US 20190307887A1 ( 19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0307887 A1 Friedman et al. ( 43 ) Pub . Date: Oct. 10 , 2019

(54 ) BODY CAVITY FOAMS A61K 31/ 7048 (2006 .01 ) A61K 38 / 12 (2006 .01 ) ( 71) Applicant: Foamix Pharmaceuticals Ltd ., A61K 38 /21 ( 2006 .01 ) Rehovot ( IL ) A61K 47 / 10 ( 2006 .01 ) A61K 47 / 14 ( 2006 . 01 ) (72 ) Inventors : Doron Friedman , Karmei Yosef ( IL ); A61K 47 / 20 ( 2006 . 01) Alex Besonov , Rehovot (IL ) ; Dov A61K 47/ 26 ( 2006 .01 ) Tamarkin , Maccabim ( IL ) ; Meir Eini, A61K 47 34 ( 2006 .01 ) Ness Ziona (IL ) A61K 9 / 107 ( 2006 .01 ) A61K 9 / 46 ( 2006 .01 ) (21 ) Appl. No. : 16 / 180 ,501 A01N 25 / 16 (2006 . 01) A61Q 19 / 04 ( 2006 .01 ) ( 22 ) Filed : Nov . 5 , 2018 A610 19 /02 ( 2006 .01 ) A610 17 /04 (2006 .01 ) Related U . S . Application Data A610 17 /02 ( 2006 .01 ) (63 ) Continuation of application No . 15 /464 ,638 , filed on A610 7 /02 (2006 .01 ) Mar . 21 , 2017 , now abandoned , which is a continu A610 7700 (2006 .01 ) ation of application No. 14 /272 , 551, filed on May 8 , A61K 31/ 137 ( 2006 .01 ) 2014 , now Pat. No . 9 ,713 ,643 , which is a continu A61K 9 / 12 ( 2006 . 01 ) ation of application No. 13 /786 , 902 , filed on Mar. 6 , A61K 9 /00 (2006 . 01 ) 2013 , now Pat. No. 8 ,722 ,021 , which is a continu A61K 8 /60 (2006 . 01) ation of application No . 11/ 116 ,761 , filed on Apr. 28 , (52 ) U . S . Cl. 2005, now Pat. No . 8 ,840 , 869 , which is a continu CPC ...... A61K 47/ 46 ( 2013 .01 ) ; A61K 2800 / 75 ation - in - part of application No . 10 /532 ,618 , filed on ( 2013 .01 ) ; A61K 8 / 046 ( 2013 .01 ) ; A61K Dec . 22 , 2005 , now abandoned , filed as application 31/ 351 ( 2013 .01 ) ; A61K 31/ 4164 ( 2013 .01 ) ; No . PCT /IB03 /05527 on Oct . 24 , 2003 , said applica A61K 31/ 4174 ( 2013 .01 ) ; A61K 31/ 522 tion No. 11/ 116 , 761 is a continuation -in -part of appli ( 2013 .01 ) ; A61K 31/ 535 (2013 . 01 ) ; A61K cation No . 10 / 911, 367 , filed on Aug. 4 , 2004 , now 31/ 567 ( 2013 . 01 ) ; A61K 31/ 573 ( 2013 . 01 ) ; abandoned . A61K 31 / 7036 ( 2013 .01 ) ; A61K 31 / 7048 ( 2013 . 01 ) ; A61K 38 / 12 (2013 .01 ) ; A61K (60 ) Provisional application No. 60 /429 , 546 , filed on Nov . 38 / 212 (2013 .01 ) ; A61K 47/ 10 (2013 .01 ) ; 29 , 2002 , provisional application No. 60 / 492 , 385 , A61K 47 /14 ( 2013 .01 ) ; A61K 47 /20 (2013 .01 ) ; filed on Aug . 4 , 2003 , provisional application No . A61K 47 / 26 ( 2013 .01 ) ; A61K 47/ 34 (2013 .01 ) ; 60 / 566 , 513 , filed on Apr. 28 , 2004 . A61K 9 / 107 ( 2013 .01 ) ; A61K 9 /0007 ( 2013 .01 ) ; AO1N 25 / 16 ( 2013 . 01 ) ; A610 ( 30 ) Foreign Application Priority Data 19 / 04 ( 2013 .01 ) ; A61Q 19 /02 ( 2013 . 01 ) ; A61Q 17/ 04 ( 2013 .01 ); A61Q 17/ 02 Oct. 25 , 2002 (IL ) ...... 152486 ( 2013 . 01 ) ; A610 7 / 02 ( 2013 .01 ) ; A610 7700 (2013 . 01 ) ; A61K 31/ 137 ( 2013 .01 ) ; A61K Publication Classification 9 / 122 ( 2013 .01 ); A61K 9 / 12 ( 2013 .01 ); A61K (51 ) Int . Cl. 9 /0034 ( 2013 .01 ) ; A61K 9 /0014 ( 2013 .01 ) ; A61K 47 /46 (2006 . 01 ) A61K 8 /60 (2013 .01 ); A61K 47 /38 (2013 . 01 ) A61K 47 / 38 ( 2006 .01 ) A61K 8 /04 (2006 .01 ) ( 57 ) ABSTRACT A61K 31 / 351 ( 2006 .01 ) The invention relates to an alcohol- free cosmetic or thera A61K 31/ 4164 ( 2006 . 01 ) peutic foam carrier comprising water , a hydrophobic organic A61K 31 /4174 ( 2006 . 01 ) carrier, a foam adjuvant agent, a surface - active agent and a A61K 31/ 522 ( 2006 .01 ) gelling agent. The cosmetic or therapeutic foam carrier does A61K 31 / 535 ( 2006 .01 ) not contain aliphatic alcohols , making it non -irritating and A61K 31/ 567 ( 2006 .01 ) non - drying . The alcohol- free foam carrier is suitable for A61K 31/ 573 ( 2006 . 01 ) inclusion of both water - soluble and oil soluble therapeutic A61K 31/ 7036 ( 2006 . 01 ) and cosmetic agents . US 2019 /0307887 A1 Oct . 10 , 2019

BODY CAVITY FOAMS tion to women . Prepubertal girls and adolescents are par ticularly vulnerable because their vaginal and cervical tis CROSS REFERENCE TO RELATED sues may be less mature and are more readily penetrated by APPLICATIONS organisms ( e . g . , chlamydia and gonococcus) . Postmeno [0001 ] This application is a continuation of and claims pausal women are more likely than younger women to get benefit of priority under 35 U .S .C . § 120 to U .S . application small abrasions in the during sexual activity as a Ser. No . 13 /786 , 902, filed Mar . 6 , 2013 , which is a continu result of thinning of the tissue and dryness. Women who ation of and claims the benefit of priority to U . S . application already have an infection ( particularly one that causes Ser. No . 11/ 116 , 761, filed Apr. 28 , 2005 , which 1 ) is a genital lesions ) are more likely to acquire or transmit continuation -in -part application of co -pending International another STD , including HIV . Other biological risks include Patent Application No . 1603 / 005527 , filed Oct. 24, 2003 , the use of vaginal douches , which increase the risk of pelvic which claims the benefit of priority under 35 U . S . C . $ 119 ( e ) inflammatory disease (PID ) , and the influence of hormonal to U . S . Provisional Application Ser . No . 60 /429 ,546 , filed contraceptives on acquiring or transmitting an STD ( e. g ., Nov . 29, 2002 , and claims the benefit of priority under 35 increased risk of chlamydial infection with use of oral U . S . C . § 119 ( a ) to Israeli Patent Application No. 152486 , contraceptives ) . filed Oct . 25 , 2002 ; 2 ) is a continuation - in - part application [0007 ] In particular , the cervix is prone to several diseases , of co -pending U . S . patent application Ser. No. 10 / 911, 367 , such as cervicitis ( an inflammation of the uterine cervix , filed Aug . 4 , 2004 , which claims the benefit of priority under usually caused by infection ) , cancer, inflammation , erosion , 35 U . S . C . § 119 (e ) to U . S . Patent Application Ser . No. intraepithelial neoplasia (CIN ) , polyps, dysplasia , human 60 /492 ,385 , filed Aug . 4 , 2003 ; and 3 ) claims the benefit of papillomavirus (HPV ) infections causing some tumors , con priority under 35 U . S . C . $ 119 ( e ) to U . S . Patent Application dylomas or warts and abnormal . [0008 ] Several factors must be taken into consideration Ser. No. 60 / 566 ,513 , filed Apr. 28 , 2004 ; all of which are when developing therapeutic delivery systems for the female incorporated by reference in their entirety herein . genital system . These factors include the vaginal anatomy, FIELD OF THE INVENTION the mucosal surface , the presence and composition of vagi nal fluids and secretions , cervical fluids (mucus ), cyclic [0002 ] The invention relates to an alcohol- free , foam changes and endogenous microflora . Drug stability to carrier for delivery of an active agent to a mucosal body enzyme activity , which is quite high in vaginal environment, cavity . More specifically , the invention relates to foam and is again a function of and lifecycle , carriers suitable for inclusion of poorly soluble , water should also be taken into account. Topical drug delivery soluble and oil soluble therapeutic agents for delivery and through the cervix , as needed to treat disorders of the cervix sustained release to the vaginal cavity. and also presents a challenge . [0009 ] Vaginal topical formulation should be compatible BACKGROUND OF THE INVENTION with daily activities , be easy to administer and provide [0003 ] The vaginal cavity , including the vagina and cer accurate dosing . Several types of formulations are known for vix , provides a unique site for delivery of therapeutic agents , delivery to the vaginal cavity . While semi- solid formula both for systemic and local action . tions, such as creams, lotions, gels and ointments are com [ 0004 ). There are multiple anatomical structures which monly used , they are often reported to be messy , require comprise the internal and external female genital tract frequent application and can be difficult to remove after use . including the clitoris , labia minora and corpus spongiosum Furthermore , application of topical gels and creams require ( vestibular ) erectile tissue, vagina , peri - urethral glans , ure several steps of operation . Solid formulations such as tab thra , Halban ' s fascia , anterior fornix erogenous zone , pubo lets , suppositories and pessaries also require frequent appli coccygeus muscle and cervix . cation , show a poor retention in vagina , and exhibit insuf [0005 ] The vagina consists of a tube of autonomically ficient spreadability. innervated smooth muscle ( longitudinal outer, inner circular [0010 ] Rectal drug administration can be directed to both layer ) lined by stratified squamous epithelium and a sub local and systemic drug delivery . It has been effectively used dermal layer rich in capillaries . The vaginal wall consists of to treat local diseases of the anorectal area as well as an an inner glandular mucous type stratified squamous cell alternative to oral administration in the systemic adminis epithelium supported by a thick lamina propia . This epithe tration of drugs. Solid suppositories are the most common lium undergoes hormone - related cyclical changes including dosage form used for rectal drug administration and repre slight keratinization of the superficial cells during the men sent the majority of rectal dosage forms; however , creams strual cycle . Deep in the epithelium lies the smooth muscles ointments and foams are also being used . of the muscularis. There is a deeper surrounding fibrous [0011 ] Current formulations for rectal administration still layer above the muscularis which provides structural support have significant disadvantages. They are difficult to insert to the vagina and is rich is collagen and elastin to allow for through the anal orifice ; they are difficult to spread through expansion of the . Three sets of skeletal muscles surround the out the target cavity ; and if spreadable , they tend to leak , vagina including the ischiocavernosum , bulbocavernosus , causing major discomfort to the patient. Such negative transverse perinei and levator ani and pubococcygeus attributes lead to their very limited use . muscles . 10012 ]. Thus , new forms are desirable in order to achieve [0006 ] Women are vulnerable to diseases of the genital better control and ease of application , while maintaining the tract as the lining of the vagina is a permeable mucous beneficial properties of such products . A product for intra membrane . Intercourse , lack of lubrication during inter vaginal and anorectal application would ideally exhibit the course , changes in the cervix during the menstrual cycle , and following properties : ( 1 ) easy insertion , thus leading to high asymptomatic infections facilitate the transmission of infec patient compliance ; ( 2 ) accurate dosing , to ensure effective US 2019 /0307887 A1 Oct . 10 , 2019 treatment; ( 3 ) expandability , for increased coverage of the from about 1 : 1 to about 1 :10 . Emollients may be included , target cavity surface and cervix ; and ( 4 ) drip free formula however, being translucent, the composition cannot com tion with good adhesive properties , for prolonged drug prise significant oil concentrations (which would make it residence. The duration of the drug inside the vagina or opaque ). Apparently the foam breaks spontaneously upon rectum is also important for ensuring extended activity . discharging from an aerosol container (with no need of any [0013 ] Use of emulsions in foam compositions is known. rubbing or sheer force application ) , thus making it imprac Emulsion systems provide a two -phase system including tical for intravaginal application . water in one phase and oily components in the second phase . [0019 ] Additionally , U . S . Pat. Nos. 5 ,536 ,743 and 5 ,840 , Emulsifiers for reducing surface tension and for improving 744 relate to a non - flowing composition and method for foam stability are included in the foam composition . Foams intravaginal treatment of bacterial vaginosis . The composi and , in particular, foam emulsions are complicated systems tion contains metronidazole with a buffer system providing which do not form under all circumstances . Slight shifts in an acidic buffered pH value in the range of 3 .75 to about foam emulsion composition , such as by the addition of 4 . 25 . Certain of the compositions disclosed are based on active ingredients , may destabilize the foam . In the case of mineral oil or petrolatum . The foam compositions disclosed oil -containing foams, high surfactant concentrations are include up to 3 % mineral oil as the hydrophobic component required to attain foams of low density and acceptable of the emulsion . texture . [0020 ] U . S . Pat . No . 6 ,544 ,530 provides a stable oil- in [0014 ] Typical vaginal foam products are aqueous formu glycerin composition comprising a continuous glycerin lations and do not include significant levels of an oil - based phase , at least one vegetable oil , at least one biodegradable solvent. For example , a nonoxynol- 9 - containing foam mar emulsifier and at least one bioactive essential oil component keted under the trademane Delfen® foam ( Advanced care , for topical, external use on skin and mucosal. The essential 12 . 5 % nonoxynol- 9 ) , Emko? foam ( Schering - Plough oil is a volatile mixture of esters , aldehydes , alcohols , Healthcare, 12 % nonoxynol- 9 ) does not contain any oily ketones , and terpenes that possess bioactivity such as topical solvent and has an ingredient list reciting " nonoxynol- 9 anti- fungal activity , topical anti - bacterial activity , topical 12. 5 % , benzoic acid , cetyl alcohol , glacial acetic acid , anti -parasitic activity , and topical anti -viral activity . methylparaben , perfume, , polyvinyl alco [0021 ] U . S . Pat . No. 5 , 993 , 846 discloses a method for hol, propellant a - 31, propylene glycol, purified water, making an oil - in -water emulsion having mucoadhesive sodium carboxymethylcellulose , sorbic acid , stearamido properties which includes forming a mixture of a mucoad ethyl diethylamine , stearic acid ” . hesive macromolecule and an aqueous phase ; emulsifying [0015 ] PCT Publication No . WO 03 /053292 discloses the mixture with a hydrophobic phase and a surfactant to drug delivery compositions, which are suitable for vaginal form an oil - in -water emulsion comprising a plurality of administration for the treatment of diseases and disorders in submicron particles having a hydrophobic core surrounded the urogenital tract. The compositionsmay be in the form of by the surfactant and the mucoadhesive macromolecule ; and a tablet, liquid suspension or dispersion ; dried powder ; providing the emulsion with a final pH of between 3 and 8 . topical ointment; cream ; foam ; suppository ; or aerosol. The [ 0022 ] U . S . Pat . No. 6 , 423 , 323 describes an aqueous foam drug delivery compositions are administered directly to the emulsion . The composition includes a hydrophobic phase vagina and do not require the use of a pressurized canister including fatty acids , emulsifiers and co - emulsifiers , and an or other foaming device . The reference does not disclose use aqueous phase containing hydrophilic moisturizers and of hydrophobic or oily solvents . emulsifiers . An optional ingredient is one or more refatting [0016 ] U .S . Pat . No . 5, 759 , 520 discloses an aqueous foamable composition having a delayed foaming action on substances . expulsion from a pressurized container . The composition [0023 ] U . S . Pat. No. 6 ,730 ,288 teaches a pharmaceutical includes ( a ) a major amount by weight of water ; ( b ) 0 . 5 to foam composition including ( a ) an active ingredient; ( b ) an 7 .0 weight percent of a foaming agent in the form of a occlusive agent; (c ) an aqueous solvent; and (d ) an organic water - immiscible liquefied gas ; ( c ) at least one foam - stabi cosolvent; wherein the active ingredient is insoluble in water lizing and emulsifying surfactant ; and ( d ) a water -soluble and insoluble in both water and the occlusive agent; and polymer. A foaming agent such as propellant gas forms a wherein there is enough occlusive agent to form an occlu foam upon discharge from the container. Water is used as the sive layer on the skin . foam vehicle and hydrophobic organic carriers such as oil or emollients are not disclosed . SUMMARY OF THE INVENTION [0017 ] PCT Publication No . WO 02 /00820 discloses a [ 0024 ] In some aspects , the present invention provides an propellant - free foamable aqueous composition for use as easy to use vaginal delivery system that will be simple to vaginal or hemorrhoidal wipe . The aqueous stable foam operate with minimal preparation , will be very tolerable includes water, at least one surfactant and at least one without having a feeling of foreign matter , will provide foam -stabilizing agent. Such compounds are storage stable accurate dose administration , will evenly spread throughout and readily dispensed by a propellantless mechanical pump. the vaginal cavity surface , will effectively reach the cervix , [0018 ] U . S . Pat. No. 5 ,679 ,324 pertains to an aerosol will not leak and will retain intravaginally an active agent for foamable fragrance composition , translucent in its pre - dis a significant period of time. In other aspects , the present pensed state , which forms a fast- breaking foam . The com invention provides a lubricating vaginal drug vehicle for position contains a surfactant selected from the group con moisture replenishing or moisturizing vaginal vehicles . In sisting of ethoxylated lanolin oil derivatives , propoxylated other aspects , the invention provides an improved delivery lanolin oil derivatives, and mixtures thereof, a propellant, a system for active agents to other body cavities, such as the fragrance , a thickener , and a cosmetic vehicle ( preferably rectum , penile urethra , nasal cavity and ear cavity and to water ) wherein the ratio of the surfactant to propellant is mucosal surfaces . US 2019 /0307887 A1 Oct . 10 , 2019

[0025 ] The present invention relates to foam compositions that contains a high level of oil or emollient as the hydro for intra -vaginal and body cavity application of a wide range phobic organic carrier . The hydrophobic organic carrier is of active ingredients . The compositions contain at least one included in the oleaginous foam composition at levels at or active agent in a biocompatible alcohol- free foamable car above 70 % , and up to about 99 % by weight. rier , including oleaginous foams, oil- in -water foams, water [0043 ] According to one embodiment, at least one of the in -oil foams, liposome- based foams and nanoparticle - based composition components , selected from the group consisting foams. These compositions provide long lasting , drip - free , of organic carrier, surface active agent, foam adjuvant or expandable formulations for drug delivery into body cavi polymeric agent can also function as an active agent. ties . [0044 ] In another aspect of the present invention , a (0026 ] According to one aspect of the present invention , method of making a foamable composition includes select an alcohol- free foamable therapeutic composition for appli ing at least one active agent; selecting a solvent that solu cation to a body cavity or a mucosal surface includes : bilizes the active agent substantially better than a hydrocar [ 0027 at least one organic carrier selected from a hydro bon solvent such as mineral oil or petrolatum , for example , phobic organic carrier, a polar solvent, an emollient and 5 fold better than mineral oil or petrolatum , or even 10 - fold mixtures thereof hydrophobic organic carrier and mixtures better than mineral oil or petrolatum ; and adjusting the type thereof, at a concentration of about 2 % to about 75 % by and concentration of surfactant and gelling agent , to provide weight ; a foamable composition . [ 0028 ] about 0 .2 % to about 5 % by weight at least one (0045 ) According to another aspect of the present inven surface - active agent; tion , a method of treating a syndrome, disease or disorder of [0029 ] about 0 .01 % to about 5 % by weight at least one a body cavity or mucosal surface includes administering an polymeric agent, selected from a bioadhesive agent , a gell alcohol- free foamable therapeutic composition . The foam ing agent, a film forming agent and a phase change agent; able composition can be an oleaginous foam , an oil - in -water (0030 ) at least one active agent at a therapeutically effec foam , a water - in - oil foam , a liposome based foam and a tive concentration ; and nanoparticle based foam . [ 0031] a liquefied or compressed gas propellant at a con [ 0046 ] In one or more embodiments of the present inven centration of about 3 % to about 25 % by weight of the total tion , the syndrome, disorder or disease of the body cavity is composition , a syndrome, disorder or disease of the vaginal cavity . In one [ 0032 ] which upon release from an aerosol container pro or more embodiments , the disorder is a microbial disorder vides an expanded foam suitable for topical administration . including bacterial vaginosis , candidiasis , candidal vaginitis [0033 ] According to one embodiment, the composition and trichomonas vaginitis . In another embodiment the further includes a foam adjuvant at a concentration less than microbial disorder is a sexually transmitted disease (STD ) about 5 % by weight. Water and optional ingredients added such as chlamydia , herpes simplex , human immunodefi to complete the totalmass to 100 % . The content of the foam ciency virus (HIV ) . In another embodiment the syndrome, compositions is presented herein as concentration (percent disorder or disease of the vaginal cavity is related to hor by weight, % w / w ) . monal or post- menopausal vaginal dryness . In yet another [ 0034 ] According to one or more embodiments of the embodiment the syndrome, disorder or disease is related to present invention , the solvent level varies and can be at a the cervix and includes malignant and benign tumors, dys level of about 2 to about 5 , about 5 % to about 20 % by plasias , human papillomavirus (HPV ) or to the vulva and weight, or at a concentration of about 20 % to about 75 % by includes lichen sclerosus, vulvodynia and other pathologies. weight. [0035 ] In another aspect of the present invention , an DETAILED DESCRIPTION OF THE alcohol free oleaginous therapeutic foam composition for INVENTION administration to a body cavity or mucosal surface includes : [0047 ] The present invention provides a foamable thera [ 0036 ] at least one organic carrier selected from a hydro peutic compositions useful for delivery of an active agent to phobic organic carrier , an emollient , a polar solvent , and a mucosal body cavity . The composition is dispensed as a mixtures thereof, at a concentration of about 70 % to about foam providing a stable product that is pleasant and easy to 99 % by weight ; use for high patient compliance . [0037 ] at least one surface- active agent at a concentration [0048 ] The foamable therapeutic composition of the pres of about 0 . 2 to about 15 % ; ent invention is suitable for facile administration into the [ 0038 ] at least one polymeric agent, selected from a bio rectum , bladder, the cavity between the uterus and the adhesive agent, a gelling agent, a film forming agent and a fallopian tubes, the ovaries and other body areas, which may phase change agent at a concentration of about 0 . 1 % to accept topically -applied products . about 5 % by weight ; [0049 ] In one or more embodiments of the present inven [ 0039 ] at least one active agent at a therapeutically effec tion , a foamable composition includes water in one phase tive concentration ; and and at least one solvent selected from a hydrophobic organic [0040 ] a liquefied or compressed gas propellant at a con carrier, a polar solvent, an emollient and mixtures thereof in centration of about 3 % to about 25 % by weight of the total the second phase . The compositions may be water - in -oil or composition , oil - in -water emulsions . [ 0041 ] which upon release from an aerosol container pro [0050 ] Despite the commonly accepted understanding that vides an expanded foam suitable for topical administration . hydrophobic organic carriers , polar solvents and emollients [ 0042 ] Water and optional ingredients are added to com are difficult to formulate into a foam - producing product and plete the total mass to 100 % . As used herein “ oleaginous that addition of such solvents interferes with the foam foam composition " means a stable foam composition , or a forming ability of a surfactant, the present invention has composition capable of forming a stable foam composition surprisingly identified a series of foam compositions, which , US 2019 /0307887 A1 Oct . 10 , 2019 upon admixing with a liquefied gas propellant in an aerosol mucosal cavities, including , but not limited to the the vagina , container, produce a stable foam composition that is suitable the rectum and penile cavities , the urinary tract, bladder, the for topical and mucosal administration to body cavities, such cavity between the uterus and the fallopian tubes , the ovaries as the vagina , rectum , penile , urethra , nasal cavity and ear and other body areas , which may accept topically -applied cavity. Upon discharge from an aerosol container , the com products . position forms an expanded foam , which does not break [ 0061 ] It has been surprisingly discovered that the propel down immediately upon discharge, and remains in the body lant helps provide a stable emulsion . The propellant makes cavity for an extended time . up part of the “ oil phase” component of the emulsion , [0051 ] Such compositions, when placed in an aerosol providing a product with long shelf - life . Thus, admixing the container and combined with a liquefied gas propellant, liquid and solid foam components with a short chain hydro create an emulsion , which , upon release from the aerosol carbon propellant, results in a stable emulsion , that does not container , provides a therapeutically beneficial foam prod undergo phase separation after stress test, including either uct . exposure to at least two freeze and though cycles. [ 0052] According to one or more embodiments of the 10062 ]. The terms “ therapy ” and “ treatment” as used herein present invention , the therapeutic foam composition for interchangeably , cover any treatment of a disease or disor administration to a body cavity or mucosal surface includes der , and includes , for example , curing the disease or disor at least one solvent selected from a hydrophobic organic der , preventing the disease or disorder from occurring in a carrier, a polar solvent, an emollient and mixtures thereof, at subject which may be predisposed to the disease but has not a level of about 2 % to about 5 % , or about 5 % to about 10 % ; yet been diagnosed with the disease or disorder, inhibiting or about 10 % to about 20 % ; or about 20 % to about 75 % ; or the disease or disorder, relieving the disease or disorder, about 70 % to about 99 % by weight. The composition also providing a prophylactic effect, evolving a beneficial immu contains about 0 . 2 % to about 5 % by weight of a surface active agent; about 0 . 01 % to about 5 % by weight of a nological effect; and improving the quality of life of a polymeric additive selected from a bioadhesive agent , a subject afflicted by a disease or disorder . gelling agent, a film forming agent and a phase change [ 0063 ] In one or more embodiments of the present inven agent; at least one active agent at a therapeutically effective tion , a therapeutic product is provided that includes an active concentration ; and a liquefied gas propellant at a concen agent in a therapeutically effective concentration . Active tration of about 3 % to about 25 % by weight of the total agents are included in each of the compositions described composition , which upon release from an aerosol container herein ; however, in some instances the solvent, which is part provides an expanded foam suitable for topical administra of the composition , provides therapeutic benefit and thus , tion . can be defined as the at least one active agent. Therapeutic [ 0053) According to one embodiment, the composition products are intended for topical treatment of human and further comprises a foam adjuvant at a concentration less animal disorders of body cavities , or any other disorder , that than about 5 % . requires topical application of a drug into a body cavity . [0054 ] Water ( to make an emulsion ) and optional ingre [0064 ] The foamable composition of the present invention dients are added to complete the total mass to 100 % . Upon can be an emulsion , or microemulsion , including an aqueous release from an aerosol container , the foamable composition phase and an organic carrier phase . The organic carrier is forms an expanded foam suitable for topical administration . selected from a hydrophobic organic carrier ( also termed 0055 ] In one or more embodiments , the foam composi herein “ hydrophobic solvent” ) , an emollient, a polar solvent, tion is formulated as an emulsion and can be an oil - in -water and a mixture thereof. emulsion or a water - in - oil emulsion . The choice of the type [0065 ] A “ hydrophobic organic carrier ” as used herein of emulsion (oil - in -water or water- in -oil ) is made in light of refers to a material having solubility in distilled water at the nature of the active agent, so that it is suitable for ambient temperature of less than about 1 gm per 100 mL , inclusion of either or both water- soluble and oil -soluble more preferable less than about 0 . 5 gm per 100 mL, and active agents . The choice of the type of emulsion is also most preferably less than about 0 . 1 gm per 100 mL . It is influenced by the type of interaction which is desirable liquid at ambient temperature . The identification of a hydro between the composition , the active agent and the target phobic organic carrier or “ hydrophobic solvent” , as used tissue . herein , is not intended to characterize the solubilization [0056 ] In one or more embodiments, the emulsion is a capabilities of the solvent for any specific active agent or any micro - emulsion . Microemulsions are dispersions of either other component of the foamable composition . Rather, such oil - in -water or water - in -oil , which are typically clear, as the information is provided to aid in the identification of mate droplet diameter is approximately 100 nanometers (nm ) or rials suitable for use as a hydrophobic carrier in the foamable less . compositions described herein . [0057 ] In one or more embodiments , the foam composi [0066 ] In one or more embodiments , the hydrophobic tion of the present invention comprises liposomes . organic carrier is an oil, such as mineral oil. Mineral oil [ 0058 ] In one or more embodiments , the foam composi (Chemical Abstracts Service Registry number 8012 - 95 - 1 ) is tion of the present invention comprises nanoparticles, and , a mixture of aliphatic , naphthalenic, and aromatic liquid for example , the diameter is about 200 nm to about 400 nm . hydrocarbons that derive from petroleum . It is typically Nanoparticles are typically introduced as an active agent . liquid ; its viscosity is in the range of between about 35 CST [0059 ] The foam composition may include a propellant and about 100 CST ( at 40° C . ) , and its pour point (the lowest substance in an amount of about 3 % to about 25 % by weight, temperature at which an oil can be handled without exces housed in an aerosol container. sive amounts of wax crystals forming so preventing flow ) is 10060 ] When released , the composition produces a foam , below 0° C . Term hydrophobic organic carrier does not suitable for facile administration into body orifices and include thick or semi- solid materials , such as white petro US 2019 /0307887 A1 Oct . 10 , 2019 latum , also termed “ Vaseline ” , which , in certain composi eryl linoleate , wheat germ glycerides, arachidyl propionate , tions is disadvantageous due to its waxy nature and semi myristyl lactate , decyl Oleate , propylene glycol ricinoleate , solid texture . isopropyl lanolate , pentaerythrityl tetrastearate, neopentyl [0067 ] According to one or more embodiments , hydro glycol dicaprylate /dicaprate , isononyl isononanoate , isotri phobic solvents are liquid oils originating from vegetable , decyl isononanoate , myristyl myristate , triisocetyl citrate , marine or animal sources . Suitable liquid oil includes satu octyl dodecanol, sucrose esters of fatty acids , octyl hydrox rated , unsaturated or polyunsaturated oils . By way of ystearate and mixtures thereof. example, the unsaturated oil may be olive oil , corn oil, 10075 ] According to one or more embodiments of the soybean oil , canola oil, cottonseed oil, coconut oil, sesame present invention , the hydrophobic organic carrier includes oil, sunflower oil , borage seed oil , syzigium aromaticum oil, a mixture of a hydrophobic solvent and an emollient . hempseed oil , herring oil , cod - liver oil, salmon oil, flaxseed According to one or more embodiments , the foamable oil, wheat germ oil, evening primrose oils or mixtures composition is a mixture of mineral oil and an emollient in thereof, in any proportion . a ratio between 2 : 8 and 8 : 2 on a weight basis . [0068 ] Suitable hydrophobic solvents also include poly 10076 A “ polar solvent” is an organic solvent, typically unsaturated oils containing poly -unsaturated fatty acids. In soluble in both water and oil. Examples of polar solvents one or more embodiments , the unsaturated fatty acids are include polyols , such as glycerol (glycerin ) , propylene gly selected from the group of omega - 3 and omega -6 fatty acids . col, hexylene glycol, diethylene glycol, propylene glycol Examples of such polyunsaturated fatty acids are linoleic n -alkanols , terpenes, di- terpenes, tri - terpenes, terpen -ols , and linolenic acid , gamma -linoleic acid (GLA ) , eicosapen limonene, terpene- ol, 1- menthol , dioxolane, ethylene glycol, taenoic acid ( EPA ) and docosahexaenoic acid (DHA ). Such other glycols , sulfoxides , such as dimethylsulfoxide unsaturated fatty acids are known for their skin - conditioning (DMSO ) , dimethylformanide , methyl dodecyl sulfoxide , effect, which contribute to the therapeutic benefit of the dimethylacetamide , monooleate of ethoxylated glycerides present foamable composition . Thus, the hydrophobic sol (with 8 to 10 ethylene oxide units ), azone ( 1 -dodecylazacy vent can include at least 6 % of an oil selected from omega - 3 cloheptan - 2 - one ) , 2 - n -nonyl ) - 1 , 3 - dioxolane , esters, such as oil , omega - 6 oil , and mixtures thereof. In the context of the isopropyl myristate /palmitate , ethyl acetate , butyl acetate , present invention , oils that possess therapeutically -benefi methyl proprionate , capric/ caprylic triglycerides , cial properties are termed “ therapeutically active oil ” . octylmyristate , dodecyl- myristate ; myristyl alcohol, lauryl 100691 Another class ofhydrophobic solvents is the essen alcohol, lauric acid , lauryl lactate ketones ; amides , such as tial oils , which are also considered therapeutically active oil, acetamide oleates such as triolein ; various alkanoic acids which contain active biologically occurring molecules and , such as caprylic acid ; lactam compounds, such as azone ; upon topical application , exert a therapeutic effect , which is alkanols , such as dialkylamino acetates , and admixtures conceivably synergistic to the beneficial effect of the thereof. in the composition . 10077 ] According to one or more embodiments , the polar [0070 ] Another class of therapeutically active oils solvent is a polyethylene glycol (PEG ) or PEG derivative includes liquid hydrophobic plant- derived oils , which are that is liquid at ambient temperature , including PEG200 known to possess therapeutic benefits when applied topi (MW (molecular weight ) about 190 -210 kD ) , PEG300 (MW cally . about 285 - 315 KD ), PEG400 (MW about 380 -420 kD ), [0071 ] Silicone oils also may be used and are desirable PEG600 MW( about 570 -630 KD ) and higher MW PEGs due to their known skin protective and occlusive properties. such as PEG 4000 , PEG 6000 and PEG 10000 and mixtures Suitable silicone oils include non - volatile silicones , such as thereof. polyalkyl siloxanes , polyaryl siloxanes, polyalkylaryl silox [0078 ] In one or more embodiments , the solvent is a anes and polyether siloxane copolymers , polydimethylsilox mixture ( emulsion ) of a hydrophobic organic carrier and anes (dimethicones ) and poly ( dimethylsiloxane) - ( diphenyl glycerin , as described , for example, in U .S . Pat . No. 6 ,544 , siloxane ) copolymers . These are chosen from cyclic or linear 530 . The ratio ofhydrophobic organic carrier to glycerin can polydimethylsiloxanes containing from about 3 to about 9 , range from about 1 : 4 to about 4 : 1 , and more preferably from preferably from about 4 to about 5 , silicon atoms. Volatile about 1: 2 to about 2 : 1 . silicones such as cyclomethicones can also be used . Silicone [0079 ] In certain cases, a given solvent can be defined as oils are also considered therapeutically active oil , due to both emollient and polar solvent. their barrier retaining and protective properties. [0080 ] Certain hydrophobic organic carriers, emollients [0072 ] In one or more embodiments , the hydrophobic and polar solvents possess high solubilization capacity for carrier includes at least 2 % by weight silicone oil or at least pharmaceutical active agents , and are identified herein as 5 % by weight . “ potent solvents ” . A potent solvent as that term is used [ 0073 ] The solvent may be a mixture of two or more of the herein , is one that solubilizes a specific active agent sub above hydrophobic solvents in any proportion . stantially better than mineral oil or petrolatum , preferably 5 [0074 ] A further class of solvents includes “ emollients ” fold better than mineral oil or petrolatum , and even 10 - fold that have a softening or soothing effect , especially when better than mineral oil or petrolatum , and even 100 - fold applied to body areas , such as the skin and mucosal surfaces . better than mineral oil or petrolatum . Emollients are not necessarily hydrophobic . Examples of 10081 ] Thus , in one or more embodiments , a foam com suitable emollients include hexyleneglycol, propylene gly position includes at least one active agent in a therapeuti col, isostearic acid derivatives, isopropyl palmitate , isopro cally effective concentration and a potent solvent . In one or pyl isostearate , diisopropyl adipate , diisopropyl dimerate , more embodiments , the composition includes at least one maleated soybean oil, octyl palmitate , cetyl lactate , cetyl active agent in a therapeutically effective concentration and ricinoleate , tocopheryl acetate , acetylated lanolin alcohol, at least one potent solvent in a sufficient amount to substan cetyl acetate , phenyl trimethicone, glyceryl Oleate , tocoph tially solubilize the active agent in the composition . In the US 2019 /0307887 A1 Oct . 10 , 2019 context of the present invention the term “ substantially emulsion . A surfactant' s hydrophilic / lipophilic balance soluble” means that at least 95 % of the active agent has been (HLB ) describes the emulsifier ' s affinity toward water or oil . solubilized , i. e . , less than about 5 % is present in the com The HLB scale ranges from 1 ( totally lipophilic ) to 20 position in a solid state. In one or more embodiments, the (totally hydrophilic ) , with 10 representing an equal balance potent solvent is more than about 40 % or more than about of both characteristics. Lipophilic emulsifiers form water 60 % by weight of the total solvent of the composition . in -oil ( w / o ) emulsions, whereas hydrophilic surfactants form [0082 ] Examples of active agent/ potent solvent combina oil - in -water ( o / w ) emulsions . The HLB of a blend of two tions include, in a non -limiting manner : emulsifiers equals the weight fraction of emulsifier A times [0083 ] Betamethasone valerate : Practically insoluble in its HLB value plus the weight fraction of emulsifier B times mineral oil ( < 0 . 01 % ) ; soluble more than 1 % ( w / w ) in its HLB value (weighted average ) . Glycofurol. [ 0095 ] Any surface - active agent or combinations thereof [0084 ] Hydrocortisone butyrate : Practically insoluble in may be used as surface -active agent. According to one or mineral oil ( < 0 .01 % ) ; soluble more than 1 % in Glyco more embodiments of the present invention , the surface furol. active agent has a hydrophilic lipophilic balance (HLB ) [0085 ] Metronidazole : Practically insoluble in mineral between about 9 and about 14 , which is the required HLB oil ( < 0 . 01 % ) ; soluble more than 1 % in dimethyl isosor ( the HLB required to stabilize an O / W emulsion of a given bide . oil) ofmost oils and hydrophobic organic carriers. Thus , in [0086 ] : Practically insoluble in mineral one or more embodiments , the composition is a single oil ( < 0 .01 % ) ; soluble more than 1 % in glycofurol, surface active agent having an HLB value between about 9 propylene glycol and dimethyl isosorbide . and 14 , and in one or more embodiments, the composition [0087 ] Mupirocin : Practically insoluble in mineral oil is more than one surface active agent and the weighted (< 0 .01 % ); soluble more than 1 % in glycofurol, hex average of their HLB values is between about 9 and about ylene glycol, dimethyl isosorbide, propylene glycol and 14 . polyethylene glycol 400 ( PEG 400 ) . [0096 ) According to one or more embodiments, the sur [0088 ] Meloxicam , a anti- inflammatory face -active agent in an oleaginous composition (hydropho agent: Practically insoluble in mineral oil ( < 0 .001 % ) ; bic organic carriers of 70 % or greater ) has a surface - active soluble in propylene glycol: 0 . 3 mg/ mL and in PEG agent with an HLB in the range of about 3 to about 9 . 400 : 3 . 7 mg/ mL . [0097 ] The surface - active agent is selected from anionic , [ 0089 ] : Practically insoluble in mineral oil cationic , nonionic , zwitterionic , amphoteric and ampholytic ( < 0 .001 % ) ; soluble in PEG 400 : 15 . 3 mg/ mL . surfactants , as well as mixtures of these surfactants . Such [ 00901 A non - limiting exemplary list of solvents that can surfactants are well known to those skilled in the therapeutic be considered as potent solvents includes polyethylene gly and cosmetic formulation art. Nonlimiting examples of col, propylene glycol, hexylene glycol, butanediols and possible surfactants include polysorbates , such as polyoxy isomers thereof, glycerol, benzyl alcohol , DMSO , ethyl ethylene ( 20 ) sorbitan monostearate ( Tween 60 ) and poly oleate , ethyl caprylate , dimethylacetamide , N -methylpyr (oxyethylene ) (20 ) sorbitan monooleate ( Tween 80 ) ; poly rolidone , N -hydroxyethylpyrrolidone , polyvinylpyrroli (oxyethylene ) (POE ) fatty acid esters , such as Myrj 45 ,Myrj done , isosorbide derivatives, such as dimethyl isosorbide , 49, Myrj 52 and Myrj 59 ; poly ( oxyethylene ) alkylyl ethers , glycofurol and ethoxydiglycol ( transcutol) . such as poly ( oxyethylene ) cetyl ether , poly ( oxyethylene ) [0091 ] The present invention also provides a method of palmityl ether , polyethylene oxide hexadecyl ether , polyeth designing a foamable composition by selecting at least one ylene glycol cetyl ether, brij 38 , brij 52, brij 56 and brij W1; active agent, selecting a solvent that solubilizes the active sucrose esters , partial esters of sorbitol and its anhydrides , agent substantially better than mineral oil or petrolatum , and such as sorbitan monolaurate and sorbitan monolaurate ; adjusting the type and concentration of surfactant and gell mono or diglycerides , isoceteth - 20 , sodium methyl cocoyl ing agent to provide a foamable composition . This is par taurate , sodium methyl oleoyl taurate , sodium lauryl sulfate , ticularly useful in fomulating foams incorporating poorly triethanolamine lauryl sulfate and betaines . soluble active agents . [0098 ]. In one or more embodiments of the present inven [0092 ] The use of a potent solvent in a foam composition tion , the surface - active agent includes at least a non - ionic provides an improved way to deliver poorly soluble active surfactant. Ionic surfactants are known to be irritants . There agents to a target area . It is known that low drug solubility fore , non - ionic surfactants are preferred in applications results in poor , leading to decreased effec including sensitive tissue such as found in most mucosal tiveness of treatment. Foam compositions according to one tissues , especially when they are infected or inflamed . We or more embodiments of the present invention for which the have surprisingly found that non - ionic surfactants alone solvent is a potent solvent are unique because the majority provide foams of excellent quality , i . e . a score of “ E ” of the active agent is in solution , rather than in particulate according to the grading scale discussed herein below . form , resulting in high delivery and improved therapy. [ 0099 ] In one or more embodiments , the surface active [0093 ] Potent solvents are typically in liquid form . Liquid agent includes a mixture of at least one non - ionic surfactant drug formulations are generally disadvantageous , since their and at least one ionic surfactant in a ratio in the range of usage causes unwanted dripping, resulting in inconvenience about 100 : 1 to 6 : 1 . In one or more embodiments , the and inadequate dosing . Unexpectedly , the foams of the non - ionic to ionic surfactant ratio is greater than about 6 : 1 , present invention are drip - free and thereby provide a supe or greater than about 8 : 1 ; or greater than about 14 : 1 , or rior vehicle for such drugs and enable convenient usage and greater than about 16 : 1 , or greater than about 20 : 1 . accurate effective dosing . [0100 ] In one or more embodiments of the present inven 10094 ] Surface -active agents ( surfactants ) include any tion , a combination of a non - ionic surfactant and an ionic agent linking oil and water in the composition in the form of surfactant (such as sodium lauryl sulphate and cocamidopro US 2019 /0307887 A1 Oct . 10 , 2019 pylbetaiine ) is employed , at a ratio of between 1 : 1 and 20 : 1 , mers includes natural and chemically modified cyclodextrin , or at a ratio of 4 : 1 to 10 : 1 . The resultant foam has a low especially hydroxypropyl- ß -cyclodextrin (HPBCD ) . Such specific gravity , e . g ., less than 0 . 1 g /ml . polymers may be present as free acids , bases , or salts , [0101 ] In one or more embodiments of the present inven usually in a final concentration of about 0 . 01 % to about tion , the surface - active agent includes mono - , di - and tri 0 . 5 % by weight esters of sucrose with food fatty acids ( sucrose esters ) , [0108 ] A suitable bioadhesive macromolecule is the fam prepared from sucrose and esters of fatty acids or by ily of acrylic acid polymers and copolymers , ( e . g ., Car extraction from sucro - glycerides . Suitable sucrose esters bopol® ) . These polymers contain the general structure include those having high monoester content , which have higher HLB values . - [CH2 - CH (COOH ) — In . Hyaluronic acid and other bio [0102 ] Unlike prior art foamable compositions , the total logically -derived polymers may be used . surface active agent required to obtain a foam that is stable , [0109 ] Exemplary bioadhesive or mucoadhesive macro of low specific gravity and has a fine bubble structure is low . molecules have a molecular weight of at least 50 kDa , or at This is desirable because lower surface active agent levels , least 300 kDa , or at least 1 , 000 kDa . Favored polymeric particularly of ionic surfactants , reduce skin irritations. Total ionizable macromolecules have not less than 2 mole percent surface active agent is in the range of about 0 . 1 to about 5 % acidic groups ( e . g ., COOH , SO H ) or basic groups (NH , , of the foamable composition , and is typically less than about NRH , NR , ) , relative to the number of monomeric units . The 2 % , preferably less than about 1 % . acidic or basic groups can constitute at least 5 mole percent , [ 0103 ] It has been unexpectedly found that it is possible to or at least 10 mole percent, or at least 25 , at least 50 more prepare stable foams with stabilizing surfactants even in percent, or even up to 100 mole percent relative to the very low concentration of less than about 1 % which enable number of monomeric units of the macromolecule . low irritating and low itching vaginal foams. “ Stable foam " [0110 ] Yet , another group of mucoadhesive agent includes denotes shelf life stability of the emulsion and also a inorganic gelling agents such as silicon dioxide ( fumed sustainable foam that does not break upon extrusion of the silica ), including but not limited to , AEROSIL 200 ( DE package to enable delivery, spreading and expansion of the GUSSA ) . foam throughout the entire vaginal cavity before collapse . [0111 ] Many mucoadhesive agents are known in the art to [ 0104 ] The foamable composition includes a polymeric also possess gelling properties . agent to increase the duration / residence time of the compo sition in the body cavity . The polymeric agent serves to [0112 ] A gelling agent controls the residence of a thera stabilize the foam composition and to control drug duration peutic composition in the target site of treatment by increas in the target organ . ing the viscosity of the composition , thereby limiting the rate [0105 ] Exemplary polymeric agents , which providemeans of its clearance from the site .Many gelling agents are known of controlling duration are classified below in a non - limiting in the art to possess mucoadhesive properties . manner. In certain cases , a given polymer can belong to [0113 ] The gelling agent can be a natural gelling agent , a more than one of the classes provided below . synthetic gelling agent and an inorganic gelling agent. 0106 ] Bioadhesion has been defined as the attachment of Exemplary gelling agents that can be used in accordance synthetic or biological macromolecules to a biological tis with one or more embodiments of the present invention sue . The term mucoadhesion refers to the special case of include, for example , naturally occurring polymeric mate bioadhesion where the biological tissue is an epithelium rials, such as locust bean gum , sodium alginate , sodium covered by mucous, for example such as found in the vagina , caseinate , egg albumin , gelatin agar, carrageenin gum , gastrointestinal tract and the nasal cavity . Mucoadhesive sodium alginate , Xanthan gum , quince seed extract, traga agents are a class of polymeric biomaterials that exhibit the canth gum , guar gum , starch , chemically modified starches basic characteristic of a hydrogel, i. e . swell by absorbing and the like , semi- synthetic polymeric materials such as water and interacting by means of adhesion with the mucous cellulose ethers ( e . g . hydroxyethyl cellulose , methyl cellu that covers epithelia . lose , carboxymethyl cellulose, hydroxy propylmethyl cellu [0107 ] Compositions of the present invention may contain lose ), guar gum , hydroxypropyl guar gum , soluble starch , a mucoadhesive macromolecule or polymer in an amount cationic celluloses , cationic guars , and the like , and syn sufficient to confer bioadhesive properties . The bioadhesive thetic polymeric materials , such as carboxyvinyl polymers , macromolecule enhances the delivery of biologically active polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid agents on or through the target surface . The mucoadhesive polymers , polymethacrylic acid polymers, polyvinyl acetate macromolecule may be selected from acidic synthetic poly polymers , polyvinyl chloride polymers, polyvinylidene mers , preferably having at least one acidic group per four chloride polymers and the like . Mixtures of the above repeating or monomeric subunit moieties, such as poly compounds are contemplated . (acrylic ) - and /or poly (methacrylic ) acid ( e. g ., Carbopol® , [0114 ] Further exemplary gelling agents include the Carbomer® ) , poly (methylvinyl ether /maleic anhydride ) acrylic acid /ethyl acrylate copolymers and the carboxyvinyl copolymer, and their mixtures and copolymers; acidic syn polymers sold , for example , by the B . F . Goodrich Company thetically modified natural polymers , such as carboxymeth under the trademark of Carbopol® resins. These resins ylcellulose (CMC ) ; neutral synthetically modified natural consist essentially of a colloidal water- soluble polyalkenyl polymers , such as ( hydroxypropyl )methylcellulose ; basic polyether crosslinked polymer of acrylic acid crosslinked amine -bearing polymers such as chitosan ; acidic polymers with from 0 .75 % to 2 % of a crosslinking agent such as obtainable from natural sources , such as alginic acid , polyallyl sucrose or polyallyl pentaerythritol. Examples hyaluronic acid , pectin , gum tragacanth , and karaya gum ; include Carbopol 934 , Carbopol® 940 , Carbopol 950 , and neutral synthetic polymers, such as polyvinyl alcohol or Carbopol® 980 , Carbopol® 951 and Carbopol® 981 . Car their mixtures . An additional group of mucoadhesive poly - bopol® 934 is a water -soluble polymer of acrylic acid US 2019 /0307887 A1 Oct . 10 , 2019 crosslinked with about 1 % of a polyallyl ether of sucrose [0123 ] The foam adjuvant according to one or more having an average of about 5 . 8 allyl groups for each sucrose embodiments of the present invention includes a mixture of molecule . fatty alcohols , fatty acids and hydroxy fatty acids and [0115 ] Yet, another group of gelling agents includes inor derivatives thereof in any proportion , providing that the total ganic gelling agents , such as silicone dioxide ( fumed silica ). amount is 0 . 1 % to 5 % ( w / w ) of the carrier mass. More [0116 ] According to one or more embodiments, the foam preferably , the total amount is 0 .4 % - 2. 5 % ( w / w ) of the composition contains at least one film forming component. carrier mass . The film forming component may include at least one [0124 ] While fatty alcohols and fatty acids serve to stabi water - insoluble alkyl cellulose or hydroxyalkyl cellulose . lize the resultant foam composition , they often provide Exemplary alkyl cellulose or hydroxyalkyl cellulose poly additional therapeutic properties . Long chain saturated and mers include ethyl cellulose , propyl cellulose, butyl cellu mono unsaturated fatty alcohols, e . g . , stearyl alcohol, erycyl lose , cellulose acetate , hydroxypropyl cellulose , hydroxy alcohol, arachidyl alcohol and docosanolhave been reported butyl cellulose , and ethylhydroxyethyl cellulose , alone or in to possess antiviral , anti infective , anti -proliferative and combination . In addition , a plasticizer or a cross linking anti - inflammatory properties ( U . S . Pat . No . 4 ,874 ,794 ) . agent may be used to modify the polymer ' s characteristics. Longer chain fatty alcohols , e . g . , tetracosanol , hexacosanol, For example , esters such as dibutyl or diethyl , heptacosanol, octacosanol, triacontanol, etc . are also known amides such as diethyldiphenyl urea , vegetable oils , fatty for their metabolism modifying properties and tissue ener acids and alcohols such as oleic and myristyl acid may be gizing properties . Long chain fatty acids have also been used in combination with the cellulose derivative . reported to possess anti- infective characteristics . Thus , the [0117 ] In one or more embodiments , the composition of therapeutic or cosmetic carrier, containing the foam adjuvant the present invention includes a phase change polymer , agent of the present invention provides an extra therapeutic which alters the composition behavior from fluid - like prior benefit in comparison with currently used vehicles, which to administration to solid - like upon contact with the target are inert and non -active . mucosal surface . Such phase change results from external [0125 ] Lower alcohols having up to 5 carbon atoms in stimuli, such as changes in temperature or pH and exposure their carbon chain skeleton , such as ethanol, propanol, isopropanol, butanol, iso - butanol, t -butanol and pentanol, to specific ( e . g . , Ca + + ) . are considered less desirable solvents or polar solvents due [0118 ] Non -limiting examples of phase change polymers to their skin - irritating effect. Thus, the composition is sub include poly ( N - isopropylamide ) , Poloxamer 407 and stantially alcohol- free and should comprise less than about Smart- Gel® ( Poloxamer + PAA ) . 5 % final concentration of lower alcohols , preferably less [0119 ] The polymeric agent is present in an amount in the than about 2 % , more preferably less than about 1 % . range of about 0 . 01 % to about 5 . 0 % by weight of the foam [0126 ] The therapeutic foam of the present invention may composition . In one or more embodiments, it is typically further optionally include a variety of formulation excipi less than about 1 wt % of the foamable composition . ents , which are added in order to fine -tune the consistency [0120 ] A foam adjuvant is optionally included in the of the formulation , protect the formulation components from foamable compositions of the present invention to increase degradation and oxidation and modify their consistency . the foaming capacity of surfactants and / or to stabilize the Such excipients may be selected , for example , from stabi foam . In one or more embodiments of the present invention , lizing agents , antioxidants , humectants, preservatives , colo the foam adjuvant agent includes fatty alcohols having 15 or rant and odorant agents and other formulation components , more carbons in their carbon chain , such as cetyl alcohol and used in the art of formulation . stearyl alcohol (or mixtures thereof) . Other examples of fatty [0127 ] Aerosol propellants are used to generate and alcohols are arachidyl alcohol (C20 ) , behenyl alcohol (C22 ) , administer the foamable composition as a foam . The total 1 - triacontanol ( C30 ) , as well as alcohols with longer carbon composition including propellant, foamable compositions chains (up to C50 ) . Fatty alcohols, derived from beeswax and optional ingredients is referred to as the foamable and including a mixture of alcohols , a majority ofwhich has carrier . The propellant makes up about 3 % to about 25 wt % at least 20 carbon atoms in their carbon chain , are especially of the foamable carrier. Examples of suitable propellants well suited as foam adjuvant agents . The amount of the fatty alcohol required to support the foam system is inversely include volatile hydrocarbons such as butane, propane, related to the length of its carbon chains. isobutane or mixtures thereof, and fluorocarbon gases . [0121 ] In one or more embodiments of the present inven tion , the foam adjuvant agent includes fatty acids having 16 Composition and Foam Physical Characteristics or more carbons in their carbon chain , such as hexadecanoic [0128 ] The compositions described herein , including acid (C16 ) stearic acid (C18 ) , arachidic acid (C20 ) , behenic water, additional solvents , formulation excipients , active acid (C22 ), octacosanoic acid (C28 ) , as well as fatty acids agents and propellant creates a stable emulsion that does not with longer carbon chains (up to C50 ) , or mixtures thereof. exhibit full phase separation at ambient temperature for at As for fatty alcohols , the amount of fatty acids required to least a year. support the foam system is inversely related to the length of [0129 ] Yet , another property of a composition is its level its carbon chain . of flow , since a composition that is not free flowing cannot [0122 ] Optionally , the carbon atom chain of the fatty flow through the dip - tube of the aerosol container and create alcohol or the fatty acid may have at least one double bond . acceptable foam . It has been noted that in the context of the A further class of foam adjuvant agent includes a branched composition of the present invention , compositions includ fatty alcohol or fatty acid . The carbon chain of the fatty acid ing semi- solid hydrophobic organic carriers , e . g ., white or fatty alcohol also can be substituted with a hydroxyl petrolatum , are excessively viscous and demonstrate poor group , such as 12 -hydroxy stearic acid . flowability . US 2019 /0307887 A1 Oct . 10 , 2019

[0130 ] The combination of at least one surface active dose valve is selected to release a foam in a volume that is agent, at least one polymeric agent and optionally at least in the size of the target body cavity to allow effective one foaming adjuvant, according to one or more embodi spreading of the active agent throughout the body cavity ments of the invention provides a low specific gravity foam with substantially minimal overflow . having superior expandability , flow properties and sheer 10143 ]. In one or more embodiments , the meter dose valve breakability ( among other attributes ) . According to one or provides a unit dose of between about 10 uL and about 1000 more embodiments of the present invention , the total UL . Assuming a representative foam density ( specific grav amount of at least one surface active agent, at least one ity ) of 0 . 06 g /mL , a 10 uL valve provides a volume of about polymeric agent and optionally at least one foaming adju 0 . 17 mL of foam , and a 1000 uL metered dose valve vant, in combination does not exceed 8 % ( w / w ) of foamable provides about 17 mL of foam . Thus, by selecting a specific composition . In one or more embodiments, the combined metered dosing valve and adjusting the foam density by fine amounts of at least one surface active agent, at least one tuning formulation parameters and adjusting the ration polymeric agent and optionally at least one foaming adju between the liquid components of the composition and the vant is less than 5 % ( w / w ) of foam composition . The low propellant, one can design an adequate dosage form accord solid content improves the flow properties of the foam , ing to the specific target organ cavity reduces unpleasant skin residue and reduces the cost of manufacture . As is demonstrated herein , the foam stability Administration and expandability are excellent , despite the low levels of these components in the foam . [0144 ] One limitation of existing vaginal and rectal dosage 0131] Expandability is an important feature of a product form relates to the dimensions of the product applicator. In that is intended to treat internal cavities of the body. Thus , order to administer 5 mL of gel (which is required to attain in one or more embodiments of the present invention , the effective coverage of the vaginal surface ) , an insert appli specific gravity of the foam , upon discharge from the foam cator, 10 cm long and about 1 . 5 cm thick is employed . It is dispenser is between about 0 .02 gr /mL and 0 .4 gr /mL , or to be understood that such a thick applicator is found between about 0 . 04 gr /mL and about 0 . 14 gr /mL . repulsive by patients, which leads to poor patient compli [0132 ] The following scale for foam quality is used to ance . Furthermore , the length of the applicator, which is evaluate foams. beyond the natural depth of a relaxed vaginal cavity, makes [ 0133 ] E (excellent ) : very rich and creamy in appear it difficult for the patient to accurately administer the com ance , does not show any bubble structure or shows a position into the target organ . very fine ( small ) bubble structure . [0145 ] By contrast , application of a foam composition 101341 G ( good ) : rich and creamy in appearance , very according to the present invention is not limited by appli small bubble size , “ dulls ” more rapidly than an excel cator dimensions. The insert is thin and thus, it is acceptable lent foam . to the patient. The thickness of the aerosol insert can range 10135 ] FG ( fairly good ) : a moderate amount of creami between about 0 . 2 cm and about 1 cm . Likewise , the aerosol ness noticeable , bubble structure is noticeable . insert can be designed in any length , to fit the dimensions of [0136 ] F ( fair ) : very little creaminess noticeable , larger the target organ . Thus, the length of a vaginal insert can bubble structure than a “ fairly good ” foam . range between about 2 cm and about 10 cm ; the length of an [0137 ] P (poor ) : no creaminess noticeable , large bubble insert for the nasal system or ear canal can be shorter and the structure . insert for rectal administration can be adjusted according to [0138 ] VP (very poor ) : dry foam , large very dull the location of the disorder , between about 1 cm and about bubbles, difficult to spread on the skin . 20 cm . In one or more embodiments , the insert is designed [ 0139] Foams that are adequate for topical administration to be flexible , to allow insertion into a body cavity that is according to the present invention have to be of quality difficult to access using a non - flexible insert . grade E or G , upon release from the foam dispenser . Smaller bubbles mean more stable foam , which does not collapse Fields of Application spontaneously immediately upon discharge from the con [0146 ] By including an appropriate active agent in the tainer. The finer foam structure looks and feels smoother , foamable composition , it is useful in the therapy and pre thus increasing its usability and appeal. vention of a variety of disorders of a body cavity or mucosal [0140 ] In one or more embodiments, the foam composi surfaces , including , but not limited to the cranial cavity , the tions are stable for a prolonged period of time. Thus, the thoracic cavity , the abdominal cavity , the ventral cavity , the foam composition does not undergo phase separation fol vagina , the rectum and penile cavities , the urinary tract , lowing at least two freeze and thaw cycles. bladder, the cavity between the uterus and the fallopian [ 0141] Upon discharge from a foam dispenser , e . g ., an tubes, the ovaries, the nasal cavity , the mouth , the eye , the aerosol can , onto a mucosal membrane at about 37° C ., the ear the peritoneum , the large and small bowel , the caecum , foam expands to reach its designated volume and stays bladder, and stomach , and other body cavities or spaces , stable as a foam for at least 60 seconds, or 2 minutes , or even which may accept topically -applied products . 3 minutes, following application . [0147 ] Exemplary treatable disorders are listed below . [0148 ] Bacterial, Fungal and Viral Infections Metered Dosing [0149 ] Bacterial , fungal and viral infections: a variety of [0142 ] In order to provide proper therapy, precise dosing anti- infective , anti -bacterial , anti - fungal and anti- viral is desired . According to one or more embodiments , the foam agents can be included in the foam of the present invention , therapeutic product is adapted for storage in a foam dis to be used for the treatment and / or prevention of diseases , penser having a metered dose valve for dispensing an such as chlamydia , gonorrhea , hepatitis B , herpes , HIVI accurate dose of drug in the form of a foam . The metered AIDS , human papallomavirus (HPV ) & genital warts ; syphi US 2019 /0307887 A1 Oct . 10 , 2019 lis ; bacterial vaginosis , candidiasis , chancroid , granuloma acteristically acidic (pH values of 3 . 4 to 6 .0 ) . Consequently , inguinale , lymphogranloma venereum , mucopurulent cervi the topical application of a formulation in which such citis (MPC ) , molluscum contagiosum , nongonococcal ure polymers would be soluble ( i. e ., PH6 ) would be expected to thritis (NGU ) , trichomoniasis , and vulvar disorders . contribute to a vaginal environment which is physiologically [ 0150 ] A variety of active agents , known in the art , can be undesirable . included in the foam to be used for the treatment and / or 10162 ]. Thus , in one embodiment of present invention , prevention of diseases such as vulvodynia ( vulvar pain ) , there is an advantage to an oily foamable carrier, comprising yeast infections , genital warts ( condyloma ) vulvar dystro solvents that solubilize water - insoluble polymenrs such as phy, vulvar intraepithelial neoplasia ( VIN ), invasive cancer mentioned above. By way of non - limiting example , such of the vulva , contact dermatitis, pelvic inflammation , pelvic solvents include polyethylene glycol, propylene glycol, hex inflammatory disease (PID ), genital cancer and cancer of the ylene glycol, benzyl alcohol, DMSO , isosorbide derivatives , cervix , vulva or vagina . such as dimethyl isosorbide, glycofurol and ethoxydiglycol [0151 ] Vaginal Dryness ( transcutol) . [0152 ] Vaginal dryness is caused by a number of condi 0163 ] In one or more embodiments of the present inven tions and can be either an occasional hassle or a chronic tion , the foam composition is useful in the therapy of problem . A variety of anti - inflammatory active agents , hor disorders that respond to transmucosal delivery of an active mones , moisturizing , refatting and lubricating agents and agent. By way of example , such disorders include , which local anesthetic agents can be included in the foam of the respond to , such as hormone replacement present invention , to be used for the treatment and/ or pre therapy , and other systemic disorders , known to be affected vention of vaginal dryness . by drugs that are delivered transmucosally. [ 0153 ] Dyspareunia [0164 ] The goal of a mucosal vaccine is to induce antigen [0154 ] Dysareunia is pain in the vagina or pelvis experi specific immune responses ( cellular and humoral) that are enced during sexual intercourse . A variety of anti -inflam detectable at the mucosal surfaces of the host. Because many matory active agents , hormones , moisturizing , refatting and pathogens initiate infection at the mucosal surfaces , patho lubricating agents and local anesthetic agents can be gen -specific mucosal immune responses may provide supe included in the foam of the present invention , to be used for rior protection against infectious diseases than immune the treatment and / or prevention of vaginal pain . Anal and responses induced by parenteral vaccines because parenteral rectal disease , such as anal abscess/ fistula , anal cancer , anal fissure , anal warts , Crohn ' s disease , hemorrhoids , anal itch , vaccines do not induce mucosal immunity . also called pruritus ani, fecal incontinence , and polyps of the 10165 ]. In the context of the present invention , the term colon and rectum all may be treated using the foamable immunization or vaccination refers to administering a prepa composition according to one or more embodiments of the ration that contains an infectious agent or its components , invention . which is able to stimulate an immune response that will [ 0155 ] The foam composition of the present invention , protect a person from illness due to that agent. Such vaccines comprising an active agent that is known to treat one of said are expected be capable of preventing the transmission or anorectal disorders and administered rectally , expands effec limiting the severity of sexually - transmitted infections, such tively in the rectal cavity and provides optimal coverage of as HIV and other infectious disease . Vaccines are usually the cavity surface , for improved therapeutic results . administered in conjunction with an adjuvant — a substance [0156 ] HIV and STD Treatment and Prevention that is used in a vaccine to improve the immune response so [ 0157 ] When comprising appropriate protective agents, that less vaccine is needed to produce a non - specific stimu the foam is active against HIV infection and other infections lator of the immune response . There are several types of ( bacterial and fungal ) , including sexually transmitted dis adjuvants , including , for example , minerals such as alumi ease (STD ) by creating a protective layer and / or decreasing num hydroxide, aluminum and phos the frequency of transmission . Non -binding examples of phate , oil emulsions, products from bacteria (their synthetic protective agents include : derivatives as well as liposomes ) or gram -negative bacteria , [0158 ] Negatively charged sulfated polymers, which have endotoxins, cholesterol, fatty acids , aliphatic amines , paraf been reported to have anti -HIV - 1 activity and are being finic and vegetable oils . considered for development as topical microbicides. [0166 ] The foam composition of the present invention , [0159 ] Dextrin sulphate , a microbicide , which in various comprising an immunizing agent, and optionally an adjuvant laboratory and pre- clinical studies , has been shown to block and administered onto the mucosal tissue of a body cavity, the transfer of HIV virus into mammalian cells while at the expands effectively in said cavity and provides optimal same time not causing injury to normal cell tissue . coverage of the cavity surface , for improved therapeutic [0160 ] Cellulose acetate phthalate , which inactivates HIV results . 1, herpesvirus types 1 ( HSV - 1) and 2 (HSV - 2) and the major [0167 ] Post -Surgical Adhesions Treatment and Prevention nonviral STD pathogens ; and found effective in animal [0168 ] Adhesions are scars that form abnormal connec models for vaginal infection by HSV - 2 and simian immu tions between tissue surfaces . Post - surgical adhesion forma nodeficiency virus . tion is a natural consequence of surgery , resulting when [ 0161] Several polymers , such as hydroxypropylmethyl tissue repairs itself following incision , cauterization , sutur cellulose phthalate , carrageenans , naphthalene sulfonate ing, or other means of trauma. When comprising appropriate polymer , sodium alginate , and cationic polymer , such as protective agents , the foam is suitable for the treatment or chitosan , are insoluble in water and can be solubilized in prevention of post surgical adhesions. The use of foam is water by adjusting the pH of the environment to about 6 or particularly advantageous because foam can expand in the above , or by the use of appropriate organic solvents . Vaginal body cavity and penetrate into hidden areas that cannot be secretions from healthy, reproductive -age women are char reached by any other alternative means of administration . US 2019 /0307887 A1 Oct . 10 , 2019

[0169 ] Hormonal Therapy Organic oxidizing agents are also included in the definition [0170 ] The foamable composition of the present invention of “ oxidizing agent” according to the present invention , such is suitable for administering a hormone to a mucosal mem as quinones . Such agents possess a potent broad spectrum brane or a body cavity , in order to deliver the hormone into activity the tissue of the target organ , in any disorder that responds [0177 ] Antibacterial compositions according to the pres to treatment with a hormone . Topically applied hormones ent invention are selected to treat infections of an afflicted can also be useful in contraception , when administered in organ . The composition of the present invention , comprising foam , using a metered dose unit . a hydrophobic component, would facilitate an enhanced rate of penetration . Furthermore, the intrinsic antibacterial and Active Agents antiinflammatory effects of the foam adjuvant agents, i . e . , [0171 ] The composition of the present invention com fatty alcohols and acids, provides a combined effect for prises at least one active agent, also referred to as " drug ( s ) ” . better therapeutic response to treatment . The at least one active agentmay consist of a single drug or [0178 ] Fungal infections are another object of treatment a combination of drugs that can be dissolved in the water using the composition of the present invention . Fungal phase or the hydrophobic phase of the carrier composition . infection of the vaginal cavity is one of the most common Examples of such drugs are antibiotic , antibacterial, anti disorders seen in gynecological practice . Candidiasis is an fungal, antiviral, antiinflammatory , anesthetic , analgesic , infection caused by the yeast like fungus Candida albicans antiallergic , corticosteroid and antiproliferative or occasionally other species of Candida . Clinical syn and mixtures thereof at any proportion . The concentration of dromes of candidiasis include : ( a ) oral candidiasis (oral drugs may be adopted to exert a therapeutic effect on a thrush ); (b ) candidiasis of the skin and genital mucous disease when applied to an afflicted area . membrane ; and ( c ) Candida paronychia , which inflicts the [0172 ] One important class of drugs comprises antibacte nail . rial agents . It is well known that bacterial infections are [ 0179 ] The therapeutic composition may comprise an anti involved in a variety of superficial disorders of mucosal fungal drug , which is active against dermatophytes and membranes and body cavities . Candida , selected from the group of, but not limited to [0173 ] In one or more embodiments , the antibiotic agent is azoles , diazoles , triazoles, miconazole , fluconazole , keto selected from the classes consisting of beta - lactam antibi conazole , , itraconazole , otics , aminoglycosides , ansa -type antibiotics , anthraquino ciclopirox , amorolfine , terbinafine, Amphotericin B , potas nes , azoles , glycopeptides , macrolides , nucleosides, antibi sium iodide , flucytosine (5FC ) and any combination thereof otic peptides, antibiotic polyenes , antibiotic polyethers , at a therapeutically effective concentration . According to quinolones, antibiotic , sulfonamides , , one preferred embodiment the active agent is metronidazole . antibiotic metals , including silver , copper, , mercury, tin , [0180 ] The composition of the present invention is par lead , bismuth , cadmium , chromium and ions and complexes ticularly beneficial in the case of viral infections including thereof, oxidizing agents and substances that release free herpes simplex Type 1 virus. Mollusca are small viral radicals and / or active oxygen , cationic antimicrobial agents , growths that appear singly or in groups on the face , trunk , quaternary ammonium compounds, biguanides , triguanides, lower abdomen , pelvis , inner thighs , or penis . Warts are a bisbiguanides and analogs and polymers thereof and natu common , benign skin tumor caused by viral infection . HPV rally occurring antibiotic compounds . (Human Papillomavirus ) is a common genital disease . [0174 ] An antibacterial drug can be active against gram [0181 ] Viral infections are currently treated with various positive and gram -negative bacteria , protozoa, aerobic bac antiviral agents , as summarized in the following table : teria and anaerobic bacteria . [0175 ] By way of example , the antibacterial drugs are selected from chloramphenicol, beta - lactam antibiotics, Drug Viruses Chemical Type aminoglycosides, ansa -type antibiotics , anthraquinones, Vidarabine Herpesviruses Nucleoside azoles , glycopeptides, macrolides , nucleosides , antibiotic analogue peptides, antibiotic polyenes , antibiotic polyethers , quino Acyclovir Herpes simplex Nucleoside lones, antibiotic steroids, sulfonamides, tetracycline , antibi (HSV ) analogue otic metals , including silver , copper, zinc , mercury , tin , lead , Gancyclovir Cytomegalovirus Nucleoside ( CMV ) analogue bismuth , cadmium , chromium and ions and complexes Nucleoside -analog reverse Retroviruses Nucleoside thereof, oxidizing agents and substances that release free transcriptase inhibitors (NRTI ) : AZT (HIV ) analogue radicals and / or active oxygen , cationic antimicrobial agents , (Zidovudine ) , ddl ( Didanosine ), ddC quaternary ammonium compounds , biguanides , triguanides , (Zalcitabine ) , d4T ( Stavudine ), 3TC (Lamivudine ) bisbiguanides and analogs and polymers thereof and natu Non - nucleoside reverse transcriptase Retroviruses Nucleoside rally occurring antibiotic compounds, metronidazlole and its inhibitors (NNRTI ) : , (HIV ) analogue derivatives and analogs , dicarboxylic acids, such as azelaic Delavirdine acid , slicylates, cyclosporines and any combination thereof Protease Inhibitors: Saquinavir , HIV Peptide , , Nelfinavir analogue at a therapeutically effective concentration . Ribavirin Broad spectrum : Triazole [ 0176 ] Another group of antibacterial agents which have HCV, HSV , carboxamide broad spectrum activity comprises strong oxidants and free measles , mumps , radical liberating compounds , such as oxygen , hydrogen Lassa fever Amantadine /Rimantadine Influenza A Tricyclic amine peroxide , benzoyl peroxide , elemental halogen species , as strains well as oxygenated halogen species , bleaching agents ( e . g ., Interferons Hepatitis B and C Protein sodium , calcium or hypochloride and the like ) , perchlorite species, iodine, iodate , and benzoyl peroxide. US 2019 /0307887 A1 Oct . 10, 2019

[ 0182 ] Any of the above antiviral agents , in a therapeuti [0195 ] xii . a steroid hormone ; cally effective concentration , can be incorporated in the f01961. xiii . a steroid hormone , selected from the group foam composition of the present invention . The composition consisting of an , an and a of the present invention , which comprises a hydrophobic [0197 ]. xiv . an androgen , selected from the group consist organic carrier, would facilitate an enhanced rate of pen ing of , testosterone cipionate, testosterone etration and better topical distribution of any of the above decanoate , testosterone enantate , testosterone isocaproate , listed antiviral drugs . Furthermore , the intrinsic antiviral testosterone phenylpropionate , , effects of the foam adjuvant agents , i . e . , fatty alcohols and testosterone undecylate , 5a - , dehy acids , provides a combined effect that should result in a droepiandrosterone ( also termed and DHEA ) , better therapeutic response to treatment. , androstanediol, , andros [0183 ] In one or more embodiments , the active agent is a tenolone, prasterone enantate , prasterone sodium sulfate , steroid , selected from the following groups. , , , methyltes [ 0184 ] i. a compound containing a cyclopenta [ a ] phenan tosterone , , delmadinone, , threne skeleton ; chlormadinone , , and tes [0185 ] ii . a compound , containing a cyclopenta [ a ] phenan tolactone; threne skeleton carrying one or more functional groups [01981 . XV . an estrogen selected from the group consisting selected from halogens, alkyl groups , aryl groups, benzyl of , , estradiol cipionate , estra groups, carboxy groups and alkoxy groups ; diol dipropionate , estradiol enantate , estradiol hexahyd [0186 ] iii. robenzoate, estradiol phenylpropionate , , , , estriol sodium succinate , , polyestriol phosphate , , (57 ) , , , estrapronicate HO and ; [0199 ] xvi. a progestogen , selected from the group con sisting of progesterone , , , norethisterone enantate , medroxyprogesterone acetate , delmadinone acetate , flugestone acetate , dydro gesterone , , , , dydro gesterone , , chlormadinone acetate , , NO , , tybolone , acetate , , ; 3a , 7a , 12a - Triydroxy - 53 - cholestan - 24 - al [0200 ] xvii. an inhibitor of a steroid hormone ; or cholaldehyde ( from cholic acid ) [0201 ] xviii. an inhibitor of a steroid hormone, selected from the group consisting of inhibitors are , [0187 ] iv . a steroid compound , selected from the families and ; of ( a ) cardanolides , ( b ) bufanolides, ( c ) spirostans, ( d ) [0202 ] xix . a vitamin D ; furostans, ( e ) steroid alkaloids, ( f ) a steroid lactone , ( g ) an [0203 ] XX . a vitamin D , selected from the group consisting oxo - steroid , ( h ) a steroid - alcohol and ( i ) a steroid - amine ; of cholecalciferol, 25 -hyd roxycholecalciferol, la , 25 - di [0188 ] V . a steroid compound , where one or more of the hydroxycholecalciferol, ergocalciferol, la , 25 -dihydroxy cyclopenta [ a ]phenanthrene rings is contracted by loss of ergocalciferol, 22 ,23 - dihydroergocalciferol, 1 ,24 ,25 - tri an unsubstituted methylene group ; hydroxycholecalciferol, previtamin D3 , tachysterolz (also [0189 ] vi. a steroid compound , where one or more of the termed tacalciol) , Isovitamin D3, dihydrotachysterolz , cyclopenta [ a ]phenanthrene rings is expandeded by inclu ( 1S ) -hydroxycalciol , (24R ) -hydroxycalcidiol , 25 - fluoro sion of a methylene group ; calciol, ercalcidiol, ertacalciol, (5E )- Isocalciol, 22, 23 [0190 ] vii. a compound , containing a cyclopenta [ a ] Dihydroercalciol, ( 24S )- methylcalciol , (5E ) - ( 10S ) - 10 , 19 phenanthrene skeleton and a carbocyclic or heterocyclic Dihydroercalciol, (248 )- Ethylcalciol and (22E ) -( 24R ) ring component fused to it ; Ethyl- 22, 23 - didehydrocalciol; and [0191 ] viii. an anti - inflammatory steroid ; [0204 ] xxi . a or a . [ 0192 ] ix . a steroid possessing immunomodulating and /or [ 0205 ] According to another embodiment according to the anti - inflammatory properties ; present invention the at least one active agent is an antiin [0193 ] X . a steroid , selected from the group of low - potency flammatory or antiallergic agent. An antiinflammatory or anti - inflammatory steroids , medium potency anti- inflam antiallergic agent can be selected from the group of corti matory steroids and high potency anti -inflammatory ste costeroids (as listed above ), non - steroidal antiinflammatory roids; drugs (NSAIDs ), anti- histamines , immunosuppressants and [ 0194 ] xi. an anti - inflammatory steroid , selected from the any combination thereof at a therapeutically effective con group consisting of hydrocortisone, hydrocortisone centration . acetate , desonide , betamethasone valerate , clobetasone [0206 ] Since corticosteroid drugs are typically hydropho 17 -butyrate , flucinonide , fluocinolone acetonide , alco bic , the carrier of the present invention , comprising a metasone dipropionate , mometasone furoate , prednicar hydrophobic organic carrier, is most suitable as a vehicle to bate , triamcinolone acetonide , betamethasone - 17 facilitate better topical distribution and an enhanced rate of benzoate , aceponate , betamethasone penetration of any of the above listed drugs . Furthermore , dipropionate, halcinonide , triamcinolone acetonide , halo the intrinsic antiviral, antibacterial and antiinflammatory betasol, clobetasol - 17 - propionate ; effects of the foam adjuvant agents , i. e ., fatty alcohols and US 2019 /0307887 A1 Oct . 10 , 2019 13 acids, provides a combined effect that should result in a [0215 ] A safe and effective amount of an anti- oxidant / better therapeutic response to treatment. radical scavenger may be added to the compositions of the [0207 ] Antihistaminic agents may comprise , among other present invention , preferably from about 0 . 1 % to about 10 % options, diphenhydramine , doxepin , phrilamine maleate , ( w / w ), more preferably from about 1 % to about 5 % (w /w ), chlorpheniramine , tripelennamine , phenothiazines , promet of the composition . hazine hydrochloride and dimethindene maleate . These [0216 ] Anti -oxidants / radical scavengers such as ascorbic drugs, as well as additional antihistamines can also be acid ( vitamin C ) and its salts , ascorbyl esters of fatty acids , incorporated in the composition of the present invention . ascorbic acid derivatives ( e . g ., magnesium ascorbyl phos [ 0208 ] A second class of anti- inflammatory agents , which phate , sodium ascorbyl phosphate , ascorbyl sorbate ), is useful in the foam of the present invention , includes the tocopherol (vitamin E ) , tocopherol sorbate , tocopherol nonsteroidal anti - inflammatory agents (NSAIDs ) . The vari acetate , other esters of tocopherol, butylated hydroxy ben ety of compounds encompassed by this group is well- known zoic acids and their salts, 6 -hydroxy - 2 , 5 , 7 , 8 - tetramethyl to those skilled in the art . Specific non - steroidal anti - inflam chroman - 2 - carboxylic acid ( commercially available under matory agents useful in the composition invention include , the tradename Trolox® ) , gallic acid and its alkyl esters , but are not limited to : oxicams, such as piroxicam , isoxicam , especially propyl gallate , uric acid and its salts and alkyl tenoxicam , sudoxicam ; salicylates , such as salicylic acid , esters , sorbic acid and its salts , , amines ( e . g . , ethyl salicylate , methyl salycilate , aspirin , disalcid , benory N , N - diethylhydroxylamine, amino - guanidine ) , sulfhydryl late, trilisate , safapryn , solprin , diflunisal , and fendosal ; compounds ( e . g . , glutathione ) , dihydroxy fumaric acid and acetic acid derivatives , such as diclofenac , fenclofenac , its salts , lycine pidolate , arginine pilolate , nordihydrogua indomethacin , sulindac , tolmetin , isoxepac, furofenac , tiopi iaretic acid , bioflavonoids , curcumin , lysine , methionine , nac , zidometacin , acematacin , fentiazac , zomepirac , clin proline, superoxide dismutase , silymarin , tea extracts , grape danac , oxepinac , felbinac , and ketorolac ; fenamates , such as skin / seed extracts , melanin , and rosemary extracts may be mefenamic , meclofenamic , flufenamic , niflumic , and tolfe used . namic acids ; propionic acid derivatives, such as ibuprofen , [0217 ] The foam of the present invention is suitable for naproxen , benoxaprofen , flurbiprofen , ketoprofen , fenopro delivering cell and tissue protecting and revitalizing anti fen , fenbufen , indopropfen , pirprofen , carprofen , oxaprozin , oxidants/ radical scavengers . Polyunsaturated fatty acids , pranoprofen , miroprofen , tioxaprofen , suprofen , alminopro containing omega - 3 and omega - 6 fatty acids ( e . g . , linoleic fen , and tiaprofenic ; and pyrazoles, such as phenylbutazone , and linolenic acid , gamma - linoleic acid (GLA ) , eicosapen oxyphenbutazone , feprazone , azapropazone , and trimetha taenoic acid ( EPA ) and docosahexaenoic acid (DHA ) are zone . beneficial in the treatment of inflammation conditions. Like [ 0209] Any further steroidal and nonsteroidal compounds, wise , emollients and silicone oils exert moisture - retaining having the capacity to prevent, alleviate the symptoms of, and protective effects on the target tissue . Thus, in a pre treat or cure inflammation processes , are generally included , ferred embodiment, a tissue protective foam is provided , as possible anti -inflammatory agents , according to the pres wherein the hydrophobic organic carrier comprises in full or ent invention . in part , a solvent , selected from the group of emollients , [0210 ] The therapeutic foam composition of the present silicone oil and oils , rich in unsaturated fatty acids , thus , invention may also comprise an antiinflammatory or antial affording a synergistic therapeutic effect of the anti- oxi lergic agent, wherein said agent reduces the occurrence of dants / radical scavenger agent and the vehicle components . pro -inflammatory cytokines or inhibits the effect of pro [0218 ] Active agents , which are known in the art of inflammatory cytokines . pharmacology to treat mucosal irritations and inhibit inflam [ 0211 ] Mixtures of such anti - inflammatory agents may mation , can be beneficially incorporated in the foam of the also be employed , as well as the dermatologically acceptable present invention . salts , esters , amides, prodrugs and derivatives of these [0219 ] Examples of such active agents include chamomile agents . extract (Matricaria recutitia ), cucumber distillate (Cucumis (0212 ]. The compositions of the present invention may sativus ) , lavender water ( Lavendula angustifolia ) , rose contain a safe and effective amount of a topical anesthetic . water (Rosa damascena ) , witch hazel (Hamamelis virgini Examples of local anesthetic drugs include benzocaine , ana ) , allantoin , bisabolol, rosehip oil , calendula oil , azu lidocaine, bupivacaine , chlorprocaine, dibucaine , etido laene , menthol and camphor. caine, mepivacaine, tetracaine , dyclonine , hexylcaine , pro [0220 ] There are several potential uses of the foam , par caine , cocaine, ketamine , pramoxine , phenol, and therapeu ticularly the silicone- oil based foam , as a lubricating foam . tically acceptable salts thereof. Mixtures of such anesthetic Typical examples are moisture protection foam and antifric agents may be synergistically beneficial . tion foam . For such purposes , the foam can be used in its [ 0213] Anti cancer agents can also be used according to basic composition (without additional formulation aids and the present invention as the drug of choice for treating for active ingredients ), or with the addition of such additives . example vaginal, cervical and rectal malignancies. In certain [0221 ] According to one embodiment, the at least one cases , topical cytotoxic and antiproliferative drugs are used active agent is selected from the group of solvent, surface to treat or prevent such cancers, including 5 -fluorouracil , active agent, foam adjuvant and polymeric agent. also called 5 - FU . 5 - FU , as well as any other anti -cancer agents , know in the art of cancer medicine , can be incorpo Penetration Enhancers rated in the foam at therapeutically effective levels . [0222 ] A penetration enhancer or permeation enhancer is [ 0214 ] A preferred family of anticancer drugs , suitable for an agent used to increase the permeability of tissue to a usage in the foam of the present formulation comprises pharmacologically active agent to increase the rate at which , such as . Tamoxifen blocks the the drug diffuses through the skin and enters the tissues and effects of the hormone estrogen in the body. bloodstream . A chemical penetration enhancer increases US 2019 /0307887 A1 Oct . 10 , 2019 14

skin permeability by reversibly altering the physiochemical Example 2 – Emulsion Foam Carrier Composition nature of the tissue to reduce its diffusional resistance . for Vaginal and Rectal Treatment According to one or more embodiments of the present invention a penetration enhancer is incorporated into the [ 0230 ] The ingredients listed in the table below are com foam composition . bined to form a foamable emulsion composition . [ 0223] Examples of penetration enhancers , according to the present invention include : polyols , such as propylene Version Version Version Version glycol, hexylene glycol, diethylene glycol, propylene glycol Ingredient No . 1 No . 2 No. 3 No . 4 n -alkanols , terpenes, di- terpenes , tri - terpenes , terpen - ols , limonene , terpene -ol , 1 -menthol , dioxolane , ethylene glycol, Hydrophobic MCT oil 30 - 15 12 organic carrier IPM 30 12 other glycols, and glycerol; sulfoxides , such as dimethyl Foam adjuvant Stearyl Alcohol R 1 .0 1 . 0 1 . 0 1 .0 sulfoxide (DMSO ) , dimethylformanide , methyl dodecyl sul Surface - active GMS 1 . 0 1 . 0 1 . 0 1 . 0 foxide , dimethylacetamide ; monooleate of ethoxylated glyc agent PEG S -40 erides (with 8 to 10 ethylene oxide units ); Azone Polysorbate -60 ??? Polymeric Xanthan Gum w 0 .3 ( 1 - dodecylazacycloheptan - 2 - one) , 2 - ( n - nonyl) - 1 , 3 - dioxo agent Methocel ELV15 0 . 4 | lane; esters , such as isopropyl myristate /palmitate , ethyl Natrosol I 1 . 5 1 . 5 acetate , butyl acetate , methyl proprionate , capric / caprylic Other Antioxidant 0 . 2 0 . 2 0 . 2 0 . 2 Ingredients Preservatives 1 . 0 1 . 0 1 . 0 1 . 0 triglycerides, octylmyristate , dodecyl- myristate ; myristyl Propellant* Propane /butane 8 . 0 8 . 0 8 . 0 8 . 0 alcohol, lauryl alcohol, lauric acid , lauryl lactate ketones ; Water Water To 100 To 100 To 100 To 100 amides , such as acetamide oleates such as triolein ; various Foam Specific ND ND ND 0 .06 surfactants, such as sodium lauryl sulfate ; various alkanoic gravity ( gr/ mL ) acids such as caprylic acid ; lactam compounds , such as azone ; alkanols , such as oleyl alcohol; dialkylamino [0231 ] The liquefied or gas propellant can be added at a acetates, and admixtures thereof. concentration of about 3 % to about 25 % . The compositions [ 0224 ] Lower alcohols , such as ethanol, propanol, isopro use only non - ionic surface active agents , and the total panol, butanol, iso - butanol, t -butanol and pentanol are less amount of surface active agent, foam adjuvants and poly desirable penetration enhancers according to the present meric agent ranged from 1 . 4 to 2 . 1 % ( w / w ) . The foam of this invention , due to their irritation properties . example is useful as a carrier of active agents , as exemplified [0225 ] Yet , another preferred class of penetration enhanc in examples below . It is also useful as lubricating foam , for ers in the cyclodextrines and related compounds. Cyclodex various purposes . trins are structurally related cyclic oligomaltoses which form a new group of therapeutic excipients . Example 3 — Further Mixed Oil Foam Carrier [0226 ] The invention is described with reference to the Composition for Vaginal and Rectal Treatment following examples . This invention is not limited to these examples and experiments. Many variations will suggest [0232 ] The ingredients listed in the table below are com themselves and are within the full intended scope of the bined to form a foamable emulsion composition . appended claims. Version Example 1 - General Procedure for Preparing Foam No . 1 Version No . 2 Composition Ingredient ~ 25 % Oil - 12 . 5 % Oil [ 0227 ] Aqueous Phase : At least one polymeric agent and Hydrophobic Mineral oil 10 . 2 at least one surface - active agent are dissolved in water , with organic carrier Isopropyl myristate 5 . 0 MCT oil 7. 0 innimcoina agitation . The solution is warmed to about 50° C . to about Foam adjuvant agent Stearyl Alcohol 2 .0 2 .0 70° C . Water soluble therapeutic active ingredients and Surface - active agent Brij 72 2 . 5 2 .5 optional water soluble ingredients are added with agitation Brij 721 1 . 0 1 . 0 Cocoa amido 0 . 5 0 . 5 to the Aqueous Phase mixture . propyl betaine [ 0228 ] Oil Phase: At least one hydrophobic organic carrier Polymeric agent Xanthan Gum is heated to same above temperature. Foam adjuvant agent Natrosol 0 .3 is added to preheated hydrophobic organic carrier. Oil Methocel ELV15 0 . 5 soluble therapeutic active agent or agents and optional oil Propellant* Propane /butane 6 . 0 6 . 0 soluble formulation ingredients are added with agitation to Water Water To 100 To 100 the Hydrophobic Phase mixture . [ 0229 ] The warm Hydrophobic Phase is gradually poured [0233 ] The liquefied or gas propellant can be added at a into the warm Aqueous Phase , with agitation , followed by concentration of about 3 % to about 25 % . The foams of this Ultraturax or Silverson homogenization . The mixture is example have a non - ionic surface active agent to ionic allowed to cool down to ambient temperature . In case ofheat surface active agent ratio ( w / w ) of 20 : 1 and 14 : 1 for versions sensitive active ingredients , the active ingredient is added 1 and 2 , respectively . Total amounts of surface active agent with agitation to the mixture after cooling to ambient foam adjuvant and polymeric agent is in the range of about temperature . The mixture , at ambient temperature , is added 1 .75 to about 3 . 5 % ( w /w ) . to an aerosol container, the container is sealed and appro [0234 ] The compositions are useful as carriers of active priate amount of propellant (about 3 % to about 25 w % of therapeutic active ingredients , as exemplified in examples the composition mass ) is added under pressure into the below . It is also useful as lubricating foam , for various container . purposes . US 2019 /0307887 A1 Oct . 10 , 2019 15

[0235 ] The following examples , representing optional - continued drug -containing foams, are prototype formulations , which have not been optimized for stability and inter- component Version 1 Version 2 Version 3 Version 4 compatibility . Such optimization is a customary need , which “ Miconazole ” “ Clotrimazole ” “ Econazole ” “ Nystatin ” can be done, using means, known to those skilled in the art Ingredient % w / w % w / w % w / w % w / w Propellant * 10 . 0 10 . 0 10 . 0 10. 0 of therapeutic formulation Propane ) butane Example4 Antibacterial Foam Composition for Water To 100 To 100 To 100 To 100 Vaginal Vaginosis and Other Vaginal and Rectal Infections [0239 ] The liquefied or gas propellant can be added at a concentration of about 3 % to about 25 % . The foams of this [0236 ] example have a non - ionic surface active agent to ionic surface active agent ratio ranging from about 16 : 1 to about 6 : 1 . Total surface active agent, foam adjuvant and polymeric % w /w % w / w % w /w agent ranges from 2 .05 to 3 .5 % (w /w ). They are useful in the Metronidazole 1 . 00 treatment of fungal and yeast infections. — 2 . 00 2 .00 Mineral oil 6 .00 6 . 00 6 . 00 Example 6 Corticosteroid Foam Composition Mineral oil 6 .00 6 . 00 6 .00 Isopropyl myristate 6 . 00 6 .00 6 .00 [0240 ] Glyceryl monostearate 1 . 00 1 . 00 1 . 00 Stearyl alcohol 1 . 00 1 .00 1 . 00 Xantan gum 0 . 30 0 . 30 0 . 30 Methocel K100M 0 . 30 0 . 30 0 . 30 % w / w % w / w % w / w % w / w % w / w 1 . 00 1 .00 1 . 00 Tween 60 5 .60 5 .60 5 . 60 MYRJ 52 3 . 00 3 . 00 3 .00 Mineral oil 5 . 60 5 . 60 Cocoamidopropylbetaine 0 . 50 0 . 50 Isopropyl myristate 5 .60 5 .60 5 .60 5 .60 5 .60 (phenoxy ethanol and methyl , ethyl 0 . 80 0 .80 0. 80 Glyceryl monostearate 0 . 45 0 .45 1 . 00 1 . 00 1 . 00 and propyl hydroxy benzoate mixture ) Stearyl alcohol 0 . 85 0 . 85 0 .85 0 .85 0 . 85 Propellant 10 .00 10 .00 10 . 00 Myrj 52 2 .60 2 . 60 2 .60 2 . 60 2 .60 Propane /butane * Xantan gum 0 . 26 - to 100 . 0 to 100 . 0 to 100. 0 Methocel K100M 0 . 26 Water Chitosan 1 . 00 Hyaluronic acid 0 .50 0 . 50 Avicel CL611 2 . 00 2 . 00 2 . 00 2 .00 [ 0237 ] The liquefied or gas propellant can be added at a TWEEN 80 0 . 90 0 . 90 0 . 90 0 . 90 0 .90 Cocoamidopropyl betaine 0 . 41 0 .41 0 . 41 0 . 41 0 . 41 concentration of about 3 % to about 25 % . The foams of this Betametasone valerate 0 . 12 - 0 . 12 0 .12 example have a non - ionic surface active agent to ionic Hydrocortisone butyrate 0 . 10 0 . 10 surface active agent ratio ranging from about 20 : 1 to about Propylene glycol 3 . 00 3 . 00 3 .00 3 . 00 3 .00 Parabens (phenoxy 0 . 8 0. 8 0 .8 0. 8 0 .8 6 : 1 . In one version , no ionic surface active agent was ethanol and methyl, ethyl present. and propyl hydroxy benzoate mixture ) Propellant 12 . 00 12. 00 12. 00 12. 00 12. 00 Example 5 — Foam Composition Propane/ butane * Water To 100 To 100 To 100 To 100 To 100 [0238 ] 10241 ] The liquefied or gas propellant can be added at a Version 1 Version 2 Version 3 Version 4 concentration of about 3 % to about 25 % . The foams of this “ Miconazole ” “ Clotrimazole ” “ Econazole ” “ Nystatin ” example have a non - ionic surfactant to ionic surfactant ratio Ingredient % w / w % w / w % w / w % w / w ranging from about 20: 1 to about 14 : 1. Total surface active Carrier agent, foam adjuvant and polymeric agent ranged from Ingredients about 2 % to about 3 . 5 % ( w / w ) . Mineral oil | 10 Isopropyl 10 Example 7 — Antiviral Foam Composition myristate MCT oil 30 10 [0242 ] MICTStearyl 2 . 0 2 . 0 Alcohol 20 20 2.0 Myrj 40 0 . 8 Version 1 Version 2 Version 3 GMS 2 .0 2 . 0 " Acyclovir ” " Acyclovir ” “ a - Interferon ” Natrosol 1 . 0 1 . 0 Ingredient % w / w % w / w % w / w Active Ingredients Carrier Ingredients Miconazole Mineral oil 48 . 4 11 . 0 5 . 4 Clotrimazole 11- Isopropyl myristate 5 .0 2 . 5 Econazole MCT oil 7 . 0 3 . 5 Nystatin lal 100 ,000 Stearyl Alcohol 0 . 7 0 . 4 0 . 2 Units/ gr Water To 100 To 100 To 100 US 2019 /0307887 A1 Oct . 10 , 2019 16

- continued Foam Preparation MetroGel Vaginal Version 1 Version 2 Version 3 Property Mean Rating Mean Rating “ Acyclovir” “ Acyclovir ” “ Q - Interferon " Ease of preparation prior to 2 . 8 0 . 6 Ingredient % w / w % w / w % w / w administration Ease of insertion 1 . 2 Sucrose ester SP70 0 . 8 0 . 8 0 . 8 Comfort upon insertion 1. 2 Distilled monoglyceride 1. 2 i Ease of dosing 1 . 5 Sodium lauryl sulphate 0 .05 in Lack of dripping 1. 3 Xanthan Gum 0 . 2 0 . 3 0 .w 3 Ease of removal 1 .6 Methocel ELV15 0 . 2 0 .a 6 Comfort upon removal 1 . 3 Active Ingredients Overall rating 2 .2 1 . 3 Acyclovir a - Interferon 105 IU / g Example 10 : Animal Model for Drug Propellant* 6 . 0 10 . 0 Propane /butane Administration and Duration [0248 ] The composition of Example 4 , Version 2 was prepared , with the addition of 0 . 2 % methylene blue as [ 0243] The liquid is added at a concentration of about 3 % coloring agent . A female sheep was administered intra to about 25 % . The foam of this example has a non - ionic vaginally one dose of the foam (metered dose , 50 UL ) . The surfactant to ionic surfactant ration ranging from 20 : 1 to vagina and cervix were observed by colposcopy and 14 : 1 . Total surface active agent, foaming adjuvant and recorded photographically. The insertion was very easy . polymeric agent ranged from about 2 % to about 3 .5 % (w /w ) . Foam expanded effectively and vaginal cavity and cervix area were fully covered . Fifteen minutes after treatment, the vagina was swabbed . Colposcopy revealed that the entire Example 8 . Compositions Consisting of vaginal cavity and cervix area were still covered by the blue Corticosteroids , Antifungal and Antiviral Agents pigment. There was no overflow of the foam and no dripping after administration . No signs of irritation were observed . [ 0244 ] Example 11 — Very Low Surfactants Formulation Ingredient % w / w % w / w % w / w % w / w [0249 ] Betamethasone valerate 0 . 1 Ketoconazole 2 . 0 2 .0 Acyclovir 5 . 0 % w / w % w / w % w / w % w / w Caprylic / Capric Triglycerides 60 . 9 60 . 0 59. 0 56 . 0 Propylene glycol 10 . 0 10 . 0 5 . 0 Mineral oil 20 .00 20. 00 30 .00 Hexylene glycol 10 . 0 Isopropyl palmitate 15 .00 Potent solvent — 5 . 0 MCT oil 15 . 00 Lecithin 10 . 0 10 . 0 10 .0 10 . 0 Glyceryl monostearate 1 . 00 1 . 00 Stearyl alcohol 5 . 0 5 . 0 5 .0 5 .0 Sucrose ester and Sorbitan stearate 0 . 20 0 . 20 0 . 20 0 . 20 Glyceryl monostearate 2 . 0 2 .0 2 .0 2 .0 (Arlatone 2121 ) PVP K90 2 . 0 2. 0 2 . 0 2 . 0 Pemulen TR1 00 . 20 Preservative 0 . 3 0 . 3 0 . 3 0 . 3 Pemulen TR2 00 . 20 00 . 20 Propellant 10 . 0 12 . 0 12 . 0 10 . 0 Methocel K100 00 . 30 00. 30 00 . 30 00 . 30 Propane /butane * Xantan Gum Purified water * * TO 100 TO 100 TO 100 TO 100 TWEEN 80 11 .00 TEA 00 . 10 . 0 . 10 00 .10 Propellant 112 .00 112. 00 112 .00 112 .00 [0245 ] The liquefied or gas propellant can be added at a Water To 100 To 100 To 100 To 100 concentration of about 3 % to about 25 % . Water content in these compositions was about 10 % [0250 . The formulations of Example 11 are made stable with unexpectedly low surfactant concentration making them highly non irritating and of lower itching potential for Example 9 — Comparative Tolerability and conditions of damaged infected or diseased condition vagi Acceptability Study of a Placebo Foam nal mucous. Composition Vs . a Conventional Gel [0251 ] Although various embodiments that incorporate the teachings of the present invention have been shown and [0246 ] Four patients compared the use of the foam prepa in detail herein , those skilled in the art can readily devise ration of Example 4 , Version 2 , with a conventional intra many other varied embodiments that incorporate these vaginal gel preparation (Metrogel Vaginal, 3M ). They were teachings . All references mentioned herein are incorporated asked to describe their feeling about the application of each by reference . of the products and to give their general rating for each of 1 . A foamable composition comprising a carrier and a the products on a scale of 0 - 3 ( 0 = poor ; 1 = barely acceptable ; liquefied or a compressed gas propellant, the carrier com 2 = acceptable and 3 = excellent) . prising : [ 0247] As demonstrated in the following table , the foam i ) a stabilizer selected from about 0 . 1 % to about 5 % by preparation obtained higher rates in all aspects of the test . weight of the carrier of at least one surface -active US 2019 /0307887 A1 Oct . 10 , 2019

agent, about 0 . 1 % to about 5 % by weight of the carrier of at least one foam adjuvant, and a mixture thereof; ii ) about 2 % to about 75 % by weight of the carrier of an organic solvent selected from the group consisting of an emollient, a polar solvent, an oil , and mixtures thereof; iii ) about 0 .01 % to about 5 % by weight of the carrier of at least one polymeric agent selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent, and a phase change agent; and iv ) water; wherein the combined amount of the stabilizer and the polymeric agent is less than about 8 % by weight of the carrier ; wherein upon release from a foam dispenser , a foam is produced ; and wherein the foam remains stable as a foam for at least 60 seconds at 37° C .