examples of fatty alcohols are arachidyl taurate, sodium methyl oleoyl taurate, sodium lauryl Sulfate, alcohol (C20), behenyl alcohol (C22), 1-triacontanol (C30), triethanolamine lauryl sulfate and betaines. as well as alcohols with longer carbon chains (up to C50). 0135) In one or more embodiments of the present inven Fatty alcohols, derived from beeswax and including a mix tion, the Surface-active agent includes at least one non-ionic ture of alcohols, a majority of which has at least 20 carbon Surfactant. Ionic Surfactants are known to be irritants. There atoms in their carbon chain, are especially well Suited as fore, non-ionic Surfactants are preferred in applications foam adjuvant agents. The amount of the fatty alcohol including sensitive tissue such as found in most mucosal required to Support the foam system is inversely related to tissues, especially when they are infected or inflamed. We the length of its carbon chains. Foam adjuvants, as defined have Surprisingly found that non-ionic Surfactants alone herein are also useful in facilitating improved spreadability provide foams of excellent quality, i.e. a score of “E” and absorption of the composition. according to the grading scale discussed herein below. 0144. In one or more embodiments of the present inven tion, the foam adjuvant agent includes fatty acids having 16 0136. In one or more embodiments, the surface active or more carbons in their carbon chain, Such as hexadecanoic agent includes a mixture of at least one non-ionic Surfactant acid (C16) stearic acid (C18), arachidic acid (C20), behenic and at least one ionic Surfactant in a ratio in the range of acid (C22), octacosanoic acid (C28), as well as fatty acids about 100:1 to 6:1. In one or more embodiments, the with longer carbon chains (up to C50), or mixtures thereof. non-ionic to ionic Surfactant ratio is greater than about 6:1, As for fatty alcohols, the amount of fatty acids required to or greater than about 8:1; or greater than about 14:1, or Support the foam system is inversely related to the length of greater than about 16:1, or greater than about 20:1. its carbon chain. 0137 In one or more embodiments of the present inven tion, a combination of a non-ionic Surfactant and an ionic 0145. In one or more embodiments, a combination of a Surfactant (Such as sodium lauryl Sulphate and cocamidopro fatty acid and a fatty ester is employed. pylbetaine) is employed, at a ratio of between 1:1 and 20:1, 0146) Optionally, the carbon atom chain of the fatty or at a ratio of 4:1 to 10:1. The resultant foam has a low alcohol or the fatty acid may have at least one double bond. specific gravity, e.g., less than 0.1 g/ml. A further class of foam adjuvant agent includes a branched fatty alcohol or fatty acid. The carbon chain of the fatty acid 0138. In certain preferred embodiments, the surface or fatty alcohol also can be substituted with a hydroxyl active agent consistst of essentially a non-ionic Surfactant or group, such as 12-hydroxy Stearic acid. a combination of non-ionic Surfactants. 0147 An important property of the fatty alcohols and 0.139. It has been surprisingly discovered that the stability fatty acids used in context of the composition of the present of the composition is especially pronounced when a com invention is related to their therapeutic properties per se. bination of at least one non-ionic surfactant having HLB of Long chain Saturated and mono unsaturated fatty alcohols, less than 9 and at least one non-ionic Surfactant having HLB e.g., Stearyl alcohol, erucyl alcohol, arachidyl alcohol and of equal or more than 9 is employed. The ratio between the behenyl alcohol (docosanol) have been reported to possess at least one non-ionic surfactant having HLB of less than 9 antiviral, antiinfective, antiproliferative and anti-inflamma and the at least one non-ionic Surfactant having HLB of tory properties (see, U.S. Pat. No. 4,874,794). Longer chain equal or more than 9, is between 1:8 and 8:1, or at a ratio of fatty alcohols, e.g., tetracosanol, hexacosanol, heptacosanol, 4:1 to 1:4. The resultant HLB of such a blend of at least two octacosanol, triacontanol, etc., are also known for their emulsifiers is between about 9 and about 14. metabolism modifying properties and tissue energizing 0140 Thus, in an exemplary embodiment, a combination properties. Long chain fatty acids have also been reported to of at least one non-ionic Surfactant having HLB of less than possess anti-infective characteristics. 9 and at least one non-ionic Surfactant having HLB of equal 0.148 Thus, in preferred embodiments of the present or more than 9 is employed, at a ratio of between 1:8 and 8:1, invention, a combined and enhanced therapeutic effect is or at a ratio of 4:1 to 1:4, wherein the HLB of the combi attained by including both an antibiotic agent and a thera nation of emulsifiers is between about 9 and about 14. peutically effective foam adjuvant in the same composition, 0141. In one or more embodiments of the present inven thus providing a simultaneous anti-inflammatory and anti tion, the Surface-active agent includes mono-, di- and tri infective effect from both components. Furthermore, in a esters of Sucrose with fatty acids (sucrose esters), prepared further preferred embodiment, the composition concurrently from sucrose and esters of fatty acids or by extraction from comprises an antibiotic agent, a therapeutically effective Sucro-glycerides. Suitable Sucrose esters include those hav foam adjuvant and a therapeutically active oil, as detailed ing high monoester content, which have higher HLB values. above. Such combination provides an even more enhanced therapeutic benefit. Thus, the foamable carrier, containing 0142. The total surface active agent is in the range of the foam adjuvant provides an extra therapeutic benefit in about 0.1 to about 5% of the foamable composition, and is comparison with currently used vehicles, which are inert and typically less than about 2% or less than about 1%. non-active. 0143 Preferably, a therapeutically effective foam adju 0.149 The foam adjuvant according to one or more pre vant is included in the foamable compositions of the present ferred embodiments of the present invention includes a US 2006/02694.85 A1 Nov.30, 2006 mixture of fatty alcohols, fatty acids and hydroxy fatty acids 0157 Foam quality can be graded as follows: and derivatives thereof in any proportion, providing that the 0158 Grade E (excellent): very rich and creamy in total amount is 0.1% to 5% (w/w) of the carrier mass. More appearance, does not show any bubble structure or shows a preferably, the total amount is 0.4%-2.5% (w/w) of the very fine (small) bubble structure: does not rapidly become carrier mass. dull; upon spreading on the skin, the foam retains the 0150 Optionally, the composition further contains a pen creaminess property and does not appear watery. etration enhancer. Non limiting examples of penetration 0159 Grade G (good): rich and creamy in appearance, enhancers include propylene glycol, butylene glycols, glyc very small bubble size, “dulls' more rapidly than an excel erol, pentaerythritol, Sorbitol, mannitol, oligosaccharides, lent foam, retains creaminess upon spreading on the skin, dimethyl isosorbide, monooleate of ethoxylated glycerides and does not become watery. having about 8 to 10 ethylene oxide units, polyethylene 0.160 Grade FG (fairly good): a moderate amount of glycol 200-600, transcutol, glycofurol and cyclodextrins. creaminess noticeable, bubble structure is noticeable; upon spreading on the skin the product dulls rapidly and becomes 0151. The therapeutic foam of the present invention may Somewhat lower in apparent viscosity. further optionally include a variety of formulation excipi ents, which are added in order to fine-tune the consistency 0.161 Grade F (fair): very little creaminess noticeable, of the formulation, protect the formulation components from larger bubble structure than a “fairly good' foam, upon degradation and oxidation and modify their consistency. spreading on the skin it becomes thin in appearance and Such excipients may be selected, for example, from stabi watery. lizing agents, antioxidants, humectants, preservatives, colo 0162 Grade P (poor): no creaminess noticeable, large rant and odorant agents and other formulation components, bubble structure, and when spread on the skin it becomes used in the art of formulation. very thin and watery in appearance. 0152 Aerosol propellants are used to generate and 0.163 Grade VP (very poor): dry foam, large very dull administer the foamable composition as a foam. The total bubbles, difficult to spread on the skin. composition including propellant, foamable compositions 0.164 Topically administratable foams are typically of and optional ingredients is referred to as the foamable quality grade E or G, when released from the aerosol carrier. The propellant makes up about 3% to about 25 wt % container. Smaller bubbles are indicative of more stable of the foamable carrier. Examples of suitable propellants foam, which does not collapse spontaneously immediately include Volatile hydrocarbons such as butane, propane, upon discharge from the container. The finer foam structure isobutane or mixtures thereof, and fluorocarbon gases. looks and feels Smoother, thus increasing its usability and 0153 Composition and Foam Physical Characteristics appeal. 0.165 A further aspect of the foam is breakability. The 0154) A pharmaceutical or cosmetic composition manu breakable foam is thermally stable, yet breaks under sheer factured using the foam carrier according to one or more force. Sheer-force breakability of the foam is clearly advan embodiments of the present invention is very easy to use. tageous over thermally induced breakability. Thermally sen When applied onto the afflicted body surface of mammals, sitive foams immediately collapse upon exposure to skin i.e., humans or animals, it is in a foam state, allowing free application without spillage. Upon further application of a temperature and, therefore, cannot be applied on the hand mechanical force, e.g., by rubbing the composition onto the and afterwards delivered to the afflicted area. body Surface, it freely spreads on the Surface and is rapidly 0166 Another property of the foam is specific gravity, as absorbed. measured upon release from the aerosol can. Typically, foams have specific gravity of less than 0.1 g/mL or less than 0155 The foam composition of the present invention 0.05 g/mL. creates a stable emulsion having an acceptable shelf life of at least one year, or at least two years at ambient tempera Fields of Pharmaceutical Applications ture. A feature of a product for cosmetic or medical use is 0.167 The foamable composition of the present invention long-term stability. Propellants, which are a mixture of low is suitable for administration to an inflicted area, in need of molecular weight hydrocarbons, tend to impair the stability treatment, including, but not limited to the skin, a body of emulsions. It has been observed, however, that emulsion Surface, a body cavity, a mucosal Surface, the nose, the foam compositions according to the present invention are mouth, the eye, the ear canal, the respiratory system, the Surprisingly stable. Following accelerated Stability studies, vagina and the rectum (severally and interchangeably they demonstrate desirable texture; they form fine bubble termed herein “target site'). structures that do not break immediately upon contact with 0168 Antibiotic agents are initially thought to affect a Surface, spread easily on the treated area and absorb disorders that involve blood circulation abnormalities, yet, quickly. in many case, circulation lays a secondary, yet influential 0156 The composition should also be free flowing, to role, which must be taken into account in order to optimize allow it to flow through the aperture of the container, e.g., treatment. For example, cutaneous malignant tumors are and aerosol container, and create an acceptable foam. Com characterized by poor blood circulation, which make them positions containing semi-solid hydrophobic solvents, e.g., less responsive to drug treatment, and therefore usage of an white petrolatum, as the main ingredients of the oil phase of antibiotic agent would be beneficial to the cancer therapy. the emulsion, exhibit high viscosity and poor flowability and 0169. Thus, by including an appropriate antibiotic agent are inappropriate candidates for a foamable composition. and optionally, additional active agents in the composition, US 2006/02694.85 A1 Nov.30, 2006 the kit and the composition of the present invention are (hirsutism), alopecia, including male pattern baldness, useful in treating an animal or a patient having one of a alopecia greata, alopecia universalis and alopecia totalis; variety of dermatological disorders (also termed "derma pseudofolliculitis barbae, keratinous cyst; toses') and/or having any secondary condition resulting from infections, which disorders and/or conditions are clas 0.178 Scaling papular diseases including psoriasis, pityri sified in a non-limiting exemplary manner according to the asis rosea, lichen planus, pityriasis rubra pilaris; following groups: 0.179 Benign tumors including moles, dysplastic nevi, 0170 Any disorders that involve a microbiological infec skin tags, lipomas, angiomas, pyogenic granuloma, Sebor tion, or disorders that respond to treatment with an antibiotic rheic keratoses, dermatofibroma, keratoacanthoma, keloid; agent, 0180 Malignant tumors including basal cell carcinoma, 0171 An infection, selected from the group of a bacterial squamous cell carcinoma, malignant melanoma, Paget’s infection, a fungal infection, a yeast infection, a viral infec disease of the nipples, Kaposi's sarcoma; tion and a parasitic infection. 0181 Reactions to sunlight including sunburn, chronic 0172 Any one of a variety of dermatological disorders, effects of Sunlight, photosensitivity; including dermatological pain, dermatological inflamma 0182 Bullous diseases including pemphigus, bullous tion, acne, acne Vulgaris, inflammatory acne, non-inflam pemphigoid, dermatitis herpetiformis, linear immunoglobu matory acne, acne fulminans, nodular papulopustular acne, acne conglobata, dermatitis, bacterial skin infections, fungal lin A disease; skin infections, viral skin infections, parasitic skin infec 0183 Pigmentation disorders including hypopigmenta tions, skin neoplasia, skin neoplasms, pruritis, cellulitis, tion Such as vitiligo, albinism and postinflammatory hypop acute lymphangitis, lymphadenitis, erysipelas, cutaneous igmentation and hyperpigmentation Such as melasma (chlo abscesses, necrotizing Subcutaneous infections, scalded skin asma), drug-induced hyperpigmentation, postinflammatory syndrome, folliculitis, furuncles, hidradenitis Suppurativa, hyperpigmentation; Disorders of cornification including ich carbuncles, paronychial infections, rashes, erythrasma, thyosis, keratosis pilaris, calluses and corns, actinic kerato impetigo, eethyma, yeast skin infections, warts, molluscum S1S, contagiosum, trauma or injury to the skin, post-operative or post-Surgical skin conditions, Scabies, pediculosis, creeping 0184 Pressure sores; eruption, eczemas, psoriasis, pityriasis rosea, lichen planus, pityriasis rubra pilaris, edematous, erythema multiforme, 0185 Disorders of Sweating; and erythema nodosum, grannuloma annulare, epidermal 0186 Inflammatory reactions including drug eruptions, necrolysis, Sunburn, photosensitivity, pemphigus, bullous toxic epidermal necrolysis; erythema multiforme, erythema pemphigoid, dermatitis herpetiformis, keratosis pilaris, cal nodosum, granuloma annulare. louses, corns, ichthyosis, skin ulcers, ischemic necrosis, miliaria, hyperhidrosis, moles, Kaposi's sarcoma, mela 0187. According to one or more embodiments of the noma, malignant melanoma, basal cell carcinoma, squamous present invention, the compositions are also useful in the cell carcinoma, poison ivy, poison oak, contact dermatitis, therapy of non-dermatological disorders by providing trans atopic dermatitis, rosacea, purpura, moniliasis, candidiasis, dermal delivery of an active antibiotic agent that is effective baldness, alopecia, Behcet’s syndrome, cholesteatoma, Der against non-dermatological disorders. cum disease, ectodermal dysplasia, gustatory Sweating, nail 0188 The same advantage is expected when the compo patella syndrome, lupus, hives, hair loss, Hailey-Hailey sition is topically applied to a body cavity or mucosal disease, chemical or thermal skin burns, Scleroderma, aging Surface (e.g., the mucosa of the nose and mouth, the eye, the skin, wrinkles, Sun spots, necrotizing fasciitis, necrotizing ear canal, vagina or rectum) to treat conditions such myositis, gangrene, Scarring, and Vitiligo. aschlamydia infection, gonorrhea infection, hepatitis B, her 0173 Dermatitis including contact dermatitis, atopic der pes, HIV/AIDS, human papillomavirus (HPV), genital matitis, seborrheic dermatitis, nummular dermatitis, chronic warts, bacterial vaginosis, candidiasis, chancroid, granu dermatitis of the hands and feet, generalized exfoliative loma Inguinale, lymphogranloma Venereum, mucopurulent dermatitis, stasis dermatitis; lichen simplex chronicus; dia cerviciitis (MPC), molluscum contagiosum, nongonococcal per rash; urethritis (NGU), trichomoniasis, Vulvar disorders, vulvo dynia, Vulvar pain, yeast infection, Vulvar dystrophy, Vulvar 0174 Bacterial infections including cellulitis, acute lym intraepithelial neoplasia (VIN), contact dermatitis, pelvic phangitis, lymphadenitis, erysipelas, cutaneous abscesses, inflammation, endometritis, Salpingitis, oophoritis, genital necrotizing Subcutaneous infections, staphylococcal scalded cancer, cancer of the cervix, cancer of the Vulva, cancer of skin syndrome, folliculitis, furuncles, hidradenitis Suppura the vagina, vaginal dryness, dyspareunia, anal and rectal tiva, carbuncles, paronychial infections, erythrasma; disease, anal abscess/fistula, anal cancer, anal fissure, anal 0175 Fungal Infections including dermatophyte infec warts, Crohn's disease, hemorrhoids, anal itch, pruritus ani, tions, yeast Infections; parasitic Infections including sca fecal incontinence, constipation, polyps of the colon and bies, pediculosis, creeping eruption; rectum. 0189 In an embodiment of the present invention, the 0176 Viral Infections, including, but not limited to her composition is useful for the treatment of wound, ulcer and pes genitalis and herpes labialis; burn. This use is particularly important since the composi 0177 Disorders of hair follicles and sebaceous glands tion of the present invention preads easily on the afflicted including acne, rosacea, perioral dermatitis, hypertrichosis area, without the need of extensive rubbing. US 2006/02694.85 A1 Nov.30, 2006

0190. In light of the expansion of the foam upon admin Example 2 istration, it is further suitable for the treatment and preven tion of post-Surgical adhesions. Adhesions are scars that Foamable Oil in Water Emulsion Base Antibiotic form abnormal connections between tissue surfaces. Post Compositions Comprising CiclopiroXolamine Surgical adhesion formation is a natural consequence of Surgery, resulting when tissue repairs itself following inci 0194 The following compositions contain ciclopiroxola Sion, cauterization, Suturing, or other means of trauma. mine, as example of an antibiotic foams comprising different When comprising an antibiotic agent an optionally, appro emulsion compositions. priate protective agents, the foam is Suitable for the treat ment or prevention of post Surgical adhesions. 0191). The invention is described with reference to the CPO-OO6 CPO-008 CPO-O11 following examples. This invention is not limited to these ngredient Name % Wiw % Wiw % Wiw examples and experiments. Many variations will suggest Ciclopiroxolamine 1.00 1.00 1.OO themselves and are within the full-intended scope of the Glyceryl monostearate O45 O.45 O45 appended claims. Light mineral oil S.OO S.OO Sopropyl myristate S.OO S.OO EXAMPLES Caprylicicapric triglyceride 1O.OO Cyclomethicone 2.00 Example 1 Dimethicone Sorbitan stearate O60 O.60 O.6O Foamable Oil in Water Emulsion Antibiotic Stearyl alcohol O.85 O.85 O.85 Compositions Steareth-21 2.00 2.OO Laureth-4 0192 An emulsion base was prepared by incorporating Cocamide DEA O.SO Phase A and Phase B with thorough mixing at elevated PEG-40 Stearate 2.60 2.60 2.60 Xanthan gum O.26 O.26 O.26 temperature (60-80° C.), followed by homogenization and Methocel A15C O.30 gradual cooling to RT. Methocel A4M Methocel K10OLV O.30 O.30 Polysorbate 80 O.90 O.90 O.90 Ingredient % Wiw Lactic acid to pH 7.0 to pH 7.0 to pH 7.0 Purified water To 100 To 100 To 100 Mineral oil 6.OO Isopropyl myristate 6.OO Glyceryl monostearate OSO Stearyl alcohol 1.OO 0195 Xanthan gum O.30 Methocel K10OM O.30 Polysorbate 80 1.OO PEG-40 Stearate 3.00 Purified water 81:10 CPO-O12 CPO-014 CPO-015 CPO-O3S Preaservative O.8O Ingredient Name % Wiw % Wiw % Wiw % Wiw Ciclopiroxolamine 1.00 1.00 1.OO 1.00 Glyceryl monostearate O.45 O.45 O45 O.45 Octyldodecanol 10.00 1O.OO 0193 The emulsion base was used to produce foamable Caprylicicapric 10.00 2.00 antibiotic compositions as detailed below. The compositions triglyceride were further examined for emulsion uniformity, emulsion Cyclomethicone 2.00 2.00 S.OO Sorbitan stearate O.60 O.60 O.6O 1.00 stability, foam quality and density and found stable, and Stearyl alcohol O.85 O.85 O.85 120 meeting the requirements of density between 0.01 and 0.1 Steareth-21 2.00 2.OO g/mL and excellent (E) quality, as shown in the table below. Laureth-4 2.00 2.60 Cocamide DEA PEG-40 Stearate 2.60 2.60 2.60 2.60 Xanthan gum O.26 O.26 O.26 O.26 Methocel A15C % Wiw % ww % Wiw % ww Methocel A4M O.30 O.30 Methocel K10OLV O.30 O.30 Emulsion Base 91.OO 91.OO 91.OO 82.OO Polysorbate 80 O.90 O.90 O.90 O.90 Chlorohexydin sol. 20% 1.OO 10.00 Lactic acid to pH 7.0 to pH 7.0 to pH 7.0 to pH 7.0 Tea tree oil 1.00 Purified water To 100 To 100 To 100 To 100 Clindamicin HCL 1.OO Propellant 8.OO 8.00 8.OO 8.00 Notes: Foam Properties The liquefied or gas propellant can be added at a concentration of about 3% to about 25%. Emulsion uniformity uniform. uniform. uniform. uniform. The compositions contain a variety of organic carriers. pH 4.92 4.89 4.54 5.05 In the majotrity of the compositions the Surface active agents are solely Foam quality E E E E non-ionic. Density O.O356 O.O417 O.O369 O.O328 The same vehicles can be used as vehicle of several additional antibiotic agents, listed in the embodiments of the present invention US 2006/02694.85 A1 Nov.30, 2006

Example 3 tion of the foam, mousse, gel or paste was observed. The test was carried out in a draught-free environment capable of Non-Flammable Foamable Oil in Water Emulsion ventilation, with the temperature controlled at 20+5° C. and Base Antibiotic Compositions, Containing PPG relative humidity in the range of 30% to 80%. According to Alky Ether and Comprising CiclopiroXolamine the standard, appearance of a stable flame which is at least 0196) 4 cm high and which is maintained for at least 2 seconds defines a product as “inflammable'. Results: foam compositions CPO32, CPO33 and CPO41 CPOO32 CPOO33 CPOO38 CPOO41 were found “non-flammable'. Ingredient % Wiw % ww % Wiw % ww Ciclopiroxolamine 1.OO 1.00 1.OO 1.00 Example 5 PPG-15 stearyl ether 1S.OO 1S.OO 1S.OO 1S.OO Isopropyl miristate 3.00 Ianolin 2.00 Foamable Oil in Water Emulsion Base Antibiotic Behenyl alcohol 1.OO 1.00 1.OO 1.00 Compositions, Containing a Combination of Steareth-21 1...SO Ceteareth 20 1...SO 1...SO 1...SO Hexylene Glycol and Propylene Glycol and Ceteth 2 2.OO 2.00 Comprising CiclopiroXolamine Laureth-4 2.OO 2.00 Carboximethyl cellulose OSO O198) Sodium Carbomer 1342 O.OS O.OS Methl cellulose O.15 O.15 O.15 Xanthan gum O.15 Glycerin USP 3.00 3.00 3.00 3.00 CPO-O58 Polyethylene glycol 400 S.OO Ingredient % Wiw Propylene glycol S.OO S.OO S.OO Sol. of NaOH (18%) to pH 8.5 to pH 8.5 to pH 8.5 to pH 8.5 Ciclopiroxolamine 1.OO Purified water To 100 To 100 To 100 To 100 Hexylene glycol S.OO CPO-052 CPO-OS6 CPO-057 Glyceryl Monostearate OSO ngredient % ww % ww % ww Sorbitane Stearate O.65 Stearyl Alcohol O.92 Ciclopiroxolamine 1.OO 1.00 1.OO Steareth-21 2.2O PPG-15 stearyl ether 1S.OO 1S.OO 1S.OO PEG-40 Stearate 2.85 Lanolin 2.OO Behenyl alcohol 1.OO Steareth-21 1...SO Methocel A4M O3S Behenyl alcohol 1.OO 1.00 1.OO Xanthan Gum O.30 Laureth-4 2.00 2.OO Macrogolryl Cetostearyl Ether 1...SO Polysorbate 80 1.OO Ceteareth 20 1.60 Propylene glycol S.OO Ceteth 2 2.OO Lactic acid To pH 7.5 Pemulen TR2 O.OS Purified Water To 100 Methocel A4M O16 O.15 CMC Sodium OSO Notes: Xanthan Gum O.15 The liquefied or gas propellant can be added at a concentration of about Glycerin USP 3.00 3.00 3.00 3% to about 25%. Propylene glycol S.40 S.40 S.OO The Surface active agents are solely non-ionic. Lactic acid To pH 7.5 To pH 7.5 To pH 7.5 The formulation contains hexylene glycol and propylene glycol (polar sol Purified Water To 100 To 100 To 100 vents), which contribute to skin penetration of the antibiotic agent The same vehicle can be used as vehicle of several additional antibiotic Notes: agents, listed in the embosiments of the present invention The liquefied or gas propellant can be added at a concentration of about 3% to about 25%. The compositions contain a variety of organic carriers. In the majority of the compositions the Surface active agents are solely Example 6 non-ionic. The formulations contain glycerin and/or propylene glycol (polar solvents), which contribute to skin penetration of the antibiotic agent Foamable Oil in Water Emulsion Base Antibiotic The same vehicles can be used as vehicle of several additional antibiotic Compositions, Containing AZelaic Acid agents, listed in the embodiments of the present invention 0.199) Example 4

Inflammability Test AZLO41 AZLO43 0197) A test according to European Standard prEN Ingredient % Wiw % Wiw 14851, titled “Aerosol containers—Aerosol foam flamma AZelaic Acid 1S.OO 1S.OO bility test” was performed on foam compositions CPO32, Caprylicicapric triglyceride 10.00 1O.OO Cetostearyl alcohol 1.00 1.OO CPO33 and CPO41. Approximately 5g of foam, mousse gel Glyceryl stearate O.SO O.SO or paste is sprayed from the aerosol container on to a watch Cholesterol 1.00 glass. An ignition source (a lighter) was placed at the base Benzoic acid O.20 O.20 of the watch glass and any ignition and Sustained combus US 2006/02694.85 A1 Nov.30, 2006 17

-continued -continued

AZLO41 AZLO43 AZLO41 AZLO43 Ingredient % Wiw % Wiw Ingredient % Wiw % Wiw Sodium hydroxide (18% sol.) To pH = 4.5 To pH = 4.5 Purified water to 100 to 100 Butylated hydroxytoluene O.10 O.10 Notes: PEG-40 Stearate 2.60 2.60 The liquefied or gas propellant can be added at a concentration of about 3% to about 25%. Methylcellulose (Methocel A4M) O.10 O.10 The Surface active agents are solely non-ionic. Xanthan gum O.25 O.25 The formulation contains PEG-400 O propylene glycol (polar solvents), which contribute to skin penetration of the antibiotic agent Polysorbate 80 O.90 O.90 PEG-400 S.OO Example 7 Dimethyl isosorbide S.OO Foamable Oil in Water Emulsion Base Antibiotic Propylene glycol S.OO 1O.OO Compositions, Containing Metronidazole 0200

MZ1. MZ1. MZ3 Ingredient Function % Wiw % Wiw % Wiw

Metronidazole O.7S 2.0 Mineral oil Hydrophobic solvent 6.O 3O.O 3O.O Isopropyl myristate Hydrophobic solvent 6.O PEG 40-Stearate Emulsifier 3.0 3.0 3.0 Stearyl alcohol Co-emulsifier; foam adjuvant 1.O 1.O 1.O Polysorbate 80 Emulsifier 1.O 1.O 1.O Glyceryl stearate Co-emulsifier; foam adjuvant O.S O.S O.S Cocamidopropylbetaine Emulsifier O.S O.S Xanthan gum Thickening agent; stabilizer O.3 O.3 O.3 Methylcellulose Thickening agent; stabilizer O.3 O.3 O.3 Preservative As needed Purified water To 100

MZ4 MZS MZ6 ngredient Function wfw % % Wiw % Wiw

Metronidazole O.7S 2.0 Mineral oil Hydrophobic solvent 6.O 6.0 6.O Sopropyl myristate Hydrophobic solvent 6.O 6.0 6.O PEG 40-Stearate Emulsifier 3.0 3.0 3.0 Stearyl alcohol Co-emulsifier; foam adjuvant 1.O 1.O 1.O Polysorbate 80 Emulsifier 1.O 1.O 1.O Glyceryl stearate Co-emulsifier; foam adjuvant O.S O.S O.S Cocamidopropylbetaine Emulsifier O.S Xanthan gum Thickening agent; stabilizer O.3 O.3 O.3 Methylcellulose Thickening agent; stabilizer O.3 O.3 O.3 Urea 2.0-2O.O Lactic acid ammonium 2.0-12.O actate Hexylene glycol 2.0-1O.O Preservative As needed Purified water To 100

MZ7 MZ8 ngredient Function wfw % % Wiw

Metronidazole O.7S 2.0 Mineral oil Hydrophobic solvent 6.O 6.O Sopropyl myristate Hydrophobic solvent 6.O 6.O PEG 40-Stearate Emulsifier 3.0 3.0 Stearyl alcohol Co-emulsifier; foam adjuvant 1.O 1.O Polysorbate 80 Emulsifier 1.O 1.O Glyceryl stearate Co-emulsifier; foam adjuvant O.S O.S Cocamidopropylbetaine Emulsifier O.S O.S Acrylates/C10–30 Alkyl Thickening agent; stabilizer O.3 O.3 Acrylate Cross-Polymer Microcrystalline cellulose O.3 Methylcellulose Thickening agent; stabilizer O.3 O.3 Preservative As needed As needed US 2006/02694.85 A1 Nov.30, 2006

-continued

TEA Neutralizer O.1 O.1 Purified water To 100 To 100

Notes: The liquefied or gas propellant can be added at a concentration of about 3% to about 25%. Formulations MZ4, MZ5 and MZ6 contain urea and lactic acid, which are keratolytic. PEG 400 or propylene glycol (polar solvents), which contribute to skin penetration of the antibiotic agent Formulation MZ6 contains hexylene glycol, which contribute to skin penetration of the antibi otic agent All formulations are of “Excellent quality foam The concentration of metronidazole in the composition may be altered in the range of about 0.75% and about 2%. t was found that formulations, comprising up to 2% metronidazole produced stable foams with “Good to “Excellent quality. t was further surprisingly found that metronidazole is substantially dissolved in the foamable composition of the present invention, up to a concentration of about 1.8%, while it is known hat the soluble concentration of Metronidazole is 0.75% and higher concentrations of metrinidazole are expected to be in Suspension

What is claimed is: about 10%; (iii) about 10% to about 20%; and (iv) about 1. A therapeutic kit to provide a safe and effective dosage 20% to about 50% by weight. of an antibiotic agent, including an aerosol packaging 8. The kit of claim 1, wherein the foamable composition assembly including: is substantially alcohol-free. 9. The kit of claim 1, further including about 0.1% to a) a container accommodating a pressurized product; and about 5% by weight of a therapeutically active foam adju b) an outlet capable of releasing the pressurized product vant is selected from the group consisting of fatty alcohols as a foam; having 15 or more carbons in their carbon chain; fatty acids wherein the pressurized product comprises a foamable having 16 or more carbons in their carbon chain; fatty composition comprising: alcohols derived from beeswax and including a mixture of alcohols, a majority of which has at least 20 carbon atoms i. an antibiotic agent; in their carbon chain; fatty alcohols having at least one ii. at least one organic carrier selected from the group double bond; fatty acids having at least one double bond; consisting of a hydrophobic organic carrier, an branched fatty alcohols; branched fatty acids; fatty acids organic polar solvent, an emollient and mixtures substituted with a hydroxyl group; cetyl alcohol; stearyl thereof, at a concentration of about 2% to about 50% alcohol: arachidyl alcohol; behenyl alcohol: 1-triacontanol: by weight; hexadecanoic acid; Stearic acid; arachidic acid; behenic acid; octacosanoic acid; 12-hydroxy Stearic acid and mixtures iii. a surface-active agent; thereof. iv. about 0.01% to about 5% by weight of at least one 10. The kit of claim 1 or 9, wherein the antibiotic agent polymeric additive selected from the group consist is selected from the group consisting of beta-lactam antibi ing of a bioadhesive agent, a gelling agent, a film otics, aminoglycosides, ansa-type antibiotics, anthraquino forming agent and a phase change agent; nes, antibiotic azoles, antibiotic glycopeptides, macrollides, antibiotic nucleosides, antibiotic peptides, antibiotic poly V. water, and enes, antibiotic polyethers, quinolones, antibiotic steroides, vi. liquefied or compressed gas propellant at a concen Sulfonamides, tetracycline, dicarboxylic acids, antibiotic tration of about 3% to about 25% by weight of the metals, oxidizing agents, Substances that release free radi total composition. cals and/or active oxygen, cationic antimicrobial agents, 2. The kit of claim 1, wherein the foamable composition quaternary ammonium compounds, biguanides, triguanides, is selected from the group consisting of an oil-in-water bisbiguanides and analogs and polymers thereof and natu emulsion and a water-in-oil emulsion. rally occurring antibiotic compounds. 3. The kit of claim 1, wherein the outlet comprises a valve, 11. The kit of claim 10, wherein the antibiotic agent is containing a stem with 1 to 4 apertures formed in the stem. selected from the group consisting of 4. The kit of claim 3, wherein each aperture formed in the i. A beta-lactam, selected from the group consisting of stem has a diameter, selected from the group consisting of (i) 2-(3-alanyl)clavam, 2-hydroxymethylclavam, 8-epi about 0.2 mm to about 1 mm; (ii) about 0.3 mm to about 0.8 thienamycin, acetyl-thienamycin, amoxicillin, amox mm; and (iii) about 0.01 mm and 1 mm. icillin Sodium, amoxicillin trihydrate, amoxicillin-po 5. The kit of claim 3, wherein the sum of cross-sectional tassium clavulanate combination, amplicillin, areas of all apertures in the stem is between about 0.04 mm ampicillin Sodium, amplicillin trihydrate, amplicillin and 0.5 mm. Sulbactam, apalcillin, aspoxicillin, azidocillin, azlocil 6. The kit of claim 3, wherein the valve is attached to lin, aztreonam, bacampicillin, biapenem, carbenicillin, metered dose device. carbenicillin disodium, carfecillin, carindacillin, car 7. The kit of claim 1, wherein the at least one organic petimycin, cefacetril, cefaclor, cefadroxil, cefalexin, carrier is present in an amount selected from the group cefaloridine, cefalotin, cefamandole, cefamandole, consisting of (i) about 2% to about 5%; (ii) about 5% to cefapirin, cefatrizine, cefatrizine propylene glycol, US 2006/02694.85 A1 Nov.30, 2006 19

cefazedone, cefazolin, cefbuperaZone, cefcapene, cef mycin (structure 6-deoxy-neomycin B),6-deoxy-neo capene pivoxil hydrochloride, cefdinir, cefditoren, mycin B, 6-deoxy-neomycin C, 6-deoxy-paromomy cefditoren pivoxil, cefepime, cefetamet, cefetamet piv cin, acmimycin, AHB-3',4'-dideoxyribostamycin, oxil, cefixime, cefinenoxime, cefinetazole, cefiminox, AHB-3'-deoxykanamycin B, AHB-3'-deoxyneamine, cefninox, cefimolexin, cefodizime, cefonicid, cefop AHB-3'-deoxyribostamycin, AHB-4"-6"-dideoxy eraZone, ceforanide, cefoselis, cefotaxime, cefotetan, dibekacin, AHB-6'-deoxydibekacin, AHB-dideox cefotiam, cefoxitin, cefoZopran, cefpiramide, cef yneamine, AHB-kanamycin B, AHB-methyl-3'-deoxy pirome, cefpodoxime, cefpodoxime proxetil, cefprozil, kanamycin B, amikacin, amikacin Sulfate, apramycin, cefauinome, cefradine, cefroxadine, cefsulodin, arbekacin, astromicin, astromicin Sulfate, bekanamy ceftazidime, cefteram, cefteram pivoxil, cefiezole, cef cin, bluensomycin, boholmycin, butirosin, butirosin B, tibuten, ceftizoxime, ceftriaxone, cefuroxime, catenulin, coumamidine gammal, coumamidine cefuroxime axetil, cephalosporin, cephamycin, chitino gamma2.D.L-1-N-(alpha-hydroxy-beta-aminopropio Vorin, ciclacillin, clavulanic acid, clometocillin, cloX nyl)-XK-62-2, dactimicin, de-O-methyl-4-N-glycyl acillin, cycloserine, deoxy pluracidomycin, dicloxacil KA-6606VI, de-O-methyl-KA-6606I, de-O-methyl lin, dihydro pluracidomycin, epicillin, epithienamycin, KA-7038I, destomycin A, destomycin B, di-N6'O3 ertapenem, faropenem, flomoxef, flucloxacillin, het demethylistamycin A, dibekacin, dibekacin Sulfate, acillin, imipenem, lenampicillin, loracarbef mecilli dihydrostreptomycin, dihydrostreptomycin Sulfate, epi nam, meropenem, metampicillin, meticillin, mezlocil formamidoylglycidylfortimicin B, epihygromycin, lin, moxalactam, nafcillin, northienamycin, oxacillin, formimidoyl-istamycin A, formimidoyl-istamycin B, panipenem, penamecillin, penicillin, phenethicillin, fortimicin B, fortimicin C, fortimicin D, fortimicin KE, piperacillin, taZobactam, pivampicillin, pivoefalexin, fortimicin KF, fortimicin KG, fortimicin KG 1 (stere pivmecillinam, pivmecillinam hydrochloride, pluraci oisomer KG1/KG2), fortimicin KG2 (stereoisomer domycin, propicillin, Sarmoxicillin, Sulbactam, Sulbe KG1/KG2), fortimicin KG3, framycetin, framycetin nicillin, talampicillin, temocillin, terconazole, thiena Sulphate, gentamicin, gentamycin Sulfate, globeomy mycin, ticarcillin; cin, hybrimycin A1, hybrimycin A2, hybrimycin B1, hybrimycin B2, hybrimycin C1, hybrimycin C2, ii. An aminoglycosides, selected from the group consist hydroxyStreptomycin, hygromycin, hygromycin B, ing of 1,2'-N-DL-isoseryl-3',4'-dideoxykanamycin B, isepamicin, isepamicin Sulfate, istamycin, kanamycin, 1,2'-N-DL-isoseryl-kanamycin B, 1,2'-N-(S)-4-amino kanamycin Sulphate, kasugamycin, lividomycin, mar 2-hydroxybutyryl-3',4'-dideoxykanamycin B, 1,2'-N- comycin, micronomicin, micronomicin Sulfate, (S)-4-amino-2-hydroxybutyryl-kanamycin B, 1-N- mutamicin, myomycin, N-demethyl-7-O-demethyl (2-Aminobutanesulfonyl) kanamycin A, 1-N-(2- celesticetin, demethylcelesticetin, methanesulfonic aminoethanesulfonyl)3',4'-dideoxyribostamycin, 1-N- acid derivative of istamycin, nebramycin, nebramycin, (2-Aminoethanesulfonyl)3'-deoxyribostamycin, 1-N- neomycin, netilmicin, oligostatin, paromomycin, quin (2-aminoethanesulfonyl)3'4'-dideoxykanamycin B, tomycin, ribostamycin, Saccharocin, seldomycin, siso 1-N-(2-aminoethanesulfonyl)kanamycin A, 1-N-(2- micin, Sorbistin, spectinomycin, streptomycin, tobra aminoethanesulfonyl)kanamycin B, 1-N-(2-aminoet mycin, trehaloSmaine, trestatin, validamycin, hanesulfonyl)ribostamycin, 1-N-(2-aminopropane Verdamycin, Xylostasin, Zygomycin; Sulfonyl)3'-deoxykanamycin B, 1-N-(2- aminopropanesulfonyl)3'4'-dideoxykanamycin B, 1-N- iii. an ansa-type antibiotics, selected from the group (2-aminopropanesulfonyl)kanamycin A, 1-N-(2- consisting of 21-hydroxy-25-demethyl-25-methylthi aminopropanesulfonyl)kanamycin B, 1-N-(L-4-amino oprotostreptovaricin, 3-methylthiorifamycin, ansami 2-hydroxy-butyryl)2,3'-dideoxy-2'-fluorokanamycin tocin, atropisostreptovaricin, awamycin, halomicin, A, 1-N-(L-4-amino-2-hydroxy-propionyl)2.3'- maytansine, naphthomycin, rifabutin, rifamide, dideoxy-2'-fluorokanamycin A, 1-N-DL-3',4'-dideoxy rifampicin, rifamycin, rifapentine, rifaximin, rubradi isoserylkanamycin B,1-N-DL-isoserylkanamycin, 1-N- rin, streptovaricin, tolypomycin; DL-isoserylkanamycin B, 1-N-L-(-)-(alpha-hydroxy gamma-aminobutyryl)-XK-62-2,2',3'-dideoxy-2'- iv. an anthraquinone, selected from the group consisting fluorokanamycin A.2-hydroxygentamycin A3, of auramycin, cinerubin, ditrisarubicin, ditrisarubicin 2-hydroxygentamycin B, 2-hydroxygentamycin B1, C. figaroic acid fragilomycin, minomycin, rabelomy 2-hydroxygentamycin JI-20A 2-hydroxygentamycin cin, rudolfomycin, Sulfurmycin; JI-20B, 3"-N-methyl-4"-C-methyl-3',4'-dodeoxy kana ... an azole, selected from the group consisting of aza mycin A, 3"-N-methyl-4"-C-methyl-3',4'-dodeoxy nidazole, bifonazole, butoconazol, chlormidazole, kanamycin B, 3"-N-methyl-4"-C-methyl-3',4'-diode chlormidazole hydrochloride, cloconazole, cloconazole oxy-6'-methyl kanamycin B, 3',4'-Dideoxy-3'-eno-ri monohydrochloride, clotrimaZol, dimetridazole, econa bostamycin.3',4'-dideoxyneamine.3',4'-dideoxyribosta Zole, econazole nitrate, enilconazole, fenticonazole, mycin, 3'-deoxy-6'-N-methyl-kanamycin B,3'- fenticonazole nitrate, fezatione, fluconazole, flutrima deoxyneamine.3'-deoxyribostamycin, Zole, isoconazole, isoconazole nitrate, itraconazole, 3'-oxysaccharocin,3,3'-nepotrehalosadiamine, ketoconazole, lanoconazole, metronidazole, metron 3-demethoxy-2"-N-formimidoylistamycin B disulfate idazole benzoate, miconazole, miconazole nitrate, neti tetrahydrate, 3-demethoxyistamycin B.3-O-demethyl conazole, nimorazole, niridazole, omoconazol, omida 2-N-formimidoylistamycin B, 3-O-demethylistamycin Zole, oxiconazole, oxiconazole nitrate, propenidazole, B,3-trehalosamine,4",6'-dideoxydibekacin, 4-N-gly secnidazol, Sertaconazole, Sertaconazole nitrate, Sul cyl-KA-6606VI, 5"-Amino-3',4',5'-trideoxy-butirosin conazole, Sulconazole nitrate, tinidazole, tioconazole, A 6'-deoxydibekacin,6'-epifortimicin A, 6-deoxy-neo Voriconazol; US 2006/02694.85 A1 Nov.30, 2006 20

vi. a glycopeptide, selected from the group consisting of pristin, Safracin, salmycin, salmycin, salmycin, sandra acanthomycin, actaplanin, avoparcin, balhimycin, mycin, Saramycetin, siomycin, sperabillin, sporamycin, bleomycin B (copper bleomycin), chloroorienticin, a streptomyces compound, Subtilin, teicoplanin agly chloropolysporin, demethylvancomycin, enduracidin, cone, telomycin, thermothiocin, thiopeptin, thiostrep galacardin, guanidylfungin, hachimycin, demethyl ton, tridecaptin, tsushimycin, tuberactinomycin, tuber Vancomycin, N-nonanoyl-teicoplanin, phleomycin, actinomycin, tyrothricin, Valinomycin, viomycin, platomycin, ristocetin, staphylocidin, talisomycin, Virginiamycin, Zervacin; teicoplanin, Vancomycin, Victomycin, Xylocandin, Zor bamycin; X. a naturally-occurring peptide that possesses an antibac terial and/or an antifungal activity; vii. a macrollide, selected from the group consisting of acetylleucomycin, acetylkitasamycin, angolamycin, xi. a peptide obtained from a herbal or a vertebrate source: azithromycin, bafilomycin, brefeldin, carbomycin, Xii. a polyene, selected from the group consisting of chalcomycin, cirramycin, clarithromycin, concanamy include, but are not limited to amphotericin, amphot cin, deisovaleryl-niddamycin, demycinosyl-mycina ericin, aureofungin, ayfactin, azalomycin, blasticidin, mycin, Di-O-methyltiacumicidin, dirithromycin, eryth candicidin, candicidin methyl ester, candimycin, can romycin, erythromycin estolate, erythromycin ethyl dimycin methyl ester, chinopricin, filipin, flavofungin, Succinate, erythromycin lactobionate, erythromycin fradicin, hamycin, hydropricin, levorin, lucensomycin, Stearate, flurithromycin, focusin, foromacidin, hateru lucknomycin, mediocidin, mediocidin methyl ester, malide, haterumalide, josamycin, josamycin ropionate, mepartricin, methylamphotericin, natamycin, niphimy juvenimycin, juvenimycin, kitasamycin, ketotiacumi cin, nystatin, nystatin methyl ester, oxypricin, partricin, cin, lankavacidin, lankavamycin, leucomycin, mache pentamycin, perimycin, pimaricin, primycin, proticin, cin, maridomycin, megalomicin, methyleucomycin, rimocidin, sistomycosin, Sorangicin, trichomycin; methymycin, midecamycin, miocamycin, mycamino Syltylactone, mycinomycin, neutramycin, niddamycin, xiii. a polyether, selected from the group consisting of nonactin, oleandomycin, phenylacetyldeltamycin, 20-deoxy-epi-narasin, 20-deoxysalinomycin, carrio pamamycin, picromycin, rokitamycin, rosaramicin, mycin, dianemycin, dihydrolonomycin, etheromycin, roXithromycin, Sedecamycin, shincomycin, spiramy ionomycin, iso-lasalocid, lasalocid, lenoremycin, lono cin, Swalpamycin, tacrolimus, tellithromycin, tiacumi mycin, lysocellin, monensin, narasin, oxolonomycin, a cin, tilmicosin, treponemycin, troleandomycin, tylosin, polycyclic ether antibiotic, salinomycin; venturicidin; Xiv. a quinolone, selected from the group consisting of viii. a nucleoside, selected from the group consisting of alkyl-methylendioxy-4-(1H)-oxocinnoline-3-carboxylic amicetin, angustmycin, azathymidine, blasticidin S. acid, alatrofloxacin, cinoxacin, ciprofloxacin, ciprof epiroprim, flucytosine, gougerotin, mildiomycin, loxacin hydrochloride, danofloxacin, dermofongin A, nikkomycin, nucleocidin, oxanosine, oxanosine, puro enoxacin, enrofloxacin, fleroxacin, flumequine, gati mycin, pyrazomycin, showdomycin, sinefungin, spar floxacin, gemifloxacin, grepafloxacin, levofloxacin, Sogenin, Spicamycin, tunicamycin, uracil polyoxin, lomefloxacin, lomefloxacin, hydrochloride, miloxacin, vengicide; moxifloxacin, nadifloxacin, nalidixic acid, nifuroquine, norfloxacin, ofloxacin, orbifloxacin, oxolinic acid, ix. apeptide, selected from the group consisting of acti paZufloxacine, pefloxacin, pefloxacin mesylate, pipe nomycin, aculeacin, alaZopeptin, amfomycin, amythia midic acid, piromidic acid, premafloxacin, roSoxacin, mycin, antifungal from Zalerion arboricola, antrimy rufloxacin, sparfloxacin, temafloxacin, to Sufloxacin, cin, apid, apidaecin, aspartocin, auromomycin, trovafloxacin; bacileucin, bacillomycin, bacillopeptin, bacitracin, bagacidin, beminamycin, beta-alanyl-L-tyrosine, bot XV. a steroid, selected from the group consisting of ami tromycin, capreomycin, caspofungine, cepacidine, cer nosterol, ascosteroside, cladosporide, dihydrofusidic exin, cillofungin, circulin, colistin, cyclodepsipeptide, acid, dehydro-dihydrofusidic acid, dehydrofusidic acid, cytophagin, dactinomycin, daptomycin, decapeptide, fusidic acid and squalamine; desoxymulundocandin, echanomycin, echinocandin B, echinomycin, ecomycin, enniatin, etamycin, fabatin, Xvi. asulfonamide, selected from the group consisting of ferrimycin, ferrimycin, ficellomycin, fluoronocathia chloramine, dapsone, mafenide, phthalylsulfathiazole, cin, fusaricidin, gardimycin, gatavalin, globopeptin, Succinylsulfathiazole, Sulfabenzamide, Sulfacetamide, glyphomycin, gramicidin, herbicolin, iomycin, iturin, Sulfachlorpyridazine, Sulfadiazine, Sulfadiazine silver, iyomycin, iZupeptin, janiemycin, janthinocin, jolipep Sulfadicramide, Sulfadimethoxine, Sulfadoxine, Sulf tin, katanosin, killertoxin, lipopeptide antibiotic, aguanidine, Sulfalene, SulfamaZone, Sulfamerazine, Sul lipopeptide from Zalerion sp., lysobactin, lysozyme, famethazine, Sulfamethizole, Sulfamethoxazole, Sul macromomycin, magainin, melittin, mersacidin, mika famethoxypyridazine, Sulfamonomethoxine, mycin, mureidomycin, mycoplanecin, mycosubtilin, SulfamoXol, Sulfanilamide, Sulfaperine, Sulfaphenazol. neopeptifluorin, neoviridogrisein, netropsin, nisin, Sulfapyridine, Sulfaquinoxaline, SulfaSuccinamide, Sul nocathiacin, nocathiacin 6-deoxyglycoside, nosihep fathiazole, Sulfathiourea, Sulfatolamide, Sulfatriazin, tide, octapeptin, pacidamycin, pentadecapeptide, pep Sulfisomidine, Sulfisoxazole, Sulfisoxazole acetyl and tifluorin, permetin, phytoactin, phytostreptin, plan Sulfacarbamide; othiocin, plusbacin, policillin, polymyxin antibiotic Xvii. a tetracycline, selected from the group consisting of complex, polymyxin B, polymyxin B1, polymyxin F, dihydrosteflimycin, demethyltetracycline, aclacinomy preneocarzinostatin, quinomycin, quinupristin-dalfo cin, akrobomycin, baumycin, bromotetracycline, ceto US 2006/02694.85 A1 Nov.30, 2006 21

cyclin, chlortetracycline, clomocycline, daunorubicin, XXVi. a polymeric biguanide; demeclocycline, doxorubicin, doxorubicin hydrochlo ride, doxycycline, lymecyclin, marcellomycin, meclo XXVii. an agent, selected from the group consisting of cycline, meclocycline Sulfosalicylate, methacycline, abomycin, acetomycin, acetoxycycloheximide, acetyl minocycline, minocycline hydrochloride, musettamy nanaomycin, an actinoplanes sp. Compound, actinopy rone, aflastatin, albacarcin, albacarcin, albofungin, cin, oxytetracycline, rhodirubin, rollitetracycline, rubo albofungin, alisamycin, alpha-RS-methoxycarbonyl mycin, serirubicin, Steflimycin and tetracycline; benzylmonate, altromycin, amicetin, amycin, amycin Xviii. a dicarboxylic acid, selected from the group con demanoyl compound, amycine, amycomycin, anandi sisting of adipic acid, pimelic acid, Suberic acid, azelaic mycin, anisomycin, anthramycin, anti-Syphilis imune acid, sebacic acid, 1.11-undecanedioic acid, 1,12-dode Substance, anti-tuberculosis imune Substance, antibi canedioic acid, 1,13-tridecanedioic acid and 1,14-tet otic from Eschericia coli, antibiotics from Streptomy radecanedioic acid. ces refitineus, anticapsin, antimycin, aplasmomycin, aranorosin, aranorosinol, arugomycin, ascofuranone, xix. an antibiotic metal or a metal ion, wherein the metal ascomycin, ascosin, Aspergillus flavus antibiotic, is selected from the group consisting of silver, copper, asukamycin, aurantinin, an Aureolic acid antibiotic Zinc, mercury, tin, lead, bismutin, cadmium, chromium Substance, aurodox, avilamycin, azidamfenicol, azidi and gold; mycin, bacillaene, a Bacillus larvae antibiotic, bacto XX. a silver compound, selected from the group consisting bolin, benanomycin, benzanthrin, benzylmonate, of silver acetate, silver benzoate, silver carbonate, bicoZamycin, bravomicin, brodimoprim, butalactin, silver iodate, silver iodide, silver lactate, silver laurate, calcimycin, calvatic acid, candiplanecin, carumonam, silver nitrate, silver oxide, silver palmitate, silver pro carzinophilin, celesticetin, cepacin, cerulenin, cervino tein, and silver Sulfadiazine; mycin, chartreusin, chloramphenicol, chloramphenicol palmitate, chloramphenicol Succinate sodium, chlorfla XXi. an oxidizing agent or a Substance that release free Vonin, chlorobiocin, chlorocarcin, chromomycin, ciclo radicals and/or active oxygen, selected from the group piroX, ciclopiroX olamine, citreamicin, cladosporin, consisting of oxygen, hydrogen peroxide, benzoyl per claZamycin, clecarmycin, clindamycin, coliformin, col oxide, elemental halogen species, as well as oxygen linomycin, copiamycin, corallopyronin, corynecandin, ated halogen species, bleaching agents (e.g., Sodium, coumermycin, culpin, cuprimyxin, cyclamidomycin, calcium or magnesium hypochloride and the like), cycloheximide, dactylomycin, danomycin, danubomy perchlorite species, iodine, iodate, and benzoyl peroX cin, delaminomycin, demethoxyrapamycin, demeth ide; ylscytophycin, dermadin, desdamethine, dexylosyl XXii. a cationic antimicrobial agent, selected from the benanomycin, pseudoaglycone, dihydromocimycin, group consisting of quaternary ammonium compounds, dihydronancimycin, diumycin, dnacin, dorrigocin, dynemycin, dynemycin triacetate, ecteinascidin, efro alkyltrimethyl ammonium bromide, cetrimide, benza tomycin, endomycin, ensanchomycin, equisetin, erica Ikonium chloride, n-alkyldimethylbenzyl ammonium mycin, esperamicin, ethylmonate, everninomicin, fel chloride, dialkylmethyl ammonium halide and dialky damycin, flambamycin, flavensomycin, florfenicol, Ibenzyl ammonium halide; fluvomycin, fosfomycin, foSfonochlorin, fredericamy XXiii. a biguanide, a biguanidine or a triguanide having a cin, frenolicin, fumagillin, fumifungin, funginon, fusa skeleton selected from: candin, fusafungin, gelbecidine, glidobactin, grahami mycin, granaticin, griseofulvin, griseoviridin, grisonomycin, hayumicin, hayumicin, haZymicin, 4 2 2 HN NH NH hedamycin, heneicomycin, heptelicid acid, holomycin, 4 6 humidin, isohematinic acid, karnatakin, kaZusamycin, 5 3 1. NH NH2 kristenin, L-dihydrophenylalanine, a L-isoleucyl-L-2-

HN HN NH2 H2N HN3 r amino-4-(4-amino-2',5'-cyclohexadienyl) derivative, Biguanide NH lanomycin, leinamycin, leptomycin, libanomycin, lin 5 comycin, lomofungin, lysolipin, magnesidin, manumy Biguanidine cin, melanomycin, methoxycarbonylmethylmonate, 6 4 2 methoxycarbonylethylmonate, methoxycarbonylphe NH NH NH nylmonate, methyl pseudomonate, methylmonate, 7 ls 5 ls 3 ls microcin, mitomalcin, mocimycin, moenomycin, HN HN HN NH2 monoacetyl cladosporin, monomethyl cladosporin, Triguanide mupirocin, mupirocin calcium, mycobacidin, myriocin, myxopyronin, pseudoaglycone, nanaomycin, nancimy cin, nargenicin, neocarcinostatin, neoenactin, neothra XXiv. a compound, selected from the group consisting of mycin, nifurtoinol, nocardicin, nogalamycin, novobio chlorhexidine acetate, chlorhexidine gluconate and cin, octylmonate, olivomycin, orthosomycin, chlorhexidine hydrochloride, picloxydine, alexidine, oudemansin, oxirapentyn, oxoglaucine methiodide, polihexanide, chlorproguanil hydrochloride, proguanil pactacin, pactamycin, papulacandin, paulomycin, hydrochloride, metformin hydrochloride, phenformin phaeoramularia fungicide, phenelfamycin, phenyl, and buformin hydrochloride: cerulenin, phenylmonate, pholipomycin, pirlimycin, pleuromutilin, a polylactone derivative, polynitroxin, XXV. a cationic polymeric antimicrobial agent; polyoxin, porfiromycin, pradimicin, prenomycin, Prop US 2006/02694.85 A1 Nov.30, 2006 22

2-enylmonate, protomycin, Pseudomonas antibiotic, (iv) from 30 to 100 parts of solvent required for 1 part of pseudomonic acid, purpuromycin, pyrinodemin, pyr Solute; rolnitrin, pyrrolomycin, amino, chloro pentenedioic acid, rapamycin, rebeccamycin, resistomycin, reuterin, (v) from 100 to 1000 parts of a solvent required for 1 part reveromycin, rhizocticin, roridin, rubiflavin, naphthy of Solute; and ridinomycin, Saframycin, Saphenamycin, Sarkomycin, (vi) 10,000 parts or more of a solvent required for 1 part Sarkomycin, Sclopularin, selenomycin, siccanin, spar of solute. tanamicin, spectinomycin, spongistatin, Stravidin, 16. The kit of claim 2, wherein the antibiotic agent is streptolydigin, Streptomyces arenae antibiotic complex, dissolved in at least one phase of the emulsion. streptonigrin, Streptothricins, streptovitacin, streptozo 17. The kit of claim 1, wherein the foamable composition tocine, a strobilurin derivative, stubomycin, Sul further contains at least one additional therapeutic agent famethoxazol-trimethoprim, Sakamycin, tejeramycin, selected from the group consisting of an a steroidal anti terpentecin, tetrocarcin, thermorubin, thermozymoci inflammatory agent, an immunosuppressive agent, an immu din, thiamphenicol, thioaurin, thiolutin, thiomarinol, nomodulator, an immunoregulating agent, a hormonal agent, thiomarinol, tirandamycin, tolytoxin, trichodermin, an antifungal agent, an antiviral agent, an antiparasitic agent, trienomycin, trimethoprim, trioxacarcin, tyrissamycin, vitamin A, a vitamin A derivative, vitamin B, a vitamin B umbrinomycin, unphenelfamycin, urauchimycin, usnic derivative, vitamin C, a vitamin C derivative, vitamin D, a acid, uredolysin, variotin, Vermisporin, Verrucarin and vitamin D derivative, vitamin E, a vitamin E derivative, analogs, salts and derivatives thereof. vitamin F, a vitamin F derivative, vitamin K, a vitamin K XXViii. a naturally occurring antibiotic compound, derivative, a wound healing agent, a disinfectant, an anes Selected from the group consisting of phenol, resorci thetic, an antiallergic agent, an alpha hydroxyl acid, lactic nol, antibiotic aminoglycosides, anamycin, quinines, acid, glycolic acid, a beta-hydroxy acid, a protein, a peptide, anthraquinones, antibiotic glycopeptides, azoles, mac a neuropeptide, a allergen, an immunogenic Substance, a rolides, avilamycin, agropyrene, cnicin, aucubin anti haptene, an oxidizing agent, an antioxidant, a dicarboxylic bioticsaponin fractions, berberine (isoquinoline alka acid, azelaic acid, sebacic acid, adipic acid, fumaric acid, a loid), arctiopicrin (Sesquiterpene lactone), lupulone, retinoid, an antiproliferative agent, an anticancer agent, a humulone (bitter acids), allicin, hyperforin, echinaco photodynamic therapy agent, benzoyl chloride, calcium side, coniosetin, tetramic acid, imanine and novoima hypochlorite, magnesium hypochlorite, an anti-wrinkle nine; agent, a radical scavenger, a metal, silver, a metal oxide, titanium dioxide, Zinc oxide, Zirconium oxide, iron oxide, XXix. a plant oil or extracts which contain antibiotic silicone oxide, talc, carbon, an anti wrinkle agent, a skin agents: whitening agent, a skin protective agent, a masking agent, an XXX. an oil or extract of a plant selected from the group anti-wart agent, a refatting agent, a lubricating agent and consisting of thyme, perilla, lavender, tea tree, terfezia mixtures thereof. clayeryi, Micromonospora, putterlickia Verrucosa, 18. The kit of claim 1, wherein the concentration of the putterlickia pyracantha putterlickia retroSpinosa, May surface active agent is between about 0.1% and about 5%. tenus ilicifolia, maytenus evonymoides, maytenus 19. The kit of claim 1, wherein the surface active agent aquifolia, faenia interjecta, cordyceps sinensis, couch includes a mixture of at least one non-ionic Surfactant and at grass, holy thistle, plantain, burdock, hops, echinacea, least one ionic Surfactant in a ratio in the range of about buchu, chaparral, myrrh, red clover and yellow dock, 100:1 to 1:1. garlic and St. John’s wort; and 20. The kit of claim 1, wherein the surface active agent esters and salts thereof. comprises a combination of a non-ionic Surfactant and an 12. The kit of claim 1 or 9, wherein the concentration ionic surfactant, at a ratio of between 1:1 and 20:1. range of the antibiotic agent is selected from the group of (i) 21. The kit of claim 1, wherein the surface active agent between about 0.005% and about 0.5%; (ii) between about consists essentially of a non-ionic Surfactant. 0.5% and about 2%; (iii) between about 2% and about 5%; 22. The kit of claim 2, wherein the emulsion is selected and (iv) between about 5% and about 12%. from: 13. The kit of claim 1 or 9, wherein the antibiotic agent is a vasodilator. i. an oil-in-water emulsion and wherein the HLB range of 14. The kit of claim 1 or 9, wherein upon release from the the surface active agent is between about 9 and about container, a shear-sensitive foam, having a density range 14; and selected from (1) between about 0.02 gr/mL and about 0.1 ii. a water-in-oil emulsion and wherein the HLB range of gr/mL; and (2) between about 0.02 gr/mL and about 0.1 the Surface active agent is between about 2 and about gr/mL, is produced. 9. 15. The kit of claim 2, wherein the graded of solubility of 23. The kit of claim 1, wherein the surface active agent the antibiotic agent in the aqueous phase of the emulsion is comprises a combination of at least one non-ionic Surfactant selected from the groups consisting of: having HLB of less than 9 and at least one non-ionic (i) less than 1 parts of solvent required for 1 part of solute; surfactant having HLB of equal or more than 9, wherein the ratio between the at least one non-ionic Surfactant having (ii) from 1 to 10 parts of solvent required for 1 part of HLB of less than 9 and the at least one non-ionic surfactant Solute; having HLB of equal or more than 9, is between 1:8 and 8:1. (iii) from 10 to 30 parts of solvent required for 1 part of 24. The kit of claim 1, wherein the polymeric agent is Solute; selected from the group consisting of a water-soluble poly US 2006/02694.85 A1 Nov.30, 2006 mer, a water-insoluble polymer, a gelling agent, an inorganic substituted with a hydroxyl group; cetyl alcohol; stearyl gelling agent, a mucoadhesive macromolecule and a film alcohol: arachidyl alcohol; behenyl alcohol: 1-triacontanol: forming polymer. hexadecanoic acid; Stearic acid; arachidic acid; behenic acid; 25. The kit of claim 24, wherein the water-soluble poly octacosanoic acid; 12-hydroxy Stearic acid and mixtures mer is selected from the group consisting of methylcellu thereof. lose, hydroxypropyl cellulose, hydroxypropyl methylcellu 36. The composition of claim 34, wherein the concentra lose (Methocel), hydroxyethyl cellulose, tion of the surface active agent is between about 0.1% and methylhydroxyethylcellulose, methylhydroxypropylcellu about 5% by weight. lose, hydroxyethylcarboxymethylcellulose, carboxymethyl 37. The composition of claim 34 or 35, wherein the cellulose, carboxymethylhydroxyethylcellulose, Xanthan antibiotic agent is selected from the group consisting of gum, guar gum, carrageenin gum, locust bean gum and beta-lactam antibiotics, aminoglycosides, ansa-type antibi tragacanth gum. otics, anthraquinones, antibiotic azoles, antibiotic glycopep 26. The kit of claim 1, wherein the foamable composition tides, macrollides, antibiotic nucleosides, antibiotic peptides, contains at least one therapeutically active oil. antibiotic polyenes, antibiotic polyethers, quinolones, anti 27. The kit of claim 1 or 9, wherein the composition biotic steroides, Sulfonamides, tetracycline, dicarboxylic further contains a penetration enhancer. acids, antibiotic metals, oxidizing agents, Substances that 28. The kit of claim 27, wherein the penetration enhancer release free radicals and/or active oxygen, cationic antimi is selected from the group consisting of propylene glycol, crobial agents, quaternary ammonium compounds, bigu butylene glycols, hexylene glycol, glycerol, pentaerythritol, anides, triguanides, bisbiguanides and analogs and polymers Sorbitol, mannitol, oligosaccharides, dimethyl isosorbide, thereof and naturally occurring antibiotic compounds. monooleate of ethoxylated glycerides having about 8 to 10 38. The composition of claim 37, wherein the antibiotic ethylene oxide units, polyethylene glycol 200-600, transcu agent is selected from the group consisting of tol, glycofurol and cyclodextrins. 29. The kit of claim 1, wherein the pH of the foamable i. A beta-lactam, selected from the group consisting of composition is selected from the group consisting of (i) 2-(3-alanyl)clavam, 2-hydroxymethylclavam, 8-epi between about 4.5 and about 7.0, wherein the composition thienamycin, acetyl-thienamycin, amoxicillin, amox is intended for skin treatment; and (ii) between about 3 and icillin Sodium, amoxicillin trihydrate, amoxicillin-po about 4.5, wherein the composition is intended for vaginal tassium clavulanate combination, amplicillin, treatment. ampicillin Sodium, amplicillin trihydrate, amplicillin 30. The kit of claim 29, wherein pH of the composition is Sulbactam, apalcillin, aspoxicillin, azidocillin, aziocil adjusted using an agent, selected from the group consisting lin, aztreonam, bacampicillin, biapenem, carbenicillin, of an acid, a base and a buffering agent. carbenicillin disodium, carfecillin, carindacillin, car 31. The kit of claim 1, wherein the organic carrier petimycin, cefacetril, cefaclor, cefadroxil, cefalexin, contains a PPG alkyl ether. cefaloridine, cefalotin, cefamandole, cefamandole, 32. The kit of claim 31, wherein the concentration of the cefapirin, cefatrizine, cefatrizine propylene glycol, PPG alkyl ether is between about 1% and about 20%. cefazedone, cefazolin, cefbuperaZone, cefcapene, cef 33. The kit of claim 32, wherein the foam is non capene pivoxil hydrochloride, cefdinir, cefditoren, flammable, when tested according to European Standard cefditoren pivoxil, cefepime, cefetamet, cefetamet piv prEN 14851. oxil, cefixime, cefinenoxime, cefinetazole, cefiminox, 34. A therapeutic foamable composition including: cefiminox, cefimolexin, cefodizime, cefonicid, cefop eraZone, ceforanide, cefoselis, cefotaxime, cefotetan, i. an antibiotic agent; cefotiam, cefoxitin, cefoZopran, ce?piramide, cef ii. a therapeutically active oil; pirome, cefpodoxime, cefpodoxime proxetil, cefprozil, cefauinome, cefradine, cefroxadine, cefsulodin, iii. a Surface-active agent; ceftazidime, cefteram, cefteram pivoxil, cefiezole, cef tibuten, ceftizoxime, ceftriaxone, cefuroxime, iv. about 0.01% to about 5% by weight of at least one cefuroxime axetil, cephalosporin, cephamycin, chitino polymeric additive selected from the group consisting Vorin, ciclacillin, clavulanic acid, clometocillin, clox of a bioadhesive agent, a gelling agent, a film forming acillin, cycloserine, deoxy pluracidomycin, dicloxacil agent and a phase change agent; lin, dihydro pluracidomycin, epicillin, epithienamycin, V. water; and ertapenem, faropenem, flomoxef, flucloxacillin, het acillin, imipenem, lenampicillin, loracarbef mecilli vi. liquefied or compressed gas propellant at a concentra nam, meropenem, metampicillin, meticillin, meZiocil tion of about 3% to about 25% by weight of the total lin, moxalactam, nafcillin, northienamycin, oxacillin, composition. panipenem, penamecillin, penicillin, phenethicillin, 35. The composition of claim 34, further including about piperacillin, taZobactam, pivampicillin, pivoefalexin, 0.1% to about 5% by weight of a therapeutically active foam pivmecillinam, pivmecillinam hydrochloride, pluraci adjuvant is selected from the group consisting of fatty domycin, propicillin, Sarmoxicillin, Sulbactam, Sulbe alcohols having 15 or more carbons in their carbon chain; nicillin, talampicillin, temocillin, terconazole, thiena fatty acids having 16 or more carbons in their carbon chain; mycin, ticarcillin; fatty alcohols derived from beeswax and including a mixture of alcohols, a majority of which has at least 20 carbon atoms ii. An aminoglycosides, selected from the group consist in their carbon chain; fatty alcohols having at least one ing of 1,2'-N-DL-isoseryl-3',4'-dideoxykanamycin B, double bond; fatty acids having at least one double bond; 1,2'-N-DL-isoseryl-kanamycin B, 1,2'-N-(S)-4-amino branched fatty alcohols; branched fatty acids; fatty acids 2-hydroxybutyryl-3',4'-dideoxykanamycin B, 1,2'-N- US 2006/02694.85 A1 Nov.30, 2006 24

(S)-4-amino-2-hydroxybutyryl-kanamycin B, 1-N- comycin, micronomicin, micronomicin Sulfate, (2-Aminobutanesulfonyl) kanamycin A, 1-N-(2- mutamicin, myomycin, N-demethyl-7-O-demethyl aminoethanesulfonyl)3',4'-dideoxyribostamycin, 1-N- celesticetin, demethylcelesticetin, methanesulfonic (2-Aminoethanesulfonyl)3'-deoxyribostamycin, 1-N- acid derivative of istamycin, nebramycin, nebramycin, (2-aminoethanesulfonyl)3'4'-dideoxykanamycin B, neomycin, netilmicin, oligostatin, paromomycin, quin 1-N-(2-aminoethanesulfonyl)kanamycin A, 1-N-(2- tomycin, ribostamycin, Saccharocin, seldomycin, siso aminoethanesulfonyl)kanamycin B, 1-N-(2-aminoet micin, Sorbistin, spectinomycin, streptomycin, tobra hanesulfonyl)ribostamycin, 1-N-(2-aminopropane mycin, trehaloSmaine, trestatin, validamycin, Sulfonyl)3'-deoxykanamycin B, 1-N-(2- Verdamycin, Xylostasin, Zygomycin; aminopropanesulfonyl)3'4'-dideoxykanamycin B, 1-N- iii. an ansa-type antibiotics, selected from the group (2-aminopropanesulfonyl)kanamycin A, 1-N-(2- consisting of 21-hydroxy-25-demethyl-25-methylthi aminopropanesulfonyl)kanamycin B, 1-N-(L-4-amino oprotostreptovaricin, 3-methylthiorifamycin, ansami 2-hydroxy-butyryl)2,3'-dideoxy-2'-fluorokanamycin tocin, atropisostreptovaricin, awamycin, halomicin, A, 1-N-(L-4-amino-2-hydroxy-propionyl)2.3'- maytansine, naphthomycin, rifabutin, rifamide, dideoxy-2'-fluorokanamycin A, 1-N-DL-3',4'-dideoxy rifampicin, rifamycin, rifapentine, rifaximin, rubradi isoserylkanamycin B,1-N-DL-isoserylkanamycin, 1-N- rin, streptovaricin, tolypomycin; DL-isoserylkanamycin B, 1-N-L-(-)-(alpha-hydroxy gamma-aminobutyryl)-XK-62-2,2',3'-dideoxy-2'- iv. an anthraquinone, selected from the group consisting fluorokanamycin A.2-hydroxygentamycin A3, of auramycin, cinerubin, ditrisarubicin, ditrisarubicin 2-hydroxygentamycin B, 2-hydroxygentamycin B1, C. figaroic acid fragilomycin, minomycin, rabelomy 2-hydroxygentamycin JI-20A 2-hydroxygentamycin cin, rudolfomycin, Sulfurmycin; JI-20B, 3"-N-methyl-4"-C-methyl-3',4'-dodeoxy kana mycin A, 3"-N-methyl-4"-C-methyl-3',4'-dodeoxy V. an azole, selected from the group consisting of aza kanamycin B, 3"-N-methyl-4"-C-methyl-3',4'-diode nidazole, bifonazole, butoconazol, chlormidazole, oxy-6'-methyl kanamycin B, 3',4'-Dideoxy-3'-eno-ri chlormidazole hydrochloride, cloconazole, cloconazole bostamycin.3',4'-dideoxyneamine.3',4'-dideoxyribosta monohydrochloride, clotrimaZol, dimetridazole, econa mycin, 3'-deoxy-6'-N-methyl-kanamycin B,3'- Zole, econazole nitrate, enilconazole, fenticonazole, deoxyneamine.3'-deoxyribostamycin, fenticonazole nitrate, fezatione, fluconazole, flutrima 3'-oxysaccharocin.3,3'-nepotrehalosadiamine, Zole, isoconazole, isoconazole nitrate, itraconazole, 3-demethoxy-2"-N-formimidoylistamycin B disulfate ketoconazole, lanoconazole, metronidazole, metron tetrahydrate, 3-demethoxyistamycin B.3-O-demethyl idazole benzoate, miconazole, miconazole nitrate, neti 2-N-formimidoylistamycin B, 3-O-demethylistamycin conazole, nimorazole, niridazole, omoconazol, ornida B,3-trehalosamine,4",6'-dideoxydibekacin, 4-N-gly Zole, oxiconazole, oxiconazole nitrate, propenidazole, cyl-KA-6606VI, 5"-Amino-3',4',5'-trideoxy-butirosin secnidazol, Sertaconazole, Sertaconazole nitrate, Sul A 6'-deoxydibekacin,6'-epifortimicin A, 6-deoxy-neo conazole, Sulconazole nitrate, tinidazole, tioconazole, mycin (structure 6-deoxy-neomycin B),6-deoxy-neo Voriconazol; mycin B, 6-deoxy-neomycin C, 6-deoxy-paromomy vi. a glycopeptide, selected from the group consisting of cin, acmimycin, AHB-3',4'-dideoxyribostamycin, acanthomycin, actaplanin, avoparcin, balhimycin, AHB-3'-deoxykanamycin B, AHB-3'-deoxyneamine, bleomycin B (copper bleomycin), chloroorienticin, AHB-3'-deoxyribostamycin, AHB-4"-6"-dideoxy chloropolysporin, demethylvancomycin, enduracidin, dibekacin, AHB-6'-deoxydibekacin, AHB-dideox galacardin, guanidylfungin, hachimycin, demethyl yneamine, AHB-kanamycin B, AHB-methyl-3'-deoxy Vancomycin, N-nonanoyl-teicoplanin, phleomycin, kanamycin B, amikacin, amikacin Sulfate, apramycin, platomycin, ristocetin, staphylocidin, talisomycin, arbekacin, astromicin, astromicin Sulfate, bekanamy teicoplanin, Vancomycin, Victomycin, Xylocandin, Zor cin, bluensomycin, boholmycin, butirosin, butirosin B, bamycin; catenulin, coumamidine gammal, coumamidine gamma2.D.L-1-N-(alpha-hydroxy-beta-aminopropio vii. a macrollide, selected from the group consisting of nyl)-XK-62-2, dactimicin, de-O-methyl-4-N-glycyl acetylleucomycin, acetylkitasamycin, angolamycin, KA-6606VI, de-O-methyl-KA-6606I, de-O-methyl azithromycin, bafilomycin, brefeldin, carbomycin, KA-7038I, destomycin A, destomycin B, di-N6'O3 chalcomycin, cirramycin, clarithromycin, concanamy demethylistamycin A, dibekacin, dibekacin Sulfate, cin, deisovaleryl-niddamycin, demycinosyl-mycina dihydrostreptomycin, dihydrostreptomycin Sulfate, epi mycin, Di-O-methyltiacumicidin, dirithromycin, eryth formamidoylglycidylfortimicin B, epihygromycin, romycin, erythromycin estolate, erythromycin ethyl formimidoyl-istamycin A, formimidoyl-istamycin B, Succinate, erythromycin lactobionate, erythromycin fortimicin B, fortimicin C, fortimicin D, fortimicin KE, Stearate, flurithromycin, focusin, foromacidin, hateru fortimicin KF, fortimicin KG, fortimicin KG 1 (stere malide, haterumalide, josamycin, josamycin ropionate, oisomer KG1/KG2), fortimicin KG2 (stereoisomer juvenimycin, juvenimycin, kitasamycin, ketotiacumi KG1/KG2), fortimicin KG3, framycetin, framycetin cin, lankavacidin, lankavamycin, leucomycin, mache Sulphate, gentamicin, gentamycin Sulfate, globeomy cin, maridomycin, megalomicin, methyleucomycin, cin, hybrimycin A1, hybrimycin A2, hybrimycin B1, methymycin, midecamycin, miocamycin, mycamino hybrimycin B2, hybrimycin C1, hybrimycin C2, Syltylactone, mycinomycin, neutramycin, niddamycin, hydroxystreptomycin, hygromycin, hygromycin B, nonactin, oleandomycin, phenylacetyldeltamycin, isepamicin, isepamicin Sulfate, istamycin, kanamycin, pamamycin, picromycin, rokitamycin, rosaramicin, kanamycin Sulphate, kasugamycin, lividomycin, mar roXithromycin, sedecamycin, shincomycin, spiramy US 2006/02694.85 A1 Nov.30, 2006 25

cin, Swalpamycin, tacrolimus, tellithromycin, tiacumi mycin, lysocellin, monensin, narasin, oxolonomycin, a cin, tilmicosin, treponemycin, troleandomycin, tylosin, polycyclic ether antibiotic, Salinomycin; venturicidin; Xiv. a quinolone, selected from the group consisting of viii. a nucleoside, selected from the group consisting of alkyl-methylendioxy-4-(1H)-oxocinnoline-3-carboxylic amicetin, angustmycin, azathymidine, blasticidin S. acid, alatrofloxacin, cinoxacin, ciprofloxacin, ciprof epiroprim, flucytosine, gougerotin, mildiomycin, loxacin hydrochloride, danofloxacin, dermofongin A, nikkomycin, nucleocidin, oxanosine, oxanosine, puro enoxacin, enrofloxacin, fleroxacin, flumequine, gati mycin, pyrazomycin, showdomycin, sinefungin, spar floxacin, gemifloxacin, grepafloxacin, levofloxacin, Sogenin, Spicamycin, tunicamycin, uracil polyoxin, lomefloxacin, lomefloxacin, hydrochloride, miloxacin, vengicide; moxifloxacin, nadifloxacin, nalidixic acid, nifuroquine, norfloxacin, ofloxacin, orbifloxacin, oxolinic acid, ix. apeptide, selected from the group consisting of acti paZufloxacine, pefloxacin, pefloxacin mesylate, pipe nomycin, aculeacin, alaZopeptin, amfomycin, amythia midic acid, piromidic acid, premafloxacin, roSoxacin, mycin, antifungal from Zalerion arboricola, antrimy cin, apid, apidaecin, aspartocin, auromomycin, rufloxacin, sparfloxacin, temafloxacin, to Sufloxacin, bacileucin, bacillomycin, bacillopeptin, bacitracin, trovafloxacin; bagacidin, berninamycin, beta-alanyl-L-tyrosine, bot XV. a steroid, selected from the group consisting of ami tromycin, capreomycin, caspofungine, cepacidine, cer nosterol, ascosteroside, cladosporide, dihydrofusidic exin, cillofungin, circulin, colistin, cyclodepsipeptide, acid, dehydro-dihydrofusidic acid, dehydrofusidic acid, cytophagin, dactinomycin, daptomycin, decapeptide, fusidic acid and squalamine; desoxymulundocandin, echanomycin, echinocandin B, echinomycin, ecomycin, enniatin, etamycin, fabatin, Xvi. asulfonamide, selected from the group consisting of ferrimycin, ferrimycin, ficellomycin, fluoronocathia chloramine, dapsone, mafenide, phthalylsulfathiazole, cin, fusaricidin, gardimycin, gatavalin, globopeptin, Succinylsulfathiazole, Sulfabenzamide, Sulfacetamide, glyphomycin, gramicidin, herbicolin, iomycin, iturin, Sulfachlorpyridazine, Sulfadiazine, Sulfadiazine silver, iyomycin, iZupeptin, janiemycin, janthinocin, jolipep Sulfadicramide, Sulfadimethoxine, Sulfadoxine, Sulf tin, katanosin, killertoxin, lipopeptide antibiotic, aguanidine, Sulfalene, SulfamaZone, Sulfamerazine, Sul lipopeptide from Zalerion sp., lysobactin, lysozyme, famethazine, Sulfamethizole, Sulfamethoxazole, Sul macromomycin, magainin, melittin, mersacidin, mika famethoxypyridazine, Sulfamonomethoxine, mycin, mureidomycin, mycoplanecin, mycosubtilin, Sulfamoxol, Sulfanilamide, sulfaperine, sulfaphenazol. neopeptifluorin, neoviridogrisein, netropsin, nisin, Sulfapyridine, Sulfaquinoxaline, SulfaSuccinamide, Sul nocathiacin, nocathiacin 6-deoxyglycoside, nosihep fathiazole, Sulfathiourea, Sulfatolamide, Sulfatriazin, tide, octapeptin, pacidamycin, pentadecapeptide, pep Sulfisomidine, Sulfisoxazole, Sulfisoxazole acetyl and tifluorin, permetin, phytoactin, phytostreptin, plan Sulfacarbamide; othiocin, plusbacin, policillin, polymyxin antibiotic Xvii. a tetracycline, selected from the group consisting of complex, polymyxin B, polymyxin B1, polymyxin F, dihydrosteflimycin, demethyltetracycline, aclacinomy preneocarzinostatin, quinomycin, quinupristin-dalfo cin, akrobomycin, baumycin, bromotetracycline, ceto pristin, Safracin, Salmycin, salmycin, salmycin, sandra cyclin, chlortetracycline, clomocycline, daunorubicin, mycin, Saramycetin, siomycin, sperabillin, sporamycin, demeclocycline, doxorubicin, doxorubicin hydrochlo a streptomyces compound, Subtilin, teicoplanin agly ride, doxycycline, lymecyclin, marcellomycin, meclo cone, telomycin, thermothiocin, thiopeptin, thiostrep cycline, meclocycline Sulfosalicylate, methacycline, ton, tridecaptin, tsushimycin, tuberactinomycin, tuber minocycline, minocycline hydrochloride, musettamy actinomycin, tyrothricin, Valinomycin, viomycin, cin, oxytetracycline, rhodirubin, rollitetracycline, rubo Virginiamycin, Zervacin; mycin, serirubicin, Steflimycin and tetracycline; X. a naturally-occurring peptide that possesses an antibac Xviii. a dicarboxylic acid, selected from the group con terial and/or an antifungal activity; sisting of adipic acid, pimelic acid, Suberic acid, azelaic acid, sebacic acid, 1,11-undecanedioic acid, 1,12-dode xi. a peptide obtained from a herbal or a vertebrate source: canedioic acid, 1,13-tridecanedioic acid and 1,14-tet xii. a polyene, selected from the group consisting of radecanedioic acid. include, but are not limited to amphotericin, amphot ericin, aureofungin, ayfactin, azalomycin, blasticidin, xix. an antibiotic metal or a metal ion, wherein the metal candicidin, candicidin methyl ester, candimycin, can is selected from the group consisting of silver, copper, dimycin methyl ester, chinopricin, filipin, flavofungin, Zinc, mercury, tin, lead, bismutin, cadmium, chromium fradicin, hamycin, hydropricin, levorin, lucensomycin, and gold; lucknomycin, mediocidin, mediocidin methyl ester, XX. a silver compound, selected from the group consisting mepartricin, methylamphotericin, natamycin, niphimy of silver acetate, silver benzoate, silver carbonate, cin, nystatin, nystatin methyl ester, oxypricin, partricin, silver iodate, silver iodide, silver lactate, silver laurate, pentamycin, perimycin, pimaricin, primycin, proticin, silver nitrate, silver oxide, silver palmitate, silver pro rimocidin, sistomycosin, Sorangicin, trichomycin; tein, and silver Sulfadiazine; xiii. a polyether, selected from the group consisting of XXi. an oxidizing agent or a Substance that release free 20-deoxy-epi-narasin, 20-deoxysalinomycin, carrio radicals and/or active oxygen, selected from the group mycin, dianemycin, dihydrolonomycin, etheromycin, consisting of oxygen, hydrogen peroxide, benzoyl per ionomycin, iso-lasalocid, lasalocid, lenoremycin, lono oxide, elemental halogen species, as well as oxygen US 2006/02694.85 A1 Nov.30, 2006 26

ated halogen species, bleaching agents (e.g., Sodium, linomycin, copiamycin, corallopyronin, corynecandin, calcium or magnesium hypochloride and the like). coumermycin, culpin, cuprimyxin, cyclamidomycin, perchlorite species, iodine, iodate, and benzoyl perox cycloheximide, dactylomycin, danomycin, danubomy ide; cin, delaminomycin, demethoxyrapamycin, demeth ylscytophycin, dermadin, desdamethine, dexylosyl xxii. a cationic antimicrobial agent, selected from the benanomycin, pseudoaglycone, dihydromocimycin, group consisting of quaternary ammonium compounds, dihydronancimycin, diumycin, dnacin, dorrigocin, alkyltrimethyl ammonium bromide, cetrimide, benza dynemycin, dynemycin triacetate, ecteinascidin, efro lkonium chloride, n-alkyldimethylbenzyl ammonium tomycin, endomycin, ensanchomycin, equisetin, erica chloride, dialkylmethyl ammonium halide and dialky mycin, esperamicin, ethylmonate, everninomicin, fel lbenzyl ammonium halide: damycin, flambamycin, flavensomycin, florfenicol, xxiii. a biguanide, a biguanidine or a triguanide having a fluvomycin, fosfomycin, fosfonochlorin, fredericamy skeleton selected from: cin, frenolicin, fumagillin, fumifungin, funginon, fusa candin, fusafungin, gelbecidine, glidobactin, grahami mycin, granaticin, griseofulvin, griseoviridin, 4 2 2 grisonomycin, hayumicin, hayumicin, haZymicin, HN NH NH hedamycin, heneicomycin, heptelicid acid, holomycin, 4 6 humidin, isohematinic acid, karnatakin, kaZusamycin, 5 l 3 ls ls -NH NH2 kristenin, L-dihydrophenylalanine, a L-isoleucyl-L-2- HN HN NH2 HN HN3 r Biguanide NH amino-4-(4-amino-2',5'-cyclohexadienyl) derivative, 5 lanomycin, leinamycin, leptomycin, libanomycin, lin Biguanidine comycin, lomofungin, lysolipin, magnesidin, manumy 6 4 2 cin, melanomycin, methoxycarbonylmethylmonate, NH NH NH methoxycarbonylethylmonate, methoxycarbonylphe nylmonate, methyl pseudomonate, methylmonate. 7 ls 5ls 3 l microcin, mitomalcin, mocimycin, moenomycin, HN HN HN NH2 monoacetyl cladosporin, monomethyl cladosporin, Triguanide mupirocin, mupirocin calcium, mycobacidin, myriocin, myxopyronin, pseudoaglycone, nanaomycin, nancimy cin, nargenicin, neocarcinostatin, neoenactin, neothra xxiv. a compound, selected from the group consisting of mycin, nifurtoinol, nocardicin, nogalamycin, novobio chlorhexidine acetate, chlorhexidine gluconate and cin, octylmonate, olivomycin, orthosomycin, chlorhexidine hydrochloride, picloxydine, alexidine, oudemansin, oxirapentyn, oxoglaucine methiodide, polihexanide, chlorproguanil hydrochloride, proguanil pactacin, pactamycin, papulacandin, paulomycin, hydrochloride, mefformin hydrochloride, phenformin phaeoramularia fungicide, phenelfamycin, phenyl, and buformin hydrochloride: cerulenin, phenylmonate, pholipomycin, pirlimycin, pleuromutilin, a polylactone derivative, polynitroxin, XXV. a cationic polymeric antimicrobial agent; polyoxin, porfiromycin, pradimicin, prenomycin, Prop XXvi. a polymeric biguanide; 2-enylmonate, protomycin, Pseudomonas antibiotic, pseudomonic acid, purpuromycin, pyrinodemin, pyr XXvii. an agent, selected from the group consisting of rolnitrin, pyrrolomycin, amino, chloro pentenedioic abomycin, acetomycin, acetoxycycloheximide, acetyi acid, rapamycin, rebeccamycin, resistomycin, reuterin, nanaomycin, an actinoplanes sp. Compound, actinopy reveromycin, rhizocticin, roridin, rubiflavin, naphthy rone, aflastatin, albacarcin, albacarcin, albofungin, ridinomycin, saframycin, saphenamycin, sarkomycin, albofungin, alisamycin, alpha-R.S.-methoxycarbonyl sarkomycin, sclopularin, selenomycin, siccanin, spar benzylmonate, altromycin, amicetin, amycin, amycin tanamicin, spectinomycin, spongistatin, stravidin, demanoyl compound, amycine, amycomycin, anandi streptolydigin, streptomyces arenae antibiotic complex, mycin, anisomycin, anthramycin, anti-syphilis imune streptonigrin, streptothricins, streptovitacin, streptoZo substance, anti-tuberculosis imune substance, antibi tocine, a strobilurin derivative, stubomycin, sul otic from Eschericia coli, antibiotics from Streptomy famethoxazol-trimethoprim, Sakamycin, tejeramycin, ces refitineus, anticapsin, antimycin, aplasmomycin, terpentecin, tetrocarcin, thermorubin, thermozymoci aranorosin, aranorosinol, arugomycin, ascofuranone, din, thiamphenicol, thioaurin, thiolutin, thiomarinol, ascomycin, ascosin, Aspergillus flavus antibiotic, thiomarinol, tirandamycin, tolytoxin, trichodermin, asukamycin, aurantinin, an Aureolic acid antibiotic trienomycin, trimethoprim, trioxacarcin, tyrissamycin, substance, aurodox, avilamycin, azidamfenicol, azidi umbrinomycin, unphenelfamycin, urauchimycin, usnic mycin, bacillaene, a Bacillus larvae antibiotic, bacto bolin, benanomycin, benzanthrin, benzylmonate. acid, uredolysin, variotin, Vermisporin, Verrucarin and bicozamycin, bravomicin, brodimoprim, butalactin, analogs, salts and derivatives thereof. calcimycin, calvatic acid, candiplanecin, carumonam, xxviii. a naturally occurring antibiotic compound, carzinophilin, celesticetin, cepacin, cerulenin, cervino selected from the group consisting of phenol, resorci mycin, chartreusin, chloramphenicol, chloramphenicol nol, antibiotic aminoglycosides, anamycin, quinines, palmitate, chloramphenicol succinate sodium, chlorfla anthraquinones, antibiotic glycopeptides, azoles, mac vonin, chlorobiocin, chlorocarcin, chromomycin, ciclo rolides, avilamycin, agropyrene, cnicin, aucubin anti pirox, ciclopirox olamine, citreamicin, cladosporin, bioticsaponin fractions, berberine (isoquinoline alka clazamycin, clecarmycin, clindamycin, coliformin, col loid), arctiopicrin (sesquiterpene lactone), lupulone, US 2006/02694.85 A1 Nov.30, 2006 27

humulone (bitter acids), allicin, hyperforin, echinaco 46. The composition of claim 45, wherein the concentra side, coniosetin, tetramic acid, imanine and novoima tion of the PPG alkyl ether is between about 1% and about nine; 20%. XXix. a plant oil or extracts which contain antibiotic 47. The composition of claim 45, wherein the foam is agents: non-flammable, when tested according to European Stan dard prEN 14851. XXX. an oil or extract of a plant selected from the group consisting of thyme, perilla, lavender, tea tree, terfezia 48. The composition of claim 41, wherein the antibiotic clayeryi, Micromonospora, putterlickia Verrucosa, agent is an antibiotic azole and wherein the penetration putterlickia pyracantha putterlickia retroSpinosa, May enhancer is selected from the group consisting of propylene tenus ilicifolia, maytenus evonymoides, maytenus glycol, hexylene glycol, glycerol, and dimethyl isosorbide. aquifolia, faenia interjecta, cordyceps sinensis, couch 49. The composition of claim 42, wherein the antibiotic grass, holy thistle, plantain, burdock, hops, echinacea, agent is an antibiotic azole and wherein the penetration buchu, chaparral, myrrh, red clover and yellow dock, enhancer is selected from the group consisting of propylene garlic and St. John’s wort; and glycol, hexylene glycol, glycerol, polyethylene glycol and esters and salts thereof. dimethyl isosorbide. 39. The composition of claim 34, wherein the foamable 50. The composition of claim 49, wherein the antibiotic composition further comprises at least one additional thera azole is metronidazole; and wherein the concentration of peutic agent. metronidazole is greater than 0.75%. 40. The composition of claim 39, wherein the additional 51. The composition of claim 50, wherein the concentra therapeutic agent is selected from the group consisting of a tion of metronidazole is between 0.9% and about 2%. steroidal anti-inflammatory agent, an immunosuppressive 52. The composition of claim 42, wherein the additional agent, an immunomodulator, an immunoregulating agent, a therapeutic agent is a dicarboxylic acid and wherein the hormonal agent, an antifungal agent, an antiviral agent, an penetration enhancer is selected from the group consisting of antiparasitic agent, vitamin A, a vitamin A derivative, Vita propylene glycol, hexylene glycol, glycerol, polyethylene min B, a vitamin B derivative, vitamin C, a vitamin C glycol and dimethyl isosorbide derivative, vitamin D, a vitamin D derivative, vitamin E, a vitamin E derivative, vitamin F, a vitamin F derivative, 53. The composition of claim 34, wherein the antibiotic Vitamin K, a vitamin K derivative, a wound healing agent, agent is azelaic acid; and wherein the concentration of a disinfectant, an anesthetic, an antiallergic agent, an alpha azelaic acid is greater than 10%. hydroxyl acid, lactic acid, glycolic acid, a beta-hydroxy 54. The composition of claim 53, wherein the concentra acid, a protein, a peptide, a neuropeptide, a allergen, an tion of azelaic acid is between about 10% and about 25%. immunogenic Substance, a haptene, an oxidizing agent, an 55. The composition of claim 39, wherein the antibiotic antioxidant, a dicarboxylic acid, aZelaic acid, sebacic acid, agent is suitable for the treatment of impetigo and the adipic acid, fumaric acid, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, additional active agent is an anti-inflammatory agent benzoyl chloride, calcium hypochlorite, magnesium 56. The composition of claim 39, wherein the antibiotic hypochlorite, an anti-wrinkle agent, a radical scavenger, a agent is suitable for the treatment of chronic ulcer and the metal, silver, a metal oxide, titanium dioxide, Zinc oxide, additional active agent is selected from the group consisting Zirconium oxide, iron oxide, silicone oxide, talc, carbon, an of a topical anesthetic agent, an antifungal, an anti viral anti wrinkle agent, a skin whitening agent, a skin protective infections and a vasoactive agent. agent, a masking agent, an anti-wart agent, a refatting agent, 57. The composition of claim 39, wherein the antibiotic a lubricating agent and mixtures thereof. agent is suitable for the treatment of acne and the additional 41. The foamable composition of claim 40, wherein the active agent is selected from the group consisting of a composition further contains a penetration enhancer. retinoid; a keratolytic acid, an alpha-hydroxy acid and 42. The foamable composition of claim 41, wherein the derivatives thereof, a beta-hydroxy acid and derivatives penetration enhancer is selected from the group consisting of thereof, a skin-drying agent, a corticosteroid, a non-steroidal propylene glycol, butylene glycols, hexylene glycol, glyc anti-inflammatory agent. and an anti-seborrhea agent. erol, pentaerythritol, Sorbitol, mannitol, oligosaccharides, 58. The composition of claim 39, wherein the antibiotic dimethyl isosorbide, monooleate of ethoxylated glycerides agent is suitable for the treatment of rosacea and the addi having about 8 to 10 ethylene oxide units, polyethylene tional active agent is selected from the group consisting of glycol 200-600, transcutol, glycofurol and cyclodextrins. a retinoid; a keratolytic acid, an alpha-hydroxy acid, a 43. The composition of claim 34, wherein the pH of the beta-hydroxy acid, a corticosteroid and a non-steroidal anti foamable composition is selected from the group consiting inflammatory agent. of (i) between about 4.5 and about 7.0, wherein the com 59. The composition of claim 39, wherein the antibiotic position is intended for skin treatment; and (ii) between agent is suitable for the treatment of otitis and the additional about 3 and about 4.5, wherein the composition is intended active agent is selected from the group consisting of an for vaginal treatment. antifungal agent, a topical anesthetic agent, a corticosteroid 44. The composition of claim 43, wherein pH of the and a non-steroidal anti-inflammatory agent. composition is adjusted using an agent selected from the 60. A method of treating, alleviating or preventing disor group consisting of an acid, a base and a buffering agent. ders of the skin, body cavity or mucosal surface, wherein the 45. The composition of claim 34, wherein the organic disorder involves inflammation as one of its etiological carrier contains a PPG alkyl ether. factors, the method comprising: US 2006/02694.85 A1 Nov.30, 2006 28

administering topically to a Subject having the disorder, a molluscum contagiosum, nongonococcal urethritis (NGU). foamed composition including: trichomoniasis, Vulvar disorders, Vulvodynia, Vulvar pain, yeast infection, Vulvar dystrophy, Vulvar intraepithelial neo (i) an antibiotic agent; plasia (VIN), contact dermatitis, osteoarthritis, joint pain, (ii) at least one organic carrier selected from a hydro hormonal disorder, pelvic inflammation, endometritis, salp phobic organic carrier, a polar solvent, an emollient ingitis, oophoritis, genital cancer, cancer of the cervix, and mixtures thereof, at a concentration of about 2% cancer of the Vulva, cancer of the vagina, Vaginal dryness, to about 50% by weight; dyspareunia, anal and rectal disease, anal abscess/fistula, anal cancer, anal fissure, anal warts, Crohn's disease, hem (iii) a Surface-active agent; orrhoids, anal itch, pruritus ani, fecal incontinence, consti (iv) about 0.01% to about 5% by weight of a polymeric pation, polyps of the colon and rectum; and wherein the additive selected from a bioadhesive agent, a gelling disorder is responsive to treatment with the antibiotic agent. agent, a film forming agent and a phase change 65. The method of claim 60, wherein the composition agent; and further comprises at least one additional therapeutic agent, selected from the group consisting of a steroidal anti (v) water, inflammatory agent, an immunosuppressive agent, an immu wherein the antibiotic agent is administered in a thera nomodulator, an immunoregulating agent, a hormonal agent, peutically effective amount. an antifungal agent, an antiviral agent, an antiparasitic agent, 61. The method of claim 60, wherein the concentration of vitamin A, a vitamin A derivative, vitamin B, a vitamin B the surface active agent is between about 0.1% and about 5% derivative, vitamin C, a vitamin C derivative, vitamin D, a by weight. vitamin D derivative, vitamin E, a vitamin E derivative, 62. The method of claim 60, wherein the composition vitamin F, a vitamin F derivative, vitamin K, a vitamin K further comprises about 0.1% to about 5% by weight of a derivative, a wound healing agent, a disinfectant, an anes therapeutically active foam adjuvant is selected from the thetic, an antiallergic agent, an alpha hydroxyl acid, lactic group consisting offatty alcohols having 15 or more carbons acid, glycolic acid, a beta-hydroxy acid, a protein, a peptide, in their carbon chain; fatty acids having 16 or more carbons a neuropeptide, a allergen, an immunogenic Substance, a in their carbon chain; fatty alcohols derived from beeswax haptene, an oxidizing agent, an antioxidant, a dicarboxylic and including a mixture of alcohols, a majority of which has acid, azelaic acid, sebacic acid, adipic acid, fumaric acid, a at least 20 carbon atoms in their carbon chain; fatty alcohols retinoid, an antiproliferative agent, an anticancer agent, a having at least one double bond; fatty acids having at least photodynamic therapy agent, benzoyl chloride, calcium one double bond; branched fatty alcohols; branched fatty hypochlorite, magnesium hypochlorite, an anti-wrinkle acids; fatty acids Substituted with a hydroxyl group; cetyl agent, a radical scavenger, a metal, silver, a metal oxide, alcohol; stearyl alcohol; arachidyl alcohol; behenyl alcohol: titanium dioxide, Zinc oxide, Zirconium oxide, iron oxide, 1-triacontanol; hexadecanoic acid; Stearic acid; arachidic silicone oxide, talc, carbon, an anti wrinkle agent, a skin acid; behenic acid; octacosanoic acid; 12-hydroxy Stearic whitening agent, a skin protective agent, a masking agent, an acid and mixtures thereof. anti-wart agent, a refatting agent, a lubricating agent and 63. The composition of claim 60 or 62, wherein the mixtures thereof. antibiotic agent is selected from the group consisting of 66. The method of claim 36, wherein the composition beta-lactam antibiotics, aminoglycosides, ansa-type antibi further contains a penetration enhancer. otics, anthraquinones, antibiotic azoles, antibiotic glycopep 67. The method of claim 41, wherein the penetration tides, macrollides, antibiotic nucleosides, antibiotic peptides, enhancer is selected from the group consisting of propylene antibiotic polyenes, antibiotic polyethers, quinolones, anti glycol, butylene glycols, hexylene glycol, glycerol, pen biotic steroids, Sulfonamides, tetracycline, dicarboxylic taerythritol, Sorbitol, mannitol, oligosaccharides, dimethyl acids, antibiotic metals, oxidizing agents, Substances that isosorbide, monooleate of ethoxylated glycerides having release free radicals and/or active oxygen, cationic antimi about 8 to 10 ethylene oxide units, polyethylene glycol crobial agents, quaternary ammonium compounds, bigu 200-600, transcutol, glycofurol and cyclodextrins. anides, triguanides, bisbiguanides and analogs and polymers 68. The method of claim 60, wherein the pH of the thereof and naturally occurring antibiotic compounds. foamable composition is selected from the group consisting 64. The method of claim 60, wherein the disorder is of (i) between about 4.5 and about 7.0, wherein the com selected from the group consisting of a dermatose, a der position is intended for skin treatment; and (ii) between matitis, a vaginal disorder, a Vulvar disorder, an anal disor about 3 and about 4.5, wherein the composition is intended der, a disorder of a body cavity, an ear disorder, a disorder for vaginal treatment. of the nose, a disorder of the respiratory system, a bacterial infection, fungal infection, viral infection, dermatosis, der 69. The method of claim 60, wherein the organic carrier matitis, parasitic infections, disorders of hair follicles and contains a PPG alkyl ether. sebaceous glands, Scaling papular diseases, benign tumors, 70. The method of claim 69, wherein the foam is non malignant tumors, reactions to Sunlight, bullous diseases, flammable, when tested according to European Standard pigmentation disorders, disorders of cornification, pressure prEN 14851. Sores, disorders of Sweating, inflammatory reactions, Xero 71. The method of claim 66, wherein the active agent is sis, ichthyosis, allergy, burn, wound, cut, chlamydia infec an antibiotic azole and wherein the penetration enhancer is tion, gonorrhea infection, hepatitis B, herpes, HIV/AIDS, selected from the group consisting of propylene glycol, human papillomavirus (HPV), genital warts, bacterial vagi hexylene glycol, glycerol, and dimethyl isosorbide. nosis, candidiasis, chancroid, granuloma Inguinale, lym 72. The method of claim 67, wherein the antibiotic agent phogranloma Venereum, mucopurulent cerviciitis (MPC), is an antibiotic azole and wherein the penetration enhancer US 2006/02694.85 A1 Nov.30, 2006 29 is selected from the group consisting of propylene glycol, surfactant having HLB of equal or more than 9, wherein the hexylene glycol, glycerol, polyethylene glycol and dimethyl ratio between the at least one non-ionic Surfactant having isosorbide. HLB of less than 9 and the at least one non-ionic surfactant 73. The method of claim 72, wherein the antibiotic azole having HLB of equal or more than 9, is between 1:4 and 4:1. is metronidazole; and wherein the concentration of metron 84. The kit of claim 83, wherein the resulting HLB value idazole is greater than 0.75%. of the combination of at least one non-ionic Surfactant 74. The method of claim 73, wherein the concentration of having HLB of less than 9 and at least one non-ionic metronidazole is between 0.9% and about 2%. surfactant having HLB of equal or more than 9 is between 75. The method of claim 67, wherein the additional about 9 and about 14. therapeutic agent is a dicarboxylic acid and wherein the 85. The composition of claim 34, wherein the surface penetration enhancer is selected from the group consisting of active agent consists of one or more non-ionic Surfactants. propylene glycol, hexylene glycol, glycerol, polyethylene 86. The composition of claim 34, wherein the surface glycol and dimethyl isosorbide active agent comprises a combination of at least one non 76. The method of claim 60, wherein the antibiotic agent ionic surfactant having HLB of less than 9 and at least one is azelaic acid; and wherein the concentration of azelaic acid non-ionic Surfactant having HLB of equal or more than 9. is greater than 10%. wherein the ratio between the at least one non-ionic surfac 77. The method of claim 76, wherein the concentration of tant having HLB of less than 9 and the at least one non-ionic azelaic acid is between about 10% and about 25%. surfactant having HLB of equal or more than 9, is between 78. The method of claim 65, wherein the antibiotic agent 1:8 and 8:1. is suitable for the treatment of impetigo and the additional 87. The composition of claim 86, wherein the resulting active agent is an anti-inflammatory agent HLB value of the combination of at least one non-ionic 79. The method of claim 65, wherein the antibiotic agent surfactant having HLB of less than 9 and at least one is suitable for the treatment of chronic ulcer and the addi non-ionic Surfactant having HLB of equal or more than 9 is tional active agent is selected from the group consisting of between about 9 and about 14. a topical anesthetic agent, an antifungal, an anti viral infec 88. The composition of claim 34, wherein the surface tions and a vasoactive agent. active agent comprises a combination of a non-ionic Surfac 80. The method of claim 65, wherein the antibiotic agent tant and an ionic Surfactant, at a ratio of between about 4:1 is suitable for the treatment of acne and the additional active and about 1:4. agent is selected from the group consisting of a retinoid; a 89. The method of claim 60, wherein the surface-active keratolytic acid, an alpha-hydroxy acid and derivatives agent comprises a combination of at least one non-ionic thereof, a beta-hydroxy acid and derivatives thereof, a surfactant having HLB of less than 9 and at least one skin-drying agent, a corticosteroid, a non-steroidal anti non-ionic Surfactant having HLB of equal or more than 9. inflammatory agent. and an anti-seborrhea agent. wherein the ratio between the at least one non-ionic surfac 81. The method of claim 65, wherein the antibiotic agent tant having HLB of less than 9 and the at least one non-ionic is suitable for the treatment of rosacea and the additional surfactant having HLB of equal or more than 9, is between active agent is selected from the group consisting of a 1:8 and 8:1. retinoid; a keratolytic acid, an alpha-hydroxy acid, a beta 90. The method of claim 89, wherein the resulting HLB hydroxy acid, a corticosteroid and a non-steroidal anti value of the combination of at least one non-ionic Surfactant inflammatory agent. having HLB of less than 9 and at least one non-ionic 82. The method of claim 65, wherein the antibiotic agent surfactant having HLB of equal or more than 9 is between is suitable for the treatment of otitis and the additional active about 9 and about 14. agent is selected from the group consisting of an antifungal 91. The method of claim 60, wherein the surface-active agent, a topical anesthetic agent, a corticosteroid and a agent comprises a combination of a non-ionic Surfactant and non-steroidal anti-inflammatory agent. an ionic Surfactant, at a ratio of between about 4:1 and about 83. The kit of claim 1, wherein the surface-active agent 1:4. comprises a combination of at least one non-ionic Surfactant having HLB of less than 9 and at least one non-ionic