Topical compositions for the treatment of atopic dermatitis and methods of using the same

Abstract

Provided herein are compositions and methods of use for treating atopic dermatitis in a subject in need thereof, wherein the method generally involves topically administering to the subject a composition. The composition generally includes one or more moisture barrier modulators; one or more emollients; one or more humectants; one or more emulsifiers; one or more microbiome modulators; one or more analgesics or astringents; and one or more pharmaceutically acceptable excipients, carriers, or diluents.

Description

TOPICAL COMPOSITIONS FOR THE TREATMENT OF ATOPIC DERMATITIS AND METHODS OF USING THE SAME CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the benefit of U.S. Provisional Application No.63 / 750,555 filed January 28, 2025, which is incorporated herein by reference in its entirety.TECHNICAL FIELD

[0002] The present disclosure generally relates to pharmaceutical compositions and methods of making and using the same, particularly in the treatment of atopic dermatitis.BACKGROUND

[0003] Eczema, or atopic dermatitis (AD), is a chronic inflammatory skin condition characterized by itchy, dry, and inflamed skin. Its pathophysiology is complex and involves a combination of genetic, immune, and environmental factors, including microbiome imbalance. Current eczema treatments fail to adequately address the breadth of these factors. While prescription medications are available, they are inaccessible to many subjects suffering from eczema due to cost and / or administrative hurdles, such as delay in ability to see a dermatologist. Additionally, these medications take weeks to provide relief.

[0004] Meanwhile, over-the-counter products fail to provide relief or have undesirable side effects. The standard of care for currently available over-the-counter treatments include emollients and corticosteroids. While corticosteroids are minimally effective, they can harm the overall quality of the skin barrier, resulting in worse overall symptoms. Treatments for the microbiome imbalance, such as hypochlorous acid, kill all bacteria, including bacteria that is beneficial for the skin microbiome

[0005] Accordingly, a need exists to develop new compositions for the treatment of eczema that are not only cost effective, but also adequately address all of the pathophysiologic causes of the condition.SUMMARY

[0006] The present disclosure concerns compositions for the use in treating atopic dermatitis in a subject in need thereof.

[0007] In some aspects, the present disclosure generally relates to a method for treating atopic dermatitis in a subject in need thereof, the method comprising topically administering to the subject a composition comprising: one or more moisture barrier modulators selected from allantoin, panthenol, colloidal oatmeal (Avena Sativa Kernel Flour), niacinimide, vitamin E, histidine, sodium hyaluronate, ceramides, hyaluronic acid, urea, linoleic acid, or combinations thereof; one or more emollients selected from sunflower seed oil, coconut oil, olive oil, safflower oil, bilberry oil, shea butter, lanolin, caprylic capric triglycerides, squalane, cetostearyl alcohol, cetyl alcohol, cetearyl alcohol, isostearyl alcohol, myristyl alcohol, oleyl alcohol, stearyl alcohol, glycerol stearate, glycerol caprylate, glyceryl undecylenate, PEGylated stearate, butyl stearate, cetyl esters wax, isopropyl myristate, isopropyl palmitate, myristyl lactate, sodium aluroyl lactate, octyl dodecanol, petrolatum, white wax, cyclomethicone, dimethicone, silicone emulsion, simethicone, cholesterol, caprylic capric triglycerides, shea butter, sunflower seed oil, squalene, squalane, coconut oil, glycerol stearate, PEGylated stearate, sodium aluroyl lactate, ceramide NP, ceramide AP, ceramide EOP, cholesterol, phytosphingosine, glyceryl caprylate, glyceryl undecylenate, xanthan gum, or combinations thereof; one or more humectants selected from glycerin, glyceryl propanediol, propylene glycol, butylene glycol, pentylene glycol, sorbitol, urea and derivatives thereof, alpha hydroxy acids, sorbitol, xylitol, mannitol, hyaluronic acid or pharmaceutically acceptable salts thereof, icodextin, protein hydrolystate, carbomer, or combinations thereof; one or more emulsifiers selected from distearyldimonium chloride, ceteareth-30, ceteth-10, ceteth-20, ceteth-2, laureth-23, laureth-4, polyoxyl glyceryl stearate, polyoxyl stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80 glycertl stearate SE, glyceryl stearate / PEG-100 stearate, emulsifying wax, or combinations thereof; one or more microbiome modulators selected from Saccharomyces cerevisiae extract, Glycyrrhiza glabra (licorice) root powder, Bifida ferment lysate, bisabolol, Lactococcus ferment lysate, Rosmarinus officinalis (rosemary) leaf extract, rosmarinic acid, Beta Vulgaris (beet) root extract, Ficus carica (Fig) fruit extract, Lactobacillus plantarum lysate, or combinations thereof; one or more analgesics or astringents selected from ocopherol acetate, laureth-9, willow bark extract, cryosim-1, aspirin, polidocanol, pramoxine hydrochloridealuminum acetate, menthol, pramoxine, or combinations thereof, and one or more pharmaceutically acceptable excipients, carriers, or diluents.

[0008] Additional features and advantages of the embodiments described herein will be set forth in the detailed description that follows, and in part will be readily apparent to those skilled in the art from that description or recognized by practicing the embodiments described herein, including the detailed description and claims that follow.DETAILED DESCRIPTION

[0009] Features and advantages of the disclosure will now be described with occasional reference to specific embodiments. However, the disclosure may be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete and will fully convey the scope of the disclosure to those skilled in the art.

[0010] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure belongs. The terminology used in the description herein is for describing particular embodiments only and is not intended to be limiting.

[0011] As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms, including “at least one,” unless the content clearly indicates otherwise. “Or” means “and / or.” As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items. It will be further understood that the terms “comprises” and / or “comprising,” or “includes” and / or “including” when used in this specification, specify the presence of stated features, regions, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, components, and / or groups thereof. It is to be further understood that where descriptions of various embodiments use the term “comprising,” and / or “including” those skilled in the art would understand that in some specific instances, an embodiment can be alternatively described using language “consisting essentially of’ or “consisting of.” The term “or a combination thereof’ means a combination including at least one of the foregoing elements.

[0012] Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth as used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless otherwise indicated, the numerical properties set forth in the specification and claims are approximations that may vary depending on the desired properties sought to be obtained in embodiments of the present disclosure. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. One of ordinary skill in the art will understand that any numerical values inherently contain certain errors attributable to the measurement techniques used to ascertain the values.

[0013] As used herein, the term “about,” when referring to a value or to an amount of mass, weight, time, volume, concentration or percentage is meant to encompass variations of in some embodiments ±20%, in some embodiments ±10%, in some embodiments ±5%, in some embodiments ±1%, in some embodiments ±0.5%, and in some embodiments ±0.1% from the specified amount, as such variations are appropriate to perform the disclosed method.

[0014] It should be understood that every numerical range given throughout this specification will include every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein. Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, examples include from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint.

[0015] Ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 25 is understood to include any number, combination of numbers, or sub-range from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25, as well as all intervening decimal values between the aforementioned integers such as, for example, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, and 1.9. With respect to sub-ranges, “nested sub-ranges” that extend from either end point of the range arespecifically contemplated. For example, a nested sub-range of an exemplary range of 1 to 25 may comprise 1 to 5, 1 to 10, 1 to 15, and 1 to 20 in one direction, or 25 to 20, 25 to 15, 25 to 10, and 25 to 5 in the other direction.

[0016] The term “subject” as used herein refers to any living organism to which a composition of the present disclosure may be administered. The term subject includes, but is not limited to, humans, nonhuman primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, sheep, pigs, goats and horses; domestic mammals such as dogs and cats; laboratory animals including rodents such as mice, rats and guinea pigs, and the like. The term does not denote a particular age or sex. Thus, adult, child, and newborn subjects, as well as fetuses, whether male or female, are intended to be covered.

[0017] An “effective amount,” as used herein, refers to an amount of a substance (e.g., a therapeutic compound and / or composition) that elicits a desired biological response. In some embodiments, an effective amount of a substance is an amount that is sufficient, when administered to a subject suffering from or susceptible to a disease, disorder, and / or condition, to treat, diagnose, prevent, and / or delay and / or alleviate one or more symptoms of the disease, disorder, and / or condition. As will be appreciated by those of ordinary skill in this art, the effective amount of a substance may vary depending on such factors as the desired biological endpoint, the substance to be delivered, the target cell or tissue, etc. For example, the effective amount of a formulation to treat a disease, disorder, and / or condition is the amount that alleviates, ameliorates, relieves, inhibits, prevents, delays onset of; reduces severity of and / or reduces incidence of one or more symptoms or features of the disease, disorder, and / or condition. Furthermore, an effective amount may be administered via a single dose or via multiple doses within a treatment regimen. In some embodiments, individual doses or compositions are considered to contain an effective amount when they contain an amount effective as a dose in the context of a treatment regimen. Those of ordinary skill in the art will appreciate that a dose or amount may be considered to be effective if it is or has been demonstrated to show statistically significant effectiveness when administered to a population of patients; a particular result need not be achieved in a particular individual patient in order for an amount to be considered to be effective as described herein.

[0018] As used herein, the terms “administer,” “administering,” “administration,” or grammatical equivalents thereof, refers to any route of administering an effective amount of atherapeutic agent and / or composition. In embodiments, the administering includes, but is not limited to, topical administration, oral administration, periocular administration, intrafollicular administration, intravenous administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, intracerebral administration, intraspinal administration, intrathecal administration, subarachnoid administration, epidural administration, intraocular administration, and the like. In a specific embodiment, the composition is administered topically.

[0019] As used herein, the terms "improve," "increase," "inhibit,” "reduce," or grammatical equivalents thereof, indicate values that are relative to a baseline or other reference measurement. In some embodiments, an appropriate reference measurement may be or comprise a measurement in a particular system (e.g., in a single subject) under otherwise comparable conditions absent presence of (e.g., prior to and / or after) a particular agent or treatment, or in presence of an appropriate comparable reference agent. In some embodiments, an appropriate reference measurement may be or comprise a measurement in comparable system known or expected to respond in a particular way, in presence of the relevant agent or treatment.

[0020] The term “independently selected from,” as used herein, is intended to mean that the referenced groups can be the same, different, or a mixture thereof, unless the context clearly indicates otherwise. Thus, under this definition, the phrase “X1, X2, and X3are independently selected from noble gases” would include the scenario where X1, X2, and X3are all the same, where X1, X2, and X3are all different, and where X1and X2are the same but X3is different.

[0021] As used herein, the term “pharmaceutically acceptable” refers to approved or approvable by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, including humans.

[0022] As used herein, the term “pharmaceutically acceptable excipient, carrier, or diluent” or the like refer to an excipient, carrier, or diluent that can be administered to a subject, together with an agent, and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic amount of the agent.

[0023] Unless otherwise stated, the structures depicted and described herein include all isomeric (e.g., enantiomeric, diastereomeric, and geometric) forms of the structure; for example,tautomers, R and S configurations for each asymmetric center, Z and E double bond isomers, and Z and E conformational isomers. Additionally, unless otherwise stated, the structures depicted and described herein include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures including the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a13C- or14C-enriched carbon are within the scope of this disclosure. Such compounds may be useful, for example, as analytical tools or as therapeutic agents.

[0024] Unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not actually recite an order to be followed by its steps or it is not otherwise specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that any particular order be inferred. Any recited single or multiple feature or aspect in any one claim can be combined or permuted with any other recited feature or aspect in any other claim or claims.

[0025] Embodiments of the present disclosure generally relate to pharmaceutical compositions and methods of using the compositions in the treatment of a skin condition, optionally atopic dermatitis. Other exemplary skin conditions that may be treated with the compositions described herein may include, but are not limited to, rashes (including diaper rash), bums, cuts and abrasions, chapped and dry skin, signs of aging, hair and scalp conditions, acne, urticaria (hives), sunburn, contact dermatitis, xerotic dermatoses, psoriasis, insect bites, skin irritation resulting from radiation and chemotherapy, and microbial infections, such as varicella.

[0026] As described briefly above, the pathophysiology of atopic dermatitis involves a combination of genetic, immune, and environmental factors. For example, and without being bound by theory, one aspect of genetic predisposition of atopic dermatitis results from mutations in the filaggrin (FLG) gene, which is associated with eczema. Filaggrin is involved in maintaining the skin barrier's integrity by forming the stratum corneum, the outermost layer of the skin. Deficiency in filaggrin results in a compromised skin barrier, characterized by increased trans-epidermal water loss (TEWL), leading to dry skin, enhanced penetration of allergens, irritants, and microbes, and reduced levels of natural moisturizing factors (NMFs) derived from filaggrin breakdown, such as urocanic acid and pyrrolidone carboxylic acid.

[0027] Atopic dermatitis may also be associated with an imbalance in the immune response, particularly involving the Th2 (T-helper type 2) pathway. Overactivation of Th2 cytokines (e.g., IL-4, IL-5, IL- 13) promotes IgE production, contributing to allergic sensitization and skin inflammation, while a dysregulated Thl / Th2 balance skews the response toward Th2, thereby suppressing the protective Th 1 -mediated responses to infections. During chronic eczema, Th22 and Thl pathways may also contribute, leading to persistent inflammation and skin thickening (lichenification).

[0028] As described herein above, the skin barrier in a subject suffering from atopic dermatitis may be weakened due to filaggrin deficiency and / or abnormal lipid composition (e.g., reduced ceramides). It will be appreciated that this dysfunction facilitates, for example, penetration of allergens (e.g., house dust mites, pollen), increased susceptibility to microbial colonization, especially Staphylococcus aureus, which exacerbates inflammation through the release of superantigens and toxins, and loss of antimicrobial peptides, further predisposing the skin to infections. Further, with an impaired skin barrier, environmental allergens can penetrate the skin, leading to activation of dendritic cells in the epidermis, presentation of allergens to naive T cells in lymph nodes, driving Th2 responses, and / or IgE-mediated sensitization, which underlies many allergic reactions in eczema patients.

[0029] Atopic dermatitis is also associated with the production of various inflammatory mediators. For example, the production of cytokines (e.g., IL-31, which drives itching) and chemokines fuels inflammation. Histamine and other mediators released by mast cells amplify itching and promote scratching, which perpetuates the itch-scratch cycle. Scratching further damages the skin, worsening barrier dysfunction and inflammation. It will be further appreciated that chronic itch in eczema is mediated by nerve fibers in the skin that release neuropeptides, interacting with immune cells to amplify inflammation. IL-31, produced by Th2 cells, specifically acts on sensory neurons to drive itch.

[0030] The compositions described herein include component(s) that treat a number of underlying mechanisms of action associated with atopic dermatitis, including microbiome modulation, barrier function, inflammations, free-radical damage, hydration, itchiness, and / or pain. It will be appreciated that a single component of the formulation may impact one of more associated mechanisms of action. In some embodiments, the component(s) are mixed with apharmaceutically acceptable excipient, carrier, or diluent to achieve the desired concentration, described in greater detail herein. In some embodiments, pharmaceutically acceptable excipient, carrier, or diluent is water.

[0031] Optionally, the composition has from about 0.01% w / w to about 99.99% w / w of the pharmaceutically acceptable excipient, carrier, or diluent, including about 0.05% w / w, about 0.1 % w / w, about 0.2 % w / w, about 0.25% w / w, about 0.3 % w / w, about 0.4% w / w, about 0.5% w / w, about 0.6 % w / w, about 0.7% w / w, about 0.75 % w / w, about 0.8% w / w, about 0.9% w / w, about 1 % w / w, about 1.25% w / w, about 1.5 % w / w, about 1.75% w / w, about 2 % w / w, about 2.25 % w / w, about 2.5 % w / w, about 2.75% w / w, about 3 % w / w, about 4 % w / w, about 5 % w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9% w / w, about 10% w / w, about 11 % w / w, about 12 % w / w, about 13 % w / w, about 14% w / w, about 15% w / w, about 20% w / w, about 25% w / w, about 30% w / w, about 35% w / w, about 45% w / w, about 50% w / w, about 55% w / w, about 60% w / w, about 65% w / w, about 70% w / w, about 75% w / w, about 80% w / w, about 85% w / w, about 90% w / w, and about 95% w / w. Optionally, the composition include from about 50% w / w to about 90% w / w, from about 55% w / w to about 85% w / w, from about 60% w / w to about 80% w / w, from about 65% w / w to about 75% w / w, from about 65% w / w to about 70% w / w, or from about 70% w / w to about 75% w / w of the pharmaceutically acceptable excipient.

[0032] In some embodiments, the compositions described herein may include one or more emollients. As used herein, “emollient” refers to a substance or formulation used to moisturize and soften the skin by forming a protective barrier that prevents moisture loss. Emollients may be used to alleviate dry, flaky, or irritated skin by improving the skin’s hydration levels and restoring its barrier function. It will be appreciated that an emollient may work by reducing transepidermal water loss (TEWL). In addition to providing hydration, emollients may have soothing and / or antiinflammatory properties, making them beneficial in the management of dermatological conditions such as eczema, psoriasis, and dermatitis.

[0033] Exemplary emollient(s) in the composition include, but are not limited to, oils or butters (e.g., sunflower seed oil, coconut oil, olive oil, safflower oil, bilberry oil, shea butter, lanolin, caprylic capric triglycerides, squalane etc.), alcohols (e.g., cetostearyl alcohol, cetyl alcohol, cetearyl alcohol, isostearyl alcohol, myristyl alcohol, oleyl alcohol, stearyl alcohol, etc.), esters or waxes (e.g., glycerol stearate, glycerol caprylate, glyceryl undecylenate, PEGylated stearate, butyl stearate, cetyl esters wax, isopropyl myristate, isopropyl palmitate, myristyl lactate, sodiumaluroyl lactate, octyl dodecanol, petrolatum, white wax, etc.), polysaccharides (e.g., xanthan gum, etc.) silicones (e.g., cyclomethicone, dimethicone, silicone emulsion, simethicone, etc.), cholesterol and derivatives thereof, combinations thereof, and the like. In some embodiments, the composition includes one or more of caprylic capric triglycerides, shea butter, sunflower seed oil, squalene, coconut oil, glycerol stearate, PEGylated stearate, sodium aluroyl lactate, ceramide NP, ceramide AP, ceramide EOP, cholesterol, phytosphingosine, glyceryl caprylate, glyceryl undecylenate, xanthan gum, and combinations thereof.

[0034] Optionally, the composition has from about 0.01% w / w to about 50% w / w of the emollient(s) either individually or in combination, including about 0.05% w / w, about 0.1% w / w, about 0.2% w / w, about 0.25% w / w, about 0.3 % w / w, about 0.4% w / w, about 0.5% w / w, about 0.6 % w / w, about 0.7% w / w, about 0.75 % w / w, about 0.8% w / w, about 0.9% w / w, about 1 % w / w, about 1.25% w / w, about 1.5 % w / w, about 1.75% w / w, about 2 % w / w, about 2.25 % w / w, about 2.5 % w / w, about 2.75% w / w, about 3 % w / w, about 4 % w / w, about 5 % w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9% w / w, about 10% w / w, about 11 % w / w, about 12 % w / w, about 13 % w / w, about 14% w / w, about 15% w / w, about 20% w / w, about 25% w / w, about 30% w / w, about 35% w / w, about 45% w / w, about 50% w / w. Optionally, the composition includes from about 0.01% w / w to about 40% w / w, from about 0.01% w / w to about 30% w / w, from about 0.01% w / w to about 10% w / w, from about 0.01% w / w to about 9% w / w, from about 0.01% w / w to about 7.5% w / w, or from about 0.01% w / w to about 5% w / w of the emollient(s).

[0035] In some embodiments, the compositions described herein may include one or more humectants. As used herein, “humectant” refers to a component that attracts moisture from the environment into the skin or other surfaces. By drawing water from the air or deeper layers of the skin, humectants help to maintain hydration, prevent dryness, and promote a smooth, plump appearance. It will be appreciated that these components may work by binding water molecules to their structure.

[0036] Exemplary humectants may include, but are not limited to, polyols (e.g., glycerin, glyceryl propanediol, propylene glycol, butylene glycol, pentylene glycol, sorbitol, etc.), urea and derivatives thereof, alpha hydroxy acids, sugar alcohols (sorbitol, xylitol, mannitol, etc.), hyaluronic acid (or pharmaceutically acceptable salts thereof), icodextin, protein hydrolystate, carbomer, combinations thereof, and the like. In some embodiments, the compositions includeone or more humectants selected from: glycerin, hyaluronic acid (or pharmaceutically acceptable salts thereof), propylene glycol, or combinations thereof.

[0037] Optionally, the composition has from about 0.01% w / w to about 50% w / w of the humectant(s) either individually or in combination, including about 0.05% w / w, about 0.1% w / w, about 0.2% w / w, about 0.25% w / w, about 0.3 % w / w, about 0.4% w / w, about 0.5% w / w, about 0.6 % w / w, about 0.7% w / w, about 0.75 % w / w, about 0.8% w / w, about 0.9% w / w, about 1 % w / w, about 1.25% w / w, about 1.5 % w / w, about 1.75% w / w, about 2 % w / w, about 2.25 % w / w, about 2.5 % w / w, about 2.75% w / w, about 3 % w / w, about 4 % w / w, about 5 % w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9% w / w, about 10% w / w, about 11 % w / w, about 12 % w / w, about 13 % w / w, about 14% w / w, about 15% w / w, about 20% w / w, about 25% w / w, about 30% w / w, about 35% w / w, about 45% w / w, about 50% w / w. Optionally, the composition includes from about 0.01% w / w to about 40% w / w, from about 0.01% w / w to about 30% w / w, from about 0.01% w / w to about 10% w / w, from about 0.01% w / w to about 9% w / w, from about 0.01% w / w to about 7.5% w / w, or from about 0.01% w / w to about 5% w / w of the humectant(s).

[0038] In some embodiments, the composition may include one or more moisture barrier modulators. As used herein, a “moisture barrier modulator” is a substance or ingredient used in skincare formulations that modifies or enhances the skin’s natural barrier function to improve its ability to retain moisture. These modulators work by reinforcing the skin's lipid barrier, which is essential for preventing trans-epidermal water loss (TEWL) and maintaining optimal hydration levels in the skin. Moisture barrier modulators often work by restoring or strengthening the skin's natural lipid composition, improving skin barrier integrity, and promoting hydration retention. It will be appreciated that one or more of the aforementioned emollients and / or humectants may serve as a moisture barrier modulator. Exemplary, non-limiting moisture barrier modulators include ceramides, hyaluronic acid, urea, fatty acids, such as linoleic acid and gamma-linoleic acid, cholesterol, vitamins (e.g., niacinamide, vitamin E, etc.) peptides (e.g., histidine) and / or extracts, which help repair and maintain the skin's protective layer, especially in conditions where the skin barrier is compromised (e.g., dry skin, eczema, or psoriasis). In some embodiments, the moisture barrier modulator(s) includes one or more of allantoin, panthenol, colloidal oatmeal (Avena Sativa (Oat) Kernel Flour), niacinimide, vitamin E, histidine, sodium hyaluronate, cyanocobalamin, and combinations thereof.

[0039] Optionally, the composition has from about 0.01% w / w to about 50% w / w of the moisture barrier modulator(s) either individually or in combination, including about 0.05% w / w, about 0.1% w / w, about 0.2% w / w, about 0.25% w / w, about 0.3 % w / w, about 0.4% w / w, about 0.5% w / w, about 0.6 % w / w, about 0.7% w / w, about 0.75 % w / w, about 0.8% w / w, about 0.9% w / w, about 1 % w / w, about 1.25% w / w, about 1.5 % w / w, about 1.75% w / w, about 2 % w / w, about 2.25 % w / w, about 2.5 % w / w, about 2.75% w / w, about 3 % w / w, about 4 % w / w, about 5 % w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9% w / w, about 10% w / w, about 11 % w / w, about 12 % w / w, about 13 % w / w, about 14% w / w, about 15% w / w, about 20% w / w, about 25% w / w, about 30% w / w, about 35% w / w, about 45% w / w, about 50% w / w. Optionally, the composition includes from about 0.01% w / w to about 40% w / w, from about 0.01% w / w to about 30% w / w, from about 0.01% w / w to about 10% w / w, from about 0.01% w / w to about 9% w / w, from about 0.01% w / w to about 7.5% w / w, or from about 0.01% w / w to about 5% w / w of the emollient(s).

[0040] In some embodiments, the composition includes one or more microbiome modulators. Optionally, the microbiome modulator is an extract or lysate. In some embodiments, the extract or lysate(s) is selected form Saccharomyces cerevisiae extract, Glycyrrhiza glabra (licorice) root powder, Bifida ferment lysate, bisabolol, Lactococcus ferment lysate, Rosmarinus officinalis (rosemary) leaf extract, rosmarinic acid, bisabolol, Beta Vulgaris (beet) root extract, Ficus carica (Fig) fruit extract, Lactobacillus plantarum lysate, or combinations thereof.

[0041] Optionally, the composition has from about 0.01% w / w to about 10% w / w of the microbiome modulator, either individually or in combination, including about 0.05% w / w, about 0.1% w / w, about 0.2% w / w, about 0.25% w / w, about 0.3 % w / w, about 0.4% w / w, about 0.5% w / w, about 0.6 % w / w, about 0.7% w / w, about 0.75 % w / w, about 0.8% w / w, about 0.9% w / w, about 1 % w / w, about 1.25 % w / w, about 1.5 % w / w, about 1.75% w / w, about 2 % w / w, about 2.25 % w / w, about 2.5 % w / w, about 2.75% w / w, about 3% w / w, about 3.25 % w / w, about 3.5 % w / w, about 3.75% w / w, about 4 % w / w, about 4.25 % w / w, about 4.5 % w / w, about 4.75% w / w about 5 % w / w, about 5.25 % w / w, about 5.5 % w / w, about 5.75% w / w about 6% w / w, about 6.25 % w / w, about 6.5 % w / w, about 6.75% w / w about 7% w / w, about 8% w / w, about 9% w / w, about 10%. Optionally, the composition includes from about 0.01% w / w to about 9% w / w, from about 0.01% w / w to about 7.5% w / w, from about 0.01% w / w to about 5% w / w, from about 0.01% w / w to about 2.5% w / w, from about 0.01% w / w to about 1.25% w / w, or from about 0.01% w / w to about 1% w / w of the extract or lysate(s).

[0042] In some embodiments, the compositions may include other pharmaceutically acceptable additives or agents, such as anti-inflammatory agents, analgesics / astringents to control itching, antimicrobials, antioxidants, buffers, emulsifiers, preservatives, thickeners, colorants / fragrances, combinations thereof, and the like. In some embodiments, any one or more of the aforementioned components serves as one or more of these agents. Any suitable component, for example any of those noted in the USP or other suitable pharmacopeia may be added to the compositions described herein without straying from the scope of the present disclosure.

[0043] Exemplary anti-inflammatories, in addition to other components described herein include topical corticosteroids, such as hydrocortisone, betamethasone, clobetasol, mometasone, fluticasone and combinations thereof, calcineurin inhibitors, such as tacrolimus and / or pimecrolimus, JAK inhibitors, such as ruxolitinib, PDE4 inhibitors, such as crisaboorole, combinations thereof, and the like. Any suitable anti-inflammatory is contemplated and possible.

[0044] Exemplary analgesics or astringents, in addition to other components described herein include tocopherol acetate, laureth-9, willow bark extract, cryosim-1, aspirin, polidocanol, pramoxine hydrochloride aluminum acetate, menthol, pramoxine, and the like. Exemplary antimicrobials include benzalkonium chloride, mupirocin, ketoconazole, and / or clotrimazole. Exemplary antioxidants include panthenol, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), vitamin E, tocopherol, tocopherol acetate, green tea polyphenols, chamomile extract, combinations thereof, and the like.

[0045] In some embodiments, the compositions include one or more colorants or fragrances, such as D&C Yellow No. 10, FD&C Blue No. 1, FD&C Yellow No. 6, caramel, ferric oxide red, Fragrance Ungerer N5195, limonene, combinations thereof, and the like.

[0046] The compositions may also include one or more emulsifiers. Exemplary emulsifiers include, but are not limited to, distearyldimonium chloride, ceteareth-30, ceteth-10, ceteth-20, ceteth-2, laureth-23, laureth-4, polyoxyl glyceryl stearate, polyoxyl stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80 glycertl stearate SE, glyceryl stearate / PEG-100 stearate, emulsifying wax, combinations thereof, and the like.

[0047] In some embodiments, the compositions include one or more preservatives. Optionally, the preservative is selected from methylparaben, propylparaben, butylparaben benzalkoniumchloride, benzyl alcohol, diazolidinyl urea, imidurea, DMDM hydantoin, methylchloroisothiazolinone, potassium sorbate, sodium metabisulfite, sorbic acid, thimerosal, combinations thereof, and the like.

[0048] Optionally, the compositions may include one or more pH adjusters or buffers. Exemplary pH adjusters or buffers include aminomethylpropanol, ammonia solution, citric acid, lactic acid, phosphoric acid, sodium hydroxide, trolamine, trisodium citrate, trisodium citrate dihydrate, sodium phosphate (monobasic and dibasic forms), anhydrous citric acid, combinations thereof and the like.

[0049] In some embodiments, the composition has a pH from about 4 to about 6, including about 4, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, and about 6, including any subrange defined by any two of the aforementioned values. In some embodiments, the pH is from about 4 to about 5. In some embodiments, the pH is from about 4.2 to about 5. In some embodiments the pH is from about 4.5 to about 5. In some embodiments, the pH is from about 4 to about 4.8. In some embodiments, the pH is from about 4.2 to about 4.8. In some embodiments, the pH is from about 4.5 to about 4.8.

[0050] In some embodiments, the composition includes one or more thickeners, stabilizers, or gelling agents. Exemplary thickeners, stabilizers, or gelling agents include, carbomer homopolymer, carbomer copolymer, hydroxyethyl cellulose, hydroxypropyl cellulose, hypromellose, xanthan gum, guar gum, carrageenan, chondrus crispus, bentonite, combinations thereof, and the like.

[0051] The compositions disclosed herein may be administered to a subject suffering from atopic dermatitis to treat the atopic dermatitis. Optionally the compositions are administered topically. In some embodiments, the compositions are administered one, two or three times daily to the affected area. In some embodiments, the compositions are administered for one week, for two weeks, for three weeks, for a month, for two months, etc.

[0052] Treatment with the compositions described herein may result in the reduction of one more clinical symptoms associated with atopic dermatitis, such as frequency and severity of itching, pain, sleep disturbance, dryness, interference with daily activities, erythema, induration, excoriation, lichenification, redness, swelling, oozing / crusting, and combinations thereof. In someembodiments, treatment with the compositions described herein may result in the reduction of two or more clinical symptoms, three or more clinical symptoms, four or more clinical symptoms, five or more clinical symptoms, six or more clinical symptoms, or more. The efficacy of the treatments may be evaluated by patient reported improvement scoring assessments (e.g., Skindex-16, Skindex-29, PROMIS, CDLQI, PGA, NRS, DLQI, POEM, etc.) and / or by clinician guided assessments (e g., EASI, SCORAD, IGA, BSA, TIS, SASSAD, oSCORAD, etc ). In some embodiments, treatment with the compositions described herein results in a lower score on the assessment compared to a baseline (with no treatment).

[0053] For example, and without being bound by theory, in some embodiments, treatment efficacy is monitored using the Eczema Area and Severity Index (EASI). The EASI score evaluates the severity of redness, thickness, scratching, and lichenification across defined body regions, combining these with the percentage of affected skin area. During treatment, regular monitoring of the EASI score enables clinicians to track changes in disease severity, quantify progress, and determine whether the intervention is meeting therapeutic goals. A reduction in the EASI score indicates a meaningful improvement in skin condition. In some embodiments, administration of the composition results in a 2 point or greater reduction on the EASI score, a 3 point or greater reduction on the EASI score, a 4 point or greater reduction on the EASI score, a 5 point or greater reduction on the EASI score, a 6 point or greater reduction on the EASI score, a 7 point or greater reduction on the EASI score, an 8 point or greater reduction on the EASI score, a 9 point or greater reduction on the EASI score, a 10 point or greater reduction on the EASI score, a 15 point or greater reduction on the EASI score, a 20 point or greater reduction on the EASI score, or a 25 point or greater reduction on the EASI score. In some embodiments, the composition effectively treats the atopic dermatitis by reducing the EASI score by 10 percent, 15 percent, 20 percent, 30 percent, 40 percent, 50 percent, or more.

[0054] In some embodiments, the composition has the formulation as shown in Table 1.

[0055] Table 1INCI Name Amount

[0056] Optionally, the formula in Table 1 further includes rosemary extract and / or rosmarinic acid.

[0057] In some embodiments, the composition has the formulation as shown in Table 2.

[0058] Table 2INCI Name Amount

[0059] Optionally, the formula in Table 2 further includes rosemary extract and / or rosmarinic acid.

[0060] Some aspects of the present disclosure may be represented by the following clauses.

[0061] A first item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), the method comprising topically administering to the subject a composition comprising: one or more moisture barrier modulators selected from allantoin, panthenol, colloidal oatmeal (Avena Sativa Kernel Flour), niacinimide, vitamin E, histidine, sodium hyaluronate, ceramides, hyaluronic acid, urea, linoleic acid, or combinations thereof; oneor more emollients selected from sunflower seed oil, coconut oil, olive oil, safflower oil, bilberry oil, shea butter, lanolin, caprylic capric triglycerides, squalane, cetostearyl alcohol, cetyl alcohol, cetearyl alcohol, isostearyl alcohol, myristyl alcohol, oleyl alcohol, stearyl alcohol, glycerol stearate, glycerol caprylate, glyceryl undecylenate, PEGylated stearate, butyl stearate, cetyl esters wax, isopropyl myristate, isopropyl palmitate, myristyl lactate, sodium aluroyl lactate, octyl dodecanol, petrolatum, white wax, cyclomethicone, dimethicone, silicone emulsion, simethicone, cholesterol, caprylic capric triglycerides, shea butter, sunflower seed oil, squalene, squalane, coconut oil, glycerol stearate, PEGylated stearate, sodium aluroyl lactate, ceramide NP, ceramide AP, ceramide EOP, cholesterol, phytosphingosine, glyceryl caprylate, glyceryl undecylenate, xanthan gum, or combinations thereof; one or more humectants selected from glycerin, glyceryl propanediol, propylene glycol, butylene glycol, pentylene glycol, sorbitol, urea and derivatives thereof, alpha hydroxy acids, sorbitol, xylitol, mannitol, hyaluronic acid or pharmaceutically acceptable salts thereof, icodextin, protein hydrolystate, carbomer, or combinations thereof one or more emulsifiers selected from distearyldimonium chloride, ceteareth-30, ceteth-10, ceteth-20, ceteth-2, laureth-23, laureth-4, polyoxyl glyceryl stearate, polyoxyl stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80 glycertl stearate SE, glyceryl stearate / PEG-100 stearate, emulsifying wax, or combinations thereof; one or more microbiome modulators selected from Saccharomyces cerevisiae extract, Glycyrrhiza glabra (licorice) root powder, Bifida ferment lysate, bisabolol, Lactococcus ferment lysate, Rosmarinus officinalis (rosemary) leaf extract, rosmarinic acid, Beta Vulgaris (beet) root extract, Ficus carica (Fig) fruit extract, Lactobacillus plantarum lysate, or combinations thereof; one or more analgesics or astringents selected from ocopherol acetate, laureth-9, willow bark extract, cryosim-1, aspirin, polidocanol, pram oxine hydrochloride aluminum acetate, menthol, pramoxine, or combinations thereof, and one or more pharmaceutically acceptable excipients, carriers, or diluents.

[0062] A second item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the one or more moisture barrier modulators are selected from allantoin, panthenol, colloidal oatmeal (Avena Sativa Kernel Flour), niacinamide, vitamin E, histidine, hyaluronic acid, cyanocobalamin, sodium hyaluronate or combinations thereof.

[0063] A third item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the one or more moisture barrier modulators comprises a combination of allantoin, panthenol, colloidal oatmeal (Avena Sativa Kernel Flour), vitamin E, histidine, and sodium hyaluronate.

[0064] A fourth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the one or more moisture barrier modulators comprises a combination of hyaluronic acid, panthenol, colloidal oatmeal (Avena Sativa Kernel Flour), niacinamide, cyanocobalamin, histidine, and allantoin.

[0065] A fifth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the one or more emollients are selected from xanthan gum, cetearyl alcohol, caprylic capric triglycerides, Butyrospermum Parkii (shea) butter, sunflower seed oil, squalane, coconut oil, glyceryl stearate, PEG- 100 stearate, ceramide NP, ceramide AP, ceramide EOP, phytosphingosine, cholesterol, sodium aluroyl lactate, carbomer, glyceryl caprylate, glyceryl undecylenate, bilberry oil or combinations thereof.

[0066] A sixth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the one or more emollients comprises a combination of xanthan gum, cetearyl alcohol, caprylic capric triglycerides, Butyrospermum Parkii (shea) butter, sunflower seed oil, squalane, coconut oil, glyceryl stearate, PEG- 100 stearate, ceramide NP, ceramide AP, ceramide EOP, phytosphingosine, cholesterol, sodium aluroyl lactate, carbomer, glyceryl caprylate, and glyceryl undecylenate.

[0067] A seventh item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the one or more emollients comprises a combination of xanthan gum, cetearyl alcohol, caprylic capric triglycerides, Butyrospermum Parkii (shea) butter, sunflower seed oil, squalane, coconut oil, glyceryl stearate, PEG- 100 stearate, ceramideNP, ceramide AP, ceramide EOP, phytosphingosine, cholesterol, sodium aluroyl lactate, carbomer, glyceryl caprylate, glyceryl undecylenate, and bilberry oil.

[0068] An eighth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the humectant is glycerin.

[0069] A ninth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the emulsifier is distearyldimonium chloride.

[0070] A tenth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the one or more microbiome modulators are selected from Saccharomyces Cerevisiae extract, bisabolol, Glycyrrhiza Glabra (licorice) root powder, bifida ferment lysate, Lactococcus ferment lysate, rosemary leaf extract, Beta Vulgaris (beet) root extract, Ficus Carica (fig) fruit extract, Lactobacillus Plantarum lysate, and combinations thereof.

[0071] An eleventh item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the one or more microbiome modulators comprises a combination of Saccharomyces Cerevisiae extract, bisabolol, Glycyrrhiza Glabra (licorice) root powder, bifida ferment lysate, and Lactococcus ferment lysate.

[0072] A twelfth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the one or more microbiome modulators comprises a combination of Saccharomyces Cerevisiae extract, bisabolol, Glycyrrhiza Glabra (licorice) root powder, bifida ferment lysate, Lactococcus ferment lysate, rosemary leaf extract, Beta Vulgaris (beet) root extract, Ficus Carica (fig) fruit extract, and Lactobacillus Plantarum lysate.

[0073] A thirteenth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the analgesic is tocopherol acetate.

[0074] A fourteenth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the pharmaceutically acceptable excipient, carrier, or diluent is water.

[0075] A fifteenth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the composition has a pH from about 4 to about 5.

[0076] A sixteenth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the composition has a pH from about 4.5 to about 4.8.

[0077] A seventeenth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the composition is administered daily.

[0078] An eighteenth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein the composition is administered daily for at least one week.

[0079] A nineteenth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for use in treating atopic dermatitis), wherein administering the composition improves atopic dermatitis of the subject relative to a baseline.

[0080] A twentieth item of the present disclosure, alone or in combination with any other item described herein, relates to a method for treating atopic dermatitis (or a composition for usein treating atopic dermatitis), wherein improving atopic dermatitis is measured by a reduction in an Eczema Area and Severity Index (EASI) score.

[0081] It is noted that the terms “substantially” and “about” may be utilized herein to represent the inherent degree of uncertainty that may be attributed to any quantitative comparison, value, measurement, or other representation. These terms are also utilized herein to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue. The term “substantially” is used herein also to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue. Thus, it is used to represent the inherent degree of uncertainty that may be attributed to any quantitative comparison, value, measurement, or other representation, referring to an arrangement of elements or features that, while in theory would be expected to exhibit exact correspondence or behavior, may in practice embody something less than exact.

[0082] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure belongs. The terminology used in the description herein is for describing particular embodiments only and is not intended to be limiting. As used in the specification and appended claims, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0083] It is noted that one or more of the following claims utilize the term “wherein” as a transitional phrase. For the purposes of defining the present technology, it is noted that this term is introduced in the claims as an open-ended transitional phrase that is used to introduce a recitation of a series of characteristics of the structure and should be interpreted in like manner as the more commonly used open-ended preamble term “comprising.”

[0084] It should be understood that where a first component is described as “comprising” or “including” a second component, it is contemplated that, in some embodiments, the first component “consists” or “consists essentially of’ the second component. Additionally, the term “consisting essentially of’ is used in this disclosure to refer to quantitative values that do not materially affect the basic and novel characteristic(s) of the disclosure.

[0085] It should be understood that any two quantitative values assigned to a property or measurement may constitute a range of that property or measurement, and all combinations of ranges formed from all stated quantitative values of a given property or measurement are contemplated in this disclosure.

[0086] While particular embodiments have been illustrated and described herein, it should be understood that various other changes and modifications may be made without departing from scope of the claimed subject matter. Moreover, although various aspects of the claimed subject matter have been described herein, such aspects need not be utilized in combination. It is therefore intended that the appended claims cover all such changes and modifications that are within the scope of the claimed subject matter.

Claims

CLAIMS1. A method for treating atopic dermatitis in a subject in need thereof, the method comprising topically administering to the subject a composition comprising:one or more moisture barrier modulators selected from allantoin, panthenol, colloidal oatmeal (Avena Sativa Kernel Flour), niacinimide, vitamin E, histidine, sodium hyaluronate, ceramides, hyaluronic acid, urea, linoleic acid, or combinations thereof;one or more emollients selected from sunflower seed oil, coconut oil, olive oil, safflower oil, bilberry oil, shea butter, lanolin, caprylic capric triglycerides, squalane, cetostearyl alcohol, cetyl alcohol, cetearyl alcohol, isostearyl alcohol, myristyl alcohol, oleyl alcohol, stearyl alcohol, glycerol stearate, glycerol caprylate, glyceryl undecylenate, PEGylated stearate, butyl stearate, cetyl esters wax, isopropyl myristate, isopropyl palmitate, myristyl lactate, sodium aluroyl lactate, octyl dodecanol, petrolatum, white wax, cyclomethicone, dimethicone, silicone emulsion, simethicone, cholesterol, caprylic capric triglycerides, shea butter, sunflower seed oil, squalene, squalane, coconut oil, glycerol stearate, PEGylated stearate, sodium aluroyl lactate, ceramide NP, ceramide AP, ceramide EOP, cholesterol, phytosphingosine, glyceryl caprylate, glyceryl undecylenate, xanthan gum, or combinations thereof;one or more humectants selected from glycerin, glyceryl propanediol, propylene glycol, butylene glycol, pentylene glycol, sorbitol, urea and derivatives thereof, alpha hydroxy acids, sorbitol, xylitol, mannitol, hyaluronic acid or pharmaceutically acceptable salts thereof, icodextin, protein hydrolystate, carbomer, or combinations thereof;one or more emulsifiers selected from distearyldimonium chloride, ceteareth-30, ceteth- 10, ceteth-20, ceteth-2, laureth-23, laureth-4, polyoxyl glyceryl stearate, polyoxyl stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80 glycertl stearate SE, glyceryl stearate / PEG-100 stearate, emulsifying wax, or combinations thereof;one or more microbiome modulators selected from Saccharomyces cerevisiae extract, Glycyrrhiza glabra (licorice) root powder, Bifida ferment lysate, bisabolol, Lactococcus ferment lysate, Rosmarinus officinalis (rosemary) leaf extract,rosmarinic acid, Beta Vulgaris (beet) root extract, Ficus carica (Fig) fruit extract, Lactobacillus plantarum lysate, or combinations thereof;one or more analgesics or astringents selected from ocopherol acetate, laureth-9, willow bark extract, cryosim-1, aspirin, polidocanol, pram oxine hydrochloride aluminum acetate, menthol, pramoxine, or combinations thereof, andone or more pharmaceutically acceptable excipients, carriers, or diluents.

2. The method according to claim 1, wherein the one or more moisture barrier modulators are selected from allantoin, panthenol, colloidal oatmeal (Avena Sativa Kernel Flour), niacinimide, vitamin E, histidine, hyaluronic acid, cyanocobalamin, sodium hyaluronate or combinations thereof.

3. The method according to claim 1, wherein the one or more moisture barrier modulators comprises a combination of allantoin, panthenol, colloidal oatmeal (Avena Sativa Kernel Flour), vitamin E, histidine, and sodium hyaluronate.

4. The method according to claim 1, wherein the one or more moisture barrier modulators comprises a combination of hyaluronic acid, panthenol, colloidal oatmeal (Avena Sativa Kernel Flour), niacinamide, cyanocobalamin, histidine, and allantoin.

5. The method according to claim 1, wherein the one or more emollients are selected from xanthan gum, cetearyl alcohol, caprylic capric triglycerides, Butyrospermum Parkii (shea) butter, sunflower seed oil, squalane, coconut oil, glyceryl stearate, PEG- 100 stearate, ceramide NP, ceramide AP, ceramide EOP, phytosphingosine, cholesterol, sodium aluroyl lactate, carbomer, glyceryl caprylate, glyceryl undecylenate, bilberry oil or combinations thereof.

6. The method according to claim 1, wherein the one or more emollients comprises a combination of xanthan gum, cetearyl alcohol, caprylic capric triglycerides, Butyrospermum Parkii (shea) butter, sunflower seed oil, squalane, coconut oil, glyceryl stearate, PEG- 100 stearate, ceramide NP, ceramide AP, ceramide EOP, phytosphingosine, cholesterol, sodium aluroyl lactate, carbomer, glyceryl caprylate, and glyceryl undecylenate.

7. The method according to claim 1, wherein the one or more emollients comprises a combination of xanthan gum, cetearyl alcohol, caprylic capric triglycerides, Butyrospermum Parkii (shea) butter, sunflower seed oil, squalane, coconut oil, glyceryl stearate, PEG- 100 stearate, ceramide NP, ceramide AP, ceramide EOP, phytosphingosine, cholesterol, sodium aluroyl lactate, carbomer, glyceryl caprylate, glyceryl undecylenate, and bilberry oil.

8. The method according to claim 1, wherein the humectant is glycerin.

9. The method according to claim 1, wherein the emulsifier is distearyldimonium chloride.

10. The method according to claim 1, wherein the one or more microbiome modulators are selected from Saccharomyces Cerevisiae extract, bisabolol, Glycyrrhiza Glabra (licorice) root powder, bifida ferment lysate, Lactococcus ferment lysate, rosemary leaf extract, Beta Vulgaris (beet) root extract, Ficus Carica (fig) fruit extract, Lactobacillus Plantarum lysate, and combinations thereof.

11. The method according to claim 1, wherein the one or more microbiome modulators comprises a combination of Saccharomyces Cerevisiae extract, bisabolol, Glycyrrhiza Glabra (licorice) root powder, bifida ferment lysate, and Lactococcus ferment lysate.

12. The method according to claim 1, wherein the one or more microbiome modulators comprises a combination of Saccharomyces Cerevisiae extract, bisabolol, Glycyrrhiza Glabra (licorice) root powder, bifida ferment lysate, Lactococcus ferment lysate, rosemary leaf extract, Beta Vulgaris (beet) root extract, Ficus Carica (fig) fruit extract, and Lactobacillus Plantarum lysate.

13. The method according to claim 1, wherein the analgesic is tocopherol acetate.

14. The method according to claim 1, wherein the pharmaceutically acceptable excipient, carrier, or diluent is water.

15. The method according to claim 1, wherein the composition has a pH from about 4 to about 5.

16. The method according to claim 1, wherein the composition has a pH from about 4.5 to about 4.8.

17. The method according to claim 1, wherein the composition is administered daily.

18. The method according to claim 1, wherein the composition is administered daily for at least one week.

19. The method according to claim 1, wherein administering the composition improves atopic dermatitis of the subject relative to a baseline.

20. The method according to claim 19, wherein improving atopic dermatitis is measured by a reduction in an Eczema Area and Severity Index (EASI) score.

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