Methods and compositions for modulating microbiome and preventing dysbiosis

Abstract

Methods and compositions for modulating the microbiome of the urogenital region or skin region of a user are disclosed. The method may include applying a composition to a urogenital region or skin region of a user, wherein the composition may include a carrier and a therapeutic agent. The therapeutic agent may comprise at least one prebiotic comprising at least one high molecular weight dextrin having two or more alpha-1, 6-glycosidic bonds, with or without a cyclic moiety. The at least one high molecular weight dextrin having two or more alpha-1, 6-glycosidic bonds comprises a highly branched cyclodextrine, a beta-limit dextrin, or a combination thereof. The method may also include promoting healthy microbiota balance in the urogenital region or skin region of the user. Further disclosed is a composition for modulating the microbiome of the urogenital region or skin region of a user wherein the composition comprises a single liquid phase comprising an aqueous solution and a therapeutic agent. The therapeutic agent may comprise at least one prebiotic compound comprising at least one high molecular weight dextrin having two or more alpha-1, 6-glycosidic bonds, having or not having a cyclic moiety, such as a highly branched cyclodextrin, a beta-limit dextrin, or a combination thereof. The disclosed methods and compositions for modulating the microbiome in the urogenital region or skin region of a user contribute to promoting the growth of healthy Lactobacillus species, thereby preventing dysbiosis and other related conditions and infections.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 573,058, filed April 2, 2024, which is expressly incorporated herein by reference in its entirety. Background Technology

[0003] Humans are colonized by microorganisms in the gastrointestinal tract, on the skin, and in other epithelial and tissue niches, such as the oral cavity, ocular surface, and vagina. A healthy microbiome in these areas can contain hundreds of different bacterial species. A healthy microbiome provides the host with a variety of benefits, including resistance to colonization of a broad spectrum of pathogens, biosynthesis and absorption of essential nutrients, and immune stimulation. A marker of a healthy microbiome is typically the presence of known healthy *Lactobacillus* bacteria. *Lactobacillus* species are commonly found on the body's external surfaces, such as the skin, epithelium, and mucous membranes. The presence of *Lactobacillus* has been shown to be important in regulating urogenital health, particularly in women, as *Lactobacillus* species are common in the vagina and bladder.

[0004] For example, a normal vagina typically contains more than about 10 ml of vaginal fluid. 4 Lactobacillus. Under normal conditions, the vaginal flora provides a mildly acidic environment that helps prevent the invasion of pathogenic microorganisms. Unfortunately, the balance of the vaginal flora can be easily disrupted by various external factors, ultimately leading to vaginal infections. Vaginal infections include, but are not limited to, bacterial vaginosis, candidal vaginitis (“yeast”), and trichomonal vaginitis (“trichomoniasis”).

[0005] Current treatment options for vaginal bacterial infections involve the use of various broad-spectrum antibiotics, such as metronidazole. However, antibiotics are often undesirable because they can kill a wide range of normal bacterial flora in the vagina, including beneficial lactobacilli. This can lead to secondary complications, as lactobacilli help regulate a variety of other opportunistic pathogens in the vagina. This treatment may then necessitate further interventions, such as ingesting cultured dairy products to replace the body's existing lactobacilli, and treatment with antifungal agents. Furthermore, elevated levels of anaerobic bacteria due to a lack of lactobacilli can further complicate the infection. Additionally, frequent intravaginal use of antibiotics can cause systemic toxicity through absorption from the vagina.

[0006] Likewise, an ecological imbalance of the normal bacterial flora in the bladder can be associated with urinary incontinence, overactive bladder symptoms, and urinary tract infections. Urinary incontinence (UI) and overactive bladder (OAB) can cause a person to experience the sensation of needing to urinate immediately, regardless of whether the bladder is full. Urinary tract infections (UTIs) can be a fairly common infection, especially in women, and can cause painful and negative symptoms, such as fever, pain, or burning while urinating, and the frequent sensation of needing to urinate.

[0007] An ecological imbalance of the bladder microbiome is a global problem. For example, approximately 800 million people worldwide suffer from UI, and of those 800 million, 70% are women. Despite the large number of people suffering from UI, there is a lack of adequate long-term treatment. There are a variety of products that provide the ability to potentially reduce or manage incontinence symptoms without medical intervention, however, these products can involve the insertion of various physical products or the provision of various stimuli in the vicinity of a person’s bladder. Furthermore, current treatment regimens for UTIs involve the use of various broad-spectrum antibiotics, which can kill beneficial lactobacilli and prevent modulation of the bladder microbiome. However, if healthy Lactobacillus bacteria can be supported, symptoms of UTIs, UI, and OAB can be reduced or potentially prevented.

[0008] Accordingly, there is a need for compositions and methods for modulating the microbiome, particularly the vaginal, bladder, and other skin areas of a user to improve the urogenital health of the user. There is also a need for compositions and methods for preventing or treating incontinence, overactive bladder, urinary tract infections, bacterial vaginosis, candidal vaginitis, and trichomonal vaginitis in a user. SUMMARY

[0009] It has now been surprisingly discovered that high molecular weight branched dextrins, which can contain two or more alpha-1,6-glycosidic linkages, with or without cyclic moieties, can help modulate the microbiome of a user’s urogenital area or skin area by promoting the growth of certain commensal bacteria, such as Lactobacillus, but maintaining or hindering the growth of certain pathogenic bacteria, such as Escherichia coli. Accordingly, it has been discovered that certain therapeutic agents comprising at least one prebiotic compound, such as a high molecular weight branched dextrin having two alpha-1,6-glycosidic linkages, with or without cyclic moieties, can be administered to a user to treat or prevent certain conditions of the urogenital area and skin.

[0010] The present disclosure relates to methods and compositions for modulating the microbiome of a user's urogenital or skin area. In one aspect, a method for modulating the microbiome of a user's urogenital or skin area is provided. The method can include applying a composition to a user's urogenital and / or skin area, the composition comprising a carrier and a therapeutic agent. The therapeutic agent may, for example, comprise at least one prebiotic compound comprising at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages. The method can further include promoting a healthy microflora balance of the user's urogenital area or skin area.

[0011] In one aspect, the prebiotic compound comprising at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages has a molecular weight greater than about 25,000 kDa. The at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages can or can not have a cyclic moiety. In preferred embodiments, the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages is a highly branched cyclic dextrin, a beta-limit dextrin, or a mixture thereof. In one embodiment, the prebiotic compound comprises only highly branched cyclic dextrin. In another embodiment, the prebiotic compound comprises only beta-limit dextrin. In further embodiments, the prebiotic compound comprises a mixture of both highly branched cyclic dextrin and beta-limit dextrin. The dextrins of the present disclosure can have a purity level of about 80% or greater, such as about 95% or greater, such as about 99% or greater.

[0012] The methods of the present disclosure can include applying a composition to a user's urogenital and / or skin area. In some embodiments, the user's urogenital area includes the vaginal canal, vulva, vagina, urethra, urinary tract, bladder, and / or surrounding areas. In other embodiments, the skin area of the body includes any external surface of the body, including but not limited to skin, epithelium, mucosa, and any other tissue forming the outer layer of the body surface.

[0013] In one embodiment, the composition has a pH of about 3 to about 6, such as about 4 to about 5. To achieve the desired properties of the composition, including pH, in other embodiments, the composition can further comprise additional prebiotics, surfactants, esters, humectants, pH adjusters, rheology modifiers, gelling agents, nitrogen sources, and / or antimicrobial agents. In alternative embodiments, the composition is in the form of a liquid, gel, cream, spray, and / or suppository. In further embodiments, the composition is free of alcohol.

[0014] In certain embodiments, the composition comprises a carrier and a therapeutic agent. The carrier, for example, can include an aqueous solution and can be greater than about 90% weight / volume of the composition. The therapeutic agent, for example, can comprise from about 0.1% weight / volume to about 20% weight / volume of the composition.

[0015] The methods of the present disclosure can comprise promoting a healthy microbiota balance of a urogenital region and / or a skin region of a user. Promoting a healthy microbiota balance can comprise promoting growth of Lactobacillus bacteria relative to growth of one or more types of bacteria comprising Escherichia coli, Staphylococcus aureus, Streptococcus anginosus, or mixtures thereof. For example, promotion of healthy Lactobacillus species can be reported as a ratio of healthy bacteria growth to harmful bacteria growth. In certain embodiments, the ratio of growth of Lactobacillus species to growth of one or more types of bacteria comprising Escherichia coli, Staphylococcus aureus, Streptococcus anginosus, or mixtures thereof is greater than about 1, such as greater than about 1.5, such as greater than about 1.75, such as greater than about 2.0, such as greater than about 2.5, such as greater than about 3.0, such as greater than about 3.5, and even greater than about 5.0 after exposure to about 1% weight / volume to about 20% weight / volume of the composition in a 48 hour competitive co-culture assay.

[0016] In alternative embodiments, the methods of the present disclosure can further comprise applying the composition to a substrate. The substrate, for example, can be a wipe, or at least a portion of an absorbent article. In some embodiments, the ratio of growth of Lactobacillus species to growth of one or more types of bacteria comprising Escherichia coli, Staphylococcus aureus, Streptococcus anginosus, or mixtures thereof is greater than about 1, such as greater than about 1.25, such as greater than about 1.5, such as greater than about 1.75, such as greater than about 2.0, and even greater than about 2.5 after exposure to about 1.5% weight / volume to about 8.5% weight / volume of the composition in a 48 hour competitive co-culture assay after application to a substrate.

[0017] In another aspect, a composition for modulating a microbiome of a urogenital region or a skin region of a user is provided. The composition, for example, can comprise a single liquid phase. The single liquid phase can comprise an aqueous solution and a therapeutic agent. The therapeutic agent, for example, can comprise at least one prebiotic compound comprising at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages.

[0018] In certain embodiments, the composition is free of alcohol. In further embodiments, the composition is not an emulsion. Notably, in certain embodiments, the composition is free of any probiotic bacteria.

[0019] Other features and aspects of the present disclosure are discussed in more detail below. BRIEF DESCRIPTION OF DRAWINGS

[0020] The complete and enabling disclosure of the present disclosure is set forth in the rest of the specification, including the references to the figures, in which:

[0021] Figure 1 Graphically illustrates the mean change in log CFU / mL (Delta) for Lactobacillus crispatus KC18-1173-1 and E. coli KC16-7171-8 after exposure to 2% w / v prebiotic compound in the competitive co-culture assay described in Example 3. Error bars represent the standard error of the mean.

[0022] Figure 2 Graphically illustrates the mean change in log CFU / mL (Delta) for Lactobacillus crispatus KC18-1173-1 and E. coli KC17-4298-8 after exposure to 2% w / v prebiotic compound in the competitive co-culture assay described in Example 3. Error bars represent the standard error of the mean.

[0023] Figure 3 Graphically illustrates the mean change in log CFU / mL (Delta) for Lactobacillus crispatus KC18-1173-1 and Staphylococcus aureus KC17-4367-2 after exposure to 2% w / v prebiotic compound in the competitive co-culture assay described in Example 3. Error bars represent the standard error of the mean.

[0024] Figure 4 Graphically illustrates the mean change in log CFU / mL (Delta) for Lactobacillus crispatus KC18-1173-1 and Angina Streptococcus KC18-1131-3B after exposure to 2% w / v prebiotic compound in the competitive co-culture assay described in Example 3. Error bars represent the standard error of the mean.

[0025] Figure 5 Graphically illustrates the mean percent cell viability (%) (MTT assay) of EPI-200 tissue after exposure to different concentrations of highly branched cyclic dextrin (HBCD) as described in Example 5. Triton X-100 was used as a positive control to demonstrate a decrease in cell viability, and Milli-Q water was used as a negative control. Error bars represent the standard deviation.

[0026] Figure 6Graphically illustrated are the mean values (pg / mL) of IL-1a and IL-8 inflammatory markers following exposure of EPI-200 tissue to different concentrations of highly branched cyclic dextrin (HBCD) as described in Example 5. Triton X-100 was used as a positive control to demonstrate an increase in IL-1a and IL-8, and Milli-Q water was used as a negative control. Error bars represent standard deviation.

[0027] Reference numbers that are repeated in the specification and drawings are intended to refer to the same or like components or elements throughout the present disclosure.

[0028] Definitions

[0029] As used herein, the term "inhibit" generally means to reduce by a measurable amount or to completely prevent.

[0030] As used herein, the term "urogenital" refers to the vaginal cavity, vulva, vagina, urethra, urinary tract, bladder, and surrounding areas.

[0031] As used herein, the term "skin" refers to epithelium, mucosa, and any other tissue forming the outer layer of the body surface.

[0032] As used herein, the term "user" or "subject" refers to a human being receiving the compositions of the present disclosure.

[0033] As used herein, the terms "effective amount" and "therapeutic amount" are an amount sufficient to inhibit, but not necessarily kill, a pathogenic microorganism that can be responsible for or contribute to a vaginal or bladder infection. In fact, although not necessary, it can be desirable to use a concentration that does not significantly affect or inhibit the growth characteristics of the normal vaginal or bladder flora or otherwise significantly irritate the vaginal or bladder tissue when used in an inhibitory, non-cytotoxic, or clinical concentration. For example, the therapeutic agent can desirably be employed at a concentration of about 0.01% weight / volume to about 20% weight / volume, in some embodiments about 0.1% weight / volume to about 10% weight / volume, in some embodiments about 0.2% weight / volume to about 7.5% weight / volume, and in some embodiments about 0.5% weight / volume to about 5.0% weight / volume. It will be appreciated that this dosage can vary with age, condition, and microbiome of the site, and can be readily determined by one skilled in the art.

[0034] As used herein, the term "treatment effect" refers to the ability of the compositions and methods of the present disclosure to stimulate the growth of Lactobacillus species relative to E. coli, S. aureus, S. anginosus, or mixtures thereof, as measured according to the treatment effect protocol described below. The treatment effect can be expressed as the ratio of Lactobacillus species to E. coli, S. aureus, S. anginosus, or mixtures thereof, and is desirably greater than about 1, such as greater than about 1.5, such as greater than about 1.75, such as greater than about 2.0, such as greater than about 2.5, such as greater than about 3, such as greater than about 3.5, and even greater than about 5.

[0035] As used herein, the designation "% weight / volume" or "weight / volume" refers to a value obtained by dividing the weight of a substance (in grams) by the volume of the solution (in milliliters), and then multiplying by 100.

[0036] As used herein, the term "soluble" when referring to a bladder treatment agent means that the substance is at least soluble according to the method described by L. Prosky et al., J. Assoc. Off. Anal. Chem. 71, 1017-1023 (1988). DETAILED DESCRIPTION

[0037] Provided herein are methods and compositions for modulating the microbiome of a user's urogenital region or skin region. The methods and compositions of the present disclosure are intended to stimulate the growth of gram-positive bacilli belonging to the Lactobacillus species. It is believed that stimulating the growth and dominance of Lactobacillus is able to reestablish a healthy flora by reducing or excluding pathogenic bacterial populations. The compositions of the present disclosure generally comprise a treatment agent capable of promoting the growth of gram-positive bacilli belonging to the Lactobacillus species. Preferably, the treatment agent of the composition comprises at least one prebiotic comprising at least one type of high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages.

[0038] Lactobacillus species promote a healthy intimate microenvironment by competitively excluding pathogens, producing hydrogen peroxide, producing bacteriocins, producing surfactants, and producing other antimicrobial products that prevent infection and train the immune system. Notably, Lactobacillus produces lactic acid, which can help lower the pH of the vagina. In addition, lactic acid can also play a role in maintaining the skin barrier. Thus, the methods and compositions disclosed herein have broad applicability and, in some embodiments, can be applied anywhere where Lactobacillus is present.

[0039] In one embodiment, a method for modulating the microbiome of a user's urogenital or skin area can include applying a composition to the user's urogenital or skin area, wherein the composition includes a carrier and a therapeutic agent to promote a healthy microflora balance of the user's urogenital or skin area.

[0040] The carrier of the composition can include, for example, a "dermatologically acceptable carrier," which refers to a carrier that is suitable for topical application to epithelium and is compatible with the therapeutic agent. The dermatologically acceptable carrier can take a wide variety of forms, such as, for example, simple solutions (water-based or oil-based) and solid forms (e.g., gels or sticks). In some embodiments, the carrier can be aqueous or non-aqueous. Non-aqueous carriers can include, for example, glycols such as propylene glycol, butylene glycol, triethylene glycol, hexylene glycol, polyethylene glycol, ethoxydiglycol, and dipropylene glycol; alcohols such as ethanol, n-propanol, and isopropanol; triglycerides; ethyl acetate; acetone; triacetin; and combinations thereof. However, in some preferred embodiments, the non-aqueous carrier is not an alcohol, such that the composition is alcohol-free.

[0041] In preferred embodiments, the carrier is an aqueous solution. For example, water is a particularly preferred aqueous carrier, such that the dermatologically acceptable carrier is used as a water-based simple solution. In some embodiments, the carrier constitutes greater than about 75% weight / volume, more preferably greater than about 85% weight / volume, and still more preferably greater than about 90% weight / volume. In other embodiments, the carrier can constitute greater than about 95% weight / volume, or greater than about 96%, 97%, 98%, or even 99% weight / volume.

[0042] Thus, in other embodiments, the compositions of the present disclosure include less than about 20% weight / volume of the therapeutic agent. In some embodiments, the total amount of the therapeutic agent is less than about 15% weight / volume, such as less than about 10% weight / volume, such as less than about 7.5% weight / volume, and such as less than about 5% weight / volume. In some embodiments, the total amount of the therapeutic agent can be from about 0.01% weight / volume to about 20% weight / volume, such as from about 0.1% weight / volume to about 10% weight / volume, such as from about 0.25% weight / volume to about 5% weight / volume, such as from about 0.5% weight / volume to about 2% weight / volume. For example, in one embodiment, the composition includes from about 0.1% weight / volume to about 2% weight / volume of the therapeutic agent, which includes beta-limit dextrin, highly branched cyclic dextrin, or a mixture thereof.

[0043] The therapeutic agent can comprise at least one prebiotic compound comprising at least one high molecular weight dextrin. The dextrin can be branched, cyclic, and / or can contain two or more alpha-1,6-glycosidic bonds. Prebiotic compounds are the most common plant fiber that is an indigestible food ingredient that is selectively used as a food source by healthy bacteria to promote their growth. Dextrins are a type of prebiotic compound that are generally low molecular weight carbohydrates produced by the hydrolysis of starches and glycogen, such that dextrins are mixtures of polymers of D-glucose units linked by alpha-1,4-glycosidic bonds and / or alpha-1,6-glycosidic bonds. Starch hydrolysis can be accomplished by heat, acid, or enzymes, or combinations thereof.

[0044] Surprisingly, it has been discovered that dextrins having a high molecular weight are effective prebiotic compounds for modulating the microbiome of a user's urogenital or skin area by promoting the growth of certain commensal bacteria, such as lactobacilli, but maintaining or hindering the growth of pathogenic bacteria. In certain embodiments, the high molecular weight dextrin has a molecular weight of greater than about 25,000 kDa, such as greater than about 30,000 kDa, such as greater than about 100,000 kDa, such as greater than about 1,000,000 kDa, and even greater than about 3,000,000 kDa. In other embodiments, the high molecular weight dextrin has a molecular weight of less than about 30,000,000 kDa, such as less than about 10,000,000 kDa, such as less than about 5,000,000 kDa, and less than about 3,500,000 kDa. In one embodiment, the high molecular weight dextrin has a molecular weight of about 30,000 kDa to about 1,000,000 kDa. In another embodiment, the high molecular weight dextrin has a molecular weight of even greater than about 3,000,000 kDa. In a preferred embodiment, the at least one high molecular weight dextrin has a molecular weight of about 25,000 kDa to about 10,000,000 kDa, such as about 30,000 kDa to about 3,000,000 kDa.

[0045] In a preferred embodiment, the therapeutic agent comprises at least one prebiotic comprising at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic bonds, such that the at least one high molecular weight dextrin is a highly branched cyclic dextrin, a beta-limit dextrin, or a mixture thereof. The number of branches in the at least one high molecular weight dextrin correlates to how many alpha-1,6-glycosidic bonds are present in the dextrin.

[0046] Highly branched cyclic dextrins and beta-limit dextrins can both be distinguished from other dextrins because they possess a high molecular weight, they have a narrow size distribution, and they have at least two alpha- 1,6-glucosidic linkages. Furthermore, these dextrins are produced via enzymatic hydrolysis of starch using amylases that differ from the more common methods that utilize heat with or without acid. In one embodiment of the present disclosure, the at least one high molecular weight dextrin having two or more alpha- 1,6-glucosidic linkages comprises only beta-limit dextrins. Beta-limit dextrin, for example, is a highly branched alpha-glucan of molecular weight about 3,000,000 kDa consisting of a straight chain of alpha- 1,4 D-glucose residues linked by alpha- 1,6-glucosidic linkages and is a derivative of amylopectin. Beta-limit dextrin, for example, is formed when beta-amylase binds to every other alpha- 1,4 glucosidic linkage from the non-reducing end of the starch polymer, thereby cleaving the consecutive maltose units. However, because beta-amylase cannot cleave alpha- 1,6-glucosidic linkages, beta-limit dextrin contains all of the original branches (e.g., all of the original alpha- 1,6-glucosidic linkages) of the starting starch molecule.

[0047] In certain embodiments of the present disclosure, beta-limit dextrin can comprise at least 2 branches, such as at least 3 branches, such as at least 4 branches, such as at least 5 branches, such as at least 8 branches, such as at least 10 branches, and even such as at least 20 branches or more.

[0048] In another embodiment of the present disclosure, the at least one high molecular weight dextrin having two or more alpha- 1,6-glucosidic linkages has cyclic moieties and comprises only highly branched cyclic dextrins. Highly branched cyclic dextrins, for example, have a molecular weight between 30,000 kDa and 1,000,000 kDa and can comprise cyclic moieties of D-glucose monomers linked together by alpha- 1,4-glucosidic linkages, where branching occurs through alpha- 1,6-glucosidic linkages. In some cases, highly branched cyclic dextrins are produced from starch sources by enzymatic hydrolysis with alpha-amylases to produce a cluster of short linear alpha- 1,4 glucose chains that are interconnected via alpha- 1,6 linkages. Cyclization via intramolecular transglycosylation is carried out by a 1,4-alpha-D-glucan branching enzyme that links adjacent branched clusters via alpha- 1,6-glucosidic linkages. In certain embodiments, highly branched cyclic dextrins can also have at least two alpha- 1,6-glucosidic linkages and can be produced from amylopectin via cyclization reactions by branching enzymes. An exemplary commercially available highly branched cyclic dextrin is CLUSTER dextrin ™which is available from Ezaki Glico Co., Ltd., Nishiyodogawa Ward, Osaka, Japan.

[0049] In other embodiments of the disclosure, the highly branched, cyclic dextrin can comprise at least 5 branches, such as at least 7 branches, such as at least 8 branches, such as at least 10 branches, and less than 50 branches, such as less than 40 branches, such as less than 30 branches, and such as less than 20 branches.

[0050] The high molecular weight dextrin having two or more a-1,6-glycosidic linkages used as part of a therapeutic agent can have unexpectedly high purity levels. In one embodiment, for example, the at least one high molecular weight dextrin having two or more a-1,6-glycosidic linkages has a purity level of about 80% or greater, such as about 92.5% or greater, such as about 95% or greater, such as about 97.5% or greater, such as about 99% or greater. Further, the purified dextrin form contains less than 5% monosaccharides, such as individual glucose molecules.

[0051] It has been discovered that high molecular weight dextrins having two or more a-1,6-glycosidic linkages, with or without cyclic moieties connecting adjacent branched clusters via a-1,6-glycosidic linkages, have an enhanced effect on promoting the growth of healthy Lactobacillus bacteria. Without intending to be bound by theory, the inventors have discovered that the presence of at least one high molecular weight dextrin having two or more a-1,6-glycosidic linkages helps to promote a healthy microbiota balance in the urogenital or skin area of a user. The inventors have discovered that the at least one high molecular weight dextrin having two or more a-1,6-glycosidic linkages exhibits a number of unique properties that make its effect on promoting the growth of Lactobacillus species relative to the growth of one or more types of bacteria including E. coli, S. aureus, S. anginosus, or mixtures thereof, unexpected. For example, the at least one high molecular weight dextrin having two or more a-1,6-glycosidic linkages exhibits a narrow size distribution and a molecular weight greater than about 25,000 kDa. Further, in certain embodiments, the high molecular weight dextrin having two or more a-1,6-glycosidic linkages is produced via enzymatic hydrolysis, whereas more common methods utilizing heat or acid can have other detrimental effects on the at least one high molecular weight dextrin. Further, the high purity level of the at least one high molecular weight dextrin having two or more a-1,6-glycosidic linkages also exhibits other chemical and economic advantages as it allows for less product to be used to achieve a therapeutic amount.

[0052] In certain embodiments, for example, the composition produces a therapeutic effect (ratio of growth of Lactobacillus spp. to growth of one or more types of bacteria including E. coli, S. aureus, S. anginosus, or mixtures thereof) of greater than about 1, such as greater than about 1.5, such as greater than about 1.75, such as greater than about 2.0, such as greater than about 2.5, such as greater than about 3, such as greater than about 3.5, such as greater than about 4.0, such as greater than about 4.5, such as greater than about 5, and even greater than about 5.5, after exposure to about 1% weight / volume to about 20% weight / volume of the composition in a 48 hour competitive co-culture assay in the urogenital or skin area of a user. In some embodiments, a therapeutic effect of greater than about 1.5 is exhibited even when the pathogenic bacteria are exposed to only about 2% weight / volume of the composition, which is a relatively low amount. Thus, without intending to be limited by theory, even small amounts of one or more therapeutic agents can promote a healthy microbiota balance in the urogenital or skin area of a user, and the ability to have exhibited a therapeutic effect even when using a minimal amount of the composition can not only provide various health and wellness related benefits to a user, but can also provide economic benefits.

[0053] Further, in other embodiments, a therapeutic effect of greater than about 2.5 can be achieved, such as when the pathogenic bacteria are exposed to about 20% weight / volume of the composition. For example, in certain embodiments, a therapeutic effect of greater than 5.5 can be achieved when the pathogenic bacteria are exposed to about 20% weight / volume of the composition.

[0054] Thus, the composition can be applied to any urogenital surface or skin surface to promote the growth of healthy bacteria and modulate a balanced microbiome. In certain embodiments, the methods and compositions disclosed herein can improve overall skin health and maintenance of the skin barrier by increasing the production of lactic acid, and can be applied to any skin surface, including but not limited to epithelium, mucosa, and any other tissue that forms the outer layer of the body surface. In preferred embodiments, the methods and compositions can improve urogenital health, and can be applied to any urogenital surface, including but not limited to the vaginal canal, vulva, vagina, urethra, urinary tract, bladder, and surrounding areas. Such methods and compounds can be considered for maintaining vaginal and bladder health, promoting skin balance in intimate areas, promoting urinary tract health, and preventing bacterial vaginosis, yeast infections, urinary tract infections, incontinence, overactive bladder, premature birth, infertility, and other bacterial infections related to intimate area health. In other embodiments, such methods and compounds disclosed herein can be related to cosmetic endpoints including healthy voiding, less itching, and reduction in vaginal malodor.

[0055] In other embodiments of the disclosure, a composition for modulating the microbiome of a urogenital or skin area of a user is disclosed. The composition, for example, comprises a single liquid phase such that the single liquid phase comprises an aqueous solution and a therapeutic agent. The therapeutic agent comprises at least one prebiotic compound comprising at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages. In preferred embodiments, the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages comprises highly branched cyclic dextrins, beta-limit dextrins, or mixtures thereof. In one embodiment of the disclosure, the at least one dextrin having two or more alpha-1,6-glycosidic linkages comprises only highly branched cyclic dextrins. In another embodiment of the disclosure, the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages comprises only beta-limit dextrins.

[0056] In certain embodiments, the single liquid phase of the composition comprises an aqueous solution. Water, for example, is a particularly preferred aqueous carrier. In preferred embodiments, the single liquid phase of the composition does not comprise an alcohol, such that the composition is alcohol-free. In one particular embodiment of the disclosure, the composition is not an emulsion.

[0057] In another particular embodiment of the disclosure, the composition is free of any probiotic bacteria. Probiotic bacteria, for example, are live microorganisms intended to maintain or improve the healthy bacteria in the body, such as bacteria and yeast. Probiotics are different from prebiotics because probiotics encompass the bacteria themselves, whereas prebiotics are merely a food source for the bacteria. Thus, while probiotics comprise live microorganisms, prebiotics do not comprise live microorganisms. Without intending to be bound by theory, the inventors have surprisingly found that therapeutic effects can be produced even without using any probiotic bacteria in the composition by using a therapeutic agent comprising at least one prebiotic compound comprising at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages.

[0058] The compositions of the disclosure can be applied to a user in several forms. For example, the compositions can be prepared into a formulation for application to a user, or can be applied to a substrate, such as a wiping substrate, for application to a user. Preferably, the therapeutic agents useful in the disclosure are soluble so that they are easily formulated for application to a user.

[0059] In some embodiments, the composition may be formulated for application to a user by external application in various forms, including but not limited to liquids, creams, gels, sprays, or suppositories. In other embodiments, the composition may be formulated as a therapeutic preparation, such that it can be formulated as a moisturizer, lotion, jelly, liniment, ointment, cream, oil, foam, film, wash, sustained-release polymer, coating agent, liquid, vaginal capsule, vaginal tablet, vaginal film, vaginal sponge, vaginal suppository, etc. The composition may also be applied to a vaginal insert, tampon, wipe, or pad, and then applied to the vagina.

[0060] In other embodiments, the composition may contain other components, such as, for example, additional prebiotics, surfactants, esters, wetting agents, pH adjusters, rheology modifiers, gelling agents, nitrogen sources, and antimicrobial agents.

[0061] Other prebiotics

[0062] In some embodiments, the composition may comprise one or more additional prebiotics other than at least one high molecular weight dextrin disclosed herein. These additional prebiotics may have a synergistic effect when combined with at least one high molecular weight dextrin having two or more α-1,6-glycosidic bonds. Suitable alternative prebiotics can be selected from the following groups: α-D-lactose, maltitol, N-acetylglucosamine, α-cyclodextrin, β-cyclodextrin, glucomannan, D-tagatose, 2-deoxy-D-ribose, α-methyl-D-glucosidase, amylopectin, β-D-fructose, β-D-glucose, D-arabinose, D-cellobiose, glucan, type I dextrin, type II dextrin, malate, D-trehalose, 4-O-β-D-galactopyranosyl-D-glucol, lactitol, lactulose, maltotriose, isomaltulose, pectin, pullullan, salicin, and xylitol.

[0063] surfactants

[0064] In some embodiments, the composition may contain one or more surfactants. In embodiments where the composition is included in a wipe, the composition may also contain one or more surfactants. These surfactants may be selected from anionic, cationic, nonionic, amphoteric, and amphoteric surfactants. The amount of surfactant may range from 0.01% to 30%, or 10% to 30%, or 0.05% to 20%, or 0.10% to 15% by weight of the total composition. In some embodiments, such as when the wetting composition is used with a wipe, the surfactant may account for less than 5% by weight of the total wetting composition.

[0065] Suitable anionic surfactants include, but are not limited to, C8 to C96.22 Alkane sulfates, ether sulfates, and sulfonates. Suitable sulfonates are primary C8 to C 22 Alkane sulfonates, primary C8 to C 22 Alkane disulfonates, C8 to C 22 Olefin sulfonates, C8 to C 22 Hydroxyalkane sulfonates or alkyl glyceryl ether sulfonates. Specific examples of anionic surfactants include ammonium lauryl sulfate, ammonium laureth sulfate, triethylamine lauryl sulfate, triethylamine laureth sulfate, triethanolamine lauryl sulfate, triethanolamine laureth sulfate, monoethanolamine lauryl sulfate, monoethanolamine laureth sulfate, diethanolamine lauryl sulfate, diethanolamine laureth sulfate, sodium lauryl glyceryl sulfate, sodium lauryl sulfate, sodium laureth sulfate, potassium laureth sulfate, sodium laurylsarcosinate, sodium laurocapram, potassium lauryl sulfate, sodium trideceth sulfate, sodium methyl lauroyl taurate, sodium lauroyl methyl isethionate, sodium laureth sulfosuccinate, sodium lauroyl sulfosuccinate, sodium tridecylbenzenesulfonate, sodium dodecylbenzenesulfonate, sodium lauryl monoethanolamide acetate, and mixtures thereof. Other anionic surfactants include C8 to C 22 Acyl glycinate salts. Suitable glycinate salts include sodium cocoyl glycinate, potassium cocoyl glycinate, sodium lauroyl glycinate, potassium lauroyl glycinate, sodium myristoyl glycinate, potassium myristoyl glycinate, sodium palmitoyl glycinate, potassium palmitoyl glycinate, sodium stearoyl glycinate, potassium stearoyl glycinate, ammonium cocoyl glycinate, and mixtures thereof. The cationic counterion for forming the glycinate salt can be selected from sodium, potassium, ammonium, alkanolammonium, and mixtures of these cations.

[0066] Suitable cationic surfactants include, but are not limited to, alkyl dimethyl amine, alkyl amido propyl amine, alkyl imidazoline derivatives, quaternized amine ethoxylates, and quaternary ammonium compounds.

[0067] Suitable nonionic surfactants include, but are not limited to, alcohols, acids, amides, or alkyl phenols reacted with alkylene oxides, especially with ethylene oxide alone or with ethylene oxide and propylene oxide. Specific nonionic surfactants are C6 to C 22 Alkyl phenol-ethylene oxide condensates, C8 to C 13Condensation products of fatty, primary or secondary, straight chain or branched alcohols with ethylene oxide, and products made by condensing the reaction products of ethylene oxide with propylene oxide and ethylenediamine. Other nonionic surfactants include long chain tertiary amine oxides, long chain tertiary phosphine oxides, and dialkyl sulfoxides, alkyl polysaccharides, amine oxides, block copolymers, castor oil ethoxylates, cetyl-oleyl alcohol ethoxylates, cetyl-stearyl alcohol ethoxylates, decanol ethoxylates, dinonyl phenol ethoxylates, dodecyl phenol ethoxylates, end-capped ethoxylates, ether amine derivatives, ethoxylated alkanolamides, ethylene glycol esters, fatty acid alkanolamides, fatty alcohol alkoxylates, lauryl alcohol ethoxylates, mono-branched alcohol ethoxylates, natural alcohol ethoxylates, nonyl phenol ethoxylates, octyl phenol ethoxylates, oleyl amine ethoxylates, random copolymer alkoxylates, sorbitan ester ethoxylates, stearic acid ethoxylates, stearyl amine ethoxylates, synthetic alcohol ethoxylates, tall oil fatty acid ethoxylates, tallow amine ethoxylates, and tridecyl alcohol ethoxylates.

[0068] Suitable zwitterionic surfactants include, for example, alkyl amine oxides, alkyl hydroxysultaines, silicone amine oxides, and combinations thereof. Specific examples of suitable zwitterionic surfactants include, for example, 4-[N,N-di(2-hydroxyethyl)-N-octadecylammonium]-butane-1-carboxylate, S-[S-3-hydroxypropyl-S-hexadecylsulfonium]-3-hydroxy-pentane-1-sulfate, 3-[P,P-diethyl-P-3,6,9-trioxatetradecylphosphonium]-2-hydroxypropane-1-phosphate, 3-[N,N-dipropyl-N-3-dodecyloxy-2-hydroxypropylammonium]-propane-1-phosphonate, 3-(N,N-dimethyl-N-hexadecylammonium)propane-1-sulfonate, 3-(N,N-dimethyl-N-hexadecylammonium)-2-hydroxypropane-1-sulfonate, 4-[N,N-di(2-hydroxyethyl)-N-(2-hydroxydodecyl)ammonium]-butane-1-carboxylate, 3-[S-ethyl-S-(3-dodecyloxy-2-hydroxypropyl)sulfonium]-propane-1-phosphate, 3-[P,P-dimethyl-P-dodecylphosphonium]-propane-1-phosphonate, 5-[N,N-di(3-hydroxypropyl)-N-hexadecylammonium]-2-hydroxy-pentane-1-sulfate, lauryl hydroxysultaine, and combinations thereof.

[0069] Suitable amphoteric surfactants include, but are not limited to, derivatives of aliphatic quaternary ammonium compounds, phosphonium compounds, and sulfonium compounds, in which the aliphatic radicals can be straight-chained or branched, and in which one of the aliphatic substituents contains about 8 to about 18 carbon atoms and one substituent contains an anionic group (e.g., carboxyl, sulfonate, sulfate, phosphate, or phosphonate). Exemplary amphoteric surfactants are coco dimethyl carboxymethyl betaine, cocamidopropyl betaine, coco-betaine, oleyl betaine, cetyl dimethyl carboxymethyl betaine, lauryl bis-(2-hydroxyethyl) carboxymethyl betaine, stearic double-(2 hydroxypropyl) carboxymethyl betaine, oleyl dimethyl gamma-carboxypropyl betaine, lauryl bis-(2-hydroxypropyl) alpha-carboxyethyl betaine, cocoamphoacetate, and combinations thereof. Sulfo-betaines can include stearic dimethyl sulfo-propyl betaine, lauryl dimethyl sulfo-ethyl betaine, lauryl bis-(2-hydroxyethyl) sulfo-propyl betaine, and combinations thereof.

[0070] esters

[0071] In some embodiments, the composition comprises one or more esters. The ester can be selected from the group consisting of cetyl palmitate, stearyl palmitate, cetyl stearate, isopropyl laurate, isopropyl myristate, isopropyl palmitate, and combinations thereof. Fatty alcohols include octyldodecanol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, and combinations thereof. Fatty acids can include, but are not limited to, decanoic acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, arachidic acid, and behenic acid. Ethers such as eucalyptol, cetearyl glucoside, dimethyl isosorbide glyceryl-3 cetyl ether, glyceryl-3 decyl tetradecyl, propylene glycol myristyl ether, and combinations thereof can also be suitably used as emollients. Other suitable ester compounds for use in the antimicrobial compositions of the present disclosure are listed in International Cosmetic Ingredient Dictionary and Handbook, 11th Edition, CTFA, (January 2006) ISBN-10: 1882621360, ISBN-13: 978-1882621361 and 2007 Cosmetic Bench Reference, Allured Pub. Corporation (July 15, 2007) ISBN-10: 1932633278, ISBN-13: 978-1932633276, both of which are incorporated herein by reference to the extent they are consistent herewith.

[0072] humectants

[0073] In some embodiments, the composition comprises one or more humectants. Suitable humectants for use as carriers in the compositions of the present disclosure include, for example, glycerin, glycerin derivatives, hyaluronic acid, hyaluronic acid derivatives, betaine, betaine derivatives, amino acids, amino acid derivatives, glycosaminoglycans, glycols, polyols, sugars, sugar alcohols, hydrogenated starch hydrolysate, hydroxy acids, hydroxy acid derivatives, salts of PCA, and the like, and combinations thereof. Specific examples of suitable humectants include honey, sorbitol, hyaluronic acid, sodium hyaluronate, betaine, lactic acid, citric acid, sodium citrate, glycolic acid, sodium glycolate, sodium lactate, urea, propylene glycol, butylene glycol, pentylene glycol, ethoxydiglycol, methyl gluceth-10, methyl gluceth-20, polyethylene glycols (as listed in the International Cosmetic Ingredient Dictionary and Handbook, such as PEG-2 to PEG 10), propylene glycol, xylitol, maltitol, or combinations thereof.

[0074] The compositions of the present disclosure can comprise one or more humectants in an amount of from about 0.01% (by total weight of the composition) to about 20% (by total weight of the composition), or from about 0.05% (by total weight of the composition) to about 10% (by total weight of the composition), or from about 0.1% (by total weight of the composition) to about 5.0% (by total weight of the composition).

[0075] pH adjusting agents

[0076] In some embodiments, the compositions of the present disclosure can be acidic, i.e., have a pH of less than about 7.0 and more preferably less than about 6.0 (such as from about 3.0 to about 6.0) and still more preferably from about 4.0 to about 5.0. In particularly preferred embodiments, the pH can be maintained at a mildly acidic level to match the normal vaginal conditions, i.e., the environment in which the composition will typically be delivered. For example, the pH can be in the range of from about 3.0 to about 6.0, in some embodiments from about 3.5 to about 5.0, and in some embodiments from about 4.0 to about 4.5. The foregoing acidic pH can also provide other benefits. For example, when the composition is configured to form a gel, such as described below, low pH levels can also improve the rate of gelation and gel strength, thereby reducing the likelihood of leakage upon initial insertion of the composition into the vagina.

[0077] The pH of the composition can be adjusted using an organic acid. Organic acids useful in the present disclosure generally consist of a mono- or poly-carboxylic acid having one or more hydroxyl functional groups, at least one of which is introduced into the alpha-position (i.e., on the carbon atom adjacent to the carboxyl functional group). Examples of particularly useful organic acids can include citric acid, lactic acid, methyl lactic acid, phenyl lactic acid, malic acid, mandelic acid, glycolic acid, tartronic acid, tartaric acid, and gluconic acid. In particularly preferred embodiments, the organic acid is selected from the group consisting of citric acid, lactic acid, malic acid, glycolic acid, and tartaric acid. In certain embodiments, the organic acid can be provided with a suitable counterion, such as calcium, sodium, or magnesium.

[0078] In view of the foregoing, in certain embodiments, the compositions and formulations of the present disclosure can have a pH of from about 3.0 to about 6.0, more preferably from about 3.5 to about 5.0, and comprise a therapeutic agent comprising at least one prebiotic compound comprising at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages, wherein the total amount of therapeutic agent is from about 0.1 % weight / volume to about 2% weight / volume.

[0079] Rheology modifiers

[0080] Optionally, one or more rheology modifiers, such as a thickening agent, can be added to the composition. Suitable rheology modifiers are compatible with the therapeutic agent. As used herein, "compatible" means a compound that does not adversely affect the properties of the therapeutic agent when mixed therewith.

[0081] Thickening systems are used in the composition to adjust the viscosity and stability of the composition. In particular, the thickening system prevents the composition from running off the hands or body during dispensing and use of the composition. When the composition is used with a wipe product, a thicker formulation can be used to prevent the composition from migrating from the wipe substrate.

[0082] The thickening system should be compatible with the compounds used in the present disclosure; that is, the thickening system should not precipitate out, form a coacervate, or prevent the user from perceiving the conditioning benefits (or other desired benefits) to be obtained from the composition when used in combination with the therapeutic agent. The thickening system can comprise a thickening agent that provides both the thickening effect required of the thickening system and a conditioning effect to the user.

[0083] Thickening agents can include cellulose, gums, acrylates, starches, and various polymers. Suitable examples include, but are not limited to, hydroxyethyl cellulose, xanthan gum, guar gum, potato starch, and corn starch. In some embodiments, PEG-150 stearate, PEG-150 distearate, PEG-175 diisostearate, polyglyceryl-10 behenate / eicosadioate, distearyl ether-100 IPDI, polyacrylamidomethyl propane sulfonic acid, butylated PVP, and combinations thereof can be suitable.

[0084] While the viscosity of the composition is generally dependent on the thickening agent used and other components of the composition, the thickening agent of the composition suitably provides a composition having a viscosity in the range of greater than 1 cP to about 30,000 cP or higher. In another embodiment, the thickening agent provides a composition having a viscosity of about 100 cP to about 20,000 cP. In yet another embodiment, the thickening agent provides a composition having a viscosity of about 200 cP to about 15,000 cP. In embodiments where the composition is included in a wipe, the viscosity can be in the range of about 1 cP to about 2000 cP. In some embodiments, it is preferred that the viscosity of the composition be less than 500 cP.

[0085] When a thickening system is included, the compositions of the present disclosure can include a thickening system in an amount of up to about 20% by total weight of the composition, or from about 0.01% by total weight of the composition to about 20% by total weight of the composition. In another aspect, the thickening system is present in the antimicrobial composition in an amount of from about 0.10% by total weight of the composition to about 10% by total weight of the composition, or from about 0.25% by total weight of the composition to about 5% by total weight of the composition, or from about 0.5% by total weight of the composition to about 2% by total weight of the composition.

[0086] In one embodiment, the composition can comprise hydrophobic and hydrophilic ingredients, such as a lotion or cream. Typically, these emulsions have a dispersed phase and a continuous phase, and are typically formed by the addition of a surfactant or a combination of surfactants with different hydrophilic / lipophilic balance values (HLB). Suitable emulsifiers include surfactants with HLB values of 0 to 20, or 2 to 18. Suitable non-limiting examples include Ceteth-20, Ceteth Glucoside, Ceteth-10, Ceteth-2, Ceteth-20, Cocamide MEA, Glyceryl Laurate, Glyceryl Stearate, PEG-100 Stearate, Glyceryl Stearate, Glyceryl Stearate SE, Ethylene Glycol Distearate, Ethylene Glycol Stearate, Isosteareth-20, Laureth-23, Laureth-4, Lecithin, Methyl Glucose Sesquistearate, Oleth-10, Oleth-2, Oleth-20, PEG-100 Stearate, PEG-20 Almond Glycerides, PEG-20 Methyl Glucose Sesquistearate, PEG-25 Hydrogenated Castor Oil, PEG-30 Dipolyhydroxystearate, PEG-4 Dilaurate, PEG-40 Sorbitan Peroleate, PEG-60 Almond Glycerides, PEG-7 Olivate, PEG-7 Glyceryl Cocoate, PEG-8 Dioleate, PEG-8 Laurate, PEG-8 Oleate, PEG-80 Sorbitan Laurate, Polysorbate 20, Polysorbate 60, Polysorbate 80, Polysorbate 85, Propylene Glycol Isostearate, Sorbitan Isostearate, Sorbitan Laurate, Sorbitan Monostearate, Sorbitan Oleate, Sorbitan Sesquioleate, Sorbitan Stearate, Sorbitan Trioleate, Stearamide MEA, Steareth-100, Steareth-2, Steareth-20, Steareth-21. The composition can also comprise a surfactant or combination of surfactants that produces a liquid crystal network or a liposome network.Suitable non-limiting examples include OLIVEM 1000 (INCI: Cetearyl Olivate (and) Sorbitan Olivate (available from HallStar Company (Chicago, IL)); ARLACEL LC (INCI: Sorbitan Stearate (and) Sorbitol Laurate, commercially available from Croda (Edison, NJ); CRYSTALCAST MM (INCI: Beta Sitosterol (and) Sucrose Stearate (and) Sucrose Distearate (and) Cetyl Alcohol (and) Stearyl Alcohol, commercially available from MMP Inc. (South Plainfield, NJ); UNIOX CRISTAL (INCI: Cetyl Stearyl Alcohol (and) Polysorbate 60 (and) Cetearyl Glucoside, commercially available from Chemyunion (Sao Paulo, Brazil). Other suitable emulsifiers include lecithin, hydrogenated lecithin, lysolecithin, phosphatidylcholine, phospholipids, and combinations thereof.

[0087] Gelling agent

[0088] In some embodiments where the composition is in the form of a gel, the dispersed phase of the gel can be formed from any of a variety of different gelling agents, including temperature-responsive ("thermogelling") compounds, ion-responsive compounds, and the like. Thermogelling systems, for example, respond to changes in temperature (e.g., an increase in temperature) by changing from a liquid to a gel. In general, the temperature range of interest is from about 25 °C to about 40 °C, in some embodiments from about 35 °C to about 39 °C, and in one particular embodiment at body temperature (about 37 °C). In some cases, thermogelling block copolymers, graft copolymers, and / or homopolymers can be employed. For example, in some embodiments of the present application, polyoxyalkylene block copolymers can be used to form thermogelling compositions. Suitable thermogelling compositions can include, for example, homopolymers such as poly(N-methyl-N-n- propylacrylamide), poly(N-n-propylacrylamide), poly(N-methyl-N- isopropylacrylamide), poly(N-n-propylmethacrylamide), poly(N- isopropylacrylamide), poly(N,n-diethylacrylamide); poly(N- isopropylmethacrylamide), poly(N-cyclopropylacrylamide), poly(N- ethylmethacrylamide), poly(N-methyl-N-ethylacrylamide), poly(N- cyclopropylmethacrylamide), and poly(N-ethylacrylamide). Still other examples of suitable thermogelling polymers can include cellulose ether derivatives such as hydroxypropyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, and ethyl hydroxyethyl cellulose. In addition, thermogelling polymers can be prepared by making copolymers between (among) monomers, or by combining such homopolymers with other water-soluble polymers such as acrylic monomers (e.g., acrylic or methacrylic acid, acrylate or methacrylate esters, acrylamide or methacrylamide, and derivatives thereof).

[0089] In one particular embodiment of the present disclosure, for example, the composition is configured to rapidly form a gel when applied to the vagina. A "gel" is a colloid in which the dispersed phase in combination with the dispersion medium results in a jelly-like, solid, or semi-solid material. The gel can form in less than about one hour, in some embodiments less than about one minute, and in some embodiments less than about 30 seconds. Such rapid gelation, among other things, reduces the likelihood of leakage during use. In addition, because the gel can form within the vagina, it is more likely to maintain its structure and shape over an extended period of time. In this way, the gel can provide for the extended release of a therapeutic agent that suppresses and / or treats a vaginal infection. For example, the gel can remain within the vagina for about 2 hours to about 48 hours, thereby providing the desired effect of modulating the user's urinary microbiome.

[0090] While a variety of compounds can be employed, water is typically employed as the dispersion medium for the gel to optimize biocompatibility. Other possible dispersion media include non-aqueous solvents, including glycols such as propylene glycol, butylene glycol, triethylene glycol, hexylene glycol, polyethylene glycol, ethoxydiglycol, and dipropylene glycol; alcohols such as ethanol, n-propanol, and isopropanol; triglycerides; ethyl acetate; acetone; triacetin; and combinations thereof. Typically, the dispersion medium (e.g., water) comprises greater than about 75% weight / volume, in some embodiments greater than about 90% weight / volume, and in some embodiments from about 95% weight / volume to about 99% weight / volume of the composition.

[0091] The compositions of the present disclosure can also include an ion- responsive compound. Such compounds are generally known in the art and tend to form gels in the presence of certain ions or at certain pHs. For example, one class of suitable ion-responsive compounds that can be used in the present disclosure are anionic polysaccharides. The anionic polysaccharides can form a three-dimensional polymeric network that acts as the dispersed phase of the gel. Generally, the anionic polysaccharides include polysaccharides having a total anionic charge, as well as neutral polysaccharides containing anionic functional groups.

[0092] Any of a variety of anionic polysaccharides that are capable of forming a gel upon contact with the vaginal mucosa can be used in the present disclosure. Such gel-forming anionic polysaccharides are generally stable at the normal acidic pH values (e.g., from about 2.5 to about 5.5) found in the vagina. For example, some suitable examples of gel-forming anionic polysaccharides include natural gums such as gellan gum and alginate gums (e.g., ammonium and alkali metal salts of alginic acid); chitosan; carboxymethylcellulose, pectin, carrageenan, xanthan gum, and derivatives or salts thereof. The particular type of anionic polysaccharide selected will depend in part on the properties of the composition and other components used therein. For example, carrageenan is sensitive to certain types of cations, e.g., it generally gels in the presence of potassium but not sodium. Similarly, the uronic acid polysaccharides generally gel in the presence of divalent cations (e.g., Ca 2+ ) but do not gel in the presence of monovalent cations (e.g., Na + ). Xanthan gum can gel in the presence of divalent cations, but only at relatively high pH.

[0093] While any of the above anionic polysaccharides can be used in the present disclosure, the use of gellan gum (whether used alone or in combination with other gelling agents) is particularly desirable in the present disclosure because gellan gum is capable of forming a gel in the presence of a variety of different cations, both monovalent and divalent. Gellan gum is intended to encompass any form of gellan gum, including native gellan gum, clarified gellan gum, deacylated gellan gum, non-acylated gellan gum (e.g., produced by genetically engineered bacteria), clarified gellan gum (in which the polysaccharide is completely or partially removed from the bacterial debris), chemically modified gellan gum, and the like. Various types of gellan gum and methods for forming such gums are described in U.S. Pat. Nos. 4,326,052, 4,326,053, 4,377,636, 4,385,123, and 4,563,366. Suitable gellan gum is commercially available from a variety of different sources. For example, GELRITE ™ Gellan gum is available from Sigma-Aldrich Chemical Co. of St. Louis, MO, and is produced from a naturally occurring polysaccharide after deacylation and clarification. Deacylated gellan gum is also available under the name KELCOGEL ® from CP Kelco U.S., Inc. of Chicago, IL.

[0094] Gellan gum can be high acyl gellan gum or low acyl gellan gum. In the high acyl (or "native") form, two acyl substituents are present, namely acetate and glycerate. These two substituents are on the same glucose residue, and on average there is one glycerate per repeat unit and one acetate per two repeat units. In the low acyl form, the acyl groups can be removed, in whole or in part, by deacylation. The degree of deacylation of deacylated gellan gum can be at least about 20%, in some embodiments at least about 50%, and in some embodiments at least about 75%. Alternatively, low acyl gellan gum can simply be "non-acylated" in that it is formed by genetically engineered bacteria in the absence of acyl groups. Regardless of how low acyl gellan gum is formed, low acyl gellan gum generally has a gelation temperature in the range of 30°C to 50°C, which can make it particularly suitable for use in the present disclosure, such that low acyl gellan gum can gel at body temperature of about 37°C, but remain stable at typical storage and transport temperatures of about 25°C. In addition, low acyl gellan gum is also strong and elastic, and thus can maintain their shape after delivery to the vaginal cavity.

[0095] In most embodiments, the one or more gelling agents are present in an amount of from about 0.01% weight / volume to about 10.0% weight / volume of the composition, in some embodiments from about 0.05% weight / volume to about 5.0% weight / volume, and in some embodiments from about 0.1% weight / volume to about 1.0% weight / volume.

[0096] If desired, the gelling composition can be provided in any desired form (e.g., liquid, powder, etc.). In fact, one particular benefit of the composition is that it can be applied as a liquid, which allows for a wider range of application techniques than would otherwise be available for solid or semi-solid gels. One technique that can be employed involves dispensing the composition into the vaginal cavity through a liquid applicator, such as a syringe or tube. The volume of the composition applied can constitute a single dose, or two or more doses. Although not necessary, the composition can also be sterilized prior to application. Sterilization can be accomplished by any technique known in the art, such as using a gas (e.g., ethylene oxide), radiation (e.g., gamma radiation), or heat (autoclaving). If desired, the composition can be subjected to one or more filtration steps to help remove contaminants prior to sterilization.

[0097] Nitrogen source

[0098] In some embodiments, the composition can include one or more nitrogen sources to drive potential synergies. Some suitable nitrogen sources include azacycles, ammonia, ammonium, urea, and amino acids. Suitable amino acids include, but are not limited to, slowly assimilated amino acids, such as proline, which are typically included to promote fermentation and to promote high productivity of secondary metabolites. Other suitable nitrogen sources include tetraoxypyrrolidine, ammonium citrate, glycine, L-cysteine, L-glutamic acid, L-glutamine, L-homoserine, L-leucine, L-lysine, L-methionine, L-tyrosine, cytidine, D-asparagine, adenosine, H-Ala-Thr-OH, D-glucuronamide, Ala-asp, Ala-His, Gly-Met, N-acetyl-D-galactosamine, pyrimidine, L-serine, inosine, D-alanine, N-acetyl-D-mannosamine, Gly-Asn, Ala-Glu, D-galactosamine HC1, D-glucosamine HC1, DL-a-amino-n-butyric acid, D-mannosamine HC1, Gly-Gln, Gly-Glu, DL-lactamide, Met-Ala, methyl(2-phenylethyl)amine hydrochloride, glycyl-alanine, DL-gamma-amino-n-butyric acid, and N-acetyl-D-glucosamine.

[0099] Antimicrobial agent

[0100] In some embodiments, the composition can include one or more antimicrobial agents to increase shelf life. Some suitable antimicrobial agents that can be used in the present disclosure include traditional antimicrobial agents. As used herein, “traditional antimicrobial agent” refers to a compound that has historically been recognized by regulatory agencies as providing an antimicrobial effect, such as those listed in the European Union’s Annex V list of preservatives allowed in cosmetics products. Traditional antimicrobial agents include, but are not limited to: succinic acid and salts thereof, propionic acid and salts thereof; salicylic acid and salts thereof; sorbic acid and salts thereof; benzoic acid and salts and esters thereof; formaldehyde; paraformaldehyde; o-phenylphenol and salts thereof; zinc pyrithione; inorganic sulfites; bisulfites; chlorobutanol; parabens such as methyl paraben, propyl paraben, butyl paraben, ethyl paraben, isopropyl paraben, isobutyl paraben, benzyl paraben, sodium methyl paraben, and sodium propyl paraben; dehydroacetic acid and salts thereof; formic acid and salts thereof; dibromohexamidine hydroxyethylsulfonate; thiomersal; phenylmercuric salts; undecylenic acid and salts thereof; hexetidine; 5-bromo-5-nitro-l,3-dioxane; 2-bromo-2-nitropropane-l,3-diol; dichlorobenzyl alcohol; triclocarban; p-chloro-m-cresol; triclosan; chloroxylenol; imidazolidinyl urea; polyaminopropyl biguanide; phenoxyethanol, methenamine; quaternium-15; climbazole; DMDM hydantoin; benzyl alcohol; piroctone olamine; bromochlorobenzene; o-cymen-5-ol; methylchloroisothiazolinone; methylisothiazolinone; benzalkonium chloride; chloroacetamide; chlorhexidine; chlorhexidine diacetate; chlorhexidine digluconate; chlorhexidine dihydrochloride; phenoxyisopropanol; alkyl (C12-C22) trimethylammonium bromides and chlorides; dimethyl oxazolidine; diazolidinyl urea; hexamidine; hexamidine diisethionate; glutaraldehyde; 7- ethylbicyclooxazolidine; chlorphenesin; sodium hydroxymethylglycinate; silver chloride; benzethonium chloride; benzalkonium chloride; benzalkonium bromide; benzyl hemiformal; iodopropynyl butylcarbamate; lauroylarginate HCI; citric acid and silver citrate.

[0101] Other antimicrobial agents that can be added to the compositions of the present disclosure include non-traditional antimicrobial agents that are known to exhibit antimicrobial effects in addition to their primary function, but have not historically been recognized by regulatory agencies (such as on the EU Annex V list) as antimicrobial agents. Examples of these non-traditional antimicrobial agents include, but are not limited to, hydroxyacetophenone, caprylyl glycol, sodium cocoyl PG-dimethylcHloride phosphate, phenylpropanol, lactic acid and its salts, caprylhydroxamic acid, levulinic acid and its salts, sodium lauroyl lactylate, phenyl ethyl alcohol, sorbitan caprylate, glyceryl caprate, glyceryl caprylate, ethylhexyl glycerin, p-anisic acid and its salts, gluconolactone, decanediol, 1,2-hexanediol, glucose oxidase and lactoperoxidase, leuconostoc / radish root ferment filtrate, and glyceryl laurate.

[0102] The amount of antimicrobial agent in the composition depends on the relative amounts of other components present within the composition. For example, in some embodiments, the antimicrobial agent can be present in the composition in an amount of between about 0.001% to about 5% by total weight of the composition, in some embodiments between about 0.01% to about 3% by total weight of the composition, and in some embodiments between about 0.05% to about 1.0% by total weight of the composition. In some embodiments, the antimicrobial agent can be present in the composition in an amount of less than 0.2% by total weight of the composition. However, in some embodiments, the composition can be substantially free of any antimicrobial agent. Thus, in some embodiments, the composition does not include a traditional antimicrobial agent or a non-traditional antimicrobial agent.

[0103] Other suitable additives that can be included in the compositions of the present disclosure include compatible colorants, deodorants, emulsifiers, antifoams (when foam is not desired), lubricants, skin conditioning agents, skin protectants, and skin benefit agents (e.g., aloe vera and tocopheryl acetate), solvents (e.g., water soluble glycols and glycol ethers, glycerin, water soluble polyethylene glycols, water soluble polyethylene glycol ethers, water soluble polypropylene glycols, water soluble polypropylene glycol ethers, dimethyl isosorbide), solubilizers, suspending agents, builders (e.g., carbonates, bicarbonates, phosphates, hydrogen phosphates, dihydrogen phosphates, bisulfates of alkali and alkaline earth metals), humectants, chelating agents, propellants, dyes and / or pigments, and combinations thereof.

[0104] The composition can alternatively or additionally be applied to the user by a delivery mechanism such as, for example, a wipe substrate, or by being applied to at least a portion of an absorbent article that can deliver the composition to the user. For example, in one embodiment, the composition can be applied to the top sheet of a feminine care pad. In some embodiments, the composition can be applied to the user by a suppository. Another way the composition can be configured to be applied to the user can be by being configured in the form of a pill that can be ingested by the user.

[0105] In certain embodiments, suitable substrates and applicators for delivery to a user include webs, such as wetlaid tissue webs or air-laid webs, gauze, cotton swabs, transdermal patches, containers or holders. In other embodiments, the substrate can be a nonwoven material, such as a nonwoven web. Particularly preferred applicators include fibrous webs, including flushable and non-flushable cellulose webs and nonwoven webs of synthetic fibrous materials. Useful webs can be wetlaid, air-laid, meltblown or spunbonded. Suitable synthetic fibrous materials include meltblown polyethylene, polypropylene, copolymers of polyethylene and polypropylene, bicomponent fibers comprising polyethylene or polypropylene, and the like. Useful nonwoven webs can be meltblown, coform, spunbond, air-laid, hydroentangled nonwoven, spunlace, bonded carded webs.

[0106] In certain embodiments, particularly those in which the composition is applied to a web, it can be desirable for the formulation to provide certain physical attributes, such as having a smooth, lubricious, non-greasy feel; the ability to at least partially transfer from the web to the user; the ability to remain on the web at about room temperature; or the ability to be compatible with the web manufacturing process. In certain embodiments, it is preferred that at least a portion of the composition be transferred from the tissue to the user for optimal therapeutic effect.

[0107] The composition can be applied to the web during web formation or after the web has been formed and dried, the latter case often referred to as off-line or post-treatment. Suitable methods of applying the composition to the web include methods known in the art, such as gravure printing, flexographic printing, spraying, WEKO ™ , slot die coating, or electrostatic spraying. One particularly preferred off-line application method is rotogravure printing.

[0108] In certain embodiments, the compositions can exhibit enhanced therapeutic effects even when applied to a substrate. For example, in some embodiments, the ratio of growth of Lactobacillus spp. to growth of one or more types of bacteria including E. coli, S. aureus, S. anginosus, or mixtures thereof, is greater than about 1, such as greater than about 1.25, such as greater than about 1.5, such as greater than about 1.75, such as greater than about 2.0, and even greater than about 2.5, after exposure to about 1.5% weight / volume to about 8.5% weight / volume of the composition in a 48 hour competitive co-culture assay after the composition has been applied to a substrate.

[0109] The application can be better understood by reference to the following examples.

[0110] Example

[0111] Example One: Preparation of Prebiotic Compounds and Positive Controls

[0112] In API ® Individual prebiotic compounds were prepared at 0.1% weight / volume, 0.25% weight / volume, 0.5% weight / volume, 1% weight / volume, 2% weight / volume, 3% weight / volume, 4% weight / volume, 5% weight / volume, 7.5% weight / volume, 10% weight / volume, 15% weight / volume, or 20% weight / volume in 50 CHL medium (bioMérieux, Marcy-l’Étoile, France). Dextrose at 2% was prepared to serve as a growth / fermentation positive control. API ® 50 CHL medium contains minimal amounts of carbon for growth and bromocresol purple as a fermentation pH indicator. The prebiotic was sterilized via UV sterilization prior to dissolution in the API ® 50 CHL medium, or by sterilizing the aqueous mixture via a 0.22 μΜ filter membrane (Corning, Corning, NY), stored at 4-6 °C until use.

[0113] Table 1. Prebiotic compounds tested.

[0114]

[0115] 1 Not available.

[0116] 2 Dextrose was used as a growth and fermentation positive control.

[0117] Example Two: High-throughput single culture assay

[0118] 180 μL of the prepared prebiotic solution from Example 1 and controls were added to sterile, flat-bottom, untreated 96-well microtiter plates (Corning). Lactobacillus strains were subcultured twice from frozen stocks into De Man, Rogosa, and Sharpe (MRS) Broth (BD Difco, Becton Dickinson, Franklin Lakes, NJ), or Tryptic Soy Broth (TSB) (BD Difco, Becton Dickinson) for E. coli, S. aureus, and S. anginosus, and then incubated anaerobically overnight at 37°C until stationary phase. The second broth subculture of Lactobacillus strains were plated onto MRS agar (Teknova, Hollister, CA); E. coli, S. aureus, and S. anginosus were plated onto Trypticase Soy Agar (TSA) (Remel, Thermo Fisher Scientific, Lenexa, KS), and incubated anaerobically overnight at 37°C until stationary phase. Individual bacterial suspensions were prepared by transferring colonies from MRS or TSA to API ® Suspension Broth (bioMerieux) to achieve a turbidity of 0.5 McFarland (for E. coli, S. aureus, S. anginosus) and 1 McFarland (Lactobacillus species). The starting cultures were enumerated via serial dilution and plating. API ® 50 CHL medium (minimal or no growth / fermentation control), API ® 50 CHL medium (positive control) and API ® The plates were placed in a spectrophotometer (Molecular Devices, San Jose, CA), and kinetic absorbance readings were taken every 20 minutes for 24 to 48 hours at three wavelengths (OD430 nm, OD590 nm, and OD660 nm). A decrease in pH causes a color change from purple to yellow, which is measured by an increase in OD430 nm and a decrease in OD590 nm, indicating that bacterial fermentation is occurring. An increase in OD660 nm values indicates an increase in turbidity and bacterial growth.

[0119] Table 2. High throughput single culture results of prebiotic solutions tested at 2% weight / volume with clinical bacterial strains isolated from the bladder and vagina. Growth and fermentation equal to or greater than the positive control was defined as++, less than the positive control was defined as+, and minimal / no growth and fermentation was defined as-.

[0120]

[0121] 1 Dextrose was used as the positive control for growth and fermentation.

[0122] 2 API without prebiotic ® 50 CHL medium was used as the minimal / no growth and fermentation control.

[0123] 3 Bacteria exhibited growth but did not exhibit fermentation of prebiotic.

[0124] Example Three: Competitive co-culture assay with solutions

[0125] Lactobacillus crispatus KC18-1173-1 was subcultured twice from frozen stock into MRS broth (BD Difco, Becton Dickinson) and Escherichia coli KC16-7171-8, Escherichia coli KC17-4298-8, Staphylococcus aureus KC17-4367-2, and Streptococcus anginosus KC18-1131-3B were subcultured twice in TSB (BD Difco, Becton Dickinson). The subcultures were incubated anaerobically at 37°C overnight to stationary phase. The second broth culture of L. crispatus was plated onto MRS agar plates (Teknova) or TSA plates (Remel, Thermo Fisher Scientific) for E. coli, S. aureus, and S. anginosus and incubated anaerobically at 37°C overnight to stationary phase. Individual bacterial suspensions were prepared by transferring colonies from MRS or TSA to API ® broth (BioMerieux) to a titer of 2.0 McFarland standard using a sterile swab. The starting cultures were enumerated via serial dilution and plating. 9.8 mL of pre-prepared prebiotic solution from Example 1, dextrose (positive control) from Example 1, and API ®50 CHL medium (minimal or no growth / fermentation control) was added to separate 15 mL conical tubes (Corning). 100 μΐ, of L. crispatus suspension and 100 μΐ, of E. coli, S. aureus, or S. anginosus was added to the tubes. The tubes were vortex mixed for 5 seconds and the two organism co-cultures were incubated anaerobically at 37°C for 48 hours. After 48 hours, the tubes were vortex mixed for 30 seconds and 100-300 μΐ, aliquots were removed from each tube. The solutions were serially diluted and plated in duplicate onto MRS and TSA to enumerate surviving bacteria. Although some of the harmful organisms do not grow well on MRS, the differentiation between the two organisms included counting large colonies as L. crispatus and small colonies as E. coli, S. aureus, or S. anginosus if available. Although L. crispatus does not always grow well on TSA plates, the differentiation between the two organisms included counting large and opaque colonies as E. coli, S. aureus, or S. anginosus and small and translucent colonies as L. crispatus if available. Each compound and concentration was tested with at least two biological replicates and the results were reported as the mean. For each organism, the mean recovered log CFU / mL was subtracted from the starting inoculum to calculate the mean log CFU / mL change (Δ) defined as an increase or decrease. Once the log CFU / mL change was calculated, the mean log CFU / mL change in the presence of prebiotic or dextrose (positive control) was subtracted from the mean log CFU / mL change in the absence of prebiotic to calculate the treatment effect ratio. A larger number indicates an increase in L. crispatus and / or a decrease in E. coli, S. aureus, or S. anginosus, while a smaller number indicates a decrease in L. crispatus and / or an increase in E. coli, S. aureus, or S. anginosus. ® The mean log CFU / mL change (Δ) of CHL medium (minimal or no growth / fermentation control).

[0126] Colony counts of L. crispatus, E. coli, S. aureus, and S. anginosus were tested in the competitive co-culture assay test method described above. The treatment effect ratio was calculated by comparing the mean log CFU / mL recovered after the competition period for both L. crispatus and E. coli, S. aureus, or S. anginosus and calculating the ratio of L. crispatus / E. coli, S. aureus, or S. anginosus. A larger number indicates an increase in L. crispatus and / or a decrease in E. coli, S. aureus, or S. anginosus, while a smaller number indicates a decrease in L. crispatus and / or an increase in E. coli, S. aureus, or S. anginosus.

[0127] Figures 1 to 4 And Tables 3-4 below demonstrate the results.

[0128] Table 3. Summary of 48 hour period of assay results between Lactobacillus and harmful strains after exposure to 2% w / v prebiotic solution concentration. Results include average starting and recovered log CFU / mL, average log CFU / mL change (Delta), and average ratio of Lactobacillus to harmful strain. Each compound and organism combination was tested with at least four biological replicates.

[0129]

[0130]

[0131] 1 Subtracting the average log CFU / mL Delta of background growth on 50 CHL from the final log CFU / mL Delta of each compound and organism combination. ® Average log CFU / mL change (Delta) of background growth on 50 CHL. Each combination is footnoted with the average log CFU / mL value subtracted.

[0132] 2 Average log CFU / mL values for L. crispatus KC18-1173-1 were obtained from MRS plates and average log CFU / mL values for E. coli KC16-7171-8, E. coli KC17-4298-8, S. aureus KC17-4367-2, and angina streptococcus KC18-1131-3B were obtained from TSA plates.

[0133] 3 Ratios were determined by dividing the recovered average log CFU / mL of L. crispatus KC18-1173-1 by the recovered average log CFU / mL of E. coli KC16-7171-8, E. coli KC17-4298-8, S. aureus KC17-4367-2, or angina streptococcus KC18-1131-3B.

[0134] 4 The average background log CFU / mL Delta for A was 0.49 for L. crispatus KC18-1173-1 and 2.36 for E. coli KC16-7171-8.

[0135] 5 The average background log CFU / mL Delta for B was 0.13 for L. crispatus KC18-1173-1 and 2.27 for E. coli KC17-4298-8.

[0136] 6The average background log CFU / mL Δ for L. crispatus KC18-1173-1 was 0.79, while for S. aureus KC17-4367-2 was 0.65.

[0137] 7 The average background log CFU / mL Δ for L. crispatus KC18-1173-1 was 0.69, while for S. anginosus KC18-1131-3B was 0.62.

[0138] 8 The average background log CFU / mL Δ for L. crispatus KC18-1173-1 was 0.61, while for E. coli KC16-7171-8 was 2.32.

[0139] Table 4. Summary of 48 hour competitive co-culture assay results between Lactobacillus and pathogenic strains after exposure to different prebiotic solution concentrations (% weight / volume). Results include average starting and recovered log CFU / mL, average log CFU / mL change (Δ), and average ratio of Lactobacillus to pathogenic strain. Each compound and organism combination was tested with at least two biological replicates.

[0140]

[0141]

[0142]

[0143]

[0144]

[0145]

[0146]

[0147]

[0148] 1 Subtracting the API ® Average log CFU / mL change (Δ) for background growth on 50 CHL. Each combination has a footnote where the average log CFU / mL value was subtracted.

[0149] 2The average log CFU / mL values for L. crispatus KC18-1173-1 were obtained from MRS plates and the average log CFU / mL values for E. coli KC16-7171-8, E. coli KC17-4298-8, S. aureus KC17-4367-2, and angina streptococcus KC18-1131-3B were obtained from TSA plates.

[0150] 3 The ratio was determined by dividing the recovered average log CFU / mL for L. crispatus KC18-1173-1 by the recovered average log CFU / mL for E. coli KC16-7171-8, E. coli KC17-4298-8, S. aureus KC17-4367-2, or angina streptococcus KC18-1131-3B.

[0151] 4 The average background log CFU / mL delta for A was 0.51 for L. crispatus KC18-1173-1 and 2.52 for E. coli KC16-7171-8.

[0152] 5 The average background log CFU / mL delta for B was -0.14 for L. crispatus KC18-1173-1 and 2.51 for E. coli KC17-4298-8.

[0153] 6 The average background log CFU / mL delta for C was 0.75 for L. crispatus KC18-1173-1 and 0.60 for S. aureus KC17-4367-2.

[0154] 7 The average background log CFU / mL delta for D was 0.47 for L. crispatus KC18-1173-1 and 0.27 for angina streptococcus KC18-1131-3B.

[0155] 8 The average background log CFU / mL delta for E was 0.68 for L. crispatus KC18-1173-1 and 2.60 for E. coli KC16-7171-8.

[0156] 9 The average background log CFU / mL delta for F was 0.70 for L. crispatus KC18-1173-1 and 0.73 for S. aureus KC17-4367-2.

[0157] 10The average background log CFU / mL delta for G was 0.49 for Lactobacillus crispatus KC18-1173-1 and 2.36 for Escherichia coli KC16-7171-8.

[0158] 11 The average background log CFU / mL delta for H was 0.13 for Lactobacillus crispatus KC18-1173-1 and 2.27 for Escherichia coli KC17-4298-8.

[0159] 12 The average background log CFU / mL delta for I was 0.79 for Lactobacillus crispatus KC18-1173-1 and 0.65 for Staphylococcus aureus KC17-4367-2.

[0160] 13 The average background log CFU / mL delta for J was 0.66 for Lactobacillus crispatus KC18-1173-1 and 0.62 for Streptococcus anginosus KC18-1131-3B.

[0161] 14 The average background log CFU / mL delta for K was 0.53 for Lactobacillus crispatus KC18-1173-1 and 2.67 for Escherichia coli KC16-7171-8.

[0162] 15 The average background log CFU / mL delta for L was -0.23 for Lactobacillus crispatus KC18-1173-1 and 2.58 for Escherichia coli KC17-4298-8.

[0163] 16 The average background log CFU / mL delta for M was 0.48 for Lactobacillus crispatus KC18-1173-1 and 2.53 for Escherichia coli KC16-7171-8.

[0164] 17 The average background log CFU / mL delta for N was 0.55 for Lactobacillus crispatus KC18-1173-1 and 2.49 for Escherichia coli KC16-7171-8.

[0165] 18 The average background log CFU / mL delta for O was 0.54 for Lactobacillus crispatus KC18-1173-1 and 0.77 for Staphylococcus aureus KC17-4367-2.

[0166] 19The average background log CFU / mL delta for P was 0.66 for Lactobacillus crispatus KC18-1173-1 and 2.58 for E. coli KC16-7171-8.

[0167] 20 The average background log CFU / mL delta for Q was 0.61 for Lactobacillus crispatus KC18-1173-1 and 2.32 for E. coli KC16-7171-8.

[0168] 21 The average background log CFU / mL delta for R was 0.51 for Lactobacillus crispatus KC18-1173-1 and 2.66 for E. coli KC16-7171-8.

[0169] 22 The average background log CFU / mL delta for S was -0.51 for Lactobacillus crispatus KC18-1173-1 and 2.58 for E. coli KC17-4298-8.

[0170] 23 The average background log CFU / mL delta for T was 0.33 for Lactobacillus crispatus KC18-1173-1 and 0.82 for Staphylococcus aureus KC17-4367-2.

[0171] 24 The average background log CFU / mL delta for U was 0.54 for Lactobacillus crispatus KC18-1173-1 and 2.56 for E. coli KC16-7171-8.

[0172] 25 The average background log CFU / mL delta for V was -0.16 for Lactobacillus crispatus KC18-1173-1 and 2.53 for E. coli KC17-4298-8.

[0173] 26 The average background log CFU / mL delta for W was 0.74 for Lactobacillus crispatus KC18-1173-1 and 0.55 for Staphylococcus aureus KC17-4367-2.

[0174] 27 The average background log CFU / mL delta for X was 0.56 for Lactobacillus crispatus KC18-1173-1 and 2.59 for E. coli KC16-7171-8.

[0175] 28The average background log CFU / mL delta for Y was -0.49 for L. crispatus KC18-1173-1 and 2.66 for E. coli KC17-4298-8.

[0176] 29 The average background log CFU / mL delta for Z was 0.77 for L. crispatus KC18-1173-1 and 0.67 for S. aureus KC17-4367-2.

[0177] 30 The average background log CFU / mL delta for AA was 0.52 for L. crispatus KC18-1173-1 and 1.51 for E. coli KC16-7171-8.

[0178] 31 The average background log CFU / mL delta for AB was 0.51 for L. crispatus KC18-1173-1 and 1.49 for E. coli KC17-4298-8.

[0179] 32 The average background log CFU / mL delta for AC was 0.50 for L. crispatus KC18-1173-1 and 1.12 for S. aureus KC17-4367-2.

[0180] 33 The average background log CFU / mL delta for AD was 0.52 for L. crispatus KC18-1173-1 and 1.07 for S. anginosus KC18-1131-3B.

[0181] As demonstrated in Table 3, 2% weight / volume of beta-limit dextrin and highly branched cyclic dextrin increased recovered L. crispatus KC18-1173-1 by >2.0 log CFU / mL while decreasing harmful bacteria by >1.9 log CFU / mL compared to the starting inoculum.

[0182] As demonstrated in Table 4, beta-limit dextrin and highly branched cyclic dextrin exhibited therapeutic effects at concentrations as low as 0.1% weight / volume. Further, Table 4 demonstrates that the compounds had stronger therapeutic effects when they were tested at higher concentrations. For example, beta-limit dextrin exhibited stronger therapeutic effects when the concentration was between 1% weight / volume and 5% weight / volume, while highly branched cyclic dextrin exhibited stronger therapeutic effects when the concentration was between 1% weight / volume and 20% weight / volume.

[0183] Example Four: Competitive Co-culture Assay with Treated Nonwoven

[0184] Lactobacillus crispatus KC18-1173-1 and Lactobacillus crispatus KC18-1174-1 were subcultured twice from frozen stocks into MRS Broth (BD Difco, Becton Dickinson) and E. coli KC17-4296-4 and S. aureus KC17-4367-2 were subcultured twice in TSB (BD Difco, Becton Dickinson). The subcultures were incubated anaerobically at 37°C overnight until stationary phase. The second broth cultures of L. crispatus were plated onto MRS Agar plates (Teknova) or TSA plates (Remel, Thermo Fisher Scientific) for E. coli and S. aureus and incubated anaerobically at 37°C overnight to stationary phase. Individual bacterial suspensions were prepared by transferring colonies from MRS or TSA to API ® Suspension Medium (bioMerieux) to achieve a titer of 2.0 McFarland standard. The starting culture was enumerated via serial dilution and plating. The treated nonwoven material was cut to the desired size (70 cm 2 150 cm 2 ) and placed in a 15 mL conical tube (Corning). Depending on the size of the nonwoven material, API ® 50 CHL Broth (2.5 mL to 5 mL) and bacterial suspension (50 μΐ to 100 μΐ) was added to saturate the nonwoven material. 9.8 mL of pre-prepared prebiotic solution from Example 1, dextrose from Example 1 (positive control), and API ®50 CHL medium (minimal or no growth / fermentation control) was added to separate 15 mL conical tubes (Corning). 100 μΐ, of L. crispatus suspension and 100 μΐ, of E. coli or S. aureus were added to the tubes. The tubes were vortex mixed for 5 seconds and the two organism co-cultures were incubated anaerobically at 37°C for 48 hours. After 48 hours, the tubes containing the solutions were vortex mixed for 30 seconds and 100-300 μΐ, aliquots were removed from each tube. The tubes containing the nonwoven were sonicated (on for 1 minute, off for 1 minute, for a total of 5 minutes of sonication) followed by vortex mixing for 30 seconds. 100-300 μΐ, aliquots were removed from each tube and the solutions were serially diluted and plated in duplicate onto MRS and TSA to enumerate surviving bacteria. Although some of the harmful organisms do not grow well on MRS, the differentiation between the two organisms included counting large colonies as L. crispatus and small colonies as E. coli or S. aureus if available. Although L. crispatus does not always grow well on TSA plates, the differentiation between the two organisms included counting large and opaque colonies as E. coli or S. aureus and small and translucent colonies as L. crispatus if available. Each compound and concentration was tested with at least three biological replicates and the results are reported as the mean. For each organism, the mean recovered log CFU / mL was subtracted from the starting inoculum to calculate the mean log CFU / mL change (Delta) defined as an increase or decrease. Once the log CFU / mL change was calculated, the mean log CFU / mL change in the presence of prebiotic or dextrose (positive control) was subtracted from the mean log CFU / mL change in the absence of prebiotic to calculate the treatment effect ratio. A ratio of 1 indicates no treatment effect. A ratio greater than 1 indicates an increase in L. crispatus and / or a decrease in E. coli or S. aureus. A ratio less than 1 indicates a decrease in L. crispatus and / or an increase in E. coli or S. aureus. ® The mean log CFU / mL change (Delta) of CHL medium (minimal or no growth / fermentation control).

[0185] Colony counts of L. crispatus, E. coli, and S. aureus were tested in the competitive co-culture assay test method as described above. The treatment effect ratio was calculated by comparing the mean log CFU / mL recovered after the competition period for both L. crispatus and E. coli or S. aureus and calculating the ratio of L. crispatus / E. coli or S. aureus. A larger number indicates an increase in L. crispatus and / or a decrease in E. coli or S. aureus, while a smaller number indicates a decrease in L. crispatus and / or an increase in E. coli or S. aureus.

[0186] Table 5 below demonstrates the results.

[0187] Table 5. Summary of 48 hour competitive co-culture assay results between Lactobacillus and harmful strains after exposure to nonwoven materials treated with highly branched cyclic dextrin at different concentrations (% weight / weight). Results include average starting and recovered log CFU / mL, average log CFU / mL change (Delta), and average ratio of Lactobacillus to harmful strain. Each material and organism combination was tested with at least three biological replicates.

[0188]

[0189]

[0190] 1 Subtracting the average log CFU / mL change (Delta) of background growth on 50 CHL from the final log CFU / mL Delta ® 50 Average log CFU / mL change (Delta) of background growth on 50 CHL. Each combination is footnoted with the average log CFU / mL value subtracted.

[0191] 2 Average log CFU / mL values for Lactobacillus crispatus KC18-1173-1 and Lactobacillus crispatus KC18-1174-1 were obtained from MRS plates and average log CFU / mL values for E. coli KC17-4296-4 and S. aureus KC17-4367-2 were obtained from TSA plates.

[0192] 3 Ratios were determined by dividing the recovered average log CFU / mL of Lactobacillus crispatus KC18-1173-1 or Lactobacillus crispatus KC18-1174-1 by the recovered average log CFU / mL of E. coli KC17-4296-4 or S. aureus KC17-4367-2.

[0193] 4 The average background log CFU / mL Delta for A was 0.32 for Lactobacillus crispatus KC18-1173-1 and 1.82 for E. coli KC17-4296-4.

[0194] 5 The average background log CFU / mL Delta for B was 0.51 for Lactobacillus crispatus KC18-1173-1 and 1.15 for S. aureus KC17-4367-2.

[0195] 6 The average background log CFU / mL Delta for C was 0.60 for Lactobacillus crispatus KC18-1174-1 and 1.13 for S. aureus KC17-4367-2.

[0196] 7 The average background log CFU / mL delta for Lactobacillus crispatus KC18-1173-1 was 0.14, while for E. coli KC17-4296-4 was 1.17.

[0197] 8 The average background log CFU / mL delta for Lactobacillus crispatus KC18-1173-1 was 0.50, while for S. aureus KC17-4367-2 was 1.08.

[0198] 9 The average background log CFU / mL delta for Lactobacillus crispatus KC18-1174-1 was 0.65, while for S. aureus KC17-4367-2 was 1.12.

[0199] 10 The average background log CFU / mL delta for Lactobacillus crispatus KC18-1173-1 was 0.46, while for S. aureus KC17-4367-2 was 1.05.

[0200] 11 The average background log CFU / mL delta for Lactobacillus crispatus KC18-1174-1 was 0.62, while for S. aureus KC17-4367-2 was 1.10.

[0201] 12 The average background log CFU / mL delta for Lactobacillus crispatus KC18-1173-1 was 0.88, while for E. coli KC17-4296-4 was 1.31.

[0202] 13 The average background log CFU / mL delta for Lactobacillus crispatus KC18-1173-1 was 0.88, while for S. aureus KC17-4367-2 was 1.00.

[0203] 14 The average background log CFU / mL delta for Lactobacillus crispatus KC18-1173-1 was 0.31, while for E. coli KC17-4296-4 was 2.14.

[0204] 15 The average background log CFU / mL delta for Lactobacillus crispatus KC18-1173-1 was 0.53, while for S. aureus KC17-4367-2 was 1.28.

[0205] 16 The average background log CFU / mL delta for Lactobacillus crispatus KC18-1174-1 was 0.56, while for Staphylococcus aureus KC17-4367-2 was 1.13.

[0206] 17 The average background log CFU / mL delta for Lactobacillus crispatus KC18-1173-1 was 0.53, while for Escherichia coli KC17-4296-4 was 1.21.

[0207] 18 The average background log CFU / mL delta for Lactobacillus crispatus KC18-1173-1 was 0.54, while for Staphylococcus aureus KC17-4367-2 was 0.90.

[0208] As demonstrated in Table 5, the highly branched cyclic dextrin exhibited a therapeutic effect at concentrations as low as 0.5% weight / volume.

[0209] Example Five: Skin Irritation Assay

[0210] A reconstituted human epidermis model (EpiDerm ™ EPI-200, MatTek Corporation, Ashland, MA) was tested with highly branched cyclic dextrin solutions. Upon arrival of the tissues, the packaging was unpacked and placed in a 6-well plate (Corning) with 0.9 mL of pre-warmed assay media per well. After the tissues were equilibrated overnight at 37°C and 5% CO2 in an incubator, the assay media was changed prior to treatment. The tissues were treated with 100 μL of each solution (four replicates per solution). The solutions tested included 5% weight / volume highly branched cyclic dextrin, 10% weight / volume highly branched cyclic dextrin, 15% weight / volume highly branched cyclic dextrin, and 20% weight / volume highly branched cyclic dextrin. Milli-Q water was tested as a negative control, and 1% volume / volume Triton X-100 (Sigma-Aldrich Chemical Company) was tested as a positive control. The treated tissues were incubated at 37°C, 5% CO2 for 24 hours. After 24 hours, the media was collected and stored at 4-6°C for use in the automated ELISA system (Ella ™Inflammation markers (IL-1a and IL-8) analysis was performed using the Cytosensor® system (Applied Biosystems, Foster City, CA) according to the manufacturer's instructions. In addition, the viability of the tissues was assessed by MTT assay, which was performed according to the instructions provided by the manufacturer of the MTT kit (MTT-100, MatTek Corporation). The tissues were rinsed three times with DPBS (Thermo Fisher Scientific) and transferred to a new 24-well plate containing MTT working solution. The plate was incubated for three hours at 37°C, 5% CO2. Each insert was gently swabbed and transferred to the MTT extraction plate. The plate was covered with aluminum foil, sealed with parafilm (Amcor, Zürich, Switzerland), placed in a Ziploc bag, and stored in the dark overnight. After the extraction period, the liquid within each insert was decanted back into the well from which it was taken, and the insert was discarded. The solution was mixed well, and 200 μL of each sample was transferred to a 96-well plate. The solution was measured at OD570nm. Background was included with the extraction reagent. Background readings at OD650nm were subtracted from all samples to improve data quality; in addition, wavelengths between OD540nm and 570nm can also be used. The percent (%) cell viability was calculated as 100 x [OD(sample) / OD(negative control)].

[0211] The results are shown in Figures 5 to 6 . As shown in Figure 5 , even highly branched cyclic dextrin ("HBCD") used at high amounts, such as 20% weight / volume, showed little to no effect on cell viability after 24 hours of exposure. As shown in Figure 6 , even highly branched cyclic dextrin ("HBCD") used at high amounts, such as 20% weight / volume, showed little to no increase in inflammatory cytokines. For example, in some cases, the use of highly branched cyclic dextrin actually decreased the amount of inflammatory cytokines compared to the negative control. Thus, Figures 5 to 6 it is shown that the use of at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages, such as highly branched cyclic dextrin, as a therapeutic agent does not exhibit any adverse skin effects.

[0212] Embodiments

[0213] In view of the foregoing description and examples, the present disclosure provides the following embodiments.

[0214] Embodiment 1 : A method for modulating the microbiome of a urogenital region or a skin region of a user, the method comprising: applying a composition to the urogenital region or the skin region of the user, the composition comprising a carrier and a therapeutic agent, the therapeutic agent comprising at least one prebiotic compound, the at least one prebiotic compound comprising at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages has a molecular weight greater than about 25,000 kDa.

[0215] Embodiment 2: The method of embodiment 1, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages has a cyclic moiety.

[0216] Embodiment 3: The method of embodiment 1, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages is a highly branched cyclic dextrin, a beta-limit dextrin, or a mixture thereof.

[0217] Embodiment 4: The method of any preceding embodiment, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages comprises only highly branched cyclic dextrin.

[0218] Embodiment 5: The method of any preceding embodiment, wherein the at least one high molecular dextrin having two or more alpha-1,6-glycosidic linkages comprises only beta-limit dextrin.

[0219] Embodiment 6: The method of any preceding embodiment, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages has a purity level of about 80% or more.

[0220] Embodiment 7: The method of any preceding embodiment, wherein the urogenital region of the user comprises a vaginal canal, a urethra, or a periurethral region.

[0221] Embodiment 8: The method of any preceding embodiment, wherein the composition has a pH of about 3 to about 5.

[0222] Embodiment 9: The method of any preceding embodiment, wherein the composition further comprises at least one of an additional prebiotic, a surfactant, an ester, a humectant, a pH adjuster, a rheology modifier, a gelling agent, a nitrogen source, and an antimicrobial agent.

[0223] Embodiment 10: The method of any preceding embodiment, wherein the carrier is an aqueous solution.

[0224] Embodiment 11: The method of any preceding embodiment, wherein the composition is in the form of a liquid, a gel, a cream, a spray, or a suppository.

[0225] Embodiment 12: The method of any preceding embodiment, wherein the composition is free of alcohol.

[0226] Embodiment 13: The method of any preceding embodiment, wherein the therapeutic agent comprises from about 0.1% weight / volume to about 20% weight / volume of the composition.

[0227] Embodiment 14: The method of any preceding embodiment, wherein the carrier comprises greater than about 90% weight / volume of the composition.

[0228] Embodiment 15: The method of any preceding embodiment, further comprising promoting a healthy microbiota balance of the urogenital region or the skin region of the user, wherein promoting a healthy microbiota balance of the urogenital region or the skin region of the user comprises promoting growth of Lactobacillus species relative to growth of one or more types of bacteria comprising Escherichia coli, Staphylococcus aureus, Streptococcus anginosus, or mixtures thereof.

[0229] Embodiment 16: The method of any preceding embodiment, wherein the ratio of growth of the Lactobacillus species to growth of the one or more types of bacteria comprising Escherichia coli, Staphylococcus aureus, Streptococcus anginosus, or mixtures thereof is greater than about 1, such as greater than about 1.5, such as greater than about 1.75, such as greater than about 2.0, and even greater than about 2.5, following exposure to 2% weight / volume of the composition in a 48 hour competitive co-culture assay.

[0230] Embodiment 17: The method of any preceding embodiment, further comprising applying the composition to a substrate comprising a wipe, or at least a portion of an absorbent article.

[0231] Embodiment 18: The method of any preceding embodiment, wherein the ratio of growth of the Lactobacillus species to growth of the one or more types of bacteria comprising Escherichia coli, Staphylococcus aureus, Streptococcus anginosus, or mixtures thereof is greater than about 1, such as greater than about 1.25, such as greater than about 1.5, such as greater than about 1.75, such as greater than about 2.0, and even greater than about 2.5, following exposure to about 1.5% weight / volume to about 8.5% weight / volume of the composition in a 48 hour competitive co-culture assay following application to the substrate.

[0232] Embodiment 19: A composition for modulating the microbiome of a urogenital or skin area of a user, the composition comprising a single liquid phase comprising an aqueous solution and a therapeutic agent, the therapeutic agent comprising at least one prebiotic compound comprising at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages has a molecular weight greater than about 25,000 kDa.

[0233] Embodiment 20: The composition of Embodiment 19, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages has a cyclic moiety.

[0234] Embodiment 21: The composition of Embodiment 19, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages is a highly branched cyclic dextrin, a beta-limit dextrin, or a mixture thereof.

[0235] Embodiment 22: The composition of any preceding embodiment, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages comprises only highly branched cyclic dextrin.

[0236] Embodiment 23: The composition of any preceding embodiment, wherein the at least one high molecular dextrin having two or more alpha-1,6-glycosidic linkages comprises only beta-limit dextrin.

[0237] Embodiment 24: The composition of any preceding embodiment, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages has a purity level of about 80% or greater.

[0238] Embodiment 25: The composition of any preceding embodiment, wherein the composition has a pH of about 3 to about 5.

[0239] Embodiment 26: The composition of any preceding embodiment, wherein the composition further comprises at least one of an additional urogenital prebiotic, a surfactant, an ester, a humectant, a pH adjuster, a rheology modifier, a gelling agent, a nitrogen source, and an antimicrobial agent.

[0240] Embodiment 27: The composition of any preceding embodiment, wherein the composition is in the form of a liquid, a gel, a cream, a spray, or a suppository.

[0241] Embodiment 28: The composition of any preceding embodiment, further comprising applying the composition to a substrate, the substrate comprising a wipe, or at least a portion of an absorbent article.

[0242] Embodiment 29: The composition of any preceding embodiment, wherein the therapeutic agent comprises about 0.1% weight / volume to about 20% weight / volume of the composition.

[0243] Embodiment 30: The composition of any preceding embodiment, wherein the composition is not an emulsion.

[0244] Embodiment 31 : The composition of any preceding embodiment, wherein the composition does not contain any probiotic bacteria.

[0245] Embodiment 32: The composition of any preceding embodiment, wherein the composition does not contain alcohol.

[0246] All documents cited in the DETAILED DESCRIPTION of the Invention are, in relevant part, incorporated herein by reference. The citation of any document is not to be construed as an admission that it is prior art with respect to the present application. To the extent that any meaning or definition of a term in this written document conflicts with any meaning or definition of the term in a document incorporated by reference, the meaning or definition assigned to the term in this written document shall prevail.

[0247] While particular embodiments of the present application have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the application. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this application.

Claims

1. A method for modulating the microbiome of a user's genitourinary or skin area, the method comprising: applying a composition to a user's genitourinary or skin area, the composition comprising: a carrier; and a therapeutic agent comprising at least one prebiotic compound comprising at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages has a molecular weight greater than about 25,000 kDa.

2. The method of claim 1, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages has a cyclic portion.

3. The method of claim 1, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages is a highly branched cyclic dextrin, a beta-limit dextrin, or a mixture thereof.

4. The method of claim 1, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages comprises only highly branched cyclic dextrin.

5. The method of claim 1, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages comprises only beta-limit dextrin.

6. The method of claim 1, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages has a purity level of about 80% or more.

7. The method of claim 1, wherein the genitourinary area of the user comprises a vaginal canal, vulva, vagina, urethra, urinary tract, bladder, and / or a surrounding area.

8. The method of claim 1, wherein the composition has a pH of about 3 to about 6.

9. The method of claim 1, wherein the composition further comprises at least one of the following: an additional prebiotic, a surfactant, an ester, a humectant, a pH adjuster, a rheology modifier, a gelling agent, a nitrogen source, and an antimicrobial agent.

10. The method of claim 1, wherein the carrier is an aqueous solution.

11. The method of claim 1, wherein the composition is in the form of a liquid, a gel, a cream, a spray, or a suppository.

12. The method of claim 1, wherein the composition is free of alcohol.

13. The method of claim 1, wherein the therapeutic agent comprises about 0.1% weight / volume to about 20% weight / volume of the composition.

14. The method of claim 1, wherein the carrier comprises greater than about 90% weight / volume of the composition.

15. The method of claim 1, further comprising promoting a healthy microbiota balance of the urogenital region or the skin region of the user, wherein promoting a healthy microbiota balance of the urogenital region or the skin region of the user comprises promoting growth of Lactobacillus species relative to growth of one or more types of bacteria comprising Escherichia coli, Staphylococcus aureus, Streptococcus anginosus, or mixtures thereof.

16. The method of claim 15, wherein a ratio of growth of Lactobacillus species to growth of one or more types of bacteria comprising Escherichia coli, Staphylococcus aureus, Streptococcus anginosus, or mixtures thereof is greater than about 1, such as greater than about 1.5, such as greater than about 1.75, such as greater than about 2.0, and even greater than about 2.5 after exposure to about 1% weight / volume to about 20% weight / volume of the composition in a 48 hour competitive co-culture assay.

17. The method of claim 1, further comprising applying the composition to a substrate comprising a wipe, or at least a portion of an absorbent article.

18. The method of claim 17, wherein a ratio of growth of Lactobacillus species to growth of one or more types of bacteria comprising Escherichia coli, Staphylococcus aureus, Streptococcus anginosus, or mixtures thereof is greater than about 1, such as greater than about 1.25, such as greater than about 1.5, such as greater than about 1.75, such as greater than about 2.0, and even greater than about 2.5 after exposure to about 1.5% weight / volume to about 8.5% weight / volume of the composition in a 48 hour competitive co-culture assay after application to the substrate.

19. A composition for modulating a microbiome of a urogenital region or a skin region of a user, the composition comprising a single liquid phase comprising: an aqueous solution; and a therapeutic agent comprising at least one prebiotic compound comprising at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages has a molecular weight greater than about 25,000 kDa.

20. The composition of claim 19, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages has a cyclic portion.

21. The composition of claim 19, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages is a highly branched cyclic dextrin, a beta-limit dextrin, or mixtures thereof.

22. The composition of claim 19, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages comprises only highly branched cyclic dextrin.

23. The composition of claim 19, wherein the at least one high molecular weight dextrin having two or more alpha-1,6-glycosidic linkages comprises only beta-limit dextrin.

24. The composition of claim 19, wherein the at least one high molecular weight dextrin having two or more a-1,6-glucosidic linkages has a purity level of about 80% or greater.

25. The composition of claim 19, wherein the composition has a pH of about 3 to about 6.

26. The composition of claim 19, wherein the composition further comprises at least one of the following: an additional urogenital prebiotic, a surfactant, an ester, a humectant, a pH adjuster, a rheology modifier, a gelling agent, a nitrogen source, and an antimicrobial agent.

27. The composition of claim 19, wherein the composition is in the form of a liquid, a gel, a cream, a spray, or a suppository.

28. The composition of claim 27, further comprising applying the composition to a substrate, the substrate comprising a wipe, or at least a portion of an absorbent article.

29. The composition of claim 19, wherein the therapeutic agent comprises about 0.1% weight / volume to about 20% weight / volume of the composition.

30. The composition of claim 19, wherein the composition is not an emulsion.

31. The composition of claim 19, wherein the composition does not contain any probiotic bacteria.

32. The composition of claim 19, wherein the composition does not contain an alcohol.

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