Azelaic acid compositions and methods of their use for treating skin conditions

Abstract

Described are topical compositions for treating skin conditions, the compositions comprising a therapeutically effective amount of azelaic acid dispersed in a lipophilic medium or a medium essentially free of ethanol, and propylene glycol, wherein the azelaic acid is essentially in the protonated acidic form. The compositions may be essentially free of water and / or alkyl alcohols. The compositions may further comprise an antioxidant such as vitamin E, vitamin C, vitamin A, or tocopheryl acetate, and siloxane compounds. Also described are kits comprising the topical composition in a monodose packaging unit such as a twist-off ampule, and methods of treating skin conditions such as acne vulgaris or rosacea by topical application of the topical composition.

Description

PATENT Attorney Docket No. N2041-04301 AZELAIC ACID COMPOSITIONS AND METHODS OF THEIR USE FOR TREATING SKIN CONDITIONS CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 780,056, filed March 28, 2025, the entire contents of which are incorporated herein by reference.FIELD

[0002] The present disclosure relates to topical compositions for treating skin conditions. More specifically, the present disclosure relates to topical compositions comprising azelaic acid in a lipophilic medium essentially free of ethanol.BACKGROUND

[0003] The following includes information that may be useful in understanding the present invention. It is not an admission that any of the information, publications or documents specifically or implicitly referenced herein is prior art, or essential, to the presently described or claimed inventions. All publications, patents, related applications, and other written or electronic materials mentioned or identified herein are hereby incorporated herein by reference in their entirety. The information incorporated is as much a part of the application as filed as if all of the text and other content was repeated in the application, and should be treated as part of the text and content of the application as filed.

[0004] Skin conditions affect millions of people worldwide and can significantly impact quality of life. These conditions can include acne vulgaris, rosacea, hyperpigmentation, and other dermatological disorders. Various treatment options exist for these conditions, but many have limitations in terms of efficacy, stability, and patient tolerability.

[0005] Dicarboxylic acids have been studied for their beneficial effects on skin. Many compounds have been explored for their potential to address various skin concerns through different mechanisms of action. Formulation challenges exist in developing stable, effective, and patient-friendly compositions that optimize the delivery and performance of active ingredients.

[0006] Single-dose packaging systems have been developed in the cosmetic and pharmaceutical industries to address concerns related to preservation, contamination, and dosing accuracy. These systems can provide improved stability for sensitive ingredients and offer convenience to users.PATENT Attorney Docket No. N2041-04301

[0007] Novel approaches to formulation and packaging of topical compositions may address challenges related to stability, efficacy, and patient compliance when treating skin conditions. Single-dose packaging systems may offer particular advantages for formulations containing ingredients that are sensitive to environmental factors or prone to degradation over time.SUMMARY

[0008] In an embodiment, a topical composition for treating a skin condition is provided, comprising a therapeutically effective amount of azelaic acid dispersed in a lipophilic medium or a medium essentially free of ethanol, and propylene glycol, wherein the azelaic acid is essentially in the protonated acidic form.

[0009] In an embodiment, the topical composition is further essentially free of water.

[0010] In an embodiment, the topical composition is further essentially free of alkyl alcohols.

[0011] In an embodiment, the topical composition further comprises an antioxidant.

[0012] In an embodiment, the antioxidant is selected from vitamin E, beta carotene, vitamin C, vitamin A, and tocopheryl acetate.

[0013] In an embodiment, the topical composition further comprises a one or a plurality of siloxane compounds selected from: dimethicone (dimethylbis (trimethylsilyloxy) silane), dimethiconol (bis [ [[ [ [hydroxy (dimethyl) silyl] oxy-dimethylsilyl]oxydimethylsilyl]oxydimethylsilyl]oxy]-dimethylsilane), trisiloxane (Dimethylbis(trimethylsilyloxy)silane), dimethicone / vinyltrimethylsiloxysilicate crosspolymer, and silica dimethyl silylate. In some embodiments, the composition comprises a trisiloxane, e.g., SeraSense SF 1.5 which is a low molecular weight, straight-chain polydimethylsiloxane, specifically an octamethyltrisiloxane. In some embodiments, the trisiloxane is SeraSense SF1. In some embodiments, the dimethicone is Seransence SF2.

[0014] In an embodiment, the topical composition further comprises 1,2,3-propanetriol octanoate and bis(2-ethylhexyl) 2-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]propanedioate decanoic acid, ester.

[0015] In an embodiment, the concentration of azelaic acid is from about 0.1 to about 20 wt.%, from about 0.1 to about 10 wt.%, from about 1 to about 20 wt.%, from about 5 to about 10 wt.%, from about 5 to about 20 wt.%, from about 15 to about 20 wt.%, or any concentration between the aforementioned values. In one embodiment, the concentration of azelaic acid is about 10 wt.%. In one embodiment, the concentration of azelaic acid is about 20 wt.%.PATENT Attorney Docket No. N2041-04301

[0016] In an embodiment, the topical composition is configured to be an ointment, cream, gel, paste, lotion, spray, liquid, or transdermal patch.

[0017] In an embodiment, a kit comprising the topical composition in a monodose packaging unit comprising a container is provided.

[0018] In an embodiment, the topical composition does not dissolve the container.

[0019] In an embodiment, the monodose packing unit comprising a container is a twist-off ampule.

[0020] In an embodiment, a method of treating a skin condition in a patient in need thereof is provided, the method comprising: administering to said patient a therapeutically effective amount of a topical composition comprising a therapeutically effective amount of azelaic acid dispersed in a lipophilic medium or a medium essentially free of ethanol, and propylene glycol, wherein the azelaic acid is essentially in the protonated acidic form, wherein the skin condition is selected from acne vulgaris, rosacea, skin blemishes, and skin spots. In one embodiment, this disclosure provides for a method of treating acne vulgaris in a patient in need thereof is provided, the method comprising: administering to said patient a therapeutically effective amount of a topical composition comprising a therapeutically effective amount of azelaic acid dispersed in a lipophilic medium or a medium essentially free of ethanol, and propylene glycol, wherein the azelaic acid is essentially in the protonated acidic form. In an embodiment, method of treating a skin condition in a patient in need thereof is provided, the method comprising: administering to said patient a therapeutically effective amount of a topical composition comprising a therapeutically effective amount of azelaic acid dispersed in a lipophilic medium or a medium essentially free of ethanol, and propylene glycol, wherein the azelaic acid is essentially in the protonated acidic form, wherein the skin condition is rosacea.

[0021] In an embodiment, administering is by application of the topical composition to the affected area of the skin of said subject.

[0022] In an embodiment, administering is by topical application.

[0023] It is noted that in this disclosure and particularly in the claims and / or paragraphs, terms such as “comprises”, “comprised”, “comprising” and the like can have the meaning attributed to it in U.S. Patent law; e.g., they can mean “includes”, “included”, “including”, and the like; and that terms such as “consisting essentially of’ and “consists essentially of’ have the meaning ascribed to them in U.S. Patent law, e.g., they allow for elements not explicitly recited, but exclude elements that are found in the prior art or that affect a basic or novel characteristic of the invention.PATENT Attorney Docket No. N2041-04301

[0024] These and other embodiments are disclosed or are obvious from and encompassed by, the following Detailed Description.BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The following detailed description, given by way of example, but not intended to limit the invention solely to the specific embodiments described, may best be understood in conjunction with the accompanying drawings.

[0026] FIG. 1 illustrates a graph showing the percentage of subjects with rosacea prone skin with recorded improvement of measured parameters over time, demonstrating that 64% of subjects saw positive results after 24 hours, 77% after 1 week, and 99% after 8 weeks of treatment.

[0027] FIG 2 depicts a graph showing the reduction in trans-epidermal water loss (TEWL) after treatment of subjects with rosacea prone skin, illustrating that 94% show trans-epidermal water loss reduction after 24 hours and after 1, 2, and 4 weeks, and 97% after 8 weeks with a total reduction in TEWL by 43.46%.

[0028] FIG. 3 shows a graph illustrating skin hydration improvement, demonstrating that 100% of subjects with rosacea prone skin show skin hydration improvement after 1, 2, 4, and 8 weeks, with skin hydration improved by 50.16%.

[0029] FIG. 4 presents a graph showing the decreased appearance of spots and blemishes over time of subjects with rosacea prone skin, with 75% of subjects showing a reduction of pigmentary lesions / blemishes after 2 weeks, 94% after 4 weeks, and 100% after 8 weeks, resulting in a reduction of spots and blemishes by 35%.

[0030] FIG. 5 illustrates graphs showing skin redness color analysis results of subjects with rosacea prone skin, demonstrating that 66% show skin redness (a*) reduction after 24 hours, 100% after 1, 2, 3, 4, and 8 weeks, with 69% showing skin redness (hemoglobin) reduction after 24 hours, 84% after 1 week, and 100% after 2, 3, 4, and 8 weeks.

[0031] FIG. 6 shows a series of Antera 3D® images at various time points (initial, 24 hours, after 1 week, after 2 weeks, after 4 weeks, and after 8 weeks), demonstrating the visual reduction in skin redness and blemishes over time in subjects with rosacea prone skin.

[0032] FIG. 7 depicts another series of Antera 3D® images at various time points (initial, 24 hours, after 1 week, after 2 weeks, after 4 weeks, and after 8 weeks), further illustrating the visual reduction in skin redness and blemishes in a different subject with rosacea prone skin.PATENT Attorney Docket No. N2041-04301

[0033] FIG. 8 shows a comprehensive graph displaying the mean variation of improvement of all tested parameters relative to initial conditions, based on measured instrumental data results across various time points in subjects with rosacea-prone skin.

[0034] FIG. 9 presents a bar chart showing results from subjective evaluation by subjects with rosacea prone skin, with various parameters assessed after 4 and 8 weeks of treatment, including the percentage of subjects reporting a soothing effect after 24 hours.

[0035] FIG. 10 illustrates a graph showing the percentage of subjects with recorded improvement of measured parameters over time in acne-prone skin, demonstrating that 63% of subjects saw positive results after 24 hours, 71% after 1 week, 83% after 2 weeks, 90% after 4 weeks, and 98% after 8 weeks of treatment.

[0036] FIG. 11 depicts a graph showing the reduction in trans-epidermal water loss (TEWE) in subjects with acne-prone skin, illustrating that 93% show trans-epidermal water loss reduction after 24 hours, 90% after 1 week, 97% after 2 and 4 weeks, and 100% after 8 weeks, with TEWL reduced by 46.23%.

[0037] FIG. 12 shows a graph illustrating skin hydration improvement in subjects with acne-prone skin, demonstrating that 80% show skin hydration improvement after 24 hours, 90% after 1 week, 77% after 2 weeks, and 97% after 8 weeks, with skin hydration improved by 49.85%.

[0038] FIG. 13 presents a graph showing the decreased appearance of spots and blemishes over time in subjects with acne-prone skin, with 75% of subjects showing a reduction of pigmentary lesions / blemishes after 2 weeks, 94% after 4 weeks, and 100% after 8 weeks, resulting in a reduction of spots and blemishes by 33.18%.

[0039] FIG. 14 illustrates graphs showing skin redness color analysis results in subjects with acne-prone skin, demonstrating that 77% show skin redness (a*) reduction after 24 hours, 83% after 1 week, 80% after 2 weeks, 90% after 4 weeks, and 100% after 8 weeks, with reductions in both skin redness parameters.

[0040] FIG. 15 shows a series of Antera 3D® images for subjects with acne-prone skin at various time points, demonstrating the visual reduction in skin redness and blemishes over time.

[0041] FIG. 16 depicts another series of Antera 3D® images for subjects with acne-prone skin at various time points, further illustrating the visual reduction in skin redness and blemishes.PATENT Attorney Docket No. N2041-04301

[0042] FIG. 17 shows a comprehensive graph displaying the mean variation of improvement of all tested parameters relative to initial conditions for subjects with acne-prone skin.

[0043] FIG. 18 presents a bar chart showing results from subjective evaluation by subjects with acne-prone skin, with various parameters assessed after 4 and 8 weeks of treatment.

[0044] FIG. 19 illustrates the results of a stability study showing various packaging options (glass jar, PET jar, blister) under different temperature and humidity conditions over 3 months, demonstrating product stability.DETAIEED DESCRIPTION

[0045] The inventions described and claimed herein have many attributes and embodiments including, but not limited to, those set forth or described or referenced in this Detailed Description. It is not intended to be all-inclusive and the inventions described and claimed herein are not limited to or by the features or embodiments identified in this Detailed Description, which is included for purposes of illustration only and not restriction.

[0046] In an embodiment, topical compositions comprise a therapeutically effective amount of azelaic acid in a stable, anhydrous formulation that is essentially free of ethanol. In an embodiment, compositions are formulated for topical application to treat skin conditions including, but not limited to, acne vulgaris and rosacea.

[0047] Azelaic acid is a naturally occurring straight-chained saturated dicarboxylic acid that is naturally present in several plants. In an embodiment, azelaic acid may help rebalance keratinization and reduce the growth of bacteria in the follicle. In a further embodiment, azelaic acid may help reduce hyperpigmentation by decreasing melanin synthesis.

[0048] When azelaic acid is applied to the skin, it may exhibit several therapeutic actions. In various embodiments, azelaic acid may help normalize the skin microflora, control melanin synthesis, act as a scavenger of reactive cytotoxic hydroxyl free radicals, help control hyperkeratinization, and help improve skin barrier function.

[0049] In an embodiment, these actions may result in several clinical benefits including reduction of dark spots and discolorations, improving overall skin tone, unclogging of pores, prevention of formation of comedones (blackheads and whiteheads), reduction in the appearance of skin redness, and a soothing effect on the skin.

[0050] In an embodiment, these multiple therapeutic actions of azelaic acid may provide synergistic benefits when formulated in a lipophilic medium essentially free of ethanol. The absence of ethanol may improve patient comfort, particularly for those with sensitive skinPATENT Attorney Docket No. N2041-04301 conditions such as rosacea or acne, where alcohol-based formulations can cause irritation, burning, or stinging sensations.

[0051] Scientific studies support the efficacy of azelaic acid in the treatment of skin disorders and in skin lightening formulations.

[0052] In an embodiment, the topical composition described herein comprises azelaic acid in a concentration from about 0.1% to about 20% by weight, for example about 10% by weight based on the total weight of the composition.

[0053] In an embodiment, the topical composition is an anhydrous formulation that is essentially free of water. This approach may avoid the necessity of including preservatives in the formulation and may enhance stability. In another embodiment, the composition is essentially free of alkyl alcohols, which may be beneficial for formulations intended for subjects with sensitive skin, rosacea, or acne.

[0054] In an embodiment, the lipophilic medium of the topical composition comprises one or more siloxane compounds. In an embodiment, siloxane compounds may include dimethicone (dimethy Ibis (trimethylsilyloxy) silane), dimethiconol (bis [[[[ [hydroxy (dimethyl) silyl] oxy-dimethylsilyl] oxy dimethylsilyl] oxy dimethylsilyl] oxy] -dimethylsilane), trisiloxane (dimethylbis(trimethylsilyloxy)silane), dimethicone / vinyltrimethylsiloxysilicate crosspolymer, silica dimethyl silylate, or combinations thereof. In an embodiment, these siloxane compounds may provide a pleasant skin feel and improve spreadability of the composition. In an embodiment, the siloxane compounds may also create a protective barrier that helps retain moisture while allowing the skin to breathe.

[0055] In an embodiment, the topical composition further comprises 1,2,3-propanetriol octanoate and bis(2-ethylhexyl) 2-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]propanedioate decanoic acid, ester. In an embodiment, these components may contribute to the skin conditioning properties of the composition.

[0056] In an embodiment, the topical composition further comprises an antioxidant. In an embodiment, the antioxidant may be selected from vitamin E, vitamin C, vitamin A, tocopheryl acetate, or combinations thereof. In an embodiment, the antioxidant may provide stability to the composition and may also contribute to the therapeutic effects of the composition. In an embodiment, the antioxidant is tocopheryl acetate (vitamin E acetate), which is converted into tocopherol in the skin, thus replenishing the skin's natural antioxidant reservoir. In an embodiment, Vitamin E may help reduce lipid peroxidation and oxidative stress induced by UV radiation and pollution. In an embodiment, the antioxidant may work synergistically withPATENT Attorney Docket No. N2041-04301 azelaic acid to enhance the overall efficacy of the composition in treating skin conditions such as acne vulgaris and rosacea.

[0057] In an embodiment, a topical composition is provided in a monodose packaging unit comprising a container. In an embodiment, the container is a twist-off ampule. In an embodiment, the monodose packaging unit protects the ingredients from exposure to harmful UV rays, air, and bacterial contamination. In an embodiment, the monodose packaging unit promotes hygiene by minimizing the risk of contamination since each ampule is used only once. In an embodiment, the monodose packaging unit eliminates the need for preservatives in the formulation. In an embodiment, the monodose packaging unit allows precise dosing for each application. In an embodiment, the capsule shape allows selection of the right amount for each daily application.

[0058] In an embodiment, the topical composition does not dissolve the container material, which may ensure stability and integrity of the packaging over time.

[0059] In an embodiment, the monodose packaging unit may be made of materials that are compatible with the lipophilic formulation, ensuring that no leaching or degradation occurs during storage. In an embodiment, the packaging material may provide protection from light, which may help maintain the stability and efficacy of light-sensitive ingredients such as antioxidants in the formulation.

[0060] In an embodiment, the topical compositions described herein may be useful for treating a variety of skin conditions, particularly acne vulgaris and rosacea. The composition may be administered by application to an affected area of skin, for example by topical application. In an embodiment, the composition may be applied once or twice daily, for example in the evening.

[0061] In an embodiment, for application, the user may twist or snip off the capsule neck to open the monodose unit, apply the formulation by lightly tapping the serum onto the skin, avoid contact with the eyes, and wash hands after the face application is completed. In an embodiment, the user may also use an SPF product during the day when using this product.

[0062] In an embodiment, the topical compositions described herein provide a therapeutically effective amount of azelaic acid in a stable, anhydrous formulation that is essentially free of ethanol and propylene glycol. These compositions may be particularly suitable for topical application to treat skin conditions including acne vulgaris and rosacea, as demonstrated by the representative human experimental studies shown in FIGS. 1-18.

[0063] In an embodiment, the topical compositions comprising azelaic acid in a lipophilic medium allow for improved penetration of the active ingredient into the skin layers wherePATENT Attorney Docket No. N2041-04301 therapeutic action is desired. The lipophilic medium may enhance the bioavailability of azelaic acid by facilitating its transport across the stratum comeum.

[0064] In an embodiment, the composition is formulated to provide sustained release of azelaic acid over time, thereby extending the therapeutic window and potentially reducing the frequency of application required.

[0065] In an embodiment, the monodose packaging unit provides precise dosing while protecting the stability of the composition, which may be particularly beneficial for topical compositions that are sensitive to external environmental factors.

[0066] Certain Exemplary Definitions

[0067] Before the present compounds, compositions, articles, devices, and / or methods are disclosed and described, it is to be understood that they are not limited to specific synthetic methods or specific recombinant biotechnology methods unless otherwise specified, or to particular reagents unless otherwise specified, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0068] As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a pharmaceutical carrier” includes mixtures of two or more such carriers, and the like.

[0069] Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value” and possible ranges between values are also disclosed. For example, if the value “10” is disclosed the “less than or equal to 10” as well as “greater than or equal to 10” is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example,PATENT Attorney Docket No. N2041-04301 if a particular data point “10” and a particular data point 15 are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as values between 10 and 15. For example, it is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed. In this application, if a data point range is disclosed, it is understood that each unit from the lowest data point to the highest stated datapoint, including the first (lowest) and last (highest) data point is disclosed. For example, if a data point range 1-20 is disclosed, it is understood that data points 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20, and each unit between any two particular units in the range are also disclosed. It is also understood that whenever a series of values are disclosed, that any range falling between any two of the recited values is also understood to be included.

[0070] In this specification and in the claims which follow, reference will be made to a number of terms which shall be defined to have the following meanings:

[0071] “Optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes embodiments where said event or circumstance occurs and embodiments where it does not.

[0072] As used herein, the terms “topical composition” and “composition” are used interchangeably and refer to a mixture of two or more compounds, elements, or molecules. In some embodiments, the composition includes a solvent, a solute, a protein, a lipid, a natural compound, or a synthetic compound. In some embodiments, the composition is therapeutic, diagnostic, or both.

[0073] As used herein, the term “lipophilic medium” refers to a substance, composition, or environment that is soluble in lipids or non-polar solvents. Eipophilic media may include, but are not limited to, oils, waxes, triglycerides, silicones, and other non-polar substances.

[0074] As used herein, “essentially free of ethanol” means that the composition contains less than about 5%, less than about 2%, less than about 1%, less than about 0.5%, or less than about 0.1% ethanol by weight of the total composition. In some embodiments, the composition contains no detectible amount of ethanol.

[0075] As used herein, “essentially free of water” means that the composition contains less than about 5%, less than about 2%, less than about 1%, less than about 0.5%, or less than about 0.1% water by weight of the total composition. In some embodiments, the composition contains no detectible amount of water.

[0076] As used herein, “essentially free of alkyl alcohols” means that the composition contains less than about 5%, less than about 2%, less than about 1%, less than about 0.5%, orPATENT Attorney Docket No. N2041-04301 less than about 0.1% alkyl alcohols by weight of the total composition. In some embodiments, the composition contains no detectible amount of alkyl alcohols.

[0077] As used herein, the term “essentially in the protonated acidic form” refers to azelaic acid that is substantially in the form of the free acid rather than a salt, ester, or other derivative. In some embodiments, at least about 90%, at least about 95%, at least about 98%, or at least about 99% of the azelaic acid in the composition is in the protonated acidic form.

[0078] As used herein, the term “therapeutically effective amount” refers to an amount of a compound, composition, or treatment that is sufficient to elicit a desired biological response, such as an improvement in the signs or symptoms of a condition being treated.

[0079] As used herein, the term “skin condition” refers to any disease, disorder, ailment, or abnormal state of the skin. Skin conditions include, but are not limited to, acne vulgaris, rosacea, psoriasis, aging of the skin, alopecia, solar keratoses, bacterial infection, malignant melanoma, melasma, lentigo maligna, hyperpigmentation, wrinkles, blemishes, lesions of the skin, perioral dermatitis, mycoplasma infection, or impetigo.

[0080] As used herein, the term “monodose packaging unit” refers to a single-use container or delivery system designed to hold one dose of a topical composition for a single administration.

[0081] As used herein, the term “twist-off ampule” refers to a sealed container that is opened by twisting or breaking off a portion of the container, typically at a predetermined breaking point or neck.

[0082] The term “subject” refers to any individual who is the target of administration or treatment. The subject can be a vertebrate, for example, a mammal. In one aspect, the subject can be human, non-human primate, bovine, equine, porcine, canine, or feline. The subject can also be a guinea pig, rat, hamster, rabbit, mouse, or mole. The subject can be a human or veterinary patient. The term subject, in some embodiments, refers to a “patient” under the treatment of a clinician, e.g., physician.

[0083] As used herein, the terms “treat” and “treatment” refer to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or decrease an undesired physiological change or disorder. For purposes of this disclosure, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. “Treatment” can also mean prolonging survival as compared to expected survival if not receiving treatment. Those in need of treatment includePATENT Attorney Docket No. N2041-04301 those already with the condition or disorder and those prone to have the condition or disorder or those in which the condition or disorder is to be prevented.

[0084] The term “preventing” means preventing in whole or in part, or ameliorating or controlling.

[0085] As used herein, the term “therapeutically effective amount” means an amount of a compound disclosed herein that (i) treats the particular disease, condition, or disorder, (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, or disorder, or (iii) prevents or delays the onset of or reduces the intensity of one or more symptoms of the particular disease, condition, or disorder described herein.

[0086] As used herein, the term “substantially the same” means an amount of expression, level, and / or activity of a gene or gene product within 90% of baseline expression, level, and / or activity as in a subject unaffected by a disease. “Substantially the same” can also mean an amount of expression, level, and / or activity of a gene or gene product within 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, to 100% of the baseline expression, level, and / or activity as in a subject unaffected by unaffected by a disease.

[0087] As described herein, any concentration range, percentage range, ratio range or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (including one-tenth and one-hundredth of an integer), unless otherwise indicated.

[0088] Topical compositions

[0089] In one embodiment, the topical composition comprises azelaic acid dispersed in a lipophilic medium or a medium essentially free of ethanol and propylene glycol, wherein the azelaic acid is essentially in the protonated acidic form. In some embodiments, the topical composition comprises, consists, or consists essentially of azelaic acid dissolved in a lipophilic medium essentially free of ethanol and propylene glycol, wherein the azelaic acid is essentially in the protonated acidic form. The concentration of azelaic acid in the composition can range from about 0.1% to about 20% by weight, preferably about 10% to about 20% by weight, and more preferably about 10% by weight based on the total weight of the composition.

[0090] In an embodiment, the anhydrous nature of the topical composition may provide several advantages, including enhanced stability of active ingredients, reduced need for preservatives, and potentially improved skin penetration of azelaic acid. In an embodiment, the absence of water may create an environment that is less conducive to microbial growth, which may contribute to the overall stability and shelf life of the product.PATENT Attorney Docket No. N2041-04301

[0091] The topical composition is preferably an anhydrous formulation that is essentially free of water. This avoids the necessity of including preservatives in the formulation and enhances stability. The composition is also preferably essentially free of alkyl alcohols, which can be drying and irritating to the skin, particularly when used in formulations intended for subjects with sensitive skin, rosacea, or acne.

[0092] Lipophilic Medium

[0093] The lipophilic medium of the topical composition can comprise one or more siloxane compounds. Suitable siloxane compounds include dimethicone (dimethylbis(trimethylsilyloxy)silane), dimethiconol (bis[[[[[hydroxy(dimethyl)silyl]oxy-dimethylsilyl] oxy dimethylsilyl] oxy dimethylsilyl] oxy] -dimethylsilane) , trisiloxane (dimethylbis(trimethylsilyloxy)silane), dimethicone / vinyltrimethylsiloxysilicate crosspolymer, and silica dimethyl silylate. These siloxane compounds provide a pleasant skin feel and improve spreadability of the composition.

[0094] The topical composition may further comprise 1,2,3-propanetriol octanoate and bis(2-ethylhexyl) 2-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]propanedioate decanoic acid, ester. These components contribute to the skin conditioning properties of the composition.

[0095] The inventors surprisingly discovered that even in the absence of water, certain azelaic acid compositions of this disclosure afford presentation to the skin a sufficient amount of azelaic acid to be therapeutically effective in treating acne vulgaris and / or rosacea.

[0096] Antioxidants

[0097] The topical composition may further comprise an antioxidant selected from vitamin E, vitamin C, vitamin A, and tocopheryl acetate. The antioxidant not only provides stability to the composition but also contributes to the therapeutic effects of the composition. In a preferred embodiment, the antioxidant is tocopheryl acetate (vitamin E acetate), which is converted into tocopherol in the skin, thus replenishing the skin's natural antioxidant reservoir. Vitamin E helps reduce lipid peroxidation and oxidative stress induced by UV radiation and pollution.

[0098] Therapeutic Benefits of Azelaic Acid

[0099] Azelaic acid, a naturally occurring straight-chained saturated dicarboxylic acid that is naturally present in several plants, has numerous beneficial effects on the skin. It helps rebalance keratinization and reduce the growth of bacteria in the follicle. Furthermore, it helps reduce hyperpigmentation by decreasing melanin synthesis.

[0100] When azelaic acid is applied to the skin, it exhibits several therapeutic actions simultaneously. The compound helps normalize the skin microflora, creating a more balanced environment on the skin surface. Additionally, azelaic acid helps control melanin synthesis,PATENT Attorney Docket No. N2041-04301 which is particularly beneficial for addressing hyperpigmentation concerns. It functions as an effective scavenger of reactive cytotoxic hydroxyl free radicals, providing antioxidant protection to the skin. Furthermore, azelaic acid helps control hyperkeratinization, which is the abnormal thickening of the outer layer of the skin. It also contributes to improving the skin barrier function, enhancing the skin's natural defense mechanisms against environmental stressors.

[0101] These multiple therapeutic actions culminate in numerous clinical benefits. Patients typically experience reduction of dark spots and discolorations, which leads to an improved overall skin tone. The formulation helps unclog pores and prevents the formation of comedones, including both blackheads and whiteheads. Users often notice a reduction in the appearance of skin redness, particularly beneficial for those with rosacea or acne-related inflammation. Overall, azelaic acid provides a soothing effect on the skin, making it suitable for sensitive skin conditions.

[0102] Scientific studies support the efficacy of azelaic acid in the treatment of skin disorders and in skin lightening formulations. In vitro studies have demonstrated the ability of azelaic acid to recover UVA-induced collagen damage on fibroblasts compared to untreated cells, and to inhibit Cutibacterium acnes activity. In vivo studies have shown that azelaic acid at 20% concentration can reduce mild to moderate acne vulgaris after 2 months of application, and reduce the number of comedones, papules, and pustules compared to placebo after 45 days of application.

[0103] Monodose Packaging

[0104] In an embodiment, the topical composition disclosed herein is provided in a monodose packaging unit comprising a container. The container may be a twist-off ampule. The monodose packaging unit provides several advantages. The monodose packaging effectively protects the active ingredients from exposure to harmful UV rays, air, and bacterial contamination, thereby maintaining the stability and efficacy of the formulation throughout its shelf life.

[0105] From a hygiene perspective, the monodose format minimizes the risk of contamination since each ampule is used only once and then discarded, preventing the introduction of contaminants that commonly occurs with repeatedly opened containers. This single-use approach eliminates the need for preservatives in the formulation, allowing for a cleaner ingredient profile and reducing potential irritants for sensitive skin.

[0106] The design facilitates precise dosing for each application, ensuring consistent results and preventing product waste. Furthermore, the capsule shape allows users to select thePATENT Attorney Docket No. N2041-04301 appropriate amount for each daily application based on their specific needs. Importantly, the topical composition is formulated to not dissolve or degrade the container material, ensuring long-term stability and integrity of both the packaging and the enclosed product throughout its intended storage period.

[0107] Methods of Treatment

[0108] The topical compositions disclosed herein are useful for treating a variety of skin conditions, particularly acne vulgaris and rosacea. The composition is administered by application to an affected area of skin, preferably by topical application. The composition may be applied once or twice daily, preferably in the evening.

[0109] For application, the user may twist or snip off the capsule neck to open the monodose unit, apply the formulation by lightly tapping the serum onto the skin, avoid contact with the eyes, and wash hands after the face application is completed. It is recommended that the user also use an SPF product during the day when using this product.

[0110] In an embodiment, the method may further comprise a regimen wherein the topical composition is applied after cleansing the skin and before the application of moisturizers or sunscreens. In an embodiment, for optimal results, the topical composition may be applied consistently for a period of at least 8 weeks, as clinical studies have demonstrated significant improvements in various skin parameters over this timeframe (FIGs 1-18). All of the measured parameters were statistically significant at the 2-week timepoint measurement.EXAMPLES

[0111] The specific methods and compositions described herein are representative of preferred embodiments and are exemplary and not intended as limitations on the scope of the invention. Other objects, aspects, and embodiments will occur to those skilled in the art upon consideration of this specification, and are encompassed within the spirit of the invention as defined by the scope of the claims. Thus, for example, in each instance herein, and in embodiments or examples disclosed herein, any of the terms “comprising”, “consisting essentially of’, and “consisting of’ may be replaced with either of the other two terms in the specification. The methods and processes illustratively described herein suitably may be practiced in differing orders of steps, and that they are not necessarily restricted to the orders of steps indicated herein or in the claims. It is also that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise. Under no circumstances may the patent be interpreted to be limited to the specific examples or embodiments or methods specifically disclosed herein. Under noPATENT Attorney Docket No. N2041-04301 circumstances may the patent be interpreted to be limited by any statement made by any Examiner or any other official or employee of the Patent and Trademark Office unless such statement is specifically and without qualification or reservation agreed to and expressly adopted in a responsive writing by Applicants.Example 1: Preparation of Azelaic Add SerumCAS INCI CONCEN FUNCTI CHEMICAL TRADE NUMBE NAME TRATION ON NAME NAMER (%)63148-62- DIMETHIC 88.000 Skin dimethylbis(trime BELSIL 9 / 70131- ONE 12.000 condition thylsilyloxy)silan GB102067-8 DIMETHIC ing e GUMONOL bis[[[[[hydroxy(d BLEND imethyl)silyl]oxydimethylsilyl] oxydimethylsilyl] oxydimethylsilyl] oxy| -dimethylsilane107-51-7 TRISILOXA 100 Skin Dimethyl- SERASENS NE condition bis(trimethylsilyl E SF 1...ing . oxy)silane123-99-9 AZELAIC Too . Skin Nonanedioic acid AZELAIC ACID lightenin ACIDg7695-91-2 TOCOPHER 100 Antioxid 3.4-Dihydro- DL-ALPHA YL ant 2, 5,7,8- TOCOPHE ACETATE tetramethyl-2- RYL(4,8,12- ACETATE trimethyltridecyl) EP,FCC,US -2H-benzopyran- P6-yl acetate"444811- . blETHYLH 90.000. Skin bis(2-ethylhexyl) OXYNEX .29-4 EXYL 10.000 condition 2-[(4-hydroxy- ST LIQUID 73398-61- SYRINGYL ing 3.5- 5 / 65381- IDENEMAL dimethoxyphenyl09-1 ONATE )methylidene]proCAPRYLIC / panedioateCAPRIC Decanoic acid,TRIGLYCE ester with 1,2,3- RIDE propanetrioloctanoate63148-62- DIMETHIC 84.000. Skin dimethylbis(trime BELSIL9 # ONE 16.000 condition thylsilyloxy)silan REG 1102DIMETHIC ing e SILICONEL ONE / VINY ASTOMERLTRIMETH RESIN GELPATENT Attorney Docket No. N2041-04301 YESIEOXY SILICATE CROSSPOL YMER68611-44- SILICA 100 Viscosity Silane, AEROSIL 9 DIMETHYL controlli dichlorodimethyl R972SILYLATE ng -, reactionproducts withsilica

[0112] The composition was prepared by mixing all ingredients under controlled conditions to ensure proper dissolution of azelaic acid in the lipophilic medium. The resulting serum was filled into twist-off ampule monodose packaging units.

[0113] In some embodiments, the composition comprises a dimethicone or a trisiloxane. In some embodiments, the composition comprises SeraSense SF1 or SeraSense SF2.Example 2: Efficacy Testing on Rosacea-Prone Skin

[0114] Methodology

[0115] The efficacy of the azelaic acid serum was evaluated in a clinical study on subjects with rosacea-prone skin. The study details were as follows:• Number of test subjects: 32 total with rosacea-prone skin (90% with self-perceived sensitive skin) with post acne / rosacea blemishes• Age: Between 37 and 65 years• Duration: 8 weeks• Sex: 30 Female & 2 Male• Frequency: Once daily• Data Collection Periods: Initial start, after 24 hours, 1, 2, 4 & 8 weeks

[0116] Selection Criteria:

[0117] The selected subjects had not used a cosmetic face cream with similar activity to the test product in the previous 2 weeks and / or topical medication within the month.

[0118] During the study, it was requested that participants do not make any changes to their normal daily routine and do not use products with similar activity to the test product throughout the duration of the study.

[0119] Self-assessment: Subjects were asked to respond to a questionnaire immediately after application and then again after 4 and 8 weeks of application.

[0120] Results

[0121] Based on measured instrumental data (FIG. 1):PATENT Attorney Docket No. N2041-04301 • 64% of subjects saw positive results after 24 hours• 77% after 1 week• 99% after 8 weeks of treatment

[0122] After the first application (FIGs. 2, 3, and 5):• Decreased trans-epidermal water loss by 19.37%• Improved skin hydration by 10.2%• Decreased skin redness color (a*) by 4.59%• Decreased skin redness (hemoglobin) by 6.2%• 75% of subjects assessed a soothing effect after 24 hours

[0123] After 8 weeks (FIGs. 2-5):• Decreased trans-epidermal water loss by 43.46%• Improved skin hydration by 50.16%• Decreased skin redness color (a*) by 27.08%• Decreased skin redness (hemoglobin) by 25.96%• Decreased pigmentary lesions / blemishes visibility by 35.19%

[0124] 94% of subjects assessed reduction of skin redness, post acne-rosacea blemishes appearance, pore visibility, and improvement of skin smoothness, tone, and hydration (FIG. 9).

[0125] The visual improvements further include a progressive reduction in skin redness and blemishes is observable over the treatment period (FIGS. 6 and 7).

[0126] The product demonstrated good skin acceptability, with only 3 subjects reporting transient sensation of discomfort that disappeared spontaneously, and no clinical sign was observed by the dermatologist.Example 3: Efficacy Testing on Acne-Prone Skin

[0127] Methodology

[0128] The efficacy of the azelaic acid serum was also evaluated in a clinical study on subjects with acne-prone skin. The study details were as follows:• Number of test subjects: 30 total with acne-prone skin (Grade I and II of IGA scale) with post acne blemishes• Age: Between 18 and 25 years• Duration: 8 weeks• Sex: 24 Female & 6 Male• Frequency: Once daily• Data Collection Periods: Initial start, after 24 hours, 1, 2, 4 & 8 weeksPATENT Attorney Docket No. N2041-04301

[0129] Selection Criteria:

[0130] The selected subjects had not used a cosmetic face cream with similar activity to the test product in the previous 2 weeks and / or topical anti-acne medication within the month.

[0131] During the study, it was requested that participants do not make any changes to their normal daily routine and do not use products with similar activity to the test product throughout the duration of the study.

[0132] Self-assessment:

[0133] Subjects were asked to respond to a questionnaire immediately after application and then again after 4 and 8 weeks of application.

[0134] Results

[0135] Based on measured instrumental data (FIG. 10):• 63% of subjects saw positive results after 24 hours;• 71% after 1 week;• 83% after 2 weeks;• 90% after 4 weeks; and• 98% after 8 weeks of treatment.

[0136] After the first application (FIG, 11, 12, and 14):• Decreased trans-epidermal water loss by 22.95%;• Improved skin hydration by 12.9%;• Decreased skin redness color (a*) by 4.78%;• Decreased skin redness (hemoglobin) by 8.25%; and• 73% of subjects assessed a soothing effect after 24 hours.

[0137] After 8 weeks (FIGs. 11-14):• Decreased trans-epidermal water loss by 46.23%;• Improved skin hydration by 49.85%;• Decreased skin redness color (a*) by 31.56%;• Decreased skin redness (hemoglobin) by 28.63%;• Decreased pigmentary lesions / blemishes visibility by 33.18%; and• 97% of subjects assessed reduction of skin redness, post acne blemishes appearance, pore visibility, skin oiliness, and improvement of skin smoothness, tone, and hydration (FIG. 18).

[0138] A progressive reduction in skin redness and blemishes is also observable over the treatment period (FIGs. 15 and 16).PATENT Attorney Docket No. N2041-04301

[0139] The product demonstrated good skin acceptability, with only 3 subjects reporting transient sensation of discomfort that disappeared spontaneously, and no clinical sign was observed by the dermatologist.Example 4: Safety Testing

[0140] In vivo Repeated Insult Patch Test (RIPT)

[0141] Method: Skin tolerance test was conducted on 54 people (54% with self-perceived sensitive skin) as follows:• Induction Phase: 9 Repeated Insult Patch tests (3 applications per week)• Challenge phase: 1 application after a rest period of 2 weeks• Skin examination was performed after 24 and 72 hours after application. Any potential appearance was recorded as a sign of irritation potential.

[0142] Result: Under the condition of repeated insult (semi-occlusive) patch test procedure, the product was "Dermatologist-Tested" and was not associated with skin irritation or allergic contact dermatitis in human subjects.

[0143] In vitro Evaluation of Ocular Potential Irritation

[0144] Evaluation of the Ocular Potential Irritancy of a Cosmetic Product by the Neutral Red Release Assay

[0145] Determination of the cytotoxicity after diffusion in agar gel

[0146] Result: The cytotoxicity is in the normal range for eligible non-irritating test products. The cytotoxicity of the topical compositions of this disclosure are not very severe.

[0147] Conclusion: The product has good skin compatibility.

[0148] Stability studies were conducted on the azelaic acid serum in different packaging types (glass jar, PET jar, and blister) under varying temperature and humidity conditions over 3 months (FIG. 19). All test conditions were found to be acceptable, demonstrating the robust stability profile of the formulation across different storage environments.

[0149] It is known from reference in vivo studies that azelaic acid at 20% concentration reduces mild to moderate acne vulgaris after 2 months of application, and reduces the number of comedones, papules, and pustules compared to placebo after 45 days of application.

[0150] The Investigators' Global Assessment Scale (IGA) was used for enrollment of subjects for the representative experiments to assess acne severity, with visual representations of severity levels ranging from 0 (clear skin with no inflammatory or noninflammatory lesions) to 4 (severe; up to many noninflammatory and inflammatory lesions, but no more than a few nodular lesions). A scale was used for enrollment of subjects for the representative experimentsPATENT Attorney Docket No. N2041-04301 to assess rosacea severity, showing 0 (absent), 1 - mild (A), 2 - moderate (B), and 3 - severe (C) levels.

[0151] Example 5: Stability Study

[0152] The stability of the azelaic acid serum composition was evaluated in different packaging types and under various storage conditions. The composition was placed in glass jar, PET jar, and blister packaging and stored for 3 months at 4°C, room temperature (R.T.), 25°C / 60% RH, and 40°C / 75% RH.

[0153] Results: After 3 months, all test conditions were found to be acceptable, indicating good stability of the formulation.

[0154] The study confirmed that the monodose packaging in twist-off ampules is suitable for the azelaic acid serum formulation, providing both stability and convenience for the user.

[0155] The stability study results (FIG. 19) demonstrated that the azelaic acid composition remained stable across multiple packaging options and storage conditions. The composition maintained its physical properties and therapeutic efficacy throughout the three-month testing period, confirming the robustness of the formulation across various environmental conditions.

[0156] Azelaic acid is known to exhibit multiple beneficial effects, including recovery of UVA-induced collagen damage on fibroblasts and inhibition of Cutibacterium acnes activity in vitro. The in vivo studies further substantiate the therapeutic efficacy of azelaic acid at 20% concentration in reducing mild to moderate acne vulgaris and decreasing the number of comedones, papules, and pustules compared to placebo.

[0157] The terms and expressions that have been employed are used as terms of description and not of limitation, and there is no intent in the use of such terms and expressions to exclude any equivalent of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention as claimed. Having thus described in detail preferred embodiments disclosed herein, it is to be understood that the invention defined by the above paragraphs is not to be limited to particular details set forth in the above description as many apparent variations thereof are possible without departing from the spirit or scope disclosed herein.

[0158] The inventions described and claimed herein have many attributes and embodiments including, but not limited to, those set forth or described or referenced in this Detailed Disclosure. It is not intended to be all-inclusive and the inventions described and claimed herein are not limited to or by the features or embodiments identified in this Detailed Disclosure, which is included for purposes of illustration only and not restriction. A person having ordinary skill in the art will readily recognize that many of the components andPATENT Attorney Docket No. N2041-04301 parameters may be varied or modified to a certain extent or substituted for known equivalents without departing from the scope of the invention. It should be appreciated that such modifications and equivalents are herein incorporated as if individually set forth. The invention also includes all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more of said steps or features.

[0159] All patents, publications, scientific articles, web sites, and other documents and materials referenced or mentioned herein are indicative of the levels of skill of those skilled in the art to which the invention pertains, and each such referenced document and material is hereby incorporated by reference to the same extent as if it had been incorporated by reference in its entirety individually or set forth herein in its entirety. Applicants reserve the right to physically incorporate into this specification any and all materials and information from any such patents, publications, scientific articles, web sites, electronically available information, and other referenced materials or documents. Reference to any applications, patents and publications in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that they constitute valid prior art or form part of the common general knowledge in any country in the world.

[0160] The specific methods and compositions described herein are representative of preferred embodiments and are exemplary and not intended as limitations on the scope of the invention. Other objects, aspects, and embodiments will occur to those skilled in the art upon consideration of this specification, and are encompassed within the spirit of the invention as defined by the scope of the claims. It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. The invention illustratively described herein suitably may be practiced in the absence of any element or elements, or limitation or limitations, which is not specifically disclosed herein as essential. Thus, for example, in each instance herein, in embodiments or examples disclosed herein, any of the terms “comprising”, “consisting essentially of’, and “consisting of’ may be replaced with either of the other two terms in the specification. Also, the terms “comprising”, “including”, containing”, etc. are to be read expansively and without limitation. The methods and processes illustratively described herein suitably may be practiced in differing orders of steps, and that they are not necessarily restricted to the orders of steps indicated herein or in the claims. It is also that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise. Under no circumstances may the patent bePATENT Attorney Docket No. N2041-04301 interpreted to be limited to the specific examples or embodiments or methods specifically disclosed herein. Under no circumstances may the patent be interpreted to be limited by any statement made by any Examiner or any other official or employee of the Patent and Trademark Office unless such statement is specifically and without qualification or reservation expressly adopted in a responsive writing by Applicants. Furthermore, titles, headings, or the like are provided to enhance the reader’ s comprehension of this document, and should not be read as limiting the scope disclosed herein. Any examples of aspects, embodiments or components of the invention referred to herein are to be considered non-limiting.

[0161] The terms and expressions that have been employed are used as terms of description and not of limitation, and there is no intent in the use of such terms and expressions to exclude any equivalent of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention as claimed. Thus, it will be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.

[0162] The invention has been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

[0163] Other embodiments are within the following claims. In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group.

Claims

1. PATENT Attorney Docket No. N2041-04301 CLAIMSWhat is claimed is:

1. A topical composition for treating a skin condition, comprising a therapeutically effective amount of azelaic acid dispersed in a lipophilic medium or a medium essentially free of ethanol, and propylene glycol, wherein the azelaic acid is essentially in the protonated acidic form.

2. The topical composition of claim 1, wherein the composition is further essentially free of water.

3. The topical composition of claim 1, wherein the composition is further essentially free of alkyl alcohols.

4. The topical composition of claim 1, further comprising an antioxidant.

5. The topical composition of claim 4, wherein the antioxidant is selected from vitamin E, vitamin C, vitamin A, and tocopheryl acetate.

6. The topical composition of claim 1, further comprising a one or a plurality of siloxane compounds selected from: dimethicone (dimethylbis(trimethylsilyloxy)silane), dimethiconol (bis [[[ [[hydroxy (dimethyl) silyl] oxydimethylsilyl] oxy dimethylsilyl] oxy dimethylsilyl] oxy] -dimethylsilane) , trisiloxane (Dimethylbis(trimethylsilyloxy)silane), dimethicone / vinyltrimethylsiloxysilicate crosspolymer, and silica dimethyl silylate.

7. The topical composition of claim 1, further comprising 1,2,3-propanetriol octanoate and bis(2-ethylhexyl) 2-[(4-hydroxy-3,5- dimethoxyphenyl)methylidene]propanedioate decanoic acid, ester.

8. The topical composition of claim 1, wherein the concentration of azelaic acid is from 0.1 to 20 wt.%.

9. The topical composition of claim 8, wherein the concentration of azelaic acid is about 10 wt.%.

10. The topical composition of claim 8, wherein the concentration of azelaic acid is about 20 wt.%.PATENT Attorney Docket No. N2041-04301 11. The topical composition of any of claims 1-10, wherein the composition is configured to be an ointment, cream, gel, paste, lotion, spray, liquid, or transdermal patch.

12. A kit comprising the topical composition of any of claims 1-11 in a monodose packaging unit comprising a container.

13. The kit of claim 12, wherein the topical composition does not dissolve the container.

14. The kit of claim 12, wherein the monodose packing unit comprising a container is a twist-off ampule.

15. A method of treating a skin condition in a patient in need thereof, the method comprising:a. administering to said patient a therapeutically effective amount of the topical composition of any of claims 1-11,wherein the skin condition is selected from acne vulgaris or rosacea.

16. The method of claim 15, wherein administering is by application of the topical composition to the affected area of the skin of said subject.

17. The method of claim 15, wherein administering is by topical application.

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