WO2018203327A1 - Composition contenant de l'alcool phénéthylique destinée au traitement d'une infection par candida - Google Patents

Composition contenant de l'alcool phénéthylique destinée au traitement d'une infection par candida Download PDF

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Publication number
WO2018203327A1
WO2018203327A1 PCT/IL2018/050470 IL2018050470W WO2018203327A1 WO 2018203327 A1 WO2018203327 A1 WO 2018203327A1 IL 2018050470 W IL2018050470 W IL 2018050470W WO 2018203327 A1 WO2018203327 A1 WO 2018203327A1
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Prior art keywords
composition
composition according
treatment
infection
concentration
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PCT/IL2018/050470
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English (en)
Inventor
Shabtay Dikstein
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Resdevco Research And Development Co. Ltd.
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Publication of WO2018203327A1 publication Critical patent/WO2018203327A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics

Definitions

  • This invention rates in general to compositions and methods for prevention and treatment of infection by Candida. It relates specifically to compositions containing phenethylalcohol and polyols, and methods that incorporate the use of such compositions.
  • Yeasts of the genus Candida are generally regarded as the most common cause of fungal infection worldwide.
  • Candida infections are especially common in mucous membranes such as that of the vagina.
  • the most common current treatment of Candida infection is the use of topical or systemic antifungal agents such as amphotericin B, clotrimazole, echinocandins, fluconazole, nystatin, or voriconazole to kill the fungus.
  • Phenethyl alcohol (2-phenylethan-l-ol) has been reported to inhibit growth of C. albicans in vitro; see Lingappa, B. T.; Prasad, M.; Lingappa, Y.; Hunt, D. F.; Biemann, K. Science 1983, 163, 192, and Han, T.-L.; Tumanov, S.; Cannon, R. D.; Villas-Boas, S. G. PLoS ONE 2013, 8, e71364.
  • a family of patents assigned to Closure Medical one example of which is U.S. Pat. No. 6585967, lists phenethyl alcohol as an anti-fungal compound without specifying the dosage or treatment conditions.
  • Xylitol is known to have antimicrobial activity and can prevent colonization by harmful bacteria; see, for example, Eros, G.; Korponyai, C; Szabo, K.; Behany, Z.; Szel, Edit; Kemeny, L. Borgyogy. Vener. Szle. 2014, 90, 152.
  • U.S. Pat. Appl. Pub. No. 2006/0189701 discloses a method for treating bacterial infection by application of xylitol to an epithelial surface, thereby lowering its ionic strength and increasing its toxicity to bacteria.
  • 2006/0106117 discloses the treatment of vaginal infection by Gardnerella bacteria by application of xylitol. Treatment with xylitol was found to be ineffective against other bacteria, particularly Lactobacillus.
  • U.S. Pat. Appl. Pub. No. 2015/0265517 discloses composition for topical treatment of skin or mucosa that comprises a combination of xylitol and alginate.
  • Xylitol is also known to inhibit or eliminate growth of Candida.
  • Japanese Pat. Appl. No. 2000333973 discloses a dental adhesive that comprises 1.5 - 10% xylitol, which acts to prevent oral candidiasis.
  • compositions for topical treatment of vaginal Candida infections comprising a xylitol-containing material that rapidly forms a gel upon contact with ions naturally found in the vaginal mucosa.
  • Compositions containing 3 - 5% xylitol almost completely eliminated Candida from cultures in vitro.
  • U.S. Pat. No. 6414035 discloses the use of polyols such as xylitol to prevent growth of yeast such as Candida on mucosa of various orifices of the body.
  • the patent additionally discloses that orally administered xylitol can increase the effectiveness of other antifungal drugs, but that the additional benefit of topically administered xylitol is only seen at xylitol levels sufficiently high to show antifungal activity alone.
  • the present invention provides topical compositions that are effective for the prevention, treatment, or alleviation of yeast infection, particularly infection by Candida (candidiasis).
  • the primary active ingredients in the composition are phenethyl alcohol and xylitol.
  • the xylitol is present at a concentration that is too low to treat yeast or bacterial infection on its own. The combination of the effects of these two components provides an effective treatment for, and prevention of, infection by yeast such Candida, particularly when the yeast infection is accompanied by bacterial infection.
  • compositions for treatment, alleviation, or prevention of yeast infection wherein said composition comprises phenethyl alcohol, no more than 5% (w/v) xylitol, and optionally a preservative; and, said composition contains no additional antifungal agent other than said preservative.
  • said composition is for treatment, alleviation, or prevention of candidiasis.
  • said composition is for treatment, alleviation, or prevention of yeast infection accompanied by bacterial infection.
  • compositions as defined in any of the above, wherein said composition is characterized by a phenethyl alcohol concentration of between 0.2% and 1.2% (w/v). In some preferred embodiments of the invention, said composition is characterized by a phenethyl alcohol concentration of 1% (w/v). In some preferred embodiments of the invention, said composition is characterized by a phenethyl alcohol concentration of 0.5% (w/v).
  • compositions as defined in any of the above, wherein said composition is characterized by a xylitol concentration of no more than 3% (w/v). In some preferred embodiments of the invention, it is characterized by a xylitol concentration of between 0.5% and 3%. In some preferred embodiments of the composition, it is characterized by a xylitol concentration of between 1% and 3% (w/v). In some preferred embodiments of the composition, it is characterized by a xylitol concentration of no more than 1.5% (w/v).
  • composition as defined in any of the above, wherein said solution comprises glycerol.
  • said composition is characterized by a glycerol concentration of between 1% and 5% (w/v).
  • the composition is characterized by a xylitol concentration of between 1% and 3% (w/v) and a glycerol concentration of between 1% and 5% (w/v).
  • composition as defined in any of the above, wherein said composition comprises an isotonic aqueous solution.
  • composition as defined in any of the above, wherein said composition is characterized by a pH that is within a normal pH range of the tissue for which the use is intended.
  • the composition is characterized by a pH of between 6.5 and 7.6, and topical application of said composition to an eye is an effective treatment for infection of said eye by yeast that is accompanied by bacterial infection.
  • the composition is characterized by a pH of between 4.0 and 7.0, and topical application of said composition to skin is an effective treatment for a skin infection by yeast that is accompanied by bacterial infection.
  • the composition is characterized by a pH of between 3.5 and 4.5, and topical application of said composition to vaginal mucosa is an effective treatment for infection of said vaginal mucosa by yeast that is accompanied by bacterial infection.
  • composition as defined in any of the above, wherein said solution is characterized by an inorganic salt concentration of less than 0.1%.
  • composition as defined in any of the above, comprising at least one polymer characterized by a molecular weight of at least 10,000 Dalton.
  • said at least one polymer is characterized by a molecular weight of at least 100,000 Dalton.
  • said at least one polymer is present in a concentration chosen to bring said composition to a predetermined viscosity.
  • said at least one polymer is present in a concentration sufficient to produce a gel.
  • said at least one polymer is anionic.
  • said polymer is selected from the group consisting of hyaluronates, carbomers, and anionic polysaccharides.
  • said polymer is a sulfated polysaccharide.
  • composition as defined in any of the above, comprising a pharmaceutically effective amount of a pharmacologically active agent.
  • composition as defined in any of the above, comprising a substance selected from the group consisting of stabilizers, preservatives, antioxidants, and buffers.
  • compositions as defined in any of the above wherein said preparation is in the form of an aqueous solution.
  • said preparation is in the form of a water-based gel.
  • compositions as defined in any of the above in a method of treatment of a yeast infection, wherein said method of treatment comprises applying said composition topically to affected tissue.
  • said yeast infection is candidiasis.
  • yeast infection is accompanied by bacterial infection.
  • said method of treatment comprises applying said composition to an affected at least once weekly. In some embodiments of the invention, said method of treatment comprises applying said composition to an affected area 1 - 3 times daily. In some embodiments of the invention, said treatment comprises applying said composition to an affected area at least until a statistically significant reduction in yeast infection is observed.
  • composition as defined in any of the above, subject to the limitation that said composition is characterized by a pH of between 6.5 and 7.6, in a method of treatment of a yeast infection accompanied by bacterial infection, wherein said yeast infection accompanied by bacterial infection is an infection of an eye and said method of treatment comprises applying said composition topically to said eye.
  • composition as defined in any of the above, subject to the limitation that said composition is characterized by a pH of between 4.0 and 7.0, in a method of treatment of a yeast infection accompanied by bacterial infection, wherein said yeast infection accompanied by bacterial infection is a skin infection and said method of treatment comprises applying said composition topically to said skin.
  • compositions as defined in any of the above, subject to the limitation that said composition is characterized by a pH of between 3.5 and 4.5, in a method of treatment of a yeast infection accompanied by bacterial infection, wherein said yeast infection accompanied by bacterial infection is an infection of vaginal mucosa; and said method of treatment comprises applying said composition topically to said vaginal mucosa.
  • compositions as defined in any of the above in a method of prevention of yeast infection, wherein said method of prevention comprises applying said composition topically at least once weekly. In some embodiments of the invention, said method of prevention comprises applying said composition topically 1 - 3 times daily.
  • composition as defined in any of the above, subject to the limitation that said composition is characterized by a pH of between 6.5 and 7.6, in a method of prevention of yeast infection of an eye, wherein said method of prevention comprises applying said composition topically to an eye at least once weekly.
  • composition as defined in any of the above, subject to the limitation that said composition is characterized by a pH of between 4.0 and 7.0, in a method of treatment for prevention of yeast infection of skin, wherein said method of prevention comprises applying said composition topically to said skin at least once weekly.
  • composition as defined in any of the above, subject to the limitation that said composition is characterized by a pH of between 3.5 and 4.5, in a method for prevention of yeast infection of vaginal mucosa, wherein said method of treatment comprises applying said composition topically to vaginal mucosa at least once weekly.
  • said method is a method for treating a yeast infection of skin, said yeast infection accompanied by bacterial infection; said composition is characterized by a pH of between 4.0 and 7.0; and said step of applying comprises applying said composition topically to affected skin.
  • the acronym "PEA” and the term “phenethyl alcohol” are used interchangeably to refer to 2-phenylethan-l-ol (CAS number 60-12-8; EC number 200-456- 2).
  • the term “inorganic salt” is used to refer to a salt that comprises only inorganic ions. For example, salts of organic acids are not considered “inorganic salts” within the meaning of the term as it is used herein.
  • high molecular weight polymer is used to refer to a polymer having an average molecular weight of greater than 10 4 Dalton.
  • the term "effective treatment” refers to a treatment that produces a statistically significant reduction in the concentration of infectious agent in or on the affected tissue.
  • the invention disclosed herein provides a composition and method for treatment and prevention of yeast infection, particularly Candida infection.
  • the composition and method are particularly useful for treatment and prevention of yeast infection when the yeast infection is accompanied by bacterial infection.
  • the composition comprises a solution containing phenethyl alcohol and ⁇ 5% (w/v) xylitol.
  • Xylitol is known to be a good moisturizer and to prevent bacterial colonization.
  • it additionally comprises a preservative. Any preservative known in the art that is compatible with the other components of the composition and with the tissue to which the composition is to be applied may be used. While the preservative may itself have antifungal activity, in preferred embodiments, the composition does not include any antifungal agents other than PEA, polyol, or the preservative.
  • the solution comprises an aqueous solution containing between 0.2% and 1.2% phenethyl alcohol. In more preferred embodiments of the invention, the solution comprises 0.5% phenethyl alcohol (w/v).
  • the composition in some preferred embodiments of the invention in which the composition is to be applied to mucous membranes, it comprises an isotonic solution comprising xylitol; in these embodiments, the xylitol concentration is preferably not greater than 3% (w/v). In some preferred embodiments of the invention in which the composition is to be applied to mucous membranes, the xylitol concentration is between 0.5% and 3% (w/v). In some more preferred embodiments of the invention in which the composition is to be applied to mucous membranes, the xylitol concentration is between 1% and 3% (w/v).
  • the composition may be in the form of a liquid (preferably aqueous) solution or in the form of a water-based gel.
  • the composition comprises at least one polyol in addition to xylitol.
  • a polyol that can be included in the composition is glycerol, which is known to be a good moisturizer and prevents and/or diminishes irritation.
  • the glycerol concentration is between 1% and 5% (w/v).
  • the xylitol concentration is between 1% and 3% (w/v) and the glycerol concentration is between 1% and 5%.
  • the polyol concentration in the composition is too low to provide an effective treatment on its own for yeast or bacterial infection, particularly infection by Candida.
  • the xylitol concentration is ⁇ 1.5%.
  • the solution is characterized by an inorganic salt concentration of less than 2 mM. In some preferred embodiments of the invention, the solution is isotonic.
  • the viscosity of the solution may be controlled by addition of one or more high molecular weight polymers (MW > 10,000 Dalton).
  • the viscosity is controlled by a polymer selected from the group consisting of hyaluronate, carbomers, and anionic polysaccharides. If the polymer is anionic, then in the absence of added salt, the solution has the additional advantage of having a non-Newtonian viscosity profile.
  • the composition additionally comprises a pharmaceutically effective concentration of at least one pharmacologically active agent.
  • any stabilizer, preservative, antioxidant, buffer or combination thereof appropriate for use with the pharmacologically active agent may be added to the solution in any concentration suitable for the intended use.
  • the composition consists of an aqueous solution of phenethyl alcohol and xylitol, and optionally one or more ingredients selected from the group consisting of additional polyols, preservatives, pharmaceutically active agents, and viscosity-controlling agents.
  • the additional polyol is glycerol.
  • the viscosity-controlling agent comprises one or more high molecular weight polymers (MW > 10,000 Dalton).
  • Non-limiting examples of polymers that can be used in the composition include hyaluronate, carbomers, and anionic polysaccharides.
  • composition may be prepared according to standard procedures and transferred to and stored in a container appropriate for storing and/or dispensing it.
  • composition disclosed herein derives from the action of the phenethyl alcohol component to inhibit growth of Candida, and the simultaneous action of the polyol to inhibit bacterial growth.
  • the topical composition disclosed herein thus provides an effective treatment for Candida infections even though the active components are present in low concentrations.
  • the topical composition disclosed herein is applied to the affected region until the infection is reduced to an acceptable level.
  • the composition is applied to the affected region 1 - 3 times per day. Statistically significant reduction in Candida infection is typically observed within a month of the start of treatment.
  • the topical composition disclosed herein is applied regularly to a region of the body (e.g. the vagina, eyes, other mucous membranes, or skin) susceptible to Candida infection.
  • the topical composition disclosed herein is applied at least once weekly to a region of the body susceptible to Candida infection.
  • composition comprising an isotonic solution of phenethyl alcohol and xylitol, was prepared for treatment or prevention of ocular candidiasis:
  • composition was prepared for treatment or prevention of ocular candidiasis:
  • composition was prepared for treatment or prevention of Candida infection on the skin:
  • composition was prepared for treatment or prevention of Candida infection of the vagina:
  • composition was prepared for treatment or prevention of Candida infection of vaginal mucous membranes:
  • composition was prepared for treatment or prevention of Candida infection of vaginal mucous membranes:
  • composition was prepared for treatment or prevention of Candida infection of vaginal mucous membranes:
  • composition was prepared for treatment or prevention of Candida infection of vaginal mucous membranes:
  • the solution was adjusted to a pH of between 3.5 and 4.5. Preservative was added to some batches.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Urology & Nephrology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Ophthalmology & Optometry (AREA)
  • Inorganic Chemistry (AREA)
  • Reproductive Health (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une nouvelle composition destinée au traitement d'une infection par une levure, en particulier une infection par Candida. La composition comprend de l'alcool phénéthylique et au moins un polyol, de préférence du xylitol ou une combinaison de xylitol et de glycérol. L'invention concerne également des méthodes de prévention et de traitement d'infections par une levure et d'infections par une levure accompagnées d'une infection bactérienne à l'aide de la nouvelle composition.
PCT/IL2018/050470 2017-04-30 2018-04-30 Composition contenant de l'alcool phénéthylique destinée au traitement d'une infection par candida WO2018203327A1 (fr)

Applications Claiming Priority (2)

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US201762492190P 2017-04-30 2017-04-30
US62/492,190 2017-04-30

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WO2018203327A1 true WO2018203327A1 (fr) 2018-11-08

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Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000333973A (ja) 1999-05-28 2000-12-05 Lion Corp キシリトールを含有する義歯安定剤
US6414035B1 (en) 1997-12-01 2002-07-02 Xyrofin Oy Use of polyols in combating yeast infection and polyol preparations for said use
US6585967B2 (en) 2001-07-05 2003-07-01 Closure Medical Corporation Adhesive treatment for tinea cruris
US20060106117A1 (en) 2004-11-12 2006-05-18 Kimberly-Clark Worldwide, Inc. Compound and method for prevention and/or treatment of vaginal infections
US20060105963A1 (en) * 2004-11-12 2006-05-18 Kimberly-Clark Worldwide, Inc. Therapeutic agents for inhibiting and/or treating vaginal infection
US20060189701A1 (en) 2000-05-19 2006-08-24 University Of Iowa Research Foundation Use of xylitol to reduce ionic strength and activate endogenous antimicrobials for prevention and treatment of infections
US7786176B2 (en) 2005-07-29 2010-08-31 Kimberly-Clark Worldwide, Inc. Vaginal treatment composition containing xylitol
EP2545899A1 (fr) * 2010-07-08 2013-01-16 Obshchestvo S Ogranichennoj Otvetstvennost'yu "WDS" Composition pour la prévention de candidoses
WO2016057563A1 (fr) * 2014-10-08 2016-04-14 Pacific Northwest Diabetes Research Institute Procédés et compositions pour augmenter l'activité d'agents antifongiques
US20160331764A1 (en) * 2014-01-28 2016-11-17 Resdevco Research And Development Co. Ltd. Composition comprising xylitol and cholecalciferol for topical treatment of skin and mucous membranes
US20170021023A1 (en) * 2005-05-16 2017-01-26 Resdevco Research And Development Co. Ltd. Topical compositions for treatment of irritation of mucous membranes

Patent Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6414035B1 (en) 1997-12-01 2002-07-02 Xyrofin Oy Use of polyols in combating yeast infection and polyol preparations for said use
JP2000333973A (ja) 1999-05-28 2000-12-05 Lion Corp キシリトールを含有する義歯安定剤
US20060189701A1 (en) 2000-05-19 2006-08-24 University Of Iowa Research Foundation Use of xylitol to reduce ionic strength and activate endogenous antimicrobials for prevention and treatment of infections
US6585967B2 (en) 2001-07-05 2003-07-01 Closure Medical Corporation Adhesive treatment for tinea cruris
US7619008B2 (en) 2004-11-12 2009-11-17 Kimberly-Clark Worldwide, Inc. Xylitol for treatment of vaginal infections
US20060105963A1 (en) * 2004-11-12 2006-05-18 Kimberly-Clark Worldwide, Inc. Therapeutic agents for inhibiting and/or treating vaginal infection
US20060106117A1 (en) 2004-11-12 2006-05-18 Kimberly-Clark Worldwide, Inc. Compound and method for prevention and/or treatment of vaginal infections
US20170021023A1 (en) * 2005-05-16 2017-01-26 Resdevco Research And Development Co. Ltd. Topical compositions for treatment of irritation of mucous membranes
US7786176B2 (en) 2005-07-29 2010-08-31 Kimberly-Clark Worldwide, Inc. Vaginal treatment composition containing xylitol
EP2545899A1 (fr) * 2010-07-08 2013-01-16 Obshchestvo S Ogranichennoj Otvetstvennost'yu "WDS" Composition pour la prévention de candidoses
US20150265517A1 (en) 2010-07-08 2015-09-24 Obshchestvo S Ogranichennoj Otvetstvennost'yu "Wds" Composition for the prophylaxis of candidiasis
US20160331764A1 (en) * 2014-01-28 2016-11-17 Resdevco Research And Development Co. Ltd. Composition comprising xylitol and cholecalciferol for topical treatment of skin and mucous membranes
WO2016057563A1 (fr) * 2014-10-08 2016-04-14 Pacific Northwest Diabetes Research Institute Procédés et compositions pour augmenter l'activité d'agents antifongiques

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
EROS, G.; KORPONYAI, C.; SZABO, K.; BEHANY, Z.; SZEL, EDIT; KEMENY, L., BORGYOGY. VENER. SZLE., vol. 90, 2014, pages 152
HAN, T.-L.; TUMANOV, S.; CANNON, R. D.; VILLAS-BOAS, S. G., PLOS ONE, vol. 8, 2013, pages e71364
LINGAPPA, B. T.; PRASAD, M.; LINGAPPA, Y.; HUNT, D. F.; BIEMANN, K., SCIENCE, vol. 163, 1983, pages 192

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