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 vagina 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 pregnancy. [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 menstrual cycle 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 uterus 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 .