Skin care methods and preparations

Abstract

Described herein is a formulation comprising at least about 50% by weight water and about 1% by weight or less sphingolipid. The formulation can be applied to a region of the skin of a subject. After the formulation is applied to a region of the skin of a subject, a biochemical pathway can be activated by the formulation to cause the production of ceramide on the region of the skin of a subject. The amount of ceramide produced on the region of the skin of a subject can be greater than the baseline amount of ceramide produced in the absence of the formulation. In various examples, the increased amount of ceramide produced after the formulation is applied to a region of the skin of a subject can modify the condition present on the region of the skin of a subject.

Description

[Technical field]

[0001] Priority claims and incorporation by reference This application claims priority to U.S. Provisional Patent Application No. 63 / 191,230, entitled "Skin Care Methods and Formulations," filed May 20, 2021, the entire contents of which are incorporated herein by reference. Additionally, the entire contents of U.S. Provisional Patent Application No. 63 / 181,821, entitled "Skin Care Methods and Formulations," filed April 29, 2021, and PCT Application No. PCT / US2022 / 027148, entitled "Analyzing Genomics Data and Analytical Data," filed April 29, 2022, are both incorporated herein by reference. [Background technology]

[0002] Mammalian skin may support many microorganisms, including bacteria, protists, archaea, fungi, and viruses. The microorganisms supported by mammalian skin may include the skin microbiota. The combination of microorganisms living on the skin and genetic material of the microorganisms may include the skin microbiome. The microbiota may vary depending on the location of the skin of the same subject. In addition, the skin microbiota may vary across individual subjects. Skin health for a particular subject may be based, at least in part, on the subject's skin microbiota. Summary of the Invention

[0003] A first embodiment relates to a formulation comprising at least about 50% by weight water and about 1% by weight or less of a sphingolipid.

[0004] A second embodiment relates to a formulation comprising about 50% to about 65% water by weight, about 20% to about 30% 1,3-butanediol by weight, about 5% to about 15% glycerin by weight, about 2% to about 10% 1,2-propanediol by weight, and about 0.0005% to about 0.005% sphingosine by weight.

[0005] A third aspect relates to a method comprising applying a formulation comprising at least about 50% by weight water and about 1% by weight or less sphingolipid to an area of ​​skin of a subject to activate the sphingosine-1-phosphate biochemical pathway and generate a subsequent amount of ceramide on the area of ​​skin that is greater than the baseline initial amount of ceramide present on the area of ​​skin of the subject in the absence of the formulation.

[0006] A fourth aspect relates to a method of treating a skin condition comprising applying to an area of ​​the skin of a subject an effective amount of a formulation comprising at least about 50% by weight water and no more than about 1% by weight sphingolipid. [Brief description of the drawings]

[0007] The present disclosure is illustrated by way of example and not limitation in the figures of the accompanying drawings in which like reference numbers indicate similar elements and in which: [Figure 1] FIG. 1 illustrates an exemplary method of applying a formulation comprising at least about 50% water by weight and about 1% or less sphingolipid by weight to an area of ​​a subject's skin, according to one or more exemplary embodiments. [Figure 2A] FIG. 1 shows a photograph of the first subject in Study #1 prior to use of a formulation described herein. [Figure 2B] FIG. 1 shows a photograph of the first subject after use of the formulation. [Figure 3A] FIG. 1 shows a photograph of the second subject in Study #1 prior to use of a formulation described herein. [Figure 3B] FIG. 13 shows a photograph of a second subject after use of the formulation. [Figure 4A]FIG. 1 shows a photograph of the third subject in Study #1 prior to use of a formulation described herein. [Figure 4B] FIG. 13 shows a photograph of a third subject after use of the formulation. [Figure 5A] FIG. 1 shows a photograph of the fourth subject in Study #1 prior to use of a formulation described herein. [Figure 5B] FIG. 13 shows a photograph of a fourth subject after use of the formulation. [Figure 6A] FIG. 1 shows a photograph of the fifth subject in Study #1 prior to use of a formulation described herein. [Figure 6B] FIG. 13 shows a photograph of a fifth subject after use of the formulation. [Figure 7A] FIG. 1 shows a photograph of the first subject who participated in Study #2 prior to use of a formulation described herein. [Figure 7B] FIG. 1 shows a photograph of the first subject after use of the formulation. [Figure 8A] FIG. 1 shows a photograph of a second subject who participated in Study #2 prior to use of a formulation described herein. [Figure 8B] FIG. 13 shows a photograph of a second subject after use of the formulation. [Figure 9A] FIG. 13 shows a photograph of a third subject who participated in Study #2 prior to use of a formulation described herein. [Figure 9B] FIG. 13 shows a photograph of a third subject after use of the formulation. [Figure 10A] FIG. 13 shows a photograph of a fourth subject who participated in Study #2 prior to use of a formulation described herein. [Figure 10B] FIG. 13 shows a photograph of a fourth subject after use of the formulation. [Figure 11A] FIG. 1 shows a photograph of a fifth subject who participated in Study #2 prior to use of a formulation described herein. [Figure 11B] FIG. 13 shows a photograph of a fifth subject after use of the formulation. [Figure 12A]FIG. 1 shows a photograph of a sixth subject who participated in Study #2 prior to use of a formulation described herein. [Figure 12B] FIG. 13 shows a photograph of a sixth subject after use of the formulation. [Figure 13A] FIG. 13 shows a photograph of a further subject with an upper wound and an underlying scar prior to use of a formulation described herein. [Figure 13B] FIG. 13 shows photographs of additional subjects after use of the formulation. [Figure 14] FIG. 1 shows normalized abundance measurements of a number of bacteria for Study #2 subjects characterized with normal skin before and after treatment with the formulation. [Figure 15] FIG. 1 shows normalized abundance measurements of a number of bacteria for Study #2 subjects characterized as having sensitive skin before and after treatment with the formulation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] Typically, cosmetics and treatments applied to the skin contain an effective amount of ingredients to treat a particular skin condition or improve skin health. In the embodiments described herein, a formulation containing prebiotics that activates a particular biochemical pathway to produce compounds used to treat a particular skin condition and improve skin health is applied to the skin of an individual.

[0009] Described herein is a formulation comprising at least about 50% water by weight and about 1% or less sphingolipid by weight. The formulation can be applied to an area of ​​skin of a subject. After the formulation is applied to an area of ​​skin of a subject, a biochemical pathway can be activated by the formulation to cause the production of ceramides on the area of ​​skin of a subject. The amount of ceramides produced on the area of ​​skin of a subject can be greater than the baseline amount of ceramides produced in the absence of the formulation. In various examples, the increase in the amount of ceramides produced after application of the formulation to an area of ​​skin of a subject can modify the conditions present on the area of ​​skin of a subject. To illustrate, as the amount of ceramides present on an area of ​​skin of a subject increases above the baseline amount of ceramides as a result of application of the formulation to an area of ​​skin of a subject, the conditions present on the area of ​​skin of a subject can be modified. In one or more examples, the conditions present on an individual area of ​​skin can be improved over the period of time that the formulation is applied to an area of ​​skin of a subject. In this manner, the formulation can include a prebiotic that activates a biochemical pathway to produce a postbiotic comprising at least one ceramide. Furthermore, the formulation does not suppress skin microflora or affect the viability of microorganisms present in the subject's microflora.Changes in microbial community can increase negative and pathogenic microorganisms, which can reduce the protective skin barrier and reduce skin health.The formulations described herein are microbiome safe and safe for the subjects to whom they can be applied.In various examples, the formulations described herein can improve the composition and amount of bacteria present on an individual's skin.

[0010] 1 illustrates an example method 100 of applying a formulation comprising at least about 50% water by weight and not more than about 1% sphingolipid by weight to an area of ​​skin of a subject, according to one or more example embodiments. The method may include, at 102, applying a formulation comprising at least about 50% water by weight and not more than about 1% sphingolipid by weight to an area of ​​skin of a subject. The subject may include a mammal. In various examples, the subject may include a human. In one or more further examples, the subject may include a mammal other than a human, such as at least one of a horse, a dog, a cow, a pig, or a mouse.

[0011] In various examples, the formulation may comprise at least about 40% water by weight, at least 42% water by weight, at least about 45% water by weight, at least about 48% water by weight, at least about 50% water by weight, at least about 52% water by weight, or at least about 55% water by weight. Additionally, the formulation may comprise up to about 70% water by weight, up to about 68% water by weight, up to about 65% water by weight, up to about 62% water by weight, or up to about 60% water by weight. In one or more illustrative examples, the formulation may comprise from about 40% water by weight to about 70% water by weight, from about 50% water by weight to about 65% water by weight, or from about 52% water by weight to about 60% water by weight.

[0012] In one or more examples, the sphingolipid may include sphingosine. The formulation may include at least about 0.0005% by weight of sphingosine, at least about 0.0008% by weight of sphingosine, at least about 0.0010% by weight of sphingosine, at least about 0.0012% by weight of sphingosine, at least about 0.0015% by weight of sphingosine, at least about 0.0018% by weight of sphingosine, or at least about 0.002% by weight of sphingosine. In addition, the formulation may include less than about 0.005% by weight of sphingosine, less than about 0.008% by weight of sphingosine, less than about 0.010% by weight of sphingosine, less than about 0.015% by weight of sphingosine, less than about 0.020% by weight of sphingosine, less than about 0.030% by weight of sphingosine, or less than about 0.050% by weight of sphingosine. In one or more illustrative examples, the formulation may contain about 0.0005% by weight sphingosine to about 0.005% by weight sphingosine, about 0.0005% by weight sphingosine to about 0.05% by weight sphingosine, or about 0.0010% by weight sphingosine to about 0.005% by weight sphingosine.

[0013] The formulation may also include one or more diols. For example, the formulation may include one or more diols having 3 to 6 carbon atoms. In one or more examples, the formulation may include at least two diols. In various examples, the formulation may include about 20% to about 40% by weight of a first diol having 3 to 6 carbon atoms and about 2% to about 10% by weight of a second diol having about 3 to 6 carbon atoms. In one or more examples, the formulation may include 1,3-butanediol. In one or more further examples, the formulation may include 1,2-propanediol. In one or more illustrative examples, the formulation may include 1,3-butanediol and 1,2-propanediol.

[0014] The formulation may contain at least about 10% by weight 1,3-butanediol, at least about 12% by weight 1,3-butanediol, at least about 15% by weight 1,3-butanediol, at least about 18% by weight 1,3-butanediol, at least about 20% by weight 1,3-butanediol, at least about 22% by weight 1,3-butanediol, or at least about 25% by weight 1,3-butanediol. The formulation may also contain up to about 40% by weight 1,3-butanediol, up to about 38% by weight 1,3-butanediol, up to about 35% by weight 1,3-butanediol, up to about 32% by weight 1,3-butanediol, or up to about 30% by weight 1,3-butanediol. In one or more illustrative examples, the formulation may include about 15% by weight 1,3-butanediol to about 30% by weight 1,3-butanediol, about 20% by weight to about 30% by weight 1,3-butanediol, or about 22% by weight to about 28% by weight 1,3-butanediol.

[0015] In addition, the formulation may contain at least about 1% by weight 1,2-propanediol, at least about 2% by weight 1,2-propanediol, at least about 3% by weight 1,2-propanediol, at least about 4% by weight 1,2-propanediol, or at least about 5% by weight 1,2-propanediol. The formulation may also contain up to about 15% by weight 1,2-propanediol, up to about 12% by weight 1,2-propanediol, up to about 10% by weight 1,2-propanediol, or up to about 8% by weight 1,2-propanediol. In one or more exemplary embodiments, the formulation may include from about 1% by weight 1,2-propanediol to about 15% by weight 1,2-propanediol, from about 2% by weight 1,2-propanediol to about 10% by weight 1,2-propanediol, or from about 2% by weight 1,2-propanediol to about 8% by weight 1,2-propanediol. In one or more exemplary embodiments, 1,2-propanediol may not be included in the formulation.

[0016] Additionally, the formulation may include an amount of glycerin. In various examples, the formulation may include at least about 2% by weight glycerin, at least about 3% by weight glycerin, at least about 5% by weight glycerin, at least about 7% by weight glycerin, or at least about 9% by weight glycerin. The formulation may also include up to about 20% by weight glycerin, up to about 18% by weight glycerin, up to about 15% by weight glycerin, or up to about 12% by weight glycerin. In one or more exemplary examples, the formulation may include from about 2% by weight glycerin to about 20% by weight glycerin, from about 3% by weight glycerin to about 15% by weight glycerin, or from about 7% by weight glycerin to about 12% by weight glycerin.

[0017] The formulation may include an amount of squalene. For example, the formulation may include at least about 0.1% by weight squalene, at least about 0.3% by weight squalene, at least about 0.5% by weight squalene, at least about 0.7% by weight squalene, or at least about 1.0% by weight squalene. In addition, the formulation may include about 3% by weight or less squalene, about 2.5% by weight or less squalene, about 2.0% by weight or less squalene, about 1.5% by weight or less squalene, or about 1.2% by weight or less squalene. In one or more illustrative examples, the formulation may include about 0.1% by weight squalene to about 3% by weight squalene, about 0.5% by weight squalene to about 2.0% by weight squalene, or about 0.7% by weight squalene to about 1.2% by weight squalene.

[0018] The formulation may also include an amount of isohexadecane. To illustrate, the formulation may include at least about 0.05% by weight isohexadecane, at least about 0.08% by weight isohexadecane, at least about 0.10% by weight isohexadecane, at least about 0.15% by weight isohexadecane, at least about 0.20% by weight isohexadecane, at least about 0.22% by weight isohexadecane, or at least about 0.25% by weight isohexadecane. The formulation may also include no more than about 0.50% by weight isohexadecane, no more than about 0.45% by weight isohexadecane, no more than about 0.40% by weight isohexadecane, no more than about 0.35% by weight isohexadecane, or no more than about 0.30% by weight isohexadecane. In one or more illustrative examples, the formulation may include about 0.05% by weight isohexadecane to about 0.50% by weight isohexadecane, about 0.10% by weight isohexadecane to about 0.40% by weight isohexadecane, or about 0.20% by weight isohexadecane to about 0.30% by weight isohexadecane.

[0019] In addition, the formulation may include an amount of palmitic acid. In one or more examples, the formulation may include at least about 0.0005% palmitic acid by weight, at least about 0.0008% palmitic acid by weight, at least about 0.0010% palmitic acid by weight, at least about 0.0012% palmitic acid by weight, at least about 0.0015% palmitic acid by weight, at least about 0.0018% palmitic acid by weight, or at least about 0.0020% palmitic acid by weight. The formulation may also include less than about 0.0050% palmitic acid by weight, less than about 0.0045% palmitic acid by weight, less than about 0.0040% palmitic acid by weight, less than about 0.0035% palmitic acid by weight, less than about 0.0030% palmitic acid by weight, or less than about 0.0025% palmitic acid by weight. In one or more illustrative examples, the formulation may include about 0.0005% palmitic acid to about 0.0050% palmitic acid by weight, about 0.0010% palmitic acid to about 0.0040% palmitic acid by weight, or about 0.0015% palmitic acid to about 0.0025% palmitic acid by weight.

[0020] The formulation may include an amount of polysorbate 80. To illustrate, the formulation may include at least about 0.04% by weight polysorbate 80, at least about 0.05% by weight polysorbate 80, at least about 0.06% by weight polysorbate 80, at least about 0.07% by weight polysorbate 80, or at least about 0.08% by weight polysorbate 80. The formulation may also include no more than about 0.20% by weight polysorbate 80, no more than about 0.18% by weight polysorbate 80, no more than about 0.15% by weight polysorbate 80, no more than about 0.12% by weight polysorbate 80, or no more than about 0.10% by weight polysorbate 80. In one or more illustrative examples, the formulation may contain about 0.04% polysorbate 80 to about 0.20% polysorbate 80 by weight, about 0.06% polysorbate 80 to about 0.15% polysorbate 80 by weight, or about 0.08% polysorbate 80 to about 0.10% polysorbate 80 by weight.

[0021] The formulation may further include an amount of sodium acrylate / sodium acryloyldimethyl taurate copolymer. For example, the formulation may comprise at least about 0.05% by weight of sodium acrylate / sodium acryloyldimethyl taurate copolymer, at least about 0.10% by weight of sodium acrylate / sodium acryloyldimethyl taurate copolymer, at least about 0.15% by weight of sodium acrylate / sodium acryloyldimethyl taurate copolymer, at least about 0.20% by weight of sodium acrylate / sodium acryloyldimethyl taurate copolymer, at least about 0.25% by weight of sodium acrylate / sodium acryloyldimethyl taurate copolymer, at least about 0.30% by weight of sodium acrylate / sodium acryloyldimethyl taurate copolymer, at least about 0.35% by weight of sodium acrylate / sodium acryloyldimethyl taurate copolymer, or at least about 0.40% by weight of sodium acrylate / sodium acryloyldimethyl taurate copolymer. Additionally, the formulation may comprise about 1.5% by weight or less of sodium acrylate / sodium acryloyldimethyl taurate copolymer, about 1.2% by weight or less of sodium acrylate / sodium acryloyldimethyl taurate copolymer, about 1.0% by weight or less of sodium acrylate / sodium acryloyldimethyl taurate copolymer, about 0.8% by weight or less of sodium acrylate / sodium acryloyldimethyl taurate copolymer, or about 0.5% by weight or less of sodium acrylate / sodium acryloyldimethyl taurate copolymer.In one or more illustrative examples, the formulation may include about 0.10% by weight sodium acrylate / sodium acryloyldimethyl taurate copolymer to about 1.5% by weight sodium acrylate / sodium acryloyldimethyl taurate copolymer, about 0.20% by weight sodium acrylate / sodium acryloyldimethyl taurate copolymer to about 1.0% by weight sodium acrylate / sodium acryloyldimethyl taurate copolymer, or about 0.40% by weight sodium acrylate / sodium acryloyldimethyl taurate copolymer to about 0.50% by weight sodium acrylate / sodium acryloyldimethyl taurate copolymer.

[0022] In one or more illustrative examples, the formulation may include an amount of water, an amount of sphingolipid, and one or more carrier compounds, such as at least one of one or more conditioning agents, one or more detergents, one or more emulsifiers, or one or more emulsion stabilizers. The one or more carrier compounds may provide a cosmetically pleasing delivery system for the prebiotics. Factors influencing the selection of carrier compounds to be included in the formulation may include long-term stability, hydrophobicity, pH, and solubility to maintain the efficacy of the formulation. The one or more carrier compounds are selected to minimize any impact of the formulation on the health of the microflora of the subject. In one or more examples, the detergent may include palmitic acid. The one or more conditioning agents may include at least one of 1,3 butanediol, isohexadecane, or squalene. In various examples, the emulsifier may include polysorbate 80. The emulsion stabilizer may include a copolymer of sodium acrylate and sodium acryloyldimethyltaurate.

[0023] In one or more examples, the formulation may include about 50% to about 65% water by weight, about 20% to about 30% 1,3-butanediol by weight, about 5% to about 15% glycerin by weight, about 2% to about 10% 1,2-propanediol by weight, and about 0.0005% to about 0.005% sphingosine by weight. The formulation may also include about 0.7% to about 1.2% squalene by weight, about 0.20% to about 0.30% isohexadecane by weight, about 0.0015% to about 0.0025% palmitic acid by weight, about 0.08% to about 0.10% polysorbate 80 by weight, and about 0.40% to about 0.50% sodium acrylate / sodium acryloyldimethyl taurate copolymer by weight.

[0024] The formulation can be made by combining an amount of water, an amount of glycerin, an amount of one or more diols, an amount of one or more conditioning agents, an amount of one or more emulsifiers, an amount of one or more emulsion stabilizers, an amount of one or more detergents, and an amount of sphingosine. In one or more examples, an amount of sphingosine is heated and combined with an amount of squalene to produce a mixture of sphingosine and squalene. In one or more illustrative examples, the mixture of sphingosine and squalene can be mixed with water, 1,3-butanediol, 1,2-propanediol, glycerin, palmitic acid, isohexadecane, polysorbate 80, and a copolymer of sodium acrylate and sodium acryloyldimethyltaurate to produce the formulation.

[0025] Additionally, the method 100 may include activating a biochemical pathway, at 104. The biochemical pathway may include a biochemical pathway that includes a sphingolipid as an intermediate component. In one or more examples, the biochemical pathway may include a sphingosine-1-phosphate biochemical pathway.

[0026] Further, at 106, the method 100 may include generating a subsequent amount of ceramide on the area of ​​skin of the subject that is greater than the baseline amount of ceramide present on the area of ​​skin in the absence of the formulation. In one or more examples, the subsequent amount of ceramide generated can be at least about 2% greater than the baseline amount of ceramide, at least about 5% greater than the baseline amount of ceramide, at least about 10% greater than the baseline amount of ceramide, at least about 15% greater than the baseline amount of ceramide, at least about 20% greater than the baseline amount of ceramide, at least about 25% greater than the baseline amount of ceramide, at least about 30% greater than the baseline amount of ceramide, at least about 40% greater than the baseline amount of ceramide, at least about 50% greater than the baseline amount of ceramide, at least about 100% greater than the baseline amount of ceramide, or at least about 200% greater than the baseline amount of ceramide.

[0027] The method 100 may also include, at 108, modifying the condition of the area of ​​skin. In various examples, the subsequent amount of ceramide generated by applying the formulation to the respective area of ​​skin may modify the condition of the area of ​​skin. In one or more illustrative examples, the above conditions may include at least one of dermatitis, erythema, precancerous lesions, spots, scales, dark spots, scars, redness, lines, or wrinkles. The subsequent amount of ceramide may be functional in that the subsequent amount of ceramide results in a change to the subject's skin that would not be caused by a baseline amount of ceramide. In at least some examples, the subsequent amount of ceramide may result in a change to the subject's skin that would not be caused by a baseline amount of ceramide over a given period of time. The formulation may modify the condition of the area of ​​skin of the subject after being applied to the area of ​​skin of the subject for at least three consecutive 48-hour periods, at least once within each consecutive 48-hour period. Further, the formulation is capable of altering the condition of an area of ​​skin of a subject after being applied to the area of ​​skin of a subject at least once per day for at least four consecutive days.

[0028] In one or more examples, the subsequent amount of ceramide is present on the area of ​​the subject's skin for at least 10 hours after the formulation is applied to the area of ​​the subject's skin. Additionally, the subsequent amount of ceramide is present on the area of ​​the subject's skin for about 0.5 hours to about 24 hours after the formulation is applied to the area of ​​the subject's skin.

[0029] In various examples, the dosage of the formulation may comprise at least 0.01 milliliters (mL), at least 0.02 mL, at least 0.05 mL, at least 0.08 mL, at least 0.10 mL, at least 0.12 mL, at least 0.15 mL, at least 0.18 mL, at least 0.20 mL, at least 0.22 mL, at least 0.25 mL, at least 0.28 mL, at least 0.30 mL, at least 0.32 mL, at least 0.35 mL, at least 0.38 mL, or at least 0.40 mL. In one or more examples, the dosage of the formulation may be 0.01 mL to 2 mL, 0.05 mL to 1 mL, 0.10 mL to 0.80 mL, 0.20 mL to 0.50 mL, 0.30 mL to 0.60 mL, or 0.30 mL to 0.50 mL. In one or more illustrative examples, an effective amount of the formulation may include at least 1 dose, at least 2 doses, at least 3 doses, at least 5 doses, at least 8 doses, at least 10 doses, at least 12 doses, at least 15 doses, at least 18 doses, or at least 20 doses.In one or more further examples, the effective amount of the formulation is from 1 to 200 doses, from 1 to 150 doses, from 1 to 100 doses, from 1 to 75 doses, from 1 to 50 doses, from 1 to 40 doses, from 1 to 30 doses, from 1 to 20 doses, from 1 to 10 doses, from 3 to 200 doses, from 3 to 150 doses, from 3 to 10 ... from 3 doses to 75 doses, from 3 doses to 50 doses, from 3 doses to 40 doses, from 3 doses to 30 doses, from 3 doses to 20 doses, from 3 doses to 10 doses, from 5 doses to 200 doses, from 5 doses to 150 doses, from 5 doses to 100 doses, from 5 doses to 75 doses, from 5 doses to 50 doses, from 5 doses to 40 doses, from 5 doses to 30 doses, from 5 doses to 20 doses, from 5 doses to 50 doses, from 6 to 10 doses, from 6 to 200 doses, from 6 to 150 doses, from 6 to 100 doses, from 6 to 75 doses, from 6 to 50 doses, from 6 to 40 doses, from 6 to 30 doses, from 6 to 20 doses, from 6 to 10 doses, from 8 to 200 doses, from 8 to 150 doses, from 8 to 100 doses, from 8 to 75 doses, The dose may be from 1 to 50 doses, 8 to 40 doses, 8 to 30 doses, 8 to 20 doses, 8 to 10 doses, 10 to 200 doses, 10 to 150 doses, 10 to 100 doses, 10 to 75 doses, 10 to 50 doses, 10 to 40 doses, 10 to 30 doses, or 10 to 20 doses.

[0030] In various examples, the formulation can be applied to an area of ​​skin in an effective amount once a day, twice a day, three times a day, four times a day, or five times a day. The formulation can also be applied to an area of ​​skin for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 15 days, at least 25 days, at least 30 days, at least 40 days, at least 50 days, at least 75 days, at least 100 days, at least 150 days, at least 200 days, at least 250 days, at least 300 days, at least 350 days to treat a skin condition. In various examples, the formulation can be applied to the skin to treat a condition until the condition is no longer present on the skin.

[0031] In one or more illustrative examples, the formulation can be applied to an individual's skin to treat one or more conditions. For example, the formulation can be applied to an individual's skin to treat atopic dermatitis. Additionally, the formulation can be applied to an individual's skin to treat melanoma. Additionally, the formulation can be applied to an individual's skin to treat redness. Additionally, the formulation can be applied to an individual's skin to treat dryness. In one or more examples, the formulation can be applied to an individual's skin to treat scarring. In one or more additional examples, the formulation can be applied to an individual's skin to treat precancerous lesions. In one or more further examples, the formulation can be applied to an individual's skin to treat acne. In yet other examples, the formulation can be applied to an individual's skin to treat wounds, such as cuts, sores, bites, or lesions. Additionally, the formulation can be applied to an individual's skin to treat wrinkles. In various examples, the formulation can be applied to an individual's skin to treat hyperpigmentation. The formulation can also be applied to an individual's skin to treat dark spots. In yet another example, the formulation can be applied to an individual's skin to treat erythema. In yet an additional example, the formulation can be applied to an individual's skin to treat uneven skin tone. In one or more examples, the formulation can be applied to an individual's skin to treat scaling. In one or more additional examples, the formulation can be applied to an individual's skin to treat scaling. In one or more further examples, the formulation can be applied to an individual's skin to treat comedones.

[0032] The formulation can also be applied to an individual's skin to increase moisture of the skin in the area being treated. Additionally, the formulation can be applied to an individual's skin to reduce redness of the skin in the area being treated. Additionally, the formulation can be applied to an individual's skin to reduce inflammation of the skin in the area being treated. In various examples, the formulation can be applied to an individual's skin to reduce sensitivity of the skin in the area being treated. In one or more illustrative examples, the condition of the skin can begin to improve in response to applying 0.15 mL to 0.50 mL of the formulation to the area of ​​skin for at least three days. In one or more examples, the formulation can be applied to the area of ​​skin twice a day. In various examples, a dose of the formulation can be dispensed as a spray from a container containing a volume of the formulation.

[0033] The formulation can be applied to many parts of the individual's body. For example, the formulation can be applied to the individual's face. In addition, the formulation can be applied to the individual's neck. Furthermore, the formulation can be applied to at least a portion of at least one of the individual's limbs or appendages. The formulation can also be applied to at least a portion of at least one of the individual's torso, back, or stomach. In one or more examples, the formulation can be applied to at least a portion of the individual's scalp.

[0034] A numbered, non-limiting list of aspects of the invention is provided below.

[0035] Aspect 1: A formulation comprising: about 50% to about 65% water by weight; about 20% to about 30% 1,3-butanediol by weight; about 5% to about 15% glycerin by weight; about 2% to about 10% 1,2-propanediol by weight; and about 0.0005% to about 0.005% sphingosine by weight.

[0036] Embodiment 2: The formulation of embodiment 1, comprising about 0.7% by weight to about 1.2% by weight of squalene and about 0.0015% by weight to about 0.0025% by weight of palmitic acid.

[0037] Embodiment 3: A formulation comprising at least about 50% by weight water and about 1% by weight or less of a sphingolipid.

[0038] Embodiment 4: The formulation of embodiment 3, wherein the sphingolipid comprises sphingosine.

[0039] Aspect 5: A formulation according to aspect 3 or 4, comprising about 20% to about 40% by weight of one or more diols having 3 to 6 carbon atoms.

[0040] Aspect 6: The formulation of aspect 5, comprising about 20% to about 40% by weight of a first diol having from 3 to 6 carbon atoms and about 2% to about 10% by weight of a second diol having from about 3 to 6 carbon atoms.

[0041] Aspect 7: The formulation of aspect 6, comprising about 20% to about 30% by weight of 1,3-butanediol and about 2% to about 10% by weight of 1,2-propanediol.

[0042] Embodiment 8: The formulation of any one of embodiments 3 to 7, comprising about 7% to about 12% by weight of glycerin.

[0043] Embodiment 9: The formulation of any one of embodiments 3 to 8, further comprising one or more modifiers.

[0044] Aspect 10: The formulation of Aspect 9, wherein the one or more adjusters include at least one of 1,3 butanediol, isohexadecane, or squalene.

[0045] Embodiment 11: The formulation of embodiment 9 or 10, comprising about 0.5 wt.% or less of isohexadecane.

[0046] Embodiment 12: The formulation of any one of embodiments 9 to 11, comprising about 0.10% to about 0.40% by weight of isohexadecane.

[0047] Embodiment 13: The formulation of any one of embodiments 9 to 12, comprising about 2% by weight or less of squalene.

[0048] Embodiment 14: The formulation of embodiment 13, comprising about 0.7% to about 1.2% by weight of squalene.

[0049] Embodiment 15: The formulation according to any one of embodiments 3 to 14, further comprising an emulsifier.

[0050] Embodiment 16: The formulation of embodiment 15, comprising about 0.2% by weight or less of polysorbate 80.

[0051] Embodiment 17: The formulation of embodiment 15 or 16, comprising about 0.06% to about 0.15% by weight of polysorbate 80.

[0052] Embodiment 18: The formulation of any one of embodiments 3 to 17, comprising an emulsion stabilizer.

[0053] Aspect 19: The formulation of aspect 18, comprising about 1% by weight or less of a copolymer of sodium acrylate and sodium acryloyldimethyltaurate.

[0054] Aspect 20: The formulation of aspect 18 or 19, comprising about 0.1% to about 1.5% by weight of the copolymer of sodium acrylate and sodium acryloyldimethyltaurate.

[0055] Embodiment 21: The formulation of any one of embodiments 3 to 20, comprising about 0.005% by weight or less of palmitic acid.

[0056] Aspect 22: A formulation described in any one of aspects 3 to 21, comprising: about 22% to about 28% by weight of 1,3-butanediol; about 8% to about 12% by weight of glycerin; and about 3% to about 8% by weight of 1,2-propanediol.

[0057] Embodiment 23: The formulation of any one of embodiments 3 to 22, comprising about 50% to about 65% water by weight.

[0058] Embodiment 24: The formulation of any one of embodiments 3 to 23, comprising about 0.0005% by weight to about 0.005% by weight of sphingosine.

[0059] Embodiment 25: A method comprising the step of applying a formulation comprising at least about 50% by weight water and about 1% by weight or less sphingolipid to an area of ​​the skin of a subject to activate the sphingosine-1-phosphate biochemical pathway and produce a subsequent amount of ceramide on the area of ​​skin that is greater than the baseline initial amount of ceramide present on the area of ​​the skin of the subject in the absence of the formulation.

[0060] Embodiment 26: The method of embodiment 25, wherein the subsequent amount of ceramide is present on the area of ​​skin of the subject for at least 10 hours after the formulation is applied to the area of ​​skin of the subject.

[0061] Embodiment 27: The method of embodiment 25 or 26, wherein the subsequent amount of ceramide is present on the area of ​​skin of the subject for about 0.5 hours to about 24 hours after the formulation is applied to the area of ​​skin of the subject.

[0062] Embodiment 28: A method according to any one of embodiments 25 to 27, wherein the formulation modifies the condition of an area of ​​the subject's skin after being applied to the area of ​​the subject's skin at least once within each of the consecutive 48 hour periods for at least three consecutive 48 hour periods.

[0063] Embodiment 29: The method according to embodiment 28, wherein the formulation modifies the condition of the area of ​​skin of the subject after application to the area of ​​skin of the subject at least once per day for at least four consecutive days.

[0064] Aspect 30: The method of aspect 28 or 29, wherein said condition comprises at least one of dermatitis, erythema, precancerous lesions, spots, scales, dark spots, scars, redness, lines, or wrinkles.

[0065] Embodiment 31 The method of any one of embodiments 25 to 30, wherein the subsequent amount of ceramide produced is at least about 5% greater than the baseline amount of ceramide.

[0066] Embodiment 32: The method of embodiment 31, wherein the subsequent amount of ceramide produced is at least about 10% greater than the baseline amount of ceramide.

[0067] Embodiment 33: A method of treating a skin condition comprising applying to an area of ​​the skin of a subject an effective amount of a formulation comprising at least about 50% water by weight and no more than about 1% by weight of a sphingolipid.

[0068] Embodiment 34: The method of embodiment 33, wherein the skin condition is atopic dermatitis.

[0069] Embodiment 35: The method according to any one of embodiments 33 to 34, wherein the skin condition is melanoma.

[0070] Aspect 36: The method of any one of aspects 33 to 35, wherein the skin condition is redness.

[0071] Aspect 37: A method according to any one of aspects 33 to 36, wherein the skin condition is dry.

[0072] Embodiment 38: A method according to any one of embodiments 33 to 37, wherein the skin condition is a scar.

[0073] Embodiment 39: The method of any one of embodiments 33 to 38, wherein the skin condition is a precancerous lesion.

[0074] Embodiment 40: A method according to any one of embodiments 33 to 39, wherein the skin condition is acne.

[0075] Embodiment 41: A method according to any one of embodiments 33 to 40, wherein the skin condition is a wound.

[0076] Aspect 42: A method according to any one of aspects 33 to 41, wherein the skin condition is wrinkles.

[0077] Embodiment 43: The method of any one of embodiments 33 to 42, wherein the skin condition is hyperpigmentation.

[0078] Embodiment 44: The method of any one of embodiments 33 to 43, wherein the skin condition is a dark spot.

[0079] Embodiment 45: A method according to any one of embodiments 33 to 44, wherein the skin condition is erythema.

[0080] Aspect 46: A method according to any one of aspects 33 to 45, wherein the skin condition is uneven skin tone.

[0081] Embodiment 47: The method of any one of embodiments 33 to 46, wherein the skin condition is scaly.

[0082] Embodiment 48: The method of any one of embodiments 33 to 47, wherein the skin condition is scaly.

[0083] Embodiment 49: A method according to any one of embodiments 33 to 48, wherein the skin condition is the presence of comedones.

[0084] Embodiment 50: A method according to any one of embodiments 33 to 49, wherein application of the formulation to an area of ​​skin increases moisture of the skin contained in that area.

[0085] Aspect 51: A method according to any one of aspects 33 to 50, wherein application of the formulation to the area reduces redness of the skin contained in the area.

[0086] Embodiment 52: A method according to any one of embodiments 33 to 51, wherein application of the formulation to the area reduces inflammation of the skin involved in the area.

[0087] Aspect 53: A method according to any one of aspects 33 to 52, wherein application of the formulation to said area reduces redness of the skin contained in said area.

[0088] Embodiment 54: A method according to any one of embodiments 33 to 53, wherein application of the formulation to the area reduces sensitivity of the skin involved in the area.

[0089] Aspect 55: A method described in any one of aspects 33 to 54, wherein the region includes at least a portion of the subject's face.

[0090] Aspect 56: A method described in any one of aspects 33 to 55, wherein the area includes at least a portion of the subject's neck.

[0091] Aspect 57: A method according to any one of aspects 33 to 56, wherein the area includes at least a portion of at least one of the subject's limbs or appendages.

[0092] Aspect 58: The method of any one of aspects 33 to 57, wherein the area includes at least a portion of at least one of the subject's torso, back, or stomach.

[0093] Aspect 59: The method of any one of aspects 33 to 58, wherein the area comprises at least a portion of the subject's scalp.

[0094] Embodiment 60: A method according to any one of embodiments 33 to 59, wherein 0.15 mL to 0.50 mL of the formulation is applied to the above-mentioned area.

[0095] Embodiment 61: A method according to any one of embodiments 33 to 60, wherein the formulation is applied to the area for at least 3 days.

[0096] Embodiment 62: A method according to any one of embodiments 33 to 61, wherein the formulation is applied to the above-mentioned area twice a day for at least three days.

[0097] Experimental Example Example 1 In the first study, 11 subjects were provided with a protocol for applying a formulation according to embodiments described herein to the area of ​​skin to be treated. The amount of the formulation used per application was estimated to be 0.15 milliliters (mL) to 0.50 mL. Subjects applied the formulation to the area to be treated for two weeks.

[0098] Figure 2A shows the first subject's photo before using the formulation described herein, and Figure 2B shows the first subject's photo after using the formulation.The subject achieves improvement in skin irritation.In addition, the subject's spots and scales are reduced.Redness and wrinkles are also reduced, hyperpigmentation is also reduced, dark spots are also reduced, and skin tone is more even.

[0099] Figure 3A shows a photograph of a second subject participating in the study before use of the formulation described herein, and Figure 3B shows a photograph of the second subject after use of the formulation. Reduction in acne was observed in the second subject after application of the formulation described herein.

[0100] Figure 4A shows a photograph of the third subject who participated in the study before using the formulation described herein, and Figure 4B shows a photograph of the third subject after using the formulation. There was a reduction in wrinkles, including a reduction in marionette lines and a reduction in vertical furrows on the upper lip. The third subject also experienced a reduction in erythema and wrinkles around the eyes.

[0101] Figure 5A shows a photograph of the fourth subject participating in the study before using the formulation described herein, and Figure 5B shows a photograph of the fourth subject after using the formulation.Reduction in scale and scaly was observed in the subject.In addition, reduction in spots and marionette lines was also achieved.

[0102] Figure 6A shows a photograph of the fifth subject who participated in the study before use of the formulation described herein, and Figure 6B shows a photograph of the fifth subject after use of the formulation. Reduction in precancerous lesions was observed in the fourth subject after application of the formulation described herein and after three days of use.

[0103] Example 2 In the second study, a total of 52 male and female subjects, ranging in age from 18 to 74 years, who met all of the inclusion criteria and no exclusion criteria outlined in the study protocol were selected as study participants. Recruitment was broad-based and based on interest in "natural skin products."

[0104] Research Summary: - 24-hour patch test before starting topical application - 6 self-assessment surveys with questions requiring you to rate each item from 0 to 100 - The survey included open-ended and multiple choice questions. - Microbiome and metabolome skin swabs at the start and end of the study - Left, right and front, before, in between and after photos - Skin evaluation of before, mid and after photos (3 sides each) was competed by an MD board certified dermatologist. Evaluation method: (1) Acceptable photos (2) Absence of any serious medically treatable (i.e., non-cosmetic) condition of the facial skin that would complicate evaluation in this study (3) Forehead lines (4) Spherical pleats (5) Skin around the eyes (6) Severity of vertical grooves on the upper lip (7) Marionette Lines (8) Severity of lines at the corners of the mouth (9) Severity of patchy pigmentation (10) Overall skin tone, skin health, and skin vitality (11) Glogau Wrinkle Scale (12) Erythema (redness) (13) Age Estimation (14) Any additional notable changes.

[0105] Participants in this study were provided with 60 mL of a topical cosmetic formulation according to embodiments herein in an airless component that was used to pump a dose of the formulation.

[0106] Each actuation of the pump device delivered 15 mL to 30 mL of the formulation. Study participants were provided with a protocol to apply the formulation using 1-2 pump actuations twice daily, once in the morning and once in the evening / night. Participants were asked to apply an amount of the formulation to the face and neck. The study duration was 15 weeks.

[0107] Statistical tests were performed as paired tests (comparing each individual's self-assessment score with their own previous score). All variables were checked for normality and, where applicable, Wilcoxon paired tests were used.

[0108] Table 1 shows a comparison of survey self-assessment scores from the beginning to the midpoint across Surveys 1 through 3 for all participants (week 1 compared to weeks 5–6).

[0109] [Table 1] Table 2 shows a comparison of survey self-assessment scores from the beginning to the midpoint (week 1 vs. weeks 5–6) for Study 1 through Study 3 for participants with sensitive skin only.

[0110] [Table 2] Table 3 shows a comparison of survey self-assessment scores from baseline to midpoint (week 1 vs. weeks 5-6) for participants with non-sensitive skin.

[0111] [Table 3] Table 4 shows a comparison of the survey self-assessment scores from start to finish (weeks 10–12) for all participants (week 1 compared to weeks 10–12).

[0112] [Table 4] Table 5 shows a comparison of the survey self-assessment scores from start to finish (weeks 10–12) for participants with sensitive skin (week 1 vs. weeks 10–12).

[0113] [Table 5] Table 6 shows a comparison of the self-assessment scores of the survey from start to finish (weeks 10–12) for participants with non-sensitive skin (week 1 vs. weeks 10–12).

[0114] [Table 6] Figure 7A shows a photograph of the first subject participating in Study #2 before use of a formulation described herein, and Figure 7B shows a photograph of the first subject after use of the formulation. The first subject experienced a reduction in hyperpigmentation after use of a formulation described herein.

[0115] Figure 8A shows a photograph of a second subject participating in Study #2 before use of the formulation described herein, and Figure 8B shows a photograph of the second subject after use of the formulation. Reduction in skin blemishes, redness, and hyperpigmentation was observed in the second subject after use of the formulation described herein.

[0116] Figure 9A shows the photograph of the third subject who participated in study #2 before using the formulation described herein, and Figure 9B shows the photograph of the third subject after using the formulation.The third subject experienced a reduction in hyperpigmentation, redness, and acne.In addition, an increase in skin vitality was observed.

[0117] Figure 10A shows a photograph of a fourth subject who participated in Study #2 before use of a formulation described herein, and Figure 10B shows a photograph of the fourth subject after use of the formulation. A reduction in blemishes and redness was observed in the fourth subject, as well as an improvement in the appearance of scars.

[0118] Figure 11A shows a photograph of a fifth subject who participated in Study #2 before use of a formulation described herein, and Figure 11B shows a photograph of the fifth subject after use of the formulation. Reductions in hyperpigmentation and comedones were observed in the fifth subject, as well as increased vitality.

[0119] Figure 12A shows a photograph of a sixth subject who participated in Study #2 before use of a formulation described herein, and Figure 12B shows a photograph of the sixth subject after use of the formulation. A reduction in the size and prominence of scar tissue was observed in the sixth subject.

[0120] Figure 13A shows a photograph of a further subject with an upper wound and an underlying scar before use of a formulation described herein, and Figure 13B shows a photograph of a further subject after use of the formulation. Healing of the wound and lack of scarring was observed in the further subject.

[0121] Figure 14 shows normalized abundance measurements of many bacteria for study #2 subjects characterized with normal skin before and after treatment with the formulation. Figure 14 shows the change in bacterial abundance. A more balanced skin microbiome is achieved after treatment with the formulation, as indicated by the relative abundance of bacteria closer together than before treatment with the formulation.

[0122] Figure 15 shows measurements of normalized abundance of a number of bacteria for study #2 subjects characterized with sensitive skin before and after treatment with the formulation. Figure 15 shows the change in bacterial abundance. The difference in normalized abundance of bacteria in Figures 14 and 15 shows the difference in the skin microbiome in individuals characterized with sensitive skin versus normal skin.

[0123] The bacterial abundances shown in Figures 14 and 15 were determined according to the following procedure.

[0124] To assess the impact on the skin microbiome, subjects were provided with two 15 mL conical tubes, each containing two pre-moistened swabs that were to be used to collect samples from three facial sites: (1) forehead and cheek, and (2) sides of the nose. One set of swabs was collected from the left side of the face, and the other set of swabs was collected from the right side of the face. Sampling was performed over a 1 in x 1 in area for approximately 10 seconds with the swabs at each site pre-moistened in 50:50 ethanol / water for mass spectrometry (MS) or 50 mM Tris pH 7.6, 1 mM EDTA, and 0.5% Tween 20 for nucleic acid analysis.

[0125] The swabs were taken when the subjects woke up in the morning, before washing or applying anything to their face. These samples were also taken at the start of the study, before any course of formulation was started and used, and at the end of the study.

[0126] After collection, one pair of swabs / tubes was extracted (the other two were duplicate swabs / tubes) in 500 μL of 50:50 ethanol / water (for mass spectrometry) or Tris-EDTA buffer (50 mM Tris pH 7.6, 1 mM EDTA, and 0.5% Tween 20) for bacterial DNA extraction. Samples were then stored at -80°C.

[0127] The first pair or tube of swabs extracted with the ethanol / water extract was subjected to mass spectrometry including MALDI-TOF for detection of metabolites, peptides, and proteins, and UPLC-QTOF for detection of smaller molecules including tandem MS (MS / MS) of molecules for molecular network analysis.

[0128] A second set of collected swabs (two swab replicates) were subjected to metagenomic shotgun sequencing to identify microbiome material present in the same locations. Two swab tubes (each tube with two swabs) were collected at the beginning and end of the study.

[0129] It should be noted that not all of the activities described in the general description above are required, that some of the specific activities may not be required, and that one or more additional activities may be performed in addition to the activities described. Furthermore, the order in which the activities are listed is not necessarily the order in which they are performed.

[0130] Certain features that are described herein for clarity in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, various features that are described for brevity in the context of a single embodiment may also be provided separately or in any subcombination. Further, references to values ​​stated in ranges include each and every value within that range.

[0131] Benefits, other advantages, and solutions to problems have been described above with respect to particular embodiments. However, the benefits, advantages, solutions to problems, and any one or more features that may cause or make any benefit, advantage, or solution to occur should not be construed as critical, necessary, or essential features of any or all of the claims.

[0132] The specification and illustrations of the embodiments described herein are intended to provide a general understanding of the structure of the various embodiments. The specification and illustrations are not intended to serve as an exhaustive and comprehensive description of all of the elements and features of the apparatus and systems that use the structures or methods described herein. Separate embodiments may also be provided in combination in a single embodiment, and conversely, various features that are described in the context of a single embodiment for brevity may also be provided separately or in any subcombination. Furthermore, references to values ​​described in ranges include each and every value within that range. Many other embodiments may become apparent to those skilled in the art only after reading this specification. Other embodiments may be used and derived from the present disclosure, such that structural substitutions, logical substitutions, or other changes may be made without departing from the scope of the present disclosure. The present disclosure is therefore to be considered illustrative and not limiting.

Claims

1. At least about 50% by weight of water, and about 1% by weight or less of sphingolipid, A formulation containing.

2. The formulation according to claim 1, wherein the sphingolipid contains sphingosine.

3. The formulation according to claim 1, comprising about 20% to about 30% by weight of 1,3 - butanediol and about 2% to about 10% by weight of 1,2 - propanediol.

4. The formulation according to claim 1, comprising about 7% to about 12% by weight of glycerin.

5. The formulation according to claim 1, comprising one or more conditioning agents containing at least one of 1,3 - butanediol, isocetadecane, or squalene.

6. The formulation according to claim 5, comprising about 0.7% to about 1.2% by weight of squalene.

7. The formulation according to claim 1, comprising about 0.06% to about 0.15% by weight of polysorbate 80, and a copolymer of about 0.1% to about 1.5% by weight of sodium acrylate and sodium acryloyldimethyltaurate.

8. The formulation according to claim 1, comprising about 0.0005% to about 0.005% by weight of palmitic acid.

9. The formulation according to claim 1, comprising about 50% to about 65% by weight of water.

10. The formulation according to claim 1, comprising about 0.0005% to about 0.005% by weight of sphingosine.

11. About 50% to about 65% by weight of water, and about 0.0005% to about 0.005% by weight of sphingosine, and about 20% to about 30% by weight of 1,3 - butanediol, and about 5% to about 15% by weight of glycerin, and from about 0.7% of squalene to about 1.2% of squalene, and from about 0.0015% of palmitic acid to about 0.0025% of palmitic acid, and about 3% to about 8% by weight of 1,2 - propanediol, and A formulation containing.

12. About 50% to about 65% by weight of water, and about 20% to about 30% by weight of 1,3 - butanediol, and about 5% to about 15% by weight of glycerin, and about 2% to about 10% by weight of 1,2 - propanediol, and about 0.0005% to about 0.005% by weight of sphingosine, and A formulation containing.

13. From about 0.7% of squalene to about 1.2% of squalene, and from about 0.0015% of palmitic acid to about 0.0025% of palmitic acid, The formulation according to claim 1, comprising

Images