Dermatologic formulation

Abstract

The present disclosure relates to dermatologic formulations for reducing skin imperfections, such as imperfections that arise from ageing. In particular, the present disclosure relates to dermatologic formulations that can provide improved complexation and / or elevate hyaluronic acid levels in the skin. The present disclosure also relates to methods for producing dermatologic formulations and uses of dermatologic formulations for providing an improved complexion.

Description

[0001] DERMATOLOGIC FORMULATION

[0002] FIELD

[0003] The present invention relates generally to a dermatologic formulation comprising an antioxidant, a biotic material, and a ceramide and / or a ceramide precursor. Also provided are methods and uses of the dermatologic formulation, including, for example, hydrating skin.

[0004] BACKGROUND

[0005] It is highly desirable to attain, and maintain, an ideal complexion that is free from skin imperfections. Such skin imperfections can include acne and blemishes, dark spots, wrinkles and fine lines, enlarged pores, scars, and the like.

[0006] With age, the skin undergoes intrinsic ageing, resulting in visible changes such as the increased presence of dark spots, wrinkles, and fine lines. This intrinsic ageing is accelerated by extrinsic factors, such as exposure to ultraviolet radiation (e.g., UV-A). Other factors, including dietary habits, smoking, excessive alcohol consumption, environmental pollution, chronic diseases, and endocrine gland dysfunctions, also contribute to skin ageing.

[0007] In particular, wrinkles are typically the most visible sign of ageing. A distinction can be made from several types of wrinkles, including superficial and deep wrinkles. Where deep wrinkles are thought to be due to dermo-hypodermal modifications, superficial wrinkles are explained by dermal / epidermal modifications. Wrinkles are most often attributed to a loss of skin elasticity. Maintaining the hydration, or moisture content, of the skin is also critical to reducing the signs of ageing. Altogether, reducing the signs of ageing leads to a more healthy -looking complexion.

[0008] One means to improve complexion, and reduce imperfections, is via invasive cosmetic procedures and surgeries. These can include fillers (e.g., Restylane, Juvaderm), laser resurfacing, and Botox. While such invasive cosmetic procedures and surgeries may provide long-lasting effects, consumers either cannot afford, or do not wish, to undergo such drastic procedures.

[0009] Instead, consumers are turning to non-invasive means. Typically, non-invasive means include cosmetic formulations that are applied to the skin, as part of a skincare routine.

[0010] Consumers are favouring dermatologic formulations wherein the label claims are supported by scientific evidence / data. Much progress has been made in recent times into the advancement of scientifically-backed dermatologic formulations, especially the emergence ofdermatologic formulations that comprise individual ingredients that specifically address the visible signs of ageing of the skin. These include, for example, Vitamin C, retinol / retinal, squalene, niacinamide, various peptides, and the like. However, these dermatologic formulations suffer from various drawbacks, and many remain limitedly successful in ameliorating skin imperfections. Indeed, there remains a need for new dermatologic formulations that reduce skin imperfections, particularly those imperfections that arise from ageing, and that lead to an overall improved complexion.

[0011] SUMMARY

[0012] The present inventors have surprisingly discovered a dermatologic formulation that provides an improved complexion. In particular, the present inventors have surprisingly discovered a dermatologic formulation that elevates hyaluronic acid levels in the skin.

[0013] In one aspect, there is provided a dermatologic formulation, comprising: an antioxidant; a biotic material; and a ceramide and / or a ceramide precursor. In some embodiments, the antioxidant is present in an amount of about 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 1.5% or 2.0% by weight. In some embodiments, the antioxidant is ectoin. In some embodiments, the biotic material is present in an amount of about 0.01%, 0.02%, 0.03%, 0.04%, 0.045%, or 0.05%, by weight of the dermatologic formulation. In some embodiments, the biotic material comprises Lactobacillus ferment lysate. In some embodiments, the Lactobacillus ferment lysate is present in an amount of about 0.03%, by weight of the dermatologic formulation. In some embodiments, the biotic material comprises dandelion leaf extract. In some embodiments, the dandelion leaf extract is present in an amount of about 0.015%, by weight of the dermatologic formulation. In some embodiments, the ceramide and / or ceramide precursor is selected from the group consisting of ceramide NP, ceramide AP, ceramide EOP, phytosphingosine, and combinations thereof. In some embodiments, the ceramide and / or ceramide precursor is present in a total amount of about 0.010%, 0.015%, 0.020%, 0.025%, 0.030%, 0.035%, 0.040%, 0.045%, or 0.050%, by weight of the dermatologic formulation. In some embodiments, the dermatologic formulation further comprises a humectant. In some embodiments, the humectant is glycerol. In some embodiments, the humectant is present in an amount of about 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 1.5%, or 2%, by weight of the dermatologic formulation. In some embodiments, the dermatologic formulation further comprises an emollient. In some embodiments, the emollient is sunflower oil, capryl triglyceride, shea butter, and combinations thereof. In some embodiments, the emollient is present in a total amount of about 0.5%, 1.0%, 1.5%, or 2.0%, by weight of the dermatologic formulation. In some embodiments, there isprovided the dermatologic formulation described herein, comprising: ectoin in an amount of about 1.0%; Lactobacillus ferment lysate and dandelion leaf extract in an amount of about 0.045%; and ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine in a total amount of about 0.0325%, by weight of the dermatologic formulation. In some embodiments, there is provided the dermatologic formulation described herein, comprising: ectoin; Lactobacillus ferment lysate and dandelion leaf extract; ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine; glycerol; sunflower oil; capryl triglyceride; and shea butter. In some embodiments, there is provided the dermatologic formulation described herein, comprising: ectoin in an amount of about 1.0%; Lactobacillus ferment lysate and dandelion extract in an amount of about 0.045%; ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine in a total amount of about 0.0325%; glycerol in an amount of about 1.0%; sunflower oil in an amount of about 0.5%; capryl triglyceride in an amount of about 1.0%; and shea butter in an amount of about 0.4%, by weight of the dermatologic formulation. In some embodiments, the dermatologic formulation does not comprise acetyl zingerone. In some embodiments, the dermatologic formulation described herein, further comprises a dermatologically acceptable excipient.

[0014] In a further aspect, there is provided use of the dermatologic formulation as described herein, for elevating hyaluronic acid levels in the skin. In some embodiments, elevating hyaluronic acid levels in the skin is an increase in hyaluronic acid production and decrease in hyaluronic acid degradation. In some embodiments, elevating hyaluronic acid levels in the skin provides increased skin hydration, improved elasticity of the skin, decreased signs of ageing of the skin (e.g., dark spots, wrinkles), increased strength of the barrier function of the skin (i.e., epidermis), and combinations thereof. In some embodiments, the elevation in hyaluronic acid is hyaluronic acid levels measured in normal human dermal fibroblast (NHDF) cells of at least 100%, 105%, 110%, 115%, or 120% after 72 hours of treatment at a concentration of 0.01% when compared to control.

[0015] In a further aspect, there is provided the dermatologic formulation as described herein, for use in a method of elevating hyaluronic acid levels in the skin.

[0016] In a further aspect, there is provided a method of elevating hyaluronic acid in the skin of a subject, comprising applying to the skin of the subject a dermatologic formulation as described herein.

[0017] In a further aspect, there is provided use of the dermatologic formulation as described herein, in the manufacture of a medicament for the elevation of hyaluronic acid in the skin.

[0018] In some embodiments, the dermatologic formulation described herein further providesantioxidant activity.

[0019] Any embodiment herein shall be taken to apply mutatis mutandis to any other embodiment unless specifically stated otherwise. For instance, as the skilled person would understand, details of the dermatologic formulation described herein may be applicable to all aspects and embodiments of the present disclosure.

[0020] The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended for the purpose of exemplification only. Functionally-equivalent products, compositions and methods are clearly within the scope of the invention, as described herein.

[0021] Throughout this specification, unless specifically stated otherwise or the context requires otherwise, reference to a single step, composition of matter, group of steps or group of compositions of matter shall be taken to encompass one and a plurality (i.e. one or more) of those steps, compositions of matter, groups of steps or group of compositions of matter.

[0022] BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graphical representation of the cell viability (MTT assay) results showing normalised cell viability after treatment of human keratinocyte cells with the tested compositions compared to on-treated control. Data are represented as mean ± standard error of the mean (SEM). Statistical significance is depicted as * for p-value < 0.05; ** p-value < 0.01; and **** p-value < 0.0001.

[0023] FIG. 2 is a bar graph showing hyaluronic acid protein levels after treatment of human fibroblasts with COMP A, COMP B, COMP C, and base (control) for 72 hours, normalised to the non-treated control. Data are represented as mean ± standard error of the mean (SEM). Statistical significance is depicted as * for p-value < 0.05; ** p-value < 0.01; and **** p-value < 0.0001.

[0024] DETAILED DESCRIPTION

[0025] General Techniques and Definitions

[0026] Unless specifically defined otherwise, all technical and scientific terms used herein shall be taken to have the same meaning as commonly understood by one of ordinary skill in the art (e.g., chemistry, medicinal chemistry and the like). As used herein, the term “and / or”, e.g., “X and / or Y” shall be understood to mean either "X and Y" or "X or Y" and shall be taken to provide explicit support for both meanings or for either meaning.As used herein, the term about, unless stated to the contrary, refers to + / - 20%, more preferably + / - 10%, of the designated value.

[0027] As used herein, singular forms “a”, “an” and “the” include plural aspects, unless the context clearly indicates otherwise.

[0028] Throughout this specification, the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

[0029] As used herein, the term “subject” refers to a human.

[0030] Dermatologic Formulation

[0031] Provided herein is a dermatologic formulation.

[0032] It has been surprisingly found that a dermatologic formulation comprising an antioxidant, a biotic material, and a ceramide and / or a ceramide precursor, provides advantageous properties to the skin, including an improved complexion. In particular, when provided together in the dermatologic formulation, the antioxidant, biotic material, and ceramide and / or a ceramide precursor impart surprising, unexpected, and advantageous properties to the skin, including, for example, an improved complexion.

[0033] As used herein, the term “complexion” refers to the natural colour, texture, and appearance of a person’s skin, and particularly the face. It will be appreciated that an ideal complexion is subjective, though typically satisfied by even colour, a smooth texture, and overall healthy appearance of a person’s skin. As used herein, the term “skin” refers to the layers of tissue forming the natural outer covering of the body of a subject (i.e., a human). The terms “dermal”, “derma”, and “dermis”, may be used interchangeably, and relate to the skin. The person skilled in the art will appreciate that the skin comprises three layers of tissue - the epidermis (outer layer), dermis (middle layer), and hypodermis (inner layer). Accordingly, in some embodiments, the dermatologic formulation disclosed herein provides advantageous properties to the skin, including advantageous properties to any one of more the epidermis, dermis, and / or hypodermis.

[0034] Accordingly, in some embodiments there is provided a dermatologic formulation comprising an antioxidant, a biotic material, and a ceramide and / or a ceramide precursor.

[0035] AntioxidantIn some embodiments, there is provided a dermatologic formulation comprising an antioxidant.

[0036] As used herein, the term “antioxidant” refers to a substance that inhibits oxidation. When applied in a dermatologic formulation, an antioxidant may provide benefits to the skin, including, for example, preventing or slowing cell damage, preventing or reducing skin inflammation, and preventing, lessening, or reversing ultraviolet (UV), particularly UVA, damage in the skin. Overall, an antioxidant may impart to the skin an anti-ageing effect.

[0037] The dermatologic formulation described herein comprises an antioxidant. In some embodiments, the antioxidant is present in the dermatologic formulation in an amount of about 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 1.5% or 2.0%, by weight of the dermatologic formulation. In some embodiments, the antioxidant is present in the dermatologic formulation in an amount of less than about 5.0%, 4.0%, 3.0%, 2.0%, 1.5%, or about 1.0%, by weight of the dermatologic formulation. In some embodiments, the antioxidant is present in the dermatologic formulation in an amount of at least about 0.01%, 0.05%, 0.1%, 0.5%, 0.75% or about 1.0%, by weight of the dermatologic formulation. In some embodiments, the antioxidant is present in the dermatologic formulation in an amount of less than about 10%, 8%, 5%, or 2%, by weight of the dermatologic formulation. In some embodiments, the antioxidant is present in the dermatologic formulation in an amount of between about 0.01% and about 5.0%, between about 0.1% and about 2.5%, or between about 0.5% and about 1.5%, by weight of the dermatologic formulation. In one example, the antioxidant is present in the dermatologic formulation in an amount of about 1.0%, by weight of the dermatologic formulation.

[0038] In some embodiments, the antioxidant is ectoin (also referred to as “ectoine”, “ectoine sodium salt monohydrate”, “THP(B)”, and “RonaCare®”). Ectoin has the preferred IUPAC name of (4S)-2-Methyl-3,4,5,6-tetrahydropyrimidine-4-carboxylic acid and the following chemical structure:

[0039]

[0040] Ectoin.

[0041] Accordingly, in some embodiments, ectoin is present in the dermatologic formulation in an amount of about 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 1.5% or 2.0%, by weight of the dermatologic formulation. In some embodiments, ectoin is present in the dermatologic formulation in an amount of less than about 5.0%, 4.0%, 3.0%, 2.0%, 1.5%, or about 1.0%, byweight of the dermatologic formulation. In some embodiments, ectoin is present in the dermatologic formulation in an amount of at least about 0.01%, 0.05%, 0.1%, 0.5%, 0.75% or about 1.0%, by weight of the dermatologic formulation. In some embodiments, ectoin is present in the dermatologic formulation in an amount of less than about 10%, 8%, 5%, or 2%, by weight of the dermatologic formulation. In some embodiments, ectoin is present in the dermatologic formulation in an amount of between about 0.01% and about 5.0%, between about 0.1% and about 2.5%, or between about 0.5% and about 1.5%, by weight of the dermatologic formulation. In one example, ectoin is present in the dermatologic formulation in an amount of about 1.0%, by weight of the dermatologic formulation.

[0042] In some embodiments, the antioxidant consists of ectoin (i.e., no other antioxidant is present in the dermatologic formulation). In some embodiments, the antioxidant is not acetyl zingerone. In some embodiments, the antioxidant is not a combination of ectoin and acetyl zingerone.

[0043] Biotic Material

[0044] In some embodiments, there is provided a dermatologic formulation comprising a biotic material. As used herein, the term “biotic material” refers to a substance that comprises living, or once living, organisms, such as microorganisms. In some embodiments, the biotic material comprises both prebiotic and probiotic functionality. Accordingly, in one example, the biotic material comprises a prebiotic. In one example, the biotic material comprises a probiotic. In one example, the biotic material comprises a prebiotic and a probiotic. Also as used herein, the term “prebiotic” refers to a substance that fosters the growth or activity of communities of beneficial microorganisms, including bacteria and fungi. Also as used herein, the term “probiotic” refers to a substance, comprising a live microorganism, (e.g., a bacterium or a fungus) that adds to communities of beneficial microorganisms. This addition may serve to increase the amount of any one or more beneficial microorganisms, or may otherwise increase the diversity of the overall community of beneficial microorganisms. When applied in a dermatologic formulation, a biotic material may provide benefits to the skin, including reducing inflammation of the skin, increasing the strength of the barrier function of the skin, minimising skin sensitivity, and reducing acne. Overall, a biotic material may impart to the skin an improved / balanced skin microbiota.

[0045] In a dermal application, microbiota, or communities of microorganisms, reside on the skin. This is particularly referred to as the “skin microbiota”. It therefore follows that a prebiotic applied to the skin may foster the growth or activity of communities of beneficialmicroorganisms in the skin microbiota. Similarly, it therefore follows that a probiotic applied to the skin may add to the communities of beneficial microorganisms.

[0046] The dermatologic formulation described herein comprises a biotic material, and the biotic material consists of a prebiotic and a probiotic. In some embodiments, the biotic material is present in the dermatologic formulation in a total amount of about 0.01%, 0.02%, 0.03%, 0.04%, 0.045%, or 0.05%, by weight of the dermatologic formulation. In some embodiments, the biotic material is present in the dermatologic formulation in a total amount of at least about 0.01%, 0.02%, 0.03%, 0.04%, or 0.05%, by weight of the dermatologic formulation. In some embodiments, the biotic material is present in the dermatologic formulation in a total amount of less than about 0.1%, 0.08%, 0.07%, 0.06%, 0.05%, or 0.045%, by weight of the dermatologic formulation. In some embodiments, the biotic material is present in the dermatologic formulation in a total amount of between about 0.01% and about 1.0%, between about 0.025% and about 0.06%, or between about 0.04% and about 0.05%, by weight of the dermatologic formulation. In one example, the biotic material is present in the dermatologic formulation in a total amount of about 0.045%, by weight of the dermatologic formulation.

[0047] In some embodiments, the prebiotic is selected from the group consisting of fructans, galacto-oligosaccharides, starch- and glucose-derived oligosaccharides, and pectic oligosaccharides. In one example, the prebiotic is a galacto-oligosaccharide. Galactooligosaccharides include the P-galactosidases.

[0048] In some embodiments, the dandelion leaf extract is present in the dermatologic formulation in an amount of at least about 0.1%, 0.2%, 0.3%, 0.4%, or 0.5%, by weight of the dermatologic formulation. In some embodiments, the dandelion leaf extract is present in the dermatologic formulation in an amount of less than about 5.0%, 2.5%, 1.5%, 1.0%, or 0.5%, by weight of the dermatologic formulation. In some embodiments, the dandelion leaf extract is present in the dermatologic formulation in an amount of between about 0.1% and about 5.0%, between about 0.2% and about 2.5%, or between about 0.4% and about 1.0%, by weight of the dermatologic formulation. In some embodiments, the dandelion leaf extract is present in the dermatologic formulation in an amount of about 0.015%, by weight of the dermatologic formulation.

[0049] In some embodiments, the probiotic is sourced from a food product containing a lactic acid bacteria (LAB). Such food products may include, for example, pickled vegetables, kimchi, pao cai, sauerkraut, and sourdough bread. In some embodiments, the probiotic is selected from the group consisting of Lactobacillus spp., Weissella spp., and Leuconostoc spp. In some embodiments, the probiotic is selected from the group consisting of Leuconostocmesenteroides, Lactobacillus plantarum, Pediococcus pentosaceus, Lactobacillus brevis, Leuconostoc citreum, Leuconostoc argentinum, Lactobacillus paraplantarum, Lactobacillus coryniformis, Lactobacillus lactis, Lactobacillus fermentum, Lactobacillus acidophilus, Bifidobacterium bifidum, Streptococcus thermophilus, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus helveticus, and Lactobacillus kefiranofaciens . In one example, the probiotic is Lactobacillus spp. Accordingly, in some embodiments, the biotic material is a mixture comprising Lactobacillus ferment lysate and dandelion leaf extract.

[0050] In some embodiments, the Lactobacillus ferment lysate is present in the dermatologic formulation in an amount of at least about 0.005%, 0.01%, 0.015%, 0.02%, 0.025%, or 0.03%, by weight of the dermatologic formulation. In some embodiments, the Lactobacillus ferment lysate is present in the dermatologic formulation in an amount of less than about 0.5%, 0.1%, 0.05%, 0.04%, or 0.03%, by weight of the dermatologic formulation. In some embodiments, the Lactobacillus ferment lysate is present in the dermatologic formulation in an amount of between about 0.005% and about 0.5%, between about 0.01% and about 0.05%, or between about 0.02% and about 0.04%, by weight of the dermatologic formulation. In some embodiments, the Lactobacillus ferment lysate is present in the dermatologic formulation in an amount of about 0.03%, by weight of the dermatologic formulation.

[0051] In some embodiments, the Lactobacillus ferment lysate and dandelion leaf extract are present in the dermatologic formulation in a total amount of about 0.01%, 0.02%, 0.03%, 0.04%, 0.045%, or 0.05%, by weight of the dermatologic formulation. In some embodiments, the Lactobacillus ferment lysate and dandelion leaf extract are present in the dermatologic formulation in a total amount of at least about 0.01%, 0.02%, 0.03%, 0.04%, or 0.05%, by weight of the dermatologic formulation. In some embodiments, the Lactobacillus ferment lysate and dandelion leaf extract are present in the dermatologic formulation in a total amount of less than about 0.1%, 0.08%, 0.07%, 0.06%, 0.05%, or 0.045%, by weight of the dermatologic formulation. In some embodiments, the Lactobacillus ferment lysate and dandelion leaf extract are present in the dermatologic formulation in a total amount of between about 0.01% and about 1.0%, between about 0.025% and about 0.06%, orbetween about 0.04% and about 0.05%, by weight of the dermatologic formulation. In one example, the Lactobacillus ferment lysate and dandelion leaf extract are present in the dermatologic formulation in a total amount of about 0.045%, by weight of the dermatologic formulation.

[0052] In some embodiments, the biotic material may be provided for inclusion in the dermatologic formulation as a biotic material composition. In one example, the biotic material is provided for inclusion in the dermatologic formulation as a biotic material compositioncomprising biotic material and excipients. Exemplary excipients include, but are not limited to, butylene glycol, 1,2-hexanediol, ethylhexylglycerine, and water. Accordingly, in some embodiments, the biotic material is provided for inclusion in the dermatologic formulation as a biotic material composition comprising biotic material and an excipient selected from the group consisting of butylene glycol, 1,2-hexanediol, ethylhexylglycerine, water, and combinations thereof. In one example, the biotic material is provided for inclusion in the dermatologic formulation as a biotic material composition comprising biotic material, butylene glycol, 1,2-hexanediol, ethylhexylglycerine, and water. In one example, the biotic material is provided for inclusion in the dermatologic formulation as a biotic material composition comprising a prebiotic, probiotic, butylene glycol, 1,2-hexanediol, ethylhexylglycerine, and water.

[0053] In some embodiments, the biotic material may be provided for inclusion in the dermatologic formulation as a biotic material composition, and the biotic material composition is provided in a total amount of about 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 4.0%, or 5.0%, by weight of the dermatologic formulation. In some embodiments, the biotic material may be provided for inclusion in the dermatologic formulation as a biotic material composition, and the biotic material composition is provided in a total amount of at least about 1.0%, 1.5%, 2.0%, 2.5%, or 3.0%, by weight of the dermatologic formulation. In some embodiments, the biotic material may be provided for inclusion in the dermatologic formulation as a biotic material composition, and the biotic material composition is provided in a total amount of less than about 10%, 8%, 6%, 5%, 4%, or 3%, by weight of the dermatologic formulation. In some embodiments, the biotic material may be provided for inclusion in the dermatologic formulation as a biotic material composition, and the biotic material composition is provided in a total amount of between about 1.0% and about 5.0%, between about 2.0% and about 4.0%, or between about 3.0% and about 4.0%, by weight of the dermatologic formulation. In some embodiments, the biotic material may be provided for inclusion in the dermatologic formulation as a biotic material composition, and the biotic material composition is provided in a total amount of about 3.0%, by weight of the dermatologic formulation.

[0054] In some embodiments, the biotic material is provided in the dermatologic formulation as a biotic material composition, having the following composition:

[0055] Aqua, 90.45%

[0056] Butylene Glycol, 5.00%

[0057] 1,2-Hexanediol, 3.00%

[0058] Lactobacillus Ferment Lysate, 1.00%Taraxacum Officinale (Dandellion) Leaf

[0059] Extract, 0.50% Ethylhexlglycerin, 0.05%

[0060] Ceramide and / or Ceramide Precursor

[0061] In some embodiments, there is provided a dermatologic formulation comprising a ceramide and / or ceramide precursor. In some embodiments, there is provided a dermatologic formulation comprising a ceramide. In some embodiments, there is provided a dermatologic formulation comprising a ceramide precursor. In some embodiments, there is provided a dermatologic formulation comprising a ceramide and a ceramide precursor.

[0062] As used herein, the term “ceramide” refers to a substance being a lipid, and specifically a sphingolipid. Also as used herein, the term “ceramide precursor” refers to a substance that promotes the synthesis of ceramides. When applied in a dermatologic formulation, a ceramide or ceramide precursor may provide benefits to the skin, including, for example, increasing the strength of the barrier function of the skin. Overall, a ceramide or ceramide precursor may impart to the skin an appearance of smoother texture.

[0063] The dermatologic formulation described herein comprises a ceramide and / or ceramide precursor. In some embodiments, the ceramide and / or ceramide precursor is present in the dermatologic formulation in a total amount of about 0.010%, 0.015%, 0.020%, 0.025%, 0.030%, 0.035%, 0.040%, 0.045%, or 0.050%, by weight. In some embodiments, the ceramide and / or ceramide precursor is present in the dermatologic formulation in a total amount of at least about 0.01%, 0.015%, 0.020%, 0.025%, 0.030%, or about 0.035%. In some embodiments, the ceramide and / or ceramide precursor is present in the dermatologic formulation in a total amount of between about 0.01% and about 0.05%, between about 0.015% and about 0.045%, or between about 0.025% and about 0.035%, by weight. In one example, the ceramide and / or ceramide precursor is present in the dermatologic formulation is present in a total amount of about 0.0325%, by weight.

[0064] The ceramide and / or ceramide precursor may comprise one or more ceramides and / or ceramide precursors. Exemplary ceramides include, but are not limited to ceramide NP ((9Z)-N-[(2S,3S,4R)-l,3,4-Trihydroxy-2-octadecanyl]-9-octadecenamide), ceramide AP (2-Hydroxy-N-[(2S,3S,4R)-l,3,4-trihydroxy-2-octadecanyl]octadecanamide), and ceramide EOP (30-Oxo-30-{[(2S,3S,4R)-l,3,4-trihydroxy-2-octadecanyl]amino}triacontyl (9Z,12Z)-9,12-octadecadienoate).Ceramide NP.

[0065] OH OH

[0066]

[0067] Ceramide EOP.

[0068] An example of a ceramide precursor is phytosphingosine.NH2OH

[0069]

[0070] OH

[0071] Phyto sphingo sine.

[0072] In some embodiments, the ceramide and / or ceramide precursor is selected from the group consisting of ceramide NP, ceramide AP, ceramide EOP, phytosphingosine, and combinations thereof. In one example, the ceramide is ceramide NP. In one example, the ceramide is ceramide AP. In one example, the ceramide is ceramide EOP. In one example, the ceramide precursor is phytosphingosine.

[0073] In some embodiments, if present, the ceramide NP is present in the dermatologic formulation in an amount of about 0.005%, 0.01%, 0.015%, 0.02%, or 0.025%, by weight of the dermatologic formulation. In some embodiments, if present, the ceramide NP is present in the dermatologic formulation in an amount of at least about 0.001%, 0.0025%, 0.005%, 0.01%, or about 0.015%, by weight of the dermatologic formulation. In some embodiments, if present, the ceramide NP is present in the dermatologic formulation in an amount of between about 0.001% and about 0.025%, between about 0.005% and about 0.025%, or between about 0.01% and about 0.02%, by weight of the dermatologic formulation. In some embodiments, if present, the ceramide NP is present in the dermatologic formulation in an amount of about 0.015%, by weight of the dermatologic formulation.

[0074] In some embodiments, if present, the ceramide AP is present in the dermatologic formulation in an amount of about 0.001%, 0.002%, 0.004%, 0.008%, 0.01%, or 0.015%, by weight of the dermatologic formulation. In some embodiments, if present, the ceramide AP is present in the dermatologic formulation in an amount of at least about 0.001%, 0.002%, 0.003%, 0.005%, or about 0.008%, by weight of the dermatologic formulation. In some embodiments, if present, the ceramide AP is present in the dermatologic formulation in an amount of between about 0.001% and about 0.015%, or between about 0.002% and about 0.012%, or between about 0.005% and about 0.01%, by weight of the dermatologic formulation. In some embodiments, if present, the ceramide NP is present in the dermatologic formulation in an amount of about 0.008%, by weight of the dermatologic formulation.

[0075] In some embodiments, if present, the ceramide EOP is present in the dermatologic formulation in an amount of about 0.00001%, 0.000015% or 0.00002%, by weight of the dermatologic formulation. In some embodiments, if present, the ceramide EOP is present in the dermatologic formulation in an amount of at least about 0.00001%, 0.000015%, or 0.00002%, by weight of the dermatologic formulation. In some embodiments, if present, theceramide EOP is present in the dermatologic formulation in an amount of about 0.000015%, by weight of the dermatologic formulation.

[0076] In some embodiments, if present, the phyto sphingosine is present in the dermatologic formulation in an amount of about 0.001%, 0.002%, 0.004%, 0.008%, 0.01%, or 0.015%, by weight of the dermatologic formulation. In some embodiments, if present, the phytosphingosine is present in the dermatologic formulation in an amount of at least about 0.001%, 0.002%, 0.003%, 0.005%, or about 0.008%, by weight of the dermatologic formulation. In some embodiments, if present, the phytosphingosine is present in the dermatologic formulation in an amount of between about 0.001% and about 0.015%, or between about 0.002% and about 0.012%, or between about 0.005% and about 0.01%, by weight of the dermatologic formulation. In some embodiments, if present, the phytosphingosine is present in the dermatologic formulation in an amount of about 0.008%, by weight of the dermatologic formulation.

[0077] The ceramide and / or ceramide precursor may be provided for inclusion in the dermatologic formulation as a commercial composition. In one example, the ceramide and / or ceramide precursor is provided as SK-Influx®. In one example, the ceramide and / or ceramide precursor is provided as SK-Influx® V MB. SK-Influx® V MB comprises ceramide NP, ceramide AP, ceramide EOP, phytosphingosine, cholesterol, sodium lauroyl lactylate, carbomer, xanthan gum, ethylhexylglycerin, phenoxyethanol, and aqua (water).

[0078] In some embodiments, the ceramide and / or ceramide precursors are provided in the dermatologic formulation as SK- Influx ® V MB, having the following composition:

[0079] Ceramide NP, 1.00%

[0080] Ceramide AP, 0.55%

[0081] Ceramide EOP, 0.001%

[0082] Phytosphingosine, 0.55%

[0083] Cholesterol, 0.50%

[0084] Sodium Lauroyl Lactylate, 10.00%

[0085] Carbomer, 0.30%

[0086] Xanthan Gum, 0.35%

[0087] Ethylhexylglycerin, 0.30%

[0088] Aqua, 85.549%

[0089] Phenoxyethanol, 0.90%.

[0090] In some embodiments, the ceramide and / or ceramide precursors are provided in the dermatologic formulation as SK-Influx ® V MB, and the SK-Influx® V MB is provided in an amount of about 0.5%, 1.0%, 1.5%, or 2.0%, by weight of the dermatologic formulation. In some embodiments, the ceramide and / or ceramide precursors are provided in the dermatologicformulation as SK- Influx ® V MB, and the SK- Influx® V MB is provided in an amount of at least about 0.5%, 1.0%, 1.5%, or 2.0%, by weight of the dermatologic formulation. In some embodiments, the ceramide and / or ceramide precursors are provided in the dermatologic formulation as SK- Influx ® V MB, and the SK-Influx® V MB is provided in an amount of between about 0.5% and 5.0%, between about 1.0% and about 3.0%, or between about 1.5% and about 2.0%, by weight of the dermatologic formulation.

[0091] Additional Components of the Dermatologic Formulation

[0092] It will be appreciated that the dermatologic formulation may comprise further excipients suitable for use in a dermatologic formulation. The excipient may or may not, itself, provide advantageous properties to the skin. As would be appreciated by the person skilled in the art, an excipient may be employed in a dermatologic formulation to improve any one or more properties of the formulation, including, for example, stability and shelf-life of the formulation, solubility of active components, texture and feel of the formulation, and penetration of the skin.

[0093] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and an excipient. In some embodiments, the excipient is selected from the group consisting of a humectant, emollient, a lubricant, an emulsifier, and combinations thereof. Accordingly, in some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and an excipient selected from the group consisting of a humectant, emollient, a lubricant, an emulsifier, and combinations thereof.

[0094] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and a humectant. As used herein, the term “humectant” refers to a substance that is hygroscopic in nature and retains or preserves moisture. When employed in a dermatologic formulation, a humectant may retain or preserve (i.e., reduce the loss of) moisture within the skin. In some embodiments, the humectant is selected from the group consisting of a diol compound, triol compound, polyol compound, and combinations thereof. Exemplary diol compounds include, but are not limited to, ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol, polyethylene glycol, and combinations thereof. Exemplary triol compounds include, but are not limited to, glycerol (also referred to as glycerin). In one example, the humectant is glycerol. Accordingly, in some embodiments there is provided adermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and glycerol.

[0095] In some embodiments, the humectant is present in the dermatologic formulation in an amount of about 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 1.5%, or 2%, by weight of the dermatologic formulation. In some embodiments, the humectant is present in the dermatologic formulation in an amount of at least about 0.01%, 0.05%, 0.1%, 0.5%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, the humectant is present in the dermatologic formulation in an amount of less than about 10%, 5.0%, 4.0%, 3.0%, 2.0%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, the humectant is present in the dermatologic formulation in an amount of between about 0.01% and about 10%, between about 0.1% and about 5%, or between about 0.5% and about 2.0%, by weight of the dermatologic formulation. In some embodiments, the humectant is present in the dermatologic formulation in an amount of about 1.0%, by weight of the dermatologic formulation.

[0096] In some embodiments, glycerol is present in the dermatologic formulation in an amount of about 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 1.5%, or 2%, by weight of the dermatologic formulation. In some embodiments, glycerol is present in the dermatologic formulation in an amount of at least about 0.01%, 0.05%, 0.1%, 0.5%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, glycerol is present in the dermatologic formulation in an amount of less than about 10%, 5.0%, 4.0%, 3.0%, 2.0%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, glycerol is present in the dermatologic formulation in an amount of between about 0.01% and about 10%, between about 0.1% and about 5%, or between about 0.5% and about 2.0%, by weight of the dermatologic formulation. In some embodiments, glycerol is present in the dermatologic formulation in an amount of about 1.0%, by weight of the dermatologic formulation.

[0097] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and an emollient. As used herein, the term “emollient” refers to a substance that may soften the skin. When employed in a dermatologic formulation, an emollient may protect, moisturise, and / or lubricate the skin, therefore providing a feeling of softness to the skin. In some embodiments, the emollient is selected from the group consisting of a dry emollient, a fatty emollient, an astringent emollient, a protective emollient, and combinations thereof. In one example, the emollient is a fatty emollient. In some embodiments, the fatty acid is selected from the group consisting of propylene glycol, octyl stearate, glyceryl stearate, jojoba oil, castor oil, safflower oil, rosehip oil, shea butter, sunflower oil, capryl triglyceride, and combinations thereof. In someembodiments, the fatty acid is selected from the group consisting of sunflower oil, capryl triglyceride, shea butter, and combinations thereof. In one example, the fatty acid is sunflower oil, capryl triglyceride, and shea butter. Accordingly, in some embodiments there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, sunflower oil, capryl triglyceride, and shea butter.

[0098] In some embodiments, the emollient is present in the dermatologic formulation in a total amount of about 1.0%, 1.2%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, or 2.0%, by weight of the dermatologic formulation. In some embodiments, the emollient is present in the dermatologic formulation in a total amount of at least about 1.0%, 1.2%, 1.4%, 1.5%, 1.8%, 1.9%, or 2.0%, by weight of the dermatologic formulation. In some embodiments, the emollient is present in the dermatologic formulation in a total amount of less than about 10%, 5.0%, 4.0%, 3.0%, 2.0%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, the emollient is present in the dermatologic formulation in a total amount of between about 0.01% and about 10%, between about 0.1% and about 5%, or between about 1.0% and about 2.0%, by weight of the dermatologic formulation. In some embodiments, the emollient is present in the dermatologic formulation in a total amount of about 1.9%, by weight of the dermatologic formulation.

[0099] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and sunflower oil. In some embodiments, the sunflower oil is present in the dermatologic formulation in an amount of about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7% or 1.0%, by weight of the dermatologic formulation. In some embodiments, the sunflower oil is present in the dermatologic formulation in an amount of at least about 0.1%, 0.2%, 0.3%, 0.4%, or 0.5%, by weight of the dermatologic formulation. In some embodiments, the sunflower oil is present in the dermatologic formulation in an amount of less than about 5.0%, 4.0%, 3.0%, 2.0%, 1.0%, or 0.5%, by weight of the dermatologic formulation. In some embodiments, the sunflower oil is present in the dermatologic formulation in an amount of between about 0.1% and about 5%, between about 0.3% and about 2%, or between about 0.5% and about 1.0%, by weight of the dermatologic formulation. In some embodiments, the sunflower oil is present in the dermatologic formulation in an amount of about 0.5%, by weight of the dermatologic formulation.

[0100] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and capryl triglyceride. In some embodiments, the capryl triglyceride is present in the dermatologic formulation in anamount of about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7% or 1.0%, by weight of the dermatologic formulation. In some embodiments, the capryl triglyceride is present in the dermatologic formulation in an amount of at least about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, the capryl triglyceride is present in the dermatologic formulation in an amount of less than about 5.0%, 4.0%, 3.0%, 2.0%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, the capryl triglyceride is present in the dermatologic formulation in an amount of between about 0.1% and about 10%, between about 0.3% and about 5%, or between about 0.5% and about 2.0%, by weight of the dermatologic formulation. In some embodiments, the capryl triglyceride is present in the dermatologic formulation in an amount of about 1.0%, by weight of the dermatologic formulation.

[0101] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and shea butter. In some embodiments, the shea butter is present in the dermatologic formulation in an amount of about 0.1%, 0.2%, 0.3%, 0.35%, 0.4%, 0.45%, or 0.5%, by weight of the dermatologic formulation. In some embodiments, the shea butter is present in the dermatologic formulation in an amount of at least about 0.1%, 0.2%, 0.3%, 0.35%, or 0.4%, by weight of the dermatologic formulation. In some embodiments, the shea butter is present in the dermatologic formulation in an amount of less than about 5.0%, 4.0%, 3.0%, 2.0%, 1.0%, or 0.5%, by weight of the dermatologic formulation. In some embodiments, the shea butter is present in the dermatologic formulation in an amount of between about 0.1% and about 2%, between about 0.2% and about 1%, or between about 0.3% and about 0.6%, by weight of the dermatologic formulation. In some embodiments, the shea butter is present in the dermatologic formulation in an amount of about 0.4%, by weight of the dermatologic formulation.

[0102] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and an emulsifier. As used herein, the term “emulisfier” refers to a substance that acts stabilise an emulsion. When employed in a dermatologic formulation, an emulsifier may stabilise the individual components of the dermatological formulation and / or the overall dermatologic formulation. In some embodiments, the emulsifier is selected from the group consisting of cetearyl alcohol, ceteareth 20, stearic acid, carbomer, and combinations thereof. In one example, the emulsifier is cetearyl alcohol. In one example, the emulsifier is ceteareth 20. In one example, the emulsifier is stearic acid. In one example, the emulsifier is carbomer.In some embodiments, the emulsifier is present in the dermatologic formulation in a total amount of about 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, or 3.0%, by weight of the dermatologic formulation. In some embodiments, the emulsifier is present in the dermatologic formulation in a total amount of at least about 0.5%, 1.0%, 1.5%, 2.0%, or 2.5%, by weight of the dermatologic formulation. In some embodiments, the emulsifier is present in the dermatologic formulation in a total amount of less than about 10%, 7.5%, 5.0%, 4.0%, 3.0%, or 2.5%, by weight of the dermatologic formulation. In some embodiments, the emulsifier is present in the dermatologic formulation in a total amount of between about 0.5% and about 10%, between about 1.0% and about 5.0%, or between about 2.0% and about 3.0%, by weight of the dermatologic formulation. In some embodiments, the emulsifier is present in the dermatologic formulation in a total amount of about 2.5%, by weight of the dermatologic formulation.

[0103] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and cetearyl alcohol. In some embodiments, the cetearyl alcohol is present in the dermatologic formulation in an amount of about 0.2%, 0.3%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, or 1.5%, by weight of the dermatologic formulation. In some embodiments, the cetearyl alcohol is present in the dermatologic formulation in an amount of at least about 0.2%, 0.4%, 0.5%, 0.7%, 0.8%, 0.9%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, the cetearyl alcohol is present in the dermatologic formulation in an amount of less than about 10%, 5.0%, 4.0%, 3.0%, 2.0%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, the cetearyl alcohol is present in the dermatologic formulation in a total amount of between about 0.1% and about 5%, between about 0.5% and about 2%, or between about 1.0% and about 1.5%, by weight of the dermatologic formulation. In some embodiments, the cetearyl alcohol is present in the dermatologic formulation in an amount of about 1.0%, by weight of the dermatologic formulation.

[0104] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and ceteareth 20. In some embodiments, the ceteareth 20 is present in the dermatologic formulation in an amount of about 0.1%, 0.2%, 0.3%, 0.4%, or 0.5%, by weight of the dermatologic formulation. In some embodiments, the ceteareth 20 is present in the dermatologic formulation in an amount of at least about 0.1%, 0.2%, 0.3%, 0.4%, or 0.5%, by weight of the dermatologic formulation. In some embodiments, the ceteareth 20 is present in the dermatologic formulation in an amount of less than about 5.0%, 1.5%, 1.0%, or 0.5%, by weight of the dermatologic formulation. In some embodiments, the ceteareth 20 is present in the dermatologic formulation in a totalamount of between about 0.1% and about 2.0%, between about 0.3% and about 1.5%, or between about 0.5% and about 1.0%, by weight of the dermatologic formulation. In some embodiments, the ceteareth 20 is present in the dermatologic formulation in an amount of about 0.5%, by weight of the dermatologic formulation.

[0105] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and stearic acid. In some embodiments, the stearic acid is present in the dermatologic formulation in an amount of about 0.1%, 0.15%, 0.2%, 0.25%, or 0.3%, by weight of the dermatologic formulation. In some embodiments, the stearic acid is present in the dermatologic formulation in an amount of at least about 0.1%, 0.15%, 0.2%, 0.25%, or 0.3%, by weight of the dermatologic formulation. In some embodiments, the stearic acid is present in the dermatologic formulation in an amount of less than about 5.0%, 1.5%, 1.0%, or 0.5%, by weight of the dermatologic formulation. In some embodiments, the stearic acid is present in the dermatologic formulation in a total amount of between about 0.1% and about 1.0%, between about 0.15% and about 0.75%, or between about 0.25% and about 0.35%, by weight of the dermatologic formulation. In some embodiments, the stearic acid is present in the dermatologic formulation in an amount of about 0.3%, by weight of the dermatologic formulation.

[0106] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and carbomer. In some embodiments, the carbomer is present in the dermatologic formulation in an amount of about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, or 0.8%, by weight of the dermatologic formulation. In some embodiments, the carbomer is present in the dermatologic formulation in an amount of at least about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, or 0.8%, by weight of the dermatologic formulation. In some embodiments, the carbomer is present in the dermatologic formulation in an amount of less than about 5.0%, 1.5%, 1.0%, or 0.75%, by weight of the dermatologic formulation. In some embodiments, the carbomer is present in the dermatologic formulation in a total amount of between about 0.1% and about 1.0%, between about 0.4% and about 0.9%, or between about 0.6% and about 0.8%, by weight of the dermatologic formulation. In some embodiments, the carbomer is present in the dermatologic formulation in an amount of about 0.7%, by weight of the dermatologic formulation.

[0107] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and a preservative. As used herein, the term “preservative” refers to a substance that prevents the decay or fouling. When employed in a dermatologic formulation, a preservative may stabilise the formulationby preventing decay or fouling of the individual components of the dermatologic formulation and / or the overall dermatologic formulation.

[0108] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and a preservative. In some embodiments, the preservative is present in the dermatologic formulation in an amount of about 0.2%, 0.3%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, or 1.5%, by weight of the dermatologic formulation. In some embodiments, the preservative is present in the dermatologic formulation in an amount of at least about 0.2%, 0.4%, 0.5%, 0.7%, 0.8%, 0.9%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, the preservative is present in the dermatologic formulation in an amount of less than about 10%, 5.0%, 4.0%, 3.0%, 2.0%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, the preservative is present in the dermatologic formulation in a total amount of between about 0.1% and about 5%, between about 0.5% and about 2%, or between about 1.0% and about 1.5%, by weight of the dermatologic formulation. In some embodiments, the preservative is present in the dermatologic formulation in an amount of about 1.0%, by weight of the dermatologic formulation.

[0109] In one example, the preservative is phenyloxyethanol. In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and phenyloxyethanol. In some embodiments, the phenyloxyethanol is present in the dermatologic formulation in an amount of about 0.2%, 0.3%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, or 1.5%, by weight of the dermatologic formulation. In some embodiments, the phenyloxy ethanol is present in the dermatologic formulation in an amount of at least about 0.2%, 0.4%, 0.5%, 0.7%, 0.8%, 0.9%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, the phenyloxy ethanol is present in the dermatologic formulation in an amount of less than about 10%, 5.0%, 4.0%, 3.0%, 2.0%, or 1.0%, by weight of the dermatologic formulation. In some embodiments, the phenyloxy ethanol is present in the dermatologic formulation in a total amount of between about 0.1% and about 5%, between about 0.5% and about 2%, or between about 1.0% and about 1.5%, by weight of the dermatologic formulation. In some embodiments, the phenyloxyethanol is present in the dermatologic formulation in an amount of about 1.0%, by weight of the dermatologic formulation.

[0110] Dermatologic FormulationIn some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, and a ceramide and / or ceramide precursor.

[0111] In some embodiments, the dermatologic formulation comprises an antioxidant, a biotic material, and a ceramide and / or ceramide precursor, and does not comprise acetyl zingerone. In some embodiments, the dermatologic formulation comprises an antioxidant, a biotic material, and a ceramide and / or ceramide precursor, and does not comprise a combination of ectoin and acetyl zingerone.

[0112] In one example, the antioxidant is ectoin. Accordingly, in some embodiments, there is provided a dermatologic formulation comprising ectoin, a biotic material, and a ceramide and / or ceramide precursor. In some embodiments, there is provided a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate, and a ceramide and / or ceramide precursor. In some embodiments, there is provided a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract, and a ceramide and / or ceramide precursor. In some embodiments, there is provided a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract, and ceramide NP, ceramide AP, and phytosphingosine. In some embodiments, there is provided a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract, and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine.

[0113] In one example, the biotic material is Lactobacillus ferment lysate and dandelion leaf extract. Accordingly, in some embodiments, there is provided a dermatologic formulation comprising an antioxidant, Lactobacillus ferment lysate and dandelion leaf extract, and a ceramide and / or ceramide precursor. In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, Lactobacillus ferment lysate and dandelion leaf extract, and ceramide NP, ceramide AP, and phytosphingosine. In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, Lactobacillus ferment lysate and dandelion leaf extract, and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine.

[0114] In one example, the ceramide and / or ceramide precursor is a combination of ceramide NP, ceramide AP, and phytosphingosine. Accordingly, in some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, and ceramide NP, ceramide AP, and phytosphingosine. In some embodiments, there is provided a dermatologic formulation comprising ectoin, a biotic material, and ceramide NP, ceramide AP, and phytosphingosine. In one example, the ceramide and / or ceramide precursor is a combination of ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine. Accordingly, in someembodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine. In some embodiments, there is provided a dermatologic formulation comprising ectoin, a biotic material, and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine.

[0115] In some embodiments, there is provided a dermatologic formulation comprising an antioxidant in an amount of between about 0.1% and about 5.0%, a biotic material in a total amount of between about 0.1% and about 1.0%, and a ceramide and / or ceramide precursor in an amount of between about 0.01% and about 0.05%, by weight of the dermatologic formulation. In some embodiments, there is provided a dermatologic formulation comprising an antioxidant in an amount of between about 0.5% and about 1.5%, a biotic material in a total amount of between about 0.04% and about 0.05%, and a ceramide and / or ceramide precursor in an amount of between about 0.025% and about 0.035%, by weight of the dermatologic formulation. In some embodiments, there is provided a dermatologic formulation comprising an antioxidant in an amount of about 1.0%, a biotic material in a total amount of about 0.045%, and a ceramide and / or ceramide precursor in an amount of about 0.0325%, by weight of the dermatologic formulation.

[0116] In some embodiments, there is provided a dermatologic formulation comprising ectoin in an amount of between about 0.01% and about 5.0%; Lactobacillus ferment lysate and dandelion leaf extract in a total amount of between about 0.01% and about 1.0%, and ceramide NP, ceramide AP, and phyto sphingosine in a total amount of between about 0.01% and about 0.05%, by weight of the dermatologic formulation.

[0117] In some embodiments, there is provided a dermatologic formulation comprising ectoin in an amount of between about 0.5% and about 1.5%; Lactobacillus ferment lysate and dandelion leaf extract in a total amount of between about 0.04% and about 0.05%, and ceramide NP, ceramide AP, and phyto sphingosine in a total amount of between about 0.025% and about 0.035%, by weight of the dermatologic formulation.

[0118] In some embodiments, there is provided a dermatologic formulation comprising ectoin in an amount of between about 0.01% and about 5.0%; Lactobacillus ferment lysate and dandelion leaf extract in a total amount of between about 0.01% and about 1.0%, and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine in a total amount of between about 0.01% and about 0.05%, by weight of the dermatologic formulation.

[0119] In some embodiments, there is provided a dermatologic formulation comprising ectoin in an amount of between about 0.5% and about 1.5%; Lactobacillus ferment lysate and dandelion leaf extract in a total amount of between about 0.04% and about 0.05%, and ceramideNP, ceramide AP, ceramide EOP, and phytosphingosine in a total amount of between about 0.025% and about 0.035%, by weight of the dermatologic formulation.

[0120] In some embodiments, there is provided a dermatologic formulation comprising ectoin in an amount of about 1.0%; Lactobacillus ferment lysate and dandelion leaf extract in a total amount of about 0.045%, and ceramide NP, ceramide AP, and phyto sphingosine in a total amount of between 0.0325%, by weight of the dermatologic formulation.

[0121] In some embodiments, there is provided a dermatologic formulation comprising ectoin in an amount of about 1.0%; Lactobacillus ferment lysate and dandelion leaf extract in a total amount of about 0.045%, and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine in a total amount of about 0.0325%, by weight of the dermatologic formulation.

[0122] In some embodiments, there is provided a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract, ceramide NP, ceramide AP, ceramide EOP, phytosphingosine, glycerol, sunflower oil, capryl triglyceride, and shea butter. In some embodiments, there is provided a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract, ceramide NP, ceramide AP, phytosphingosine, glycerol, sunflower oil, capryl triglyceride, and shea butter.

[0123] In some embodiments, there is provided a dermatologic formulation comprising ectoin in an amount of about 1.0%; Lactobacillus ferment lysate and dandelion leaf extract in an amount of about 0.045%; ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine in a total amount of about 0.0325%; glycerol in an amount of about 1.0%; sunflower oil in an amount of about 0.5%; capryl triglyceride in an amount of about 1.0%; and shea butter in an amount of about 0.4%, by weight of the dermatologic formulation.

[0124] In some embodiments, there is provided a dermatologic formulation comprising ectoin in an amount of about 1.0%; Lactobacillus ferment lysate and dandelion leaf extract in an amount of about 0.045%; ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine in a total amount of about 0.0325%; glycerol in an amount of about 1.0%; sunflower oil in an amount of about 0.5%; capryl triglyceride in an amount of about 1.0%; and shea butter in an amount of about 0.4%, by weight of the dermatologic formulation, wherein the dermatologic formulation does not comprise acetyl zingerone.

[0125] In some embodiments, there is provided a dermatologic formulation comprising ectoin in an amount of about 1.0%; Lactobacillus ferment lysate and dandelion leaf extract in an amount of about 0.045%; ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine in a total amount of about 0.0325%; glycerol in an amount of about 1.0%; sunflower oil in anamount of about 0.5%; capryl triglyceride in an amount of about 1.0%; and shea butter in an amount of about 0.4%, by weight of the dermatologic formulation, wherein the dermatologic formulation does not comprise a combination of ectoin and acetyl zingerone.

[0126] In some embodiments, the dermatologic formulation described herein comprises one or more excipients. In some embodiments, the dermatologic formulation described herein comprises one or more dermatologically acceptable excipients. In some embodiments, the dermatological formulation comprises an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and a dermatologically acceptable excipient. In some embodiments, the dermatological formulation comprises an antioxidant, a biotic material, a ceramide and / or ceramide precursor, and a dermatologically acceptable excipient selected from the group consisting of a humectant, an emollient, an emulsifier, a preservative, and combinations thereof. In some embodiments, the dermatological formulation comprises an antioxidant, a biotic material, a ceramide and / or ceramide precursor, a humectant, an emollient, an emulsifier, and a preservative. In some embodiments, the dermatologic formulation described herein further comprises aqua (water). In some embodiments, the dermatological formulation comprises an antioxidant, a biotic material, a ceramide and / or ceramide precursor, a humectant, an emollient, an emulsifier, a preservative, and water.

[0127] In some embodiments, the dermatologic formulation described herein comprises an antioxidant in an amount of about 1.0%, a biotic material in a total amount of about 0.045%, a ceramide and / or ceramide precursor in a total amount of about 0.0325%, by weight of the dermatologic formulation, and a dermatologically acceptable excipient and / or water to a total amount of 100%, by weight of the dermatologic formulation. In some embodiments, the dermatologic formulation described herein comprises ectoin in an amount of about 1.0%; Lactobacillus ferment lysate and dandelion leaf extract in an amount of about 0.045%; ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine in a total amount of about 0.0325%; and a dermatologically acceptable excipient and / or water to a total amount of 100%, by weight of the dermatologic formulation.

[0128] In some embodiments, there is provided a dermatologic formulation comprising ectoin in an amount of about 1.0%; Lactobacillus ferment lysate and dandelion leaf extract in an amount of about 0.045%; ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine in a total amount of about 0.0325%; humectant in a total amount of about 1.0%; emollient in a total amount of about 1.9%; emulsifier in a total amount of about 2.5%; and preservative in a total amount of about 1.0%; by weight of the dermatologic formulation.In some embodiments, there is provided a dermatologic formulation comprising ectoin in an amount of about 1.0%; Lactobacillus ferment lysate and dandelion leaf extract in an amount of about 0.045%; ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine in a total amount of about 0.0325%; glycerol in an amount of about 1.0%; sunflower oil in an amount of about 0.5%; capryl triglyceride in an amount of about 1.0%; shea butter in an amount of about 0.4%; glycerol in an amount of about 1.0%; sunflower oil in an amount of about 0.5%; capryl triglyceride in an amount of about 1.0%; shea butter in an amount of about 0.4%; cetearyl alcohol in an amount of about 1.0%; ceteareth 20 in an amount of about 0.5%; stearic acid in an amount of about 0.3%; carbomer in an amount of about 0.7%; phenyloxyethanol in an amount of about 1.0%; by weight of the dermatologic formulation.

[0129] In some embodiments, the dermatologic formulation consists of ectoin; Lactobacillus ferment lysate and dandelion leaf extract; ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine; glycerol; sunflower oil; capryl triglyceride; shea butter; and one or more dermatologically acceptable excipients and / or water. In some embodiments, the dermatologic formulation consists of ectoin; Lactobacillus ferment lysate and dandelion leaf extract; ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine; glycerol; sunflower oil; capryl triglyceride; shea butter; cetearyl alcohol; ceteareth 20; stearic acid; carbomer; phenyloxy ethanol; and water. In some embodiments, the dermatologic formulation defined herein further comprises sodium hydroxide.

[0130] In some embodiments, the dermatologic formulation is:

[0131] Water Aqua 88.099985%

[0132] Antioxidant Ectoin 1.000%

[0133] Aqua 2.7135%

[0134] Butylene Glycol 0.150%

[0135] 1,2-Hexanediol 0.090%

[0136] Biotic material Lactobacillus Ferment Lysate 0.030%

[0137] Taraxacum Officinale „ „1

[0138] (Dandelion) Leaf Extract ’ °

[0139] Ethylhexlglycerin 0.002%

[0140] Ceramide and / or Ceramide NP 0.015%

[0141]

[0142] ceramide Ceramide AP 0.00825%precursor (SK- Ceramide EOP 0.000015%

[0143] Influx V MB) Phyto sphingosine 0.00825%

[0144] Cholesterol 0.008%

[0145] Sodium Lauroyl Lacty late 0.150%

[0146] Carbomer 0.005%

[0147] Xanthan Gum 0.00525%

[0148] Ethylhexylglycerin 0.005%

[0149] Aqua 1.28325%

[0150] Phenoxyethanol 0.0135%

[0151] Humectant Glycerol 1.000%

[0152] Caprylic / Capric Triglyceride 1.000%

[0153] Helianthus Annuus (Sunflower) „

[0154] Emollient Seed Oil °'500%

[0155] Butyrospermum Parkii (Shea) 400*7

[0156] Butter

[0157] Cetearyl Alcohol 1.000%

[0158] _ . ... Ceteareth 20 0.500%

[0159] Emuls,fierstear.c Ac.d 0.300%

[0160] Carbomer 0.700%

[0161] ~ . Phenoxyethanol, Caprylyl1

[0162] Preservativer1.000%

[0163]

[0164] Glycol

[0165] Methods and Uses

[0166] Provided herein are methods and uses of the dermatologic formulation described herein. Hyaluronic Acid

[0167] Hyaluronic acid (HA), also called hyaluronan, is a liner biodegradable polysaccharide that belongs to the glycosaminoglycan (GAG) family, and consists of disaccharide units of N-acetyl glucosamine and D-glucuronic acid, connected alternately by P 1-3 and 1-4 glycosidic bonds. HA is naturally present in almost all body fluids and tissues such as the skin; synovial fluid; ligaments; eye vitreous humor; connective tissues; epithelial tissues; and neural tissues; and plays important biological functions in wound healing regulating cell adhesion, connective tissue organization, water holding, motility, differentiation, and proliferation. It belongs to the family of extracellular matrix (ECM) molecules, and is produced primarily by mesenchymal cells.

[0168] Regarding the skin, HA is found in both layers - dermis and epidermis - where it is understood to have a protective, structure stabilizing, and shock- absorbing function. Indeed, the total amount of HA in human skin is estimated to be about the half of the total amount of HA in the entire human body. With increasing age, the content of hyaluronan in the skin decreases, which may contribute to loss of freshness, hydration, moisture, and elasticity in theskin, and ultimately, the development of wrinkles. For these reasons, HA is a high important molecule in skin aging and the cosmetic industry.

[0169] In particular, skin aging is associated with loss of skin moisture and the key molecule involved in skin moisture is HA, due to its unique capacity to retain water molecules. It is believed that hydration of the skin critically depends on the HA-bound water in the dermis and in the vital area of the epidermis, while maintenance of hydration essentially depends on the stratum granulosum. Extensive loss of the stratum granulosum in patients with burns may cause serious clinical problems due to dehydration.

[0170] It has been surprisingly found that the dermatologic formulation, described herein, provides unexpected advantages when applied to the skin. The Applicant has demonstrated that the dermatologic formulation provides an unexpected increase in hyaluronic acid in normal human dermal fibroblast (NHDF) cells. The person skilled in the art will appreciate that NHDF present a model of the skin of a human subject. As a result of the increased hyaluronic acid, the dermatologic formulation described herein may find application in numerous dermatologic applications, including hydration of the skin, improved elasticity of the skin, decreased signs of ageing of the skin (e.g., dark spots, wrinkles), and / or increased strength of the barrier function of the skin, particularly the epidermis.

[0171] Accordingly, in some embodiments, the dermatologic formulation described herein provides an increase in hyaluronic acid levels in normal human dermal fibroblast (NHDF) cells of at least 100%, 105%, 110%, 115%, or 120%, after 72 hours of treatment at a concentration of 0.01% when compared to control. In some embodiments, the dermatologic formulation described herein provides an increase in hyaluronic acid levels in normal human dermal fibroblast (NHDF) cells of between about 100% and about 200%, between about 105% and about 150%, or between about 110% and about 120%, after 72 hours of treatment at a concentration of 0.01% when compared to control. In some embodiments, the dermatologic formulation described herein provides an increase in hyaluronic acid levels in normal human dermal fibroblast (NHDF) cells of about 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, or 200%, after 72 hours of treatment at a concentration of 0.01% when compared to control.

[0172] It will be appreciated that an increase in hyaluronic acid may arise due to 1) an increase in production of hyaluronic acid, and / or 2) a decrease in hyaluronic acid degradation. Accordingly, in some embodiments, the dermatologic formulation described herein provides an increase in hyaluronic acid production. In some embodiments, the dermatologic formulation described herein provides a decrease in hyaluronic acid degradation. In some embodiments,the dermatologic formulation described herein provides an increase in hyaluronic acid via an increase in hyaluronic acid production and / or decrease in hyaluronic acid degradation.

[0173] Accordingly, in some embodiments, there is provided use of a dermatologic formulation comprising an antioxidant, a biotic material, and a ceramide and / or ceramide precursor, for elevating hyaluronic acid levels in the skin. “In the skin” will be taken to mean in any one or more layers of the dermis, as described herein. It will be appreciated that the dermatologic formulation is applied to the skin (i.e., the surface of the skin) in such uses and methods, as would be accepted for such a dermatologic formulation.

[0174] In some embodiments, there is provided use of a dermatologic formulation comprising ectoin; Lactobacillus ferment lysate and dandelion leaf extract; and ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine; for elevating hyaluronic acid levels in the skin. In some embodiments, there is provided use of a dermatologic formulation comprising ectoin; Lactobacillus ferment lysate and dandelion leaf extract; and ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine; for elevating hyaluronic acid levels in the skin, wherein the dermatologic formulation does not comprise acetyl zingerone.

[0175] In some embodiments, there is provided use of a dermatologic formulation, comprising ectoin in an amount of about 1.0%; Lactobacillus ferment lysate and dandelion leaf extract in an amount of about 0.045%; and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine in a total amount of about 0.0325%, by weight of the dermatologic formulation; for elevating hyaluronic acid levels in the skin. In some embodiments, there is provided use of a dermatologic formulation, comprising ectoin in an amount of about 1.0%; Lactobacillus ferment lysate and dandelion leaf extract in an amount of about 0.045%; and ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine in a total amount of about 0.0325%, by weight of the dermatologic formulation; for elevating hyaluronic acid levels in the skin, wherein the dermatologic formulation does not comprise acetyl zingerone.

[0176] In some embodiments, elevation of hyaluronic acid provides increased skin hydration, improved elasticity of the skin, decreased signs of ageing of the skin (e.g., dark spots, wrinkles), and / or increased strength of the barrier function of the skin (i.e., epidermis). It will be appreciated that the comparison is made in relation to skin that has not been treated with a dermatologic formulation. In one example, elevation of hyaluronic acid provides increased skin hydration. In one example, elevation of hyaluronic acid provides improved elasticity of the skin. In one example, elevation of hyaluronic acid provides decreased signs of ageing of the skin (e.g., dark spots, wrinkles). In one example, elevation of hyaluronic acid provides increased strength of the barrier function of the skin (i.e., epidermis). Increased skin hydration,improved elasticity of the skin, decreased signs of ageing of the skin, and increased strength of the barrier function of the skin may be assessed via any means known in the art. In some embodiments, assessment is via visual analysis.

[0177] Accordingly, in some embodiments, there is provided use of the dermatologic formulation described herein for hydrating skin. The term “hydrating skin” will be understood to mean an increase in moisture, or water, within the skin. As discussed herein, it is believed that the dermatologic formulation described herein hydrates the skin by increasing the amount of hyaluronic acid in the skin. In some embodiments, there is provided use of the dermatologic formulation described herein for improving the elasticity of the skin. The term “elasticity of the skin” will be understood to mean the ability of the skin to stretch and retain its shape. In some embodiments, there is provided use of the dermatologic formulation described herein for decreasing signs of ageing of the skin. In one example, a sign of ageing of the skin is increased dark spots (i.e., lentigos). In one example, a sign of ageing of the skin is wrinkles. In some embodiments, there is provided use of the dermatologic formulation described herein for increasing the strength of the barrier function of the skin (i.e., epidermis).

[0178] In some embodiments, the dermatologic formulation described herein provides antioxidant activity in the skin. As will be appreciated by the person skilled in the art, an antioxidant may be employed in dermatologic formulations to protect skin cells against the damaging effect of reactive oxygen species (ROS) (i.e., by reducing reactive oxygen species (ROS) in the skin). Accordingly, in some embodiments, there is provided use of a dermatologic formulation, as described herein, for decreasing reactive oxygen species (ROS) in the skin. In some embodiments, there is provided use of a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract, and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine, for decreasing reactive oxygen species (ROS) in the skin. In some embodiments, there is provided use of a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract, and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine, for preventing or slowing cell damage in the skin. In some embodiments, there is provided use of a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract, and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine, for preventing or reducing skin inflammation in the skin. In some embodiments, there is provided use of a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract, and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine, for preventing, lessening, or reversing ultraviolet B damage in the skin.In some embodiments, the dermatologic formulation described herein provides an improved / balanced skin microbiota. In some embodiments, there is provided use of a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract, and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine, for improving / balancing skin microbiota.

[0179] In some embodiments, the dermatologic formulation described herein provides an increased barrier strength of the barrier function of the skin. In some embodiments, there is provided use of a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract, and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine, for increasing the strength of the barrier function of the skin.

[0180] Similarly, methods and methods of treatment are provided herein.

[0181] In some embodiments, there is provided a method of elevating hyaluronic acid in the skin of a subject, comprising applying to the skin of the subject a dermatologic formulation as described herein. In some embodiments, there is provided a method of elevating hyaluronic acid in the skin of a subject, comprising applying to the skin of the subject a dermatologic formulation comprising an antioxidant, a biotic material, and a ceramide and / or ceramide precursor. In some embodiments, there is provided a method of elevating hyaluronic acid in the skin of a subject, comprising applying to the skin of the subject a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract; and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine. In some embodiments, there is provided a method of elevating hyaluronic acid in the skin of a subject, comprising applying to the skin of the subject a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract; and ceramide NP, ceramide AP, and phytosphingosine. In some embodiments, there is provided a method of elevating hyaluronic acid in the skin of a subject, comprising applying to the skin of the subject a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract; and ceramide NP, ceramide AP, and phytosphingosine, and wherein the dermatologic formulation does not comprise acetyl zingerone.

[0182] In some embodiments, there is provided a dermatologic formulation, as described herein, for use in a method of elevating hyaluronic acid levels in the skin. In some embodiments, there is provided a dermatologic formulation comprising an antioxidant, a biotic material, and a ceramide and / or ceramide precursor, for use in a method of elevating hyaluronic acid levels in the skin. In some embodiments, there is provided a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract; and ceramide NP,ceramide AP, ceramide EOP, and phytosphingosine, for use in a method of elevating hyaluronic acid levels in the skin. In some embodiments, there is provided a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract; and ceramide NP, ceramide AP, and phytosphingosine, for use in a method of elevating hyaluronic acid levels in the skin. In some embodiments, there is provided a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract; and ceramide NP, ceramide AP, and phytosphingosine, for use in a method of elevating hyaluronic acid levels in the skin, and wherein the dermatologic formulation does not comprise acetyl zingerone.

[0183] In some embodiments, there is provided use of a dermatologic formulation, as described herein, in the manufacture of a medicament for elevating hyaluronic acid levels in the skin. In some embodiments, there is provided use of a dermatologic formulation comprising an antioxidant, a biotic material, and a ceramide and / or ceramide precursor in the manufacture of a medicament for elevating hyaluronic acid levels in the skin. In some embodiments, there is provided use of a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract; and ceramide NP, ceramide AP, ceramide EOP, and phytosphingosine, in the manufacture of a medicament for elevating hyaluronic acid levels in the skin. In some embodiments, there is provided use of a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract; and ceramide NP, ceramide AP, and phytosphingosine, in the manufacture of a medicament for elevating hyaluronic acid levels in the skin. In some embodiments, there is provided use of a dermatologic formulation comprising ectoin, Lactobacillus ferment lysate and dandelion leaf extract; and ceramide NP, ceramide AP, and phytosphingosine, in the manufacture of a medicament for elevating hyaluronic acid levels in the skin, and wherein the dermatologic formulation does not comprise acetyl zingerone.

[0184] The present application claims priority from Australian Provisional Patent Application No. 2025901340 filed on 17 April 2025, and the entire contents of this application are incorporated herein by reference.

[0185] The present disclosure will now be described with reference to the following examples which illustrate some particular aspects of the present disclosure. However, it is to be understood that the particularity of the following description of the present disclosure is not to supersede the generality of the preceding description of the present disclosure.

[0186] EXAMPLESExample 1: In Vitro Assessment of Compositions in the Regulation of Hyaluronic Acid (HA) Biosynthesis in Human Fibroblasts

[0187] Objectives

[0188] To evaluate the in vitro effect of three compositions - “Comp A”, “Comp B”, and “Comp C” - on the regulation of hyaluronic acid biosynthesis in human fibroblasts.

[0189] Methodology

[0190] Working concentrations of COMP A, COMP B, COMP C and base were determined using the MTT cell viability assay in human fibroblasts. Then, cells were cultured with medium containing products at concentration 0.01 % and 0.03 % for 72 h. Negative control (non-treated cells) and positive control (cells treated with antioxidant - Vitamin C at concentration 200 pM) were included in the study. Hyaluronic acid protein levels were quantified using a specific Enzyme Linked Immunosorbent Assay (ELISA) kit. All data were statistically analysed.

[0191] COMPA Ectoin 1.0%; Biotic material composition 3.0%; SK-Influx 1.5%; Acetyl Zingerone 0.5%; Glycerol 1.0%; Shea butter 0.4%; Sunflower oil 0.5%; Caprylic triglycerides 1.0%

[0192] COMPB Ectoin 1.0%; Biotic material composition 3.0%; SK-Influx 1.5%;

[0193] Glycerol 1.0%; Shea butter 0.4%; Sunflower oil 0.5%; Caprylic triglycerides 1.0%

[0194] COMP C Biotic material composition 3.0%; SK-Influx 1.5%; Acetyl Zingerone 0.5%; Gycerol 1.0%; Shea butter 0.4%; Sunflower oil 0.5%; Caprylic triglycerides 1.0%

[0195] BASE Glycerol 1.0%; Shea butter 0.4%; Sunflower oil 0.5%; caprylic triglycerides 1.0%

[0196]

[0197] All components of the compositions were purchased from commercial sources. The compositions were stored at room temperature.

[0198] The biotic material composition was provided in the form of Prebiome®, which comprises water, butylene glycol, 1,2-hexanediol, Lactobacillus ferment lysate, dandelion leaf extract, and ethylhexylglycerin. Prebiome® was obtained from commercial sources.

[0199] Materials and Methods

[0200] Analytical equipmentInverted microscope, laminar flow hood, cell culture incubator (37°C, 5 % CO2, 90 % relative humidity (RH), Biirker chamber, pipettes, rack, plate reader spectrophotometer, freezer -80°C, freezer -20°C, statistical analysis software.

[0201] Reagents

[0202] Distilled Water (Braun), NHDF specific culture medium and supplements (Gibco), PBS (Gibco), Trypan Blue (Bio-Rad), Trypsin (Sigma- Aldrich), PBS (Gibco), Penicillin / Streptomycin (Fisher), Human Hyaluronic Acid ELISA kit (Abeam).

[0203] Procedure

[0204] Cell viability (MTT assay): Cell numbers and viability were determined using Trypan-Blue staining and counting in a Biirker chamber under the microscope. For the MTT viability assay, human fibroblasts were cultured overnight at a 10.000 cells / well density in a 96 well plate, in supplemented growth medium. 24 h later, the culture medium was replaced with fresh medium containing the tested product at 8 different concentrations. After 24 h of incubation, the medium was removed, and MTT solution was added to each well. Plates were incubated at 37°C for 3 h. MTT reagent was removed and DMSO at 100 % was added to each well to solubilize formazan crystals, then the absorbance was measured at 550 nm and 620 nm as a reference on a scanning multi-well spectrophotometer.

[0205] Hyaluronic acid quantification - ELISA assay: To assess Hyaluronic Acid (HA) protein levels, NHDF cells were cultured overnight at a density of 50000 cells / well density in 24-well plates. After 24 hours, cells were treated with products at 0.01% and 0.03% for 72 hours. After the incubation period, samples were processed, and HA protein levels were quantified by specific ELISA kit, following the manufacturer’s instructions.

[0206] Statistical analysis: The MTT assay was set with 8 replicates per condition and 16 for control, and ELISA quantification assay was set with 5 replicates per condition. Data outliers were identified with ROUT method (Q = 5 %) and excluded from the analysis if found. Both, raw and normalized data were statistically analyzed by one way ANOVA test and Dunnet’s post hoc multiple comparisons test. Statistical significance was declared at p < 0.05, 95 % of confidence. Bars in the charts represent the mean value for each condition and error bars indicate the standard error of the mean (SEM) for each group of values.

[0207] Results

[0208] Cell Viability (MTT Assay)

[0209] Results showed that:• Treatment with COMP A did not affect cell viability when used at concentrations below 0.01%;

[0210] • Treatment with COMP B and COMP C does not affect cell viability when used at concentrations lower than 0.03%; and

[0211] • Treatment with BASE did not affect cell viability when used at concentrations below 0.3% (see Figure 1).

[0212] Hyaluronic Acid Quantification (ELISA Assay)

[0213] The human HA ELISA kit is an immunoassay developed for in vitro quantitative measurements in different sample types. The substrate content in each sample is determined by interpolation of the sample absorbance from a standard curve provided by the manufacturer.

[0214] Results showed that:

[0215] • Treatment with COMP A at 0.01 % significantly increased Hyaluronic acid levels by 63.3 ± 10.1% after 72 h in human fibroblasts; and

[0216] • Treatment with COMP B at 0.01% and 0.03% significantly increased Hyaluronic acid levels by 121 ± 6.3% and 84.4 ± 6.3%, respectively after 72 h in human fibroblast (see Figure 2).

[0217] Conclusion

[0218] • Treatment with COMP A and COMP B significantly increases hyaluronic acid levels in human fibroblasts after a 72-hour treatment; and

[0219] • The treatment with COMP C and Base has not shown a positive effect on the elevation of hyaluronic acid levels in human fibroblasts after 72 hours.

[0220] These findings suggest that COMP A and COMP B effectively promote skin hydration, elasticity, and overall skin health by stimulating hyaluronic acid production and reducing its degradation.

[0221] Surprisingly, the results show that COMP B, which includes only ectoin as the antioxidant (as opposed to COMP A, which includes the additional antioxidant of acetyl zingerone), was more effective at elevating hyaluronic acid levels. This is despite both COMP A and COMP B otherwise comprising the same ingredients. However, when an antioxidant is not present (COMP C), the dermatologic formulation was not effective at elevating hyaluronic acid levels.

[0222] Accordingly, the results demonstrate that a formulation comprising the single antioxidant, ectoin (COMP B), is more effective at elevating hyaluronic acid levels in the skinthan either of 1) a combination of antioxidants (ectoin and acetyl zingerone, COMP A), or 2) a single antioxidant, acetyl zingerone (COMP C).ITEMISED LIST OF EMBODIMENTS

[0223] Disclosed herein are the following numbered embodiments.

[0224] Item 1. A dermatologic formulation, comprising:

[0225] - an antioxidant;

[0226] - a biotic material; and

[0227] - a ceramide and / or a ceramide precursor.

[0228] Item 2. The dermatologic formulation of item 1, wherein the antioxidant is present in an amount of about 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 1.5% or 2.0% by weight.

[0229] Item 3. The dermatologic formulation of item 1 or item 2, wherein the antioxidant is ectoin. Item 4. The dermatologic formulation of any one of items 1 to 3, wherein the biotic material is present in an amount of about 0.01%, 0.02%, 0.03%, 0.04%, 0.045%, or 0.05%, by weight of the dermatologic formulation.

[0230] Item 5. The dermatologic formulation of any one of items 1 to 4, wherein the biotic material comprises Lactobacillus ferment lysate and dandelion leaf extract.

[0231] Item 6. The dermatologic formulation of item 5, wherein the Lactobacillus ferment lysate is present in an amount of about 0.03%, by weight of the dermatologic formulation.

[0232] Item 7. The dermatologic formulation of any one of items 1 to 6, wherein the biotic material comprises dandelion leaf extract.

[0233] Item 8. The dermatologic formulation of item 7, wherein the dandelion leaf extract is present in an amount of about 0.015%, by weight of the dermatologic formulation.

[0234] Item 9. The dermatologic formulation of any one of items 1 to 8, wherein the ceramide and / or ceramide precursor is selected from the group consisting of ceramide NP, ceramide AP, ceramide EOP, phytosphingosine, and combinations thereof.

[0235] Item 10. The dermatologic formulation of any one of items 1 to 9, wherein the ceramide and / or ceramide precursor is present in a total amount of about 0.010%, 0.015%, 0.020%, 0.025%, 0.030%, 0.035%, 0.040%, 0.045%, or 0.050%, by weight of the dermatologic formulation. Item 11. The dermatologic formulation of any one of items 1 to 10, further comprising a humectant.

[0236] Item 12. The dermatologic formulation of item 11, wherein the humectant is glycerol.

[0237] Item 13. The dermatologic formulation of item 11 or item 12, wherein the humectant is present in an amount of about 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 1.5%, or 2%, by weight of the dermatologic formulation.

[0238] Item 14. The dermatologic formulation of any one of items 1 to 13, further comprising anemollient.

[0239] Item 15. The dermatologic formulation of item 14, wherein the emollient is sunflower oil, capryl triglyceride, shea butter, and combinations thereof.

[0240] Item 16. The dermatologic formulation of item 14 or item 15, wherein the emollient is present in a total amount of about 0.5%, 1.0%, 1.5%, or 2.0%, by weight of the dermatologic formulation.

[0241] Item 17. The dermatologic formulation of any one of items 1 to 16, comprising:

[0242] - ectoin in an amount of about 1.0%;

[0243] - Lactobacillus ferment lysate and dandelion leaf extract in a total amount of about 0.045%; and

[0244] - ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine in a total amount of about 0.0325%, by weight of the dermatologic formulation.

[0245] Item 18. The dermatologic formulation of any one of items 1 to 17, comprising:

[0246] - ectoin;

[0247] - Lactobacillus ferment lysate and dandelion leaf extract;

[0248] - ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine;

[0249] - glycerol;

[0250] - sunflower oil;

[0251] - capryl triglyceride; and

[0252] - shea butter.

[0253] Item 19. The dermatologic formulation of any one of items 1 to 18, comprising:

[0254] - ectoin in an amount of about 1.0%;

[0255] - Lactobacillus ferment lysate and dandelion leaf extract in a total amount of about 0.045%;

[0256] - ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine in a total amount of about 0.0325%;

[0257] - glycerol in an amount of about 1.0%;

[0258] - sunflower oil in an amount of about 0.5%;

[0259] - capryl triglyceride in an amount of about 1.0%; and

[0260] - shea butter in an amount of about 0.4%, by weight of the dermatologic formulation. Item 20. The dermatologic formulation of any one of items 1 to 19, wherein the dermatologic formulation does not comprise acetyl zingerone.

[0261] Item 21. The dermatologic formulation of any one of items 1 to 20, further comprising a dermatologically acceptable excipient.Item 22. Use of the dermatologic formulation according to any one of items 1 to 21, for elevating hyaluronic acid levels in the skin.

[0262] Item 23. The use of item 22, wherein elevating hyaluronic acid levels in the skin is an increase in hyaluronic acid production and decrease in hyaluronic acid degradation.

[0263] Item 24. The use of item 21 or item 22, wherein elevating hyaluronic acid levels in the skin provides increased skin hydration, improved elasticity of the skin, decreased signs of ageing of the skin (e.g., dark spots, wrinkles), increased strength of the barrier function of the skin (i.e., epidermis), and combinations thereof.

[0264] Item 25. The use of any one of items 22 to 24, wherein the elevation in hyaluronic acid is hyaluronic acid levels measured in normal human dermal fibroblast (NHDF) cells of at least 100%, 105%, 110%, 115%, or 120% after 72 hours of treatment at a concentration of 0.01% when compared to control.

[0265] Item 26. The dermatologic formulation of any one of items 1 to 21, for use in a method of elevating hyaluronic acid levels in the skin.

[0266] Item 27. A method of elevating hyaluronic acid in the skin of a subject, comprising applying to the skin of the subject a dermatologic formulation of any one of items 1 to 21.

[0267] Item 28. Use of the dermatologic formulation of any one of items 1 to 21, in the manufacture of a medicament for the elevation of hyaluronic acid in the skin.

[0268] Item 29. The use of any one of items 22 to 25, wherein the dermatologic formulation further provides antioxidant activity.

Claims

CLAIMS1. A dermatologic formulation, comprising:- an antioxidant;- a biotic material; and- a ceramide and / or a ceramide precursor.

2. The dermatologic formulation of claim 1, wherein the antioxidant is present in an amount of about 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 1.5% or 2.0% by weight.

3. The dermatologic formulation of claim 1 or claim 2, wherein the antioxidant is ectoin.

4. The dermatologic formulation of any one of claims 1 to 3, wherein the biotic material is present in an amount of about 0.01%, 0.02%, 0.03%, 0.04%, 0.045%, or 0.05%, by weight of the dermatologic formulation.

5. The dermatologic formulation of any one of claims 1 to 4, wherein the biotic material comprises Lactobacillus ferment lysate.

6. The dermatologic formulation of claim 5, wherein the Lactobacillus ferment lysate is present in an amount of about 0.03%, by weight of the dermatologic formulation.

7. The dermatologic formulation of any one of claims 1 to 6, wherein the biotic material comprises dandelion leaf extract.

8. The dermatologic formulation of claim 7, wherein the dandelion leaf extract is present in an amount of about 0.015%, by weight of the dermatologic formulation.

9. The dermatologic formulation of any one of claims 1 to 8, wherein the ceramide and / or ceramide precursor is selected from the group consisting of ceramide NP, ceramide AP, ceramide EOP, phytosphingosine, and combinations thereof.

10. The dermatologic formulation of any one of claims 1 to 9, wherein the ceramide and / or ceramide precursor is present in a total amount of about 0.010%, 0.015%, 0.020%, 0.025%, 0.030%, 0.035%, 0.040%, 0.045%, or 0.050%, by weight of the dermatologic formulation.

11. The dermatologic formulation of any one of claims 1 to 10, further comprising a humectant.

12. The dermatologic formulation of claim 11, wherein the humectant is glycerol.

13. The dermatologic formulation of claim 11 or claim 12, wherein the humectant is present in an amount of about 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 1.5%, or 2%, by weight of the dermatologic formulation.

14. The dermatologic formulation of any one of claims 1 to 13, further comprising an emollient.

15. The dermatologic formulation of claim 14, wherein the emollient is sunflower oil, capryl triglyceride, shea butter, and combinations thereof.

16. The dermatologic formulation of claim 14 or claim 15, wherein the emollient is present in a total amount of about 0.5%, 1.0%, 1.5%, or 2.0%, by weight of the dermatologic formulation.

17. The dermatologic formulation of any one of claims 1 to 16, comprising:- ectoin in an amount of about 1.0%;- Lactobacillus ferment lysate and dandelion leaf extract in a total amount of about 0.045%; and- ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine in a total amount of about 0.0325%, by weight of the dermatologic formulation.

18. The dermatologic formulation of any one of claims 1 to 17, comprising:- ectoin;- Lactobacillus ferment lysate and dandelion leaf extract;- ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine;- glycerol;- sunflower oil;- capryl triglyceride; and- shea butter.

19. The dermatologic formulation of any one of claims 1 to 18, comprising:- ectoin in an amount of about 1.0%;- Lactobacillus ferment lysate and dandelion extract in a total amount of about 0.045%; - ceramide NP, ceramide AP, ceramide EOP, and phyto sphingosine in a total amount of about 0.0325%;- glycerol in an amount of about 1.0%;- sunflower oil in an amount of about 0.5%;- capryl triglyceride in an amount of about 1.0%; and- shea butter in an amount of about 0.4%, by weight of the dermatologic formulation.

20. The dermatologic formulation of any one of claims 1 to 19, wherein the dermatologic formulation does not comprise acetyl zingerone.

21. The dermatologic formulation of any one of claims 1 to 20, further comprising a dermatologically acceptable excipient.

22. Use of the dermatologic formulation according to any one of claims 1 to 21, for elevating hyaluronic acid levels in the skin.

23. The use of claim 22, wherein elevating hyaluronic acid levels in the skin is an increase in hyaluronic acid production and decrease in hyaluronic acid degradation.

24. The use of claim 21 or claim 22, wherein elevating hyaluronic acid levels in the skin provides increased skin hydration, improved elasticity of the skin, decreased signs of ageing of the skin (e.g., dark spots, wrinkles), increased strength of the barrier function of the skin (i.e., epidermis), and combinations thereof.

25. The use of any one of claims 22 to 24, wherein the elevation in hyaluronic acid is hyaluronic acid levels measured in normal human dermal fibroblast (NHDF) cells of at least 100%, 105%, 110%, 115%, or 120% after 72 hours of treatment at a concentration of 0.01% when compared to control.

26. The dermatologic formulation of any one of claims 1 to 21, for use in a method of elevating hyaluronic acid levels in the skin.

27. A method of elevating hyaluronic acid in the skin of a subject, comprising applying to the skin of the subject a dermatologic formulation of any one of claims 1 to 21.

28. Use of the dermatologic formulation of any one of claims 1 to 21, in the manufacture of a medicament for the elevation of hyaluronic acid in the skin.

29. The use of any one of claims 22 to 25, wherein the dermatologic formulation further provides antioxidant activity.

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