WO2020150532A1 - Compositions et procédés pour la maîtrise et le traitement de candida auris - Google Patents

Compositions et procédés pour la maîtrise et le traitement de candida auris Download PDF

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WO2020150532A1
WO2020150532A1 PCT/US2020/013962 US2020013962W WO2020150532A1 WO 2020150532 A1 WO2020150532 A1 WO 2020150532A1 US 2020013962 W US2020013962 W US 2020013962W WO 2020150532 A1 WO2020150532 A1 WO 2020150532A1
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auris
chloride
phmb
weight
composition
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PCT/US2020/013962
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Bradley BURNAM
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Global Health Solutions Llc
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    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
    • 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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • A61K31/74—Synthetic polymeric materials
    • A61K31/785—Polymers containing nitrogen
    • 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
    • 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
    • A61K9/0031—Rectum, anus
    • 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
    • A61K9/0043—Nose
    • 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61K9/08—Solutions
    • 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
    • A61P31/10—Antimycotics

Definitions

  • the present disclosure is broadly concerned with compositions and methods for the control and treatment of Candida auris.
  • the disclosure is particularly concerned with the treatment of surfaces, mucous membranes, and the skin with compositions comprising polihexanide biguanide, also known as poly(hexamethylenebiguanide) hydrochloride (PHMB), and/or biguanide polyaminopropyl biguanide (PAPB), and or chlorhexidine gluconate (CHG).
  • polihexanide biguanide also known as poly(hexamethylenebiguanide) hydrochloride (PHMB), and/or biguanide polyaminopropyl biguanide (PAPB), and or chlorhexidine gluconate (CHG).
  • Candida auris is an emerging fungus which presents a serious global health threat according to the Centers for Disease Control and Prevention (CDC).
  • C. auris is one of the few species of the Candida genus which cause candidiasis in humans. Although C. auris was not described until 2009 and does not appear to have been previously a common colonizer of humans, C. auris is quickly becoming more common. For example, within just a few years in some international healthcare facilities, C. auris has emerged from being a relatively unknown pathogen to the cause of 40% of invasive Candida infections. C. auris can spread between patients in healthcare facilities and cause outbreaks. C. auris is frequently multidrug-resistant and can colonize a patient’s skin for months or longer.
  • C. auris can also live on surfaces for a month or more and conventional healthcare disinfection techniques appear to be inadequate in controlling C. auris in at least some instances. Accordingly, additional compositions and methods for the treatment and control of C. auris on surfaces, mucous membranes, and skin are desirable.
  • patients may be asymptomatically colonized with C. auris on skin, nares, oropharynx, rectum, and other body surfaces.
  • Patients colonized with C. auris can transmit C. auris to other patients, particularly within healthcare facilities, and may themselves be at risk for invasive C. auris infections.
  • Screening patients for C. auris colonization allows facilities to identify those patients with C. auris colonization and take remedial infection prevention and control measures. Therefore, there is a need for additional compositions and methods for decolonizing the skin, nares, oropharynx, rectum, and other body surfaces of subjects that are asymptomatically colonized with C. auris. Further, there is a need for additional pre treatment compositions and methods for preventing C. auris colonization or infection of body surfaces of subjects not yet colonized or infected by C. auris.
  • FIG. 1 depicts a graph showing the reduction of C. auris CDC AR #0381 test microorganisms according to a modified ASTM International Method El 153 test following administration of Formulation 1 of Example 1, according to an exemplary embodiment of the present disclosure.
  • FIG. 2 depicts a graph showing the reduction of C. auris CDC AR #0381 test microorganisms according to a modified ASTM International Method El 153 test following administration of Formulation 2 of Example 3, according to an exemplary embodiment of the present disclosure.
  • FIG. 3 depicts a graph showing the reduction of C. auris CDC AR #0381 test microorganisms according to a ASTM International Method E2315 test following administration of Formulation 2 of Example 3, according to an exemplary embodiment of the present disclosure.
  • FIG. 4 depicts a graph showing the reduction of C. auris CDC AR Bank #0384 test microorganisms according to a ASTM International Method E2315 test following administration of Formulation 2 of Example 3, according to an exemplary embodiment of the present disclosure.
  • FIG. 5 depicts a graph showing the reduction of C. auris CDC AR Bank #0385 test microorganisms according to a ASTM International Method E2315 test following administration of Formulation 2 of Example 3, according to an exemplary embodiment of the present disclosure.
  • FIG. 6 depicts a graph showing the reduction of C. auris CDC AR Bank #0386 test microorganisms according to a ASTM International Method E2315 test following administration of Formulation 2 of Example 3, according to an exemplary embodiment of the present disclosure.
  • FIG. 7 depicts a graph showing the reduction of C. auris CDC AR Bank #0389 test microorganisms according to a ASTM International Method E2315 test following administration of Formulation 2 of Example 3, according to an exemplary embodiment of the present disclosure.
  • FIG. 8 depicts a graph showing the reduction of C. auris CDC AR Bank #0390 test microorganisms according to a ASTM International Method E2315 test following administration of Formulation 2 of Example 3, according to an exemplary embodiment of the present disclosure.
  • FIG. 9 depicts CFU counts of longitudinal ear swabs from mice after topical association with high concentration inoculation.
  • FIG. 10 depicts CFU counts of longitudinal back swabs from mice after topical association with medium concentration inoculation.
  • FIG. 11 depicts CFU counts of longitudinal ear swabs from mice after topical associated with medium concentration inoculation.
  • FIG. 12 depicts CFU counts of ground ear tissue from mice after topical association at medium and high concentration inoculation at Day 10 of the study.
  • FIG. 13 depicts CFU counts of longitudinal back swabs from mice after topical association with high concentration inoculation in comparison to pre-treatment group.
  • the disclosure provides for compositions and methods for the treatment and control of C. auris in the skin and mucous membranes of a patient as well as for the treatment of surfaces colonized by C. auris.
  • composition comprising polihexanide biguanide (PHMB) for the topical treatment of mucous membranes or skin infected with Candida auris (C. auris) is provided.
  • PHMB polihexanide biguanide
  • the composition may include a pharmaceutically effective amount of PHMB, or from about 0.1% to about 5% by weight PHMB, or from about 0.1% to about 3.5% by weight PHMB, or from about 0.1% to about 2.5% by weight PHMB, or from about 0.5% to about 2.5% by weight PHMB, or from about 1.5% to about 2.5% by weight PHMB, from about 0.5% to about 3% by weight PHMB, or at least 1% by weight PHMB, or at least 2% by weight PHMB.
  • the composition may be an aqueous solution comprising PHMB, or a foam comprising PHMB, or an aerosol spray comprising PHMB, or a gel comprising PHMB, or a petrolatum-based composition comprising PHMB.
  • the aqueous solution may comprise ethanol.
  • PHMB is closely related to the polymeric biguanide polyaminopropyl biguanide (PAPB). Therefore, in at least some instances, a pharmaceutically effective amount of polyaminopropyl biguanide (PAPB) may be substituted for the pharmaceutically effective amount of PHMB in the presently disclosed compositions and methods.
  • PAPB polyaminopropyl biguanide
  • the composition may include from about 0.005% to about 5% by weight PAPB, or from about 0.01% to about 5% by weight PAPB, or from about 0.05% to about 5% by weight PAPB, or from about 0.05% to about 3% by weight PAPB, or from about 0.1% to about 1% by weight PAPB, or from about 0.2% to about 0.6% by weight PAPB, or from about 0.3% to about 0.5% by weight PAPB, or from about 0.1% to about 3.5% by weight PAPB, or from about 0.05% to about 2.5% by weight PAPB, or from about 0.5% to about 3% by weight PAPB, or from about 0.5% to about 2.5% by weight PAPB, or from about 1.5% to about 2.5% by weight PAPB.
  • the presently disclosed compositions may further include one or more quaternary ammonium compounds.
  • the presently disclosed compositions may include benzalkonium chloride (BZK), alkyl dimethyl benzyl ammonium chloride (ADBAC), cetrimide, benzethonium chloride (BZT), benzalkonium bromide, benzethonium bromide, benzalkonium fluoride, benzethonium fluoride, cetyl pyridinium chloride, alkylamidopropalkonium chloride, behenalkonium chloride, behentrimonium metho sulphate, behenamidopropylethyldimonium ethosulfate, stearalkonium chloride, olealkonium chloride, cetrimonium chloride, dequalinium chloride, and any combination thereof.
  • BZK benzalkonium chloride
  • ADBAC alkyl dimethyl benzyl ammonium chloride
  • BZT
  • the presently disclosed compositions may further include comprising chlorhexidine, also known as chlorhexidine gluconate (CHG).
  • the presently disclosed compositions may also include triclosan.
  • the presently disclosed compositions may also include a compound that stimulates healing such as TGF-alpha, TGF-beta (TGFpi, TGFP2, TGFP3), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor also referred to as keratinocyte growth factor (FGF1, FGF2, FGF4, FGF7), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), connective tissue growth factor (CTGF), activin, interleukin- 1 (IFla, IL1 b), TNFa, GM-CSF, and any combination thereof.
  • TGF-alpha TGF-beta
  • PDGF platelet-derived growth factor
  • EGF epidermal growth factor
  • the presently disclosed composition may be a petrolatum- based composition.
  • the petrolatum-based composition may comprises greater than about 80% by weight petrolatum, or greater than 90% by weight petrolatum, or greater than 95% by weight petrolatum.
  • the petrolatum-based PHMB compositions may include no emulsifier or exclude an added emulsifier.
  • the presently disclosed petrolatum-based PHMB compositions may include from about 0.1% to about 1% by weight PHMB, or from about 0.2% to about 0.6% by weight PHMB, or from about 0.3% to about 0.5% by weight PHMB.
  • the petrolatum-based PHMB compositions may also include at least one cationic biocide, such as, for example, benzalkonium chloride, cetrimide, chlorhexidine, and any combination thereof.
  • the presently disclosed petrolatum-based PHMB compositions may include from about 0.001% to about 0.01% by weight benzalkonium chloride (BZK), or from about 0.001% to about 0.15% by weight BZK, or from about 0.005% to about 0.007% by weight BZK.
  • the presently disclosed PHMB compositions may also be effective for the topical treatment of candidiasis, including when the candidiasis is caused by C. auris. In at least some instances, the presently disclosed compositions may be effective against multi-drug resistant C. auris.
  • the composition for the topical treatment of mucous membranes or skin infected with Candida auris may be a cationic biocide composition comprising one or more cationic biocides selected from the group consisting of polihexanide biguanide (PHMB), polyaminopropyl biguanide (PAPB), chlorhexidine (CHG), and any combination thereof.
  • the cationic biocide composition may be an aqueous solution comprising from about 0.1% to about 2.5% by weight of the one or more cationic biocides.
  • the aqueous solution may comprise ethanol.
  • the cationic biocide composition may be a petrolatum-based composition comprising from about 0.1% to about 2.5% by weight of the one or more cationic biocides and greater than about 90% by weight petrolatum.
  • a method of treating the skin of a patient infected with C. auris includes topical administration of any one of the presently disclosed PHMB compositions to the skin of the patient infected with C. auris.
  • a method of treating the mucous membranes of a patient infected with C. auris is also provided.
  • the method includes topical administration of any one of the presently disclosed PHMB compositions to the mucous membranes of the patient infected with C. auris.
  • the present disclosure further provides a method of treating candidiasis caused by C. auris in a patient in need thereof.
  • the method includes topical administration of a pharmaceutically effective amount of any of the presently disclosed PHMB compositions to the skin or mucous membrane of the patient in need of treatment.
  • the presently disclosed PHMB compositions are effective for the treatment of surfaces colonized by C. auris. In at least some instances, the presently disclosed compositions are effective for the control of C. auris on one or more surfaces upon topical application of the composition to the one or more surfaces. In such applications, the presently disclosed PHMB compositions may further include hydrogen peroxide, sodium hypochlorite, or any combination thereof.
  • a method of decolonizing a surface of a subject asymptomatically colonized with by Candida auris is provided.
  • the method may include topical administration of a cationic biocide composition to the surface of the subject, wherein the cationic biocide composition comprises one or more cationic biocides selected from the group consisting of polihexanide biguanide (PHMB), polyaminopropyl biguanide (PAPB), chlorhexidine (CHG), and any combination thereof.
  • the surface of the subject may be selected from the skin, the nares, and the rectum of the subject.
  • the C may be selected from the skin, the nares, and the rectum of the subject.
  • auris may be multi-drug resistant C. auris.
  • the cationic biocide composition may be an aqueous solution comprising from about 0.1% to about 2.5% by weight of the one or more cationic biocides.
  • the cationic biocide composition is a petrolatum-based composition comprising from about 0.1% to about 2.5% by weight of the one or more cationic biocides and greater than about 90% by weight petrolatum.
  • the cationic biocide composition may also comprise from about 0.5% to about 1.5% by weight of at least one additional anti-fungal agent selected from the group consisting of terbinafine HC1, ciclopirox, ciclopirox olamine, fluconazole, itraconazole, ketoconazole, amorolfine, efinaconazole, clotrimazole, miconazole (miconazole nitrate), and any combination thereof.
  • additional anti-fungal agent selected from the group consisting of terbinafine HC1, ciclopirox, ciclopirox olamine, fluconazole, itraconazole, ketoconazole, amorolfine, efinaconazole, clotrimazole, miconazole (miconazole nitrate), and any combination thereof.
  • the cationic biocide composition may further include one or more quaternary ammonium compounds selected from the group consisting of benzalkonium chloride (BZK), alkyl dimethyl benzyl ammonium chloride (ADBAC), cetrimide, benzethonium chloride (BZT), benzalkonium bromide, benzethonium bromide, benzalkonium fluoride, benzethonium fluoride, cetyl pyridinium chloride, alkylamidopropalkonium chloride, behenalkonium chloride, behentrimonium metho sulphate, behenamidopropylethyldimonium ethosulfate, stearalkonium chloride, olealkonium chloride, cetrimonium chloride, dequalinium chloride, and any combination thereof.
  • the cationic biocide composition may also include from about 0.001% to about 0.15% by weight benzalkonium chloride (BZK), al
  • a method of preventing colonization or infection by Candida auris (C. auris) of a portion of the skin or mucous membrane of a subject may include pre-treating the portion of the skin or mucous membrane in need of treatment by topical administration of a cationic biocide composition to the skin or mucous membrane.
  • the cationic biocide composition may include one or more cationic biocides selected from the group consisting of polihexanide biguanide (PHMB), polyaminopropyl biguanide (PAPB), chlorhexidine (CHG), and any combination thereof.
  • the method may include topical administration of the cationic biocide composition to the nares of a subject. In other instances, the method may include topical administration of the cationic biocide composition to the skin or rectum of the patient. In at least some instances, the C. auris may be multi-drug resistant C. auris.
  • the cationic biocide composition used in the method may be an aqueous solution comprising from about 0.1% to about 2.5% by weight of the one or more cationic biocides.
  • the cationic biocide composition is a petrolatum-based composition comprising from about 0.1% to about 2.5% by weight of the one or more cationic biocides and greater than about 90% by weight petrolatum.
  • the cationic biocide composition may also comprise from about 0.5% to about 1.5% by weight of at least one additional anti- fungal agent selected from the group consisting of terbinafine HC1, ciclopirox, ciclopirox olamine, fluconazole, itraconazole, ketoconazole, amorolfine, efinaconazole, clotrimazole, miconazole (miconazole nitrate), and any combination thereof.
  • additional anti- fungal agent selected from the group consisting of terbinafine HC1, ciclopirox, ciclopirox olamine, fluconazole, itraconazole, ketoconazole, amorolfine, efinaconazole, clotrimazole, miconazole (miconazole nitrate), and any combination thereof.
  • the cationic biocide composition may further include one or more quaternary ammonium compounds selected from the group consisting of benzalkonium chloride (BZK), alkyl dimethyl benzyl ammonium chloride (ADBAC), cetrimide, benzethonium chloride (BZT), benzalkonium bromide, benzethonium bromide, benzalkonium fluoride, benzethonium fluoride, cetyl pyridinium chloride, alkylamidopropalkonium chloride, behenalkonium chloride, behentrimonium metho sulphate, behenamidopropylethyldimonium ethosulfate, stearalkonium chloride, olealkonium chloride, cetrimonium chloride, dequalinium chloride, and any combination thereof.
  • the cationic biocide composition may also include from about 0.001% to about 0.15% by weight benzalkonium chloride (BZK), al
  • Formulation 1 was prepared by mixing a 20% polihexanide biguanide, also known as poly(hexamethylenebiguanide) hydrochloride (PHMB), solution (Cosmocil CQ), and water to form a 2% PHMB aqueous solution.
  • PHMB poly(hexamethylenebiguanide) hydrochloride
  • Example 2 Efficacy of Formulation 1 of Example 1 on Candida auris ( C . auris)
  • Example 1 A study was conducted on the formulation of Example 1, referred to herein as “Formulation 1” to assess efficacy to treat or control C. auris.
  • ASTM International Standard Test Method El 153 was used as a quantitative test method to assess the antimicrobial effectiveness of Formulation 1 as a sanitizer on pre-cleaned inanimate, non-porous, non-food contact surfaces.
  • C. auris CDC AR Bank #0381 test organism was cultured to produce a test culture. Sterilized carriers were inoculated with a volume of the test culture and inoculated slides were dried in an incubator. Only completely dried carriers were used in the test.
  • Control carriers were harvested following the dry time to determining the initial inoculation concentration. Test carriers were treated with the test substance and incubated for the predetermined contact time. At the conclusion of the contact time, test carriers were chemically neutralized. Dilutions of the neutralized test substance were evaluated using appropriate growth media to determine the surviving microorganisms at the respective contact time. The effect of the test substance was compared to the effect of the control substance in order to determine microbial reductions.
  • Formulation 1 is effective in killing C. auris under the conditions of the test. As a result, it is expected that Formulation 1 is effective in the treatment and control of C. auris on surfaces as well as in the topical treatment of mucous membranes or skin infected with C. auris.
  • Formulation 2 was prepared by adding 2540.3 pounds of white petrolatum to a tank that has been cleaned and sterilized in accordance with SOP protocol. In the tank was used to heat the petrolatum to 110°C to 113°F to melt the petrolatum. In a separate clean and sanitized container 133.70 pounds of water and the desired amount of BZK and PHMB were added and heated to 122°F. When both phases were at temperature, the solution phase was slowly added to the petrolatum with mixing. The heat was decreased slowly to 96 to 104°F. The product was tested for quality control and transferred to polypropylene drums. The resulting composition was shiny and white to slightly yellow in appearance.
  • Example 4 Efficacy of Formulation 2 of Example 3 on Candida auris (C. auris ) CDC AR Bank #0381
  • Example 3 A study was conducted on the formulation of Example 3, referred to herein as“Formulation 2” to assess efficacy to treat or control C. auris.
  • ASTM International Standard Test Method El 153 was used as a quantitative test method to assess the antimicrobial effectiveness of Formulation 1 as a sanitizer on pre-cleaned inanimate, non-porous, non-food contact surfaces.
  • C. auris CDC AR Bank #0381 test organism was cultured to produce a test culture. Sterilized carriers were inoculated with a volume of the test culture and inoculated slides were dried in an incubator. Only completely dried carriers were used in the test.
  • Control carriers were harvested following the dry time to determining the initial inoculation concentration. Test carriers were treated with the test substance and incubated for the predetermined contact time. At the conclusion of the contact time, test carriers were chemically neutralized. Dilutions of the neutralized test substance were evaluated using appropriate growth media to determine the surviving microorganisms at the respective contact time. The effect of the test substance was compared to the effect of the control substance in order to determine microbial reductions.
  • Formulation 1 is effective in killing C. auris CDC Bank AR #0381 under the conditions of the test. As a result, it is expected that Formulation 1 is effective in the treatment and control of C. auris on surfaces as well as in the topical treatment of mucous membranes or skin infected with C. auris.
  • Example 5 Efficacy of Formulation 2 of Example 3 on Candida auris (C. auri ) CDC AR Bank #0381 Inoculated Vitro Skin
  • Example 3 A study was conducted on the formulation of Example 3, referred to herein as“Formulation 2” to assess efficacy to treat or control C. auris on skin.
  • ASTM International Standard Test Method El 153 was used as a quantitative test method to assess the antimicrobial effectiveness of Formulation 2 on inoculated vitro skin that was incubated at body temperature (37°C).
  • C. auris CDC AR Bank #0381 test organism was cultured to produce a test culture.
  • Vitro skin carriers were inoculated with a volume of the test culture and inoculated vitro skin was incubated at 37°C. Control carriers were harvested following the incubation period to determine the initial inoculation concentration.
  • Test vitro skin carriers were treated with the test substance and incubated at 37°C for the predetermined contact time. At the conclusion of the contact time, test vitro skin carriers were chemically neutralized. Dilutions of the neutralized test substance were evaluated using appropriate growth media to determine the surviving microorganisms at the respective contact time. The effect of the test substance was compared to the effect of the control substance in order to determine microbial reductions.
  • Formulation 2 is effective in killing C. auris CDC AR Bank #0381 under the conditions of the vitro skin test. As a result, it is expected that Formulation 2 is effective in the treatment and control of C. auris on skin as well as in the topical treatment of mucous membranes or skin infected with C. auris.
  • Example 6 Efficacy of Formulation 2 of Example 3 on Candida auris ( C . auris ) CDC AR Bank #0381
  • Example 3 A study was conducted on the formulation of Example 3, referred to herein as“Formulation 2” to assess efficacy to treat or control C. auris.
  • ASTM International Standard Test Method E2315 was used as a quantitative test method to assess the antimicrobial activity of Formulation 2 against C. auris using a time-kill procedure in an antimicrobial liquid suspension.
  • C. auris CDC AR Bank #0381 test organism was cultured to produce a test culture. The suspension of test microorganisms was standardized, as needed, by dilution in a buffered saline solution. Test and control substances were dispensed in identical volumes to sterile vessels.
  • test and control substances were inoculated with each test microorganism, then mixed and incubated. Control substances were immediately harvested and represent the concentration present at the start of the test, or time zero. At the conclusion of the contact time, a volume of the liquid test solution was harvested and chemically neutralized. Dilutions of the neutralized test solution were assayed using appropriate growth media to determine the surviving microorganisms at the respective contact times. Reductions of microorganisms were calculated by comparing initial microbial concentrations to final microbial concentrations. Enumeration plates were incubated for 72-120 hours. No additional growth or re-colonization was observed after this period. [0048] The results of the test are shown in Table 6 and FIG. 3. The Percent reduction was determined according to the following formula:
  • B the number of viable test microorganisms in the control substance immediately after inoculation
  • A the number of viable test microorganisms in the test substance after the contact time.
  • Formulation 2 is effective in killing C. auris CDC AR Bank #0381 under the conditions of the test. As a result, it is expected that Formulation 2 is effective in the treatment and control of C. auris on surfaces as well as in the topical treatment of mucous membranes or skin infected with C. auris.
  • Example 7 Efficacy of Formulation 2 of Example 3 on Candida auris ( C . auris ) CDC AR Bank #0384
  • Example 3 A study was conducted on the formulation of Example 3, referred to herein as“Formulation 2” to assess efficacy to treat or control C. auris.
  • ASTM International Standard Test Method E2315 was used as a quantitative test method to assess the antimicrobial activity of Formulation 2 against C. auris using a time-kill procedure in an antimicrobial liquid suspension.
  • C. auris CDC AR Bank #0384 test organism was cultured to produce a test culture. The suspension of test microorganisms was standardized, as needed, by dilution in a buffered saline solution. Test and control substances were dispensed in identical volumes to sterile vessels.
  • test and control substances were inoculated with each test microorganism, then mixed and incubated. Control substances were immediately harvested and represent the concentration present at the start of the test, or time zero. At the conclusion of the contact time, a volume of the liquid test solution was harvested and chemically neutralized. Dilutions of the neutralized test solution were assayed using appropriate growth media to determine the surviving microorganisms at the respective contact times. Reductions of microorganisms were calculated by comparing initial microbial concentrations to final microbial concentrations. Enumeration of plates was performed after -48 hours incubation. No additional growth or re-colonization was observed after this period.
  • the control substance was phosphate-buffered saline (PBS).
  • the culture growth media and plating media used was potato dextrose agar and the culture dilution media used was PBS.
  • the inoculum concentration was >1.0 x 10 6 CFU/mL and the contact time was 8, 16, and 24 hours. 9 mL of D/E broth was used as the neutralizer.
  • the contact temperature was ⁇ 25°C ⁇ 2°C (ambient) and the enumeration plate incubation temperature was 28°C ⁇ 2°C.
  • the inoculum volume was 0.100 mL and the volume harvested was 1.0 mL
  • B equals the number of viable test microorganisms in the control substance immediately after inoculation and A equals the number of viable test microorganisms in the test substance after the contact time.
  • B equals the number of viable test microorganisms in the control substance immediately after inoculation
  • A equals the number of viable test microorganisms in the test substance after the contact time.
  • Formulation 2 is effective in killing C. auris CDC AR Bank #0384 under the conditions of the test.
  • Formulation 2 is effective in the treatment and control of C. auris on surfaces as well as in the topical treatment of mucous membranes or skin infected with C. auris.
  • Example 8 Efficacy of Formulation 2 of Example 3 on Candida auris ( C . auris ) CDC AR Bank #0385
  • Example 3 A study was conducted on the formulation of Example 3, referred to herein as“Formulation 2” to assess efficacy to treat or control C. auris.
  • ASTM International Standard Test Method E2315 was used as a quantitative test method to assess the antimicrobial activity of Formulation 2 against C. auris using a time-kill procedure in an antimicrobial liquid suspension.
  • C. auris CDC AR Bank #0385 test organism was cultured to produce a test culture. The suspension of test microorganisms was standardized, as needed, by dilution in a buffered saline solution. Test and control substances were dispensed in identical volumes to sterile vessels.
  • test and control substances were inoculated with each test microorganism, then mixed and incubated. Control substances were immediately harvested and represent the concentration present at the start of the test, or time zero. At the conclusion of the contact time, a volume of the liquid test solution was harvested and chemically neutralized. Dilutions of the neutralized test solution were assayed using appropriate growth media to determine the surviving microorganisms at the respective contact times. Reductions of microorganisms were calculated by comparing initial microbial concentrations to final microbial concentrations. Enumeration of plates was performed after -48 hours incubation. No additional growth or re-colonization was observed after this period.
  • the control substance was phosphate-buffered saline (PBS).
  • the culture growth media and plating media used was potato dextrose agar and the culture dilution media used was PBS.
  • the inoculum concentration was >1.0 x 10 6 CFU/mF and the contact time was 8, 16, and 24 hours. 9 mL of D/E broth was used as the neutralizer.
  • the contact temperature was ⁇ 25°C ⁇ 2°C (ambient) and the enumeration plate incubation temperature was 28°C ⁇ 2°C.
  • the inoculum volume was 0.100 mL and the volume harvested was 1.0 mL
  • Formulation 2 is effective in killing C. auris CDC AR Bank #0385 under the conditions of the test. As a result, it is expected that Formulation 2 is effective in the treatment and control of C. auris on surfaces as well as in the topical treatment of mucous membranes or skin infected with C. auris.
  • Example 9 Efficacy of Formulation 2 of Example 3 on Candida auris ( C . auris ) CDC AR Bank #0386
  • Example 3 A study was conducted on the formulation of Example 3, referred to herein as“Formulation 2” to assess efficacy to treat or control C. auris.
  • ASTM International Standard Test Method E2315 was used as a quantitative test method to assess the antimicrobial activity of Formulation 2 against C. auris using a time-kill procedure in an antimicrobial liquid suspension.
  • C. auris CDC AR Bank #0386 test organism was cultured to produce a test culture. The suspension of test microorganisms was standardized, as needed, by dilution in a buffered saline solution. Test and control substances were dispensed in identical volumes to sterile vessels.
  • test and control substances were inoculated with each test microorganism, then mixed and incubated. Control substances were immediately harvested and represent the concentration present at the start of the test, or time zero. At the conclusion of the contact time, a volume of the liquid test solution was harvested and chemically neutralized. Dilutions of the neutralized test solution were assayed using appropriate growth media to determine the surviving microorganisms at the respective contact times. Reductions of microorganisms were calculated by comparing initial microbial concentrations to final microbial concentrations. Enumeration of plates was performed after -48 hours incubation. No additional growth or re-colonization was observed after this period.
  • the control substance was phosphate-buffered saline (PBS).
  • the culture growth media and plating media used was potato dextrose agar and the culture dilution media used was PBS.
  • the inoculum concentration was >1.0 x 10 6 CFU/mF and the contact time was 8, 16, and 24 hours. 9 mL of D/E broth was used as the neutralizer.
  • the contact temperature was - 25°C ⁇ 2°C (ambient) and the enumeration plate incubation temperature was 28°C ⁇ 2°C.
  • the inoculum volume was 0.100 mL and the volume harvested was 1.0 mL
  • Formulation 2 is effective in killing C. auris CDC AR Bank #0386 under the conditions of the test. As a result, it is expected that Formulation 2 is effective in the treatment and control of C. auris on surfaces as well as in the topical treatment of mucous membranes or skin infected with C. auris.
  • Example 10 Efficacy of Formulation 2 of Example 3 on Candida auris ( C . auris ) CDC AR Bank #0389
  • Example 3 A study was conducted on the formulation of Example 3, referred to herein as“Formulation 2” to assess efficacy to treat or control C. auris.
  • ASTM International Standard Test Method E2315 was used as a quantitative test method to assess the antimicrobial activity of Formulation 2 against C. auris using a time-kill procedure in an antimicrobial liquid suspension.
  • C. auris CDC AR Bank #0389 test organism was cultured to produce a test culture. The suspension of test microorganisms was standardized, as needed, by dilution in a buffered saline solution. Test and control substances were dispensed in identical volumes to sterile vessels.
  • test and control substances were inoculated with each test microorganism, then mixed and incubated. Control substances were immediately harvested and represent the concentration present at the start of the test, or time zero. At the conclusion of the contact time, a volume of the liquid test solution was harvested and chemically neutralized. Dilutions of the neutralized test solution were assayed using appropriate growth media to determine the surviving microorganisms at the respective contact times. Reductions of microorganisms were calculated by comparing initial microbial concentrations to final microbial concentrations. Enumeration of plates was performed after -48 hours incubation. No additional growth or re-colonization was observed after this period.
  • the control substance was phosphate-buffered saline (PBS).
  • the culture growth media and plating media used was potato dextrose agar and the culture dilution media used was PBS.
  • the inoculum concentration was >1.0 x 10 6 CFU/mF and the contact time was 8, 16, and 24 hours. 9 mL of D/E broth was used as the neutralizer.
  • the contact temperature was - 25°C ⁇ 2°C (ambient) and the enumeration plate incubation temperature was 28°C ⁇ 2°C.
  • the inoculum volume was 0.100 mL and the volume harvested was 1.0 mL
  • B equals the number of viable test microorganisms in the control substance immediately after inoculation and A equals the number of viable test microorganisms in the test substance after the contact time.
  • B equals the number of viable test microorganisms in the control substance immediately after inoculation
  • A equals the number of viable test microorganisms in the test substance after the contact time.
  • Formulation 2 is effective in killing C. auris CDC AR Bank #0389 under the conditions of the test.
  • Formulation 2 is effective in the treatment and control of C. auris on surfaces as well as in the topical treatment of mucous membranes or skin infected with C. auris.
  • Example 11 Efficacy of Formulation 2 of Example 3 on Candida auris ( C . auris ) CDC AR Bank #0390
  • Example 3 A study was conducted on the formulation of Example 3, referred to herein as“Formulation 2” to assess efficacy to treat or control C. auris.
  • ASTM International Standard Test Method E2315 was used as a quantitative test method to assess the antimicrobial activity of Formulation 2 against C. auris using a time-kill procedure in an antimicrobial liquid suspension.
  • C. auris CDC AR Bank #0390 test organism was cultured to produce a test culture. The suspension of test microorganisms was standardized, as needed, by dilution in a buffered saline solution. Test and control substances were dispensed in identical volumes to sterile vessels.
  • test and control substances were inoculated with each test microorganism, then mixed and incubated. Control substances were immediately harvested and represent the concentration present at the start of the test, or time zero. At the conclusion of the contact time, a volume of the liquid test solution was harvested and chemically neutralized. Dilutions of the neutralized test solution were assayed using appropriate growth media to determine the surviving microorganisms at the respective contact times. Reductions of microorganisms were calculated by comparing initial microbial concentrations to final microbial concentrations. Enumeration of plates was performed after -48 hours incubation. No additional growth or re-colonization was observed after this period.
  • the control substance was phosphate-buffered saline (PBS).
  • the culture growth media and plating media used was potato dextrose agar and the culture dilution media used was PBS.
  • the inoculum concentration was >1.0 x 10 6 CFU/mF and the contact time was 8, 16, and 24 hours. 9 mL of D/E broth was used as the neutralizer.
  • the contact temperature was - 25°C ⁇ 2°C (ambient) and the enumeration plate incubation temperature was 28°C ⁇ 2°C.
  • the inoculum volume was 0.100 mL and the volume harvested was 1.0 mL
  • B equals the number of viable test microorganisms in the control substance immediately after inoculation and A equals the number of viable test microorganisms in the test substance after the contact time.
  • B equals the number of viable test microorganisms in the control substance immediately after inoculation
  • A equals the number of viable test microorganisms in the test substance after the contact time.
  • Formulation 2 is effective in killing C. auris CDC AR Bank #0390 under the conditions of the test.
  • Formulation 2 is effective in the treatment and control of C. auris on surfaces as well as in the topical treatment of mucous membranes or skin infected with C. auris.
  • Example 12 Efficacy of Topical Administration of Formulation 2 of Example 3 on the Decolonization of Candida auris ( C . auris) from Skin and Ear Surfaces in a Subject using a Mouse Model
  • Example 3 A study was conducted on the formulation of Example 3, referred to herein as“Formulation 2” to assess efficacy to cause the decolonization of C. auris from the skin and other surfaces of a patient or subject.
  • a mouse model was used in which the back of the mouse was shaved 5 days prior to inoculation with C. auris. Skin corresponding to the shaved back as well as the ears of the mouse were inoculated with C. auris on Day 0 in order to cause colonization of the skin and ears of the mouse.
  • mice When mice are inoculated in such a manner, generally the mouse surfaces substantially decolonize with respect to C. auris within 3-10 days when left untreated.
  • the mice were inoculated with either a medium concentration inoculation corresponding to lxlO 7 cells/mouse or a high concentration inoculation corresponding to lxlO 9 cells/mouse.
  • the skin and ear surfaces of the mouse were either treated with a saline saturated gauze as a control or with topical administration of Formulation 2 of Example 3 every other day, (i.e., on Days 1, 3, 5, and 7).
  • the ears and back of the mice were swabbed on Days 3, 5, 7, and 10.
  • tissue samples corresponding to the treated ear and back were obtained and ground.
  • the swabs and ground tissue were plated to determine colony forming units (CFU) per swab (CFU/swab) or CFU/g for the ground tissue samples.
  • FIG. 9 depicts CFU counts of longitudinal ear swabs from mice after topical association with high concentration inoculation. As shown in FIG. 9, topical administration of Formulation 2 resulted in lower CFU/swab on Days 3 and 5 as compared to the control treatment and likely resulted in earlier substantially complete decolonization of the ear as compared to the control (based on extrapolation from the results of Days 5 and 7).
  • FIG. 10 depicts CFU counts of longitudinal back swabs from mice after topical association with medium concentration inoculation. As shown in FIG. 10, treatment with formulation 2 resulted in significantly reduced colonization of back skin as compared to the treatment control on Days 3, 5, and 7.
  • FIG. 9 depicts CFU counts of longitudinal ear swabs from mice after topical association with high concentration inoculation. As shown in FIG. 9, topical administration of Formulation 2 resulted in lower CFU/swab on Days 3 and 5 as compared to the control treatment and likely resulted in earlier substantially complete decolonization of the
  • FIG. 11 depicts CFU counts of longitudinal ear swabs from mice after topical associated with medium concentration inoculation. As shown in FIG. 11, treatment with formulation 2 resulted in significantly reduced colonization of the mice ear on Days 3, 7, and 9 (but not day 5) as compared to the control treatment. Treatment with formulation 2 also resulted in substantial decolonization of the mouse ear by Day 7, while the treatment control did not result in substantial decolonization by Day 9.
  • FIG. 12 depicts CFU counts of ground ear tissue from mice after topical association at medium and high concentration inoculation at Day 10 of the study. As shown in FIG. 12, treatment with formulation 2 resulted in a significant decrease in colonization of C.
  • mice ears that were inoculated with the medium concentration inoculation there was little difference between the control treatment and treatment with formulation 2 after 10 days as both treatments resulted in few CFUs/g as compared with the results from the high concentration inoculation group.
  • Formulation 2 of Example 3 resulted in greater decolonization by C. auris and a faster rate of decolonization (e.g., less number of days for decolonization) than the control treatment.
  • a faster rate of decolonization e.g., less number of days for decolonization
  • topical administration of Formulation 2 is effective in the decolonization of C. auris on animal surfaces such as mucous membranes or skin infected with C. auris.
  • Example 13 Efficacy of Topical Administration of Formulation 2 of Example 3 on the Prevention of Colonization by Candida auris ( C . auris) from Skin Surfaces in a Subject using a Mouse Model
  • Example 2 A study was conducted on the formulation of Example 3, referred to herein as“Formulation 2” to assess efficacy to cause the decolonization of C. auris from the skin and other surfaces of a patient or subject.
  • a mouse model was used similar to the study presented in Example 12. The back of eight mice were shaved 5 days prior to inoculation with C. auris. One day after shaving, the shaved back skin of four mice corresponding to the pre-treatment group were pretreated with formulation 2 by topical administration of formulation 2 to the back skin. Formulation 2 was reapplied daily to the back skin of the pre-treatment group for three additional days.
  • Formulation 3 was prepared by mixing polyaminopropyl biguanide
  • PAPB PAPB
  • Formulation 4 was prepared by adding 2540.3 pounds of white petrolatum to a tank that has been cleaned and sterilized in accordance with SOP protocol. In the tank was used to heat the petrolatum to 110°C to 113°F to melt the petrolatum. In a separate clean and sanitized container 133.70 pounds of water and the desired amount of BZK and PAPB were added and heated to 122°F. When both phases were at temperature, the solution phase was slowly added to the petrolatum with mixing. The heat was decreased slowly to 96 to 104°F. The product was tested for quality control and transferred to polypropylene drums. The resulting composition was shiny and white to slightly yellow in appearance.
  • Formulation 5 was prepared by mixing chlorhexidine (CHG) and water to form a 2% Chlorhexidine (CHG) aqueous solution.
  • Formulation 6 was prepared by adding 2540.3 pounds of white petrolatum to a tank that has been cleaned and sterilized in accordance with SOP protocol. In the tank was used to heat the petrolatum to 110°C to 113°F to melt the petrolatum. In a separate clean and sanitized container 133.70 pounds of water and the desired amount of BZK and Chlorhexidine were added and heated to 122°F. When both phases were at temperature, the solution phase was slowly added to the petrolatum with mixing. The heat was decreased slowly to 96 to 104°F. The product was tested for quality control and transferred to polypropylene drums. The resulting composition was shiny and white to slightly yellow in appearance.
  • Example 18 Topical Administration of PHMB Compositions Improves Clinical Outcomes in Subjects Having Skin Infection Caused by C. auris
  • the effect of topical administration of the presently disclosed PHMB compositions in the treatment of human subjects having skin infection caused by C. auris will be studied using a randomized, double-blind clinical study.
  • a group of human subjects will be topically administered one of the presently disclosed PHMB compositions including, but not limited to, Formulation 1 and Formulation 2.
  • the PHMB composition will be applied to a portion of the skin of a subject having or otherwise affected by C. auris.
  • Subjects receiving treatment using the presently disclosed PHMB compositions are expected to have improved standard clinical outcomes.
  • subjects receiving treatment according to the presently disclosed methods and techniques are expected to exhibit a reduced rate of occurrence of C.
  • Example 19 Topical Administration of PHMB Compositions Improves Clinical Outcomes in Subjects Having Infection of Mucous Membranes Caused by C. auris
  • the effect of topical administration of the presently disclosed PHMB compositions in the treatment of human subjects having a mucous membrane infection caused by C. auris will be studied using a randomized, double-blind clinical study.
  • a group of human subjects will be topically administered one of the presently disclosed PHMB compositions including, but not limited to, Formulation 1 and Formulation 2.
  • the PHMB composition will be applied to a portion of the mucous membranes of a subject having or otherwise affected by C. auris.
  • Subjects receiving treatment using the presently disclosed PHMB compositions are expected to have improved standard clinical outcomes.
  • subjects receiving treatment according to the presently disclosed methods and techniques are expected to exhibit a reduced rate of occurrence of C. auris in the portion of the mucous membrane receiving treatment as well as reduced clinical signs of C. auris infection.
  • Example 20 Topical Administration of PHMB Compositions Improves Clinical Outcomes in Subjects Having Candidiasis Caused by C. auris
  • the effect of topical administration of the presently disclosed PHMB compositions in the treatment of human subjects having candidiasis caused by C. auris will be studied using a randomized, double-blind clinical study.
  • a group of human subjects will be topically administered one of the presently disclosed PHMB compositions including, but not limited to, Formulation 1 and Formulation 2.
  • the PHMB composition will be applied to a portion of the subject having or otherwise affected by candidiasis.
  • Subjects receiving treatment using the presently disclosed PHMB compositions are expected to have improved standard clinical outcomes.
  • subjects receiving treatment according to the presently disclosed methods and techniques are expected to exhibit a reduced rate of occurrence of candidiasis in the portion of the mucous membrane receiving treatment as well as reduced clinical signs of candidiasis.
  • Example 21. Topical Administration of PHMB Compositions Improves Clinical Outcomes in Decolonization of C. auris from Nares, Skin, Rectum, or Other Surface in a Subject
  • the effect of topical administration of the presently disclosed PHMB compositions in the treatment of human subjects asymptomatically colonized with C. auris on the nares, skin, or rectum will be studied using a randomized, double-blind clinical study.
  • a group of human subjects will be topically administered one of the presently disclosed PHMB compositions including, but not limited to, Formulation 1 and Formulation 2.
  • the PHMB composition will be applied to the skin, nares, rectum, or other surface of the subject that has been asymptomatically colonized by C. auris.
  • Subjects receiving treatment using the presently disclosed PHMB compositions are expected to have improved standard clinical outcomes.
  • subjects receiving treatment according to the presently disclosed methods and techniques are expected to exhibit one or more of the following clinical outcomes: reduced colonization of the treated surface, substantial decolonization of the treated surface, or achieve faster decolonization of the treated surface.
  • Example 22 Topical Administration of PHMB Compositions as Pre-Treatment to the Nares, Skin, Rectum, or Other Surface of a Subject Improves Clinical Outcomes in Reducing Colonization or Infection by C. auris
  • PHMB compositions As a Pre-Treatment of human subjects not yet infected or colonized with C. auris on will be studied using a randomized, double-blind clinical study.
  • a group of human subjects not yet infected or colonized with C. auris will be topically administered one of the presently disclosed PHMB compositions including, but not limited to, Formulation 1 and Formulation 2.
  • the PHMB composition will be applied to the skin, nares, rectum, or other surface of the subject that has not been colonized or infected with C. auris.
  • Subjects receiving the pre-treatment using the presently disclosed PHMB compositions are expected to have improved standard clinical outcomes.
  • subjects receiving pre-treatment according to the presently disclosed methods and techniques are expected to exhibit one or more of the following clinical outcomes following exposure to C. auris : reduced colonization of the treated surface, substantially delayed colonization of the treated surface, reduced infection by C. auris of the treated surface, or achieve faster decolonization of the treated surface.
  • Example 23. Topical Administration of PAPB Compositions Improves Clinical Outcomes in Subjects Having Skin Infection Caused by C. auris
  • the effect of topical administration of the presently disclosed PAPB compositions in the treatment of human subjects having skin infection caused by C. auris will be studied using a randomized, double-blind clinical study.
  • a group of human subjects will be topically administered one of the presently disclosed PAPB compositions including, but not limited to, Formulation 3 and Formulation 4.
  • the PAPB composition will be applied to a portion of the skin of a subject having or otherwise affected by C. auris.
  • Subjects receiving treatment using the presently disclosed PAPB compositions are expected to have improved standard clinical outcomes.
  • subjects receiving treatment according to the presently disclosed methods and techniques are expected to exhibit a reduced rate of occurrence of C. auris in the portion of the skin receiving treatment as well as reduced clinical signs of C. auris infection.
  • Example 24 Topical Administration of PAPB Compositions Improves Clinical Outcomes in Subjects Having Infection of Mucous Membranes Caused by C. auris
  • the effect of topical administration of the presently disclosed PAPB compositions in the treatment of human subjects having a mucous membrane infection caused by C. auris will be studied using a randomized, double-blind clinical study.
  • a group of human subjects will be topically administered one of the presently disclosed PAPB compositions including, but not limited to, Formulation 3 and Formulation 4.
  • the PAPB composition will be applied to a portion of the mucous membranes of a subject having or otherwise affected by C. auris.
  • Subjects receiving treatment using the presently disclosed PAPB compositions are expected to have improved standard clinical outcomes.
  • subjects receiving treatment according to the presently disclosed methods and techniques are expected to exhibit a reduced rate of occurrence of C.
  • Example 25 Topical Administration of PAPB Compositions Improves Clinical Outcomes in Subjects Having Candidiasis Caused by C. auris
  • the effect of topical administration of the presently disclosed PAPB compositions in the treatment of human subjects having candidiasis caused by C. auris will be studied using a randomized, double-blind clinical study.
  • a group of human subjects will be topically administered one of the presently disclosed PAPB compositions including, but not limited to, Formulation 3 and Formulation 4.
  • the PAPB composition will be applied to a portion of the subject having or otherwise affected by candidiasis.
  • Subjects receiving treatment using the presently disclosed PAPB compositions are expected to have improved standard clinical outcomes.
  • subjects receiving treatment according to the presently disclosed methods and techniques are expected to exhibit a reduced rate of occurrence of candidiasis in the portion of the mucous membrane receiving treatment as well as reduced clinical signs of candidiasis.
  • Example 26 Topical Administration of PAPB Compositions Improves Clinical Outcomes in Decolonization of C. auris from Nares, Skin, Rectum, or Other Surface in a Subject
  • subjects receiving treatment according to the presently disclosed methods and techniques are expected to exhibit one or more of the following clinical outcomes: reduced colonization of the treated surface, substantial decolonization of the treated surface, or achieve faster decolonization of the treated surface.
  • Example 27. Topical Administration of PAPB Compositions as Pre-Treatment to the Nares, Skin, Rectum, or Other Surface of a Subject Improves Clinical Outcomes in Reducing Colonization or Infection by C. auris
  • PAPB compositions As a Pre-Treatment of human subjects not yet infected or colonized with C. auris on will be studied using a randomized, double-blind clinical study.
  • a group of human subjects not yet infected or colonized with C. auris will be topically administered one of the presently disclosed PAPB compositions including, but not limited to, Formulation 3 and Formulation 4.
  • the PAPB composition will be applied to the skin, nares, rectum, or other surface of the subject that has not been colonized or infected with C. auris.
  • Subjects receiving the pre-treatment using the presently disclosed PAPB compositions are expected to have improved standard clinical outcomes.
  • subjects receiving pre-treatment according to the presently disclosed methods and techniques are expected to exhibit one or more of the following clinical outcomes following exposure to C. auris : reduced colonization of the treated surface, substantially delayed colonization of the treated surface, reduced infection by C. auris of the treated surface, or achieve faster decolonization of the treated surface.
  • Example 28 Topical Administration of Chlorhexidine (CHG) Compositions Improves Clinical Outcomes in Subjects Having Skin Infection Caused by C. auris
  • the effect of topical administration of the presently disclosed CHG compositions in the treatment of human subjects having skin infection caused by C. auris will be studied using a randomized, double-blind clinical study.
  • a group of human subjects will be topically administered one of the presently disclosed CHG compositions including, but not limited to, Formulation 5 and Formulation 6.
  • the CHG composition will be applied to a portion of the skin of a subject having or otherwise affected by C. auris.
  • Subjects receiving treatment using the presently disclosed CHG compositions are expected to have improved standard clinical outcomes.
  • subjects receiving treatment according to the presently disclosed methods and techniques are expected to exhibit a reduced rate of occurrence of C.
  • Example 29 Topical Administration of CHG Compositions Improves Clinical Outcomes in Subjects Having Infection of Mucous Membranes Caused by C. auris
  • the effect of topical administration of the presently disclosed CHG compositions in the treatment of human subjects having a mucous membrane infection caused by C. auris will be studied using a randomized, double-blind clinical study.
  • a group of human subjects will be topically administered one of the presently disclosed CHG compositions including, but not limited to, Formulation 5 and Formulation 6.
  • the CHG composition will be applied to a portion of the mucous membranes of a subject having or otherwise affected by C. auris.
  • Subjects receiving treatment using the presently disclosed CHG compositions are expected to have improved standard clinical outcomes.
  • subjects receiving treatment according to the presently disclosed methods and techniques are expected to exhibit a reduced rate of occurrence of C. auris in the portion of the mucous membrane receiving treatment as well as reduced clinical signs of C. auris infection.
  • Example 30 Topical Administration of CHG Compositions Improves Clinical Outcomes in Subjects Having Candidiasis Caused by C. auris
  • subjects receiving treatment according to the presently disclosed methods and techniques are expected to exhibit a reduced rate of occurrence of candidiasis in the portion of the mucous membrane receiving treatment as well as reduced clinical signs of candidiasis.
  • Example 31. Topical Administration of CHG Compositions Improves Clinical Outcomes in Decolonization of C. auris from Nares, Skin, Rectum, or Other Surface in a Subject
  • Example 32 Topical Administration of CHG Compositions as Pre-Treatment to the Nares, Skin, Rectum, or Other Surface of a Subject Improves Clinical Outcomes in Reducing Colonization or Infection by C. auris
  • subjects receiving pre-treatment according to the presently disclosed methods and techniques are expected to exhibit one or more of the following clinical outcomes following exposure to C. auris : reduced colonization of the treated surface, substantially delayed colonization of the treated surface, reduced infection by C. auris of the treated surface, or achieve faster decolonization of the treated surface.
  • Statement 1 A composition comprising polihexanide biguanide (PHMB) for the topical treatment of mucous membranes or skin infected with Candida auris (C. auris).
  • PHMB polihexanide biguanide
  • Statement 2 The composition according to Statement 1, wherein the C. auris is multi drug resistant C. auris.
  • Statement 3 The composition according to Statement 1 or Statement 2, wherein the composition is an aqueous solution comprising PHMB.
  • Statement 4 The composition according to Statement 1 or Statement 2, wherein the composition is a foam comprising PHMB.
  • Statement 5 The composition according to Statement 1 or Statement 2, wherein the composition is a gel comprising PHMB.
  • Statement 6 The composition according to Statement 1 or Statement 2, wherein the composition is an aerosol spray comprising PHMB.
  • Statement 7 The composition according to Statement 1 or Statement 2, wherein the composition is a petrolatum-based composition comprising PHMB.
  • Statement 8 The composition according to any one of the preceding Statements 1-7, wherein the composition comprises a pharmaceutically effective amount of PHMB.
  • Statement 9 The composition according to any one of the preceding Statements 1-8, where in the composition comprises from about 0.1% to about 5% by weight PHMB.
  • Statement 10 The composition according to any one of the preceding Statements 1-8, wherein the composition comprises from about 0.1% to about 3.5% by weight PHMB.
  • Statement 11 The composition according to any one of the preceding Statements 1-8, wherein the composition comprises from about 0.1% to about 2.5% by weight PHMB.
  • Statement 12 The composition according to any one of the preceding Statements 1-8, wherein the composition comprises from about 0.5% to about 2.5% by weight PHMB.
  • Statement 13 The composition according to any one of the preceding Statements 1-8, wherein the composition comprises from about 1.5% to about 2.5% by weight PHMB.
  • Statement 14 The composition according to any one of the preceding Statements 1-8, wherein the composition comprises from about 0.5% to about 3% by weight PHMB.
  • Statement 15 The composition according to any one of the preceding Statements 1-8, wherein the composition comprises at least 1% by weight PHMB.
  • Statement 16 The composition according to any one of the preceding Statements 1-8, wherein the composition comprises at least 2% by weight PHMB.
  • Statement 17 The composition according to any one of the preceding Statements 1-16, further comprising one or more quaternary ammonium compounds.
  • Statement 18 The composition according to Statement 17, wherein the one or more quaternary ammonium compounds is selected from the group consisting of benzalkonium chloride (BZK), alkyl dimethyl benzyl ammonium chloride (ADBAC), cetrimide, benzethonium chloride (BZT), benzalkonium bromide, benzethonium bromide, benzalkonium fluoride, benzethonium fluoride, cetyl pyridinium chloride, alkylamidopropalkonium chloride, behenalkonium chloride, behentrimonium metho sulphate, behenamidopropylethyldimonium ethosulfate, stearalkonium chloride, olealkonium chloride, cetrimonium chloride, dequalinium chloride, and any combination thereof.
  • BZK benzalkonium chloride
  • ADBAC alkyl dimethyl benzyl ammonium chloride
  • BZT benz
  • Statement 19 The composition according to any one of the preceding Statements 1-18, further comprising chlorhexidine (chlorhexidine gluconate).
  • Statement 20 The composition according to any one of the preceding Statements 1-19, further comprising triclosan.
  • Statement 21 The composition according to any one of the preceding Statements 1-20, further comprising sodium hypochlorite.
  • Statement 22 The composition according to any one of the preceding Statements 1-21, further comprising hydrogen peroxide.
  • Statement 23 The composition according to any one of the preceding Statements 1-22, further comprising a compound that stimulates healing.
  • Statement 24 The composition according to Statement 23, wherein the compound that stimulates healing is selected from the group consisting of collagen and growth factors such as TGF-alpha, TGF-beta (TGFpl, TGFp2, TGFp3), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor also referred to as keratinocyte growth factor (FGF1, FGF2, FGF4, FGF7), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), connective tissue growth factor (CTGF), activin, interleukin- 1 (ILla, IL1 b), TNFa, GM-CSF, and any combination thereof.
  • TGF-alpha TGF-beta
  • PDGF platelet-derived growth factor
  • EGF epidermal growth factor
  • FGF1, FGF2, FGF4, FGF7 fibroblast growth factor also referred to as keratinocyte growth factor (FGF1, FGF2, FGF4, FGF7)
  • VEGF
  • Statement 26 The composition according to Statement 7, wherein the petrolatum- based composition comprises greater than about 90% by weight petrolatum.
  • Statement 27 The composition according to Statement 7, wherein the petrolatum- based composition comprises greater than about 95% by weight petrolatum.
  • Statement 28 The composition according to any one of the preceding Statements 7 and 25-27, wherein the petrolatum-based composition contains no emulsifier.
  • Statement 29 The composition according to any one of the preceding Statements 7 and 25-27, wherein the petrolatum-based composition excludes an added emulsifier.
  • Statement 30 The composition according to any one of the preceding Statements 7 and 25-29, wherein the petrolatum-based composition comprises from about 0.1% to about 1% by weight polihexanide biguanide (PHMB).
  • PHMB polihexanide biguanide
  • Statement 31 The composition according to any one of the preceding Statements 7 and 25-29, wherein the petrolatum-based composition comprises from about 0.2% to about 0.6% by weight polihexanide biguanide (PHMB).
  • PHMB polihexanide biguanide
  • Statement 32 The composition according to any one of the preceding Statements 7 and 25-29, wherein the petrolatum-based composition comprises from about 0.3% to about 0.5% by weight polihexanide biguanide (PHMB).
  • PHMB polihexanide biguanide
  • Statement 33 The composition according to any one of the preceding Statements 7 and 25-32, further comprising at least one cationic biocide.
  • Statement 34 The composition according to Statement 33, wherein the cationic biocide is selected from the group consisting of benzalkonium chloride, cetrimide, chlorhexidine, and any combination thereof.
  • Statement 35 The composition according to any one of the preceding Statements 7 and 25-34, wherein the petrolatum-based composition comprises from about 0.001% to about 0.15% by weight benzalkonium chloride (BZK).
  • BZK benzalkonium chloride
  • Statement 36 The composition according to any one of the preceding Statements 7 and 25-34, wherein the petrolatum-based composition comprises from about 0.001% to about 0.01% by weight or from about 0.005% to about 0.007% by weight benzalkonium chloride (BZK).
  • Statement 37 The composition according to any one of the preceding Statements 7 and 25-36, wherein the petrolatum-based composition comprises less than about 1% by weight cationic biocide.
  • Statement 38 The composition according to any one of the preceding Statements 7 and 25-37, wherein the petrolatum-based composition further comprises a compound that stimulates healing.
  • Statement 39 The composition according to Statement 38, wherein the compound that stimulates healing is selected from the group consisting of collagen and growth factors such as TGF-alpha, TGF-beta (TGFpl, TGFp2, TGFp3), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor also referred to as keratinocyte growth factor (FGF1, FGF2, FGF4, FGF7), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), connective tissue growth factor (CTGF), activin, interleukin- 1 (ILla, IL1 b), TNFa, GM-CSF, and any combination thereof.
  • TGF-alpha TGF-beta
  • PDGF platelet-derived growth factor
  • EGF epidermal growth factor
  • FGF1, FGF2, FGF4, FGF7 fibroblast growth factor also referred to as keratinocyte growth factor (FGF1, FGF2, FGF4, FGF7)
  • Statement 40 A composition comprising polihexanide biguanide (PHMB) for the topical treatment of candidiasis, wherein the candidiasis is caused by Candida auris (C. auris).
  • PHMB polihexanide biguanide
  • Statement 41 The composition according to Statement 40, wherein the candidiasis is localized to one or more mucous membranes.
  • Statement 42 The composition according to Statement 40, wherein the candidiasis is localized to the skin of a subject.
  • Statement 43 The composition according to any one of the preceding Statements 40-
  • Statement 44 The composition according to any one of the preceding Statements 40-
  • composition is an aqueous solution comprising PHMB.
  • Statement 45 The composition according to any one of the preceding Statements 40- 43, wherein the composition is a foam comprising PHMB.
  • Statement 46 The composition according to any one of the preceding Statements 40- 43, wherein the composition is a gel comprising PHMB.
  • Statement 47 The composition according to any one of the preceding Statements 40- 43, wherein the composition is an aerosol spray comprising PHMB.
  • Statement 48 The composition according to any one of the preceding Statements 40- 43, wherein the composition is a petrolatum-based composition comprising PHMB.
  • Statement 49 The composition according to any one of the preceding Statements 40-
  • composition comprises a pharmaceutically effective amount of PHMB.
  • Statement 50 The composition according to any one of the preceding Statements 40-
  • composition comprises from about 0.1% to about 5% by weight PHMB.
  • Statement 51 The composition according to any one of the preceding Statements 40- 49, wherein the composition comprises from about 0.1% to about 3.5% by weight PHMB.
  • Statement 52 The composition according to any one of the preceding Statements 40- 49, wherein the composition comprises from about 0.1% to about 2.5% by weight PHMB.
  • Statement 53 The composition according to any one of the preceding Statements 40- 49, wherein the composition comprises from about 0.5% to about 2.5% by weight PHMB.
  • Statement 54 The composition according to any one of the preceding Statements 40- 49, wherein the composition comprises from about 1.5% to about 2.5% by weight PHMB.
  • Statement 55 The composition according to any one of the preceding Statements 40- 49, wherein the composition comprises from about 0.5% to about 3% by weight PHMB.
  • Statement 56 The composition according to any one of the preceding Statements 40- 49, wherein the composition comprises at least 1% by weight PHMB.
  • Statement 57 The composition according to any one of the preceding Statements 40- 49, wherein the composition comprises at least 2% by weight PHMB.
  • Statement 58 The composition according to any one of the preceding Statements 40- 57, further comprising one or more quaternary ammonium compounds.
  • Statement 59 The composition according to Statement 58, wherein the one or more quaternary ammonium compounds is selected from the group consisting of benzalkonium chloride (BZK), alkyl dimethyl benzyl ammonium chloride (ADBAC), cetrimide, benzethonium chloride (BZT), benzalkonium bromide, benzethonium bromide, benzalkonium fluoride, benzethonium fluoride, cetyl pyridinium chloride, alkylamidopropalkonium chloride, behenalkonium chloride, behentrimonium metho sulphate, behenamidopropylethyldimonium ethosulfate, stearalkonium chloride, olealkonium chloride, cetrimonium chloride, dequalinium chloride, and any combination thereof.
  • BZK benzalkonium chloride
  • ADBAC alkyl dimethyl benzyl ammonium chloride
  • Statement 60 The composition according to any one of the preceding Statements 40-
  • chlorhexidine chlorhexidine gluconate
  • Statement 61 The composition according to any one of the preceding Statements 40-
  • Statement 62 The composition according to any one of the preceding Statements 40-
  • Statement 63 The composition according to any one of the preceding Statements 40-
  • Statement 64 The composition according to any one of the preceding Statement 40-
  • Statement 65 The composition according to Statement 64, wherein the compound that stimulates healing is selected from the group consisting of collagen and growth factors such as TGF-alpha, TGF-beta (TGFpl, TGFp2, TGFp3), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor also referred to as keratinocyte growth factor (FGF1, FGF2, FGF4, FGF7), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), connective tissue growth factor (CTGF), activin, interleukin- 1 (ILla, IL1 b), TNFa, GM-CSF, and any combination thereof.
  • TGF-alpha TGF-beta
  • PDGF platelet-derived growth factor
  • EGF epidermal growth factor
  • FGF1, FGF2, FGF4, FGF7 fibroblast growth factor also referred to as keratinocyte growth factor (FGF1, FGF2, FGF4, FGF7)
  • Statement 66 The composition according to Statement 48, wherein the petrolatum- based composition comprises greater than about 80% by weight petrolatum.
  • Statement 67 The composition according to Statement 48, wherein the petrolatum- based composition comprises greater than about 90% by weight petrolatum.
  • Statement 68 The composition according to Statement 48, wherein the petrolatum- based composition comprises greater than about 95% by weight petrolatum.
  • Statement 69 The composition according to any one of the preceding Statements 48 and 66-68, wherein the petrolatum-based composition contains no emulsifier.
  • Statement 70 The composition according to any one of the preceding Statements 48 and 66-68, wherein the petrolatum-based composition excludes an added emulsifier.
  • Statement 71 The composition according to any one of the preceding Statements 48 and 66-70, wherein the petrolatum-based composition comprises from about 0.1% to about 1% by weight polihexanide biguanide (PHMB).
  • PHMB polihexanide biguanide
  • Statement 72 The composition according to any one of the preceding Statements 48 and 66-70, wherein the petrolatum-based composition comprises from about 0.2% to about 0.6% by weight polihexanide biguanide (PHMB).
  • PHMB polihexanide biguanide
  • Statement 73 The composition according to any one of the preceding Statements 48 and 66-70, wherein the petrolatum-based composition comprises from about 0.3% to about 0.5% by weight polihexanide biguanide (PHMB).
  • Statement 74 The composition according to any one of the preceding Statements 48 and 66-73, further comprising at least one cationic biocide.
  • Statement 75 The composition according to Statement 74, wherein the cationic biocide is selected from the group consisting of benzalkonium chloride, cetrimide, chlorhexidine, and any combination thereof.
  • Statement 76 The composition according to any one of the preceding Statements 48 and 66-75, wherein the petrolatum-based composition comprises from about 0.001% to about 0.15% by weight benzalkonium chloride (BZK).
  • BZK benzalkonium chloride
  • Statement 77 The composition according to any one of the preceding Statements 48 and 66-75, wherein the petrolatum-based composition comprises from about 0.001% to about 0.01% by weight or from about 0.005% to about 0.007% by weight benzalkonium chloride (BZK).
  • BZK benzalkonium chloride
  • Statement 78 The composition according to any one of the preceding Statements 48 and 66-75, wherein the petrolatum-based composition comprises less than about 1% by weight cationic biocide.
  • Statement 79 The composition according to any one of the preceding Statements 48 and 66-78, wherein the petrolatum-based composition further comprises a compound that stimulates healing.
  • Statement 80 The composition according to Statement 79, wherein the compound that stimulates healing is selected from the group consisting of collagen and growth factors such as TGF-alpha, TGF-beta (TGFpl, TGFp2, TGFp3), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor also referred to as keratinocyte growth factor (FGF1, FGF2, FGF4, FGF7), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), connective tissue growth factor (CTGF), activin, interleukin- 1 (ILla, IL1 b), TNFa, GM-CSF, and any combination thereof.
  • TGF-alpha TGF-beta
  • PDGF platelet-derived growth factor
  • EGF epidermal growth factor
  • FGF1, FGF2, FGF4, FGF7 fibroblast growth factor also referred to as keratinocyte growth factor (FGF1, FGF2, FGF4, FGF7)
  • Statement 81 A method of treating the skin of a patient infected with Candida auris (C. auris), the method comprising topical administration of the composition according to any one of Statements 1-80 to the skin of the patient infected with C. auris.
  • Statement 82 A method of treating the mucous membranes of a patient infected with Candida auris (C. auris), the method comprising topical administration of the composition according to any one of Statements 1-80 to the mucous membranes of the patient infected with C. auris.
  • Statement 83 The method according to Statement 81 or Statement 82, wherein the C. auris is multi-drug resistant C. auris.
  • Statement 84 A method of treating candidiasis caused by Candida auris (C. auris) in a patient in need thereof, the method comprising topical administration of a pharmaceutically effective amount of the composition according to any one of Statements 1-80 to the skin or mucous membrane of the patient in need of treatment.
  • Statement 85 The method according to Statement 84, wherein the C. auris is multi drug resistant C. auris.
  • Statement 86 The method according to Statement 84 or claim 85, wherein the candidiasis is localized to one or more mucous membranes.
  • Statement 87 The method according to Statement 84 or Statement 85, wherein the candidiasis is localized to the skin of the patient.
  • Statement 88 A composition comprising polihexanide biguanide (PHMB) for the treatment of surfaces colonized by Candida auris (C. auris).
  • PHMB polihexanide biguanide
  • Statement 89 The composition according to Statement 88, wherein the composition is effective for the control of C. auris on one or more surfaces upon topical application of the composition to the one or more surfaces.
  • Statement 90 The composition according to Statement 88 or Statement 89, wherein the C. auris is multi-drug resistant C. auris.
  • Statement 91 The composition according to any one of Statements 88-90, wherein the composition is an aqueous solution comprising PHMB.
  • Statement 92 The composition according to any one of Statements 88-90, wherein the composition is a foam comprising PHMB.
  • Statement 93 The composition according to any one of Statements 88-90, wherein the composition is a gel comprising PHMB.
  • Statement 94 The composition according to any one of Statements 88-90, wherein the composition is an aerosol spray comprising PHMB.
  • Statement 95 The composition according to any one of Statements 88-90, wherein the composition is a petrolatum-based composition comprising PHMB.
  • Statement 96 The composition according to any one of Statements 88-95, wherein the composition comprises from about 0.1% to about 5% by weight PHMB.
  • Statement 97 The composition according to any one of Statements 88-95, wherein the composition comprises from about 0.1% to about 3.5% by weight PHMB.
  • Statement 98 The composition according to any one of Statements 88-95, wherein the composition comprises from about 0.1% to about 2.5% by weight PHMB.
  • Statement 99 The composition according to any one of Statements 88-95, wherein the composition comprises from about 0.5% to about 2.5% by weight PHMB.
  • Statement 100 The composition according to any one of Statements 88-95, wherein the composition comprises from about 1.5% to about 2.5% by weight PHMB.
  • Statement 101 The composition according to any one of Statements 88-95, wherein the composition comprises from about 0.5% to about 3% by weight PHMB.
  • Statement 102 The composition according to any one of Statements 88-95, wherein the composition comprises at least 1% by weight PHMB.
  • Statement 103 The composition according to any one of Statements 88-95, wherein the composition comprises at least 2% by weight PHMB.
  • Statement 104 The composition according to any one of Statements 88-103, further comprising one or more quaternary ammonium compounds.
  • Statement 105 The composition according to Statement 104, wherein the one or more quaternary ammonium compounds is selected from the group consisting of benzalkonium chloride (BZK), alkyl dimethyl benzyl ammonium chloride (ADBAC), cetrimide, benzethonium chloride (BZT), benzalkonium bromide, benzethonium bromide, benzalkonium fluoride, benzethonium fluoride, cetyl pyridinium chloride, alkylamidopropalkonium chloride, behenalkonium chloride, behentrimonium metho sulphate, behenamidopropylethyldimonium ethosulfate, stearalkonium chloride, olealkonium chloride, cetrimonium chloride, dequalinium chloride, and any combination thereof.
  • BZK benzalkonium chloride
  • ADBAC alkyl dimethyl benzyl ammonium chloride
  • Statement 106 The composition according to any one of Statements 88-105, further comprising chlorhexidine (chlorhexidine gluconate).
  • Statement 107 The composition according to any one of Statements 88-106, further comprising triclosan.
  • Statement 108 The composition according to any one of Statements 88-107, further comprising sodium hypochlorite.
  • Statement 109 The composition according to any one of Statements 88-108, further comprising hydrogen peroxide.
  • Statement 110 The composition according to Statement 95, wherein the petrolatum- based composition comprises greater than about 80% by weight petrolatum.
  • Statement 111 The composition according to Statement 95, wherein the petrolatum- based composition comprises greater than about 90% by weight petrolatum.
  • Statement 112 The composition according to Statement 95, wherein the petrolatum- based composition comprises greater than about 95% by weight petrolatum.
  • Statement 113 The composition according to any one of the preceding Statements 95 and 110-112, wherein the petrolatum-based composition contains no emulsifier.
  • Statement 114 The composition according to any one of the preceding Statements 95 and 110-112, wherein the petrolatum-based composition excludes an added emulsifier.
  • Statement 115 The composition according to any one of the preceding Statements 95 and 110-114, wherein the petrolatum-based composition comprises from about 0.1% to about 1% by weight polihexanide biguanide (PHMB).
  • PHMB polihexanide biguanide
  • Statement 116 The composition according to any one of the preceding Statements 95 and 110-114, wherein the petrolatum-based composition comprises from about 0.2% to about 0.6% by weight polihexanide biguanide (PHMB).
  • PHMB polihexanide biguanide
  • Statement 117 The composition according to any one of the preceding Statements 95 and 110- 114, wherein the petrolatum-based composition comprises from about 0.3% to about 0.5% by weight polihexanide biguanide (PHMB).
  • PHMB polihexanide biguanide
  • Statement 118 The composition according to any one of the preceding Statements 95 and 110-117, further comprising at least one cationic biocide.
  • Statement 119 The composition according to Statement 118, wherein the cationic biocide is selected from the group consisting of benzalkonium chloride, cetrimide, chlorhexidine, and any combination thereof.
  • Statement 120 The composition according to any one of the preceding Statements 95 and 110-119, wherein the petrolatum-based composition comprises from about 0.001% to about 0.15% by weight benzalkonium chloride (BZK).
  • BZK benzalkonium chloride
  • Statement 121 The composition according to any one of the preceding Statements 95 and 110-119, wherein the petrolatum-based composition comprises from about 0.001% to about 0.01% by weight or from about 0.005% to about 0.007% by weight benzalkonium chloride (BZK).
  • Statement 122 The composition according to any one of the preceding Statements 95 and 110-119, wherein the petrolatum-based composition comprises less than about 1% by weight cationic biocide.
  • Statement 123 A method for the treatment of one or more surfaces colonized by Candida auris (C. auris), the method comprising topical application of the composition according to any one of Statements 88-122 to the one or more surfaces.
  • Statement 124 A method for the control of Candida auris (C. auris) in a hospital or healthcare setting, the method comprising topical application of the composition according to any one of Statements 88-122 to the one or more surfaces in the hospital or healthcare setting.
  • Statement 125 The method according to Statement 123 or Statement 124, wherein the C. auris is multi-drug resistant C. auris.
  • Statement 126 The method according to any one of Statements 123-125, wherein the C. auris is resistant to one or more quaternary ammonium compounds.
  • Statement 127 The method according to any one of Statements 123-126, wherein the C. auris is resistant to chlorhexidine (chlorhexidine gluconate).
  • Statement 128 The method according to any one of Statements 123-127, wherein the C. auris is resistant to triclosan.
  • Statement 129 The method according to any one of Statements 123-128, wherein the composition further comprises at least one additional anti-fungal agent selected from the group consisting of terbinafine HC1, ciclopirox, ciclopirox olamine, fluconazole, itraconazole, ketoconazole, amorolfine, efinaconazole, clotrimazole, miconazole (miconazole nitrate), and any combination thereof.
  • additional anti-fungal agent selected from the group consisting of terbinafine HC1, ciclopirox, ciclopirox olamine, fluconazole, itraconazole, ketoconazole, amorolfine, efinaconazole, clotrimazole, miconazole (miconazole nitrate), and any combination thereof.
  • Statement 130 The method according to any one of Statements 81-87, wherein the composition further comprises at least one additional anti-fungal agent selected from the group consisting of terbinafine HC1, ciclopirox, ciclopirox olamine, fluconazole, itraconazole, ketoconazole, amorolfine, efinaconazole, clotrimazole, miconazole (miconazole nitrate), and any combination thereof.
  • additional anti-fungal agent selected from the group consisting of terbinafine HC1, ciclopirox, ciclopirox olamine, fluconazole, itraconazole, ketoconazole, amorolfine, efinaconazole, clotrimazole, miconazole (miconazole nitrate), and any combination thereof.
  • Statement 131 The composition according to any one of Statements 88-122, further comprising at least one additional anti-fungal agent selected from the group consisting of terbinafine HC1, ciclopirox, ciclopirox olamine, fluconazole, itraconazole, ketoconazole, amorolfine, efinaconazole, clotrimazole, miconazole (miconazole nitrate), and any combination thereof.
  • additional anti-fungal agent selected from the group consisting of terbinafine HC1, ciclopirox, ciclopirox olamine, fluconazole, itraconazole, ketoconazole, amorolfine, efinaconazole, clotrimazole, miconazole (miconazole nitrate), and any combination thereof.
  • Statement 132 The composition according to any one of Statements 1-80, further comprising at least one additional anti-fungal agent selected from the group consisting of terbinafine HC1, ciclopirox, ciclopirox olamine, fluconazole, itraconazole, ketoconazole, amorolfine, efinaconazole, clotrimazole, miconazole (miconazole nitrate), and any combination thereof.
  • additional anti-fungal agent selected from the group consisting of terbinafine HC1, ciclopirox, ciclopirox olamine, fluconazole, itraconazole, ketoconazole, amorolfine, efinaconazole, clotrimazole, miconazole (miconazole nitrate), and any combination thereof.

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  • Pharmacology & Pharmacy (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Otolaryngology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
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  • Oncology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne des compositions et des procédés pour le traitement topique de membranes muqueuses, de peau et de surfaces infectées par Candida auris (C. auris), y compris le C. auris multirésistant. Les compositions peuvent contenir d'environ 0,1 % à environ 5 % en poids d'un biocide cationique choisi parmi le polyhexanide biguanide (PHMB), le poly(biguanide d'aminopropyle) (PAPB), la chlorhexidine (CHG) et toute combinaison de ceux-ci.
PCT/US2020/013962 2019-01-16 2020-01-16 Compositions et procédés pour la maîtrise et le traitement de candida auris WO2020150532A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022150407A1 (fr) * 2021-01-05 2022-07-14 Sanders Mitchell C Solution désinfectante de peroxyde d'hydrogène améliorée et purifiée pour une inactivation rapide de la covid-19 et d'autres pathogènes
WO2023278316A1 (fr) * 2021-06-30 2023-01-05 Johnson Lanny Leo Désinfectant pour candida auris

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022150407A1 (fr) * 2021-01-05 2022-07-14 Sanders Mitchell C Solution désinfectante de peroxyde d'hydrogène améliorée et purifiée pour une inactivation rapide de la covid-19 et d'autres pathogènes
WO2023278316A1 (fr) * 2021-06-30 2023-01-05 Johnson Lanny Leo Désinfectant pour candida auris

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