US 2016O220601A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0220601 A1 KLEN (43) Pub. Date: Aug. 4, 2016

(54) COMPOSITIONS COMPRISING SULFATED A61E36/42 (2006.01) POLYSACCHARDES AND USES THEREOF A61E36/537 (2006.01) A61E36/28 (2006.01) (71) Applicant: ALGAMED THERAPEUTICS A61E36/886 (2006.01) (A.M.T) LTD, Rosh Pina (IL) A647/42 (2006.01) A647/22 (2006.01) (72) Inventor: Ronnie KLEIN, Haifa (IL) A619/00 (2006.01) 52) U.S. C. (21) Appl. No.: 15/095,475 (52) CPC ...... A6 IK3I/737 (2013.01); A61 K9/0034 (22) Filed: Apr. 11, 2016 38.2013.01); A61E36/05A6IK36/03 (2013.01);33. A6 IK36/55IK 36/04 O O (2013.01); A61 K3I/353 (2013.01); A61 K Related U.S. Application Data 36/48 (2013.01); A61 K3I/7028 (2013.01); (63) Continuation-in-part of application No. PCT/IL2015/ A61K47/12 (2013.01); A61K 47/26 (2013.01); 050993, filed on Oct. 6, 2015. A61K 47/183 (2013.01); A61K47/32 (2013.01); A61 K9/06 (2013.01); A61K 47/36 (60) Synal application No. 62/060,054, filed on Oct. (2013.01); A61 K36/82 (2013.01); A61K 36/87 s (2013.01); A61 K36/23 (2013.01); A61K 36/53 O O (2013.01); A61 K36/752 (2013.01); A61 K Publication Classification 36/22 (2013.01); A61K 36/45 (2013.01); A61 K (51) Int. Cl. 36/42 (2013.01); A61K 36/537 (2013.01); A 6LX3L/737 (2006.01) A61K 36/28 (2013.01); A61 K36/886 A6 IK36/03 (2006.01) (2013.01); A61 K47/42 (2013.01); A61K47/22 A6 IK36/04 (2006.01) (2013.01) A6 IK36/05 2006.O1 A6 IK36/55 3:08: (57) ABSTRACT A6 IK3I/353 (2006.01) The present invention relates to a composition for intravagi A6 IK36/48 (2006.01) nal and/or for internal mucosal application, comprising an A6 IK3I/7028 (2006.01) effective amount of a Sulfated polysaccharide, one or more of A6 IK 47/12 (2006.01) a natural quaternary polymer, a quaternary molecular com A6 IK 47/26 (2006.01) pound, a metalloproteinase inhibitor, one or more anti-in A6 IK 47/8 (2006.01) flammatory agent, an acid pH control buffering system or any A6 IK 47/32 (2006.01) combination thereof, and a pharmaceutically acceptable car A6 IK9/06 (2006.01) rier. The invention is further related to a method of treating or A6 IK 47/36 (2006.01) alleviating vaginal infection, vaginal dryness, vaginal or A6 IK36/82 (2006.01) Vulvo Vaginal atrophy, vaginal itching, dyspareunia, vaginal A6 IK36/87 (2006.01) or Vulvar pain, vaginal or perivaginal inflammation or for A6 IK 36/23 (2006.01) promoting vaginal or wound healing, vaginal atrophy/dry A6 IK36/53 (2006.01) ness caused by radiotherapy, chemotherapy and/or hormonal A6 IK36/752 (2006.01) treatment and decreased vaginal boundary lubrication or a A6 IK 36/22 (2006.01) disease or condition associated therewith or of improving A6 IK 36/45 (2006.01) vaginal boundary lubrication Patent Application Publication Aug. 4, 2016 US 2016/0220601 A1

4 hr 88 hr x 24 hr

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S. S S 4hr & 8hr

3. N24 hr US 2016/0220601 A1 Aug. 4, 2016

COMPOSITIONS COMPRISING SULFATED invention, the percent of sulfation is between 3-10% of the POLYSACCHARDES AND USES THEREOF polysaccharide chain. According to an embodiment of the invention, the percent of sulfation is between 3-4% of the 0001. This application is a continuation-in-part of PCT polysaccharide chain. According to an embodiment of the International Application No. PCT/IL2015/050993, interna invention, the percent of sulfation is between 4-5% of the tional filing date Oct. 6, 2015, entitled “Compositions com polysaccharide chain. According to an embodiment of the prising Sulfated polysaccharides and uses thereof, which in invention, the percent of sulfation is between 5-6% of the turn claims priority from U.S. Provisional application 62/060, polysaccharide chain. According to an embodiment of the 054, filed Oct. 6, 2014, both of which are incorporated herein invention, the percent of sulfation is between 6-7% of the by reference. polysaccharide chain. According to an embodiment of the invention, the percent of sulfation is between 7-8% of the FIELD OF THE INVENTION polysaccharide chain. According to an embodiment of the 0002 The present invention relates to compositions com invention, the percent of sulfation is between 8-9% of the prising Sulfated polysaccharides and uses thereof. polysaccharide chain. According to an embodiment of the invention, the percent of sulfation is between 9-10% of the BACKGROUND OF THE INVENTION polysaccharide chain. According to an embodiment of the invention, the percent of sulfation is between 10-35% of the 0003. According to the world health organization (WHO), polysaccharide chain. reproductive and sexual ill-health accounts for 20% of the 0011. In some embodiments, the at least one red microalga global sickness in women and therefore advances in women's Sulfated polysaccharide is characterized by having a glucu health are a necessity. ronic acid chain segment in the Sulfated polysaccharide poly 0004 Women's health considerations may encompass mer in an amount of at least 4%. In some embodiment, the issues such as fertility, sexually transmitted diseases, local amount of the glucuronicacid chain segment is between reproductive tract infections and neoplasms, pregnancy, as 4-15%. In some embodiments, the amount of the glucuronic well as perimenopause and post-menopause care. Perimeno acid chain segment is between 4-7%. In some embodiment, pause and post-menopause symptoms as well as breast feed the amount of the glucuronic acid chain segment is between ing, anti-hormonal therapy and contraceptive pills may 7-8%. In some embodiment, the amount of the glucuronic include vaginal and Vulvar pain, irritation, burning, itching, acid chain segment is between 8-9%. In some embodiment, discharge, dyspareunia. the amount of the glucuronic acid chain segment is between 0005 Atrophic vaginitis is a hormone-dependent disease 9-10%. In some embodiment, the amount of the glucuronic involving the genital tract and lower urinary tract. Atrophic acid chain segment is between 10-11%. In some embodiment, vaginitis occurs during or after menopause, and its symptoms the amount of the glucuronic acid chain segment is between increase with age. Due to loss, the vagina is short 11-12%. In some embodiment, the amount of the glucuronic ened narrowed, and the vaginal walls become thinner and less acid chain segment is between 12-13%. In some embodiment, elastic. Dyspareunia, burning and chronic vaginitis do not the amount of the glucuronic acid chain segment is between disappear with time. Further, Vaginal dryness occurs. The 13-14%. In some embodiment, the amount of the glucuronic vaginal Surface becomes friable, with petechiae, ulcerations, acid chain segment is between 14-15%. and bleeding often occurring after minimal trauma. 0012. In some embodiments of the invention, the compo 0006 Chemotherapy, radiotherapy and hormonal therapy sition further comprises one or more of a moisturizing agent, (in particular aromatase inhibitors) in cancer patients can lead a chelating agent, a lubricant, a preservative or any combina to vaginal atrophy and/or dryness. tion thereof. 0007 Simple and safe treatments for these conditions are 0013. In some embodiments of the invention, the compo limited, and to date there has been no single simple platform sition further comprises water. to address women's reproductive health issues. 0014. In some embodiments of the invention, the sulfated polysaccharide is characterized by a percent Sulfation of the SUMMARY OF THE INVENTION polymeric chain between 0.01-32%. 0008. One object of the present invention to provide a 0015. In some embodiments of the invention, the sulfated composition for intravaginal application, comprising Sulfated polysaccharide is in an amount of 0.01-10% wit/wt of the polysaccharides and use thereof for promoting women's Solution. reproductive health. 0016. In some embodiments of the invention, the compo 0009. In some aspects of this invention, there is provided a sition further comprises one or more of an antimicrobial, an composition for intravaginal application, comprising Sulfated antiviral, an antifungal, an anti-inflammatory, anti-irritating, polysaccharides. In some embodiments of the invention, the anti-itching, a hormone or a spermicidal compound. composition for intravaginal and/or for internal mucosal 0017. In some embodiments of the invention, the compo application, comprises an effective amount of a sulfated sition may be used in the manufacture of a medicament for polysaccharide, one or more of a natural quaternary polymer, treating vaginal infection, vaginal dryness, vaginal or Vulvo a quaternary molecular compound, a metalloproteinase vaginal atrophy, vaginal itching, dyspareunia, vaginal or Vul inhibitor, an anti-inflammatory agent, an acid pH control var pain, vaginal or perivaginal inflammation or for promot buffering system or any combination thereof, and a pharma ing vaginal wound healing. ceutically acceptable carrier. 0018. In some embodiments of the invention, the compo 0010. In some embodiments, the sulfated polysaccharides sition may be used in the manufacture of a medicament for from at least one alga, which may be red, brown or green is treating oralleviating decreased vaginal boundary lubrication characterized by a percent Sulfation of the polysaccharide or a disease or condition associated therewith or of improving chain of between 3-35%. According to an embodiment of the vaginal boundary lubrication. US 2016/0220601 A1 Aug. 4, 2016

0019. In some embodiments of the invention, the disease phosphate, sodium lactate, citric acid, or any combination or the condition associated with decreased vaginal boundary thereof. According to Some embodiments, the composition lubrication is vaginal atrophy, dyspareunia, Sjogren's Syn further comprises one or more of a moisturizing agent, a drome, menopause, androgen deficiency, estrogen deficiency, chelating agent, a lubricant, a preservative or any combina estrogen replacement therapy, allergy, chronic inflammation, tion thereof. According to some embodiments, the moistur menopause, premature menopause, chemotherapy, hormonal izing agent is saccharide isomerate, the lubricant is lubrasil therapy for cancer patients (specially aromatase inhibitors), DM hydrogel and the chelating agent is EDTA breastfeeding, Surgical removal of the ovaries before meno 0028. According to some embodiments, the composition pause, genital lichen Sclerosis, Vulvodynia, bacterial vagino further comprises one or more of extract of Chondrus Chris sis, herpes, candida, psoriasis, contact dermatitis, condylo pus, , caprylhydroxamic acid, caprylyl glycol, mata, or side effects of medications and aging. glycerin, undecylenic acid, allantoin, monoester of caprylic 0020. In some embodiments of the invention, the compo acid, an extract of any one of echinaccea, propolis, comfrey, sition may be used in the manufacture of a medicament for melissa, grapefruit, mango seed, cranberry, cucumber, green preventing episiotomy or for treating tissue damages after tea, Salvia, Chamomile, Geranium, lavender, lemon, juniper, episiotomy wherein if used for preventing episiotomy, the clove bud, lotus, moringa, Grape seed or Gotu Kola (Centella composition of the administered a week, two weeks, three asiatica extracts) or any combination thereof. weeks or a month before the date of delivery of a newborn. 0029. According to some embodiments, the composition 0021. In some embodiments of the invention, the compo further comprises water. According to Some embodiments, sition comprises an effective amount of a natural quaternary the composition further comprises chitosan. According to polymer or a quaternary molecular compound. In some Some embodiments, the Sulfated polysaccharide is character embodiments of the invention, the quaternary molecular ized by a percent sulfation of the polymeric chain between compound is laurylpyridinium chloride, cetylpyridinium 0.01-32%. According to some embodiments, the sulfated chloride, hydroxypropyltrimonium hydrolyzed proteins, polysaccharide is in an amount of 0.01-10% wit/wt of the hydroxypropyl guar hydroxypropyltrimonium chloride, beta Solution. According to Some embodiments, the Sulfated glucan hydroxypropyltrimonium chloride or berberine. polysaccharide comprises a polymeric chain comprising at 0022. In some embodiments of the invention, the compo least 4% glucuronic acid. According to Some embodiments, sition comprises chitosan composition further comprises one or more of an antimicro 0023. In some embodiments of the invention, the sulfated bial, an antiviral, an antifungal, an anti-inflammatory, anti polysaccharide is characterized by a percent sulfation of the irritating, anti-itching, growth factor, a hormone or a spermi polymeric chain of between 4-35%. cidal compound. 0024. Embodiments of the invention are directed to a com 0030. According to some embodiments, the composition position for intravaginal and/or for internal mucosal applica is in a form of a cream, an ointment, a solution, a gel, a tion, comprising an effective amount of a Sulfated polysac Suppository, an emulsion, a foam, a capsule, a pill or a tablet. charide, one or more of a natural quaternary polymer, a According to some embodiments, the natural quaternary quaternary molecular compound, a metalloproteinase inhibi polymer is quaternary guar. According to some embodiments, tor, one or more anti-inflammatory agent, an acid pH control the quaternary molecular compound is laurylpyridinium buffering system or any combination thereof, and a pharma chloride, cetylpyridinium chloride, hydroxypropyltrimonium ceutically acceptable carrier. hydrolyzed proteins, beta glucan hydroxypropyltrimonium 0025. According to some embodiments, the sulfated chloride, berberine or Hydroxypropyl Guar Hydroxypropyl polysaccharide is derived from alga. According to some trimonium Chloride. According to some embodiments, Sul embodiments, the alga is a red alga, green alga and/or a brown fated polysaccharide is characterized by a percent Sulfation of alga. According to further embodiments, the red alga is Por phyridium sp., P aerugineum, Porphyridium Cruentum, por the polymeric chain of between 0.01-16%. phyridium purpureum, R. reticulata. Cyanidioschyzon mero 0031. Embodiments of the invention are directed to a lae, Atractophora hypnoides, Gelidiella calcicola, Lemanea, method for treating vaginal infection, vaginal dryness, vagi Palmaria palmata, Schmitzia hiscockiana, Chondrus crispus, nal or Vulvo Vaginal atrophy, vaginal itching, dyspareunia, Mastocarpus Stellatus, and/or Acrochaetium efiorescens. vaginal or Vulvarpain, vaginal or perivaginal inflammation or The brown alga is in Some embodiments, Undaria pinnati for promoting vaginal or wound healing or vaginal atrophy or fida, Larninaria saccharina. L. digitata, Fucus evanescens. F. dryness during or following chemotherapy or hormonal serratus, F. distichus, F spiralis, Ascophylium nodosum and/ therapy comprising administering the composition as or Fucus vesiculosus and the green alga/cyanobacteria is in detailed herein. Some embodiments Prasinococcus capsulatus, Spirulina, 0032 Embodiments of the invention are directed to a Chlorella, Isochrysis and/or Dunaliella. method for treating oralleviating decreased vaginal boundary 0026. According to some embodiments, the metallopro lubrication oradisease or condition associated therewithor of teinase inhibitor is one or more of Soy isoflavone aglycone, improving vaginal boundary lubrication comprising admin Green tea (Camelia sinensis), Grape seed or Gotu Kola (Cen istering the composition as detailed herein. tella asiatica) extracts. According to some embodiments, the 0033 According to some embodiments, the disease or the anti-inflammatory agent is one or more of Green tea (Camel condition associated with decreased vaginal boundary lubri lia sinensis), Grape seed or Gotu Kola (Centella asiatica) cation is vaginal atrophy, dyspareunia, Sjogren's syndrome, extracts, sodium carboxymethyl betaglucan, Chondrus menopause, androgen deficiency, estrogen deficiency, estro Chrispus, melissa, grape fruit, mango seed, cranberry, gen replacement therapy, allergy, chronic inflammation, cucumber, Salvia, chamomile, and aloevera. menopause, premature menopause, chemotherapy, breast 0027. According to some embodiments, the acid pH con feeding, Surgical removal of the ovaries before menopause, trol buffering system is lactic acid, Sodium dibasic hydrogen genital lichen Sclerosis, Vulvodynia, bacterial vaginosis, her US 2016/0220601 A1 Aug. 4, 2016 pes, candida, psoriasis, contact dermatitis, condylomata, or ceutically acceptable carrier, wherein the composition is in a side effects of medications and aging. form for intravaginal application, internal mucosal applica 0034 Embodiments of the invention are directed to a tion, or both. According to Some embodiments, the hormonal method for preventing episiotomy or for treating tissue dam therapy includes aromatase inhibitors. ages after episiotomy comprising administering a composi 0042. According to some embodiments, the sulfated tion as detailed herein. According to some embodiments, if polysaccharide is derived from alga. According to some used for preventing episiotomy, the composition of the embodiments, the alga is a red alga, green alga and/or a brown administered a week, two weeks, three weeks or a month alga. According to further embodiments, the red alga is Por before the date of delivery of a newborn. phyridium sp., P aerugineum, Porphyridium Cruentum, por 0035 Embodiments of the invention are directed to a phyridium purpureum, R. reticulata. Cyanidioschyzon mero method for preventing or for treating tissue damages associ lae, Atractophora hypnoides, Gielidiella calcicola, Lemanea, ated with chemotherapy or hormonal therapy for cancer Palmaria palmata, Schmitzia hiscockiana, Chondrus crispus, patients treated with drugs that blockestrogen receptors, low Mastocarpus Stellatus, and/or Acrochaetium efiorescens. ering estrogen level or progesterone-based agents comprising The brown alga is in Some embodiments, Undaria pinnati administering a composition as detailed herein. According to fida, Laminaria saccharine, L. digitata, Films evanescens, F. Some embodiments, the hormonal therapy for cancer patients serratus, F, distichus, F spiralis, Ascophyllum nodosum and/ includes an aromatase inhibitor. According to Some embodi or Fucus vesiculosus and the green alga/cyanobacteria is in ments, the composition of the invention is administered dur Some embodiments Prasinococcus capsulatus, Spirulina, ing or at the end of a chemotherapy/hormonal treatment. Chlorella, Isochrysis and/or Dunaliella. 0.036 Embodiments of the invention are directed to a 0043 Embodiments of the invention are directed to a com method for treating vaginal infection, vaginal dryness, vagi position for intravaginal and/or for internal mucosal applica nal or Vulvo Vaginal atrophy, vaginal itching, dyspareunia, tion, comprising an effective amount of a Sulfated polysac vaginal or Vulvar pain, vaginal or perivaginal inflammation or charide, one or more of a natural quaternary polymer, a for promoting vaginal or wound healing, vaginal atrophy/ quaternary molecular compound, a metalloproteinase inhibi dryness caused by radiotherapy, chemotherapy and/or hor tor, one or more anti-inflammatory agent, an acid pH control monal treatment comprising administering a composition buffering system or any combination thereof, and a pharma comprising an effective amount of a Sulfated polysaccharide ceutically acceptable carrier. and a pharmaceutically acceptable carrier, wherein the com 0044 According to some embodiments, the metallopro position is in a form for intravaginal application, internal teinase inhibitor is one or more of soy isoflavone aglycone, mucosal application, or both. Green tea (Camellia sinensis), Grape seed or Gotu Kola (Cen 0037 Embodiments of the invention are directed to a tella asiatica) or wherein the anti-inflammatory agent is one method for treating oralleviating decreased vaginal boundary or more of Green tea (Camelia sinensis), Grape seed or Gotu lubrication oradisease or condition associated therewithor of Kola (Centella asiatica) extracts, sodium carboxymethyl improving vaginal boundary lubrication comprising admin betaglucan, Chondrus Chrispus, melissa, grape fruit, mango istering a composition comprising an effective amount of a seed, cranberry, cucumber, Salvia, chamomile, and aloe Vera Sulfated polysaccharide and a pharmaceutically acceptable eXtractS. carrier, wherein the composition is in a form for intravaginal 0045. According to some embodiments, the acid pH con application, internal mucosal application, or both. trol buffering system is lactic acid, Sodium dibasic hydrogen 0038 According to some embodiments, the disease or the phosphate, sodium lactate, citric acid, or any combination condition associated with decreased vaginal boundary lubri thereof. cation is vaginal atrophy, dyspareunia, Sjogren's syndrome, 0046 According to some embodiments, the composition menopause, androgen deficiency, estrogen deficiency, estro further comprises one or more of Saccharide isomerate as a gen replacement therapy, allergy, chronic inflammation, moisturizing agent, ethylenediaminetetraacetic acid (EDTA) menopause, premature menopause, chemotherapy, breast as a chelating agent, and lubrasil DM hydrogel as a lubricant. feeding, Surgical removal of the ovaries before menopause, According to Some embodiments, the composition further genital lichen Sclerosis, Vulvodynia, bacterial vaginosis, her comprises one or more of extract of Chondrus Chrispus, pes, candida, psoriasis, contact dermatitis, condylomata, or Xanthan gum, caprylhydroxamic acid, caprylylglycol, glyc side effects of medications and aging. erin, undecylenic acid, allantoin, monoester of caprylic acid, 0.039 Embodiments of the invention are directed to a an extract of any one of echinaccea, propolis, comfrey, mel method for preventing episiotomy or for treating tissue dam issa, grapefruit, mango seed, cranberry, cucumber, green tea, ages after episiotomy comprising administering a composi salvia, Chamomile, Geranium, lavender, lemon, juniper, tion comprising an effective amount of a Sulfated polysaccha clove bud, lotus, moringa, Grape seed or Gotu Kola (Centella ride and a pharmaceutically acceptable carrier, wherein the asiatica extracts) or any combination thereof. According to composition is in a form for intravaginal application, internal Some embodiments, the composition further comprises chi mucosal application, or both. tOSan. 0040. According to some embodiments, if administered 0047 According to some embodiments, the sulfated for preventing episiotomy, the composition is administered polysaccharide is in an amount of 0.005-5% wt/wt of the for a week, two weeks, three weeks or a month before the date Solution. According to Some embodiments, the Sulfated of delivery of a newborn. polysaccharide comprises a polymeric chain comprising at 0041 Embodiments of the invention are directed to a least 4% glucuronic acid. According to Some embodiments, method for preventing or treating vaginal atrophy or dryness the composition further comprises one or more of an antimi during and following chemotherapy and/or hormonal therapy crobial, an antiviral, an antifungal, an anti-inflammatory, anti comprising administering a composition comprising an irritating, anti-itching, growth factor, a hormone or a spermi effective amount of a Sulfated polysaccharide and a pharma cidal compound. According to Some embodiments, the US 2016/0220601 A1 Aug. 4, 2016

composition is in a form of a cream, an ointment, a solution, Mastocarpus Stellatus, and/or Acrochaetium efiorescens. a gel, a Suppository, an emulsion, foam, a capsule, a pill or a The brown alga is in Some embodiments, Undaria pinnati tablet. fida, Laminaria saccharina, L. digitata, Fucus evanescens, F. 0048. According to some embodiments, the natural qua serratus, F, distichus, F spiralis, Ascophyllum nodosum and/ ternary polymer is Guar Hydroxypropyltrimonium Chloride. or Fucus vesiculosus and the green alga/cyanobacteria is in According to some embodiments, the quaternary molecular Some embodiments Prasinococcus capsulatus, Spirulina, compound is laurylpyridinium chloride, cetylpyridinium Chlorella, Isochrysis and/or Dunaliella. chloride, hydroxypropyltrimonium hydrolyzed proteins, beta glucan hydroxypropyltrimonium chloride, berberine or BRIEF DESCRIPTION OF THE DRAWINGS Hydroxypropyl Guar Hydroxypropyltrimonium Chloride. 0055. The subject matter regarded as the invention is par 0049 Embodiments of the invention are further directed to ticularly pointed out and distinctly claimed in the concluding a method for treating or alleviating decreased vaginal bound portion of the specification. The invention, however, both as ary lubrication or a disease or condition associated therewith or of improving vaginal boundary lubrication, vaginal dam to organization and method of operation, together with ages, vaginal infection, vaginal dryness, vaginal or Vulvo objects, features and advantages thereof, may best be under vaginal atrophy, vaginal itching, dyspareunia, vaginal or Vul stood by reference to the following detailed description when var pain, vaginal or perivaginal inflammation or for promot read with the accompanied drawings. Embodiments of the ing vaginal or wound healing, vaginal atrophy/dryness invention are illustrated by way of example and not limitation caused by radiotherapy, chemotherapy and/or hormonal treat in the figures of the accompanying drawings, in which like ment comprising administering a composition comprising an reference numerals indicate corresponding, analogous or effective amount of a Sulfated polysaccharide and a pharma similar elements, and in which: ceutically acceptable carrier, wherein the composition is in a 0056 FIG. 1 presents the water loss of three formulations form for intravaginal application, internal mucosal applica as measured at three different time points, after incubation at tion, or both. 24°C.; and 0050. According to some embodiments, the disease or the 0057 FIG. 2 presents the water retention of the same three condition associated with decreased vaginal boundary lubri formulations as measured at three different time points, after cation is vaginal atrophy, dyspareunia, Sjogren's syndrome, incubation at 24°C. menopause, androgen deficiency, estrogen deficiency, estro gen replacement therapy, allergy, chronic inflammation, DETAILED DESCRIPTION OF THE INVENTION menopause, premature menopause, chemotherapy, breast 0058. It is noted that throughout, all ranges and numeric feeding, Surgical removal of the ovaries before menopause, figures are considered to be approximate even when the term genital lichen Sclerosis, Vulvodynia, bacterial vaginosis, her “about is not used, such that the document is considered to pes, candida, psoriasis, contact dermatitis, condylomata, or cover +10% of the disclosed range or figure, unless specifi side effects of medications and aging. cally mentioned otherwise. It is further noted that the term 0051. Further embodiments are directed to a method for “about is also considered to cover +10% of the disclosed preventing episiotomy or for treating tissue damages after range or figure, unless specifically mentioned otherwise. episiotomy comprising administering a composition com 0059. It is further noted that throughout, the terms immune prising an effective amount of a sulfated polysaccharide and enhancing and anti-inflammatory are interchangeable. a pharmaceutically acceptable carrier, wherein the composi 0060. In some aspects of this invention, there is provided a tion is in a form for intravaginal application, internal mucosal composition for intravaginal application comprising Sulfated application, or both. polysaccharides. 0052 According to some embodiments, if administered 0061 According to some embodiments of the invention, for preventing episiotomy, the composition is administered there is provided a composition for intravaginal and/or for for a week, two weeks, three weeks or a month before the date internal mucosal application, comprising an effective amount of delivery of a newborn. of a Sulfated polysaccharide and one or more of a natural 0053. Further embodiments are directed to a method for quaternary polymer, a quaternary molecular compound, a preventing or treating vaginal damages, atrophy or dryness metalloproteinase inhibitor, an anti-inflammatory agent, an during and following chemotherapy and/or hormonal therapy acid pH control buffering system or any combination thereof. for cancer patients treated with drugs that block estrogen Further provided is a pharmaceutically acceptable carrier. receptors, lowering estrogen level or progesterone-based The addition of a quaternium molecule or quaternary polymer agents comprising administering a composition comprising to the polysaccharide may initiate a deposition process where, an effective amount of a Sulfated polysaccharide and a phar a homogenous, thin, longer lasting coating, a more intimately maceutically acceptable carrier, wherein the composition is attachment of formula to the vaginal tissue is formed and the in a form for intravaginal application, internal mucosal appli formulation has increased ability to retain water therefore, to cation, or both, wherein the hormonal therapy includes aro hydrates and moisturizes the vaginal tissue. Cell wall mem matase inhibitors. branes are usually negatively charged and a quaternary poly 0054 According to some embodiments, the sulfated mer is usually a cationic polymer or compound. The negative polysaccharide is derived from alga. According to some charge of the cell wall membranes attracts to positively embodiments, the alga is a red alga, green alga and/or a brown charged quaternary molecules therefore allowing a longer alga. According to further embodiments, the red alga is Por lasting coating of formula with higher water content. In some phyridium sp., P aerugineum, Porphyridium Cruentum, por embodiments of the invention, the addition of a quaternium phyridium purpureum, R. reticulata. Cyanidioschyzon mero molecule or quaternary polymer to the polysaccharide can lae, Atractophora hypnoides, Gelidiella calcicola, Lemanea, reduce trans-epidermal water loss (TEWL) in the vaginal Palmaria palmata, Schmitzia hiscockiana, Chondrus crispus, tissue and improve drug delivery. US 2016/0220601 A1 Aug. 4, 2016

0062. In some embodiments of the invention, the quater embodiments of the invention the quaternary guar is pre nary compound is a polymeric quaternium ammonium salt of sented in an amount of between 1.0-2.0% wit/wt. According to hydroxyemylcellulose, berberine, quaternary guar and/or Some embodiments of the invention the quaternary guar is Hydroxypropyl guar hydroxypropyltrimonium chloride. presented in an amount of between 2.0-3.0% wit/wt. Accord 0063. In some embodiments of the invention, the natural ing to some embodiments of the invention the quaternary guar quaternary polymer/quaternary molecular compound is is presented in an amount of between 3.0-4.0% wit/wt. hydroxypropyltrimonium hydrolyzed proteins or beta glucan According to Some embodiments of the invention the quater hydroxypropyltrimonium chloride. nary guar is presented in an amount of between 0.2-5% wit/wt. 0064. According to some embodiments of the invention According to some embodiments, Xanthan gum is present in the natural quaternary polymer or the quaternary molecular an amount of between about 0.1-5%. According to some compound is presented in an amount of between 0.01-5.0% embodiments, Xanthan gum is present in an amount of wit/wt. According to some embodiments of the invention the between about 0.1-1.0%. According to some embodiments, natural quaternary polymer or the quaternary molecular com Xanthan gum is present in an amount of between about 1.0- pound is presented in an amount of between 0.01-1.0% wit/wt. 2.0%. According to some embodiments, Xanthan gum is According to some embodiments of the invention the natural present in an amount of between about 2.0-3.0%. According quaternary polymer or the quaternary molecular compound is to some embodiments, Xanthan gum is present in an amount presented in an amount of between 1.0-2.0% wit/wt. Accord of between about 3.0-4.0%. According to some embodi ing to some embodiments of the invention the natural quater ments, Xanthan gum is present in an amount of between about nary polymer or the quaternary molecular compound is pre 40-50%. sented in an amount of between 2.0-3.0% wit/wt. According to 0068. In some embodiments of the invention, the quater Some embodiments of the invention the natural quaternary nary molecular compound is an ammonium compound, polymer or the quaternary molecular compound is presented wherein the quaternary nitrogen is in or amide form, in an amount of between 3.0-4.0% wit/wt. According to some possibly Substituted with one or two alkyl groups, lauryl embodiments of the invention the natural quaternary polymer pyridinium chloride, cetylpyridinium chloride, hydroxypro or the quaternary molecular compound is presented in an pyltrimonium, hydrolyzed protein, Such as oats, rice, bran, amount of between 4.0-5.0% wit/wt. Soy, and wheat (Such as for example, hydroxypropyltrimo 0065 According to some embodiments of the invention nium hydrolyzed wheat protein), berberine, beta glucan the natural quaternary polymer or the quaternary molecular hydroxypropyltrimonium chloride or hydroxypropyl guar compound is presented in an amount of between 0.1-5% hydroxypropyltrimonium chloride. In some embodiments of wit/wt. According to some embodiments of the invention the the invention, the metalloproteinase inhibitor is soy isofla natural quaternary polymer or the quaternary molecular com Vone aglycone. In some embodiments of the invention, the pound is presented in an amount of between 0.1-1.0% wit/wt. metalloproteinase inhibitor is Green tea extract, Gotu Kola According to some embodiments of the invention the natural (Centalla asiatica) extract, Grape seed extract, ursolic acid, quaternary polymer or the quaternary molecular compound is roSmarinic acid or Soy isoflavone aglycone, or any combina presented in an amount of between 1.0-2.0% wit/wt. Accord tion thereof. In some embodiments of the invention, there is a ing to some embodiments of the invention the natural quater synergy between the Sulfated polysaccharide and the metall nary polymer or the quaternary molecular compound is pre proteinase inhibitor in treating inflammation, reducing irrita sented in an amount of between 2.0-3.0% wit/wt. According to tion and/or strengthening the vaginal tissue. Some embodiments of the invention the natural quaternary 0069. According to some embodiments of the invention, polymer or the quaternary molecular compound is presented the anti-inflammatory agent is sodium carboxymethyl beta in an amount of between 3.0-4.0% wit/wt. According to some glucan (CMBeta glucan). In some embodiments of the inven embodiments of the invention the natural quaternary polymer tion, the anti-inflammatory agent is Green tea extract, Gotu or the quaternary molecular compound is presented in an Kola (Centalla asiatica) extract, Grape seed extract, sodium amount of between 4.0-5.0% wit/wt. carboxymethyl betaglucan, epicatechin, glycyrrhiza, resvera 0066. According to some embodiments of the invention trol (polyphenol), Chondrus Chrispus, melissa, grape fruit, the quaternary guar which may be hydroxypropyl guar mango seed, cranberry, cucumber, Salvia, chamomile, aloev hydroxypropyltrimonium chloride, is presented in an amount era or a combination thereof. In some embodiments of the of between 0.2-5% wit/wt. According to some embodiments invention, there is a synergy between the Sulfated polysac of the invention the quaternary guar is presented in an amount charide and the Sodium carboxymethyl betaglucan, epicat of between 0.2-1.0% wit/wt. According to some embodiments echin, glycyrrhiza, Green tea extract, Gotu Kola (Centalla of the invention the quaternary guar is presented in an amount asiatica) extract, Grape seed extract Chondrus Chrispus, of between 1.0-2.0% wit/wt. According to some embodiments melissa, grapefruit, mango seed, cranberry, cucumber, Salvia, of the invention the quaternary guar is presented in an amount chamomile, aloevera and/or the resveratrol or the combina of between 2.0-3.0% wit/wt. According to some embodiments tion thereof in treating inflammation and/or irritation. of the invention the quaternary guar is presented in an amount 0070 According to some embodiments of the invention, of between 3.0-4.0% wit/wt. According to some embodiments the acid pH control buffering system is lactic acid, sodium of the invention the quaternary guar is presented in an amount lactate, citric acid, acetic acid, Sorbic acid, propionic acid, of between 4.0–5.0% wit/wt. Sodium dibasic hydrogen phosphate or any combination 0067. According to some embodiments of the invention thereof. the quaternary guar is presented in an amount of between 0071. In some embodiments of the invention, the compo 0.01-4.0% wit/wt. According to some embodiments of the sition for intravaginal and/or for internal mucosal application, invention the quaternary guar, which may be hydroxypropyl comprising an effective amount of a Sulfated polysaccharide; guar hydroxypropyltrimonium chloride, is presented in an one or more of a metalloproteinase inhibitor, an anti-inflam amount of between 0.01-1.0% wit/wt. According to some matory agent, an acid pH control buffering system or any US 2016/0220601 A1 Aug. 4, 2016

combination thereof, and a pharmaceutically acceptable car embodiments of the invention, the lubricant is a natural lubri rier, further comprises one or more of a moisturizing agent, a cant, comprises of Lubrasil-DMHydrogel, glyceril polyacry chelating agent, a lubricant, a preservative or any combina late, alginic acid, Sodium salt, guar neutral, Xanthan gum or tion thereof. Chondrus Chrispus, Sulfated polysaccharide, Guar gum, 0072. In some embodiments of the invention, the moistur Hydroxypropyl Guar Hydroxypropyltrimonium Chloride or izing agent is saccharide isomerate, aquaxyl (Xlyltylgluco any combination thereof. side, anhydroxylitol. Xlyltol) or ammonium lactate, pyroli I0083. According to further embodiments, the composition donecarboxylic acid (PCA) and/or derivated esters (lauryl, comprises about 0.1-1.0% wit/wt sodium polyacrylate. isopropyl, benzyl) and/or sodium, potassium salts. According to further embodiments, the composition com 0073. In some embodiments of the invention, the chelating prises about 0.1-1.0% wit/wt lubrasil DM hydrogel. It is noted agent is EDTA, Di & Tetra sodium, tetrasodium etidronate, that wit/wt is equivalent to w/w. According to further embodi Sodium and/or potassium phosphate, polyphosphate and/or ments, the composition comprises about 0.1-1.0% w/w alg pyrophosphate salt. inic acid. According to further embodiments, the composition 0074. In some embodiments of the invention, the compo comprises about 0.1-1.0% w/w sodium salt. According to sition further comprises flax seed extract. further embodiments, the composition comprises about 0.1- 0075. In some embodiments of the invention, the compo 1.0% w/w guar natural. According to further embodiments, sition further comprises chitosan. the composition comprises about 0.1-1.0% w/w Chondrus 0076. In some embodiments of the invention, the compo Chrispus. According to further embodiments, the composi sition of the invention further comprises a preservative. In tion comprises about 1.0-1.5% wit/wt flax seed extract. Some embodiments of the invention, the preservative is a According to further embodiments, the composition com natural preservative. In some embodiments of the invention, prises about 0.02-0.04% wt/wt EDTA. According to further the preservative is one or more of a mixture of pentylene embodiments, the composition comprises about 0.02-0.04% glycol, glyceryl caprylate and glyceryl undecylenate or wit/wt Di & Tetra sodium editronate. According to further monoester of caprylic acid and/or undecylenic acid, a mixture embodiments, the composition comprises about 0.02-0.04% of caprilhydroxamic acid, caprylylglycol, glycerin, caprylyl wit/wt sodium and/or potassium phosphate, pyrophosphate, glycerin or any combination thereof. and/or polyphosphate. According to further embodiments, 0077. In some embodiments of the invention, the compo the composition comprises about 0.3-2.0% wit/wt lactic acid sition for intravaginal and/or for internal mucosal application, and/or sodium lactate. According to further embodiments, the comprising an effective amount of a sulfated polysaccharide; composition comprises about 0.5-1.0% wit/wt glyceryl capry one or more of a natural quaternary polymer, a quaternary late. According to further embodiments, the composition molecular compound, a metalloproteinase inhibitor, an anti comprises about 0.5-1.0% wit/wt monoesters of caprylic acid inflammatory agent, an acid pH control buffering system, or and undecylenic esters. According to further embodiments, any combination thereof, and a pharmaceutically acceptable the composition comprises about 0.1-2.0% wit/wt Hydrox carrier, including one or more extracts of Green tea extract, ypropyl Guar Hydroxypropyltrimonium Chloride. According Gotu Kola (Centalla asiatica) extract, Grape seed extract, to further embodiments, the composition comprises about Chondrus Chrispus, echinaccea, propolis, comfrey, melissa, 0.7-1.5% wt/wt of Lactic acid and Sodium dibasic hydrogen grapefruit, mango seed, cranberry, cucumber, Salvia, chamo phosphate. According to further embodiments, the composi mile, aloevera, geranium, lavender, lemon, juniper, clove bud, tion comprises about 0.01-1.0% wit/wt of at least one of Green lotus, moringa or any combination thereof. tea extract, Gotu Kola (Centalla asiatica) extract, and/or 0078. In some embodiments of the invention, the compo Grape seed extract, melissa, grape fruit, mango seed, cran sition for intravaginal and/or for internal mucosal application, berry, allantoin, cucumber, Salvia, chamomile, aloevera, comprising an effective amount of a Sulfated polysaccharide; caprylhydroxamic acid, caprylyl glycol and glycerin, or of one or more of a metalloproteinase inhibitor, an anti-inflam their various combinations. According to further embodi matory agent, an acid pH control buffering system, or any ments, the composition comprises about 0.5-2% of Pentylene combination thereof, and a pharmaceutically acceptable car Glycol, Glyceryl Caprylate and Glyceryl Undecylenate. rier further comprises water. According to further embodiments, the composition com 0079 According to some embodiments, the composition prises about 0.1-2% of Xanthan gum. According to further for intravaginal and/or for internal mucosal application, com embodiments, the composition comprises about 0.01-2% of prising an effective amount of a Sulfated polysaccharide; one Chitosan. According to further embodiments, the composi or more of a metalloproteinase inhibitor, an anti-inflamma tion comprises about 0.1-2% of Allantoin. tory agent, an acid pH control buffering system, or any com I0084. According to further embodiments, the composition bination thereof, and a pharmaceutically acceptable carrier. comprises about 0.01-1.0% w/w of one or more natural 0080 According to some embodiments, the composition extracts, such as Green tea (Camelia sinensis) extract, Gotu comprises sulfated polysaccharide is in an amount of 0.005 Kola (Centalla asiatica) extract, Grape seed extract, echinac 5% wit/wt of the solution. According to some embodiments, cea, comfrey, melissa, propolis, mango seed, grape fruit, the composition comprises about 0.01-5.0% wit/wt sulfated cucumber, cranberry, chamomile, Salvia, geranium, lavender, polysaccharide. lemon, juniper, clove bod, lotus, moringa, resveratrol, or any 0081. According to further embodiments, the composition combination thereof. In some embodiments of the invention, comprises about 0.1-3.0% wit/wt Chondrus Chrispus extract resveratrol may be added to the composition. (silicone plant). According to further embodiments, the com I0085. In some embodiments of the invention, the compo position of the invention comprises about 1.0-5.0% wit/wt sition further comprises water. saccharide isomerate (plant derivative). I0086. In some embodiments of the invention, the compo 0082 In some embodiments of the invention, the compo sition further comprises a vitamin, such as for example, with sition of the invention further comprises a lubricant. In some out limitation, Vitamin E. US 2016/0220601 A1 Aug. 4, 2016

0087. In some embodiments of the invention, the compo fated polysaccharides. According to this aspect, and in some sition further comprises a chitosan. embodiments, the red, brown or green alga Sulfated polysac 0088. In some embodiments of the invention, the sulfated charide is characterized by a percent sulfation of between polysaccharide is derived from alga. In an embodiment of the 0.01-35% of the polysaccharide chain. In some embodiments invention, the alga is a red alga, a green alga, a brown alga of the invention the percent sulfation is between 20-35% of and/or Chondrus Chrispus the polysaccharide chain. In some embodiments of the inven 0089. In one aspect, this invention provides a composition tion the percent sulfation is between 0.1-20% of the polysac for intravaginal application, comprising an effective amount charide chain. In some embodiments of the invention the of at least one red, green or brown alga Sulfated polysaccha percent sulfation is between 0.1-10% of the polysaccharide ride. chain. In some embodiments of the invention the percent 0090. In some embodiments, the term “red microalga?e' sulfation is between 1-10% of the polysaccharide chain. In or “red algale' is to be understood to encompass any of the some embodiments of the invention the percent sulfation is 6,500 to 10,000 known species (W. J. Woelkerling (1990). between 2-10% of the polysaccharide chain. In some embodi “An introduction'. In K. M. Cole & R. G. Sheath. Biology of ments of the invention the percent sulfation is between 2-11% the Red Algae. Cambridge University Press, Cambridge. pp. of the polysaccharide chain. In some embodiments of the 1-6; M. D. Guiry. “Rhodophyta: red algae'. National Univer invention the percent sulfation is between 2-3% of the sity of Ireland, Galway. Archived from the original on 2007 polysaccharide chain. In some embodiments of the invention May 4. Retrieved 2007 Jun. 28). Some examples of species the percent sulfation is between 3-4% of the polysaccharide and genera of red algae may include Cyanidioschyzon mero chain. In some embodiments of the invention the percent lae, Porphyridium Cruentum, Atractophora hypnoides, Geli sulfation is between 4-5% of the polysaccharide chain. In diella calcicola, Lemanea, Palmaria palmata, Schmitzia his some embodiments of the invention the percent sulfation is cockiana, Chondrus crispus, Mastocarpus stellatus, or between 5-6% of the polysaccharide chain. In some embodi Acrochaetium efiorescens. In an embodiment of the inven ments of the invention the percent sulfation is between 6-7% tion, the sulfated polysaccharide is derived from Porphy of the polysaccharide chain. In some embodiments of the ridium SP, Porphyridium Cruentum or porphyridium pur invention the percent sulfation is between 7-8% of the pureum. polysaccharide chain. In some embodiments of the invention 0091 Red microalga sulfated polysaccharides, in some the percent sulfation is between 8-9% of the polysaccharide embodiments, are obtained from the cell walls by different chain. In some embodiments of the invention the percent procedures, e.g., by extraction. In some embodiments, the sulfation is between 9-10% of the polysaccharide chain. In polysaccharide is secreted by the alga into the growth some embodiments of the invention the percent sulfation is medium, and then utilized. between 4-10% of the polysaccharide chain. 0092. In some embodiments, the red microalga are grown 0099. According to this aspect, and in some embodiments, as described in U.S. Pat. No. 5,534,417 (fully incorporated by the degree of sulfation of the polysaccharides for use in the reference herein), and the Sulfated polysaccharides are iso compositions and methods of this invention provides a com lated therefrom, using established methods. position with sufficient activity. 0093. In some embodiments of the invention, the extrac 0100. In some embodiments, the composition of the tion of the sulfated polysaccharide is carried out in the pres invention may further comprise, inter-alia, a "drug or "com ence of ethyl and the sulfated polysaccharide of the pound” or "agent', which refers in some embodiments, to a present invention may be selectively extracted with an aque Substance applicable for use in the treatment, prevention, ous solvent, which in Some embodiments, is conducted in the alleviation, Suppression, a delay in progression or reduction presence of 5-40% wit/wt ethyl alcohol or, in some embodi in incidence of a disease, disorder, condition or infection. ments, 8-15% wit/wt ethyl alcohol. 0101 The compound, drug or agent may be one or more of 0094. In some embodiments of the invention, the tempera an antimicrobial, an antiviral, an antifungal, an anti-inflam ture for extracting the sulfated polysaccharide of the present matory, anti-irritating, anti-itching, a hormone or a spermi invention is 50° C. or lower and in some embodiments, 15-30° cidal compound or any other compound that can treat or C alleviate or prevent a condition associated with woman’s 0.095. In some embodiments of the invention, the extrac health, such as vaginitis, Vulivitis, vestibulitis, Vulvadynia, tion may be carried out with stirring and in Some embodi Vulval itching or Vulvavaginitis, vaginal atrophy, sexually ments; it is carried out under a non-shearing condition transmitted diseases, vaginal atrophy and/or dryness follow whereby the sulfated polysaccharide of the present invention ing chemotherapy or during hormone therapy (adjuant, neo can be efficiently prepared. adjuvant or as the treatment itself) for cancer patients (such as 0096. In some embodiments of the invention, if the extract aromatase inhibitors) and other local reproductive tract infec is contaminated with impurities such as neutral Sugars and tions. proteins, then in Some embodiments, removal of neutral Sug 0102 Sexually transmitted diseases, also referred to as ars can be easily achieved by means known in the art such as sexually transmitted infections (STI) and venereal diseases ultrafiltration where the excluding molecular weight is about (VD), are illnesses that have a significant probability of trans 100,000 or less. In some embodiments, removing the pro mission between humans by means of human sexual behav teins, i.e. by treatment with protease, etc. may be used. ior, including vaginal intercourse, oral sex, and anal sex. 0097. In other embodiments, the sulfated polysaccharide 0103) In some embodiments, the sexually transmitted dis may be treated with endo-sulfated polysaccharide degrading eases which may be treated/prevented/alleviated by the com enzyme, which in turn may liberate specific, desired sulfated positions and methods of this invention include those of bac saccharide products. terial, viral, fungal, parasitic or protozoal in origin. In some 0098. In some embodiments, the compositions of this embodiments, the sexually transmitted diseases which may invention are distinguished in that they contain highly Sul be treated/prevented/alleviated by the compositions and US 2016/0220601 A1 Aug. 4, 2016

methods of this invention include Chancroid (such as Hae include , Viscous agents such as, without mophilus ducreyi), Chlamydia (Such as Chlamydia trachoma being limited, microcrystalline cellulose, or chitosan. tis), Gonorrhea (such as Neisseria gonorrhoeae), Granuloma 0108. In some embodiments of the invention, the compo inguinale (such as Klebsiella granulomatis) or Syphilis (Such sition is formulated in a form of a cream, an ointment, a as Treponema pallidum); Candidiasis; Viral hepatitis, Herpes Solution, a gel, a Suppository, an emulsion, foam, a capsule, a simplex virus, HIV (Human Immunodeficiency Virus), HPV pill or a tablet. (Human Papillomavirus), Molluscum contagiosum (mollus 0109. In some embodiments, the drug, compound or agent cum contagiosum virus MCV); Crab louse, (such as Pthirus may comprise, inter-alia, anticlotting agents, antihistamines, pubis), Scabies (such as Sarcoptes scabiei), or Trichomonia histamine, anti-inflammatory, agents that treat autoimmune sis (Trichomonas vaginalis). disorder, antibacterial and antifungal agents, antibiotics, anti 0104. In some embodiments, the added compound, drug viral agents, anti-neoplastics, anticoagulants, androgens, cor or agent is a synthetic molecule and in some embodiments, ticoids, anabolic agents, growth hormone secretagogues, the agent is a natural product. In some embodiments, the anti-infective agents, antiprotozoals, anesthetics, platelet agent is a nucleic acid, a hormone, a growth factor, a cytokine, inhibitors and glycogen phosphorylase inhibitors, diagnostic a chemokine, protein, an enzyme, a peptide, a drug, a label or markers, drugs used for the control of birth, natural products, a combination thereof. cell mediators, cell inhibitors, antimitotic agents, alkylating 0105. In some embodiments, the composition of the agents, immunomodulators, analgesics, Vaccines, antimusca invention may comprise, inter-alia, an antibody or antibody rinic and antispasmodic agents, immunosuppressive agents, fragment, a peptide, an oligonucleotide, a ligand for a bio Vitamins, parasiticides or any combination thereof. logical target, an immunoconjugate, a chemomimetic func 0110. In some embodiments, the added compound, drug tional group, a glycolipid, a labelling agent, an enzyme, a or agent may comprise, inter-alia, an anti-impotence agent, metalion chelate, an enzyme cofactor, a cytotoxic compound, Such as sildenafil citrate; anti-neoplastics, such as chloram a bactericidal compound, a bacteriostatic compound, a fun bucil, lomustine or echinomycin; anti-inflammatory agents, gicidal compound, a fungistatic compound, a chemothera Such as betamethasone, prednisolone, piroXicam, , peutic, a growth factor, a hormone, a cytokine, a toxin, a flurbiprofen and (+)-N-4-3-(4-fluorophenoxy)phenoxy-2- prodrug, an antimetabolite, a microtubule inhibitor, a radio cyclopenten-1-yl)-N-hyroxyurea; antivirals, such as acyclo active material, a targeting moiety, or any combination Vir, nelfinavir, or virazole; vitamins/nutritional agents, such thereof. In some embodiments, the drug, agent or compound as retinol and vitamin E; an anticoagulant, such as dicumarol; may comprise, inter-alia, a peptide. In some embodiments, androgens, such as 17-methyltestosterone and testosterone; a the term "peptide' refers to native peptides (either degrada mineral corticoid, such as desoxycorticosterone; an antibi tion products, synthetically synthesized peptides or recombi otic, such as amplicillin and penicillin G or belonging to the nant peptides) and/or peptidomimetics (typically, syntheti family of penicillines, cephalosporins, aminoglycosidics, cally synthesized peptides). Such as peptoids and macrollides, carbapenem and penem, beta-lactam monocy semipeptoids which are peptide analogs, which may have, for clic, inhibitors of beta-lactamases, tetracyclins, polipeptidic example, modifications rendering the peptides more stable antibiotics, and derivatives, fusidic acid, while in a body or more capable of penetrating into cells. Such lincomicyn, novobiocine, spectinomycin, poly-etheric iono modifications include, but are not limited to N terminus modi phores, quinolones; an anti-infective Such as benzalkonium fication, C terminus modification, peptide bond modification, chloride or chlorhexidine; an antifungal Such as econazole, including, but not limited to, CH, NH, CH, S, CH terconazole, fluconazole, Voriconazole or griseofulvin; an S—O, O—C NH, CH, O, CH, CH, S=C NH, antiprotozoal Such as metronidazole; an imidazole-type anti CH=CH or CF=CH, backbone modifications, and residue neoplastic Such as tubulazole; an anthelmintic agent Such as modification. In one embodiment, the term "amino acid' or thiabendazole or oxfendazole; an antihistamine Such as “amino acids” is understood to include the 20 naturally occur astemizole, levocabastine, cetirizine, or cinnarizine; an anes ring amino acids; those amino acids often modified post thetic Such as lidocaine; an antibacterial Such as cotrimox translationally in vivo, including, for example, hydroxypro azole; a platelet inhibitor Such as prostacyclin; a tetracycline line, phosphoserine and phosphothreonine; and other unusual antibiotic Such as oxytetracycline or minocycline; a mac amino acids including, but not limited to,2-aminoadipic acid, rolide antibiotic Such as azithromycin, clarithromycin, eryth hydroxylysine, isodesmosine, nor-valine, nor-leucine and romycin or spiramycin; and glycogen phosphorylase inhibi ornithine. Furthermore, the term “amino acid may include tors such as R—(R*S*)-5-chloro-N-2-hydroxy both D- and L-amino acids. 3{methoxymethylamino-3-oxo-1-(phenylmethyl)-propyl IH-indole-2-carboxamide O 5-chloro-1-Hindole-2- 0106. In some embodiments, the drug, agent or compound (IS)-benzyl (2R)-hydroxy-3-((3R,4S) may comprise, inter-alia, an oligonucleotide, a nucleic acid, dihydroxy-pyrrolidin-1-yl-)-oxypropyl amide. or a vector. In some embodiments, the term "oligonucleotide' 0111. In some embodiments, the drug, compound or agent is interchangeable with the term “nucleic acid, and may refer may comprise, inter-alia, the anti-fungal fluconazole, the to a molecule, which may include, but is not limited to, anti-inflammatory piroXicam and celicoxib and Valdicoxib, prokaryotic sequences, eukaryotic mRNA, cDNA from and the antibiotics carbenicillinindanyl sodium, bacampicil eukaryotic mRNA, genomic DNA sequences from eukary lin hydrochloride, troleandomycin, and doxycycline hyclate. otic (e.g., mammalian) DNA, and synthetic DNA sequences. In some embodiments, the drug, compound or agent may The term also refers to sequences that include any base analog comprise, inter-alia, other antineoplastic agents such as plati of DNA and RNA. num compounds (e.g., spiroplatin, cisplatin, and carbopl 0107. In some embodiments, the composition is in the atin), methotrexate, fluorouracil, adriamycin, mitomycin, form of a gel, which in one embodiment is a hydrogel. In ansamitocin, bleomycin, cytosine arabinoside, arabinosyl Some embodiments of the invention, the composition may adenine, mercaptopolylysine, Vincristine, buSulfan, chloram US 2016/0220601 A1 Aug. 4, 2016 bucil, melphalan (e.g., PAM, L-PAM or phenylalanine mus chloroprocaine hydrochloride, etidocaine hydrochloride, tard), mercaptopurine, mitotane, procarbazine hydrochloride lidocaine hydrochloride, mepivacaine hydrochloride, dactinomycin (actinomycin D), daunorubicin hydrochloride, procaine hydrochloride and tetracaine hydrochloride; anes doxorubicin hydrochloride, paclitaxel and other taxenes, thetics such as droperidol, etomidate, fentanyl citrate with rapamycin, manumycin A, TNP-470, plicamycin (mithramy droperidol, ketamine hydrochloride, methohexital sodium cin), aminoglutethimide, Sodium, and thiopental sodium; and radioactive particles or ions such flutamide, leuprolide acetate, megestrol acetate, tamoxifen as strontium, iodide rhenium and yttrium. citrate, testolactone, triloStane, amsacrine (m-AMSA). 0112 In some embodiments, the drug, compound or agent asparaginase (L-asparaginase) Erwina asparaginase, inter may comprise, inter-alia, a molecule, which when provided to feron alpha.-2a, interferon alpha.-2b, teniposide (VM-26), a Subject in need, provides a beneficial effect. In some cases, vinblastine sulfate (VLB), Vincristine sulfate, bleomycinsul the molecule is therapeutic in that it functions to replace an fate, hydroxyurea, procarbazine, and dacarbazine; mitotic absence or diminished presence of Such a molecule in a Sub inhibitors such as etoposide, colchicine, and the Vinca alka ject. In one embodiment, the molecule is a nucleic acid coding loids, radiopharmaceuticals such as radioactive iodine and for the expression of a protein is absent, Such as in cases of an phosphorus products; hormones Such as progestins, estrogens endogenous null mutant being compensated for by expres and antiestrogens; anti-helmintics, antimalarials, biologicals sion of the foreign protein. In other embodiments, the endog Such as immune serums, antitoxins and antivenoms; bacterial enous protein is mutated, and produces a non-functional pro vaccines; viral vaccines; blood products such as parenteral tein, compensated for by the expression of a heterologous iron, hemin, hematoporphyrins and their derivatives; biologi functional protein. In other embodiments, expression of a cal response modifiers such as muramyldipeptide, muramyl heterologous protein is additive to low endogenous levels, tripeptide, microbial cell wall components, lymphokines resulting in cumulative enhanced expression of a given pro (e.g., bacterial endotoxin such as lipopolysaccharide, mac tein. In other embodiments, the molecule stimulates a signal rophage activation factor), Sub-units of bacteria (Such as ing cascade that provides for expression, or secretion, or Mycobacteria, Corynebacteria), the synthetic dipeptide others of a critical element for cellular or host functioning. N-acetyl-muramyl-L-alanyl-D-isoglutamine; anti-fungal 0113. In another embodiment, the compound, drug or agents such as ketoconazole, nystatin, griseofulvin, flucy agent may be a cytotoxic agent such as, for example, taxol. tosine (5-fc), miconazole, Amphotericin B, ricin, cyclospor cytochalasin B, gramicidin D, ethidium bromide, emetine, ins, and B-lactam antibiotics (e.g., Sulfazecin); hormones mitomycin, etoposide, tenoposide, Vincristine, vinblastine, such as growth hormone, , beclomethasone dipropi colchicin, doxorubicin, daunorubicin, dihydroxy anthra onate, betamethasone, betamethasone acetate and betametha cinedione, mitoxantrone, mithramycin, actinomycin D, 1-de Sone sodium phosphate, Vetamethasone disodium phosphate, hydrotestosterone, , procaine, tetracaine, Vetamethasone sodium phosphate, cortisone acetate, dexam lidocaine, propranolol, and puromycin and analogs or ethasone, dexamethasone acetate, dexamethasone sodium homologs thereof. phosphate, flunisolide, hydrocortisone, hydrocortisone 0114. The compositions of the invention can be provided acetate, hydrocortisone cypionate, hydrocortisone sodium in any Suitable vehicle. Thus, for instance, pharmaceutically phosphate, hydrocortisone sodium Succinate, methylpred acceptable vehicles and/or carriers and/or adjuvants are con nisolone, methylprednisolone acetate, methylprednisolone templated for incorporation therein. Sodium Succinate, paramethasone acetate, prednisolone, 0.115. In some embodiments, the additional drug, com prednisolone acetate, prednisolone sodium phosphate, pred pound or agent is effective as a contraceptive. In some nisolone tebutate, prednisone, triamcinolone, triamcinolone embodiments, the additional drug, compound or agent is acetonide, triamcinolone diacetate, triamcinolone hexac effective against vaginitis, Vulivitis, Vestibulitis, Vulvadynia, etonide, fludrocortisone acetate, oxytocin, vassopressin, and Vulval itching or Vulvavaginitis. their derivatives; vitamins such as cyanocobalamin neinoic 0116. In some embodiments of the invention, there is pro acid, retinoids and derivatives such as retinol palmitate, and vided a use of a composition for intravaginal and/or for inter ..alpha.-tocopherol; peptides, such as manganese Super oxide nal mucosal application, wherein the composition comprises dismutase; enzymes such as alkaline phosphatase; anti-aller an effective amount of a Sulfated polysaccharide and a phar gic agents such as amelexanox; anti-coagulation agents such maceutically acceptable carrier in the manufacture of a medi as phenprocoumon and ; antivirals such as amanta cament for treating vaginal infection, vaginal dryness, vagi dine azidothymidine (AZT, DDI, Foscarnet, or Zidovudine), nal or Vulvo Vaginal atrophy, vaginal itching, dyspareunia, ribavirin and Vidarabine monohydrate (adenine arabinoside, vaginal or Vulvarpain, vaginal or perivaginal inflammation or ara-A); anticoagulants such as phenprocoumon, heparin; for promoting vaginal or wound healing and for treating vagi antibiotics such as dapsone, chloramphenicol, neomycin, nal atrophy/drynessfirritation during and/or following radio cefaclor, cefadroxil, cephalexin, cephradine erythromycin, therapy, chemotherapy or hormone therapy related to cancer clindamycin, lincomycin, amoxicillin, amplicillin, bacampi (such as aromatase inhibitors). cillin, carbenicillin, dicloxacillin, cyclacillin, picloxacillin, 0117. In some embodiments, there is provided a method hetacillin, methicillin, nafcillin, oxacillin, penicillin includ for treating vaginal infection, vaginal dryness, vaginal or ing penicillin G and penicillin V, ticarcillin rifampin and Vulvo Vaginal atrophy, vaginal itching, dyspareunia, vaginal tetracycline; antiinflammatories such as diflunisal, ibuprofen, or Vulvar pain, vaginal or perivaginal inflammation or for indomethacin, meclofenamate, mefenamic acid, naproxen, promoting vaginal or wound healing and for treating vaginal oxyphenbutaZone, phenylbutaZone, piroxicam, Sulindac, tol atrophy/drynessfirritation during and/or following chemo metin, aspirin and Salicylates; antiprotozoans such as chloro therapy or hormone therapy related to cancer (Such as aro quine, hydroxychloroquine, metronidazole, quinine and matase inhibitors) wherein the composition comprises an meglumine antimonate; antirheumatics Such as penicil effective amount of a sulfated polysaccharide and a pharma lamine; local anesthetics such as bupivacaine hydrochloride, ceutically acceptable carrier. US 2016/0220601 A1 Aug. 4, 2016

0118. In some embodiments of the invention, there is pro tion thereof, and a pharmaceutically acceptable carrier in the vided a use of a composition for intravaginal and/or for inter manufacture of a medicament for treating vaginal infection, nal mucosal application, wherein the composition comprises vaginal dryness, vaginal or Vulvo Vaginal atrophy, vaginal an effective amount of a Sulfated polysaccharide and a phar itching, dyspareunia, vaginal or Vulvar pain, vaginal or maceutically acceptable carrier in the manufacture of a medi perivaginal inflammation or for promoting vaginal or wound cament for treating oralleviating decreased vaginal boundary healing. lubrication oradisease or condition associated therewithor of 0.125. In some embodiments of the invention, there is pro improving vaginal boundary lubrication. vided a method for treating vaginal infection, vaginal dry 0119. In some embodiments of the invention, there is pro ness, vaginal or Vulvo Vaginal atrophy, vaginal itching, dys vided a method for treating or alleviating decreased vaginal pareunia, vaginal or Vulvar pain, vaginal or perivaginal boundary lubrication or a disease or condition associated inflammation or for promoting vaginal or wound healing therewith or of improving vaginal boundary lubrication com comprising the step of vaginally administering a composition prising the step of vaginally administering a composition comprising an effective amount of a Sulfated polysaccharide, comprising an effective amount of a Sulfated polysaccharide one or more of a natural quaternary polymer, a quaternary and a pharmaceutically acceptable carrier. molecular compound, a metalloproteinase inhibitor, an anti 0120. The disease or the condition associated with inflammatory agent, an acid pH control buffering system or decreased vaginal boundary lubrication are typically vaginal any combination thereof, and a pharmaceutically acceptable atrophy, dyspareunia, Sjogren's syndrome, menopause, carrier. androgen deficiency, estrogen deficiency, estrogen replace I0126. In some embodiments of the invention, there is pro ment therapy, allergy, chronic inflammation, menopause, pre vided a use of a composition for intravaginal and/or for inter mature menopause, chemotherapy, hormonal therapy for can nal mucosal application, wherein the composition comprises cer patients (such as aromatase inhibitors), breastfeeding, an effective amount of a Sulfated polysaccharide, one or more Surgical removal of the ovaries before menopause, genital of a natural quaternary polymer, a quaternary molecular com lichen Sclerosis, Vulvodynia, bacterial vaginosis, herpes, can pound, a metalloproteinase inhibitor, an anti-inflammatory dida, psoriasis, contact dermatitis, condylomata, or side agent, an acid pH control buffering system or any combina effects of medications and aging. tion thereof, and a pharmaceutically acceptable carrier, in the 0121. In some embodiments of the invention, there is pro manufacture of a medicament for treating or alleviating vided a use of a composition for intravaginal and/or for inter decreased vaginal boundary lubrication or a disease or con nal mucosal application, comprising an effective amount of a dition associated therewith or of improving vaginal boundary Sulfated polysaccharide and a pharmaceutically acceptable lubrication. carrier, in the manufacture of a medicament for preventing episiotomy or for treating tissue damages after episiotomy. In I0127. In some embodiments of the invention, there is pro Such a case for using the composition for preventing epi vided a method for treating or alleviating decreased vaginal Siotomy, the composition of the administered a week, two boundary lubrication or a disease or condition associated weeks, three weeks or a month before the date of delivery of therewith or of improving vaginal boundary lubrication com a newborn. prising the step of vaginally administering a composition 0122. In some embodiments of the invention, there is pro comprising an effective amount of a Sulfated polysaccharide, vided a method for preventing episiotomy or for treating one or more of a natural quaternary polymer, a quaternary tissue damages after episiotomy comprising the step of vagi molecular compound, a metalloproteinase inhibitor, an anti nally administering a composition comprising an effective inflammatory agent, an acid pH control buffering system or amount of a sulfated polysaccharide and a pharmaceutically any combination thereof, and a pharmaceutically acceptable acceptable carrier. carrier. 0123. According to some embodiments, the sulfated 0128. The disease or the condition associated with polysaccharide is derived from alga. According to some decreased vaginal boundary lubrication are typically vaginal embodiments, the alga is a red alga, green alga and/or a brown atrophy, dyspareunia, Sjogren's syndrome, menopause, alga. According to further embodiments, the red alga is Por androgen deficiency, estrogen deficiency, estrogen replace phyridium sp., P aerugineum, Porphyridium Cruentum, por ment therapy, allergy, chronic inflammation, menopause, pre phyridium purpureum, R. reticulata. Cyanidioschyzon mero mature menopause, chemotherapy, radiotherapy, hormonal lae, Atractophora hypnoides, Gelidiella calcicola, Lemanea, treatment for cancer patients (aromatase inhibition), breast Palmaria palmata, Schmitzia hiscockiana, Chondrus crispus, feeding, Surgical removal of the ovaries before menopause, Mastocarpus Stellatus, and/or Acrochaetium efiorescens. genital lichen Sclerosis, Vulvodynia, bacterial vaginosis, her The brown alga is in Some embodiments, Undaria pinnati pes, candida, psoriasis, contact dermatitis, condylomata, or fida, Laminaria saccharina, L. digitata, Fucus evanescens, F. side effects of medications and aging. serratus, F. distichus, F spiralis, Ascophyllum nodosum and/ I0129. In some embodiments of the invention, there is pro or Fucus vesiculosus and the green alga/cyanobacteria is in vided a use of a composition for intravaginal and/or for inter Some embodiments Prasinococcus capsulatus, Spirulina, nal mucosal application, wherein the composition comprises Chlorella, Isochrysis and/or Dunaliella. an effective amount of a Sulfated polysaccharide, one or more 0.124. In some embodiments of the invention, there is pro of a natural quaternary polymer, a quaternary molecular com vided a use of a composition for intravaginal and/or for inter pound, a metalloproteinase inhibitor, an anti-inflammatory nal mucosal application, wherein the composition comprises agent, an acid pH control buffering system or any combina an effective amount of a Sulfated polysaccharide, one or more tion thereof, and a pharmaceutically acceptable carrier, in the of a natural quaternary polymer, a quaternary molecular com manufacture of a medicament for preventing episiotomy or pound, a metalloproteinase inhibitor, an anti-inflammatory for treating tissue damages after episiotomy. In Such a case for agent, an acid pH control buffering system or any combina using the composition for preventing episiotomy, the compo US 2016/0220601 A1 Aug. 4, 2016

sition of the administered a week, two weeks, three weeks or a medicament for treating or promoting healing of episiotomy a month before the date of delivery of a newborn. is specifically contemplated. In some embodiments of the 0130. In some embodiments of the invention, there is pro invention, the composition may be used for the prevention of vided a use of a composition for intravaginal and/or for inter episiotomy. nal mucosal application, wherein the composition comprises 0.138. In some embodiments, according to these aspects, an effective amount of a Sulfated polysaccharide, one or more use of the compositions of this invention in the preparation of of a natural quaternary polymer, a quaternary molecular com a medicament for treating or promoting healing of vaginal pound, a metalloproteinase inhibitor, an anti-inflammatory dryness during or following chemotherapy or hormonal treat agent, an acid pH control buffering system or any combina ment for cancer patients is specifically contemplated. In some tion thereof, and a pharmaceutically acceptable carrier, in the embodiments of the invention, the composition may be used manufacture of a medicament for preventing and treating to alleviate vaginal dryness associated with chemotherapy or vaginal atrophy in cancer patients as a results of chemo hormonal therapy related to cancer. Hormonal treatment for therapy or hormonal treatment (drugs that blocks estrogen cancer patient can be used as adjuvant, neoadjuvant or as the receptors, treatments that lower estrogen level Such as aro treatment itself. The treatments include drugs that block matase inhibitiors and progesterone-like drugs). When using estrogen receptors (such as Tamoxifen, Fulvestrant), lower the composition for preventing chemotherapy or hormonal ing estrogen level (Aromatase inhibitors) or progesterone therapy associated conditions, the composition may be based therapy. In order to alleviate chemotheraphy and/or administered during and/or following the chemotherapy/hor hormonal therapy-associated damage, the composition of the monal therapy. invention is administered during or at the end of the chemo 0131. In some embodiments, the composition may be used therapy/hormonal treatment. in the manufacture of a medicament for preventing or for treating tissue damages associated with chemotherapy or hor 0.139. According to some embodiments of the invention, monal therapy for cancer patients treated with drugs that there is provided a use of a composition of the invention, in block estrogen receptors, lowering estrogen level or proges the manufacture of a medicament for treating oralleviating at terone-based agents. least one menopause-associated symptom in a female patient. 0.132. In some embodiments the hormonal therapy for can 0140. The compositions of the invention are used for man cer patients include use of aromatase inhibitors. In some aging vaginal lubrication and to protect the vaginal epithe embodiments, the composition is used to cure the tissue dam lium against shear forces (including significant shear forces) ages caused by the hormonal therapy. and discomfort generated from the undesirable conditions 0133. In some embodiments of the invention, there is pro including, for example, vaginal atrophy, dyspareunia, vided a method for preventing episiotomy or for treating Sjogren's syndrome, androgen deficiency, estrogen defi tissue damages after episiotomy comprising the step of vagi ciency, estrogen replacement therapy, allergy, chronic nally administering a composition comprising an effective inflammation, menopause, premature menopause, chemo amount of a Sulfated polysaccharide, one or more of a natural therapy, breastfeeding, Surgical removal of the ovaries before quaternary polymer, a quaternary molecular compound, a menopause, genital lichen Sclerosis, Vulvodynia, bacterial metalloproteinase inhibitor, an anti-inflammatory agent, an vaginosis, herpes, candida, psoriasis, contact dermatitis, acid pH control buffering system or any combination thereof, condylomata, side effects of medications and aging. Symp and a pharmaceutically acceptable carrier. toms or indications of vaginal lubrication deficiency include, 0134. Using formula on a daily basis up to one month by way of non-limiting example, vaginal dryness, vaginalitch before delivery date will hydrate and soften the cervix orifice or a burning sensation, painful sexual intercourse, and light and birth canal allowing it to expend and become elastic vaginal bleeding after intercourse. enough to avoid episiotomy and allow faster wound healing 0.141. According to some embodiments of the invention, process after episiotomy. there is provided a use of the composition of the invention in 0135 According to some embodiments, the sulfated the manufacture of a medicament for treating or alleviating polysaccharide is derived from alga. According to some decreased vaginal boundary lubrication or a disease associ embodiments, the alga is a red alga, green alga and/or a brown ated therewith or of improving vaginal boundary lubrication. alga. According to further embodiments, the red alga is Por The disease or the conditions associated with decreased vagi phyridium sp., P aerugineum, Porphyridium Cruentum, por nal boundary lubrication is vaginal atrophy, dyspareunia, phyridium purpureum, R. reticulata. Cyanidioschyzon mero Sjogren's syndrome, menopause, androgen deficiency, estro lae, Atractophora hypnoides, Gelidiella calcicola, Lemanea, gen deficiency, estrogen replacement therapy, allergy, Palmaria palmata, Schmitzia hiscockiana, Chondrus crispus, chronic inflammation, menopause, premature menopause, Mastocarpus Stellatus, and/or Acrochaetium efiorescens. chemotherapy, breastfeeding, Surgical removal of the ovaries The brown alga is in Some embodiments, Undaria pinnati before menopause, genital lichen Sclerosis, Vulvodynia, bac fida, Laminaria saccharina, L. digitata, Fucus evanescens, F. terial vaginosis, herpes, candida, psoriasis, contact dermati serratus, F. distichus, F spiralis, Ascophyllum nodosum and/ tis, condylomata, or side effects of medications and aging. or Fucus vesiculosus and the green alga/cyanobacteria is in 0142. A deficiency, as well as an improvement in vaginal Some embodiments Prasinococcus capsulatus, Spirulina, lubrication and symptoms associated therewith can be deter Chlorella, Isochrysis and/or Dunaliella. mined by any Suitable method. For example, qualitatively 0136. In some embodiments, this invention provides a use (e.g., a feeling of low lubrication, discomfort, vaginal dry of a composition as herein described, in the manufacture of a ness, vaginal itch or a burning sensation, painful sexual inter medicament for treating vaginal or perivaginal inflammation course, and light vaginal bleeding after intercourse etc.) or or promoting vaginal or perivaginal wound healing. quantitatively (e.g., measured through mechanical, histologi 0.137 In some embodiments, according to these aspects, cal, PAP Smear, biochemical, electrical, optical, question use of the compositions of this invention in the preparation of naires) or any other method. US 2016/0220601 A1 Aug. 4, 2016

0143. In some embodiments of the invention the compo severity of the affliction, the manner of administration, the sition is designed as a gel. The amount of the gel that is judgment of the prescribing physician, etc. administered to the subject is between 1-5 ml per dose. In some embodiments of the invention the amount is 2.5-4.0 ml per dose. EXAMPLES 0144. In some embodiments of the invention, the compo sition of the invention is administered once, twice or three Example 1 times a week or more. In some embodiments of the invention, the composition of the invention is administered once, twice Comparing a Preparation of Sulfated Polysaccharide or three times a day or more. In some embodiments of the invention, the composition is administered for a week, two 0152. A study will be conducted on about 30 womenaged weeks, month, six months or more. 50-75 suffering from post-menopausal conditions which 0145. In some embodiments of the invention, the compo sition of the invention is used for preventing episiotomy or for include one or more of vaginal Surface irritation, burning treating tissue damages after episiotomy. In order to prevent during urination, dyspareunia, intermittent light bleeding episiotomy, the composition of the invention is administered after intercourse, inflamed vaginal epithelium, with patchy a week, two weeks, three weeks or a month before the date of erythema, petechiae, or increased friability, or a minimal or a delivery of the newborn. significant Vulvar lesion, or a thin endometrium of around 4 0146 In some embodiments of the invention, the compo mm in width, or appearance of thin, pale vaginal walls that sition of the invention is used for preventing or for treating can be determined by a pelvic examination. tissue damages during and/or after chemotherapy or hormone 0153. The women will be subjected to once a day or twice therapy (adjuvant, neoadjuvant or as the treatment itself) for weekly treatment with the composition detailed in Table I or cancer patients treated with drugs that block estrogen recep II with possible modifications below for about 45 days. A tors (such as Tamoxifen, Fulvestrant), lowering estrogen level certain percentage of the participants will receive a placebo. (Aromatase inhibitors) or progesterone-based therapy. In The participant condition will be evaluated by doctors. Fur order to alleviate chemotherapy and/or hormonal therapy ther, each participant will complete a questionnaire regarding associated damage, the composition of the invention is their symptoms of urogenital atrophy. An improvement in one administered during or at the end of the chemotherapy/hor or more of the symptoms will be determined. In certain monal treatment. instances, the symptoms will be completely alleviated, or 0147 Determination of a therapeutically effective amount improved from severe to tolerable. in the method of treating and the use described herein is well within the capability of those skilled in the art, and depends TABLE I on the severity of the disease, its type, the mode of adminis tration and the like. Ingredient Proposed % Function 0148 For any preparation used in the methods of the Sulfated polysaccharide O.10-300 Anti-Irritant, anti-Bacterial, invention, the therapeutically effective amount or dose can be Vaginal Care estimated initially from in vitro other assays known in the art. Condrus Crispus Extract O.10-300 Anti-Irritant, Hydration, (plantsilicone) Film Forming, Lubricant Toxicity and therapeutic efficacy of the active ingredients Saccaride Isomerate 1.OO-5.OO Moisturizer described herein can be determined by standard pharmaceu (100% Plant derivate) tical procedures in vitro or in-vivo, in cell cultures, experi Sodium Polyacrylate O.10-100 Viscosity Modifier mental animals or on skin of healthy Volunteers. The data Lubricant, Texturizer Lubrasil DM Hydrogel O.10-100 Viscosity Modifier obtained from these in vitro and cell culture assays, animal Lubricant, Texturizer and human studies can be used in formulating a range of Flax Seed Extract 1.00-150 Biofunctional, dosage for use in humans. The dosage may vary depending cosmobiotic,with probiotic upon the dosage form employed and the route of administra effect. Normalizes natural microflora tion utilized. The exact formulation, route of administration Soflavone aglycone (soy 1.OO-5.OO Collagen Booster and dosage can be chosen by the individual physician in view aglycon) Metalloproteinases inhibitor of the patient’s condition. (See e.g., Fingl, et al., 1975, in “The Sodium Carboxymethyl O.O2-0.10 Immune-enhancing, increases Pharmacological Basis of Therapeutics' Ch. 1 p. 1). Betaglucan self protecting capacity EDTA O.O2-0.04 Chelating Agent 0149 Dosage amount and interval may be adjusted indi Lactic Acid Sodium Lactate O.30-100 Acid pH control (3.8-4.5) vidually to ensure levels of the active ingredient are sufficient buffering system to induce or suppress the biological effect (minimal effective Monoesters of Caprylic OSO-1.OO Multi-functional, all-natural andfor system for preservative free concentration, MEC). The MEC will vary for each prepara Undecylenic Acids and or and self-preserving. tion, but can be estimated from in vitrofin-vivo data. Dosages Caprylhydroxamic acid and/or Biostatic activity necessary to achieve the MEC will depend on individual Caprylyl Glycol Glycerin characteristics and route of administration. Detection assays Natural extracts, Echinaccea, 1.00-50.00, According to the specific Propolis, Comfrey, Melissa Each one or function requested can be used to determine plasma concentrations. Grape Fruit, Mango Seed, different 0150. Depending on the severity and responsiveness of the Cranberry, Cucumber, mixtures condition to be treated, dosing can be of a single or a plurality Green Tea, Salvia, thereof. of administrations, with course of treatment lasting from Chamomile, Geranium, Lavender, Lemon, several days to several weeks or until cure is effected or Juniper, Clove Bud, Lotus, diminution of the disease state is achieved. Moringa, Water 0151. The amount of a composition to be administered will, of course, be dependent on the subject being treated, the US 2016/0220601 A1 Aug. 4, 2016 13

TABLE II ing between about 0.001-1.0%. Each mixture will be put in a petri dish containing keratinocyte cells. The anti-inflamma Ingredient Proposed % Function tory effect and the tissue repair activity of the compound as Water 80-97% well as the Synergistic effect of Such compounds together Sulfated polysaccharide O.OS-3.OO Anti-Irritant, with the sulfated polysaccharide will be measured to exhibit anti-Bacterial, elevated/synergistic anti-inflammatory, and tissue repair Vaginal Care activity. hydroxypropyltrimonium O. 1-5 quaternary hydrolyzed proteinsbeta glucan molecular hydroxypropyltrimonium compound Example 4 chloride? Hydroxypropyl Guar Hydroxypropyltrimonium Chloride, Berberine Use of a Composition Comprising Sulfated Lactic Acid Sodium Lactate O5-2 Acid pH control Polysaccharides for Treating Deficient Vaginal And Sodium dibasic hydrogen (3.8-4.5) Boundary Lubrication in a Cancer Patient Treated phosphate buffering system with Chemotherapy and/or Hormonal Treatment Natural extracts: O. 1-3 According to Green TeaGrape seed? Gotu Each one the specific (Aromatase Inhibitor) Kola (Centella asiatica). or different function requested Chondrus Chrispus melissa mixtures 0158. A study will be conducted on about 40 womenaged grape fruitmango seed thereof. 20-75 with breast cancer, treated with aromataz inhibitors cranberry/cucumber salvia Suffering from vaginal atrophy, which include one or more of chamomilefaloevera, vaginal Surface irritation, burning during urination, dyspareu Water Pentylene Glycol, Glyceryl O.S.-1.5 PRESERVATIVE nia, intermittent light bleeding after intercourse, inflamed Caprylate, Glyceryl Undecylenate vaginal epithelium, with patchy erythema, petechiae, or Chitosan O.O1-2% Moisturizing increased friability, or a minimal or a significant Vulvar lesion, or a thin endometrium of around 4 mm in width, or appearance of thin, pale vaginal walls that can be determined Example 2 by a pelvic examination. 0159. The women will be subjected to once a day or twice weekly treatment with the composition detailed in Table I or Determination of Water Retention of a Composition Table II for about 60 days. Each participant will complete a Comprising a Sulfated Polysaccharide questionnaire regarding their symptoms of urogenital atro 0154 Determination of transepidermal loss (TEWL) and/ phy. or skin hydration (measured by Corneometer) in 5-50 partici 0160 An improvement in one or more of the symptoms pants of a composition described in Table I or Table II with or will be determined. In certain instances, the symptoms will be without a quaternary molecular compound, will be performed completely alleviated, or improved from severe to tolerable to exhibit the increased efficacy of the quaternary molecular when treated with the composition detailed in Table I or Table compound combined with the sulfated polysaccharide to II. reduce TEWL. (O155 The compositions described in Table I or Table II Example 5 with or without the quaternary molecule will be measured for skin hydration by Corneometer to determine the increased Assessment of the Synergistic Effect Between the efficacy of the formulation containing quaternary molecular Sulfated Polysaccharide and Natural Botanic Extract combined with the sulfated polysaccharide versus the sul in Treating Irritation & Inflammation fated polysaccharide alone 0.161 The ability of the sulfated polysaccharide in combi Example 3 nation with one or more of the compounds: Green tea extract, Gotu Kola (Centalla asiatica) extract, Grape seed extract, An In-Vitro Test for Evaluation of a Formula of Chondrus Chrispus, melissa, grape fruit, mango seed, cran Sulfated Polysaccharide for Treating Irritation and berry, cucumber, Salvia, chamomile, aloe Vera will be mea Inflammation sured in patch test study with irritation conducted by SLS. The skin of 5-50 subjects will be irritated with SLS and skin 0156 An in-vitro test for evaluation of the metalloprotein coloration (redness) will be measured. Optional: TEWL will ase inhibition activity and the immune activity of one or more be measured as well as an indicator for barrier function and of Green tea extract, Gotu Kola (Centalla asiatica) extract, integrity. Grape seed extract, Chondrus Chrispus, melissa, grape fruit, 0162 The formulation was assessed in patch test on 50 test mango seed, cranberry, cucumber, Salvia, chamomile, aloev Subjects: 27 normal healthy, 6 eczema, 4 allergy and 13 Sub era with or without the sulfated polysaccharide for treating jects with sensitive skin. The product was applied to the back irritation and inflammation will be conducted. A polysaccha of panellists for a period of 48 hours. proper adherence of the ride of red microalga and the extracts indicates above will be test patches was assured by the inclusion of Sodium dodecyl applied to a keratinocyte or immune cell line and will be sulphate (SDS) in one concentration (1%) as a positive con measured as MMP inhibitors and cytokine inhibitors. trol. Water was used as a negative control. The treatment sites 0157 Different combinations of sulfated polysaccharide were assessed for the presence of irritation by a trained evalu will be prepared by mixing it with either Green tea extract, ator using a point visual scale at 48 h (30 min after patch Gotu Kola (Centalla asiatica) extract, Grape seed extract, removal) and 72 h after patch application. Results: no Chondrus Chrispus, melissa, grape fruit, mango seed, cran erythema, Scaling or fissure was seen in all 50 Subjects mea berry, cucumber, Salvia, chamomile or aloevera w/w % rang Sured (data not shown). US 2016/0220601 A1 Aug. 4, 2016 14

Example 6 placed in the incubator/oven. After four hours, the oven was opened and the sample dishes therein were covered quickly. Comparing the Water Retention Ability of a The dishes were then transferred to a desiccator, and let to Formulation Containing Sulfated Polysaccharides cool to room temperature for 15 minutes, after which they Alone and Sulfated Polysaccharides Combined with were weighed. The above procedure was repeated after 8 and a Quaternary Molecule 24 hours. 0163 Two formulations, one comprising a quaternary molecule combined with the sulfated polysaccharides Results—24°C. Fucoidan, extracted from Undaria pinnatifida (Brown alga) (0166 and the Sulfated polysaccharide extracted from porphyridium Cruentum (Red alga), and the other comprising only the TABLE IV Sulfated polysaccharides, were combined in the gels described in Table III or Table IV, detailed below. A control Water loss (%)-24 hr formulation, containing neither the quaternary molecule, nor FABO3-No Guar FAB06-Including Guar the Sulfated polysaccharides was also prepared. The gels were hydroxypropyltrimonium hydroxypropyltrimonium weighed on an analytical scale and the equivalent weight chloride (quaternary chloride (quaternary FABO7 from each formulation was placed in an incubator. A sample Hr molecule) molecule) Control from each gel was removed of the incubator at different time O O O O points and was measured using an analytical scale to prove 4 94.9 77 96.2 that the gel containing the quaternary molecule retains more 8 94.8 92.2 96.5 water. The gels were dried and weighed again. It is noted that 24 93.9 92.6 96.4 unless explicitly mentioned otherwise, the Sulfated polysac charides related to herein are the Fucoidan extracted from Undaria pinnatifida (Brown alga) and the Sulfated polysac 0.167 FIGS. 1 and 2 present the water loss and water charide extracted from porphyridium Cruentum (Red alga). retention results after 4, 8 and 24 hour of incubation at 24°C. 0164 Particularly, the following three formulation were (0168 Particularly, FIG. 1 shows that the water loss of the prepared: FAB06 formulation, which included both sulfated polysac charides extracted from the alga extracts (Fluicodan extracted FAB03: sulfated polysaccharides (Fuicodan and Porphy from Undaria pinnatifida, and Porphyridium polysaccha ridium polysaccharides) only (not including the quaternary rides) as well as the quaternary molecule Guar Hydroxypro molecule guar hydroxypropyltrimonium chloride) pyltrimonium Chloride, presented the lowest water loss per FAB06: sulfated polysaccharides, and the quaternary mol centages at all times tested. Further, after four hours, the ecule guar hydroxypropyltrimonium chloride differences between the water loss of the FAB06 formulation FAB07: Control (no sulfated polysaccharides, or guar and the otherformulations are the largest. Further, the FAB03 hydroxypropyltrimonium chloride (quaternary molecule)) formulation, containing only the alga extracts, not the quater nary molecule guar hydroxypropyltrimonium chloride, dem TABLE III onstrated a lower water loss than the FAB07 control at all times tested. Formulation number FABO3 FABO6 FABO7 Composition 9% WW 9% WW 9% WW 0169. As presented in FIG. 2, the water retention ability FUICODAN: 1 1 O was the highest in the FAB06 formulation. As further pre Undaria pinnatifida extract sented in FIG. 2, the water retention ability was higher in the (Brown alga) FAB03 formulation in comparison to the FAB07 control. SULFATED POLYSACCHARIDE O.1 O.1 O (Porphyridium polysaccharide) Glyceryl Caprylate, Pentylene 1 1 1 CONCLUSIONS Glycol, Glyceryl Undecylenate (preservative) (0170 From the comparison between the FAB03 and the Guar Hydroxypropyltrimonium O 2 O FAB07 control formulations it appears that the sulfated Chloride (quaternary molecule) polysaccharides (Fuicodan and Porphyridium polysaccha Green Tea Extract O.1 O.1 O Xanthan gum 1.8 O 1.8 rides) have water retention abilities, while the addition of a Lactic acid 1 1 1 quaternary molecule (Guar Hydroxypropyltrimonium Chlo Allantoin O.2 O.2 O.2 ride) further enhances the water retention abilities of the Sodium dibasic hydrogen phosphate O.2 O.2 O.2 formulation, as shown when comparing the FAB06 formula Purified water 94.6 94.4 95.8 tion to the FAB03 and FAB07 formulations. The higher the Total 1OO 100 1OO water retention ability of the formulation, the lower the water loss and accordingly, the formulations providing high water retention present low water loss and vice versa. Procedure 0171 It will be understood by those skilled in the art that various changes in form and details may be made therein Water-Release Rate at 24°C. without departing from the spirit and scope of the invention as set forth in the appended claims. Those skilled in the art will 0.165. Approximately 100 mg of each sample were trans recognize, or be able to ascertain using no more than routine ferred to a separate weighed and labeleddish. The dishes were experimentation, many equivalents to the specific embodi Subsequently covered and weighed. Once the incubator/oven ments of the invention described herein. Such equivalents are was preheated to 24°C., the samples were uncovered and intended to be encompassed in the scope of the claims. US 2016/0220601 A1 Aug. 4, 2016

What is claimed is: ral, an antifungal, an anti-inflammatory, anti-irritating, anti 1. A composition for intravaginal and/or for internal itching, growth factor, a hormone or a spermicidal compound. mucosal application, comprising an effective amount of a 13. The composition of claim 1, in a form of a cream, an Sulfated polysaccharide, one or more of a natural quaternary ointment, a solution, a gel, a Suppository, an emulsion, a polymer, a quaternary molecular compound, a metallopro foam, a capsule, a pill or a tablet. 14. The composition of claim 1, wherein the quaternary teinase inhibitor, one or more anti-inflammatory agent, an molecular compound is laurylpyridinium chloride, cetylpy acid pH control buffering system or any combination thereof, ridinium chloride, hydroxypropyltrimonium hydrolyzed pro and a pharmaceutically acceptable carrier. teins, beta glucan hydroxypropyltrimonium chloride, ber 2. The composition of claim 1, wherein the sulfated berine or guar Hydroxypropyltrimonium chloride. polysaccharide is derived from alga. 15. The composition of claim 1, wherein the natural qua 3. The composition of claim 2, wherein the alga is a red ternary polymer is guar Hydroxypropyltrimonium chloride. microalga, green alga-cyanobacteria and/or a brown alga. 16. A method for treating or alleviating decreased vaginal 4. The composition of claim3, wherein the red microalga is boundary lubrication or a disease or condition associated Porphyridium sp., P. aerugineum, Porphyridium Cruentum, therewith or of improving vaginal boundary lubrication, vagi porphyridium purpureum, R. reticulata, Cyanidioschyzon nal damages, vaginal infection, vaginal dryness, vaginal or merolae, Atractophora hypnoides, Gielidiella calcicola, Vulvo Vaginal atrophy, vaginal itching, dyspareunia, vaginal Lemanea, Palmaria palmata, Schmitzia his cockiana, Chon or Vulvar pain, vaginal or perivaginal inflammation or for drus Crispus, Mastocarpus Stellatus, or Acrochaetium efflo promoting vaginal or wound healing, vaginal atrophy/dry rescens, brown alga is Undaria pinnatifida, Laminaria sac ness caused by radiotherapy, chemotherapy and/or hormonal charina, L. digitata, Fucus evanescens, F serratus, F. treatment comprising administering a composition compris distichus, F spiralis, Ascophyllum nodosum and/or Fucus ing an effective amount of a Sulfated polysaccharide and a vesiculosus. Green alga-cyanobacteria is Prasinococcus cap pharmaceutically acceptable carrier, wherein said composi sulatus Spirulina, Chlorella, Isochrysis and/or Dunaliella tion is in a form for intravaginal application, internal mucosal 5. The composition of claim 1, wherein said metallopro application, or both. teinase inhibitor is one or more of Soy isoflavone aglycone, 17. The method of claim 16, wherein the disease or the Green tea (Camelia sinensis), Grape seed or Gotu Kola (Cen condition associated with decreased vaginal boundary lubri tella asiatica) or wherein said anti-inflammatory agent is one cation is vaginal atrophy, dyspareunia, Sjogren's syndrome, or more of Green tea (Camellia sinensis), Grape seed or Gotu menopause, androgen deficiency, estrogen deficiency, estro Kola (Centella asiatica) extracts, sodium carboxymethyl gen replacement therapy, allergy, chronic inflammation, betaglucan, Chondrus Chrispus, melissa, grape fruit, mango menopause, premature menopause, chemotherapy, breast seed, cranberry, cucumber, Salvia, chamomile, and aloe Vera feeding, Surgical removal of the ovaries before menopause, eXtractS. genital lichen Sclerosis, Vulvodynia, bacterial vaginosis, her 6. The composition of claim 1, wherein said acid pH con pes, candida, psoriasis, contact dermatitis, condylomata, or trol buffering system is lactic acid, Sodium dibasic hydrogen side effects of medications and aging. phosphate, sodium lactate, citric acid, or any combination 18. A method for preventing episiotomy or for treating thereof. tissue damages after episiotomy comprising administering a 7. The composition of claim 1, wherein the composition composition comprising an effective amount of a sulfated further comprises one or more of Saccharide isomerate as a polysaccharide and a pharmaceutically acceptable carrier, moisturizing agent, ethylenediaminetetraacetic acid (EDTA) wherein said composition is in a form for intravaginal appli as a chelating agent, and lubrasil DM hydrogel as a lubricant. cation, internal mucosal application, or both. 8. The composition of claim 1, wherein the composition 19. The method of claim 18, wherein if administered for further comprises one or more of extract of Chondrus Chris preventing episiotomy, the composition is administered for a pus, Xanthan gum, caprylhydroxamic acid, caprylyl glycol, week, two weeks, three weeks or a month before the date of glycerin, undecylenic acid, monoester of caprylic acid, allan delivery of a newborn. toin, an extract of any one of echinaccea, propolis, comfrey, 20. A method for preventing or treating vaginal damages, melissa, grapefruit, mango seed, cranberry, cucumber, green atrophy or dryness during and following chemotherapy and/ tea, Salvia, Chamomile, Geranium, lavender, lemon, juniper, or hormonal therapy for cancer patients treated with drugs clove bud, lotus, moringa, Grape seed or Gotu Kola (Centella that block estrogen receptors, lowering estrogen level or asiatica extracts) or any combination thereof. progesterone-based agents comprising administering a com 9. The composition of claim 1, further comprising chito position comprising an effective amount of a sulfated Sa. polysaccharide and a pharmaceutically acceptable carrier, 10. The composition of claim 1, wherein the sulfated wherein said composition is in a form for intravaginal appli polysaccharide is in an amount of 0.005-5% wt/wt of the cation, internal mucosal application, or both, wherein the Solution. hormonal therapy includes aromatase inhibitors. 11. The composition of claim 1, wherein the sulfated 21. The method of claim 16, wherein the sulfated polysac polysaccharide comprises a polymeric chain comprising at charide is derived from alga. least 4% glucuronic acid. 22. The method of claim 21, wherein the alga is a red 12. The composition of claim 1, wherein said composition microalga, green alga and/or a brown alga. further comprises one or more of an antimicrobial, an antivi k k k k k