Compositions comprising a stable water-in-silicone emulsion, kits, and their uses for preventing and treating diseases or conditions.

Description

1 / 109 Compositions comprising a stable water-in-silicone emulsion, kits, and their uses for preventing and treating diseases or conditions. Separated from BR112020012195-9, filed on December 14, 2018. Related patent applications

[001] This patent application claims the benefits of priority to U.S. Provisional Patent Application No. 62 / 609,127, filed December 21, 2017, and U.S. Provisional Patent Application No. 62 / 607,286, filed December 18, 2017, the full text of each being incorporated herein by reference. FIELD OF THE INVENTION

[002] The present invention relates to compositions, methods and kits for vulvovaginal applications and other conditions in an individual. CONTEXT

[003] Various compositions are needed to provide lubrication and / or to protect the skin and other tissues from damage and / or infection. Such compositions are useful alone or with one or more active and / or bioactive agents, wherein the composition serves as a drug delivery vehicle (e.g., as a transdermal drug delivery vehicle).

[004] Furthermore, vulvovaginal health continues to be a neglected medical need, as most markets in this area are largely undifferentiated, especially with regard to non-prescription or over-the-counter products. For this reason, gynecological patients in all demographics, from pre-menopause to post-menopause, who suffer from one or more vulvovaginal conditions, are often treated with prescription products or regimens, which typically have characteristics of products Petition 870260042611, dated 06 / 05 / 2026, page 5 / 250 2 / 109 to undesirable, including, (1) insufficient duration of effectiveness of a single application, (2) inadequate restoration of physiological stasis, (3) undesirable side effects and (4) unsustainable health risks.

[005] Thus, there remains a need for a variety of compositions that provide lubrication, protect the skin and other tissues, and / or facilitate the delivery of medications. In particular, there is a need for compositions and formulations capable of providing relief from vulvovaginal symptoms, treating the underlying pathophysiology or infection of the vulvovaginal anatomy, or prophylactically protecting the vulvovaginal anatomy with respect to a range of vulvovaginal health conditions. SUMMARY

[006] Herein are provided, inter alia, compositions, formulations, and methods that provide lubrication, protect the skin, mucosa, and other tissues, and facilitate drug delivery. Compositions, formulations, and methods are also provided for treating, preventing, and / or reducing the severity of symptoms of vulvovaginal and other conditions. Herein are provided vulvovaginal compositions designed to provide relief of vulvovaginal symptoms, treat the underlying pathophysiology or infection of the vulvovaginal anatomy, or prophylactically protect the vulvovaginal anatomy in an individual. In some embodiments of the present invention, the vulvovaginal compositions comprise a stable silicone water emulsion, an emulsifier, a cell membrane fluidity enhancer, a fatty acid, a preservative, and at least one of the group consisting of a bioactive agent, a pH buffer system, a viscosity enhancer, an antioxidant, a tocopherol, and an active agent.In other configurations, vulvovaginal compositions consist of a stable silicone-water emulsion, an emulsifier, a cell membrane fluidity enhancer, a fatty acid, a preservative, and at least one other ingredient. Petition 870260042611, dated 06 / 05 / 2026, page 6 / 250 3 / 109 in one of the group of, a bioactive agent, a pH buffer system, a viscosity-improving agent, an antioxidant, a tocopherol, and an active agent. In other configurations, the vulvovaginal compositions consist essentially of a stable silicone-water emulsion, an emulsifier, a cell membrane fluidity-improving agent, a fatty acid, a preservative, and at least one of the group of a bioactive agent, a pH buffer system, a viscosity-improving agent, an antioxidant, a tocopherol, and an active agent.

[007] Compositions, formulations and methods are also provided for treating or protecting the skin. Dermatological compositions designed to provide treatment or protection of the skin in an individual are provided herein. In some embodiments, the dermatological compositions comprise a stable silicone water emulsion, an emulsifier, a cell membrane fluidity improver, a fatty acid, a preservative, and at least one of, a bioactive agent, a pH buffer system, a viscosity improver, an antioxidant, a tocopherol, a ceramide and an active agent. In other embodiments, the dermatological compositions consist of a stable silicone water emulsion, an emulsifier, a cell membrane fluidity improver, a fatty acid, a preservative, and at least one of, a bioactive agent, a pH buffer system, a viscosity improver, an antioxidant, a tocopherol, a ceramide and an active agent.In other configurations, dermatological compositions consist essentially of a stable water-in-silicone emulsion, an emulsifier, a cell membrane fluidity enhancer, a fatty acid, a preservative, and at least one bioactive agent, a pH buffer system, a viscosity enhancer, an antioxidant, a tocopherol, a ceramide, and an active agent. Petition 870260042611, dated 06 / 05 / 2026, page 7 / 250 4 / 109

[008] Methods of preventing or treating a vaginal condition in an individual are also provided herein, said method comprising administering to an individual a composition comprising a stable water-in-silicone emulsion, wherein the emulsion has a sterol in a concentration of about 0.1% to about 4% by weight of the total weight of the emulsion. In configurations, the composition is administered into the vagina, into and / or around the vulva, or any combination thereof.

[009] In other examples, the methods described here are used to prevent or treat a vaginal condition, including menopause, perimenopause, postmenopause, vaginal dryness, dyspareunia, a bacterial infection, a viral infection, or a fungal infection.

[0010] In the settings, the methods described herein provide an effective therapeutic dose for up to 1 hour, 2 hours, 3 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours, 48 ​​hours, 3 days, 5 days, 7 days, or 14 days. Furthermore, the methods comprise administering the composition every 1 hour, 2 hours, 3 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours, 48 ​​hours, 3 days, 5 days, 7 days, or 14 days.

[0011] Methods are also provided herein for preparing a water-in-silicone emulsion comprising preparing an aqueous phase comprising water, a pH buffer system, at least one active or bioactive agent and a preservative, and separately preparing a silicone phase comprising a silicone oil, a silicone gum and a sterol, a fatty acid, a tocopherol and a preservative, and adding the aqueous phase to the silicone phase, and mixing the combined phases until the water-in-silicone emulsion is formed, wherein the silicone phase comprises about 20-80% by weight of the composition and the aqueous phase comprises about 20-80% by weight of the composition, based on the total weight of the composition. In configurations, the method further includes adding the aqueous phase to the phase of Petition 870260042611, dated 06 / 05 / 2026, page 8 / 250 5 / 109 silicone under high shear agitation, for example, where high shear agitation utilizes a rotor-stator homogenizer.

[0012] Methods for providing relief of vulvovaginal symptoms, treating the underlying pathophysiology or infection of the vulvovaginal anatomy, or prophylactically protecting the vulvovaginal anatomy in an individual, comprising administering to said individual a vulvovaginal composition comprising, consisting of, or essentially consisting of, a stable silicone water emulsion, an emulsifier, a cell membrane fluidity enhancer, a fatty acid, a preservative and at least one of, a bioactive agent, a pH buffer system, a viscosity enhancer, an antioxidant, a tocopherol and an active agent, are also disclosed herein.

[0013] Methods for treating and protecting the skin in an individual, comprising administering to said individual a dermatological composition comprising, consisting of or essentially consisting of, a stable silicone water emulsion, an emulsifier, a cell membrane fluidity improver, a fatty acid, a preservative, and at least one of, a bioactive agent, a pH buffer system, a viscosity improver, an antioxidant, a tocopherol, a ceramide and an active agent, are also disclosed herein.

[0014] Furthermore, kits are provided to produce vulvovaginal compositions to provide relief of vulvovaginal symptoms, treat underlying pathophysiology or infection of the vulvovaginal anatomy, or prophylactically protect the vulvovaginal anatomy in an individual.

[0015] In addition, kits are provided for producing dermatological compositions to treat and protect the skin in an individual. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] This invention will be more fully understood at Petition 870260042611, dated 06 / 05 / 2026, p. 9 / 250 6 / 109 from the following detailed description taken in conjunction with the accompanying drawings, in which:

[0017] Figure 1A-1B illustrates exemplary stable water-in-silicone (W / O) emulsions comprising an emulsifier, a cell membrane fluidity enhancer, a fatty acid, a preservative, a bioactive agent, a pH buffer system, an antioxidant, and a tocopherol. Figure 1A shows an exemplary physicochemical orientation of the emulsifier, cell membrane fluidity enhancer, and fatty acid constituents, wherein only the emulsifier stabilizes the water-silicone interface. Figure 1B shows a second exemplary physicochemical orientation of the emulsifier, cell membrane fluidity enhancer, and fatty acid constituents, in which the emulsifier, the cell membrane fluidity enhancer, and the fatty acid cooperatively stabilize the water-silicone interface.

[0018] Figure 2A-2B illustrates exemplary stable water-in-silicone (W / O) emulsions comprising an emulsifier, a cell membrane fluidity enhancer, a fatty acid, a preservative, a bioactive agent, a pH buffer system, an antioxidant, and a tocopherol. Figure 2A shows an exemplary physicochemical orientation of the emulsifier, cell membrane fluidity enhancer, and fatty acid constituents, wherein only the emulsifier stabilizes the water-silicone interface. Figure 1B shows a second exemplary physicochemical orientation of the emulsifier, cell membrane fluidity enhancer, and fatty acid constituents, in which the emulsifier, the cell membrane fluidity enhancer, and the fatty acid cooperatively stabilize the water-silicone interface.

[0019] Figure 3A-3C illustrates the optical image of Formulation #8. Figure 3A is a macroscopic optical image of Formulation #8 on day Petition 870260042611, dated 06 / 05 / 2026, page 10 / 250 7 / 109 1. Figure 3B is an optical microscopic image of Formulation #8 on day 1. Figure 3C is an optical microscopic image of Formulation #8 on day 6. The scale bar is 300 microns.

[0020] Figure 4A-4C illustrates the optical image of Formulation #9. Figure 4A is a macroscopic optical image of Formulation #9 on day 1. Figure 4B is a microscopic optical image of Formulation #9 on day 1. Figure 4C is a microscopic optical image of Formulation #9 on day 31. Scale bar is 100 microns.

[0021] Figure 5A-5C illustrates the optical image of Formulation #10. Figure 5A is a macroscopic optical image of Formulation #10 on day 1. Figure 5B is a microscopic optical image of Formulation #10 on day 1. Figure 5C is a microscopic optical image of Formulation #10 on day 14. The scale bar is 100 microns.

[0022] Figures 6A-6E illustrate the optical image of Formulations #13 and #14. Figure 6A is a macroscopic optical image of Formulation #13 on day 1. Figure 6B is a microscopic optical image of Formulation #13 on day 1. Figure 6C is a macroscopic optical image of Formulation #14 on day 1. Figure 6D is a microscopic optical image of Formulation #14 on day 1. Figure 6E is an optical image of Formulation #14 showing phase separation. The scale bar is 100 microns.

[0023] Figure 7A-7D illustrates flow stress sweep analysis graphs of Formulation #9. Figure 7A is a flow stress sweep of Formulation #9 at 25°C, where viscosity is plotted against shear rate. Figure 7B is a flow stress sweep of Formulation #9 at 25°C, where viscosity is plotted against stress. Figure 7C is a flow stress sweep of Formulation #9 at 37°C, where viscosity is plotted against shear rate. Figure 7D is a flow stress sweep of Formulation #9 at 37°C, where viscosity is plotted against stress. Petition 870260042611, dated 06 / 05 / 2026, page 11 / 250 8 / 109

[0024] Figure 8A-8B illustrates an oscillatory amplitude sweep of Formulation #9. Figure 8A is an oscillatory amplitude sweep of Formulation #9 at 25°C. Figure 8B is an oscillatory amplitude sweep of Formulation #9 at 37°C.

[0025] Figure 9A-9B illustrates an oscillatory frequency sweep of Formulation #9. Figure 9A is an oscillatory frequency sweep of Formulation #9 at 25°C. Figure 9B is an oscillatory frequency sweep of Formulation #9 at 37°C.

[0026] Figure 10 is an oscillatory temperature sweep of Formulation #9 from 20°C to 40°C. DETAILED DESCRIPTION OF ILLUSTRATIVE CONFIGURATIONS

[0027] Some exemplary configurations will now be described to provide a general understanding of the principles of the compositions, methods, and kits disclosed herein. One or more examples of such configurations are illustrated in the accompanying drawings. Those skilled in the art will understand that the compositions, methods, and kits specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary configurations and that the scope of the present invention is defined solely by the claims. The features illustrated or described in connection with an exemplary configuration may be combined with the features of other configurations. Such modifications and variations are considered to be included within the scope of the present invention.

[0028] Furthermore, in the present disclosure, similar components of configurations generally have similar characteristics and, therefore, within a particular configuration each characteristic of each similar component is not necessarily fully elaborated.

[0029] The compositions provided here are stable emulsions, which are in the form of a liquid, lotion, ointment or cream, relatively Petition 870260042611, dated 06 / 05 / 2026, page 12 / 250 9 / 109 viscous, lubricating. The compositions are stable as emulsions until expiration and can remain stable after application for up to about one week. The compositions can be used for a variety of purposes, as described herein, including topical application, rectal application, and vulvovaginal application. Furthermore, the compositions can be used with or without an active and / or bioactive agent. More particularly, compositions comprising a water-in-silicone (W / O) emulsion are provided herein, inter alia, wherein the emulsion has a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition.Methods are also provided herein for preventing or treating vulvovaginal and other conditions (e.g., for rectal use, dermatological use, sunscreens, transdermal drug delivery, or ophthalmic use) in an individual in need thereof, including applying the compositions (e.g., the emulsion composed of a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition), and kits including the composition and reagents. Although the disclosure often refers to the composition being useful for addressing vulvovaginal indications, it is understood that this is one of many exemplary uses of the compositions disclosed herein. One skilled in the art will understand that the compositions described have utility beyond vulvovaginal applications as described herein. DEFINITIONS

[0030] The following definitions are included for the purpose of understanding the present subject matter and for the construction of the attached patent claims. The abbreviations used herein have their conventional meaning within chemical and biological techniques.

[0031] Unless otherwise defined, all technical and scientific terms used herein have their commonly understood meaning. Petition 870260042611, dated 06 / 05 / 2026, p. 13 / 250 10 / 109 by a person skilled in the art to which this disclosure pertains. The following references provide a version with a general definition of many of the terms used in this disclosure: The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). As used herein, the following terms have the meanings assigned to them below, unless otherwise specified.

[0032] Unless specifically stated or obvious from the context, as used here, the term or is understood to be inclusive. Unless specifically stated or obvious from the context, as used here, the terms a, an, or are understood to be singular or plural.

[0033] The term approximately, when used in reference to numerical ranges, cutoffs, or specific values, is used to indicate that the recited values ​​may vary up to 25% of the listed value. As many of the numerical values ​​used herein are experimentally determined, it should be understood by those skilled in the art that such determinations may vary, and often do vary, between different experiments. The values ​​used herein should not be considered unduly limiting because of this inherent variation. The term approximately is used to encompass variations of ± 25% or less, variations of ± 20% or less, variations of 10% or less, variations of ± 5% or less, variations of ± 1% or less, variations of ± 0.5% or less, or variations of ± 0.1% or less of the specified value. "Approximately" can be understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the declared value.Unless clear from the context, all numerical values ​​given here are modified by the term approximately.

[0034] As used herein, administer to the said individual and Petition 870260042611, dated 06 / 05 / 2026, page 14 / 250 11 / 109 similar terms indicate a procedure by which the described vulvovaginal compositions are introduced, instilled, implanted, applied within or applied to an individual, such that cells, tissues, mucosa or target segments of the individual's body are contacted with the composition.

[0035] The term administer, as used herein, refers to any mode of transfer, delivery, introduction or transport of an agent, for example, to an individual in need of treatment for a disease or condition. Such modes include, but are not limited to, oral, topical, intravenous, vaginal, mucous membrane, intraperitoneal, intramuscular, intradermal, intranasal and subcutaneous administration.

[0036] The ranges provided here are understood to be abbreviations for all values ​​within the range. For example, a range from 1 to 50 is understood to include any number, combination of numbers, or subrange of 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, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50, as well as all decimal values ​​intervening 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 regard to sub-ranges, nested sub-ranges that extend from both endpoints of the range are specifically contemplated. For example, a nested sub-range of an exemplary range from 1 to 50 might include 1 to 10, 1 to 20, 1 to 30, and 1 to 40 in one direction, or 50 to 40, 50 to 30, 50 to 20, and 50 to 10 in the other direction.

[0037] As used herein, the term analogue refers to a chemical compound that is structurally similar to another, but differs slightly in composition (such as in the substitution of an atom for an atom of a different element or in the presence of a particular functional group, or in the substitution of a functional group for an atom of a different element). Petition 870260042611, dated 06 / 05 / 2026, p. 15 / 250 12 / 109 another functional group). Thus, an analogue is a compound that is similar or comparable in function and appearance, but not in structure or origin to the reference compound. As used herein, the term derivative refers to compounds that have a common central structure and are replaced by various groups as described herein.

[0038] As used herein, the term emulsion refers to a liquefied mixture containing at least two distinguishable substances (or phases) that will not readily mix and dissolve. As used herein, an emulsion comprises a continuous phase (or matrix) that holds within it discontinuous droplets, bubbles, and / or particles of the other phase or substance. The term emulsion may thus refer to foams comprising gas bubbles suspended in a continuous liquid phase, emulsions in which droplets of a first liquid are dispersed throughout a continuous phase composed of a second liquid with which the first liquid is immiscible, and continuous liquid phases throughout which solid particles are distributed.As used herein, the term emulsion encompasses continuous liquid phases throughout which gas bubbles are distributed, continuous liquid phases throughout which solid particles (e.g., solid catalyst) are distributed, continuous phases of a first liquid throughout which droplets of a second liquid substantially insoluble in the continuous phase are distributed, and liquid phases throughout which any one or a combination of solid particles, immiscible liquid droplets, and gas bubbles are distributed. Therefore, an emulsion can exist as a homogeneous mixture in some cases (e.g., liquid / liquid phase), or as a heterogeneous mixture (e.g., gas / liquid, solid / liquid, or gas / solid / liquid), depending on the nature of the materials selected for combination.

[0039] As used herein, the term stable or stability refers Petition 870260042611, dated 06 / 05 / 2026, page 16 / 250 13 / 109 refers to the water-in-silicone emulsion as described herein. Stability may refer to the ability of the emulsion to resist changes in its properties over time under appropriate storage conditions. For example, stability may typically mean that the composition does not separate phase when stored at room temperature (e.g., approximately 20°C to 25°C) for at least 1 month, or when stored in its final packaging at room temperature (e.g., approximately 20°C to 25°C) for at least 12 months. Other exemplary stability characteristics include the stability of the final packaged product in terms of expiration.For example, stability can mean that the constituents of the product (e.g., active or inactive ingredients) have not altered, degraded, or decomposed the product's properties (e.g., emulsion stability, zero-rate viscosity) as defined in its Certificate of Analysis, the product's preservation system remains functional, or any combination of these has not been altered. The stability of emulsions can be characterized using techniques described herein, including, for example, light scanning, optical microscopy, freeze / thaw cycles, centrifugation, and rheology.

[0040] Furthermore, as used herein, stable or stability refers to the composition comprising the water-in-silicone emulsion described herein (e.g., the composition comprising the emulsion and additional agents described herein in the stable composition). For example, the composition may include carrier(s) and / or other materials suitable for the composition to comprise a variety of active agents (e.g., active ingredients), and wherein the active agents will be stable for a long period of time as described herein. In addition, the active agent, according to some configurations, must be stable for a period of time in Petition 870260042611, dated 06 / 05 / 2026, page 17 / 250 14 / 109 composition as described here.

[0041] As used in the context of the composition of this disclosure, the term stable means physical and chemical stability. Chemical stability refers to chemical changes in an active or inactive agent (e.g., degradation of agents, oxidation of agents). In the settings of this disclosure, the storage or shelf life of a composition is a measure of chemical stability. Physical stability refers to the mechanical properties, physical state (e.g., crystallinity, crystal structure) and release properties of the active agent (or drug).

[0042] Stability is measured after storing the composition of this disclosure under temperature and relative humidity (RH) conditions of approximately 25°C / 60% RH to approximately 40°C / 75% RH. Accelerated time and real-time shelf-life testing of the composition is performed in order to confirm the shelf life and determine the product expiration date. In addition, the shelf life of the composition is also tested under expected packaging conditions.

[0043] The stability of the composition should be understood as meaning the maintenance of the homogeneous appearance of the composition, without phase separation, precipitation or flocculation of particles, for at least 6 months at 25°C. In other configurations, the composition is stable for at least 9 months, at least 12 months, at least 18 months, or at least 24 months at 25°C.

[0044] As used herein, the term cream may refer to a thick liquid (high zero-rate viscosity), semi-liquid or semi-solid formulation, which may be used for the therapeutic treatment of a disease, syndrome or condition (i.e., a vulvovaginal disease, syndrome or condition).

[0045] As used herein, the term lotion may refer to a moderately thick liquid (zero viscosity rate mo Petition 870260042611, dated 06 / 05 / 2026, page 18 / 250 15 / 109 derada) semiliquid or semisolid formulation, which can be used for the therapeutic treatment of a disease, syndrome or condition (i.e., a vulvovaginal disease, syndrome or condition).

[0046] As used herein, the term ointment may refer to a highly viscous liquid or semi-liquid formulation that may be used for the therapeutic treatment of a disease, syndrome or condition (i.e., a vulvovaginal disease, syndrome or condition).

[0047] Liquid as used herein is a dosage form consisting of a composition in its liquid state. A liquid can be poured; it flows and conforms to its container at room temperature. Liquids exhibit Newtonian or pseudoplastic flow behavior. In configurations, a semiliquid or semisolid, as used herein, may have properties of both a liquid and another formulation (i.e., a dispersion, a suspension, an emulsion, a lotion, a cream, and the like).

[0048] The term humectant, as used herein, refers to improving the hydration of a surface, such that the water-binding capacity of the surface increases. The term to wet, or derivatives thereof, refers to the conversion or enhancement of the water content of an individual's surfaces.

[0049] As used herein, zero-rate viscosity refers to the resistance of a fluid or semi-solid to flow when the shear rate approaches zero.

[0050] In the descriptions above and in the claims, phrases such as at least one or one or more may occur followed by a conjunctive list of elements or characteristics. The term and / or may also occur in a list of two or more elements or characteristics. Unless otherwise implicitly or explicitly contradicted by the context in which it is used, such a phrase means any of the elements or characteristics listed individually or Petition 870260042611, dated 06 / 05 / 2026, p. 19 / 250 16 / 109 any of the cited elements or features in combination with any of the other cited elements or features. For example, the sentences at least one of A and B; one or more of A and B; and A and / or B are each intended to mean A only, B only, or A and B together. A similar interpretation is also intended for lists including three or more items. For example, the sentences at least one of A, B, and C; one or more of A, B, and C; and A, B, and / or C are each intended to mean A only, B only, C only, A and B together, A and C together, B and C together, or A and B and C together. Furthermore, the use of the term based on, above, and in the claims, means based at least in part, such that an unsolicited feature or element is also permitted.

[0051] By mitigating, it is understood to decrease, suppress, attenuate, diminish, halt or stabilize the development or progression of a disease or condition such as, for example, a pseudoallergic reaction.

[0052] The terms subject, patient, individual, and the like, as used herein, are not intended to be limiting and may generally be interchangeable. An individual described as a subject, patient, individual, and the like, does not necessarily have a particular disease but may simply be seeking medical advice. The terms subject, patient, individual, and the like, as used herein, include all members of the animal kingdom who may suffer from the indicated disorder. In some respects, the subject is a mammal, and in some respects, the subject is a human being.

[0053] The term "around" when used in reference to the site of administration of the vulvovaginal compositions described should be understood by those skilled in the art to mean administered to the anatomical area of ​​interest, within the limits of traditionally practiced procedures. For example, administration around the site Petition 870260042611, dated 06 / 05 / 2026, page 20 / 250 17 / 109 anatomically relevant refers to a location that is not directly within or on the site, but sufficiently close to the site to provide a physiologically or therapeutically relevant effect. Those commonly skilled in the art can readily determine the maximum distance from a given anatomical site that will be sufficient to provide a physiologically or therapeutically relevant effect using a vulvovaginal composition according to the present disclosure.

[0054] Pharmaceutically acceptable refers to those properties and substances that are acceptable to the patient from a pharmacological / toxicological point of view and to the pharmaceutical manufacturing chemist from a physical / chemical point of view in relation to composition, formulation, stability, patient acceptance and bioavailability.

[0055] Acceptable pharmaceutical excipient and acceptable pharmaceutical carrier refer to a substance that assists the administration of an active agent to an individual, or assists absorption by an individual, or enhances the stability or other properties of the active agent, and may be included in the compositions of the present invention without causing a significant adverse toxicological effect on the patient. Unless otherwise indicated, the terms active agent, active ingredient, therapeutically active agent, therapeutic agent, bioactive agent and the like are used synonymously.Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, normal saline solutions, Ringer's lactate, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavorings, salt solutions (such as Ringer's solution), alcohols, oils, gelatins, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidine, polyethylene glycol, colorants and the like. Such preparations may be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, etc. Petition 870260042611, dated 06 / 05 / 2026, page 21 / 250 18 / 109 humectants, emulsifiers, salts to influence osmotic pressure, buffers, colorants and / or aromatic substances, and the like, which do not react adversely with the compounds of the invention. Anyone skilled in the art will recognize that other pharmaceutical excipients are useful in the present invention.

[0056] As used herein, the terms active agent, active ingredient, therapeutically active agent, therapeutic agent, bioactive agent, mean possessing biological activity, such as biochemical, pharmacological, or therapeutic activity. In some settings, bioactivity provides symptom relief, treats underlying pathophysiology or infection of the vulvovaginal anatomy, or prophylactically protects the vulvovaginal anatomy in an individual. In certain settings, bioactivity is the enhancement of skin function and / or effect on skin homeostasis. In other examples, bioactivity is the enhancement of the rectal system and anatomy. In other examples, bioactivity is the enhancement of the ophthalmic system and anatomy. Additionally, as provided, bioactivity is for the treatment or prevention of sun damage (e.g., sunscreen).

[0057] In certain configurations, the biological activity is, without limitation, analgesic, antifungal, antiviral, anti-infective, anti-inflammatory, antineoplastic, immunostimulant, immunosuppressive, immunomodulatory, endocrine-modulating, cell viability enhancer, cell membrane fluidization, antioxidant, oxygen carrier, contraceptive, cell recruitment, cell attachment, angiogenesis, wound healing activity, mobilization of host stem or progenitor cells, cell proliferation, stimulation of cell migration to sites of injury, attenuation of cell and tissue fibrosis, or any combination thereof.

[0058] Effective therapeutic dose refers to an amount of Petition 870260042611, dated 06 / 05 / 2026, page 22 / 250 19 / 109 a composition, as described herein, effective in achieving a particular physiological, biological, or therapeutic result, such as, but not limited to, the physiological, biological, or therapeutic results disclosed, described, or exemplified herein. These physiological, biological, or therapeutic results include, but are not limited to, restoring pH, providing lubrication, promoting healthy flora, or eliminating infections (e.g., restoring vaginal pH, providing vaginal lubrication, promoting healthy flora, eliminating infections, or providing contraception). The therapeutic dose may vary according to factors such as disease status, age, sex, and weight of the individual, as well as the ability of the composition to elicit the desired response in an individual. Such results may include, but are not limited to, providing symptom relief, treating the underlying pathophysiology, or prophylactically protecting the vagina, as determined by any appropriate means in the art.

[0059] The terms treat, treating, or treatment refer to any success or indication of success in attenuating or mitigating an infection, pathology, or condition, including any objective or subjective parameter, such as reduction, revocation, remission, decrease of symptoms, or making the infection, pathology, or condition more tolerable for the patient, delaying disease progression, making the condition less debilitating, or improving an individual's physical or mental well-being. Treatment may be evaluated by objective or subjective parameters; including the results of a physical examination.

[0060] As used here, protects prophylactically or protect prophylactically means treating a condition (e.g., a vulvar or vaginal condition) preventively.

[0061] As used herein, incorporated within means the emulsifier, cell membrane fluidity enhancer, fatty acid, preservative, and at least one of the bio-agent group. Petition 870260042611, dated 06 / 05 / 2026, page 23 / 250 20 / 109 active ingredient, pH buffer system, viscosity improving agent, antioxidant, tocopherol, ceramide, the active agent, or any combination thereof, are at least partially covered by, contained within, dispersed within, distributed within, enveloped within, or trapped by the water and silicone emulsion. Depending on the type of constituent, excipient, or agent, the constituent, excipient, or agent may be located in the aqueous phase, in the silicone phase, or both.

[0062] Each configuration disclosed here is contemplated as being applicable to each of the other configurations disclosed. Thus, all combinations of the various elements described here are within the scope of the invention.

[0063] Other features and advantages of the invention will become apparent from the following description of the preferred configurations thereof and of the claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning commonly understood by one commonly skilled in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein may be used in the practice or testing of the present invention, suitable methods and materials are described below. All published foreign patents and patent applications cited herein are incorporated herein by reference. Genbank and NCBI submissions indicated by registration number, cited herein, are incorporated herein by reference. All other published references, documents, manuscripts and scientific literature cited herein are incorporated herein by reference.In case of conflict, this specification, including definitions, shall govern. Additionally, the materials, methods, and examples are for illustrative purposes only and are not intended to be exhaustive. COMPOSITIONS

[0064] The present disclosure provides compositions comprising Petition 870260042611, dated 06 / 05 / 2026, page 24 / 250 21 / 109 a water-in-silicone (W / O) emulsion comprising a cell membrane fluidity enhancer. In configurations, the cell membrane fluidity enhancer is at a concentration of about 0.1% to about 4% by weight of the total weight of the composition.

[0065] In configurations, the compositions disclosed here are stable water and silicone emulsions, which include, but are not limited to, creams, lotions, ointments, moisturizers or personal lubricants.

[0066] Suitable water-silicone emulsions include, but are not limited to, water-in-silicone (W / O), silicone-in-water (O / W), or water-in-silicone-in-water (W / O / W). In some configurations, the water-silicone emulsion is a W / O emulsion. In preferred examples, a suitable emulsion is a water-in-silicone (W / O) emulsion. For example, without intending to limit, W / O emulsions may have an aqueous phase comprising up to and including 50% by weight of water, and a silicone phase comprising between 20% and 95% by weight of silicone, inclusive.

[0067] In some examples, the water-in-silicone emulsion comprises a silicone phase, wherein the silicone phase comprises a silicone oil, a silicone wax, a silicone gum, or any combination thereof.

[0068] In creating a water-in-silicone emulsion, a range of silicone oils, silicone gums, or silicone waxes may be selected from those known in the art. For the purposes of this disclosure, suitable silicone oils include, but are not limited to, dimethicone, cyclomethicone, caprylyl methicone, cyclopentasiloxane, cyclohexasiloxane, or any combination thereof. For the purposes of this disclosure, suitable silicone gums include, but are not limited to, dimethiconol. For the purposes of this disclosure, suitable silicone waxes include, but are not limited to, stearyl dimethicone. Petition 870260042611, dated 06 / 05 / 2026, page 25 / 250 22 / 109

[0069] In some configurations, the continuous phase (e.g., the phase used to disperse small particles or droplets) can be stabilized to create a stable emulsion. Exemplary agents used to stabilize to create a stable emulsion include, but are not limited to, emulsifiers and coemulsifiers. Suitable emulsifiers and co-emulsifiers for stabilizing the resulting emulsion (e.g., liquid-liquid droplets) include, but are not limited to, a sterol, a sterol derivative, cholesterol, cholesterol derivatives, glyceryl stearate, glyceryl monostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan tristearate, sorbitan monooleate, sorbitan trioleate, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monooleate,Polyoxyethylene sorbitan trioleate, polyoxyethylene monolaurate, polyoxyethylene monostearate, polyoxyethylene monopalmitate, polyoxyethylene monooleate, lecithin, PEG / PPG-18 / 18 dimethicone, cetyl PEG / PPG10 / 1 dimethicone, dimethicone copolyol, octyl dodecanol, polyvinyl alcohol, Pluronic, Poloxamer, Carbomer, isopropyl myristate or any combination thereof.

[0070] In some examples, the compositions described herein may include one or more (e.g., at least one) cell membrane fluidity-enhancing agents to enable (e.g., promote) increased cell membrane fluidity, increased cell penetration, increased absorption of desired constituents, excipients or agents, increased lubrication and wetting, or any combination thereof. Suitable cell membrane fluidity-enhancing agents include, but are not limited to, sterols (e.g., steroid alcohols). Sterols are a subgroup of steroids with a hydroxyl group at the 3' position of ring A. They are amphipathic lipids synthesized. Petition 870260042611, dated 06 / 05 / 2026, page 26 / 250 23 / 109 of them from acetyl-coenzyme A. The chemical structure of the sterol is es-

[0071] One or more cell membrane flow enhancers may be incorporated within the emulsion. In some configurations, one or more cell membrane flow enhancers are incorporated within the aqueous phase of the emulsion. In other configurations, one or more cell membrane flow enhancers are incorporated within the silicone phase of the emulsion. In still other configurations, one or more cell membrane flow enhancers are incorporated within both the aqueous and silicone phases of the emulsion.

[0072] In some configurations, the cell membrane fluidity enhancer may be formulated to comprise up to 0.1% by weight, inclusive, of the composition. In some configurations, the cell membrane fluidity enhancer may be formulated to comprise up to 0.25% by weight, inclusive, of the composition. In some configurations, the cell membrane fluidity enhancer may be formulated to comprise up to 0.5% by weight, inclusive, of the composition. In some configurations, the cell membrane fluidity enhancer may be formulated to comprise up to 1% by weight, inclusive, of the composition. In some configurations, the cell membrane fluidity enhancer may be formulated to comprise up to 1.5% by weight, inclusive, of the composition. In some configurations, the cell membrane fluidity enhancer may be formulated to comprise up to 2% by weight, inclusive, of the composition. In some configurations, the fluidity enhancer may be formulated to comprise up to 2% by weight, inclusive, of the composition. Petition 870260042611, dated 06 / 05 / 2026, p. 27 / 250 24 / 109 The cell membrane fluidity enhancer can be formulated to comprise up to 2.5% by weight, inclusive, of the composition. In some configurations, the cell membrane fluidity enhancer can be formulated to comprise up to 3% by weight, inclusive, of the composition. In some configurations, the cell membrane fluidity enhancer can be formulated to comprise up to 3.5% by weight, inclusive, of the composition. In some configurations, the cell membrane fluidity enhancer can be formulated to comprise up to 4% by weight, inclusive, of the composition. In some configurations, the cell membrane fluidity enhancer can be formulated to comprise up to 4.5% by weight, inclusive, of the composition. In some configurations, the cell membrane fluidity enhancer can be formulated to comprise up to 5% by weight, inclusive, of the composition.In some configurations, the cell membrane fluidity enhancer may be formulated to comprise up to 5.5% by weight of the composition.

[0073] Throughout this disclosure, the term "cell membrane flow enhancer" may refer to more than one cell membrane flow enhancer if more than one such agent is present in the composition. For example, when only one cell membrane flow enhancer is incorporated into the emulsion, a reference to 50% by weight of the cell membrane flow enhancer means that 50% of the single cell membrane flow enhancer is present. When more than one cell membrane flow enhancer is incorporated into the emulsion, the term "50% by weight of the cell membrane flow enhancer" means that 50% of the total complement of cell membrane flow enhancers is incorporated into the emulsion. Thus, if the composition includes 1 mg of a cell membrane flow enhancer Petition 870260042611, dated 06 / 05 / 2026, page 28 / 250 25 / 109 cell and 1 mg of a second cell membrane fluidity enhancer, so 50% by weight of the cell membrane fluidity enhancer may mean that 50% of the total complement of 2 mg of cell membrane fluidity enhancers are incorporated within the emulsion.

[0074] The term sterol, as used herein, may refer to plant or animal sterols, natural or synthetic. Exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof. Other sterols include diosgenin, stigmastanol, tigogenin, α-sitosterol, β-sitosterol, stigmasterol, ergosterol, campesterol, oleanolic acids, soy sapogenols (e.g., soy sapogenol A or soy sapogenol B), protoascigenin, and protopanaxaldiols. In some settings, the sterol is cholesterol. When the sterol is cholesterol, its physicochemical and biochemical properties enable it to function uniquely and simultaneously as a cell membrane fluidity enhancer, as an emulsifier that plays a critical role in stabilizing the water-silicon droplet interface, and as a bioactive agent.

[0075] In other examples, the compositions described herein may include one or more (e.g., at least one) fatty acids. Fatty acids are carboxylic acids with a long aliphatic chain that is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of a uniform number of carbon atoms, for example, from 4 to 28 carbon atoms. In settings, fatty acids can facilitate cellular interactions with the formulation. Suitable fatty acids include, but are not limited to, caprylic acid, lauric acid, myristic acid, caproleic acid, lauroleic acid, myristoleic acid, palmitoleic acid, oleic acid, stearic acid, palmitic acid, linoleic acid, arachidonic acid, stearidonic acid, docosahexaenoic acid (DHA), Petition 870260042611, dated 06 / 05 / 2026, page 29 / 250 26 / 109 eicosapentaenoic acid (EPA) or any combination thereof.

[0076] One or more fatty acids may be incorporated within the emulsion. In some configurations, one or more fatty acids are incorporated within the aqueous phase of the emulsion. In other configurations, one or more fatty acids are incorporated within the silicone phase of the emulsion. In other configurations, one or more fatty acids are incorporated within both the aqueous and silicone phases of the emulsion.

[0077] In some configurations, the fatty acid may be formulated to comprise up to 0.1% by weight, inclusive, of the composition. In some configurations, the fatty acid may be formulated to comprise up to 0.25% by weight, inclusive, of the composition. In some configurations, the fatty acid may be formulated to comprise up to 0.5% by weight, inclusive, of the composition. In some configurations, the fatty acid may be formulated to comprise up to 1% by weight, inclusive, of the composition. In some configurations, the fatty acid may be formulated to comprise up to 1.5% by weight, inclusive, of the composition. In some configurations, the fatty acid may be formulated to comprise up to 2% by weight, inclusive, of the composition. In some configurations, the fatty acid may be formulated to comprise up to 2.5% by weight, inclusive, of the composition. In some configurations, the fatty acid may be formulated to comprise up to 3% by weight, inclusive, of the composition.In some configurations, the fatty acid may be formulated to comprise up to 4% by weight, inclusive, of the composition. In some configurations, the fatty acid may be formulated to comprise up to 5% by weight, inclusive, of the composition. In some configurations, the fatty acid may be formulated to comprise up to 6% by weight, inclusive, of the composition. In some configurations, the fatty acid may be formulated to comprise up to 8% by weight, inclusive, of the composition. In some configurations, the fatty acid may be... (Petition 870260042611, dated 06 / 05 / 2026, page 30 / 250.) 27 / 109 modulated to make up to 10% by weight, inclusive, of the composition.

[0078] Throughout this disclosure, the term fatty acid may refer to more than one fatty acid if more than one of these agents is present in the composition. For example, when only one fatty acid is incorporated into the emulsion, a reference to 50% by weight of the fatty acid means that 50% of the single fatty acid is present. When more than one fatty acid is incorporated into the emulsion, the language referring to 50% by weight of the fatty acid means that 50% of the total complement of fatty acids is incorporated into the emulsion. Thus, if the composition includes 1 mg of one fatty acid and 1 mg of a second fatty acid, then 50% by weight of the fatty acid may mean that 50% of the total complement of 2 mg of fatty acids is incorporated into the emulsion.

[0079] In other examples, the term fatty acid may refer to more than one fatty acid derivative if more than one of such agent is present in the composition. Appropriate fatty acid derivatives include, but are not limited to, a caprylic acid derivative, a lauric acid derivative, a myristic acid derivative, a caproleic acid derivative, a lauroleic acid derivative, a myristoleic acid derivative, a palmitoleic acid derivative, an oleic acid derivative, a stearic acid derivative, a palmitic acid derivative, a linoleic acid derivative, a arachidonic acid derivative, a stearidonic acid derivative, or any combination thereof.

[0080] In configurations, the disclosed compositions may include one or more preservatives. Preservatives, for example, may be used to control the stability and expiration of the formulation, where stability and expiration are evaluated by methods known to those skilled in the art. Suitable preservatives include, but are not limited to, sorbic acid, potassium sorbate, Petition 870260042611, dated 06 / 05 / 2026, page 31 / 250 28 / 109 boric acid, sodium borate, benzoic acid, sodium benzoate, benzalkonium chloride, benzethonium chloride, EDTA, parabens or any combination thereof.

[0081] One or more preservatives may be incorporated within the composition comprising the emulsion. In some configurations, one or more preservatives are incorporated within the aqueous phase of the emulsion. In other configurations, one or more preservatives are incorporated within the silicone phase of the emulsion. In other configurations, one or more preservatives are incorporated within both the aqueous and silicone phases of the emulsion.

[0082] In some configurations, the preservative may be formulated to comprise up to 0.01% by weight, inclusive, of the emulsion. In some configurations, the preservative may be formulated to comprise up to 0.025% by weight, inclusive, of the composition. In some configurations, the preservative may be formulated to comprise up to 0.05% by weight, inclusive, of the composition. In some configurations, the preservative may be formulated to comprise up to 0.1% by weight, inclusive, of the composition. In some configurations, the preservative may be formulated to comprise up to 0.2% by weight, inclusive, of the composition. In some configurations, the preservative may be formulated to comprise up to 0.5% by weight, inclusive, of the composition. In some configurations, the preservative may be formulated to comprise up to 1% by weight, inclusive, of the composition. In some configurations, the preservative may be formulated to comprise up to 2% by weight, inclusive, of the composition.In some configurations, the preservative may be formulated to comprise up to 4% by weight, inclusive, of the composition.

[0083] Throughout this disclosure, the term preservative may refer to more than one preservative if more than one such agent is present in the composition. For example, when only one preservative is incorporated within the emulsion, a reference to. Petition 870260042611, dated 06 / 05 / 2026, p. 32 / 250 29 / 109 50% by weight of preservative means that 50% of the single preservative is present. When more than one preservative is incorporated into the emulsion, the term 50% by weight of preservative means that 50% of the total preservative content is incorporated into the emulsion. Thus, if the composition includes 1 mg of one preservative and 1 mg of a second preservative, then 50% by weight of preservative may mean that 50% of the total 2 mg of preservative content is incorporated into the emulsion.

[0084] The disclosed compositions may include bioactive agents. In the settings, the bioactive agents may affect the biochemistry or cellular physiology of the desired condition (e.g., vulvar or vaginal anatomy). Suitable bioactive agents include, but are not limited to, glycogen, cholesterol, lactic acid, lactate salts, tocopherols, or any combination thereof. Additional bioactive agents are described in detail below.

[0085] Throughout this disclosure, the term "bioactive agent" may refer to more than one bioactive agent if more than one such agent is present in the composition. For example, one or more bioactive agents may be incorporated within the emulsion. In some configurations, one or more bioactive agents are incorporated within the aqueous phase of the emulsion. In other configurations, one or more bioactive agents are incorporated within the silicone phase of the emulsion. In other configurations, one or more bioactive agents are incorporated into both the aqueous and silicone phases of the emulsion.

[0086] In some examples, the bioactive agent may be used in amounts of about 0.01% by weight to about 100% by weight, based on the total weight of the composition. In other examples, the active agent may be used in amounts of about 0.01% by weight to about 90% by weight, from about 0.01% by weight to about 80% Petition 870260042611, dated 06 / 05 / 2026, page 33 / 250 30 / 109 by weight, from about 0.01% by weight to about 70% by weight, from about 0.01% by weight to about 60% by weight, from about 0.01% by weight to about 50% by weight, from about 0.01% by weight to about 40% by weight, from about 0.01% by weight to about 30% by weight, from about 0.01% by weight to about 20% by weight, from about 0.01% by weight to about 10% by weight, from about 0.01% by weight to about 1% by weight, or from about 0.01% by weight to about 0.1% by weight of the composition.

[0087] In configurations, the disclosed composition may include one or more pH buffer systems. For example, pH buffer systems may be able to restore physiological pH (e.g., of the vagina). Suitable pH buffer systems include, but are not limited to, lactic acid and lactic acid salts. In some configurations, the pH buffer system is lactic acid and sodium lactate. In other configurations, the pH buffer system is lactic acid and calcium lactate. Additionally, the composition (e.g., a vulvovaginal composition) may have a pH of 3.8 and the pH buffer system may have a buffering capacity within the range of 3.5–4.2.

[0088] In examples, the present disclosure includes compositions (e.g., emulsion) having a pH buffer system composed of one or more pH adjusting agents. The pH adjusting agent may be, for example, sodium hydroxide, hydrochloric acid, citric acid, malic acid, tartaric acid, acetic acid, phosphoric acid, maleic acid, glycine, sodium lactate, lactic acid, sodium citrate, ascorbic acid, sodium acetate, acetic acid, sodium bicarbonate, sodium carbonate, carbonic acid, sodium succinate, sodium benzoate, benzoic acid, sodium phosphates, tris(hydroxymethyl)aminomethane, histidine, histidine hydrochloride, or any combination thereof.

[0089] Useful compounds as pH adjusting agents include, but are not limited to, boric acid, sodium borate, sodium phosphate Petition 870260042611, dated 06 / 05 / 2026, page 34 / 250 31 / 109 (including basic mono-, di-, tri-phosphate and mixtures thereof). Any other physiologically relevant buffers may be used to stabilize the pH level of the composition, imparting a physiological pH approved for pharmaceuticals. As these buffers are only examples and are well known in this field, a person skilled in the art may choose suitable buffers that can be used for the composition of the present disclosure.

[0090] In some examples, the pH of the formulation is from about 2 to about 9. In other examples, the pH is in a range of about 3 to 9, or about 4 to 9, or about 5 to 9, or about 6 to 9, or about 7 to 9, or about 8 to 9. In other examples, the pH is in a range of about 3 to 8, or about 4 to 8, or about 5 to 8, or about 6 to 8, or about 7 to 8. In other examples, the pH is in a range of about 3 to 7, or about 4 to 7, or about 5 to 7, or about 6 to 7. In other examples, the pH is in a range of about 3 to 6, or about 4 to 6, or about 5 to 6.

[0091] Also as described herein, the disclosed compositions may include one or more viscosity-improving agents, for example, to obtain desired mechanical properties. In some examples, the mechanical properties may be measured by rheological methods known to those skilled in the art. Suitable viscosity-improving agents include, but are not limited to, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, ethyl cellulose, hyaluronic acid, sodium hyaluronate, carbomer, carbopol, polyacrylic acid, guar gum, xanthan gum, and any combination thereof.

[0092] In configurations, the zero-rate viscosity of the stable water-in-silicone emulsion can be between 100 Pa.s and 1000 kPa.s. For determination of the zero-rate viscosity of the emulsion, the methods Petition 870260042611, dated 06 / 05 / 2026, page 35 / 250 32 / 109 suitable characterization methods include, but are not limited to, rheometry and viscometry.

[0093] Throughout this disclosure, the term "viscosity-improving agent" may refer to more than one viscosity-improving agent if more than one agent is present in the composition. For example, one or more viscosity-improving agents may be incorporated within the emulsion. In some configurations, one or more viscosity-improving agents are incorporated within the aqueous phase of the emulsion. In other configurations, one or more viscosity-improving agents are incorporated within the silicone phase of the emulsion. In other configurations, viscosity-improving agents are incorporated into both the aqueous and silicone phases of the emulsion.

[0094] The disclosed compositions may include one or more antioxidants to improve formulation stability, affect cellular physiology, or any combination thereof. Suitable antioxidants include, but are not limited to, ascorbic acid, sodium ascorbate, a polyphenol, or any combination thereof.

[0095] Throughout this disclosure, the term antioxidant may refer to more than one antioxidant if more than one agent is present in the composition. For example, one or more antioxidants may be incorporated within the emulsion. In some configurations, one or more antioxidants are incorporated within the aqueous phase of the emulsion. In other configurations, one or more antioxidants are incorporated within the silicone phase of the emulsion. In other configurations, one or more antioxidants are incorporated within both the aqueous and silicone phases of the emulsion.

[0096] The compositions disclosed herein may include one or more tocopherols to affect cellular physiology, lubrication, or any combination thereof. Suitable tocopherols include, but are not limited to, Petition 870260042611, dated 06 / 05 / 2026, page 36 / 250 33 / 109 a, alpha-tocopherol, vitamin E, vitamin E-TPGS, tocopheryl acetate, or any combination thereof. Tocopherols (e.g., vitamin E) may provide lubrication, antioxidant properties, or any combination thereof.

[0097] Throughout this disclosure, the term tocopherol may refer to more than one tocopherol if more than one agent is present in the composition. For example, one or more tocopherols may be incorporated within the emulsion. In some configurations, one or more tocopherols are incorporated within the aqueous phase of the emulsion. In other configurations, one or more tocopherols are incorporated within the silicone phase of the emulsion. In other configurations, tocopherols are incorporated within both the aqueous and silicone phases of the emulsion.

[0098] The compositions disclosed herein may include one or more active agents to provide symptom relief, treat underlying pathophysiology or infection, or prophylactically protect the individual's anatomy (e.g., vagina). Suitable classes of active agents include, but are not limited to, antifungals, antibiotics, spermicides, estrogens, estrogen derivatives, progesterone, progesterone derivatives, estrogen precursors, steroids, anti-inflammatory drugs, antivirals / antiretrovirals (e.g., CCR5 antagonists, nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors, post-attachment inhibitors, integrase inhibitors, pharmacokinetic enhancers). Suitable active agents include, but are not limited to, miconazole, metronidazole, clotrimazole, estradiol, prasterone, nonoxynol-9, or any combination thereof.In some configurations, the active agent is miconazole. In some configurations, the active agent is metronidazole. In some configurations, the active agent is clotrimazole. In some... Petition 870260042611, dated 06 / 05 / 2026, page 37 / 250 In configurations 34 / 109, the active agent is estradiol. In some configurations, the active agent is prasterone. In some configurations, the active agent is nonoxynol-9.

[0099] The compositions disclosed herein may include one or more active agents to treat or protect the individual's skin. Suitable classes of active agents include, but are not limited to, antibiotics, antimicrobials, antifungals, antiseptics, local anesthetics, analgesics, anti-inflammatories, immunosuppressants, steroids, corticosteroids, calcineurin inhibitors, PDE4 inhibitors, salicylic acid, retinoids, antihistamines, benzoyl peroxide, nanocrystalline silver, or any combination thereof.

[00100] Exemplary antibiotics include, but are not limited to, amoxicillin, doxycycline, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, sulfamethoxazole / trimethoprim, amoxicillin / clavulanate, and levofloxacin. Additional antibiotics include micacin, gentamicin, kanamycin, neomycin, netilmicin, tobramycin, paromomycin, streptomycin, spectinomycin (Bs), geldanamycin, herbimycin, rifaximin, loracarbef, ertapenem, doripenem, imipenem / cilastatin, meropenem, cefadroxil, cefazolin, cefradine, cefapirin, cephalothin, cephalexin, cefaclor, cefoxitin, cefotetan, cefamandole, roxithromycin, telithromycin, epiramycin, fidaxomicin, furazolidone, nitrofurantoin (Bs), linezolid, posizolid, radezolid, torezolid, ampicillin, azlocillin, dicloxacillin, flucloxacillin, mezlocillin, methicillin, nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, penicillin G, temocillin, ticarcillin, ampicillin / sulbactam, piperacillin / tazobactam, ticarcillin / clavulanate,bacitracin, colistin, polymyxin B, ciprofloxacin, enoxacin, gatifloxacin, gemifloxacin, levofloxacin, norfloxacin, ofloxacin, trovafloxacin, minocycline, oxytetracycline, tetracycline, clofazimine, dapsone, capreomycin, cycloserinem pyrazinamide, rifampicin, rifabutin, rifapentine, streptomycin, metronidazole and mupirocin. Petition 870260042611, dated 06 / 05 / 2026, page 38 / 250 35 / 109

[00101] Exemplary antimicrobials include, but are not limited to, amoxicillin, doxycycline, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, sulfamethoxazole / trimethoprim, amoxicillin / clavulanate, and levofloxacin.

[00102] Exemplary antifungals include, but are not limited to, miconazole, clotrimazole, amphotericin B, ketoconazole, fluconazole, isavuconazole, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, and flucytosine.

[00103] Exemplary antiseptics include ethanol, sodium hypochlorite, chlorhexidine, hexachlorophene, povidone iodide, sodium hypochlorite, sodium hypochlorite, benzethonium chloride, triclosan, sodium oxychlorosene, benzalkonium chloride, and silver nitrate.

[00104] Exemplary local anesthetics include amylocaine, ambucaine, articaine, benzocaine, benzonatate, bupivacaine, butacaine, butanilicaine, chloroprocaine, cinchocaine (INN), cocaine, cyclomethicaine, dibucaine, diperodon, dimethocaine, eucaine, etidocaine, hexylcaine, fomocaine, fotocaine, hydroxyprocaine, isobucaine, levobupivacaine, lidocaine (lignocaine), mepivacaine. meprilcaine, metabutoxycaine, nitracaine, orthocaine, oxetacaine (oxetazaine), oxybuprocaine, paraethoxycaine, fenacaine, piperocaine, pyridocaine, pramocaine, prilocaine, primacaine, procaine, procainamide, proparacaine, propoxycaine, pyrrocaine, quinisocaine (INN), ropivacaine, trimecaine, tetracaine, tolicaine and tropacocaine.

[00105] Exemplary analgesics include codeine, fentanyl, hydrocodone (Hysingla, Zohydro), hydrocodone / acetaminophen (Lorcet, Lortab, Norco, Vicodin), hydromorphone (Dilaudid, Exalgo), meperidine (Demerol), methadone (Dolophine, Methadose), morphine (Kadian, MS Contin, Morphabond), oxycodone (OxyContin, Oxaydo), oxycodone and acetaminophen (Percocet, Roxicet), oxycodone and naloxone.

[00106] Exemplary anti-inflammatory drugs include celecoxib (Cele Petition 870260042611, dated 06 / 05 / 2026, page 39 / 250 36 / 109 brex), diclofenac (Cambia, Cataflam, Voltaren-XR, Zipsor, Zorvolex), diflunisal (Dolobid), etodolac (Lodine), ibuprofen (Motrin, Advil), indomethacin (Indocin), ketoprofen (Active-Ketoprofen), ketorolac, nabumetone naproxen (Aleve, Anaprox, Naprelan, Naprosyn), oxaprozin (Daypro), piroxicam (Feldene), salsalate, sulindac and tolmetin.

[00107] Exemplary immunosuppressants include corticosteroids (e.g., prednisone (Deltasone, Orasone), budesonide (Entocort CE), prednisolone (Millipred)), Janus kinase inhibitors (e.g., tofacitinib (Xeljanz)), calcineurin inhibitors, e.g., cyclosporine (Neoral, Sandimmune, SangCya) and tacrolimus (Astagraf XL, Envarsus XR, Prograf), mTOR inhibitors, e.g., sirolimus (Rapamune), and everolimus (Afinitor, Zortress), IMDH inhibitors, e.g., azathioprine (Azasan, Imuran), leflunomide (Arava), and mycophenolate (CellCept, Myfortic), biologics, e.g., abatacept (Orencia), adalimumab (Humira),anakinra (Kineret), certolizumabe (Cimzia), etanercept (Enbrel), golimumabe (Simponi), infliximabe (Remicade), ixekizumab (Taltz), natalizumab (Tysabri), rituximab (Rituxan), secukinumab (Cosentyx), tocilizumab (Actemra), Actemra (Stelara), us vedolizumabe (Entyvio), and monoclonal antibodies, for example, basiliximabe (Simulect), daclizumabe (Zinbryta) and muromonabe (Orthoclone OKT3).,

[00108] Calcineurin inhibitors include Astagraf XL, cyclosporine, ophthalmic cyclosporine, Elidel, Envarsus XR, Gengraf, Hecoria, Neoral, pimecrolimus, Prograf, Protopic, Restasis, Sandimmune, tacrolimus, and tacrolimus ointment.

[00109] Phosphodiesterase 4 (PDE4) inhibitors include adibendan, aminophylline, dehydrated aminophylline, amipizone, apremilast, arophylline, atizoram, befuraline, Bemarinone hydrochloride, bemoradan, benafenthrine, bucladesin, buflomedil, buquinone, CC-108, carbazeran, catramilast, cilomilast, cilostamide, cilostazol, cipamphylin, chrysaborole, Petition 870260042611, 06 / 05 / 2026, pág. 40 / 250 37 / 109 daxalipram, denbufilina, dimabefilina, dindiprofilina, dipiridamol, doxofilina, drotaverina, difilina, enoximona, etamifilina, etofilina, filaminast, flufilina, fluprofilina, furafilina, imazodan, cloridrato de imazodan, inamrinona, lactato de inamrinona, isbufilina, lirimilast, lisofilina, lomifilina, medorinona, metescufilina, midaxifilina, milrinona, lactato de milrinona, motapizona, nanterinona, nestifilina, nitraquazona, oglemilast, oglemilast de sódio, olprinona, oxagrelato, oxtrifilina, papaverina, hidrocloridrato de papaverina, sulfato de papaverina, parogrelila, pelrinona hydrochloride, pentiphylline, pentoxiphilin, perbuphilin, piclamilast, pimephilin, pimobendan, piroximona, prinoxodan, proxiphilin, pumafentrine, quazinona, quazodine, revamilast, revizinona, roflumilast, rolipram, ronomilast, saterinona, senazodan, siguazodan, tetomilast, tofimilast, trapidil, vesnarinona and zardaverine.

[00110] The disclosed compositions may include one or more active agents to provide symptom relief or treat the underlying pathophysiology, or protect the individual's anatomy (e.g., rectum). Suitable classes of active agents include, but are not limited to, vasoconstrictors, anti-inflammatory drugs, steroids, local anesthetics, alpha-adrenergic receptor agonists, onabotulinumtoxin A, calcium channel blockers, nitrates, or any combination thereof.

[00111] One or more active agents may be incorporated within the emulsion. In some configurations, one or more active agents are incorporated within the aqueous phase of the emulsion. In other configurations, one or more active agents are incorporated within the silicone phase of the emulsion. In other configurations, one or more active agents are incorporated within both the aqueous and silicone phases of the emulsion.

[00112] In some configurations, the active agent may be formulated to be present in a typical amount for such an agent. For example, the agent may be formulated to make up to 0.01% in Petition 870260042611, dated 06 / 05 / 2026, page 41 / 250 38 / 109 by weight, inclusive, of the composition. In some configurations, the active agent may be formulated to comprise up to 0.025% by weight, inclusive, of the composition. In some configurations, the active agent may be formulated to comprise up to 0.05% by weight, inclusive, of the composition. In some configurations, the active agent may be formulated to comprise up to 0.1% by weight, inclusive, of the composition. In some configurations, the active agent may be formulated to comprise up to 1% by weight, inclusive, of the composition. In some configurations, the active agent may be formulated to comprise up to 2% by weight, inclusive, of the composition. In some configurations, the active agent may be formulated to comprise up to 4% by weight, inclusive, of the composition. In some configurations, the active agent may be formulated to comprise up to 6% by weight, inclusive, of the composition. In some configurations, the active agent may be formulated to comprise up to 8% by weight, inclusive, of the composition.In some configurations, the active ingredient can be formulated to comprise up to 10% by weight of the composition.

[00113] Throughout this disclosure, the term "active agent" may refer to more than one active agent if more than one of these agents is present in the composition. For example, when only one active agent is incorporated within the emulsion, a reference to 50% by weight of the active agent means that 50% of the single active agent is present. When more than one active agent is incorporated within the emulsion, the language referring to 50% by weight of the active agent means that 50% of the total complement of active agents is incorporated within the emulsion. Thus, if the composition includes 1 mg of one active agent and 1 mg of a second active agent, then 50% by weight preservative may mean that 50% of the total complement of 2 mg of active agents is incorporated within the emulsion.

[00114] The compositions of the present invention may contain a Petition 870260042611, dated 06 / 05 / 2026, p. 42 / 250 39 / 109 safe and effective quantity of a conditioning agent, for example, humectants, emollients, moisturizers and skin conditioners. A variety of these materials may be employed and may be present at a level of about 0.01% to about 80%, more preferably from about 0.1% to about 25%, and even more preferably from about 0.5% to about 10%, by weight of the composition. The exact content (%) of humectants, emollients, moisturizers and conditioning agents to be used in the compositions will depend on the humectant, emollient, moisturizer and conditioning agent used, as such agents vary widely in potency.

[00115] Humectants are ingredients that help maintain moisture levels in the skin. Humectants include, for example, polyhydric alcohols, water-soluble nonionic alkoxylated polymers, and mixtures thereof. Useful polyhydric alcohols here include the aforementioned polyhydroxylated alcohols and glycerin, hexylene glycol, ethoxylated glucose, 1,2-hexanediol, dipropylene glycol, trehalose, diglycerin, maltitol, maltose, glucose, fructose, sodium chondroitin sulfate, sodium hyaluronate, sodium adenosine phosphate, sodium lactate, pyrrolidone carbonate, glucosamine, cyclodextrin, and mixtures thereof. Non-ionic, alkoxylated, water-soluble polymers useful here include polyethylene glycols and polypropylene glycols having a molecular weight of up to about 1000, such as those with CTFA nomenclature of PEG-200, PEG-400, PEG-600, PEG-1000 and mixtures thereof.Additional humectants include acetyl arginine, algae extract, aloe barbadensis leaf extract, 2,3-butanediol, lauroyl chitosan glycinate, diglyceride-7 malate, diglycerin, guanidine diglycol succinate, erythritol, fructose, glucose, glycerin, honey, hydrolyzed proteins, hydroxypropyl trimonium hyaluronate, inositol, lactitol, maltitol, maltose, mannitol, mannose, methoxy polyethylene glycol, guanidine myristamidobutyl acetate, polyglyceryl sorbitol, potassium pyrrolidone carboxylic acid (PCA). Petition 870260042611, dated 06 / 05 / 2026, page 43 / 250 40 / 109 propylene glycol, butylene glycol, sodium pyrrolidone carboxylic acid (PCA), sorbitol, sucrose, dextran sulfate (i.e., of any molecular weight), natural moisturizing factors and / or urea.

[00116] Skin conditioners may include, but are not limited to, guanidine, urea, glycolic acid, glycolate salts (e.g., ammonium and quaternary alkyl ammonium), salicylic acid, lactic acid, lactate salts (e.g., ammonium and quaternary alkyl ammonium), aloe vera in any of its variety of forms (e.g., aloe vera gel), polyhydroxylated alcohols such as sorbitol, mannitol, xylitol, erythritol, hexane triol, butane triol, propylene glycol, butylene glycol, hexylene glycol and the like, polyethylene glycols, propoxylated glycerols, sugars (e.g., melibiose), starches, sugar and starch derivatives (e.g., alkoxylated glucose, fructose, glucosamine), C1-C30 monoesters and polyesters of sugars and related materials, acid hyaluronic acid, monoethanolamine lactamide, monoethanolamine acetamide, panthenol, dexpanthenol, allantoin, and mixtures thereof.Skin conditioners may also include fatty acids, fatty acid esters, lipids, ceramides, cholesterol, cholesterol esters, beeswax, petrolatum, and mineral oil.

[00117] Emulsions may be configured to be administered and / or applied to an individual. Suitable methods of administration include, but are not limited to, being introduced into, instilled into, implanted, applied, or applied to the vulvovaginal anatomy, rectal anatomy, skin, or eye of an individual. For example, in some aspects, the emulsion is configured to be applied to the vagina of an individual. In other aspects, the emulsion is configured to be applied to and around the vulva of an individual.

[00118] Anatomical and physiological interactions, physiological release, diffusion, or any combination thereof, may lead to the release of the cell membrane fluidity-enhancing agent, fatty acid, and Petition 870260042611, dated 06 / 05 / 2026, page 44 / 250 41 / 109 at least one of the following groups: bioactive agent, pH buffer system, antioxidant, tocopherol, ceramide, active agent, or any combination thereof, of the stable water-in-silicone emulsion, thus providing an effective therapeutic dose to the individual.

[00119] In some configurations, the emulsified formulation provides an effective therapeutic dose for up to two hours from a single dose. In some configurations, the emulsified formulation provides an effective therapeutic dose for up to 4 hours from a single dose. In some configurations, the emulsified formulation provides an effective therapeutic dose for up to 8 hours from a single dose. In some configurations, the emulsified formulation provides an effective therapeutic dose for up to 12 hours from a single dose. In some configurations, the emulsified formulation provides an effective therapeutic dose for up to 18 hours from a single dose. In some configurations, the emulsified formulation provides an effective therapeutic dose for up to 24 hours from a single dose. In some configurations, the emulsified formulation provides an effective therapeutic dose for up to 48 hours from a single dose.In some configurations, the emulsified formulation provides an effective therapeutic dose for up to 3 days from a single dose. In some configurations, the emulsified formulation provides an effective therapeutic dose for up to 5 days from a single dose. In some configurations, the emulsified formulation provides an effective therapeutic dose for up to 7 days from a single dose. In some configurations, the emulsified formulation provides an effective therapeutic dose for up to 14 days from a single dose.

[00120] In settings, composition can be administered as needed, such as once a day, two to five times a day, up to twice or up to three times a day, or up to eight times a day. Petition 870260042611, dated 06 / 05 / 2026, p. 45 / 250 42 / 109 day. In configurations, the compound is administered three times a day, twice a day, once a day, on fourteen days (four times a day, three times a day or twice a day or once a day) and 7 days off in a 3-week cycle, up to five or seven days onwards (four times a day, three times a day or twice a day, or once a day) and 14-16 days off in a 3-week cycle, or once every two days, or once a week, or once every two weeks, or once every 3 weeks.

[00121] In other examples, the compound is administered once a week, or once every two weeks, or once every 3 weeks, or once every 4 weeks, for at least one week; in some settings, for one to four weeks, two to six weeks, two to eight weeks, two to ten weeks, or two to twelve weeks, two to sixteen weeks, or more (e.g., 1, 2, 3, 4, 4, 6, 7, 8, 9, 10, 11, 12, 36, 48 or more weeks).

[00122] Pharmaceutically acceptable constituents, excipients, or agents may also be included in the compositions described herein. In some respects, pharmaceutically acceptable agents may stabilize the composition, allow it to be readily administered to the vulvovaginal anatomy (e.g., the vulva, vagina, or both), the rectal anatomy, the skin, or the eye of an individual, enhance its ability to provide symptom relief, treat the underlying pathophysiology or infection, or prophylactically protect the vagina of an individual, or otherwise make the composition suitable for therapeutic use in an individual. Thus, the described composition may further include a pharmaceutically acceptable excipient, as should be known to a person skilled in the relevant art.Given the inclusion of active agents in some of the vulvovaginal, rectal, dermatological or ophthalmic compositions described herein, these are also pharmaceutical compositions having a stable water-in-silico emulsion. Petition 870260042611, dated 06 / 05 / 2026, page 46 / 250 43 / 109 ne, an emulsifier, a cell membrane fluidity enhancer, a fatty acid, a preservative, and at least one of the following bioactive agents: a pH buffer system, a viscosity enhancer, an antioxidant, a tocopherol, a ceramide, and an active agent, as provided herein. The pharmaceutical compositions described may be administered to an individual in order to provide symptom relief, treat underlying pathophysiology or infection, or prophylactically protect an individual's vagina.

[00123] This disclosure also provides methods comprising combination therapy for the treatment or prevention of the diseases and conditions described herein. As used herein, combination therapy or co-therapy includes the administration of a composition described herein, for example, a composition comprising a stable silicone water emulsion having a continuous silicone phase and an aqueous phase, wherein the emulsion comprises a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition, with at least one additional agent, as disclosed herein, as part of a specific treatment regimen intended to provide the beneficial effect of the combined action of these therapeutic compositions.

[00124] In combination therapy settings, at least one additional agent may be a therapeutic agent or a non-therapeutic agent. The beneficial effect of the combination includes, but is not limited to, joint pharmacokinetic or pharmacodynamic action resulting from the combination of therapeutic compounds and the composition disclosed herein. The beneficial effect of the combination may also relate to the mitigation of a toxicity, side effect, or adverse event associated with another agent in the combination. Combination therapy may be, but generally is not, intended to encompass the administration of two or more of these therapeutic compounds as part of regimens. Petition 870260042611, dated 06 / 05 / 2026, page 47 / 250 44 / 109 of separate monotherapy, which incidentally and arbitrarily result in the combinations of this disclosure.

[00125] In the context of combination therapy, the administration of the compositions described herein may be simultaneous with or sequential to the administration of one or more additional agents. In another aspect, the administration of the different components of a combination therapy may be at different frequencies. One or more additional agents may be administered before (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, one hour, two hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, one week, two weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), concurrently with, or subsequent to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, one hour, two hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, one week, two weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) the administration of a compound of this disclosure.

[00126] One or more additional agents may be formulated for co-administration with a composition of this disclosure, in a single dosage form, as described herein. One or more additional agents may be administered separately from the dosage form comprising the composition of this disclosure. When the additional agent is administered separately from a composition of this disclosure, it may be by the same or a different route of administration, such as the composition of the instant disclosure.

[00127] Preferably, administration of a composition of the present disclosure, in combination with one or more additional agents, provides a synergistic response in the individual having a disorder, disease or condition of the present disclosure. In this context, the term Petition 870260042611, dated 06 / 05 / 2026, page 48 / 250 45 / 109 synergistic refers to the effectiveness of the combination being more effective than the additional effects of any single therapy. The synergistic effect of combination therapy, according to the disclosure, may allow the use of lower doses and / or less frequent administration of at least one agent in the combination compared to its dose and / or frequency outside the combination. The synergistic effect may manifest in the prevention or reduction of adverse or undesirable side effects associated with the use of any combination therapy alone.

[00128] Combination therapy also includes administering the composition of this disclosure in combination with non-drug therapies (e.g., surgery or radiation treatment). When combination therapy further comprises a non-drug treatment, the non-drug treatment may be performed at any appropriate time, provided that a beneficial effect from the combined action of the therapeutic compounds and the non-drug treatment is achieved. Physical and chemical properties of water-in-silicone emulsion. Droplet size.

[00129] In some examples, the emulsion described herein comprises droplets (alternatively, particles). The liquid-liquid droplets comprising the emulsified formulation may have a median diameter of up to 250 microns. For example, the droplets may have a median diameter of about 10 to about 250 microns, about 50 to 250 microns, about 100 to 250 microns, about 150 to 250 microns, or about 200 to 250 microns. In some examples, the droplet / particle is about 10 to about 100,000 nanometers (100 μm) in diameter. For example, the droplet / particle can be approximately 10, 50, 100, 200, 300, 400, 500, 1000, 10,000, or 100,000 nanometers in diameter. In some configurations, a device Petition 870260042611, dated 06 / 05 / 2026, page 49 / 250 46 / 109 or device can be used to deliver a droplet / particle to the individual.

[00130] Droplet size can be analyzed by methods known in the art. Suitable methods for droplet size analysis include, but are not limited to, light microscopy, dynamic light scattering, and laser diffraction. Preparation Methods

[00131] Here, too, methods are provided for preparing compositions comprising a water-in-oil emulsion. In some examples, the emulsion can be prepared using techniques including, but not limited to, rotor-stator emulsification, static mixing, or high-shear mixing.

[00132] In settings, the composition is emulsified to form a stable emulsion with the desired droplet size. High-shear cutting devices that can be used include, but are not limited to, the IKA Ultra-Turrax disperser, IKA DispaxReactor DR and DRS (Dispax-Reactor shear mixers include the DR3-6 with three-stage rotor / stator combinations and the tip speed of the rotor / stator generators can be varied by a variable frequency drive that controls the motor), Silverson mixer (a two-stage mixer, which incorporates a rotor / stator design and has high-volume pumping characteristics similar to a centrifugal pump), Silverson Corporation in-line shear mixers (with a rotor-stator emulsification approach), jet mixers (venturi / cavitation style shear mixers), Sonic Corporation Ultrasonolator (with an ultrasonic emulsification approach).Microfluidizing shear mixers made available by the manufacturer Microfluidics Inc (high-pressure homogenization shear mixers), ultrasonic mixers and any other mixer. Petition 870260042611, dated 06 / 05 / 2026, page 50 / 250, 47 / 109 high shear pain available.

[00133] In other configurations, the composition is emulsified to form a stable emulsion using a static mixer. A static mixer is a precision-engineered device for the continuous mixing of fluid materials without moving components. Composition, generally

[00134] As described herein, certain aspects of the present invention relate to the use of the compositions to make cosmetics, personal care products, feminine care products, hygiene products, dermatological products, ophthalmic products, pharmaceutical preparations or medicines for maintaining healthy skin, skin rejuvenation, restoration of damaged skin, including, but not limited to, cosmetics on the skin after aesthetic and dermatological procedures, wound healing, treatment of atrophy of any human tissue, including vulvovaginal atrophy, and / or other skin and mucous membrane conditions, disorders and diseases in humans associated with alterations in extracellular matrix components.

[00135] This is done by topical application of the composition of the invention to the skin or mucous membrane of the human being requiring such treatment. In some limited cases, this can be done by topical administration of the composition of the invention to a human being requiring such treatment.

[00136] Certain aspects of the present invention also relate to methods of using such compositions for treatment or prevention in dermatological applications, as well as for improving wound healing, reducing atrophy of any human tissue, including vulvovaginal atrophy, and for improving other conditions, disorders and diseases of the skin and mucous membranes in humans. These methods generally involve applying the composition topically to the affected skin. Petition 870260042611, dated 06 / 05 / 2026, page 51 / 250 48 / 109 or to the affected anatomy when necessary, in the quantity and frequency most appropriate for the purpose. Methods to prevent, delay the onset of, or treat a skin or mucosal condition, disorder, or disease are also contemplated.

[00137] Those skilled in the art may further recognize that the administration of any of the compositions and / or formulations of the invention treats, relieves or alleviates skin and mucous membrane conditions, disorders and diseases in humans, for example, injured skin, damaged skin after aesthetic and dermatological procedures, skin and mucous membrane atrophy due to causes other than aging (for example, emotional stress, use of oral contraceptive pills, use of aromatase inhibitors, due to surgery, etc.), and for other skin and mucous membrane conditions, disorders and diseases in humans. Vulvovaginal compositions

[00138] Vulvar and vaginal atrophy (VVA), resulting from the loss of estrogen stimulation in vaginal and vulvar tissue, is a common medical condition in peri- and postmenopausal women. VVA often manifests with discomfort, which may be experienced as vaginal dryness, lack of lubrication, roughness, burning, irritation, inflammation, atrophic vaginitis, dyspareunia (pain during sexual intercourse), and general pain. VVA occurs most frequently after menopause, but can also develop during breastfeeding, as a consequence of breast cancer treatment, or at any other time when a woman's estrogen production decreases. Furthermore, recent evidence indicates that women taking oral contraceptives (which can cause a decline in the production of certain sex hormones, such as testosterone) may also experience vulvovaginal atrophy. VVA will occur in most postmenopausal women at some point in their lives. It is estimated that Petition 870260042611, dated 06 / 05 / 2026, page 52 / 250 49 / 109 There are 64 million postmenopausal women in the United States, and about 32 million women may suffer from VVA symptoms.

[00139] Existing non-prescription treatments (e.g., non-hormonal, over-the-counter (OTC) moisturizing and lubricating creams) have shortcomings in several areas, for example, they are not able to restore stasis to anatomy and physiology; they often contain ingredients that are not well tolerated in the vaginal canal; they are often not isotonic; and they are far inferior to Hormone Replacement Therapies (HRT) in terms of symptom relief and treatment of the underlying pathology.

[00140] The pathophysiology of VVA is such that decreasing estrogen levels, associated with peri- and post-menopause, cause (1) a thinning of the superficial cells and stratified epithelial cells lining the vaginal mucosa, and (2) a decrease in squamous epithelial glycogenation, resulting in a decrease in exfoliated and glycogenated cells. Glycogen is an important biomolecule responsible for maintaining vaginal health. The conversion of glycogen to lactic acid by lactobacilli, the beneficial flora of the vaginal mucosa, is essential for maintaining a healthy and low vaginal pH. In the absence of glycogen, vaginal pH increases, resulting in a decrease in lactobacilli and a potential for overgrowth of harmful bacteria, which can lead to infection and inflammation. Furthermore, the decline in estrogen levels leads to decreased vulvovaginal blood flow, decreased mucus production, and decreased vaginal lubrication.Thus, compositions and methods are provided here that address these needs. Vulvovaginal compositions (e.g., lubricants, moisturizers, creams) are provided here that are non-hormonal, isotonic, long-lasting, and capable of slowing the progression of VVA (e.g., by restoring pH balance, providing significant lubrication, and providing symptom relief - dryness). Petition 870260042611, dated 06 / 05 / 2026, page 53 / 250 50 / 109 vaginal - for at least 24 hours from a single application), and comprise only well-tolerated, generally recognized as safe (GRAS) ingredients that are compatible with latex lactobacilli.

[00141] Compositions are provided herein, for example, vulvovaginal compositions. In some configurations, vulvovaginal compositions are specifically formulated to not require active agents for the treatment of a particular indication. Alternatively, this disclosure also provides vulvovaginal compositions that are formulated to enable the incorporation of active agents. In both cases, the formulation method is specifically selected to exert control over 1) formulation stability, 2) mechanical properties, and 3) therapeutically relevant incorporation of desired constituents, excipients, or agents.

[00142] The disclosed vulvovaginal compositions can be administered by application. For example, vulvovaginal compositions can be applied inside the vagina using an applicator known to those skilled in the art. Additionally, vulvovaginal compositions can be applied to the vulva by methods known to those skilled in the art. In some settings, the vulvovaginal composition can be administered into the vagina. In some aspects, the vulvovaginal composition can be applied to the vagina. In other settings, the vulvovaginal composition can be administered on or around the vulva. In some aspects, the vulvovaginal composition can be applied to or around the vulva. In other settings, the vulvovaginal composition can be administered on or around superficial vaginal cells. In some aspects, the vulvovaginal composition can be applied on or around superficial vaginal cells.In other settings, the vulvovaginal composition may be administered on or around epithelial cells. Petition 870260042611, dated 06 / 05 / 2026, page 54 / 250 51 / 109 vaginal squamous cells. In some respects, the vulvovaginal composition can be applied over or around vaginal squamous epithelial cells.

[00143] The disclosed vulvovaginal compositions can be used to provide relief of vaginal symptoms, treat underlying pathophysiology or infection of the vaginal anatomy, or prophylactically protect the vagina in an individual, for example, by administering the composition into the vagina. The disclosed vulvovaginal compositions can be used to provide relief of vulvar symptoms, treat underlying pathophysiology or infection of the vulvar anatomy, or prophylactically protect the vulva in an individual, for example, by administering the composition onto the vulva.

[00144] In settings, the vulvovaginal composition can be used to prevent or treat bacterial vaginosis, vulvovaginal atrophy, yeast infections, as a sexually transmitted infection (STI) and / or sexually transmitted disease (STD), prophylaxis as a personal lubricant, vaginal moisturizer, local hormone replacement therapy, or as contraception.

[00145] In addition, the compositions disclosed herein may be used to provide relief of vulvovaginal symptoms, treat underlying pathophysiology or infection of the vulvovaginal anatomy, or prophylactically protect the vulvovaginal anatomy in an individual. The need for treatment or prophylaxis may arise from a number of conditions, including but not limited to menopause, perimenopause, postmenopause, decreased estrogen concentration, atrophic vaginitis, vulvar and vaginal atrophy, bacterial vaginosis, vaginal dryness, vaginal itching, vaginal irritation, dyspareunia, bacterial infection, yeast infection, urinary tract infection, need for vaginal lubrication and moistening, sexual intercourse, need for contraceptive prophylaxis, or any combination thereof. Petition 870260042611, dated 06 / 05 / 2026, page 55 / 250 52 / 109

[00146] In some instances, the disclosed vulvovaginal compositions may include a bioactive agent. Examples of contemplated bioactive agents include, but are not limited to, glycogen, lactic acid, cholesterol, or any combination thereof.

[00147] In some examples, the disclosed vulvovaginal compositions may include an active agent.Examples of eligible active agents include, but are not limited to, antifungals, antibiotics, spermicides, estrogens, estrogen derivatives, progesterone, progesterone derivatives, estrogen precursors, steroids, anti-inflammatory drugs, antivirals / antiretrovirals (e.g., CCR5 antagonists, nucleoside reverse transcriptase inhibitors (NRTIs) as described herein), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) (e.g., atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva), indinavir (Crixivan), lopinavir / ritonavir (Kaletra), nelfinavir (Viracept), riattonavir (Norvir), saquinavir (Invirase), tipranavir (Aptivus), atazanavir / cobicistat (Evotaz), and darunavir / cobicistat). (Prezcobix)), fusion inhibitors (e.g., T-2 (enfuvirtide, Fuzeon)), integrase inhibitors, e.g., raltegravir, dolutegravir, and cabotegravir), post-attachment inhibitors, and pharmacokinetic enhancers.

[00148] In certain configurations, the active agent for the vulvovaginal composition may include a steroidal anti-inflammatory agent. Exemplary steroidal anti-inflammatory bioactive agents include, but are not limited to, corticosteroids such as prasterone, hydrocortisone, triamcinolone hydroxyl, alpha-methyl dexamethasone, dexamethasone phosphate, beclomethasone dipropionate, clobetasol valerate, desonide, desoximetasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflutolone valerate, fluadrenolone, fluchlorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortin butyl ester, fluocortolone, fluprednidene Petition 870260042611, dated 06 / 05 / 2026, page 56 / 250 53 / 109 (fluprednilidene) acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methyl prednisolone, triamcinolone acetonide, cortisone, cortodoxane, fludrocortisone flucetonide, difluorosone diacetate, fluadrenolone acetonide, medrisone, amcinafel, amcinafide, betamethasone and the balance of its esters, chlorprednisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, difluprednate, fluchloronide, flunisolide, fluorometholone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortate, meprednisone, paramethasone, prednisolone, beclomethasone dipropionate, Triamcinolone, and mixtures thereof, may be used.

[00149] In other configurations, the active agent comprises a second class of anti-inflammatory agents that is useful in the compositions, and includes non-steroidal anti-inflammatory agents. The variety of compounds encompassed by this group is well known to those skilled in the art.

[00150] In one configuration, the additional agent is an antiviral agent. Non-limiting examples of antiviral agents that may be used in combination with a composition described herein include acemannan; acyclovir; acyclovir sodium; adefovir; aloiudine; alvircept sudotox; amantadine hydrochloride; aranotin arildone; atevirdine mesylate; avridine; cidofovir; cipamfilline; cytarabine hydrochloride; delavirdine mesylate; desciclovir; didanosine; desoxaryl; edoxudine; enviradene; enviroxime; famciclovir; famotine hydrochloride; fiacitabine; fialuridine; foscarnet sodium; fosfonet sodium; ganciclovir; ganciclovir sodium; odoxuridine; ketoxal; lamivudine; lobucavir; memotine hydrochloride; methizone; nevirapine; penciclovir; pirodavir; ribavirin; rimantadine hydrochloride; saquinavir mesylate; somantadine hydrochloride; sorivudine; statolon; staiudine; tilorone hydrochloride; trifluridine; valacyclovir hydrochloride; vidarabine; vidarabine phosphate; vidarabine phosphate Petition 870260042611, dated 06 / 05 / 2026, page 57 / 250 54 / 109 sodium; viroxime; zalcitabine; zidovudine; and zinviroxime. Combinations of antiviral agents are also contemplated in the compositions described herein.

[00151] In some configurations, the vulvovaginal composition includes one or more active and / or bioactive agents. In some configurations, the vulvovaginal composition includes two active agents, for example, estradiol and prasterone. In another example, the vulvovaginal composition includes one active and one bioactive agent, for example, estradiol and glycogen, respectively.

[00152] In configurations, the vulvovaginal composition includes an active agent from about 0.0001% by weight to about 90% by weight of the composition, from about 0.0001% by weight to about 1% by weight, from about 0.0001% by weight to about 10% by weight, from about 0.0001% by weight to about 20% by weight, from about 0.0001% by weight to about 30% by weight, from about 0.0001% by weight to about 40% by weight, from about 0.0001% by weight to about 50% by weight, from about 0.0001% by weight to about 60% by weight, from about 0.0001% by weight to about 70% by weight, from about 0.0001% by weight to about 80% by weight, from about 0.001% by weight to about 90% by weight of the composition, from about 0.001% by weight to about 1% by weight, from about 0.001% by weight to about 10% by weight, from about 0.001% by weight to about 20% by weight, from about 0.001% by weight to about 30% by weight, from about 0.001% by weight to about 40% by weight, from about 0.001% by weight to about 50% by weight,from about 0.001% by weight to about 60% by weight, from about 0.001% by weight to about 70% by weight, from about 0.001% by weight to about 80% by weight, from about 0.01% by weight to about 90% by weight of the composition, from about 0.01% by weight to about 1% by weight, from about 0.01% by weight to about 10% by weight, of, Petition 870260042611, dated 06 / 05 / 2026, page 58 / 250 55 / 109 approximately 0.01% by weight to approximately 20% by weight, from approximately 0.01% by weight to approximately 30% by weight, from approximately 0.01% by weight to approximately 40% by weight, from approximately 0.01% by weight to approximately 50% by weight, from approximately 0.01% by weight to approximately 60% by weight, from approximately 0.01% by weight to approximately 70% by weight, from approximately 0.01% by weight to approximately 80% by weight, from approximately 0.1% by weight to approximately 90% by weight of the composition, from approximately 0.1% by weight to approximately 1% by weight, from approximately 0.1% by weight to approximately 10% by weight, from approximately 0.1% by weight to approximately 20% by weight, from approximately 0.1% by weight to approximately from 30% by weight, from about 0.1% by weight to about 40% by weight, from about 0.1% by weight to about 50% by weight, from about 0.1% by weight to about 60% by weight, from about 0.1% by weight to about 70% by weight, from about 0.1% by weight to about 80% by weight of the composition, and any range between these.

[00153] In configurations, the vulvovaginal composition includes a bioactive agent of about 0.0001% by weight to about 90% by weight of the composition, from about 0.0001% by weight to about 1% by weight, from about 0.0001% by weight to about 10% by weight, from about 0.0001% by weight to about 20% by weight, from about 0.0001% by weight to about 30% by weight, from about 0.0001% by weight to about 40% by weight, from about 0.0001% by weight to about 50% by weight, from about 0.0001% by weight to about 60% by weight, from about 0.0001% by weight to about 70% by weight, from about 0.0001% by weight to about from about 80% by weight, from about 0.001% by weight to about 90% by weight of the composition, from about 0.001% by weight to about 1% by weight, from about 0.001% by weight to about 10% by weight, from about 0.001% by weight to about 20% by weight, from about 0.001% by weight to about 30% by weight, from about 0.001% by weight to about 40% by weight, of Petition 870260042611, dated 06 / 05 / 2026, p. 59 / 250 56 / 109 approximately 0.001% by weight to approximately 50% by weight, approximately 0.001% by weight to approximately 60% by weight, approximately 0.001% by weight to approximately 70% by weight, approximately 0.001% by weight to approximately 80% by weight, approximately 0.01% by weight to approximately 90% by weight of the composition, approximately 0.01% by weight to approximately 1% by weight, approximately 0.01% by weight to approximately 10% by weight, approximately 0.01% by weight to approximately 20% by weight, approximately 0.01% by weight to approximately 30% by weight, approximately 0.01% by weight to approximately 40% by weight, approximately 0.01% by weight to approximately 50% by weight, approximately 0.01% by weight to about 60% by weight, from about 0.01% by weight to about 70% by weight, from about 0.01% by weight to about 80% by weight, from about 0.1% by weight to about 90% by weight of the composition, from about 0.1% by weight to about 1% by weight, from about 0.1% by weight to about 10% by weight, from about 0.1% by weight to about 20% by weight, from about 0.1% by weight to about 30% by weight,from about 0.1% by weight to about 40% by weight, from about 0.1% by weight to about 50% by weight, from about 0.1% by weight to about 60% by weight, from about 0.1% by weight to about 70% by weight, from about 0.1% by weight to about 80% by weight of the composition, and any range between these.

[00154] In configurations, the present disclosure includes a vulvovaginal composition, including a cell membrane fluidity enhancer (for example, a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols or any combination thereof) and a preservative. Examples of preservatives include an antimicrobial preservative, for example, benzalkonium chloride, thimerosal, chlorhexidine, chlorobutanol, methylparaben, propylparaben, phenylethyl alcohol, disodium edetate, sorbic acid, benzoic acid, cetyl bromide, pyridinium cetyl chloride, benzyl bromide, Petition 870260042611, dated 06 / 05 / 2026, page 60 / 250 57 / 109 EDTA, phenylmercury nitrate, phenylmercury acetate, thimerosal, merthiolate, phenylmercury acetate and borate, polymyxin B sulfate, methyl and propyl parabens, quaternary ammonium chloride, sodium benzoate, potassium sorbate, sodium propionate and sodium perborate, or any combination thereof.

[00155] In configurations, preservatives may be used in appropriate amounts. For example, the preservative may be used in an amount of approximately 0.001% by weight - 1.0% by weight, based on the total weight of the composition.

[00156] In some settings, the vulvovaginal composition, including a cell membrane fluidity enhancer (e.g., a sterol, where exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof), has a pH of about 3 to about 4.5. In other settings, the pH is about 3.8.

[00157] In some examples, the vulvovaginal composition, including a cell membrane fluidity enhancer (e.g., a sterol, where exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has an osmolarity of about 280 to about 380 mOsm / kg.

[00158] The vulvovaginal composition must have a zero-rate viscosity, which is a resistant change over time and / or temperature. The terms viscous, viscosity, zero-rate viscosity, and the like, refer herein, in the usual and customary sense, to a measure of a material's resistance to deformation (e.g., liquid behavior) upon the application of a force (e.g., shear stress or tensile stress). The viscosity of emulsions may also depend on temperature, along with several other effects such as shear rate, average droplet size, and droplet size distribution. As described herein, Petition 870260042611, dated 06 / 05 / 2026, p. 61 / 250 58 / 109 Viscosity can typically mean that the vulvovaginal composition has a zero-rate viscosity of about 50 kPa.s to about 1000 kPa.s at 25°C. In examples, the composition has the desired zero-rate viscosity (e.g., about 200 kPa.s at 25°C) for at least 12 months.

[00159] In some examples, the vulvovaginal composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has a zero-rate viscosity of about 50 kPa.s to about 1000 kPa.s at 25°C.

[00160] In some instances, the vulvovaginal composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has rheological properties that have negligible variation with temperature between 25°C and 37°C. Vulvovaginal Methods

[00161] Methods are also provided herein for providing relief of vulvovaginal symptoms, treating the underlying pathophysiology or infection of the vulvovaginal anatomy, or prophylactically protecting the vulvovaginal anatomy in an individual, comprising administering to an individual any of the compositions disclosed herein. In some configurations, the methods for providing relief of vulvovaginal symptoms, treating the underlying pathophysiology or infection of the vulvovaginal anatomy, or prophylactically protecting the vulvovaginal anatomy in an individual, comprise administering to an individual vulvovaginal compositions comprising a stable silicone water emulsion, an emulsifier, a cell membrane fluidity enhancer, a fatty acid, a preservative, and at least one of the following: Petition 870260042611, dated 06 / 05 / 2026, page 62 / 250 59 / 109 po consisting of a bioactive agent, a pH buffer system, a viscosity-improving agent, an antioxidant, a tocopherol, and an active agent. In other configurations, methods for providing relief of vulvovaginal symptoms, treating the underlying pathophysiology or infection of the vulvovaginal anatomy, or prophylactically protecting the vulvovaginal anatomy in an individual, comprise administering to an individual a vulvovaginal composition consisting of a stable water-in-silicone emulsion, an emulsifier, a cell membrane fluidity-improving agent, a fatty acid, a preservative, and at least one of the following groups: a bioactive agent, a pH buffer system, a viscosity-improving agent, an antioxidant, a tocopherol, and an active agent.In still other configurations, methods for providing relief of vulvovaginal symptoms, treating underlying pathophysiology or infection of the vulvovaginal anatomy, or prophylactically protecting the vulvovaginal anatomy in an individual, may comprise administering to an individual a vulvovaginal composition consisting essentially of a stable silicone water emulsion, an emulsifier, a cell membrane fluidity enhancer, a fatty acid, a preservative and at least one of the following groups: a bioactive agent, a pH buffer system, a viscosity enhancer, an antioxidant, a tocopherol and an active agent. Dermatological Compositions.

[00162] Dermatological compositions are also provided herein. The dermatological compositions described herein may be used as a skin protectant or moisturizer. In other examples, the dermatological compositions may be used to treat or prevent eczema, psoriasis, plaque psoriasis, dry skin, cracked skin, rash, diaper rash, hives, poison ivy, skin pain, postherpetic neuralgia, burns, wound healing, skin infections, dermatitis, atopic dermatitis, acne, impetigo, melanoma, rosacea, skin Petition 870260042611, dated 06 / 05 / 2026, page 63 / 250 60 / 109 cracked, chapped lips or skin wrinkles. In some settings, dermatological compositions may be formulated as cosmetics, skin lotions, skin moisturizers or skin creams.

[00163] In some instances, the disclosed dermatological compositions may include a bioactive agent. Examples of contemplated bioactive agents include, but are not limited to, hyaluronic acid, cholesterol or any combination thereof.

[00164] In some examples, the disclosed dermatological composition may include an active agent. Exemplary active agents contemplated include, but are not limited to, antibiotics, antimicrobials, antifungals, antiseptics, local anesthetics, analgesics, anti-inflammatories, immunosuppressants, steroids, corticosteroids, calcineurin inhibitors, PDE4 inhibitors, salicylic acid, retinoids, antihistamines, benzoyl peroxide, and nanocrystalline silver.

[00165] Exemplary antibiotics include, but are not limited to, amoxicillin, doxycycline, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, sulfamethoxazole / trimethoprim, amoxicillin / clavulanate, and levofloxacin.Additional antibiotics include micacin, gentamicin, kanamycin, neomycin, netilmicin, tobramycin, paromomycin, streptomycin, spectinomycin (Bs), geldanamycin, herbimycin, rifaximin, loracarbef, ertapenem, doripenem, imipenem / cilastatin, meropenem, cefadroxil, cefazolin, cefradine, cefapirin, cephalothin, cephalexin, cefaclor, cefoxitin, cefotetan, cefamandole, roxithromycin, telithromycin, epiramycin, fidaxomicin, furazolidone, nitrofurantoin (Bs), linezolid, posizolid, radezolid, torezolid, ampicillin, azlocillin, dicloxacillin, flucloxacillin, mezlocillin, methicillin, nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, penicillin G, temocillin, ticarcillin, ampicillin / sulbactam, piperacillin / tazobactam, ticarcillin / clavulanate, bacitracin, colistin, polymyxin B, ciprofloxacin, enoxacin, gatifloxacin, gemifloxacin, levofloxacin, norfloxacin, ofloxacin, trovafloxacin, minoci. Petition 870260042611, dated 06 / 05 / 2026, page 64 / 250 61 / 109 cline, oxytetracycline, tetracycline, clofazimine, dapsone, capreomycin, cycloserinem pyrazinamide, rifampicin, rifabutin, rifapentine, streptomycin, metronidazole and mupirocin.

[00166] Exemplary antimicrobials include, but are not limited to, amoxicillin, doxycycline, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, sulfamethoxazole / trimethoprim, amoxicillin / clavulanate, and levofloxacin.

[00167] Exemplary antifungals include, but are not limited to, miconazole, clotrimazole, amphotericin B, ketoconazole, fluconazole, isavuconazole, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, and flucytosine.

[00168] Exemplary antiseptics include ethanol, sodium hypochlorite, chlorhexidine, hexachlorophene, povidone iodide, sodium hypochlorite, sodium hypochlorite, benzethonium chloride, triclosan, sodium oxychlorosene, benzalkonium chloride, and silver nitrate.

[00169] Exemplary local anesthetics include amylocaine, ambucaine, articaine, benzocaine, benzonatate, bupivacaine, butacaine, butanilicaine, chloroprocaine, cinchocaine (INN), cocaine, cyclomethicaine, dibucaine, diperodon, dimethocaine, eucaine, etidocaine, hexylcaine, fomocaine, fotocaine, hydroxyprocaine, isobucaine, levobupivacaine, lidocaine (lignocaine), mepivacaine. meprilcaine, metabutoxycaine, nitracaine, orthocaine, oxetacaine (oxetazaine), oxybuprocaine, paraethoxycaine, fenacaine, piperocaine, pyridocaine, pramocaine, prilocaine, primacaine, procaine, procainamide, proparacaine, propoxycaine, pyrrocaine, quinisocaine (INN), ropivacaine, trimecaine, tetracaine, tolicaine and tropacocaine.

[00170] Exemplary analgesics include codeine, fentanyl, hydrocodone (Hysingla, Zohydro), hydrocodone / acetaminophen (Lorcet, Lortab, Norco, Vicodin), hydromorphone (Dilaudid, Exalgo), meperidine (Demerol), methadone (Dolophine, Methadose), morphine (Kadian, MS Contin, Petition 870260042611, dated 06 / 05 / 2026, p. 65 / 250 62 / 109 Morphabond), oxycodone (OxyContin, Oxaydo), oxycodone and acetaminophen (Percocet, Roxicet), oxycodone and naloxone.

[00171] Exemplary anti-inflammatory drugs include celecoxib (Celebrex), diclofenac (Cambia, Cataflam, Voltaren-XR, Zipsor, Zorvolex), diflunisal (Dolobid), etodolac (Lodine), ibuprofen (Motrin, Advil), indomethacin (Indocin), ketoprofen (Active-Ketoprofen), ketorolac, nabumetone, naproxen (Aleve, Anaprox, Naprelan, Naprosyn), oxaprozin (Daypro), piroxicam (Feldene), salsalate, sulindac, and tolmetin.

[00172] Exemplary immunosuppressants include corticosteroids (e.g., prednisone (Deltasone, Orasone), budesonide (Entocort CE), prednisolone (Millipred)), Janus kinase inhibitors (e.g., tofacitinib (Xeljanz)), calcineurin inhibitors, e.g., cyclosporine (Neoral, Sandimmune, SangCya) and tacrolimus (Astagraf XL, Envarsus XR, Prograf), mTOR inhibitors, e.g., sirolimus (Rapamune) and everolimus (Afinitor, Zortress), IMDH inhibitors, e.g., azathioprine (Azasan, Imuran), leflunomide (Arava) and mycophenolate (CellCept, Myfortic), biologics,for example, abatacept (Orencia), adalimumabe (Humira), anakinra (Kineret), certolizumabe (Cimzia), etanercept (Enbrel), golimumabe (Simponi), infliximabe (Remicade), ixekizumab (Taltz), natalizumab (Tysabri), rituximabe (Rituximabe), sesentkinum, tocilizumab (Actemra), ustekinumab (Stelara), vedolizumabe (Entyvio), and monoclonal antibodies, for example, basiliximabe (Simulect), daclizumabe (Zinbryta) and muromonabe (Orthoclone OKT3).,

[00173] Calcineurin inhibitors include Astagraf XL, cyclosporine, ophthalmic cyclosporine, Elidel, Envarsus XR, Gengraf, Hecoria, Neoral, pimecrolimus, Prograf, Protopic, Restasis, Sandimmune, tacrolimus, and tacrolimus ointment.

[00174] Phosphodiesterase 4 (PDE4) inhibitors include adibendan, aminophylline, dehydrated aminophylline, amipizone, apremilast, arophylline, ati Petition 870260042611, of 06 / 05 / 2026, p. 66 / 250 63 / 109 zoram, befuralin, hidrocloridrato de Bemarinone, bemoradan, benafentrin, bucladesina, buflomedil, buquineran, CC-1088, carbazeran, catramilast, cilomilast, cilostamida, cilostazol, cipamfilina, crisaborole, daxalipram, denbufilina, dimabefilina, dindiprofilina, dipiridamol, doxofilina, drotaverine, difilina, enoximona, etamifilina, etofilina, filaminast, flufilina, fluprofilina, furafilina, imazodan, cloridrato de imazodan, inamrinona, lactato de inamrinona, isbufilina, lirimilast, lysofilina, lomifilina, medorinona, metescufilina, midaxifilina, milrinona, lactato de milrinona, motapizona, nanterinona, nestifilin, nitraquazona, oglemilast, oglemilast de sodium, olprinona, oxagrelate, oxtrifilin, papaverine, papaverine hydrochloride, papaverine sulphate, parogrelila, pelrinona hydrochloride, pentiphylline, pentoxiphilin, perbuphilin, piclamilast, pimephilin, pimobendan, piroximona, prinoxodan, proxiphilin, pumafentrine, quazinona, quazodine, revamilast, revizinona,roflumilast, rolipram, ronomilast, saterinone, senazodan, siguazodan, ceilingmilast, tofimilast, trapidil, vesnarinone and zardaverine.

[00175] In some configurations, the dermatological composition includes one or more active and / or bioactive agents. In some configurations, the dermatological composition includes two active agents, for example, lidocaine and clindamycin. In another example, the dermatological composition includes one active and one bioactive agent, for example, retinol and hyaluronic acid, respectively.

[00176] In configurations, the dermatological composition includes an active agent from about 0.0001% by weight to about 90% by weight of the composition, from about 0.0001% by weight to about 1% by weight, from about 0.0001% by weight to about 10% by weight, from about 0.0001% by weight to about 20% by weight, from about 0.0001% by weight to about 30% by weight, from about 0.0001% by weight to about 40% by weight, from about 0.0001% by weight to about 50% by weight, from about 0.0001% by weight to about 60% by weight Petition 870260042611, dated 06 / 05 / 2026, page 67 / 250 64 / 109 weight, from about 0.0001% by weight to about 70% by weight, from about 0.0001% by weight to about 80% by weight, from about 0.001% by weight to about 90% by weight of the composition, from about 0.001% by weight to about 1% by weight, from about 0.001% by weight to about 10% by weight, from about 0.001% by weight to about 20% by weight, from about 0.001% by weight to about 30% by weight, from about 0.001% by weight to about 40% by weight, from about 0.001% by weight to about 50% by weight, from about 0.001% by weight to about 60% by weight, from about 0.001% by weight to approximately 70% by weight, from approximately 0.001% by weight to approximately 80% by weight, from approximately 0.01% by weight to approximately 90% by weight of the composition, from approximately 0.01% by weight to approximately 1% by weight, from approximately 0.01% by weight to approximately 10% by weight, from approximately 0.01% by weight to approximately 20% by weight, from approximately 0.01% by weight to approximately 30% by weight, from approximately 0.01% by weight to approximately 40% by weight, from approximately 0,0.01% by weight to about 50% by weight, from about 0.01% by weight to about 60% by weight, from about 0.01% by weight to about 70% by weight, from about 0.01% by weight to about 80% by weight, from about 0.1% by weight to about 90% by weight of the composition, from about 0.1% by weight to about 1% by weight, from about 0.1% by weight to about 10% by weight, from about 0.1% by weight to about 20% by weight, from about 0.1% by weight to about 30% by weight, from about 0.1% by weight to about 40% by weight, from about 0.1% by weight to about 50% by weight, from about 0.1% by weight to about 60% by weight, from about 0.1% by weight to about 70% by weight, from about 0.1% by weight to about 80% by weight of the composition, and any range between these.

[00177] In settings, the dermatological composition includes a bioactive agent from about 0.0001% by weight to about 90% by weight. Petition 870260042611, dated 06 / 05 / 2026, page 68 / 250 65 / 109 weight of the composition, from about 0.0001% by weight to about 1% by weight, from about 0.0001% by weight to about 10% by weight, from about 0.0001% by weight to about 20% by weight, from about 0.0001% by weight to about 30% by weight, from about 0.0001% by weight to about 40% by weight, from about 0.0001% by weight to about 50% by weight, from about 0.0001% by weight to about 60% by weight, from about 0.0001% by weight to about 70% by weight, from about 0.0001% by weight to about 80% by weight, from about 0.001% by weight to about 90% by weight of the composition, from about 0.001% by weight to about 1% by weight, from about 0.001% by weight to about 10% by weight, from about 0.001% by weight to about 20% by weight, from about 0.001% by weight to about 30% by weight, from about 0.001% by weight to about 40% by weight, from about 0.001% by weight to about 50% by weight, from about 0.001% by weight to about 60% by weight, from about 0.001% by weight to about 70% by weight, from about 0,0.01% by weight to about 80% by weight, from about 0.01% by weight to about 90% by weight of the composition, from about 0.01% by weight to about 1% by weight, from about 0.01% by weight to about 10% by weight, from about 0.01% by weight to about 20% by weight, from about 0.01% by weight to about 30% by weight, from about 0.01% by weight to about 40% by weight, from about 0.01% by weight to about 50% by weight, from about 0.01% by weight to about 60% by weight, from about 0.01% by weight to about 70% by weight, from about 0.01% by weight to about 80% by weight, from about 0.1% by weight to about 90% by weight weight of the composition, from about 0.1% by weight to about 1% by weight, from about 0.1% by weight to about 10% by weight, from about 0.1% by weight to about 20% by weight, from about 0.1% by weight to about 30% by weight, from about 0.1% by weight to about 40% by weight, from about 0.1% by weight to about, Petition 870260042611, dated 06 / 05 / 2026, page 69 / 250 66 / 109 50% by weight, from about 0.1% by weight to about 60% by weight, from about 0.1% by weight to about 70% by weight, from about 0.1% by weight to about 80% by weight of the composition, and any range between these.

[00178] In configurations, the present disclosure includes a dermatological composition, including a cell membrane fluidity enhancer (for example, a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols or any combination thereof) and a preservative. Examples of preservatives include an antimicrobial preservative, for example, benzalkonium chloride, thimerosal, chlorhexidine, chlorobutanol, methylparaben, propylparaben, phenylethyl alcohol, disodium edetate, sorbic acid, benzoic acid, cetyl bromide, pyridinium cetyl chloride, benzyl bromide, EDTA, phenylmercury nitrate, phenylmercury acetate, thimerosal, merthiolate, phenylmercury acetate and borate, polymyxin B sulfate, methyl and propylparabens, quaternary ammonium chloride, sodium benzoate, potassium sorbate, sodium propionate and sodium perborate, or any combination thereof.

[00179] In configurations, preservatives may be used in appropriate amounts. For example, the preservative may be used in an amount of approximately 0.001% by weight - 1.0% by weight, based on the total weight of the composition.

[00180] In some settings, the dermatological composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof), has a pH of about 4.5 to about 6.5. In other settings, the pH is about 5.5.

[00181] In some examples, the dermatological composition, including an agent to improve cell membrane fluidity (e.g. Petition 870260042611, dated 06 / 05 / 2026, page 70 / 250 67 / 109 plo, a sterol (exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof), has an osmolarity of about 200 to about 500 mOsm / kg.

[00182] The dermatological composition must have a zero-rate viscosity, which is a resistant change over time and / or temperature. The terms viscous, viscosity, zero-rate viscosity, and the like, refer herein, in the usual and customary sense, to a measure of a material's resistance to deformation (e.g., liquid behavior) upon the application of a force (e.g., shear stress or tensile stress). The viscosity of emulsions may also depend on temperature, along with several other effects such as shear rate, average droplet size, and droplet size distribution. As described herein, viscosity may typically mean that the dermatological composition has a zero-rate viscosity of about 100 kPa.s to about 1000 kPa.s at 25°C.

[00183] In some examples, the dermatological composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has a zero-rate viscosity of about 100 kPa.s to about 1000 kPa.s at 25°C.

[00184] In some examples, the dermatological composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has rheological properties that have negligible variation with temperature between 25°C and 37°C.

[00185] As described herein, an example of a dermatological composition comprises ceramide. Petition 870260042611, dated 06 / 05 / 2026, page 71 / 250 68 / 109 Dermatological Methods

[00186] Methods are also provided here for providing relief of dermatological symptoms, treating the underlying pathophysiology or infection, or prophylactically protecting an individual, comprising administering to an individual any of the compositions disclosed herein.

[00187] In some settings, the methods for dermatological utility comprise treating or preventing conditions including, but not limited to, eczema, psoriasis, plaque psoriasis, dry skin, cracked skin, rash, diaper rash, hives, poison ivy, skin pain, postherpetic neuralgia, burns, wound healing, skin infections, dermatitis, atopic dermatitis, acne, impetigo, melanoma, rosacea, cracked skin, chapped lips, or skin wrinkles. In other examples of settings, the dermatological utility of the compositions disclosed herein provides that the compositions may be formulated as cosmetics, skin lotions, skin moisturizers, skin creams, or skin protectors. Rectal Compositions

[00188] Rectal compositions are also provided here. For example, the compositions can be used to treat or prevent hemorrhoids or anal fissures.

[00189] In some instances, the disclosed rectal compositions may include an active agent. Examples of contemplated active agents include, but are not limited to, vasoconstrictors, anti-inflammatory drugs, steroids, local anesthetics, alpha-adrenergic receptor agonists, onabotulinumtoxin A, calcium channel blockers, and nitrates.

[00190] In some configurations, the rectal composition includes one or more active agents. In some configurations, the rectal composition includes two active agents, for example, lidocaine and hydrocortisone. Petition 870260042611, dated 06 / 05 / 2026, page 72 / 250 69 / 109

[00191] In configurations, the rectal composition includes an active agent from about 0.0001% by weight to about 90% by weight of the composition, from about 0.0001% by weight to about 1% by weight, from about 0.0001% by weight to about 10% by weight, from about 0.0001% by weight to about 20% by weight, from about 0.0001% by weight to about 30% by weight, from about 0.0001% by weight to about 40% by weight, from about 0.0001% by weight to about 50% by weight, from about 0.0001% by weight to about 60% by weight, from about 0.0001% by weight to about 70% by weight, from about 0.0001% by weight to about 80% by weight weight, from about 0.001% by weight to about 90% by weight of the composition, from about 0.001% by weight to about 1% by weight, from about 0.001% by weight to about 10% by weight, from about 0.001% by weight to about 20% by weight, from about 0.001% by weight to about 30% by weight, from about 0.001% by weight to about 40% by weight, from about 0.001% by weight to about 50% by weight, from about 0,from about 0.001% by weight to about 60% by weight, from about 0.001% by weight to about 70% by weight, from about 0.001% by weight to about 80% by weight, from about 0.01% by weight to about 90% by weight of the composition, from about 0.01% by weight to about 1% by weight, from about 0.01% by weight to about 10% by weight, from about 0.01% by weight to about 20% by weight, from about 0.01% by weight to about 30% by weight, from about 0.01% by weight to about 40% by weight, from about 0.01% by weight to about 50% by weight, from about 0.01% by weight to about 60% by weight, from about 0.01% by weight to about 70% by weight, from about 0.01% by weight to about 80% by weight, from about 0.1% by weight to about 90% by weight of the composition, from about 0.1% by weight to about 1% by weight, from about 0.1% by weight to about 10% by weight, from about 0.1% by weight to about 20% by weight, from about 0.1% by weight to, Petition 870260042611, dated 06 / 05 / 2026, page 73 / 250 70 / 109 approximately 30% by weight, from approximately 0.1% by weight to approximately 40% by weight, from approximately 0.1% by weight to approximately 50% by weight, from approximately 0.1% by weight to approximately 60% by weight, from approximately 0.1% by weight to approximately 70% by weight, from approximately 0.1% by weight to approximately 80% by weight of the composition, and any range between these.

[00192] In configurations, the rectal composition includes a bioactive agent from about 0.0001% by weight to about 90% by weight of the composition, from about 0.0001% by weight to about 1% by weight, from about 0.0001% by weight to about 10% by weight, from about 0.0001% by weight to about 20% by weight, from about 0.0001% by weight to about 30% by weight, from about 0.0001% by weight to about 40% by weight, from about 0.0001% by weight to about 50% by weight, from about 0.0001% by weight to about 60% by weight, from about 0.0001% by weight to about 70% by weight, from about 0.0001% by weight to about 80% by weight, from about 0.001% by weight to about 90% by weight of the composition, from about 0.001% by weight to about 1% by weight, from about 0.001% by weight to about 10% by weight, from about 0.001% by weight to about 20% by weight, from about 0.001% by weight to about 30% by weight, from about 0.001% by weight to about 40% by weight, from about 0.001% by weight to about 50% by weight, from about 0,0.001% by weight to about 60% by weight, from about 0.001% by weight to about 70% by weight, from about 0.001% by weight to about 80% by weight, from about 0.01% by weight to about 90% by weight of the composition, from about 0.01% by weight to about 1% by weight, from about 0.01% by weight to about 10% by weight, from about 0.01% by weight to about 20% by weight, from about 0.01% by weight to about 30% by weight, from about 0.01% by weight to about 40% by weight, from about 0.01% by weight to about 50% by weight, from about 0.01% by weight to about 60% by weight, from about 0.01%, Petition 870260042611, dated 06 / 05 / 2026, page 74 / 250 71 / 109 by weight to about 70% by weight, from about 0.01% by weight to about 80% by weight, from about 0.1% by weight to about 90% by weight of the composition, from about 0.1% by weight to about 1% by weight, from about 0.1% by weight to about 10% by weight, from about 0.1% by weight to about 20% by weight, from about 0.1% by weight to about 30% by weight, from about 0.1% by weight to about 40% by weight, from about 0.1% by weight to about 50% by weight, from about 0.1% by weight to about 60% by weight, from about 0.1% by weight to about 70% by weight, from about 0.1% by weight to about 80% by weight of the composition and any range between these.

[00193] In configurations, the present disclosure includes a rectal composition comprising a cell membrane fluidity enhancer (for example, a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols or any combination thereof) and a preservative. Examples of preservatives include an antimicrobial preservative, for example, benzalkonium chloride, thimerosal, chlorhexidine, chlorobutanol, methylparaben, propylparaben, phenylethyl alcohol, disodium edetate, sorbic acid, benzoic acid, cetyl bromide, pyridinium cetyl chloride, benzyl bromide, EDTA, phenylmercury nitrate, phenylmercury acetate, thimerosal, merthiolate, phenylmercury acetate and borate, polymyxin B sulfate, methyl and propylparabens, quaternary ammonium chloride, sodium benzoate, potassium sorbate, sodium propionate and sodium perborate, or any combination thereof.

[00194] In configurations, preservatives may be used in any suitable amounts. For example, the preservative may be used in an amount of approximately 0.001% by weight to 1.0% by weight, based on the total weight of the composition.

[00195] In settings, the rectal composition, including a cell membrane fluidity enhancer (e.g., a sterol, Petition 870260042611, dated 06 / 05 / 2026, page 75 / 250 72 / 109 (in which exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof), has a pH of about 7 to about 8. In other configurations, the pH is about 7.4.

[00196] In some examples, the rectal composition, including a cell membrane fluidity enhancer (e.g., a sterol, where exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has an osmolarity of about 200 to about 500 mOsm / kg.

[00197] The rectal composition must have a zero-rate viscosity that is a resistant change over time and / or temperature. The terms viscous, viscosity, zero-rate viscosity, and the like, refer herein, in the usual and customary sense, to a measure of a material's resistance to deformation (e.g., liquid behavior) upon the application of a force (e.g., shear stress or tensile stress). The viscosity of emulsions may also depend on temperature, along with several other effects such as shear rate, average droplet size, and droplet size distribution. As described herein, viscosity may typically mean that the rectal composition has a zero-rate viscosity of about 50 kPa.s to about 1000 kPa.s at 25°C.

[00198] In some examples, the rectal composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has a zero-rate viscosity of about 50 kPa.s to about 1000 kPa.s at 25°C.

[00199] In some examples, the rectal composition, including a cell membrane fluidity enhancer (e.g., a sterol, where exemplary sterols include cholesterol, derivatives of Petition 870260042611, dated 06 / 05 / 2026, p. 76 / 250 73 / 109 cholesterol, phytosterols, or any combination thereof) has rheological properties that vary negligibly with temperature between 25°C and 37°C. Rectal methods

[00200] Methods are also provided here for providing relief of rectal symptoms, treating the underlying pathophysiology or infection in an individual, comprising administering to an individual any of the compositions disclosed herein.

[00201] In some settings, methods for rectal utility include treating conditions including, but not limited to, hemorrhoids and anal fissures. Sunscreen Compositions

[00202] Sunscreen compositions are also provided herein. For example, the compositions can be used to treat or prevent sun damage (e.g., damage caused by ultraviolet radiation). The regulation of skin darkening resulting from exposure to ultraviolet light can be achieved using the compositions described herein. Useful sunscreens include, for example, zinc oxide and titanium dioxide. Ultraviolet light is a predominant cause of skin darkening.

[00203] In configurations, sunscreen compositions may include an active agent. Exemplary active agents (e.g., UV absorbing agents) in the sunscreen compositions described herein include, but are not limited to, zinc oxide, titanium dioxide, oxybenzone, avobenzone, octisalate, octocrylene, octinoxate homosalate, and para-aminobenzoic acid (e.g., PABA).

[00204] In some embodiments, the sunscreen composition includes one or more active agents capable of absorbing UV radiation. In some embodiments, the sunscreen composition includes two active agents, for example, zinc oxide and oxybenzone. Petition 870260042611, dated 06 / 05 / 2026, page 77 / 250 74 / 109

[00205] In configurations, the sunscreen composition includes an active agent from about 0.0001% by weight to about 90% by weight of the composition, from about 0.0001% by weight to about 1% by weight, from about 0.0001% by weight to about 10% by weight, from about 0.0001% by weight to about 20% by weight, from about 0.0001% by weight to about 30% by weight, from about 0.0001% by weight to about 40% by weight, from about 0.0001% by weight to about 50% by weight, from about 0.0001% by weight to about 60% by weight, from about 0.0001% by weight to about 70% by weight, from about 0.0001% by weight to about 80% by weight, from about 0.001% by weight to about 90% by weight of the composition, from about 0.001% by weight to about 1% by weight, from about 0.001% by weight to about 10% by weight, from about 0.001% by weight to about 20% by weight, from about 0.001% by weight to about 30% by weight, from about 0.001% by weight to about 40% by weight, from about 0.001% by weight to about 50% by weight,from about 0.001% by weight to about 60% by weight, from about 0.001% by weight to about 70% by weight, from about 0.001% by weight to about 80% by weight, from about 0.01% by weight to about 90% by weight of the composition, from about 0.01% by weight to about 1% by weight, from about 0.01% by weight to about 10% by weight, from about 0.01% by weight to about 20% by weight, from about 0.01% by weight to about 30% by weight, from about 0.01% by weight to about 40% by weight, from about 0.01% by weight to about 50% by weight, from about 0.01% by weight to about 60% by weight, from about 0.01% by weight weight to about 70% by weight, from about 0.01% by weight to about 80% by weight, from about 0.1% by weight to about 90% by weight of the composition, from about 0.1% by weight to about 1% by weight, from about 0.1% by weight to about 10% by weight, from about 0.1% by weight to about 20% by weight, from about 0.1%, Petition 870260042611, dated 06 / 05 / 2026, page 78 / 250 75 / 109 by weight to about 30% by weight, from about 0.1% by weight to about 40% by weight, from about 0.1% by weight to about 50% by weight, from about 0.1% by weight to about 60% by weight, from about 0.1% by weight to about 70% by weight, from about 0.1% by weight to about 80% by weight of the composition and any range in between.

[00206] In configurations, the sunscreen composition includes a bioactive agent from about 0.0001% by weight to about 90% by weight of the composition, from about 0.0001% by weight to about 1% by weight, from about 0.0001% by weight to about 10% by weight, from about 0.0001% by weight to about 20% by weight, from about 0.0001% by weight to about 30% by weight, from about 0.0001% by weight to about 40% by weight, from about 0.0001% by weight to about 50% by weight, from about 0.0001% by weight to about 60% by weight, from about 0.0001% by weight to about 70% by weight, from about 0.0001% by weight to about 80% by weight, from about 0.001% by weight to about 90% by weight of the composition, from about 0.001% by weight to about 1% by weight, from about 0.001% by weight to about 10% by weight, from about 0.001% by weight to about 20% by weight, from about 0.001% by weight to about 30% by weight, from about 0.001% by weight to about 40% by weight, from about 0.001% by weight to about 50% by weight,from about 0.001% by weight to about 60% by weight, from about 0.001% by weight to about 70% by weight, from about 0.001% by weight to about 80% by weight, from about 0.01% by weight to about 90% by weight of the composition, from about 0.01% by weight to about 1% by weight, from about 0.01% by weight to about 10% by weight, from about 0.01% by weight to about 20% by weight, from about 0.01% by weight to about 30% by weight, from about 0.01% by weight to about 40% by weight, from about 0.01% by weight to about 50% by weight, from about 0.01% by weight to about 60% by weight, from, Petition 870260042611, dated 06 / 05 / 2026, page 79 / 250 76 / 109 approximately 0.01% by weight to approximately 70% by weight, from approximately 0.01% by weight to approximately 80% by weight, from approximately 0.1% by weight to approximately 90% by weight of the composition, from approximately 0.1% by weight to approximately 1% by weight, from approximately 0.1% by weight to approximately 10% by weight, from approximately 0.1% by weight to approximately 20% by weight, from approximately 0.1% by weight to approximately 30% by weight, from approximately 0.1% by weight to approximately 40% by weight, from approximately 0.1% by weight to approximately 50% by weight, from approximately 0.1% by weight to approximately 60% by weight, from approximately 0.1% by weight to approximately 70% by weight, from approximately 0.1% by weight to approximately 80% by weight of the composition and any range in between.

[00207] In configurations, the present disclosure includes a sunscreen composition comprising a cell membrane fluidity enhancer (for example, a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols or any combination thereof) and a preservative. Examples of preservatives include an antimicrobial preservative, for example, benzalkonium chloride, thimerosal, chlorhexidine, chlorobutanol, methylparaben, propylparaben, phenylethyl alcohol, disodium edetate, sorbic acid, benzoic acid, cetyl bromide, pyridinium cetyl chloride, benzyl bromide, EDTA, phenylmercury nitrate, phenylmercury acetate, thimerosal, merthiolate, phenylmercury acetate and borate, polymyxin B sulfate, methyl and propylparabens, quaternary ammonium chloride, sodium benzoate, potassium sorbate, sodium propionate and sodium perborate, or any combination thereof.

[00208] In configurations, preservatives may be used in any suitable amounts. For example, the preservative may be used in an amount of approximately 0.001% by weight to 1.0% by weight, based on the total weight of the composition.

[00209] In settings, the composition of sunscreen, including Petition 870260042611, dated 06 / 05 / 2026, page 80 / 250 77 / 109 of a cell membrane fluidity-enhancing agent (e.g., a sterol, where exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof), has a pH of about 4.5 to about 6.5. In other settings, the pH is about 5.5.

[00210] In some examples, the sunscreen composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has an osmolarity of about 200 to about 500 mOsm / kg.

[00211] The sunscreen composition must have a zero-rate viscosity that is a resistant change over time and / or temperature. The terms viscous, viscosity, zero-rate viscosity, and the like, refer herein, in the usual and customary sense, to a measure of a material's resistance to deformation (e.g., liquid behavior) upon the application of a force (e.g., shear stress or tensile stress). The viscosity of emulsions may also depend on temperature, along with several other effects such as shear rate, average droplet size, and droplet size distribution. As described herein, viscosity may typically mean that the sunscreen composition has a zero-rate viscosity of about 100 kPa.s to about 1000 kPa.s at 25°C.

[00212] In some examples, the sunscreen composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has a zero-rate viscosity of about 50 kPa.s to about 1000 kPa.s at 25°C.

[00213] In some examples, the composition of sunscreen includes Petition 870260042611, dated 06 / 05 / 2026, page 81 / 250 78 / 109 going an agent that improves cell membrane fluidity (for example, a sterol, where exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has rheological properties that have negligible variation with temperature between 25°C and 37°C. Sunscreen Methods

[00214] Methods are also provided here for prophylactically protecting an individual from UV damage comprising administering to the individual any of the compositions disclosed herein.

[00215] In some settings, the methods for utility as a sunscreen comprise treating or preventing conditions including, but not limited to, UV damage (e.g., sun damage) in an individual. For this purpose, as described herein, the compositions may be used to protect against or treat exposure to UVA and / or UVB. Transdermal drug delivery compositions

[00216] Also provided here are compositions for transdermal drug delivery. Transdermal drug delivery works well for high-potency drugs (e.g., oral dosage less than 10 mg) used to treat subchronic and chronic indications. Transdermal drug delivery offers a desirable route of administration as it avoids first-pass, hepatic circulation, and release. For example, the compositions can be used to treat or prevent pain, diabetes, neurological diseases or disorders, hormonal deficiency, or nausea.

[00217] In some instances, disclosed transdermal drug delivery compositions may include a bioactive agent. Examples of contemplated bioactive agents include, but are not limited to, serine proteases, chemical penetration enhancers, cholesterol, or any combination thereof. Petition 870260042611, dated 06 / 05 / 2026, page 82 / 250 79 / 109

[00218] In some examples, the disclosed transdermal drug delivery composition may include an active agent. Exemplary active agents contemplated include, but are not limited to, analgesics, local anesthetics, hormones, steroids, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase 4 (DDP-4) inhibitors, insulins, selective sodium-glucose transporter-2 (SGLT-2) inhibitors, antidepressants, anticonvulsants, antipsychotics, antiparkinsonian drugs, and antiemetics.

[00219] In some configurations, the transdermal drug delivery composition includes one or more active and / or bioactive agents. In some configurations, the transdermal drug delivery composition includes two active agents, for example, estrogen and progesterone. In other examples, the transdermal drug delivery composition includes one active agent and one bioactive agent, such as testosterone and serine protease, respectively.

[00220] In configurations, the transdermal drug delivery composition includes an active agent from about 0.0001% by weight to about 90% by weight of the composition, from about 0.0001% by weight to about 1% by weight, from about 0.0001% by weight to about 10% by weight, from about 0.0001% by weight to about 20% by weight, from about 0.0001% by weight to about 30% by weight, from about 0.0001% by weight to about 40% by weight, from about 0.0001% by weight to about 50% by weight, from about 0.0001% by weight to about 60% by weight, from about 0.0001% by weight to about 70% by weight, from about 0.0001% by weight to about from about 80% by weight, from about 0.001% by weight to about 90% by weight of the composition, from about 0.001% by weight to about 1% by weight, from about 0.001% by weight to about 10% by weight, from about Petition 870260042611, dated 06 / 05 / 2026, page 83 / 250 80 / 109 0.001% by weight to about 20% by weight, from about 0.001% by weight to about 30% by weight, from about 0.001% by weight to about 40% by weight, from about 0.001% by weight to about 50% by weight, from about 0.001% by weight to about 60% by weight, from about 0.001% by weight to about 70% by weight, from about 0.001% by weight to about 80% by weight, from about 0.01% by weight to about 90% by weight of the composition, from about 0.01% by weight to about 1% by weight, from about 0.01% by weight to about 10% by weight, from about 0.01% by weight to about 20% by weight, from about 0.01% by weight to about 30% by weight, from about 0.01% by weight to about 40% by weight, from about 0.01% by weight to about 50% by weight, from about 0.01% by weight to about 60% by weight, from about 0.01% by weight to about 70% by weight, from about 0.01% by weight to about 80% by weight, from about 0.1% by weight to about 90% by weight of the composition, from about 0.1% by weight to about 1% by weight,from about 0.1% by weight to about 10% by weight, from about 0.1% by weight to about 20% by weight, from about 0.1% by weight to about 30% by weight, from about 0.1% by weight to about 40% by weight, from about 0.1% by weight to about 50% by weight, from about 0.1% by weight to about 60% by weight, from about 0.1% by weight to about 70% by weight, from about 0.1% by weight to about 80% by weight of the composition and any range in between.

[00221] In configurations, the transdermal drug delivery composition includes a bioactive agent comprising approximately 0.0001% by weight to approximately 90% by weight of the composition, approximately 0.0001% by weight to approximately 1% by weight, approximately 0.0001% by weight to approximately 10% by weight, approximately 0.0001% by weight to approximately 20% by weight, approximately 0.0001% by weight to approximately 30% by weight, approximately 0.0001% by weight to approximately 40% by weight, approximately Petition 870260042611, dated 06 / 05 / 2026, page 84 / 250 81 / 109 0.0001% by weight to about 50% by weight, from about 0.0001% by weight to about 60% by weight, from about 0.0001% by weight to about 70% by weight, from about 0.0001% by weight to about 80% by weight, from about 0.001% by weight to about 90% by weight of the composition, from about 0.001% by weight to about 1% by weight, from about 0.001% by weight to about 10% by weight, from about 0.001% by weight to about 20% by weight, from about 0.001% by weight to about 30% by weight, from about 0.001% by weight to about 40% by weight, from about 0.001% by weight to about 50% by weight, from about from 0.001% by weight to about 60% by weight, from about 0.001% by weight to about 70% by weight, from about 0.001% by weight to about 80% by weight, from about 0.01% by weight to about 90% by weight of the composition, from about 0.01% by weight to about 1% by weight, from about 0.01% by weight to about 10% by weight, from about 0.01% by weight to about 20% by weight, from about 0.01% by weight to about 30% by weight,from about 0.01% by weight to about 40% by weight, from about 0.01% by weight to about 50% by weight, from about 0.01% by weight to about 60% by weight, from about 0.01% by weight to about 70% by weight, from about 0.01% by weight to about 80% by weight, from about 0.1% by weight to about 90% by weight of the composition, from about 0.1% by weight to about 1% by weight, from about 0.1% by weight to about 10% by weight, from about 0.1% by weight to about 20% by weight, from about 0.1% by weight to about 30% by weight, from about 0.1% by weight to about 40% by weight, from about 0.1% by weight to about 50% by weight, from about 0.1% by weight to about 60% by weight, from about 0.1% by weight to about 70% by weight, from about 0.1% by weight to about 80% by weight of the composition, and any range between these.

[00222] In settings, this disclosure includes a with Petition 870260042611, dated 06 / 05 / 2026, page 85 / 250 82 / 109 transdermal delivery position of a medicine including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols or any combination thereof) and a preservative. Examples of preservatives include an antimicrobial preservative, for example, benzalkonium chloride, thimerosal, chlorhexidine, chlorobutanol, methylparaben, propylparaben, phenylethyl alcohol, disodium edetate, sorbic acid, benzoic acid, cetyl bromide, pyridinium cetyl chloride, benzyl bromide, EDTA, phenylmercury nitrate, phenylmercury acetate, thimerosal, merthiolate, phenylmercury acetate and borate, polymyxin B sulfate, methyl and propylparabens, quaternary ammonium chloride, sodium benzoate, potassium sorbate, sodium propionate and sodium perborate, or any combination thereof.

[00223] In configurations, preservatives may be used in any suitable amounts. For example, the preservative may be used in an amount of approximately 0.001% by weight to 1.0% by weight, based on the total weight of the composition.

[00224] In some configurations, the transdermal drug delivery composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof), has a pH of about 4.5 to about 6.5. In other configurations, the pH is about 5.5.

[00225] In some examples, the transdermal drug delivery composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has an osmolarity of about 200 to about 500 mOsm / kg.

[00226] Transdermal drug delivery composition Petition 870260042611, dated 06 / 05 / 2026, p. 86 / 250 83 / 109 must have a zero-rate viscosity, which is a resistant change over time and / or temperature. The terms viscous, viscosity, zero-rate viscosity, and the like, refer here, in the usual and customary sense, to a measure of a material's resistance to deformation (e.g., liquid behavior) upon the application of a force (e.g., shear stress or tensile stress). The viscosity of emulsions may also depend on temperature, along with several other effects such as shear rate, average droplet size, and droplet size distribution. As described here, viscosity may typically mean that the transdermal drug delivery composition has a zero-rate viscosity of about 100 kPa.s to about 1000 kPa.s at 25°C.

[00227] In some examples, the transdermal drug delivery composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has a zero-rate viscosity of about 100 kPa.s to about 1000 kPa.s at 25°C.

[00228] In some examples, the transdermal drug delivery composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has rheological properties that have negligible variation with temperature between 25°C and 37°C. Transdermal Methods

[00229] Methods are also provided here for providing a transdermal drug delivery system, the method comprising administering to an individual any of the compositions disclosed herein. Petition 870260042611, dated 06 / 05 / 2026, page 87 / 250 84 / 109

[00230] In some settings, the methods for a transdermal drug delivery system comprise treating or preventing conditions, including but not limited to pain, diabetes, neurological disorders or diseases, hormonal deficiency, or nausea. Ophthalmic Compositions

[00231] Ophthalmic compositions are also provided herein. The ophthalmic compositions described herein may be used to treat or prevent ocular surface disorders, ophthalmic diseases, ophthalmic disorders, and the like, which include, but are not limited to, dry eyes, styes, epithelial defects, retinal detachment, conjunctivitis (such as viral conjunctivitis, bacterial conjunctivitis, or allergic conjunctivitis), superior limbal keratoconjunctivitis, keratoconjunctivitis sicca, eurotrophic keratopathy, Sjögren's syndrome, ocular cicatricial pemphigoid (OCP), drug-induced conjunctivitis, corneal ulcerations and erosions, and macular degeneration. Furthermore, ophthalmic composites can be used before or after eye surgery, including, for example, retinal surgery, penetrating keratoplasty, and laser-assisted refractive surgery in situ keratomileusis (LASIK), laser epithelial keratomileusis (LASEK), or photorefractive keratectomy (PRK).

[00232] As used herein, the term ophthalmic composition refers to a composition intended for application to the eye or its related or surrounding tissues, such as, for example, the eyelid or onto the cornea. The term also includes compositions intended to therapeutically treat conditions of the eye itself or the tissues surrounding the eye. The ophthalmic composition may be applied topically or by other techniques known to persons skilled in the art, such as injection into the eye. Examples of suitable topical administration to the eyes include administration of eye drops and spray formulations. Another suitable route of topical administration is by subcutaneous injection. Petition 870260042611, dated 06 / 05 / 2026, page 88 / 250 85 / 109 conjunctival. The compositions may also be provided to the eye periocularly or retro-orbitally.

[00233] In some examples, the disclosed ophthalmic composition may include an active agent. Exemplary active agents contemplated include, but are not limited to, antibiotics, antimicrobials, antivirals, antiseptics, local anesthetics, antihistamines, vasoconstrictors, analgesics, anti-inflammatories, immunosuppressants, immunostimulants, immunomodulators, steroids, and corticosteroids.

[00234] In some configurations, the ophthalmic composition includes one or more active agents. For example, the ophthalmic composition includes a vasoconstrictor and an antihistamine, for example, naphazoline and pheniramine.

[00235] In configurations, the ophthalmic composition includes an active agent from about 0.0001% by weight to about 90% by weight of the composition, from about 0.0001% by weight to about 1% by weight, from about 0.0001% by weight to about 10% by weight, from about 0.0001% by weight to about 20% by weight, from about 0.0001% by weight to about 30% by weight, from about 0.0001% by weight to about 40% by weight, from about 0.0001% by weight to about 50% by weight, from about 0.0001% by weight to about 60% by weight, from about 0.0001% by weight to about 70% by weight, from about 0.0001% by weight to about 80% by weight, from about 0.001% by weight to about 90% by weight of the composition, from about 0.001% by weight to about 1% by weight, from about 0.001% by weight to about 10% by weight, from about 0.001% by weight to about 20% by weight, from about 0.001% by weight to about 30% by weight, from about 0.001% by weight to about 40% by weight, from about 0.001% by weight to about 50% by weight, from about 0,from about 0.001% by weight to about 60% by weight, from about 0.001% by weight to about 70% by weight, from about 0.001% by weight to about 80% by weight, Petition 870260042611, dated 06 / 05 / 2026, page 89 / 250 86 / 109 weight, from about 0.01% by weight to about 90% by weight of the composition, from about 0.01% by weight to about 1% by weight, from about 0.01% by weight to about 10% by weight, from about 0.01% by weight to about 20% by weight, from about 0.01% by weight to about 30% by weight, from about 0.01% by weight to about 40% by weight, from about 0.01% by weight to about 50% by weight, from about 0.01% by weight to about 60% by weight, from about 0.01% by weight to about 70% by weight, from about 0.01% by weight to about 80% by weight, from about 0.1% by weight to about 90% by weight of the composition, from about 0.1% by weight to about 1% by weight, from about 0.1% by weight to about 10% by weight, from about 0.1% by weight to about 20% by weight, from about 0.1% by weight to about 30% by weight, from about 0.1% by weight to about 40% by weight, from about 0.1% by weight to about 50% by weight, from about 0.1% by weight to about 60% by weight, from about 0.1% by weight to about 70% by weight,from about 0.1% by weight to about 80% by weight of the composition and any range in between.

[00236] In configurations, the ophthalmic composition includes a bioactive agent from about 0.0001% by weight to about 90% by weight of the composition, from about 0.0001% by weight to about 1% by weight, from about 0.0001% by weight to about 10% by weight, from about 0.0001% by weight to about 20% by weight, from about 0.0001% by weight to about 30% by weight, from about 0.0001% by weight to about 40% by weight, from about 0.0001% by weight to about 50% by weight, from about 0.0001% by weight to about 60% by weight, from about 0.0001% by weight to about 70% by weight, from about 0.0001% by weight to about 80% by weight, from about 0.001% by weight to about 90% by weight of the composition, from about 0.001% by weight to about 1% by weight, from about 0.001% by weight to about 10% by weight, from about 0.001% by weight to about Petition 870260042611, dated 06 / 05 / 2026, page 90 / 250 87 / 109 of 20% by weight, from about 0.001% by weight to about 30% by weight, from about 0.001% by weight to about 40% by weight, from about 0.001% by weight to about 50% by weight, from about 0.001% by weight to about 60% by weight, from about 0.001% by weight to about 70% by weight, from about 0.001% by weight to about 80% by weight, from about 0.01% by weight to about 90% by weight of the composition, from about 0.01% by weight to about 1% by weight, from about 0.01% by weight to about 10% by weight, from about 0.01% by weight to about 20% by weight, from about 0.01% by weight to about from about 30% by weight, from about 0.01% by weight to about 40% by weight, from about 0.01% by weight to about 50% by weight, from about 0.01% by weight to about 60% by weight, from about 0.01% by weight to about 70% by weight, from about 0.01% by weight to about 80% by weight, from about 0.1% by weight to about 90% by weight of the composition, from about 0.1% by weight to about 1% by weight, from about 0,1% by weight to about 10% by weight, from about 0.1% by weight to about 20% by weight, from about 0.1% by weight to about 30% by weight, from about 0.1% by weight to about 40% by weight, from about 0.1% by weight to about 50% by weight, from about 0.1% by weight to about 60% by weight, from about 0.1% by weight to about 70% by weight, from about 0.1% by weight to about 80% by weight of the composition, and any range between these.

[00237] In configurations, the present disclosure includes an ophthalmic composition comprising a cell membrane fluidity enhancer (for example, a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols or any combination thereof) and a preservative. Examples of preservatives include an antimicrobial preservative, for example, benzalkonium chloride, thimerosal, chlorhexidine, chlorobutanol, methylparaben, propylparaben, phenylethyl alcohol, disodium edetate, sorbic acid, benzyl acid Petition 870260042611, dated 06 / 05 / 2026, page 91 / 250 88 / 109 zoic acid, cetyl bromide, cetyl pyridinium chloride, benzyl bromide, EDTA, phenylmercury nitrate, phenylmercury acetate, thimerosal, merthiolate, phenylmercury acetate and borate, polymyxin B sulfate, methyl and propyl parabens, quaternary ammonium chloride, sodium benzoate, potassium sorbate, sodium propionate and sodium perborate, or any combination thereof.

[00238] In configurations, preservatives may be used in any suitable amounts. For example, the preservative may be used in an amount of approximately 0.001% by weight to 1.0% by weight, based on the total weight of the composition.

[00239] In some settings, the transdermal drug delivery composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof), has a pH of about 7 to about 7.4 (e.g., neutral pH or physiological pH). In other settings, the pH is about 7.

[00240] In some examples, the ophthalmic composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has an osmolarity of about 200 to about 500 mOsm / kg.

[00241] The ophthalmic composition must have a zero-rate viscosity, which is a resistant change over time and / or temperature. The terms viscous, viscosity, zero-rate viscosity, and the like, refer here, in the usual and customary sense, to a measure of a material's resistance to deformation (e.g., liquid behavior) upon the application of a force (e.g., shear stress or tensile stress). The viscosity of emulsions may also be temperature-dependent, along with Petition 870260042611, dated 06 / 05 / 2026, p. 92 / 250 89 / 109 with several other effects, such as shear rate, average droplet size, and droplet size distribution. As described here, viscosity can typically mean that the ophthalmic composition has a zero-rate viscosity of about 100 kPa.s to about 1000 kPa.s at 25°C.

[00242] In some examples, the ophthalmic composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has a zero-rate viscosity of about 100 kPa.s to about 1000 kPa.s at 25°C.

[00243] In some examples, the ophthalmic composition, including a cell membrane fluidity enhancer (e.g., a sterol, wherein exemplary sterols include cholesterol, cholesterol derivatives, phytosterols, or any combination thereof) has rheological properties that have negligible variation with temperature between 25°C and 37°C. Ophthalmic Methods

[00244] Methods are also provided herein for providing relief of ophthalmic symptoms, treating underlying pathophysiology or infection, or prophylactically protecting an individual, comprising administering to an individual the compositions disclosed herein. In settings, the methods for ophthalmic utility comprise treating or preventing conditions including, but not limited to, ocular surface disorders, ophthalmic diseases, ophthalmic disorders, and the like, which include, but are not limited to, dry eyes, styes, epithelial defects, retinal detachment, conjunctivitis (such as, for example, viral conjunctivitis, bacterial conjunctivitis, or allergic conjunctivitis), superior limbal keratoconjunctivitis, keratoconjunctivitis sicca, eurotrophic keratopathy, Sjögren's syndrome, ocular cicatricial pemphigoid (OCP), medial conjunctivitis Petition 870260042611, dated 06 / 05 / 2026, page 93 / 250 90 / 109 corneal ulcers and erosions, and macular degeneration. Furthermore, the ophthalmic compositions can be used before or after eye surgery, including, for example, retinal surgery, penetrating keratoplasty, and laser-assisted refractive surgery in situ keratomileusis (LASIK), laser epithelial keratomileusis (LASEK), or photorefractive keratectomy (PRK). In other exemplary configurations, the ophthalmic utility of the disclosed compositions provides that the compositions can be formulated as a solution, a suspension, a semisolid, an emulsion, a semiliquid, an ointment, or a sustained-release / controlled-release vehicle. For example, the composition can be in the form of a contact lens solution, eye drops, ophthalmic ointment, and the like.

[00245] In settings, the method of treating ophthalmic conditions includes treating dry eye associated with or resulting from treating inflammation of the eye surface, lacrimal gland, or conjunctiva; dry eye associated with any disease process that alters the components of tears; dry eye associated with an increase in the eye surface, such as in thyroid disease when the eye protrudes forward; and / or dry eye associated with cosmetic surgery, for example, if the eyelids are opened too widely during surgery.

[00246] In settings, the method of treating ophthalmic conditions includes alleviating a symptom, including: burning or stinging of the eye; a gritty or irritating sensation as if something were in the eye; episodes of excessive tearing after periods of very dry eyes; a stringy discharge from the eye; eye pain and redness; episodes of blurred vision; heavy eyelids; inability to cry when emotionally stressed; uncomfortable contact lenses; decreased tolerance to reading, computer work, or any activity requiring sustained visual attention; and / or Petition 870260042611, dated 06 / 05 / 2026, page 94 / 250 91 / 109 eye strain. ADDITIONAL APPLICATIONS

[00247] The compositions, as described herein, can also be formulated for a variety of industrial applications, including, but not limited to, providing lubrication, protection or hydration of the surfaces to which they are applied.

[00248] For example, the compositions of the present invention have many applications in areas such as motorsports and motor racing applications; boat applications; agricultural applications; garage / workshop applications; hobby and craft applications; and home and garden applications. For example, the composition can be used to provide a protective coating on metal objects to prevent rust formation; to provide lubrication upon contact with metal parts; to clean and lubricate moving parts; to lubricate and penetrate stuck objects; to clean and lubricate tools, saws and blades; to restore or polish a surface (after physical-chemical change to the surface). Exemplary surfaces include wood, porcelain, enamel, tile, stainless steel, fiberglass, chrome and rubber. KITS

[00249] Kits are also provided here for a composition for symptom relief, treating the underlying pathophysiology or infection of the anatomy associated with the condition, or prophylactically protecting the anatomy in an individual. In some configurations, the kit comprises a stable water-in-silicone emulsion and a cell membrane fluidity enhancer. In other configurations, the kit also includes an emulsifier, a fatty acid, a preservative, and at least one of the group of a bioactive agent, a pH buffer system, a viscosity enhancer, an antioxidant, a tocopherol, a ceramide or an active agent, and instructions for the production of the Petition 870260042611, dated 06 / 05 / 2026, page 95 / 250 92 / 109 composition. The instructions may describe the steps and reagents for producing the composition by emulsification. Such steps and reagents may conform to those disclosed in this patent application for emulsification.

[00250] In this application, kits are provided for producing a vulvovaginal composition to provide relief of vulvovaginal symptoms, treat underlying pathophysiology or infection of the vulvovaginal anatomy, or prophylactically protect the vulvovaginal anatomy in an individual; the kit comprising, consisting of, or essentially consisting of a stable water-in-silicone emulsion, an emulsifier, a cell membrane fluidity enhancer, a fatty acid, a preservative, and at least one of the following groups: a bioactive agent, a pH buffer system, a viscosity enhancer, an antioxidant, a tocopherol, and an active agent, and instructions for producing the vulvovaginal composition. The instructions may describe the steps and reagents for producing the vulvovaginal composition by emulsification. Such steps and reagents may conform to those disclosed in this patent application for emulsification.

[00251] Dermatological kits comprising the compositions described herein are also provided herein. The dermatological kits provided herein are for treating or preventing conditions including, but not limited to, eczema, psoriasis, plaque psoriasis, dry skin, cracked skin, rash, diaper rash, hives, poison ivy, skin pain, postherpetic neuralgia, burns, wound healing, skin infections, dermatitis, atopic dermatitis, acne, impetigo, melanoma, rosacea, cracked skin, chapped lips, or skin wrinkles. In some exemplary configurations, the dermatological kits of the described compositions provide that the compositions of the kits can be formulated as cosmetics, skin lotions, skin moisturizers, or skin creams.

[00252] In other examples, kits are also provided herein re Petition 870260042611, dated 06 / 05 / 2026, p. 96 / 250 93 / 109 comprising the compositions described herein. The rectal kits provided herein are for treating or preventing conditions including, but not limited to, hemorrhoids or anal fissures.

[00253] In other examples, sunscreen kits comprising the compositions described herein are also provided herein. The sunscreen kits provided herein are for treating or preventing conditions, including but not limited to UV damage (e.g., sun damage).

[00254] In other examples, transdermal drug delivery system kits comprising the compositions described herein are also provided herein. The transdermal drug delivery system kits provided herein are for treating or preventing conditions including, but not limited to, pain, diabetes, neurological disorders or diseases, hormonal deficiency or nausea.

[00255] In other examples, ophthalmic kits comprising the compositions described herein are also provided herein. The ophthalmic kits provided herein are for treating or preventing conditions, including, but not limited to, ocular surface disorders, ophthalmic diseases, ophthalmic disorders and the like. EXAMPLES

[00256] Below, examples are provided to facilitate a more complete understanding of the invention. The following examples illustrate exemplary ways of making and practicing the invention. However, the scope of the invention is not limited to specific configurations disclosed in these Examples, which are for illustrative purposes only, since alternative methods can be used to obtain similar results. Example 1: Vulvovaginal cream produced by water-in-silicone (W / O) emulsification.

[00257] An O / W emulsified cream is manufactured using a method of Petition 870260042611, dated 06 / 05 / 2026, page 97 / 250 94 / 109 high shear mixture, using a rotor-stator homogenizer. An aqueous dispersing phase, comprising a lactic acid buffer system (lactic acid / sodium lactate, pH 3.8, 250 mOsm / kg), 0.5 wt% glycogen, 0.1 wt% sodium ascorbate and 0.1 wt% potassium sorbate, is prepared by dissolving the components in deionized water. A continuous silicone phase comprising 1 wt% Span 80, 2 wt% Tween 80, 1 wt% cholesterol, 0.2 wt% stearic acid, 0.2 wt% oleic acid, 0.2 wt% linoleic acid, 1 wt% tocopheryl acetate and 0.1 wt% benzoic acid, is prepared by dissolving these components in dimethicone. The resulting aqueous dispersing phase (250 ml) is added to the resulting continuous silicone phase (500 ml), under constant high shear stirring, using a rotor-stator homogenizer.The resulting stable microemulsion is homogenized for 30 minutes to yield a stable, water-in-silicone emulsion cream.

[00258] An O / W emulsified cream is manufactured using a high-shear mixing method, utilizing a rotor-stator homogenizer. An aqueous dispersing phase, comprising a lactic acid buffer system (lactic acid / sodium lactate, pH 3.8, 250 mOsm / kg), 0.5% by weight glycogen, 0.1% by weight sodium ascorbate and 0.1% by weight potassium sorbate, is prepared by dissolving the components in deionized water. A continuous silicone phase comprising 2 wt% PEG / PPG 18-18 dimethicone, 1 wt% octyldodecanol, 1 wt% cholesterol, 0.2 wt% stearic acid, 0.2 wt% oleic acid, 0.2 wt% linoleic acid, 1 wt% tocopheryl acetate and 0.1 wt% benzoic acid is prepared by dissolving these components in dimethicone. The resulting aqueous dispersing phase (250 ml) is added to the resulting continuous silicone phase (500 ml) under constant pressure. Petition 870260042611, dated 06 / 05 / 2026, page 98 / 250 95 / 109 high shear agitation, using a rotor-stator homogenizer. The resulting stable microemulsion is homogenized for 30 minutes to yield a stable water-in-silicone emulsified cream. Example 2: Vulvovaginal cream with active agent, produced by emulsification of water in silicone (W / O) Vulvovaginal cream with 2% miconazole produced by water-in-water emulsification (W / O).

[00259] An O / W emulsified cream is manufactured using a high shear mixing method, utilizing a rotor-stator homogenizer. An aqueous dispersing phase, comprising a lactic acid buffer system (lactic acid / sodium lactate, pH 3.8, 250 mOsm / kg), 0.5% by weight glycogen, 0.1% by weight sodium ascorbate and 0.1% by weight potassium sorbate, is prepared by dissolving the components in deionized water. A continuous silicone phase comprising 2% by weight PEG / PPG 18-18 dimethicone, 1% by weight octyldodecanol, 1% by weight cholesterol, 0.2% by weight stearic acid, 0.2% by weight oleic acid, 0.2% by weight linoleic acid, 1% by weight tocopheryl acetate, 0.1% by weight benzoic acid and 3% by weight miconazole, is prepared by dissolving these components in dimethicone.The resulting aqueous dispersing phase (250 ml) is added to the resulting continuous silicone phase (500 ml), under constant high shear stirring, using a rotor-stator homogenizer. The resulting stable microemulsion is homogenized for 30 minutes to yield a stable water-in-silicone emulsion cream. Vulvovaginal cream with 1% clotrimazole, produced by water-in-water emulsification (W / O).

[00260] An emulsified W / O cream is manufactured using a high-shear mixing method, utilizing a rotor-stator homogenizer. An aqueous dispersing phase, comprising a system Petition 870260042611, dated 06 / 05 / 2026, page 99 / 250 96 / 109 Lactic acid buffer (lactic acid / sodium lactate, pH 3.8, 250 mOsm / kg), 0.5% by weight glycogen, 0.1% by weight sodium ascorbate and 0.1% by weight potassium sorbate, is prepared by dissolving the components in deionized water. A continuous silicone phase comprising 2% by weight PEG / PPG 18-18 dimethicone, 1% by weight octyldodecanol, 1% by weight cholesterol, 0.2% by weight stearic acid, 0.2% by weight oleic acid, 0.2% by weight linoleic acid, 1% by weight tocopheryl acetate, 0.1% by weight benzoic acid and 1.5% by weight clotrimazole, is prepared by dissolving these components in dimethicone. The resulting aqueous dispersing phase (250 ml) is added to the resulting continuous silicone phase (500 ml), under constant high shear stirring, using a rotor-stator homogenizer. The resulting stable microemulsion is homogenized for 30 minutes to yield a stable water-in-silicone emulsion cream. Vulvovaginal cream with 1% metronidazole, produced by water-in-water emulsification (W / O).

[00261] An O / W emulsified cream is manufactured using a high-shear mixing method, utilizing a rotor-stator homogenizer. An aqueous dispersing phase, comprising a lactic acid buffer system (lactic acid / sodium lactate, pH 3.8, 250 mOsm / kg), 0.5% by weight glycogen, 0.1% by weight sodium ascorbate, 0.1% by weight potassium sorbate and 1.5% by weight metronidazole, is prepared by dissolving the components in deionized water. A continuous silicone phase comprising 2% by weight PEG / PPG 18-18 dimethicone, 1% by weight octyldodecanol, 1% by weight cholesterol, 0.2% by weight stearic acid, 0.2% by weight oleic acid, 0.2% by weight linoleic acid, 1% by weight tocopheryl acetate and 0.1% by weight benzoic acid, is prepared by dissolving these components in dimethicone. [The text abruptly ends here, so the translation also ends here.] 97 / 109 resulting aqueous solution (250 ml) is added to the resulting continuous silicone phase (500 ml), under constant high shear stirring, using a rotor-stator homogenizer. The resulting stable microemulsion is homogenized for 30 minutes to yield a stable water-in-silicone emulsion cream. Vulvovaginal cream with 4% nonoxynol-9, produced by water-in-water emulsification (W / O).

[00262] An O / W emulsified cream is manufactured using a high-shear mixing method, utilizing a rotor-stator homogenizer. An aqueous dispersing phase, comprising a lactic acid buffer system (lactic acid / sodium lactate, pH 3.8, 250 mOsm / kg), 0.5% by weight glycogen, 0.1% by weight sodium ascorbate and 0.1% by weight potassium sorbate, is prepared by dissolving the components in deionized water. A continuous silicone phase comprising 2 wt% PEG / PPG 18-18 dimethicone, 1 wt% octyldodecanol, 1 wt% cholesterol, 0.2 wt% stearic acid, 0.2 wt% oleic acid, 0.2 wt% linoleic acid, 1 wt% tocopheryl acetate, 0.1 wt% benzoic acid and 6 wt% nonoxynol-9, is prepared by dissolving these components in dimethicone.The resulting aqueous dispersing phase (250 ml) is added to the resulting continuous silicone phase (500 ml), under constant high shear stirring, using a rotor-stator homogenizer. The resulting stable microemulsion is homogenized for 30 minutes to yield a stable water-in-silicone emulsion cream. Vulvovaginal cream with 0.1% estradiol, produced by water-in-water emulsification (W / O).

[00263] An O / W emulsified cream is manufactured using a high-shear mixing method, utilizing a rotor-stator homogenizer. An aqueous dispersing phase, comprising a system Petition 870260042611, dated 06 / 05 / 2026, page 101 / 250 98 / 109 lactic acid buffer (lactic acid / sodium lactate, pH 3.8, 250 mOsm / kg), 0.5% by weight glycogen, 0.1% by weight sodium ascorbate and 0.1% by weight potassium sorbate, is prepared by dissolving the components in deionized water. A continuous silicone phase comprising 2% by weight PEG / PPG 18-18 dimethicone, 1% by weight octyldodecanol, 1% by weight cholesterol, 0.2% by weight stearic acid, 0.2% by weight oleic acid, 0.2% by weight linoleic acid, 1% by weight tocopheryl acetate, 0.1% by weight benzoic acid and 0.15% by weight estradiol, is prepared by dissolving these components in dimethicone. The resulting aqueous dispersing phase (250 ml) is added to the resulting continuous silicone phase (500 ml), under constant high shear stirring, using a rotor-stator homogenizer. The resulting stable microemulsion is homogenized for 30 minutes to yield a stable water-in-silicone emulsion cream.

[00264] Those skilled in the art will appreciate that numerous changes and modifications can be made to the preferred configurations of the invention and that such changes and modifications can be made without departing from the spirit of the invention. It is therefore intended that the appended claims cover all equivalent variations, as they fall within the true spirit and scope of the invention. Example 3: Vulvovaginal cream prepared by water-in-silicone (W / O) emulsification. Methods

[00265] A water-emulsified silicone cream was manufactured using a high-shear mixing method, utilizing a Silverson rotor-stator homogenizer. Briefly, an aqueous dispersing phase comprising 36.4 wt% of lactic acid buffer system (100 mM lactic acid / sodium lactate buffer, pH 3.8, 300 mOsm / kg), and 0.1 wt% glycogen, was prepared by Petition 870260042611, dated 06 / 05 / 2026, page 102 / 250 99 / 109 Dissolving the components in deionized water, with stirring at 80°C (the deionized water was compensated to account for evaporative loss during heating). A continuous silicone phase, comprising 13 wt% 2-octyldodecanol, 0.25 wt% Span 60, 2 wt% cholesterol, 0.2 wt% stearic acid and 0.1 wt% tocopheryl acetate, was prepared by dissolving these components in a mixture of 35.65 wt% dimethicone and 12.3 wt% dimethicone / dimethiconol, with stirring at 80°C. The resulting aqueous dispersing phase (80°C) was added to the resulting continuous silicone phase (80°C), under constant high shear stirring, using a Silverson rotor-stator homogenizer, operating at 6500 RPM, for 10 minutes. The emulsification shear rate was then increased to 8000 RPM for 5 minutes, to yield a solidified water-in-silicone emulsified cream.The stable microemulsion was then transferred to an air stirrer for equilibration cooling at room temperature to yield a stable, solidified water-in-silicone emulsion cream. All weight percentages of the constituents represent percentages of the total composition. Rheology: Flux voltage sweep protocol

[00266] A flux voltage sweep protocol was performed on a TA Instruments Discovery HR-3 controlled voltage rheometer, with a 20 mm parallel plate geometry and a 1000 μm aperture, at 25°C and 37°C. To run the protocol, the instrument parameters were set as follows: Step 1) Conditioning - Options Mode disabled Purge gas only (no active cooling): Off mode disabled Step 2) Flow scan Petition 870260042611, dated 06 / 05 / 2026, page 103 / 250 100 / 109 Temperature 25°C inherited set point: off Immersion time 60.0 sec. Waiting time for temperature: on Logarithmic scan Voltage: 0.1-500 Pa Points per decade: 5 Steady-state sensor: On (max. equilibrium time 60.0 sec.) Sample period: 10.0 sec. % tolerance: 5.0 Consecutive within: 3 Average staggered time: off Rheology: Oscillatory Frequency and Amplitude Sweep Protocol

[00267] An oscillatory frequency and amplitude sweep protocol was performed on a TA Instruments Discovery HR-3 controlled-strain rheometer, with a 20 mm parallel plate geometry and a 1000 μm aperture, at 25°C and 37°C. To execute the protocol, the instrument parameters were defined as follows: Step 1) Oscillation - Frequency Temperature retention point: On Immersion time: 0.0 sec. Waiting for temperature: Off. Voltage %: 1% Logarithmic sweep Frequency: 0.1-30 Hz Points per decade: 5 Step 2) Oscillation - Frequency Temperature retention point: On Immersion time: 0.0 sec. Wait for temperature: Off. Voltage %: 1% Logarithmic sweep Frequency: 30-0.1 Hz Petition 870260042611, dated 06 / 05 / 2026, page 104 / 250 101 / 109 Points per decade: 5 Step 3) Oscillation - Amplitude Temperature retention point: On Angular Frequency: 10 rad / s Logarithmic sweep Voltage %: 0.1-100% Points per decade: 10 Rheology: Oscillatory temperature scanning protocol

[00268] An oscillatory temperature sweep protocol was performed on a TA Instruments Discovery HR-3 voltage-controlled rheometer, with a 20 mm parallel plate geometry and a 1000 μm aperture, from 20°C to 40°C, with a voltage of 5 Pa and a frequency of 10 rad / s. To run the protocol, the instrument parameters were set as follows: Step 1) Conditioning - Sample Temperature held at 20°C, setting point: Off. Immersion time 600.0 sec. Waiting for temperature: On. Waiting for axial force: Off. Perform pre-shear: Off Perform the balancing: Off Step 2) Oscillation - Temperature ramp Starting temperature: 20°C Immersion time: 60.0 sec. Waiting time for temperature: On. Final temperature: 40°C. Immersion time after ramp: 0.0 sec. Ramp rate: 0.5°C / min Sampling interval: 10 s / pt Stress: 5 Pa Single point Angular frequency: 10 rad / s Petition 870260042611, dated 06 / 05 / 2026, page 105 / 250 102 / 109 Rheology: Results and Discussion Table 1: Formulation matrix of water-in-silicone emulsified cream Formulation # DiM DiM / DiM-ol 2-octyl dodecanol Col Span 60 SA TA Gli c LA Stable emulsion ? 1 60.0 — 5.0 2.0 0.5 — — — 32.5 N 2 50.0 10.0 5.0 2.0 0.5 — — — 32.5 N 3 50.0 10.0 5.0 4.0 0.5 — — — 30.5 N 4 50.0 10.0 5.0 2.0 1.0 — — — 32.0 N 5 45.0 10.0 10.0 2.0 0.5 — — — 32.5 N 6 40.0 15.0 10.0 2.0 0.5 — — — 32.5 N 7 40.0 15.0 10.0 2.0 0.25 — — — 32.75 N 8 40.0 15.0 13.0 2.0 0.25 — — — 29.75 Initial S 9 35.0 12.5 13.0 2.0 0.25 — — — 36.25 S 10 35.75 12.3 13.0 2.0 0.25 0.2 — 0.1 36.4 S 11 35.65 12.3 13.0 2.0 0.25 0.2 0.1 0.1 36.4 S 12 12.3 36.65 13.0 2.0 0.25 0.2 0.1 0.1 36.4 N 13 37.95 10.00 13.00 2.0 0.25 0.2 0.1 0.1 36.4S 14 37.95 10.00 15.00 0.0 0.25 0.2 0.1 0.1 36.4 N Abbreviations: DiM = Dimethicone, DiM / DiM-ol = Dimethicone / Dimethiconol, Col = Cholesterol, SA = Stearic acid, TA = Tocopheryl acetate, Glic = Glycogen, LA = Aqueous lactic acid buffer / Sodium lactate

[00269] The formulations were generated according to Table 1 and analyzed using macroscopic and microscopic optical imaging to determine stability. Formulation #1 yielded a white, moderately viscous cream in the absence of classic emulsion, which was stable. Phase separation began on day 10 and a progressive increase was observed. Formulation #2 yielded a white cream with higher viscosity in the absence of stable classic emulsion. The higher viscosity was attributed to the incorporation of dimethiconol. Phase separation began Petition 870260042611, dated 06 / 05 / 2026, page 106 / 250 Formulation #3 yielded a viscous white cream in the absence of a stable, classic emulsion. Phase separation was initially observed on day 1, indicating the existence of an upper limit to cholesterol incorporation. Formulation #4 failed to yield both a viscous white cream and a stable, classic emulsion. Phase separation was observed immediately after emulsification, indicating the existence of an upper limit to Span 60 incorporation. This phenomenon was likely correlated with the Span 60 concentration being above the critical micelle concentration (CMC) of Span 60 in the mixed silicone. Formulation #5 yielded a viscous white cream in the absence of a stable, classic emulsion. Phase separation began on day 14 and a progressive increase was observed.This phenomenon was likely correlated with the increase in 2-octyldodecanol, creating a better interface with Span 60 and cholesterol, to better stabilize the water droplets at the water-silicone interface. Formulation #6 yielded a viscous white cream, in the absence of a stable, classic emulsion. Phase separation began on day 4 and a progressive increase was observed. This phenomenon indicated that attempting to physically stabilize the emulsion by increasing the waxy component and dimethiconol is futile; therefore, the stability of the emulsion is predominantly governed by physicochemical and thermodynamic parameters. Formulation #7 yielded a viscous white cream, in the absence of a stable, classic emulsion. Phase separation began on day 5 and a progressive increase was observed. This phenomenon indicated the usefulness of decreasing the concentration of Span 60.Formulation #8 yielded a viscous white cream in the presence of a more consistent emulsion with a stable, classic emulsion (Figure 3A-3C). Exudation of the silicone phase was observed on day 6, although the emulsion maintained moderate stable integrity. Phase separation began on day 15 and an increase in pro- Petition 870260042611, dated 06 / 05 / 2026, page 107 / 250 104 / 109 progressive. This phenomenon further supports the hypothesis that a specific balance of emulsifiers is essential to confer stability to the emulsion. Furthermore, the exudation of the oil phase indicated that the water-to-silicone ratio should be altered to incorporate a more aqueous dispersing phase. Formulation #9 yielded a viscous white cream in the presence of a stable, classic emulsion (Figure 4A4C). This cream showed no signs of phase separation or instability, confirming the importance of the water-to-silicone ratio for emulsion stability. Formulation #10 (Figure 5A-5C) and Formulation #11 also yielded a viscous white cream in the presence of a stable, classic emulsion. These creams showed no signs of phase separation or instability. Formulation #12 yielded a viscous white cream in the absence of a stable, classic emulsion. This phenomenon demonstrated the importance of controlling the constituents of the silicone phase.Formulation #13 also yielded a viscous white cream in the presence of a stable, classic emulsion. Removing the cholesterol from Formulation #13 to create Formulation #14 resulted in complete phase separation and a lack of emulsion formation (Figures 6A-6E). This phenomenon demonstrated the importance of cholesterol as an emulsifier and interfacial stabilizer.

[00270] The mechanical properties of the selected formulations were examined by rheometry and the results are summarized in Table 2 below. Table 2: Comparison of rheological properties with predicated vulvovaginal creams Zero-rate viscosity formulation (kPa.s) Frequency sweep comparison Amplitude sweep comparison (crossover) Amplitude sweep comparison (strain) 25°C 37°C 25°C 37°C 25°C 37°C Monistat 7 45 95 Some amplification 1800 Pa 1.9 Pa 0.5% 1.3% Petition 870260042611, dated 06 / 05 / 2026, page 108 / 250 105 / 109 Formulation Zero-rate viscosity (kPa.s) Frequency Sweep Comparison Amplitude Sweep Comparison (Crossover) Amplitude Sweep Comparison (Stress) 25°C 37°C 25°C 37°C 25°C 37°C Vagisil 329 142 Some amplification 386.8 Pa 326.2 Pa 29.2% 30.4% #9 95 105 No amplification 323.6 Pa 435.6 Pa 10.4% 11.3% #10 346.4 198.6 No amplification 336.1 Pa 248.3 Pa 12.1% 11.9% #11 166.8 261.1 No amplification 288.2 Pa 374.8 Pa 7.45% 8.56% #13 315.8 143.2 without enlargement 384.2 Pa 292.3 Pa 12.4% 12.5%

[00271] Using a flow stress sweep protocol, zero-rate viscosities of 95 kPa.s and 105 kPa.s were determined at 25°C and 37°C, respectively, for Formulation #9 (Figure 7A-7D). An oscillatory frequency sweep showed a mostly parallel relationship between the storage modulus (G') and the loss modulus (G), with some convergence at high frequency (Figure 8A-8B). Furthermore, no amplification or hysteresis was observed throughout the frequency domain, and the difference between G' and G at 25°C and 37°C was found to be negligible. An oscillatory amplitude sweep showed only a small difference between the crossover points of G' and G and the stresses at 25°C and 37°C, thus indicating that the solid-to-liquid transition is similar across the defined temperature range (Figure 9A-9B). An oscillatory temperature scan revealed a slight negative slope for G', G and complex viscosity (Figure 10).Furthermore, this provided further evidence supporting the negligible differences in Formulation #9 at 25°C and 37°C. Taken together, these rheological properties demonstrate ideal properties for a vulvovaginal cream designed to be stored at room temperature and applied to the anatomy at body temperature. These ideal properties were also observed in Formulation #11. Comparison of Mechanical Properties and Osmolarities: Formulation #9 versus Predicated Creams for Vaginal Application Petition 870260042611, dated 06 / 05 / 2026, page 109 / 250 106 / 109

[00272] A comparison was made between the mechanical properties and osmolarities of Formulation #9 and these properties of predicated creams (such as Monistat 7, Vagisil and Clotrimazole 2%) for vaginal application, with the results detailed in Table 3 below. Table 3: Comparison of Mechanical Properties and Osmolarities Formulation Zero-rate viscosity Frequency sweep comparison Amplitude sweep comparison Osmolarity (mOsm / kg) Monistat 7 45 kPa.s @ 25C 95 kPa.s @ 37C Some amplification 25C Crossover @ ~1800 Pa 25C Strain @ ~0.5% 37C Crossover @ ~1.9 Pa 37C Strain @ 1.3% ND Vagisil 329 kPa.s @ 25C 142 kPa.s @ 37C Some amplification 25C Crossover @ 386.8 Pa 25C Strain @ 29.2% 37C Crossover @ 326.2 Pa 37C Strain @ 30.4% 1374 Clotrimazole 590 kPa.s @ 25C 281 kPa.s @ 37C Some amplification 25C Crossover @ 2552.4 Pa 25C Stress @ 29% 37C Crossover @ 1703.3 Pa 37C Stress @ 5.4% 125 #9 95 kPa.s @ 25C 105 kPa.s @ 37C No amplification 25C Crossover @ 323.6 Pa 25C Stress @ 10.4% 37C Crossover @ 435.6 Pa 37C Stress @ 11.3% 300 OTHER SETTINGS

[00273] Although the invention has been described in conjunction with the Petition 870260042611, dated 06 / 05 / 2026, page 110 / 250 107 / 109 detailed description, the preceding description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages and modifications are within the scope of the following claims.

[00274] The patent and scientific literature referred to herein establish the knowledge available to those skilled in the art. All U.S. patents and patent applications, published or unpublished in the United States, cited herein are incorporated by reference. All foreign published patents and patent applications cited herein are incorporated by reference. GenBank and NCBI submissions indicated by accession number, cited herein, are incorporated by reference. All other published references, documents, manuscripts, and scientific literature cited herein are incorporated by reference.

[00275] Although this invention has been particularly presented and described with reference to preferred configurations, it will be understood by those skilled in the art that various changes in form and details may be made to it without departing from the scope of the invention encompassed by the claims. Additional Sample Configurations Include:

[00276] In one embodiment, a dermatological composition is provided comprising a stable water-in-silicone emulsion having a continuous silicone phase and an aqueous phase, wherein the emulsion comprises a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition. In other embodiments, the sterol comprises cholesterol, or cholesterol derivatives.

[00277] In one configuration, methods are provided herein for preventing and treating a dermatological condition in an individual, the method comprising administering to the individual a composition comprising a stable water-in-silicone emulsion, wherein the Petition 870260042611, dated 06 / 05 / 2026, page 111 / 250 The 108 / 109 emulsion comprises a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition.

[00278] In one embodiment, a rectal composition is provided comprising a stable water-in-silicone emulsion having a continuous silicone phase and an aqueous phase, wherein the emulsion comprises a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition. In other embodiments, the sterol comprises cholesterol, or cholesterol derivatives.

[00279] In one configuration, methods are provided here for treating a rectal condition in an individual, comprising administering to the individual a composition comprising a stable water-in-silicone emulsion, wherein the emulsion comprises a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition.

[00280] In one embodiment, a sunscreen composition is provided, comprising a stable water-in-silicone emulsion having a continuous silicone phase and an aqueous phase, wherein the emulsion comprises a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition. In other embodiments, the sterol comprises cholesterol, or cholesterol derivatives.

[00281] In one embodiment, methods are provided for preventing UV radiation damage in an individual, the method comprising administering to the individual a composition comprising a stable water-in-silicone emulsion, wherein the emulsion has a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition.

[00282] In one embodiment, a transdermal drug delivery composition is provided herein, comprising a stable water-in-silicone emulsion having a continuous silicone phase and an aqueous phase, wherein the emulsion comprises a sterol in a con Petition 870260042611, dated 06 / 05 / 2026, page 112 / 250 109 / 109 concentration of approximately 0.1% to approximately 4% by weight of the total composition. In configurations, sterol comprises cholesterol, or cholesterol derivatives.

[00283] In one configuration, methods are provided here for treating pain, diabetes, neurological disorders or diseases, hormonal deficiency or nausea in an individual, the method comprising administering to the individual a composition comprising a stable water-in-silicone emulsion, wherein the emulsion has a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition.

[00284] In one embodiment, an ophthalmic composition is provided herein, comprising a stable water-in-silicone emulsion having a continuous silicone phase and an aqueous phase, wherein the emulsion comprises a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition. In other embodiments, the sterol comprises cholesterol, or cholesterol derivatives.

[00285] In one configuration, methods are provided here for preventing or treating ophthalmic conditions in an individual, the method comprising administering to the individual a composition comprising a stable water-in-silicone emulsion, wherein the emulsion has a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition. Petition 870260042611, dated 06 / 05 / 2026, page 113 / 250

Claims

1 / 9 CLAIMS 1. Composition, characterized in that it comprises a stable water-silicone emulsion, having a continuous silicone phase and an aqueous phase, wherein the emulsion comprises a sterol at a concentration of about 0.1% to about 4% by weight of the total weight of the composition, provided that the matter covered in patent application BR112020012195-9 is excluded.

2. Composition according to claim 1, characterized in that: (i) the sterol is at a concentration of about 1% to about 2% by weight of the total weight of the composition; and / or (ii) the sterol comprises cholesterol or cholesterol derivatives.

3. Composition according to claim 1, characterized in that: (i) the silicone phase comprises a silicone oil, a silicone gum or a combination thereof, optionally wherein: (a) the silicone oil comprises dimethicone, cyclomethicone, caprylyl methicone or cyclopentasiloxane; and / or (b) the silicone gum comprises dimethiconol;and / or (ii) the composition further comprises at least one coemulsifier, optionally wherein the coemulsifier comprises glyceryl stearate, glyceryl monostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan tristearate, sorbitan monooleate, sorbitan trioleate, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan trioleate, polyoxyethylene monolaurate, polyoxyethylene monostearate, polyoxyethylene monopalmitate, Petition 870260042611, dated 06 / 05 / 2026, pg. 114 / 250 2 / 9 polyoxyethylene, lecithin, PEG / PPG-18 / 18 dimethicone, cetyl PEG / PPG10 / 1 dimethicone, dimethicone copolyol, octyl dodecanol, polyvinyl alcohol, Pluronic, Poloxamer, Carbomer, isopropyl myristate or any combination thereof;and / or (iii) the aqueous phase comprises a pH buffer system, optionally wherein the pH buffer system comprises lactic acid and its conjugate base; and / or (iv) the composition further comprises at least one preservative, optionally wherein the preservative comprises sorbic acid, potassium sorbate, boric acid, sodium borate, benzoic acid, sodium benzoate, benzalkonium chloride, EDTA, parabens or combinations thereof; and / or (v) the composition further comprises a tocopherol, optionally wherein the tocopherol comprises alpha-tocopherol, vitamin E, vitamin E-TPGS or tocopherol acetate; and / or (vi) the composition further comprises an antioxidant, optionally wherein the antioxidant comprises ascorbic acid, sodium ascorbate, polyphenol or combinations thereof;and / or (vii) the composition further comprises at least one fatty acid, optionally wherein the fatty acid comprises caprylic acid, lauric acid, myristic acid, caproleic acid, lauroleic acid, myristoleic acid, palmitoleic acid, oleic acid, stearic acid, palmitic acid, linoleic acid, arachidonic acid, stearidonic acid, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) or combinations thereof; and / or (vii) the composition further comprises at least one viscosity-increasing agent; and / or (vii i) the composition further comprises hydroxy methyl cellulose, hydroxy ethyl cellulose, hydroxy propyl cellulose, hydroxy propyl methyl cellulose, carboxy methyl cellulose, ethyl cellulose, hyaluronic acid, sodium hyaluronate, Carbomer, Carbopol, polyacrylic acid, polycarbophil, guar gum, xanthan gum, combinations thereof;and / or (ix) the composition further comprises at least one bioactive agent, optionally wherein the bioactive agent comprises glycogen; and / or (x) the composition further comprises at least one active agent, optionally wherein the active agent comprises miconazole, metronidazole, clotrimazole, estradiol, prasterone or nonoxynol-9.

4. Composition according to claim 1, characterized in that: (i) the pH of the composition is from about 3 to about 5; and / or (ii) the osmolarity of the composition is from about 200 to 500 mOsm / kg; and / or (iii) the composition has a zero-rate viscosity of about 50 kPa.s to 1000 kPa.s; and / or (iv) the composition is formulated as a personal lubricant, as a moisturizer, as an ointment, as a lotion, as a topical cream, for wound care, for skin care, for drug delivery, for ophthalmic care; and / or (v) the composition is a vulvovaginal composition.

5. Composition, characterized in that it comprises a stable water-silicone emulsion having a continuous silicone phase comprising about 55% to about 75% of the composition and an aqueous phase, wherein the silicone phase is formed by a silicone oil and a silicone gum, wherein the silicone oil comprises dimethicone and is about 35% to about 45% by weight of the composition, wherein the silicone gum comprises a mixture of dimethiconol:dimethicone and is about 10% to about 15% by weight of the composition, Petition 870260042611, dated 06 / 05 / 2026, p. 116 / 250 4 / 9 wherein the emulsion comprises a silicone-free emulsifier comprising cholesterol or a cholesterol derivative at a concentration of about 0.1% to about 4% by weight of the total weight of the composition and a sorbitan ester, wherein the composition is free of a silicone-based emulsifier, and wherein the pH of the composition is about 3 to about 5 and is effective for vulvovaginal administration.

6. Use of a stable water-in-silicone emulsion having a continuous silicone phase and an aqueous phase, wherein the emulsion comprises a silicone-free emulsifier comprising cholesterol or a cholesterol derivative at a concentration of about 0.1% to about 4% w / w a sorbitan ester, or use of a composition as defined in any of claims 1 to 5, characterized in that it is in the preparation of a kit and / or product and / or cosmetic composition for treating or preventing a vaginal condition in a subject, wherein the cosmetic composition, kit or product is free of a silicone-based emulsifier.

7. Use according to claim 6, characterized in that: (i) the tissue surface comprises an epithelial surface or a mucosal surface; and / or (ii) the vaginal condition comprises a decrease in estrogen concentration, atrophic vaginitis, vulvar and vaginal atrophy, bacterial vaginosis, vaginal dryness, vaginal itching, vaginal irritation, dyspareunia, bacterial infection, fungal infection, urinary tract infection, menopause, peri-menopause, post-menopause, a sexually transmitted infection, sexually transmitted disease or combinations thereof; optionally, wherein the estrogen comprises estradiol; and / or (iii) the composition is administered to the tissue surface via topical administration, vaginal administration or mucosal administration; and / or (iv) the cosmetic composition is formulated as a personal lubricant, as a moisturizer, as an ointment, as a lotion, as a topical cream,as a skin protectant or for drug administration; and / or (v) the cosmetic composition further comprises one or more active agents, optionally, wherein one or more active agents comprise an antifungal agent, an antibiotic, a spermicide, estrogen, an estrogen derivative, progesterone, a progesterone derivative, an estrogen precursor, a steroid, an anti-inflammatory agent, an antiviral agent, an antiretroviral agent, a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, fusion inhibitors, an integrase inhibitor,a post-fixation inhibitor or combinations thereof; and / or (vi) the cosmetic composition further comprises glycogen; and / or (vii) the cosmetic composition has a pH of about 3 to about 5; and / or (viii) the cosmetic composition has an osmolarity of about 200 to about 500 mOsm / kg; and / or (ix) wherein the vaginal condition comprises vulvar and vaginal atrophy (VVA); and / or (x) wherein the composition further comprises at least one co-emulsifier, optionally, wherein the co-emulsifier comprises at least one of glyceryl stearate, glyceryl monostearate, mono Petition 870260042611, dated 06 / 05 / 2026, page. 118 / 250 6 / 9 sorbitan laurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan ursorate, sorbitan monooleate, sorbitan trioleate, sorbitan trioleate, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan Tristearate,polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan monolaurate, polyethylene polyoxyethylene monolaurate, polyoxyethylene monolaurate, polyoxyethylene monolaurate, polyoxyethylene monolaurate, polyoxyethylene monolaurate, polyoxyethylene monolaurate, polyethylene monolaurate, polyoxyethylene monolaurate, polyoxyethylene monolaurate, polyoxyethylene monolaurate, polyethylene monolaurate, polyethylene-polyethylene-polyoxyethylene monolaurate, polyoxyethylene monolaurate, polyethylene-polyethylene-polyoxyethylene monolaurate, polyethylene-polyethanolate, polyethylene oxide) -poly(propylene oxide) -poly(ethylene oxide) triblock copolymer, poly(acrylic acid) or isopropyl myristate.

8. Cosmetic composition for treating or preventing a vaginal condition in a subject, according to claim 6, characterized in that the cosmetic composition is used in such a way as to comprise the following steps: applying to a tissue surface the cosmetic composition, which comprises a stable water-in-silicone emulsion with a continuous silicone phase and an aqueous phase, wherein the emulsion comprises a silicone-free emulsifier comprising cholesterol or a cholesterol derivative in a concentration of about 0.1% to about 4% by weight of the total weight of the cosmetic composition and a sorbitan ester, wherein the cosmetic composition does not use a silicone-based emulsifier, and wherein the composition is used in an amount effective to treat said vaginal condition.

9. Pharmaceutical composition for treating or preventing a vaginal condition in a subject, according to claim 6, characterized in that it is used in such a way as to comprise the following steps: applying to a tissue surface the pharmaceutical composition, comprising a stable water-silicone emulsion with a continuous silicone phase and an aqueous phase, wherein the emulsion comprises a silicone-free emulsifier comprising cholesterol or a cholesterol derivative in a concentration of about 0.1% to about 4% by weight of the total weight of the pharmaceutical composition and a sorbitan ester, wherein the pharmaceutical composition does not utilize a silicone-based emulsifier, and wherein the composition is used in an amount effective for treating said vaginal condition.

10. Use of a stable water-in-silicone emulsion having a continuous silicone phase and an aqueous phase, wherein the emulsion comprises a silicone-free emulsifier comprising cholesterol or a cholesterol derivative at a concentration of about 0.1% to about 4% w / w, or use of a composition as defined in any of claims 1 to 9, characterized in that it is in the preparation of a composition and / or a kit and / or a product for treating or preventing an infection on the surface of a subject's tissue.

11. Use according to claim 10, characterized in that: (i) the tissue surface comprises an epithelial surface or a mucosal surface; and / or Petition 870260042611, dated 06 / 05 / 2026, p. 120 / 250 8 / 9 (ii) the infection comprises a vaginal infection, a dermatological infection, a rectal infection or an ophthalmic infection, optionally: (a) wherein the vaginal infection comprises a decrease in estrogen concentration, atrophic vaginitis, vulvar and vaginal atrophy, bacterial vaginosis, vaginal dryness, vaginal itching, vaginal irritation, dyspareunia, bacterial infection, fungal infection, urinary tract infection, menopause, perimenopause, postmenopause, a sexually transmitted infection (STI), sexually transmitted disease (STD) or combinations thereof;and / or (b) wherein the dermatological infection comprises eczema, psoriasis, plaque psoriasis, dry skin, chafed skin, diaper rash, skin eruptions, hives, poison ivy, skin pain, postherpetic neuralgia, burns, wound healing, skin infections, dermatitis, atopic dermatitis, acne, impetigo, melanoma, rosacea, cracked skin, chapped lips, skin wrinkles or combinations thereof; and / or (c) wherein the rectal infection comprises hemorrhoids, anal fissures or combinations thereof;and / or (d) wherein the ophthalmic infection comprises ocular surface disorders, ophthalmic diseases, ophthalmic disorders, dry eyes, styes, epithelial defects, retinal detachment, conjunctivitis, viral conjunctivitis, bacterial conjunctivitis, allergic conjunctivitis, superior limbal keratoconjunctivitis, Sjögren's syndrome, ocular cicatricial pemphigoid (OCP), drug-induced conjunctivitis, corneal ulcerations and erosions, macular degeneration or combinations thereof; 12. Use, according to claim 10, characterized in that: (i) the composition is administered to the surface of the tissue via Petition 870260042611, dated 06 / 05 / 2026, page.121 / 250 9 / 9 oral administration, topical administration, intravenous administration, vaginal administration, mucosal administration, intraperitoneal administration, intramuscular administration, intradermal administration, intranasal administration or subcutaneous administration; and / or (ii) the composition is formulated as a personal lubricant, as a moisturizer, as an ointment, as a lotion, as a topical cream, for wound care, for skin care, for drug administration or for ophthalmic care; and / or (iii) the composition further comprises estradiol, prasterone, glycogen or combinations thereof; and / or (iv) the composition further comprises lidocaine, clindamycin, retinol, hyaluronic acid or combinations thereof; and / or (v) the composition further comprises lidocaine, hydrocortisone or combinations thereof; and / or (vi) the composition further comprises a vasoconstrictor, an antihistamine, naphazoline, pheniramine or combinations thereof.

13. Kit, characterized in that it comprises a stable water-in-silicone emulsion and a cell membrane fluidity enhancer, optionally wherein the kit also includes an emulsifier, a fatty acid, a preservative and at least one from the group of a bioactive agent, a pH buffer system, a viscosity enhancer, an antioxidant, a tocopherol, a ceramide or an active agent and instructions.

14. Use of a stable water-in-silicone emulsion, characterized by the fact that it is used in the preparation of a composition to prevent and treat diseases and / or conditions.

15. Invention, characterized by its embodiments or categories of claims, for example, product or process or use encompassed by the subject matter initially described, disclosed or illustrated in the patent application. Petition 870260042611, dated 06 / 05 / 2026, pp. 122 / 250

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