Antimicrobial compositions

Abstract

Provided herein are antimicrobial compositions which can be useful for treating, reducing, or preventing malodors, or retarding the growth of microbes associated with skin or skin structures.

Description

[0001] ANTIMICROBIAL COMPOSITIONS

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to US provisional application no. 63 / 662,047, filed June 20, 2024, which is hereby incorporated by reference.

[0004] BACKGROUND

[0005] With the development and popularization of treatments for diabetes, heart failure, and chronic kidney disease that are based on administration of inhibitors of SGLT2, a need has arisen for products that reduce the risk of development of undesirable microbial growth on the skin of the groin that is fostered by contamination of the skin with glucose from urine. There is also a need in the setting of diabetes for a broad- spectrum antimicrobial agent that can be used to thwart the expansion of microorganisms on the surface of the skin, particularly the skin of the feet.

[0006] BRIEF SUMMARY OF THE INVENTION

[0007] Compositions of the invention are broadly useful in retarding microbial growth providing convenient management of multiple undesirable personal conditions caused by microbial action.

[0008] In one aspect, the present disclosure provides a topical composition comprising: glucose oxidase, a base, an iron chelating agent, an enzyme stabilizer, and a surfactant.

[0009] In some embodiments, the glucose oxidase is present at a concentration of from 1 to 10,000 units per milliliter. In some embodiments, the glucose oxidase is present at a concentration of from 10 to 1000 units per milliliter.

[0010] In some embodiments, the base is NaHCCh, (NH^CCh, KHCO3, or tri s(hydroxymethyl)aminom ethane. In some embodiments, the base is present in a concentration of from 0.1% to 15% (w / v).

[0011] In some embodiments, the iron chelating agent comprises ethylenediaminetetraacetic acid (EDTA) or a salt thereof. In some embodiments, the iron chelating agent comprises EDTA disodium salt or tetrasodium salt. In some embodiments, the concentration of iron chelating agent is from 10 to 300 mM. In some embodiments, the enzyme stabilizer is gluconolactone, gluconic acid or gluconate thereof, metabisulfite, ascorbate, sodium chloride, monosodium phosphate dihydrate, trisodium citrate dehydrate, tetra potassium pyrophosphate, ammonium sulfate, ammonium tartrate or tetra sodium pyrophosphate. In some embodiments, the concentration of the enzyme stabilizer is from 1 to 33% (w / v).

[0012] In some embodiments, the surfactant is ionic. In some embodiments, the surfactant is nonionic. In some embodiments, the surfactant is cocoyl glutamate (e.g., disodium). In some embodiments, the concentration of the surfactant is from 0.1 % to 10% (w / v).

[0013] In some embodiments, the composition further comprises a thickener. In some embodiments, the thickener is polyethylene oxide or carboxymethylcellulose. In some embodiments, the concentration of the thickener is from 0.5% to 5% (w / v).

[0014] In some embodiments, the composition further comprises a carrier. In some embodiments, the carrier is mineral oil, water, or aloe vera gel.

[0015] In some embodiments, the composition further comprises an a-hydroxy acid. In some embodiments, the a-hydroxy acid is gluconic acid, glycolic acid, salicylic acid, citric acid, lactic acid, malic acid, tartaric acid, or 2-hydroxyalkanoic acid or a salt or lactone thereof. In some embodiments, the concentration of the a-hydroxy acid is from 3% and 33% (w / v).

[0016] In some embodiments, the pH of the composition is from 4 to 7.

[0017] In some embodiments, the glucose oxidizer is glucose oxidase, the base is tris(hydroxymethyl)aminomethane, the iron chelating agent is EDTA, the enzyme stabilizer is gluconolactone, and the surfactant is cocoyl glutamate (e.g., disodium). In some embodiments, the concentration of glucose oxidase is about 0.5 mg / mL, the concentration of tri s(hydroxymethyl)aminom ethane is about 7.5%, the concentration of EDTA is about 100 mM, the concentration of gluconolactone is about 10%, and the concentration of disodium cocoyl glutamate is about 1.5%, wherein all percentages are (w / v).

[0018] In some embodiments, the composition is formulated as a spray.

[0019] In some embodiments, the composition is sulfate free, paraben free, or aluminum free.

[0020] In one aspect, the present disclosure provides a method of treating or preventing a disease or condition mediated by glucose-stimulated microbial growth by topically administering, e.g., to vulnerable skin, an effective amount of a composition described herein to a subject in need thereof.

[0021] In some embodiments, the condition is redness, inflammation, irritation, malodor, pain, pruritis, or discomfort. In some embodiments, the subject has glycosuria. In some embodiments, the subject is taking an SGLT inhibitor. In some embodiments, the subject has diabetes, chronic kidney disease, or heart failure. In some embodiments, the topically administering comprises spraying the composition on the subject.

[0022] In one embodiment, the present disclosure provides a composition comprising a chelating agent having an affinity for iron at a concentration of between 30 and 300 mM.

[0023] In another embodiment, the present disclosure provides a method of treating, reducing, or preventing a malodor on a subject in need thereof, the method comprising administering to the skin of the subject a composition of the present disclosure, thereby treating, reducing, or preventing the malodor.

[0024] In another embodiment, the present disclosure provides a method of treating a disease or condition mediated by glucose-stimulated microbial growth, the method comprising administering to the skin of the subject a composition of the present disclosure, thereby treating the disease or condition mediated by glucose-stimulated microbial growth.

[0025] DETAILED DESCRIPTION OF THE INVENTION

[0026] I. DEFINITIONS

[0027] “Composition” as used herein is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product, which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. By “pharmaceutically acceptable” it is meant that the composition of the described invention is safe, non-toxic, and is suitable for topical use in subjects in need thereof, to reduce irritation, redness, microbial activity, and / or malodor.

[0028] “Chelating agent” refers to an agent that bonds to a metal ion through at least two coordinate bonds between the chelating agent (ligand) and the metal ion. A representative chelating agent includes, but is not limited to, ethylenediaminetetraacetic acid (EDTA). “High affinity” refers to a chelating agent that forms a strong bond with a metal ion, such as having a logarithm of the equilibrium constant K = [ML] [M]1[L]1(i.e., a log K for the interaction of a metal M and a ligand L) for the iron-chelator complex of greater than 9 for Fe2+and greater than 15 for Fe3+as described, for example by Anderegg et al. Pure Appl. Chem., 77: 1445-1495, 2005. doi: 10.1351 / pac200577081445.

[0029] “Alpha-hydroxy acid” or “a-hydroxy acid” refers to a carboxylic acid having a hydroxy group alpha to the acid. An exemplary formula is: wherein R is any suitable group, e.g., an alkyl group of 1 to 6 carbons optionally substituted with one or more hydroxyl (-OH) or carboxyl groups (-COOH). A simple a-hydroxy acid is lactic acid: CH3CH(OH)C(O)OH. Other a-hydroxy acids include, but are not limited to, gluconic acid, glycolic acid, salicylic acid, citric acid, lactic, malic acid, tartaric acid, and 2- hydroxyalkanoic acids. The term also encompasses ionized, salt, and lactone forms of the acid.

[0030] “Surfactant” refers to any agent that lowers the surface tension of a substance, e.g., alters the surface properties of the oil and water components in a composition to aid in the formation of an emulsion. Surfactants useful in the present disclosure include, but are not limited to, a non-ionic surfactant, an ionic surfactant such as a cationic surfactant or an anionic surfactant, an amphoteric surfactant, an ampholytic surfactant, a fatty alcohol, a fatty acid and fatty acid salts thereof. A surfactant’s hydrophilic / lipophilic balance (HLB) describes the surfactant’s affinity toward water or oil (1-30, with 1 being lipophilic and 30 being hydrophilic). The HLB of a blend of two surfactants equals the weight fraction of surfactant A times its HLB value plus the weight fraction of surfactant B times its HLB value (weighted average). Anionic surfactants include, but are not limited to soaps including alkali soaps, such as sodium, potassium and ammonium salts of aliphatic carboxylic acids, usually fatty acids, such as sodium stearate. Additional anionic surfactants include organic amine soaps such as organic amine salts of aliphatic carboxylic acids, usually fatty acids, such as triethanolamine stearate. Cationic surfactants include, but are not limited to, quaternary ammonium salts such as octadecyl ammonium chloride and benzalkonium chloride. One of skill in the art will appreciate that other surfactants are useful in the present disclosure. “Surfactant of biological origin” refers to a surfactant in which the components are derived from natural products, for example soaps, which are alkali metal salts of the fatty acids released by alkaline hydrolysis of fats or oils of various natural origin, such as vegetable oils or fats such as palm or coconut oil, or animal fats such as tallow or lard. A surfactant of biological origin can be a semisynthetic compound, in which the surfactant is not found, or is found in negligible concentration, in nature, but results from at least one bond-forming step that transforms a natural substrate into a composition having the desired surfactant properties. Examples of semisynthetic surfactants are cocamidopropyl betaine, cocoyl glutamate (e.g., disodium), alkyl glucosides, maltosides or xylosides, sorbitan derivatives, alkyl sulfates or alkyl polyethers that are formed from alkanols created by reduction of fatty acids of natural origin, esters of fatty acids of natural origin with polyethers or with betaines, surfactants based on bile acids or conjugated bile acids, and the like.

[0031] “Non-comedogenic” refers to the absence of comedones being formed following application of a substance, i.e., enlarged or plugged hair follicles.

[0032] “Thickener” refers to substances which, when added to a mixture, increase its viscosity without substantially modifying its other properties. Thickeners may provide body, increase stability, and / or improve suspending action. Thickeners useful in the compositions of the instant invention include, but are not limited to, agar, algin, arrowroot, collagen, cornstarch, fecula, gelatin, guar gum, katakuriko, locust bean gum, pectin, wheat flour, tapioca, and xanthan gum. One of skill in the art will appreciate that other thickeners are useful in the present disclosure.

[0033] “Polymer of biological origin” refers to a polymeric substance found in nature such as cellulose, collagen, cornstarch, guar gum, locust bean gum, and the like, or that is a semisynthetic derivative thereof, that is formed by modification of a natural polymer, for example by alkylation, acylation, sulfation, or hydrolysis to form polymers such as carboxymethylcellulose, hydroxypropyl cellulose or gelatin.

[0034] “Plant extract” refers to a crude or semi-purified composition derived from a natural plant source, such as the leaves, bark, stem, flowers, seeds, roots, tubers and the like, and which may have been derived by extraction with a solvent, often at elevated temperature, for example by reflux in a Soxhlet extractor or the like, or that is a naturally derived exudate or liquid, such as a juice or sap. “Plant-derived gel” refers to a plant extract that has the rheological properties of a gel, that is, a semi-solid substance that does not assume a shape determined by a container in which it is placed (unlike a liquid).

[0035] “Therapeutically effective amount or dose” or “therapeutically sufficient amount or dose” or “effective or sufficient amount or dose” refer to a dose that produces therapeutic effects for which it is administered. The exact dose will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins). In sensitized cells, the therapeutically effective dose can often be lower than the conventional therapeutically effective dose for non-sensitized cells.

[0036] “Treat”, “treating” and “treatment” refers to any indicia of success in the treatment or amelioration of an injury, pathology, condition, or symptom (e.g., pain, redness, inflammation, irritation, pruritis, and microbial activity associated with malodor), including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the symptom, injury, pathology or condition more tolerable to the patient; decreasing the frequency or duration of the symptom or condition. The treatment or amelioration of symptoms can be based on any objective or subjective parameter; including, e.g., the result of a physical examination.

[0037] “Reduce”, “reducing” or “reduction” refers to a decrease in any measurable aspect of an injury, pathology, condition, or symptom (e.g., pain, redness, inflammation, irritation, pruritis, and microbial activity associated with malodor), including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the symptom, injury, pathology or condition more tolerable to the patient; decreasing the frequency or duration of the symptom or condition. The reduction of a measurable aspect can be based on any objective or subjective parameter.

[0038] “Prevent,” “preventing” and “prevention” refers to the prevention of the onset, recurrence or spread of a disease or disorder, or of one or more symptoms thereof. In certain embodiments, the terms refer to the treatment prior to the onset of symptoms, particularly to subjects at risk of disease or disorders provided herein. The terms encompass the inhibition or reduction of a symptom of the particular disease. In certain embodiments, subjects who have a history of recurring symptoms are potential candidates for prevention. In certain embodiments, subjects administered a medication that increases the risk of another disease or condition are candidates for prevention.

[0039] “Disease” refers to abnormal cellular function in an organism, which is not due to a direct result of a physical injury. Diseases can refer to any condition that causes distress, dysfunction, disability, disorder, infection, pain, or even death.

[0040] “Malodor” refers to an unpleasant smell of the subject.

[0041] “Glucose-stimulated microbial growth” refers to microbial growth stimulated by glucose produced or excreted by the subject, such as glucose in urine, or glucosuria.

[0042] “Administering” refers to contact of a composition with the subject.

[0043] “Subject” refers to animals such as mammals, including, but not limited to, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice and the like. In certain embodiments, the subject is a human.

[0044] “Microbial growth-retarding” or “retarding the growth of a microbial infection” refers to the preventing or retarding of growth of bacteria or fungi using a composition of the present disclosure. Microbial growth retardation encompasses the actions of microbiostatic agents, which block growth but do not necessarily produce cell death, and the actions of microbicidal agents, which cause the death of bacteria or fungi. Growth retardation refers to a consequence of exposure to a composition that results in a reduction of the rate of replication a microbe to 80% or less of the rate of an unexposed microbe, or to 60% or less, or 40% or less, or 20% or less, or 10% or less or results in a cessation of replication. Growth retardation also refers to a consequence of exposure in which the total mass of microbial burden does not increase, or increases by a rate that is 10%, or 20%, or 40%, or 60%, or 80% of the rate of increase in total mass of microbial burden compared to the rate of increase of unexposed microbes. Hence growth retardation refers to reductions of increases in microbial count and / or microbial mass.

[0045] “Vulnerable skin” refers to any skin or skin structure, and any superficially exposed or susceptible mucosal surfaces, such as the superficially exposed susceptible mucosal surfaces of the internal and external structures of the genitalia of either sex such as the penis, vagina, and vulva, that is prone to colonization by undesired microbes. Vulnerability can be a consequence of anatomical location, age, hormonal status, medication, immune deficiency, conditions or diseases affecting the skin or internal genitalia, exposure to heat, humidity, ultraviolet light, or substances that induce inflammatory or allergic reactions, or as a result of the apposition of garments or the composition of the garments apposed, or can be due to physical effects such as chafing or similar recurrent physical stresses.

[0046] “Undesirable effects of microbes” includes, without limitation, pruritis, pain, rash, swelling, inflammation, malodor, changes of skin color or texture such as erythema or peau d’orange, the formation of infected skin and skin structures or other manifestations or consequences of bacterial infections (pyodermas) that give rise to impetigo, folliculitis, pitted keratolysis, erythrasma, trichomycosis, intertrigo, toe web infection, pseudofolliculitis of the beard, vaginitis, balanoposthitis, acute infectious eczematoid dermatitis, abscesses, erysipelas, cellulitis, or toxic epidermal necrolysis, and their complications or sequelae, such as osteomyelitis, endocarditis, lymphangitis, myositis, gangrene, necrotizing fasciitis, or sepsis, all of which can originate from an infectious nidus in the skin. Undesirable effects of microbes also include the manifestations or consequences of fungal (mycotic) infections such as the tinea dermatophytoses, for example tinea pedis, tinea cruris, tinea corporis, or tinea capitis, or fungal manifestations of vulvovaginitis or balanoposthitis such as vulvovaginal candidiasis.

[0047] “Fungus” and “fungal” are used in the established sense as referring to mycotic organisms (e.g., molds or yeasts) or their attributes.

[0048] “Suitable for application to vulnerable skin” refers to a characteristic of a composition that imbues it with the appropriate properties to be conveniently applied to vulnerable skin and that does not produce unacceptable consequences of application. Common physical forms that are well-known in the art include lotions, foams, creams, gels, liquids, sprays, sticks, wipes and the like. Preferred compositions are those that allow complete coverage of vulnerable skin and that have properties that allow the penetration of pores and related structures that harbor microbes.

[0049] “Unacceptable consequences of application” refers to consequences of application that are deemed by a subject to be insufficiently tolerable so as to favor continued use of the product. The phrase does not include such consequences as transient discomfort or irritation, for example transient itching or stinging, or other effects, such as transient wetness or erythema or other coloration, that the subject finds acceptable in consideration of the benefits provided.

[0050] “About” refers to a deviation from the stated value in the range of ±10%. A composition that is “free” of an ingredient is meant a composition that is not formulated with that ingredient.

[0051] II. ANTIMICROBIAL COMPOSITIONS

[0052] A. General

[0053] The present disclosure discloses a composition, e.g., suitable for application to vulnerable skin, that provides protection from the undesirable effects of microbes. The composition reduces undesirable effects, e.g., by preventing or retarding growth of any existing microbes on the vulnerable skin at the time of application. For example, if applied after the skin is washed or sanitized, it retards the rate of regrowth of microbes and reduces the severity of the undesirable effects of microbes.

[0054] The composition of the invention thus provides relief from common discomforts and undesirable conditions such as malodor and itching, e.g., by deterring the growth of both bacteria and fungi. In some embodiments it is particularly well adapted to address diseases or conditions resulting from elevated concentrations of glucose on vulnerable skin. Elevated concentrations of glucose on vulnerable skin may arise as a result of diabetes or other disease or may be iatrogenic in origin, e.g., stemming from the effects of medications.

[0055] In one aspect of the invention, the antimicrobial composition can be used to reduce the burden of undesirable skin-dwelling pathogens or commensals through various mechanisms, e.g., that lower glucose and / or that sequester iron. A preferred agent to lower glucose is glucose oxidase. Preferred iron sequestrants are compositions that have high affinity, limited potential for systemic absorption, little or no aromatic content, and regulatory histories that indicate high safety in topical application. Particularly preferred compositions do not contain or represent compounds that have elicited unfavorable consumer sentiment, such as sulfates, parabens, polyethers, and aluminum.

[0056] In one embodiment, the present disclosure provides a composition comprising glucose oxidase, a chelating agent having an affinity for iron, a base, an enzyme stabilizer, and a surfactant. In some embodiments the composition consists of a limited number of ingredients, e.g., 5, 6, 7, or 8 ingredients. A. Glucose Oxidase

[0057] Glucose oxidase (EC 1.1.3.4) may be from any suitable source, such as fungal (e.g., A. riiger) or insect. The enzyme can be present in the composition in any suitable amount.

[0058] Representative amounts of the glucose oxidase in the composition include, but are not limited to, about 1 to 10,000 units per mL, or about 2 to 9000, or about 3 to 8000, or about 4 to 7000, or about 5 to 6,000, or about 6 to 5000, or about 7 to 4000, or about 8 to 3,000, or about 9 to 2000, or about 10 to 1000, or about 25 to 500, or about 30 to 300 units per mL. In some embodiments, one unit of glucose oxidase will oxidize 1.0 pmol of P-D-glucose to D- gluconolactone and H2O2 per minute at pH 5.1 at 35 °C (equivalent to an O2 uptake of 22.4 pL per minute).

[0059] In some embodiments, the present disclosure provides a composition wherein the glucose oxidase is present at a concentration of from 1 to 10,000 units per mL. In some embodiments, the present disclosure provides a composition wherein the glucose oxidase is present at a concentration of from 10 to 1000 units per mL. In some embodiments, the present disclosure provides the composition wherein the glucose oxidase is present at a concentration of from 30 to 300 units per mL.

[0060] B. Chelating Agents

[0061] Exemplary chelating agents with a high affinity for iron include ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTP A), 3,6,9, 12-tetrakis(carboxymethyl)- 3,6,9, 12-tetraazatetradecanedioic acid (triethylenetetraminehexaacetic acid; TTHA), 2, 2’, 2”- (l,4,7-triazanonane-l,4,7-triyl)triacetic acid (NOTA), 2,2’,2”,2’”-(l,4,7,10- tetraazacyclododecane -1,4,7,10-tetrayl) tetraacetic acid, (DOTA), 2,2’,2”,2”’-(l,4,8,l l- tetraazacyclotetradecane-l,4,8,l l-tetrayl) tetraacetic acid (TETA), deferoxamine, deferasirox, deferiprone, combinations thereof, and salts thereof.

[0062] A particularly preferred chelating agent with a high affinity for iron is EDTA, for example disodium EDTA or tetrasodium EDTA.

[0063] In some embodiments, the chelating agent comprises ethylenediaminetetraacetic acid (EDTA). In some embodiments, the chelating agent comprises ethylenediaminetetraacetic acid (EDTA) disodium salt. In some embodiments, the chelating agent comprises ethylenediaminetetraacetic acid (EDTA) tetrasodium salt. The chelating agent can be present in the composition in any suitable concentration. Representative concentrations include, but are not limited to, 10 to 1000 mM, 20 to 750 mM, 25 to 500 mM, 30 to 400 mM, 40 to 300 mM, 50 to 250 mM, 75 to 200 mM, 80 to 175 mM, 85 to 150 mM, 90 to 125 mM, or 95 to 105 mM. Other concentrations of the chelating agent useful in the compositions of the present disclosure include, but are not limited to, about 50, 75, 80, 85, 90, 95, 100, 110, 125, 150, 175, 200, 225, 250, 275, 300, 350, 400, 450, or 500 mM.

[0064] In some embodiments, the composition comprises ethylenediaminetetraacetic acid (EDTA) at a concentration of from 50 to 250 mM. In some embodiments, the composition comprises ethylenediaminetetraacetic acid (EDTA) at a concentration of from 75 to 200 mM. In some embodiments, the composition comprises ethylenediaminetetraacetic acid (EDTA) at a concentration of about 100 mM.

[0065] C. Base

[0066] Any suitable base may be employed. Suitable bases include alkali metal salts such as sodium or potassium hydroxide, carbonate, or bicarbonate; organic tertiary amine bases such as tetramethyl or tetraethylammonium hydroxide, carbonate, or bicarbonate; ammonium salts such as ammonium hydroxide, carbonate, or bicarbonate; amine bases such as tris- hydroxymethylaminomethane (TRIS®, tromethamine), trimethylamine, triethylamine, triethanolamine, N-methylmorpholine, N-methylpiperidine, dimethylpiperazine, dimethylamine, diethylamine, dipropylamine, pyrrolidine, morpholine, piperidine, piperazine, imidazole, or pyrazole. Preferred bases include carbonates, bicarbonates, and tris- hydroxymethylaminomethane.

[0067] Extremities of pH are undesirable and can produce or exacerbate stinging sensations. The microbial growth-retarding composition of the invention has a pH preferably between 2 and 9, more preferably between 3 and 6 or between 4 and 7. Products for application to or near the vagina are recommended to have pH values approximating the normal pH of the organ secretions, 3.5 to 4.5.

[0068] D. Enzyme Stabilizer

[0069] Any suitable enzyme stabilizer for glucose oxidase may be included, e.g. gluconolactone, gluconic acid or gluconate thereof, metabisulfite, ascorbate, sodium chloride, monosodium phosphate dihydrate, trisodium citrate dehydrate, tetra potassium pyrophosphate, ammonium sulfate, ammonium tartrate or tetra sodium pyrophosphate. Gluconic acid salts stabilize glucose oxidase and are a-hydroxy acids with favorable properties for skin hydration. Gluconic acid in solution is in equilibrium with the lactone form, D-glucono-8-lactone. Representative amounts of the enzyme stabilizer include, but are not limited to, about 1% to 50% (w / v), or about 1% to 33%, about 2% to 40%, or about 3% to 30%, or about 4% to 20%, or about 5% to 10% (w / v). Other amounts of the enzyme stabilizer in the composition include, but are not limited to, about 1% (w / v), or 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% (w / v).

[0070] E. Surfactants

[0071] The composition includes a surfactant. Surfactants may aid in pore penetration or facilitate spreading of the composition. Ionic and nonionic detergents are well-known surfactants. In some embodiments, the surfactant is an ionic surfactant. In some embodiments, the surfactant is a non-ionic surfactant. In some embodiments, the surfactant is a surfactant of biological origin, for example cocamidopropyl betaine, cocoyl glutamate (e.g., disodium), polyoxyethylene lauryl ethers (e.g., BRIJ® 35’ and BRIJ® 57), cocamide monoethanolamine, cocamide diethanolamine, octyl glucoside and the like. In some embodiments, the surfactant is non-comedogenic.

[0072] Suitable surfactants include, but are not limited to cationic, anionic, nonionic, amphoteric and ampholytic surfactants. In some embodiments, the surfactants are non-stinging or nonirritating nonionic and amphoteric surfactants. In some embodiments, the surfactant can be present in an amount ranging from about 0.1% to 10% (w / v). The surfactant can have an HLB (hydrophilic-lipophilic balance) value of 18-30 not to interfere with the enzymatic activity of the glucose oxidase.

[0073] Suitable nonionic surfactants include, but are not limited to, ethylene oxide / propylene oxide block copolymers, called poloxamers, reverse poloxamers, poloxamines, or reverse poloxamines. Poloxamers have a central block of polypropylene oxide with two flanking blocks of polyethylene oxide, whereas reverse poloxamers have the block compositions reversed. Poloxamines terminate in primary amines whereas poloxamers terminate in alcohols. Poloxamers and poloxamines are preferred, and poloxamers are most preferred.

[0074] A range of poloxamers and poloxamines are available, for example manufactured by BASF (Ludwigshafen, Germany) as Pluronic® R and Tetronic® R series surfactants, respectively. Among these are Pluronic® F38, having a HLB of 31, Pluronic® F68 having a HLB of 29, Pluronic® 68LF having a HLB of 26, Pluronic® F77 having a HLB of 25, Pluronic® F87 having a HLB of 24, Pluronic® F88 having a HLB of 28, Pluronic® F98 having a HLB of 28, Pluronic® F108 having a HLB of 27, Pluronic® F127 (also known as Poloxamer 407) having a HLB of 18-23, and Pluronic® L35 having a HLB of 19.

[0075] Other nonionic surfactants include octylphenol ethoxylates such as the Triton X-series (e.g., Triton X-100, Triton X-l 14, Triton X-405) or IGEPAL CA-630, and ethers of polyoxyethylene and fatty alcohols (fatty alcohol ethoxylates), such as Brij® 35, Brij® 57 and Brij® 97, which are polyethers joining C12 - C14 alcohols to approximately 35 ethyloxy units, Ci6 - Ci8 alcohols to approximately 57 ethyloxy units, and C20 - C22 alcohols to approximately 97 ethyloxy units, respectively. Similar products are offered by HELM AG, BASF AG (Lutensol A - N surfactants) and Galaxy. Various alkyl glycosides are also well known in the art, such as the glucosides n-octyl-P-D-glucoside, n-decyl-P-D-glucoside, and / ?- dodecyl(lauryl)-P-D-glucoside; or alkyl maltosides such as u-dccyl-P-D-maltopyranosidc, n- dodecyl-P-D-maltopyranoside and 6-cyclohexyL 1 -hexyl-P-D-maltopyranoside.

[0076] Salts of fatty acids, alkyl benzenesulfonic acids, alkanol sulfates, such as sodium dodecyl sulfate, and the like are common ionic soaps or detergents that can produce a desirable decreased surface tension. Another class of popular ionic detergent comprises the alkanols joined to oligomers of ethylene glycol that terminate in a sulfate monoester, such as sodium laureth-3 sulfate, which bears three oxyethylene groups between dodecanol and sulfate.

[0077] Other examples of nonionic surfactants include decyl glucoside (e.g., Plantacare® 2000), lauryl glucoside (e.g., Plantacare® 1200), cocamide DEA (e.g., Comperlan® KD), cocamide MEA (e.g., Comperlan® 100), PEG-7 glyceryl cocoate (e.g., Cetiol® HE), sorbitan oleate (e.g., Span® 80), sorbitan stearate (e.g., Span® 60), polysorbate 20 (e.g., Tween® 20), polysorbate 80 (e.g., Tween® 80), cetyl alcohol, stearyl alcohol, cetearyl alcohol, PEG-40 hydrogenated castor oil (e.g., Cremophor® RH 40), glyceryl stearate (e.g., Tegin®), and cocamidopropylamine oxide (e.g., Amphoteric® CO).

[0078] Examples of ionic surfactants include sodium lauryl sulfate (SLS) (e.g., Texapon® K 12), sodium laureth sulfate (SLES) (e.g., Texapon® N 70), ammonium lauryl sulfate (e.g., Standapol® A), ammonium laureth sulfate (e.g., Standapol® EA-2), cocamidopropyl betaine (e.g., Tegobetaine® L7), sodium stearate, sodium lauroyl sarcosinate (e.g., Sarkosyl® O), disodium laureth sulfosuccinate (e.g., Rewopol® SB FA 30), sodium myreth sulfate, cetyltrimethylammonium chloride, benzalkonium chloride, and stearalkonium chloride (e.g., Varisoft®).

[0079] Zwitterionic surfactants (sometimes classified as amphoteric surfactants) are ionic compounds bearing both positive and negative charges at neutral pH and are suitable for use in antimicrobial compositions of the present disclosure. They are often found in the form of betaines (zwitterions that contain a positive charge that cannot be neutralized, such as a quaternary amine, or tertiary sulfur, as in a sulfobetaine). Like many surfactants they are often created from saturated fatty acids of vegetable oils, such as coconut or palm oils. The fatty acids are used to acylate amine-containing compounds, and their common names often reflect their origin, such as cocamidopropyl betaine or disodium cocoamphodiacetate. Ionic surfactants having carboxylic acids and an amphoteric character are advantageous in compositions of skin care products because they do not produce sebum rebound overproduction when removed, as alkyl sulfates are prone to do.

[0080] Examples of amphoteric surfactants include cocamidopropyl betaine (e.g., Tegobetaine® L7), coco betaine (e.g., Dehyton® AB-30), lauryl betaine, cocamidopropyl hydroxysultaine (e.g., Mirataine® CBS), sodium cocoamphoacetate (e.g., Miranol® C2M), disodium cocoamphodiacetate (e.g., Miranol® Ultra C-32), sodium lauroamphoacetate, and lauramidopropyl betaine.

[0081] A related family of surfactants are amides of fatty acids with the amino acid glutamate. The resulting compounds have two carboxylic acid residues and one amide bond and are typically of natural origin. Cocoyl glutamate (e.g., disodium) is one example. Related monodisperse surfactants include sodium stearoyl glutamate and sodium lauroyl glutamate, which are amides of Cis and C12 alkanoic acids, respectively.

[0082] Non-detergent macromolecules may also be employed. The non-detergent macromolecules can be natural in origin, for example plant extracts or gels, such as aloe vera gel, their constituent proteins, or synthetic polymers such as high molecular weight polyethylene oxide or carboxymethylcellulose. In some cases, the macromolecules can serve a dual purpose, increasing viscosity and providing for reduced surface tension.

[0083] The surfactant can be present in the composition in any suitable amount. Representative amounts of the surfactant include, but are not limited to, 0.1% to 50% (w / w), or 0.2% to 25%, or 0.3% to 10%, or 1% to 7.5% (w / v). In some embodiments, the surfactant is present in an amount of from 0.3% to 10% (w / v). The composition of the present disclosure can include other suitable components and excipients. Representative components that can be included in the composition of the present disclosure include, but are not limited to, a carrier, an a-hydroxy acid, a thickener, and / or an excipient. In some embodiments, the composition further comprises one or more of a carrier, an a-hydroxy acid, and a thickener. In some embodiments, the composition further comprises two or more of a carrier, an a-hydroxy acid, and a thickener.

[0084] F. Carrier

[0085] In some embodiments, the composition includes a carrier. Suitable carriers include liquids and gels. Examples of liquid carriers are mineral oil and water or aqueous solution. An example of a gel carrier is aloe vera gel. The carrier can be present in the composition in any suitable amount. In some embodiments, the carrier is present at a concentration of between 1% and 99% (v / v). In some embodiments, the present disclosure provides the composition wherein the carrier is present at a concentration of from 10% to 96% (v / v).

[0086] G. Alpha-Hydroxy Acids

[0087] In some embodiments, the composition further comprises one or more a-hydroxy acids, e.g., in addition to any gluconic acid present. In some embodiments, the one or more a-hydroxy acids are selected from lactic acid, gluconic acid, glycolic acid, salicylic acid, or a lactone thereof. In some embodiments, the a-hydroxy acid is lactic acid.

[0088] The a-hydroxy acid can be present in the composition in any suitable amount. Representative amounts of the a-hydroxy acid include, but are not limited to, about 1% to 50% (w / v), or about 2% to 40%, or about 3% to 33%, or about 4% to 20%, or about 5% to 10% (w / v). Other amounts of the a-hydroxy acid in the composition include, but are not limited to, about 1% (w / v), or 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% (w / v). In some embodiments, the present disclosure provides the composition wherein the one or more a-hydroxy acids are present at a concentration of between about 3% and 33% (w / v).

[0089] H. Thickeners

[0090] In some embodiments, the composition further comprises a thickener. In some embodiments, the thickener is a polymer of biological origin or a modified polymer of biological origin, such as guar gum, pectin, locust bean gum, gum arabic, gum tragacanth, xanthan, carrageenan, sodium alginate, carboxymethylcellulose, hydroxypropyl cellulose, and the like.

[0091] In some embodiments, the thickener is a plant extract or plant-derived gel, such as aloe vera gel, okra, pectin, chamomile flower extract, nettle leaf extract, melissa leaf extract, peppermint leaf extract, horsetail leaf extract, or yucca vera leaf extract.

[0092] Polymers useful as thickeners include, but are not limited to, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxymethylchitosan, alginate, carrageenan, gum arabic, gellan gum, locust bean gum, tamarind gum, xanthan gum, guar gum, hydroxypropylguar, hydroxypropylmethylguar, carboxymethylguar, aloe vera gel, scleroglucan, schizophyilan, poly(vinyl alcohol), poly(ethylene glycol) / poly(ethylene oxide), poly(methyl vinyl ether), carbomer and its salts, poly(acrylic acid) and its salts, poly (methacrylic acid) and its salts, acrylates / C 10-30 alkyl acrylate crosspolymer, polyquatemium-10, polyglyceryl- 10 stearate, sodium poly(2-acrylamido 2-methylpropanesulfonate), polyacrylamide, poly(N,N- dimethylacrylamide), poly(N-vinylacetamide), poly(N-vinylformamide), poly(2- hydroxyethyl methacrylate), poly (glyceryl methacrylate), poly(N-vinylpyrrolidone), poly(N- isopropylacrylamide) and poly(N-vinylcaprolactam), and combinations thereof.

[0093] Thickening or increase in viscosity can also be promoted by the formation of emulsions or reverse emulsions. Emulsions can be formed from lipohilic and hydrophilic phases that are constituted from the components of the invention. In some embodiments the active ingredients are retained in the hydrophilic phase, and in some embodiments the chelating agent can be partly retained in the hydrophilic phase and partly in the hydrophobic phase, for example at the interface, or as a result of an octanol: water portioning coefficient that results in at least 1% of the chelating agent having a high affinity for iron in the hydrophobic phase, or at least 10%, 50%, 90%, or 99%, or greater. The properties of the phases can be adjusted by suitable excipients that adjust the hydrophilic / lipophilic balance, such as monoalkyl glycols or glyeroalkyl ethers.

[0094] Examples of monoalkyl glycols include, but are not limited to, 1,2-propanediol (propylene glycol), 1 ,2-butanediol, 1 ,2-pentanediol, 1 ,2-hexanediol, 1 ,2-heptanediol, 1 ,2-octanediol (caprylyl glycol), 1 ,2-nonanediol, 1,2-decanediol, 1 ,2-undecanediol, 1 ,2-dodecanediol, 1,2- tridecanediol, 1 ,2-tetradecanediol, 1,2-pentadecanediol, 1,2- hexadecanediol, 1,2- heptadecanediol and 1,2-octadecanediol. Non-vicinal glycols can also be added to enhance biocidal activity. Exemplary non-vicinal glycols include, but are not limited to, 2-methyl-2,4- pentanediol. 1,3- butanediol, diethylene glycol, triethylene glycol, and glycol bis(hydroxyethyl)ether.

[0095] Examples of glycerolalkyl ethers include, but are not limited to, 1 -O-heptylglycerol, 1-0- octylglycerol, 1-0-nonylglycerol, 1-0-decylglycerol. 1-0-undecylglycerol, 1-0- dodecylglycerol, 1-0-tridecylglycerol, 1 -O-tetradecylglycerol, 1-0-pentadecylglycerol, 1-0- hexadecylglycerol (chimyl alcohol), 1 -O-heptadecyiglycerol, 1-0-octadecylg lycerol (batyl alcohol), l-O-octadec-9-enyl glycerol (selachyl alcohol), glycerol 1 -(2-ethylhexyl)ether (also known as octoxyglycerin, 2-ethylhexyl glycerin, 3-(2-ethylhexyloxy)propane-l,2-diol, and Sensiva® RSC 50), glycerol 1 -heptyl ether, glycerol 1 -octyl ether, glycerol 1 -decyl ether, and glycerol 1 -dodecyl ether, glycerol 1 -tridecyl ether, glycerol 1 -tetradecyl ether, glycerol 1- pentadecyl ether, glycerol 1 -hexadecyl ether and glycerol 1 -octadecyl ether.

[0096] Examples of monoacylglycerols useful in the compositions described herein include, but are not limited to, 1-0-decanoylglycerol (monocaprin), 1 -O-undecanoylglycerol, 1-0- undecenoylglycerol, 1-0-dode canoylglycerol (monolaurin, also called glycerol mono laurate and Lauricidin® R), 1-0-tridecanoylglycerol, 1-0-tetradecanoylglycerol (monomyristin), 1- O-pentadecanoylglycerol, 1-0-hexadecanoylglycerol, 1-0-heptadecanoylglycerol, and 1-0- octanoylglycerol (monocaprylin). In general, glycerols substituted in the 1-0 position are more preferred than those substituted in the 2-0 position, or disubstituted in the 1-0 and 2-0 positions.

[0097] Suitable reverse emulsion surfactants include sodium bis(2-ethylhexyl)sulfosuccinate (Aerosol AOT, also called AOT, docusate sodium, DSS, Aerosol OT, and sodium l,4-bis(2- ethylhexoxy)-l ,4-dioxobutane-2-sulfonate), sodium bis(tridecyl)sulfosuccinate, bis(dialkyl)sulfosuccinate salts, copolymers of poly dimethylsiloxane and polyethylene / polypropylene-oxide, polyoxypropylene (12) dimethicone, cetyl PEG / PPG-10 / 1 dimethicone, hexyl laurate and polyglyceryl -4-isostearate, PEG- 10 dimethicone, sorbitan monolaurate, sorbitan monooleate, polyoxyethylenesorbitan trioleate, polyoxyethylene octyl phenyl ether, polyoxyethylene 10 cetyl ether, polyoxyethylene 20 cetyl ether, polyethylene glycol tert-octylphenyl ether, sodium di(2-ethylhexyl) phosphate, sodium di(oleyl)phosphate, sodium di(tridecyl) phosphate, sodium dodecylbenzenesulfonate, sodium 3- dodecylaminopropanesulfonate, sodium 3 -dodecylamino propionate, sodium N-2- hydroxydodecyl-N-methyltaurate, lecithin, sucrose fatty acid esters, 2-ethylhexylglycerin, caprylyl glycol, long chain hydrophobic vicinal diols of monoalkyl glycols, monoalkyl glycerols, or monoacylglycerols, polyoxyl castor oil derivatives, polyethylene glycol hydrogenated castor oil, tetraethylene glycol dodecyl ether, potassium oleate, sodium oleate, cetylpyridynium chloride, alkyltrimethylammonium bromides, benzalkonium chloride, didodecyldimethylammonium bromide, trioctylmethylammonium bromide, cetyltrimethylammonium bromide, cetyldimethylethylammonium bromide, and the like, with or without added alkanols such as isopropanol, 1 -butanol, and 1 -hexanol, and combinations thereof. The reverse emulsion surfactants can be dialkylsulfosuccinate salts, such as sodium bis(2-ethylhexyl)sulfosuccinate.

[0098] The thickener can be present in the composition in any suitable amount. Representative amounts of the thickener in the composition include, but are not limited to, about 0.1% to 10% (w / w), or about 0.2% to 5% (w / v). In some embodiments, the thickener is present in an amount of from about 0.2% to 5% (w / v).

[0099] I. Excipients

[0100] Various fragrances can be added to the composition to produce a pleasing scent or to distinguish compositions by brand. For products that appeal to the consumer seeking natural products, essential oils can also be added to the composition as fragrance or aromatic agents, and / or as antimicrobial agents. Examples of essential oils useful in the compositions described herein include, but are not limited to, thymol, menthol, sandalwood, camphor, cardamom, cinnamonjasmine, lavender, geranium uniper, menthol, pine, lemon, rose, eucalyptus, clove, orange, oregano, mint, linalool, spearmint, peppermint, lemongrass, bergamot, citronella, cypress, nutmeg, spruce, tea tree, Wintergreen, patchouli, coconut, vanilla, combinations thereof, and the like. In some embodiments, the essential oils can be selected from thymol, sandalwood oil, Wintergreen oil, eucalyptol, pine oil, coconut, vanilla and combinations thereof. In some embodiments, essential oils can be present in an amount ranging from about 0 to 5 wt % (w / v). In some embodiments, chlorophyllin can be used to control odor and to provide anti-inflammatory properties. In some embodiments, chlorophylin can be present in an amount ranging from about 0 to 5 (w / v). In some embodiments the composition contains a preformulated fragrance. In some embodiments the composition contains a preformulated fragrance that has a controlled release mechanism.

[0101] Cyclodextrins can be added to the microbial growth-retarding agent to absorb malodor or to serve as a repository for fragrance. Naturally occurring cyclodextrins are cyclic oligomers of a(l,4) linked glucose that consist of 6 (a-cyclodextrin), 7 (P-cyclodextrin), or 8 (y- cyclodextrin) glucose units. Semisynthetic cyclodextrins are well-known in the art and are natural cyclodextrins modified by chemical reaction to add side chains, most frequently to the primary hydroxyls (glucose 6 position) of the molecule. Examples of semisynthetic cyclodextrins include hydroxypropyl-P-cyclodextrin, methyl-P-cyclodextrin, sulfobutyl ether- P-cyclodextrin, carboxymethyl-P-cyclodextrin, hydroxyethyl-P-cyclodextrin, trimethyl-P- cyclodextrin, and hydroxypropyl-y-cyclodextrin.

[0102] Especially preferred compositions contain excipients that are safe and of natural origin, or have been assigned favorable ratings by consumer standards groups., such as the United States Food and Drug Administration (FDA), the United States Pharmacopoeia (USP), European Pharmacopoeia (Eur. Ph.), the Japanese Pharmacopoeia (JP), the British Pharmacopoeia (BP), the International Pharmacopoeia (IntPh), the Environmental Working Group, and the Personal Care Products Council. Excipients (inactive ingredients) that have USP monographs or equivalent are preferred.

[0103] In some embodiments, compositions are free of molecules that have been implicated as, or are suspected to be, carcinogens; molecules that act as agonists of estrogen receptors or other endocrine nuclear hormone receptors, such as the thyroid hormone receptor; compounds that are precursors of carcinogens or are prone to undergo degradation into carcinogens, such as amines and associated nitrosamines, heavy metals, aluminum, materials that are shunned because of concerns about contamination with precursors or byproducts that may have adverse health effects, such as polyethers, aromatic ingredients, elements such as zinc and iron, or vitamins and vitamin derivatives, particularly vitamin A and vitamin E or their esters. Compositions may also be free of alkyl sulfate surfactants.

[0104] Preferred microbial growth-retarding compositions of the present disclosure are non- comedogenic, that is, do not form comedones, enlarged or plugged hair follicles commonly referred to in many contexts as pimples, but the description of which encompasses a broader variety of manifestations, including whiteheads, blackheads, papules, pustules, nodules and cysts, in increasing severity of presentation. The penetration of the active ingredients of the composition into follicles may be desirable to aid in suppression of the superficial microbiota in the pores themselves as well as the surrounding skin.

[0105] An important consumer acceptability characteristic of a composition is the sensation it produces when spread on the skin or mucosal surfaces. Stinging or itching sensations are undesirable but may be multifactorial in their origin and difficult to reduce in a complex product. They may also be location or skin type-specific, so that a product that produces an acceptable effect on the axillae or on the feet may produce undesirable sensations when applied to the groin or to the face. Skin that is irritated, for example by rash or other condition, such as recent shaving or injury causing breakage of the skin, may be more sensitive. Compositions of the present disclosure are preferably not irritating to the subject.

[0106] J. Forms

[0107] Compositions of the invention are intended for topical application to the skin or mucus membranes and can be formulated as liquids (e.g., a spray), lotions, creams, gels, and solids such as sticks. In some cases, they are intended to be applied directly from the container, for example in the form of sprays, roll-on packaging, or stick formulations, and in other cases, to be manually distributed, for example as wipes or pads or dress pad, or as liquids, lotions or gels and the like to be applied to the fingers and spread on the targeted area. For the composition of the present disclosure, a uniform distribution over the entire surface is desirable and hence manual application is preferred, which may follow deposition by other means, for example from a spray, roll-on, tube, dispenser, or stick.

[0108] The active ingredients may be combined with additional ingredients such as organic oils, silicone compounds, cyclomethicone, water, various polymers that control viscosity, film formation, or other mechanical or fluid properties, fragrances, coloring agents, encapsulated compounds, solvents, propellants, and the like.

[0109] Any suitable dispenser and method of application may be considered. In one version, the composition is provided in a flexible, squeezable tube with an opening for release in response to pressure applied to the tube.

[0110] Various dispensers and applicators can be used to deliver effective quantities of compositions to the surface of a body. An aerosol can with a manually activated spray nozzle may be used for dispensing a composition according to certain embodiments of the present disclosure. Any known methods can be used for preparing a suitable solution or suspension for dispensing via aerosol, and any suitable propellants may be used. Alternatively, a bottle affixed with a fine mist sprayer may be employed. With any type of spray, the composition may be sprayed directly on the body or sprayed on the fingers and then manually applied to the body.

[0111] A stick dispenser may be used comprising a stick of the composition contained within the walls of a container, e.g., having a knob attached to a threaded spindle that drives the motion of an associated platform on which the stick of the composition rests. By turning the knob, the amount of the stick of the composition rising above the walls of the container can be adjusted. Manual movement of the platform, e.g., by pressing on a plate at the bottom of the container may also be employed. A cap for the container may be included.

[0112] A wipe system may be used for applying compositions according to certain embodiments of the present disclosure. The wipe system comprises an openable pouch, which may be a polymeric, foil, paper, or composite pouch, within which is a folded or unfolded wipe impregnated or coated with a quantity of the formulation.

[0113] Any wipe structures and / or methods of making the wipe structures commonly known in the art may be used in the present disclosure. The wipe comprises a flexible dispensing means, such as papers, cloths, non-wovens, films, foams, sponges, rollers, pads, tissues, cotton balls, and the like. Preferred wipe substrates comprise a porous material, such as the non-woven substrates, foams, or sponges, which are capable of holding the composition within the pores of the substrates. Examples of cellulosic non-wovens particularly useful and economic in the present disclosure is described in U.S. Pat. No. 4,191,609, which is incorporated herein by reference in its entirety.

[0114] Techniques for combining the wipe substrates with the composition of the present disclosure are well known in the art. Examples of common methods of combining the composition to the wipe substrate may involve coating, immersing, dipping, sprinkling, or spraying, the wipe substrate with the composition of the present disclosure. The composition of the present disclosure is added to the wipe substrate at a level sufficient to provide the desired odor control and / or other desired skin benefits of the present disclosure. III. METHODS OF TREATMENT

[0115] The compositions disclosed herein are useful for treating, reducing and preventing microbial, e.g., bacterial and fungal, growth and associated symptoms upon administration to the vulnerable skin of a subject. Symptoms that may be reduced include pruritis, pain, rash, swelling, inflammation, malodor, changes of skin color or texture such as erythema or peau d’ orange, the formation of infected skin and skin structures or other manifestations or consequences of bacterial infections (pyodermas) that give rise to impetigo, folliculitis, pitted keratolysis, erythrasma, trichomycosis, intertrigo, toe web infection, pseudofolliculitis of the beard, vaginitis, balanoposthitis, acute infectious eczematoid dermatitis, abscesses, erysipelas, cellulitis, or toxic epidermal necrolysis, and their complications or sequelae, such as osteomyelitis, endocarditis, lymphangitis, myositis, gangrene, necrotizing fasciitis, or sepsis, the manifestations or consequences of fungal (mycotic) infections such as the tinea dermatophytoses, for example tinea pedis, tinea cruris, tinea corporis, or tinea capitis, or fungal manifestations of vulvovaginitis or balanoposthitis such as vulvovaginal candidiasis. In some embodiments, the composition is used to treat, reduce, or prevent malodor, redness, or irritation.

[0116] The composition may be employed on any subject susceptible to microbial overgrowth. Such subjects include those with excess glucose on the skin or mucus membranes. Such subjects include those with glycosuria, diabetes (type 1 or type 2), chronic kidney disease, or heart failure. A subject may be being treated with a SGLT1 or SGLT2 inhibitor.

[0117] As discussed above, the subject may apply an amount of the composition to provide a thin coating to the desired area, e.g., axillae, groin, face, intertriginous skin (e.g., under the breasts, gluteal cleft, or between fingers and toes), or feet. Administration may occur daily or more than once per day. Administration may also be repeated for a period of at least one week.

[0118] IV. EXAMPLES

[0119] General

[0120] Malodor or axillary deodorant efficacy can be determined using the industry standard ASTM- E1207-09 “Standard Guide for Sensory Evaluation of Axillary Deodorancy”. Example 1.

[0121] To a screw-capped polypropylene bottle containing 14% ammonium lactate with mineral oil (Major Pharmaceuticals) was added one ninth volume of 0.5 M Na4 EDTA. The mixture was shaken well, resulting in a small decrease in viscosity. The resulting lotion was applied to the axillae, groin and feet daily over the course of several months, resulting in a suppression of malodor that was not complete over the axillae and groin.

[0122] Example 2.

[0123] To a screw capped polypropylene bottle containing 14% ammonium lactate with mineral oil (Major Pharmaceuticals) was added one quarter volume of 0.5 M Na4 EDTA. The mixture was shaken well, resulting in a decrease in viscosity. The resulting lotion was applied to the axillae, groin and feet daily over the course of several months, resulting in a suppression of malodor that was effective at all locations and more effective than the composition containing 50 mM EDTA.

[0124] Example 3.

[0125] To a screw capped 1 L polycarbonate bottle was added 600 g of aloe vera gel (Fruit of the Earth) followed by 150 mL of 0.5 M Na4 EDTA and 75 g of potassium gluconate, and the mixture was shaken thoroughly, after which the mixture transformed from a gel to a viscous fluid with an increase in turbidity. The mixture was applied to the axillae, groin and feet daily over the course of approximately one month with suppression of malodor at all locations.

[0126] Example 4.

[0127] A series of small-scale formulations ranging in volume from 25 mL to 800 mL were prepared according to Table 1. Formulations marked with AVG as a thickener used aloe vera gel as the carrier. All other formulations used water as the carrier. Some of the preparations included glucose oxidase from Aspergillus niger. Food grade glucose oxidase was obtained from Amano (Japan) and LEAP Chemical (China), and pharmacy grade glucose oxidase was obtained from Bioven (India).

[0128] For the preparation of solutions of higher viscosity, high molecular weight polyethylene oxide (approximately 4 million Da), carboxymethyl cellulose, or aloe vera gel were added to, or in the case of the aloe vera gel, served as the carrier for, the composition. Dissolution of the synthetic polymers required prolonged stirring in a beaker with a magnetic stirring bar and was typically carried out over at least 12 h. The compositions were dispensed into 2 oz pump action bottles delivering 0.25 mL per pump. For liquids the dispensing head had a spray nozzle (fine aperture) directed horizontally whereas for gels and viscous liquids the dispensing head had a larger aperture and dispensed vertically downward. If the composition could be delivered as a spray or as a consolidated jet, it was scored as a liquid, otherwise, it was scored as a viscous liquid or a gel. The distinction between viscous liquid and gel was made on the basis of the behavior when the bottle was inverted. If the composition remained in place, it was considered a gel, whereas if it flowed, it was considered a liquid. All compositions were manually applied, either by spray followed by spreading with the fingers, or by application to the fingers and subsequent spreading, to the axillae, groin, feet and face.

[0129] Table 1. Additional Formulations Tested

[0130] Key: a-OH Acid or Enzyme Stabilizer (L = gluconolactone, K = potassium salt, Na = sodium salt, AL = ammonium lactate);

[0131] EDTA: sodium salt form;

[0132] Base: added base;

[0133] Surfactant: Na2CG = Disodium cocoyl glutamate;

[0134] Thickener: PEO = polyethylene oxide MW 4,000,000, CMC = carboxymethylcellulose, AVG = aloe vera gel; pH: pH measured > 2 days after formulation;

[0135] Vise. = viscous; Liq. = liquid; Gel = non-flowing material; Susp. = suspension

[0136] Irrit. : at least one incidence of stinging sensation (+) or mild stinging sensation (+ / -);

[0137] Odor: degree of axillary odor, high (+), medium (+ / -), or none (-);

[0138] GOX: glucose oxidase concentration in mg mL1(>100,000 units / g) (J = Japan source; C = China source; no letter = India source).

[0139] All percentages expressed as weight of the component per volume of the composition (w / v). Natural thickening agents were also evaluated, including alginate, guar gum, gum arabic, carrageenan, and carbomer. Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, one of skill in the art will appreciate that certain changes and modifications may be practiced within the scope of the appended claims. In addition, each reference provided herein is incorporated by reference in its entirety to the same extent as if each reference was individually incorporated by reference. Where a conflict exists between the instant application and a reference provided herein, the instant application shall dominate.

Claims

WHAT IS CLAIMED IS:

1. A topical composition comprising: glucose oxidase, a base, an iron chelating agent, an enzyme stabilizer, and a surfactant.

2. The composition of claim 1, wherein the glucose oxidase is present at a concentration of from 1 to 10,000 units per milliliter.

3. The composition of claim 1, wherein the glucose oxidase is present at a concentration of from 10 to 1000 units per milliliter.

4. The composition of claim 1, wherein the base is NaHCCh, (NH^CCh, KHCO3, or tris(hydroxymethyl)aminomethane.

5. The composition of claim 1, wherein the base is present in a concentration of from 0.1% to 15% (w / v).

6. The composition of claim 1, wherein the iron chelating agent comprises ethylenediaminetetraacetic acid (EDTA) or a salt thereof.

7. The composition of claim 1, wherein the iron chelating agent comprises EDTA disodium salt or tetrasodium salt.

8. The composition of claim 1, wherein the concentration of iron chelating agent is from 10 to 300 mM.

9. The composition of claim 1, wherein the enzyme stabilizer is gluconolactone, gluconic acid or gluconate thereof, metabisulfite, ascorbate, sodium chloride, monosodium phosphate dihydrate, trisodium citrate dehydrate, tetra potassium pyrophosphate, ammonium sulfate, ammonium tartrate or tetra sodium pyrophosphate.

10. The composition of claim 1, wherein the concentration of the enzyme stabilizer is from 1 to 33% (w / v).

11. The composition of claim 1, wherein the surfactant is ionic.

12. The composition of claim 1, wherein the surfactant is non-ionic.

13. The composition of claim 1, wherein the surfactant is cocoyl glutamate.

14. The composition of claim 1, wherein the concentration of the surfactant is from 0.1 % to 10% (w / v).

15. The composition of claim 1, further comprising a thickener.

16. The composition of claim 15, wherein the thickener is polyethylene oxide or carboxymethylcellulose.

17. The composition of claim 15, wherein the concentration of the thickener is from 0.5% to 5% (w / v).

18. The composition of claim 1, further comprising a carrier.

19. The composition of claim 18, wherein the carrier is mineral oil, water, or aloe vera gel.

20. The composition of any claim 1, further comprising an a-hydroxy acid.

21. The composition of claim 20, wherein the a-hydroxy acid is gluconic acid, glycolic acid, salicylic acid, citric acid, lactic acid malic acid, tartaric acid, or 2-hydroxyalkanoic acid or a salt or lactone thereof.

22. The composition of claim 1, wherein the concentration of the a-hydroxy acid is from 3% and 33% (w / v).

23. The composition of claim 1, wherein the pH is from 4 to 7.

24. The composition of claim 1, wherein the glucose oxidizer is glucose oxidase, the base is tris(hydroxymethyl)aminomethane, the iron chelating agent is EDTA, the enzyme stabilizer is gluconolactone, and the surfactant is disodium cocoyl glutamate.

25. The composition of claim 24, wherein the concentration of glucose oxidase is about 0.5 mg / mL, the concentration of tri s(hydroxymethyl)aminom ethane is about 7.5%, the concentration of EDTA is about 100 mM, the concentration of gluconolactone is about 10%, and the concentration of disodium cocoyl glutamate is about 1.5%, wherein all percentages are (w / v).

26. The composition of claim 25, further comprising a carrier that is water.

27. The composition of claim 1, wherein the composition is formulated as a spray.

28. The composition of claim 1, wherein the composition is formulated as a lotion.

29. The composition of claim 1, wherein the composition is combined with a wipe substrate.

30. The composition of claim 1, wherein the composition is sulfate free, paraben free, or aluminum free.

31. A method of treating or preventing a disease or condition mediated by glucose- stimulated microbial growth, the method comprising topically administering an effective amount of a composition of any one of claims 1 to 30 to a subject in need thereof.

32. The method of claim 31, wherein the condition is redness, inflammation, irritation, malodor, pain, pruritis, or discomfort.

33. The method of claim 31, wherein the subject has glycosuria.

34. The method of claim 31, wherein the subject is taking an SGLT inhibitor.

35. The method of claim 31, wherein the subject has diabetes, chronic kidney disease, or heart failure.

36. The method of claim 31, wherein the topically administering comprises spraying the composition on the subject.

Images