Anti-inflammatory topical compositions

Abstract

Anti-inflammatory topical compositions are disclosed in which niacinamide and polylysine dendrimer synergistically reduce the release of inflammatory markers (e.g., IL-8) from skin cells. Also disclosed are anti-inflammatory topical compositions in which polylysine dendrimer and various plant extracts reduce the release of inflammatory markers (e.g., IL-8) from skin cells. The pro-oxidative activity of polylysine dendrimer may be reduced by including an antioxidant (e.g., tocopherol and / or tocopheryl acetate) to an anti-inflammatory topical composition. Anti-inflammatory topical compositions comprising polylysine dendrimer and niacinamide and / or plant extracts (e.g., aloe vera extract, edelweiss extract, scuatline, etc.) may be used for treating inflammatory skin conditions (e.g., acne) by reducing the release of inflammatory markers (e.g., IL-8) from skin cells.

Description

ANTI-INFLAMMATORY TOPICAL COMPOSITIONSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to European Patent Application No. 24164632.2, filed March 19, 2024, the entire contents of all of which are hereby incorporated by reference herein.BACKGROUND

[0002] The present disclosure relates to the field of anti-inflammatory topical compositions. Inflammatory skin disorders are well-known and may include acne, psoriasis, hives, eczema, rosacea, vitiligo, keratosis and dermatitis. Acne vulgaris is a common chronic inflammatory skin disease with a complex pathogenesis developing in the sebaceous follicles. Four key pathogenic factors have been identified: (i) an alteration in the pattern of keratinisation within the follicle, (ii) increased sebum production, (iii) colonization with Propionibacterium acnes, and (iv) inflammation. In acne-prone skin, inflammatory processes may precede the development of a visibly apparent lesion in skin that appears otherwise clinically normal; thus, targeting inflammation is an essential part of acne therapy.

[0003] Skin insult or inflammatory skin disorders induce the release of IL- lb, a pro- inflammatory mediator, which activates the NF-kB signaling pathway, including the production and release of the generic inflammatory effector IL-8. Inhibiting IL-lb-induced release of IL-8, including by blocking the NF-kB pathway is one method for providing antiinflammatory effects. Thus, it would be advantageous to provide anti-inflammatory topical compositions which inhibit the release of IL-8 (e.g., by blocking the NF-kB pathway).SUMMARY

[0004] In one aspect, which may be combined with any other aspect or embodiment, the present disclosure relates to a topical composition for reducing skin inflammation, the composition comprising: a polylysine dendrimer; niacinamide; and an antioxidant. In some embodiments, the polylysine dendrimer comprises unconjugated poly-L-lysine dendrimer.

[0005] In some embodiments, the antioxidant comprises tocopheryl acetate, tocopherol, or a combination thereof. In some embodiments, the tocopheryl acetate is present at a concentration of about 0.00002 wt.% to about 5.4 wt.%, relative to the total weight of the composition. In some embodiments, the tocopheryl acetate is present at a concentration of about 0.01 wt.% to about 1.5 wt.%, relative to the total weight of the composition. In some embodiments, the tocopherol is present at a concentration of about 0.00002 wt % to about 5.4 wt %, relative to the total weight of the composition. In some embodiments, the tocopherol is present at a concentration of about 0.01 wt.% to about 1.5 wt.%, relative to the total weight of the composition.

[0006] In some embodiments, the niacinamide is present at a concentration of about 0.0001 wt.% to about 3 wt.%, relative to the total weight of the composition. In some embodiments, the niacinamide is present at a concentration of about 0.01 wt.% to about 1.5 wt.%, relative to the total weight of the composition.

[0007] In some embodiments, the polylysine dendrimer is present at a concentration of about 0.1 ppm to about 100 ppm, relative to the total weight of the composition. In some embodiments, the polylysine dendrimer is present at a concentration of about 0.5 ppm to about 10 ppm, relative to the total weight of the composition. In some embodiments, the polylysine dendrimer is present at a concentration of about 1 ppm to about 5 ppm, relative to the total weight of the composition.

[0008] In some embodiments, the anti-inflammatory topical composition comprises gelling agents at a concentration of 0.5 wt.% to 5 wt.%, relative to the total weight of the composition.

[0009] In some embodiments, the anti-inflammatory topical composition comprises D- panthenol at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.

[0010] In some embodiments, the anti-inflammatory topical composition comprises sebum regulating agent wherein the sebum regulating agent is selected from the group consisting of zinc gluconate, clascoterone, and isotretinoin. In some embodiments, the one or more sebum-regulating agents comprises zinc gluconate, isopropylcarbonate benzoyl peroxide, clascoterone, isotretinoin, salicylic acid, sulfur, one or more clays (e.g., kaolin, bentonite, hectorite, perlite, ghassoul (rhassoul), etc.), silica, Enantia chlorantha bark extract, one or more starches, or a combination thereof. In some embodiments, the sebum regulating agent is zinc gluconate at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.

[0011] In some embodiments, the anti-inflammatory topical composition comprises glycerin at a concentration of 0.5 wt.% to 5 wt.%, relative to the total weight of the composition.

[0012] In some embodiments, the anti-inflammatory topical composition comprises at least one selected from the group consisting of: aloe vera extract, edelweiss, and scutaline.

[0013] In some embodiments, the anti-inflammatory topical composition comprises squalene at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.

[0014] In some embodiments, the anti-inflammatory topical composition comprises the polylysine dendrimer at a concentration of 0.1 ppm to about 100 ppm, relative to the total weight of the composition; niacinamide at a concentration of 1 wt.% to 5 wt.%, relative to the total weight of the composition; an antioxidant, wherein the antioxidant is tocopherol or tocopheryl acetate, or a combination thereof, present at a concentration of 00002 wt % to 5.4 wt %; and one or more humectants or emollients.

[0015] In some embodiments, the composition is formulated as a gel, emulsion, or cream. In some embodiments, the composition is formulated for leave-on topical application.

[0016] In some embodiments, the composition is effective to reduce or prevent inflammation when applied to the skin of a subject by reducing IL-8 release by at least about 20%, relative to the amount of IL-8 released in skin to which the composition is not applied.

[0017] In some embodiments, the polylysine dendrimer and the niacinamide are present in amounts effective to exhibit synergistic reduction of inflammation when applied to the skin of a subject.

[0018] In another aspect, which may be combined with any other aspect or embodiment, the present disclosure relates to a topical composition for reducing skin inflammation, the composition comprising: a polylysine dendrimer; and at least one selected from the group consisting of: aloe vera extract, edelweiss, and scutaline.

[0019] In some embodiments, the polylysine dendrimer comprises unconjugated poly-L- lysine dendrimer. In some embodiments, the polylysine dendrimer is present at a concentration of about 0.1 ppm to about 100 ppm, relative to the total weight of the composition. In some embodiments, the polylysine dendrimer is present at a concentration of about 0.5 ppm to about 10 ppm, relative to the total weight of the composition. In some embodiments, the polylysine dendrimer is present at a concentration of about 1 ppm to about 5 ppm, relative to the total weight of the composition.

[0020] In some embodiments, the anti-inflammatory topical composition comprises an antioxidant. In some embodiments, the antioxidant comprises tocopheryl acetate, tocopherol, or a combination thereof. In some embodiments, the tocopheryl acetate is present at a concentration of about 0.00002 wt.% to about 5.4 wt.%, relative to the total weight of the composition. In some embodiments, the tocopheryl acetate is present at a concentration of about 0.01 wt.% to about 1.5 wt.%, relative to the total weight of the composition. In some embodiments, the tocopherol is present at a concentration of about 0.00002 wt % to about 5.4 wt %, relative to the total weight of the composition. In some embodiments, the tocopherol is present at a concentration of about 0.01 wt.% to about 1.5 wt.%, relative to the total weight of the composition.

[0021] In some embodiments, the anti-inflammatory topical composition comprises niacinamide, wherein the niacinamide is present at a concentration of about 0.0001 wt.% to about 3 wt.%, relative to the total weight of the composition. In some embodiments, the niacinamide is present at a concentration of from 0.5 wt.% to 5 wt.%, relative to the total weight of the composition.

[0022] In some embodiments, the anti-inflammatory topical composition comprises gelling agents at a concentration of 0.5 wt.% to 5 wt.%, relative to the total weight of the composition.

[0023] In some embodiments, the anti-inflammatory topical composition comprises D- panthenol at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.

[0024] In some embodiments, the anti-inflammatory topical composition comprises a sebum regulating agent wherein the sebum regulating agent is selected from the group consisting of zinc gluconate, clascoterone, and isotretinoin. In some embodiments, the one or more sebumregulating agents comprises zinc gluconate, isopropylcarbonate benzoyl peroxide, clascoterone, isotretinoin, salicylic acid, sulfur, one or more clays (e.g., kaolin, bentonite, hectorite, perlite, ghassoul (rhassoul), etc.), silica, Enantia chlorantha bark extract, one or more starches, or a combination thereof. In some embodiments, the sebum regulating agent is zinc gluconate at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.

[0025] In some embodiments, the anti-inflammatory topical composition comprises glycerin at a concentration of 0.5 wt.% to 5 wt.%, relative to the total weight of the composition.

[0026] In some embodiments, the anti-inflammatory topical composition comprises squalene at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.

[0027] In some embodiments, the anti-inflammatory topical composition comprises: the polylysine dendrimer at a concentration of about 0.1 ppm to about 100 ppm, relative to the total weight of the composition; and the aloe vera extract, edelweiss, or scutaline, at a concentration of 0.00001 wt.% to 1 wt.%, relative to the total weight of the composition.

[0028] In some embodiments, the composition is formulated as a gel, emulsion, or cream. In some embodiments, the composition is formulated for leave-on topical application.

[0029] In some embodiments, the composition is effective to reduce or prevent inflammation when applied to the skin of a subject by reducing IL-8 release by at least about 20%, relative to the amount of IL-8 released in skin to which the composition is not applied.

[0030] In some embodiments, the polylysine dendrimer and the aloe vera extract, edelweiss, and / or scutaline are present in amounts effective to exhibit synergistic reduction of inflammation when applied to the skin of a subject.

[0031] In another aspect, which may be combined with any other aspect or embodiment, the present disclosure relates to a method of treating an inflammatory skin disorder, the method comprising administering to the skin of a subject an effective amount of the antiinflammatory topical composition disclosed herein. In some embodiments, the administration is twice daily. In some embodiments, the inflammatory skin disorder is selected from acne, atopic dermatitis, rosacea, psoriasis, and eczema.

[0032] In another aspect, which may be combined with any other aspect or embodiment, the present disclosure relates to a method of preventing or reducing skin inflammation, the method comprising administering to the skin of a subject an effective amount of the composition of the anti-inflammatory topical composition disclosed herein. In some embodiments, the administration is twice daily.

[0033] In another aspect, which may be combined with any other aspect or embodiment, the present disclosure relates to a method of improving skin clarity, the method comprising administering to the skin of a subject an effective amount of the anti-inflammatory topical composition disclosed herein. In some embodiments, the administration is twice daily.

[0034] In another aspect, which may be combined with any other aspect or embodiment, the present disclosure relates to a method of reducing IL-8 release in skin, the method comprising administering to the skin of a subject an effective amount of the anti-inflammatory topical composition disclosed herein. In some embodiments, the administration is twice daily.

[0035] In another aspect, which may be combined with any other aspect or embodiment, the present disclosure relates to a method of reducing oxidative degradation of skin-bound squalene, the method comprising administering to the skin of a subject an effective amount of the composition disclosed herein. In some embodiments, the administration is twice daily.

[0036] In another aspect, which may be combined with any other aspect or embodiment, the present disclosure relates to a method of reducing a ratio of squalene monohydroperoxide tosqualene in skin, the method comprising administering to the skin of a subject an effective amount of the composition disclosed herein. In some embodiments, the administration is twice daily.

[0037] In another aspect, which may be combined with any other aspect or embodiment, the present disclosure relates to a method of preventing or reducing oxidative damage to skin, the method comprising administering to the skin of a subject an effective amount of the composition disclosed herein. In some embodiments, the administration is twice daily.

[0038] In another aspect, which may be combined with any other aspect or embodiment, the present disclosure relates to a method of reducing PGE2 expression in skin, the method comprising administering to the skin of a subject an effective amount of the composition disclosed herein. In some embodiments, the administration is twice daily.

[0039] In another aspect, which may be combined with any other aspect or embodiment, the present disclosure relates to use of a composition according to any one of the embodiments disclosed herein in treating an inflammatory skin disorder, preventing or reducing skin inflammation, improving skin clarity, reducing inflammation in skin, reducing IL-8 release in skin, reducing oxidative degradation of skin-bound squalene, reducing a ratio of squalene monohydroperoxide to squalene in skin, or preventing or reducing oxidative damage to skin. In some embodiments, the inflammatory skin disorder is acne.

[0040] In another aspect, which may be combined with any other aspect or embodiment, a composition for use in treating an inflammatory skin disorder, preventing or reducing skin inflammation, improving skin clarity, reducing inflammation in skin, reducing IL-8 release in skin, reducing oxidative degradation of skin-bound squalene, reducing a ratio of squalene monohydroperoxide to squalene in skin, or preventing or reducing oxidative damage to skin, wherein the composition is a composition according to any of the embodiments disclosed herein. In some embodiments, the inflammatory skin disorder is acne.

[0041] In another aspect, which may be combined with any other aspect or embodiment, the present disclosure relates to use of a composition according to any one of the embodiments disclosed herein, in the manufacture of a medicament for treating an inflammatory skindisorder, preventing or reducing skin inflammation, improving skin clarity, reducing inflammation in skin, reducing IL-8 release in skin, reducing oxidative degradation of skinbound squalene, reducing a ratio of squalene monohydroperoxide to squalene in skin, or preventing or reducing oxidative damage to skin. In some embodiments, the inflammatory skin disorder is acne.

[0042] Additional aspects and / or embodiments of the invention will be provided, without limitation, in the detailed description of the present technology set forth below. The following detailed description is exemplary and explanatory, but it is not intended to be limiting.BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Various objects, aspects, features, and advantages of the disclosure will become more apparent and better understood by referring to the detailed description taken in conjunction with the accompanying figures.

[0044] FIG. 1 is a schematic illustration of experimental design for assays measuring cellular IL-8 released after incubation in the presence of active ingredients.

[0045] FIG. 2 is a plot of IL-8 released (pg / ml), versus control, for cells incubated in a composition comprising DENDRICLEAR™ (concentration 1 = 0.123 vol.%; concentration 2 = 0.37 vol.%, expressed as v / v dilution from manufacturer’s solution) and niacinamide (concentration 1 = 0.367 mg / ml; concentration 2 = 1.1 mg / ml), individually and in combination.

[0046] FIG. 3 is a plot of IL-8 released (pg / ml), versus control, for cells incubated in a composition comprising DENDRICLEAR™ (concentration 1 = 0.123 vol.%; concentration 2 = 0.37 vol.%, expressed as v / v dilution from manufacturer’s solution) and adding aloe leaf juice (aloe extract, 200X dilution from manufacturer’s solution) at concentration 1 (0.041 mg / ml of the 200X dilution) and concentration 2 (0.123 mg / ml of the 200X dilution).

[0047] FIG. 4 is a plot of IL-8 released (pg / ml), versus control, for cells incubated in a composition comprising DENDRICLEAR™ (concentration 1 = 0.123 vol.%; concentration 2 = 0.37 vol.%, expressed as v / v dilution from manufacturer’s solution) and edelweiss extract(concentration 1 = 0.014 vol.% dilution from manufacturer’s solution; concentration 2 = 0.041 vol.% dilution from manufacturer’s solution).

[0048] FIG. 5 is a plot of IL-8 released (pg / ml), versus control, for cells incubated in a composition comprising DENDRICLEAR™ (concentration 1 = 0.123 vol.%; concentration 2 = 0.37 vol.%, expressed as v / v dilution from manufacturer’s solution) and scutaline (concentration 1 = 0.005 vol.% dilution from manufacturer’s solution; concentration 2 = 0.014 vol.% dilution from manufacturer’s solution).

[0049] FIG. 6 is a plot of IL-8 released (pg / ml), versus control, for cells incubated in a composition comprising DENDRICLEAR™ (concentration 1 = 0.123 vol.%; concentration 2 = 0.37 vol.%, expressed as v / v dilution from manufacturer’s solution) and quercetin (95%, Nutraceuticals) (concentration 1 = 0.367 pg / ml; concentration 2 = 1.1 pg / ml).

[0050] FIG. 7 is a plot of IL-8 released (pg / ml), versus control, for cells incubated in a composition comprising DENDRICLEAR™ (concentration 1 = 0.123 vol.%; concentration 2 = 0.37 vol.%, expressed as v / v dilution from manufacturer’s solution) and lycopene (>98% from tomato) (concentration 1 = 3.33 pg / ml; concentration 2 = lOpg / ml).

[0051] FIG. 8 is a schematic illustration of experimental design for assays measuring antioxidant activity for cells exposed to ultraviolet activity in the presence of antioxidant compositions.

[0052] FIG. 9 shows bar charts from two tests measuring the extent of oxidation (via fluorescence emission (515 nm) of 5-aminofluroescein), relative to control, measured by flow cytometry for cells pre-incubated with butylated hydroxyanisole (BHA) and DENDRICLEAR™ (0.123 vol.% and 0.37 vol.%) after UVA+UVB irradiation verus control and non-irradiated cells.

[0053] FIG. 10 is a bar chart showing the extent of oxidation (via fluorescence emission (515 nm) of 5-aminofluroescein), relative to control, measured by flow cytometry for cells preincubated with butylated hydroxyanisole (BHA), two different concentrations of tocopheryl acetate (0.011 wt.% and 0.033 wt.%), two different concentrations of DENDRICLEAR™ (0.123 vol.% and 0.37 vol.%), and two different tocopheryl acetate + DENDRICLEAR™compositions (0.011 wt.% tocopheryl acetate + 0.123 vol. % DENDRICLEAR™; and 0.033 wt.% tocopheryl acetate + 0.37 vol.% DENDRICLEAR™) after UVA+UVB irradiation, versus control and non-irradiated cells.

[0054] FIG. 11 shows side-by-side front view images of an exemplary mean case at baseline and day 57, with 9 inflammatory lesions at baseline and 0 inflammatory lesions at day 57.DETAILED DESCRIPTION

[0055] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present technology. Particular exemplary embodiments of the present technology may be implemented without some or all of these specific details. In other instances, well known process operations have not been described in detail in order not to unnecessarily obscure the present technologies.Polylysine Dendrimer

[0056] Anti-inflammatory compositions according to the present disclosure comprise a polylysine dendrimer. As used herein, the term “dendrimer” refers to a macromolecular, highly branched compound formed by iterative reaction sequences starting from an initial core molecule, with successive layers or stages added in successive “generations” to produce a three-dimensional polymeric compound. Dendrimers may be produced by methods disclosed in the art (e.g., U.S. Patent Nos. 4,289,872 and 4,410,688, and WIPO Publication No. WO 2020 / 197669, which disclose dendrimers based on lysine, the entire disclosures of which are hereby incorporated by reference herein). As used herein, the term “dendrigraff ’ refers to a “grafted dendrimer” prepared in a generation-based scheme involving protective group manipulation combined with polymerization, as described in the following publications: WIPO Publication No. WO 2020 / 197669; Klok & Rodriguez-Hernandez, 35 Macromolecules 8718-23 (2002); and Teertstra & Gauthier, 29 Prog. Polym. Sci. 277-327 (2004), the entire disclosures of which are hereby incorporated by reference herein.

[0057] In some embodiments, the polylysine dendrimer is a poly-L-lysine dendrimer. In some embodiments, the polylysine dendrimer is a second generation (“G2”) grafted polylysine dendrimer, also referred interchangeably herein as “G2 poly-L-lysine dendrigraft,”“G2 dendrimer,” “grafted dendrimer,” “grafted polylysine dendrimer,” or “grafted homopolylysine dendrimer,” “lysine dendri graft,” or “DGL”. Herein, the terms “polylysine dendrimer” and “polylysine dendrigraff ’ are used interchangeably. In some embodiments, the G2 dendrimer according the present disclosure may be prepared as described in the following publications: WIPO Publication No. WO 2020 / 197669; U.S. Patent Publication No. 2008 / 0206183; and Collet et al., 16 Chem. Eur. J. 2309-16 (2010), the entire disclosures of which are hereby incorporated by reference herein.

[0058] In some embodiments, the polylysine dendrimer is a G2 dendrimer (e.g., DENDRICLEAR™ by Lucas Meyer Cosmetics). In some embodiments, the polylysine dendrimer is a G2 homopolylysine dendrigraft comprising or consisting of 30 to 70 lysine residues, 35 to 65 lysine residues, 40 to 60 lysine residues, 45 to 55 residues, or about 48 lysine residues. In embodiments herein, the number of lysine residues refers to the average degree of polymerization of the dendrimer or dendrigraft.

[0059] In some embodiments, the polylysine dendrimer comprises or consists of a linear polylysine core wherein the side chain NH2 groups (s-amino groups) of one or several (preferably all) lysine residues of said core are substituted with a polylysine moiety. For instance, the polylysine dendrimer comprises or consists of a linear poly-L -lysine core (e.g., a-poly-L -lysine) wherein the s-amino groups of each lysine residue is substituted with a poly- L-lysine moiety (e.g., a-poly-L-lysine). In some embodiments, the linear core comprises from 2 to 10 lysine residues, from 4 to 10 lysine residues, from 6 to 10 lysine residues, from 2 to 8 lysine residues, from 4 to 8 lysine residues, from 6 to 8 lysine residues. In some embodiments, the linear core comprises or consists of 8 lysine residues. In some embodiments, each of the poly-L -lysine substituents may comprise or consist of from 2 to 10, from 3 to 10, from 3 to 9, from 3 to 8, from 4 to 8, from 4 to 7, or from 4 to 6 lysine residues. In some embodiments, each of the poly-L -lysine substituents may comprise or consist of 5 lysine residues.

[0060] In some embodiments, the polylysine dendrimer may comprise compounds of formula (I):wherein n is an integer from 2 to 10 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10). In some embodiments, n is 6, 7, 8, or 9. In some embodiments, n is 7. [Lys] indicates a lysine residue, and nl denotes the number of lysine moieties linked together to form a polylysine moiety (e.g., a a- polylysine moiety), wherein each nl is an integer independently selected from 2 to 10 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10). In some embodiments, nl is selected from 2, 3, 4, 5, 6, 7, or 8. In some embodiments, nl is selected from 3, 4, 5, 6, or 7. In some embodiments, nl is selected from 4, 5, or 6. In some embodiments, all values of nl in a polylysine dendrimer or dendrigraft are identical (e.g., all nl are equal to 5).

[0061] As used herein, the “average degree of polymerization” or (“DPn”) means the average number of lysine monomers per dendrimer molecule. The average degree of polymerization (DPn) of the polylysine dendrimer may be from 30 to 70, from 40 to 60, from 42 to 58, from 46 to 50, or any range or value therein between. In some embodiments, the DPn is about 48.

[0062] In some embodiments, the mass average molar weight (Mw) of the polylysine dendrimer is from 1000 g / mol to 20000 g / mol, from 2000 g / mol to 18000 g / mol, from 5000 g / mol to 15000 g / mol, from 6000 g / mol to 10000 g / mol from 8000 g / mol to 10000 g / mol, from 8400 g / mol to 8800 g / mol, or any range or value therein between. In some embodiments, the Mw of the polylysine dendrimer is about 1000 g / mol, about 2000 g / mol, about 3000 g / mol, about 4000 g / mol, about 5000 g / mol, about 5500 g / mol, about 6000 g / mol, about 6500 g / mol, about 7000 g / mol, about 7200 g / mol, about 7400 g / mol, about 7600 g / mol,about 7800 g / mol, about 8000 g / mol, about 8200 g / mol, about 8400 g / mol, about 8600 g / mol, about 8800 g / mol, about 9000 g / mol, about 9200 g / mol, about 9400 g / mol, about 9600 g / mol, about 9800 g / mol, about 10000 g / mol, about 10500 g / mol, about 11000 g / mol, about 11500 g / mol, about 12000 g / mol, about 12500 g / mol, about 13000 g / mol, about 13500 g / mol, about 14000 g / mol, about 15000 g / mol, or any range or value therein between.

[0063] The polylysine dendrimer is a polycationic polymer and include salts thereof. The polylysine dendrimer may include any suitable counter-ion, including but not limited to, bicarbonate, carbonate, dihydrogen phosphate, fluoride, chloride, bromide, iodide, citrate, trifluoroacetate (TFA), acetate, or any combination thereof. In some embodiments, the counter-ion is acetate.

[0064] In some embodiments, the polylysine dendrimer is unconjugated. As used herein the term “unconjugated” referring to a polylysine dendrimer means the polylysine dendrimer has not been covalently attached or associated with another material such as a pharmaceutically active ingredient or excipient. In some embodiments, the polylysine dendrimer may be conjugated (covalently attached or associated) with another material, such as a pharmaceutically active ingredient or excipient.

[0065] In some embodiments, the polylysine dendrimer is provided as a commercially- available product (e.g., DENDRICLEAR™) in which the polylysine is present in solution with water and / or glycerin. In some embodiments, the commercially-available product further comprises glycine.

[0066] The polylysine dendrimer is present in the anti-inflammatory compositions of the present disclosure at a concentration effective to achieve reduction inflammation (e.g., reduction in release of IL-8). In some embodiments, the polylysine dendrimer is present at a concentration, by weight relative to the total weight of the composition, of at least 0.0001 wt.%, at least 0.00015 wt.%, at least 0.0002 wt.%, at least 0.00025 wt.%, at least 0.0003 wt.%, at least 0.00035 wt.%, at least 0.0004 wt.%, at least 0.00045 wt.%, at least 0.0005 wt.%, at least 0.00055 wt.%, at least 0.0006 wt.%, at least 0.00065 wt.%, at least 0.0007 wt.%, at least 0.00075 wt.%, at least 0.0008 wt.%, at least 0.00085 wt.%, at least 0.0009 wt.%, at least 0.00095 wt.%, at least 0.001 wt.%, at least 0.002 wt.%, at least 0.003 wt.%, atleast 0.004 wt.%, at least 0.005 wt.%, at least 0.006 wt.%, at least 0.007 wt.%, at least 0.008 wt.%, at least 0.009 wt.%, at least 0.01 wt.%, at least 0.02 wt.%, at least 0.03 wt.%, at least 0.04 wt.%, at least 0.05 wt.%, at least 0.06 wt.%, at least 0.07 wt.%, at least 0.08 wt.%, at least 0.09 wt.%, at least 0.1 wt.%, at least 0.2 wt.%, at least 0.3 wt.%, at least 0.4 wt.%, at least 0.5 wt.%, at least 0.6 wt.%, at least 0.7 wt.%, at least 0.8 wt.%, at least 0.9 wt.%, at least1 wt.%, or any range or value therein between.

[0067] In some embodiments, the polylysine dendrimer is present at a concentration, by weight relative to the total weight of the composition, of no greater than 1 wt.%, no greater than 0.9 wt.%, no greater than 0.8 wt.%, no greater than 0.7 wt.%, no greater than 0.6 wt.%, no greater than 0.5 wt.%, no greater than 0.4 wt.%, no greater than 0.3 wt.%, no greater than 0.2 wt.%, no greater than 0.1 wt.%, no greater than 0.09 wt.%, no greater than 0.08 wt.%, no greater than 0.07 wt.%, no greater than 0.06 wt.%, no greater than 0.05 wt.%, no greater than 0.04 wt.%, no greater than 0.03 wt.%, no greater than 0.02 wt.%, no greater than 0.01 wt.%, no greater than 0.009 wt.%, no greater than 0.008 wt.%, no greater than 0.007 wt.%, no greater than 0.006 wt.%, no greater than 0.005 wt.%, no greater than 0.004 wt.%, no greater than 0.003 wt.%, no greater than 0.002 wt.%, no greater than 0.001 wt.%, no greater than 0.00095 wt.%, no greater than 0.00090 wt.%, no greater than 0.00085 wt.%, no greater than 0.0008 wt.%, no greater than 0.00075 wt.%, no greater than 0.007 wt.%, no greater than 0.00065 wt.%, no greater than 0.0006 wt.%, no greater than 0.00055 wt.%, no greater than 0.0005 wt.%, no greater than 0.00045 wt.%, no greater than 0.0004 wt.%, no greater than 0.00035 wt.%, no greater than 0.0003 wt.%, no greater than 0.00025 wt.%, no greater than 0.0002 wt.%, no greater than 0.00015 wt.%, no greater than 0.0001 wt.%, or any range or value therein between.

[0068] In some embodiments, the polylysine dendrimer is present at a concentration, by weight relative to the total weight of the composition, of about 0.0001 wt.%, about 0.00015, about 0.0002 wt.%, about 0.00025 wt.%, about 0.0003 wt.%, about 0.00035 wt.%, about 0.0004 wt.%, about 0.00045 wt.%, about 0.0005 wt.%, about 0.00055 wt.%, about 0.0006 wt.%, about 0.00065 wt.%, about 0.0007 wt.%, about 0.00075 wt.%, about 0.0008 wt.%, about 0.00085 wt.%, about 0.0009 wt.%, about 0.00095 wt.%, about 0.001 wt.%, about 0.0015 wt.%, about 0.002 wt.%, about 0.0025 wt.%, about 0.003 wt.%, about 0.0035 wt.%,about 0.004 wt.%, about 0.0045 wt.%, about 0.005 wt.%, about 0.0055 wt.%, about 0.006 wt.%, about 0.0065 wt.%, about 0.007 wt.%, about 0.0075 wt.%, about 0.008 wt.%, about 0.0085 wt.%, about 0.009 wt.%, about 0.0095 wt.%, about 0.01 wt.%, about 0.015 wt.%, about 0.02 wt.%, about 0.025 wt.%, about 0.03 wt.%, about 0.035 wt.%, about 0.04 wt.%, about 0.045 wt.%, about 0.05 wt.%, about 0.055 wt.%, about 0.06 wt.%, about 0.065 wt.%, about 0.07 wt.%, about 0.075 wt.%, about 0.08 wt.%, about 0.085 wt.%, about 0.09 wt.%, about 0.095 wt.%, about 0.1 wt.%, about 0.2 wt.%, about 0.3 wt.%, about 0.4 wt.%, about 0.5 wt.%, about 0.6 wt.%, about 0.7 wt.%, about 0.8 wt.%, about 0.9 wt.%, or about 1 wt.%, or any range or value therein between.

[0069] In some embodiments, the polylysine dendrimer is present at a concentration, by weight relative to the total weight of the composition, of about 0.0001 wt.% to about 5 wt.%, about 0.0001 wt.% to about 1 wt.%, about 0.0001 wt.% to about 0.5 wt.%, about 0.0001 wt.% to about 0.1 wt.%, about 0.0001 wt.% to about 0.05 wt.%, about 0.0001 wt.% to about 0.01 wt.%, about 0.0001 wt.% to about 0.005 wt.%, about 0.0001 wt.% to about 0.001 wt.%, or about 0.0001 wt.% to about 0.0005 wt.%, or any range or value therein between.

[0070] In any embodiment, the concentration by weight of any ingredient, expressed in wt.%, may be expressed in the equivalent concentration in parts per million (ppm). For instance, 1 wt.% is equal to 10,000 ppm, or 0.0001 wt.% is equal to 1 ppm. Thus, in some embodiments, the polylysine dendrimer is present at a concentration of about 0.1 ppm to about 100 ppm, about 0.1 ppm to about 50 ppm, about 0.1 ppm to about 20 ppm, about 0.1 ppm to about 10 ppm, about 0.1 ppm to about 5 ppm, about 0.1 ppm to about 2 ppm, about 0.1 ppm to about 1 ppm, about 0.1 ppm to about 0.5 ppm, about 0.5 ppm to about 100 ppm, about 0.5 ppm to about 50 ppm, about 0.5 ppm to about 20 ppm, about 0.5 ppm to about 10 ppm, about 0.5 ppm to about 9 ppm, about 0.5 ppm to about 8 ppm, about 0.5 ppm to about 7 ppm, about 0.5 ppm to about 6 ppm, about 0.5 ppm to about 5 ppm, about 0.5 ppm to about 4 ppm, about 0.5 ppm to about 3 ppm, about 0.5 ppm to about 2 ppm, about 0.5 ppm to about 1 ppm, about 1 ppm to about 100 ppm, about 1 ppm to about 50 ppm, about 1 ppm to about 20 ppm, about 1 ppm to about 10 ppm, about 1 ppm to about 9 ppm, about 1 ppm to about 8 ppm, about 1 ppm to about 7 ppm, about 1 ppm to about 6 ppm, about 1 ppm to about 5 ppm, or any range or value therein between.Niacinamide

[0071] In some embodiments, the anti-inflammatory topical compositions according to the present disclosure comprise niacinamide. The niacinamide may be present at any concentration suitable to achieve a conditioning effect or anti-inflammatory effect on the skin. The niacinamide may be present at any concentration effective to achieve a synergistic activity with the polylysine dendrimer (e.g., a reduction of inflammation, such as by reducing release of IL-8) when applied to the skin of a subject.

[0072] In some embodiments, the niacinamide may be present at a concentration by weight, relative to the total weight of the composition, of at least about 0.00001 wt.%, at least about 0.00002 wt.%, at least about 0.00003 wt.%, at least about 0.00004 wt.%, at least about 0.00005 wt.%, at least about 0.00006 wt.%, at least about 0.00007 wt.%, at least about 0.00008 wt.%, at least about 0.00009 wt.%, at least about 0.0001 wt.%, at least about 0.0002 wt.%, at least about 0.0003 wt.%, at least about 0.0004 wt.%, at least about 0.0005 wt.%, at least about 0.0006 wt.%, at least about 0.0007 wt.%, at least about 0.0008 wt.%, at least about 0.001 wt.%, at least about 0.002 wt.%, at least about 0.003 wt.%, at least about 0.004 wt.%, at least about 0.005 wt.%, at least about 0.006 wt.%, at least about 0.007 wt.%, at least about 0.008 wt.%, at least about 0.009 wt.%, at least about 0.01 wt.%, at least about 0.02 wt.%, at least about 0.03 wt.%, at least about 0.04 wt.%, at least about 0.05 wt.%, at least about 0.06 wt.%, at least about 0.07 wt.%, at least about 0.08 wt.%, at least about 0.09 wt.%, at least about 0.1 wt.%, at least about 0.2 wt.%, at least about 0.3 wt.%, at least about 0.4 wt.%, at least about 0.5 wt.%, at least about 0.6 wt.%, at least about 0.7 wt.%, at least about 0.8 wt.%, at least about 0.9 wt.%, at least about 1.0 wt.%, at least about 1.2 wt.%, at least about 1.5 wt.%, at least about 1.8 wt.%, at least about 2.0 wt.%, at least about 2.5 wt.%, at least about 3.0 wt.%, at least about 3.5 wt.%, at least about 4.0 wt.%, at least about 4.5 wt.%, at least about 5.0 wt.%, at least about 5.5 wt.%, at least about 6.0 wt.%, at least about 6.5 wt.%, at least about 7.0 wt.%, at least about 7.5 wt.%, at least about 8.0 wt.%, at least about 8.5 wt.%, at least about 9.0 wt.%, at least about 9.5 wt.%, at least about 10 wt.%, or any range or value therein between.

[0073] In some embodiments, the niacinamide may be present at a concentration by weight, relative to the total weight of the composition, of no greater than about 10.0 wt.%, no greater than about 9.5 wt.%, no greater than about 9.0 wt.%, no greater than about 8.5 wt.%, no greater than about 8.0 wt.%, no greater than about 7.5 wt.%, no greater than about 7.0 wt.%, no greater than about 6.5 wt.%, no greater than about 6.0 wt.%, no greater than about 5.5 wt.%, no greater than about 5.0 wt.%, no greater than about 4.5 wt.%, no greater than about 4.0 wt.%, no greater than about 3.5 wt.%, no greater than about 3.0 wt.%, no greater than about 2.5 wt.%, no greater than about 2.0 wt.%, no greater than about 1.5 wt.%, no greater than about 1.0 wt.%, no greater than about 0.9 wt.%, no greater than about 0.8 wt.%, no greater than about 0.7 wt.%, no greater than about 0.6 wt.%, no greater than about 0.5 wt.%, no greater than about 0.4 wt.%, no greater than about 0.3 wt.%, no greater than about 0.2 wt.%, no greater than about 0.1 wt.%, no greater than about 0.09 wt.%, no greater than about 0.08 wt.%, no greater than about 0.07 wt.%, no greater than about 0.06 wt.%, no greater than about 0.05 wt.%, no greater than about 0.04 wt.%, no greater than about 0.03 wt.%, no greater than about 0.02 wt.%, no greater than about 0.01 wt.%, no greater than about 0.009 wt.%, no greater than about 0.008 wt.%, no greater than about 0.007 wt.%, no greater than about 0.006 wt.%, no greater than about 0.005 wt.%, no greater than about 0.004 wt.%, no greater than about 0.003 wt.%, no greater than about 0.002 wt.%, no greater than about 0.001 wt.%, no greater than about 0.0009 wt.%, no greater than about 0.0008 wt.%, no greater than about 0.0007 wt.%, no greater than about 0.0006 wt.%, no greater than about 0.0005 wt.%, no greater than about 0.0004 wt.%, no greater than about 0.0003 wt.%, no greater than about 0.0002 wt.%, no greater than about 0.0001 wt.%, no greater than about 0.00009 wt.%, no greater than about 0.00008 wt.%, no greater than about 0.00007 wt.%, no greater than about 0.00006 wt.%, no greater than about 0.00005 wt.%, or any range or value therein between.

[0074] In some embodiments, the niacinamide may be present at a concentration by weight, relative to the total weight of the composition, of about 0.0001 wt.%, about 0.0002 wt.%, about 0.0005 wt.%, about 0.0008 wt.%, about 0.001 wt.%, about 0.002 wt.%, about 0.005 wt.%, about 0.008 wt.%, about 0.01 wt.%, about 0.02 wt.%, about 0.05 wt.%, about 0.08 wt.%, about 0.1 wt.%, about 0.2 wt.%, about 0.5 wt.%, about 0.8 wt.%, about 1.0 wt.%, about 1.2 wt.%, about 1.5 wt.%, about 1.8 wt.%, about 2.0 wt.%, about 2.2 wt.%, about 2.5 wt.%, about 2.8 wt.%, about 3.0 wt.%, about 3.2 wt.%, about 3.5 wt.%, about 3.8 wt.%, about 4.0wt.%, about 4.2 wt.%, about 4.5 wt.%, about 4.8 wt.%, about 5.0 wt.%, about 5.5 wt.%, about6.0 wt.%, about 6.5 wt.%, about 7.0 wt.%, about 7.5 wt.%, about 8.0 wt.%, about 8.5 wt.%, about 9.0 wt.%, about 9.5 wt.%, about 10.0 wt.%, or any range or value therein between.

[0075] In some embodiments, the niacinamide may be present at a concentration by weight, relative to the total weight of the composition, of about 0.0001 wt.% to about 10 wt.%, about 0.0001 wt.% to about 5 wt.%, about 0.0001 wt.% to about 4 wt.%, about 0.0001 wt.% to about 3 wt.%, about 0.0001 wt.% to about 2 wt.%, about 0.0001 wt.% to about 1 wt.%, about 0.0001 wt.% to about 0.5 wt.%, about 0.0001 wt.% to about 0.4 wt.%, about 0.0001 wt.% to about 0.3 wt.%, about 0.0001 wt.% to about 0.2 wt.%, about 0.0001 wt.% to about 0.1 wt.%, about 0.0001 wt.% to about 0.05 wt.%, about 0.0001 wt.% to about 0.04 wt.%, about 0.0001 wt.% to about 0.03 wt.%, about 0.0001 wt.% to about 0.02 wt.%, about 0.0001 wt.% to about 0.01 wt.%, about 0.0001 wt.% to about 0.005 wt.%, about 0.0001 wt.% to about 0.004 wt.%, about 0.0001 wt.% to about 0.003 wt.%, about 0.0001 wt.% to about 0.002 wt.%, about 0.0001 wt.% to about 0.001 wt.%, about 0.0001 wt.% to about 0.0005 wt.%, about 0.001 wt.% to about 10 wt.%, about 0.001 wt.% to about 5 wt.%, about 0.001 wt.% to about 4 wt.%, about 0.001 wt.% to about 3 wt.%, about 0.001 wt.% to about 2 wt.%, about 0.001 wt.% to about 1 wt.%, about 0.001 wt.% to about 0.5 wt.%, about 0.001 wt.% to about 0.4 wt.%, about 0.001 wt.% to about 0.3 wt.%, about 0.001 wt.% to about 0.2 wt.%, about 0.001 wt.% to about 0.1 wt.%, about 0.001 wt.% to about 0.05 wt.%, about 0.001 wt.% to about 0.04 wt.%, about 0.001 wt.% to about 0.03 wt.%, about 0.001 wt.% to about 0.02 wt.%, about 0.001 wt.% to about 0.01 wt.%, 0.01 wt.% to about 10 wt.%, about 0.01 wt.% to about 5 wt.%, about 0.01 wt.% to about 4 wt.%, about 0.01 wt.% to about 3 wt.%, about 0.01 wt.% to about 2 wt.%, about 0.01 wt.% to about 1 wt.%, about 0.01 wt.% to about 0.5 wt.%, about 0.01 wt.% to about 0.4 wt.%, about 0.01 wt.% to about 0.3 wt.%, about 0.01 wt.% to about 0.2 wt.%, about 0.01 wt.% to about 0.1 wt.%, about 0.5 wt.% to about 10.0 wt.%, about 0.5 wt.% to about 8 wt.%, about 0.5 wt.% to about 5 wt.%, about 0.5 to about 4 wt.%, about 0.5 wt.% to about 3 wt.%, about 0.5 wt.% to about 2 wt.%, about 0.5 to about 1 wt.%, about 1 wt.% to about 10 wt.%, about 1 wt.% to about 8 wt.%, about 1 wt.% to about 5 wt.%, about 1 wt.% to about 4 wt.%, about 1 wt.% to about 3 wt.%, about 1 wt.% to about 2 wt.%, about 3 wt.% to about 10 wt.%, about 3 wt.% to about 8 wt.%, about 3 wt.% to about 5 wt.%, about 5 wt.% to about 10 wt.%, about 5 wt.% to about 8 wt.%, or any range or value therein.

[0076] In some embodiments, the polylysine dendrimer and the niacinamide are present in amounts effective to exhibit synergistic reduction of inflammation when applied to the skin of a subject. As used herein, the term “synergy” or “synergistic” refers to an effect of two or more agents working in combination that is greater than the expected additive effect of said agents. For instance, if an observed effect for a first agent is greater after adding a second agent whose activity is null when administered alone, then the effect is synergistic, rather than additive.Plant Extracts

[0077] In some embodiments, the anti-inflammatory topical compositions according to the present disclosure comprise one or more plant extracts. The plant extracts may include, but are not limited to, aloe vera extract, edelweiss extract, scutaline, lycopene, rosemary extract (e.g., AquaRO X®), quercetin, Marigold extract (e.g., lutein), or any combination thereof. In some embodiments, the plant extracts are selected from: aloe vera extract, edelweiss extract, scutaline, and combinations thereof. In some embodiments, the plant extract is aloe vera extract. In some embodiments, the plant extract is edelweiss extract. In some embodiments, the plant extract is scutaline.

[0078] The one or more plant extracts may be present at any concentration, individually or collectively, suitable to achieve a conditioning effect or anti-inflammatory effect on the skin. The one or more plant extracts may be present at any concentration effective to achieve a synergistic activity with the polylysine dendrimer (e.g., a reduction of inflammation, such as by reducing release of IL-8) when applied to the skin of a subject.

[0079] In some embodiments, the one or more plant extracts may be present, individually or collectively, at a concentration by weight, relative to the total weight of the composition, of at least about 0.00001 wt.%, at least about 0.00002 wt.%, at least about 0.00003 wt.%, at least about 0.00004 wt.%, at least about 0.00005 wt.%, at least about 0.00006 wt.%, at least about 0.00007 wt.%, at least about 0.00008 wt.%, at least about 0.00009 wt.%, at least about 0.0001 wt.%, at least about 0.0002 wt.%, at least about 0.0003 wt.%, at least about 0.0004 wt.%, at least about 0.0005 wt.%, at least about 0.0006 wt.%, at least about 0.0007 wt.%, at least about 0.0008 wt.%, at least about 0.001 wt.%, at least about 0.002 wt.%, at least about 0.003wt.%, at least about 0.004 wt.%, at least about 0.005 wt.%, at least about 0.006 wt.%, at least about 0.007 wt.%, at least about 0.008 wt.%, at least about 0.009 wt.%, at least about 0.01 wt.%, at least about 0.02 wt.%, at least about 0.03 wt.%, at least about 0.04 wt.%, at least about 0.05 wt.%, at least about 0.06 wt.%, at least about 0.07 wt.%, at least about 0.08 wt.%, at least about 0.09 wt.%, at least about 0.1 wt.%, at least about 0.2 wt.%, at least about 0.3 wt.%, at least about 0.4 wt.%, at least about 0.5 wt.%, at least about 0.6 wt.%, at least about 0.7 wt.%, at least about 0.8 wt.%, at least about 0.9 wt.%, at least about 1.0 wt.%, at least about 1.2 wt.%, at least about 1.5 wt.%, at least about 1.8 wt.%, at least about 2.0 wt.%, at least about 2.5 wt.%, at least about 3.0 wt.%, at least about 3.5 wt.%, at least about 4.0 wt.%, at least about 4.5 wt.%, at least about 5.0 wt.%, at least about 5.5 wt.%, at least about 6.0 wt.%, at least about 6.5 wt.%, at least about 7.0 wt.%, at least about 7.5 wt.%, at least about 8.0 wt.%, at least about 8.5 wt.%, at least about 9.0 wt.%, at least about 9.5 wt.%, at least about 10 wt.%, or any range or value therein between.

[0080] In some embodiments, the one or more plant extracts may be present, individually or collectively, at a concentration by weight, relative to the total weight of the composition, of no greater than about 10.0 wt.%, no greater than about 9.5 wt.%, no greater than about 9.0 wt.%, no greater than about 8.5 wt.%, no greater than about 8.0 wt.%, no greater than about 7.5 wt.%, no greater than about 7.0 wt.%, no greater than about 6.5 wt.%, no greater than about 6.0 wt.%, no greater than about 5.5 wt.%, no greater than about 5.0 wt.%, no greater than about 4.5 wt.%, no greater than about 4.0 wt.%, no greater than about 3.5 wt.%, no greater than about 3.0 wt.%, no greater than about 2.5 wt.%, no greater than about 2.0 wt.%, no greater than about 1.5 wt.%, no greater than about 1.0 wt.%, no greater than about 0.9 wt.%, no greater than about 0.8 wt.%, no greater than about 0.7 wt.%, no greater than about 0.6 wt.%, no greater than about 0.5 wt.%, no greater than about 0.4 wt.%, no greater than about 0.3 wt.%, no greater than about 0.2 wt.%, no greater than about 0.1 wt.%, no greater than about 0.09 wt.%, no greater than about 0.08 wt.%, no greater than about 0.07 wt.%, no greater than about 0.06 wt.%, no greater than about 0.05 wt.%, no greater than about 0.04 wt.%, no greater than about 0.03 wt.%, no greater than about 0.02 wt.%, no greater than about 0.01 wt.%, no greater than about 0.009 wt.%, no greater than about 0.008 wt.%, no greater than about 0.007 wt.%, no greater than about 0.006 wt.%, no greater than about 0.005 wt.%, no greater than about 0.004 wt.%, no greater than about 0.003 wt.%, no greater thanabout 0.002 wt.%, no greater than about 0.001 wt.%, no greater than about 0.0009 wt.%, no greater than about 0.0008 wt.%, no greater than about 0.0007 wt.%, no greater than about 0.0006 wt.%, no greater than about 0.0005 wt.%, no greater than about 0.0004 wt.%, no greater than about 0.0003 wt.%, no greater than about 0.0002 wt.%, no greater than about 0.0001 wt.%, no greater than about 0.00009 wt.%, no greater than about 0.00008 wt.%, no greater than about 0.00007 wt.%, no greater than about 0.00006 wt.%, no greater than about 0.00005 wt.%, or any range or value therein between.

[0081] In some embodiments, the one or more plant extracts may be present, individually or collectively, at a concentration by weight, relative to the total weight of the composition, of about 0.00001 wt.%, about 0.00002 wt.%, about 0.00005 wt.%, about 0.00008 wt.%, about 0.0001 wt.%, about 0.0002 wt.%, about 0.0005 wt.%, about 0.0008 wt.%, about 0.001 wt.%, about 0.002 wt.%, about 0.005 wt.%, about 0.008 wt.%, about 0.01 wt.%, about 0.02 wt.%, about 0.05 wt.%, about 0.08 wt.%, about 0.1 wt.%, about 0.2 wt.%, about 0.5 wt.%, about 0.8 wt.%, about 1.0 wt.%, about 1.2 wt.%, about 1.5 wt.%, about 1.8 wt.%, about 2.0 wt.%, about 2.2 wt.%, about 2.5 wt.%, about 2.8 wt.%, about 3.0 wt.%, about 3.2 wt.%, about 3.5 wt.%, about 3.8 wt.%, about 4.0 wt.%, about 4.2 wt.%, about 4.5 wt.%, about 4.8 wt.%, about 5.0 wt.%, about 5.5 wt.%, about 6.0 wt.%, about 6.5 wt.%, about 7.0 wt.%, about 7.5 wt.%, about 8.0 wt.%, about 8.5 wt.%, about 9.0 wt.%, about 9.5 wt.%, about 10.0 wt.%, or any range or value therein between.

[0082] In some embodiments, the one or more plant extracts may be present, individually or collectively, at a concentration by weight, relative to the total weight of the composition, of about 0.00001 wt.% to about 10.0 wt.%, about 0.00001 wt.% to about 8 wt.%, about 0.00001 wt.% to about 5 wt.%, about 0.00001 to about 4 wt.%, about 0.00001 wt.% to about 3 wt.%, about 0.00001 wt.% to about 2 wt.%, about 0.00001 wt.% to about 1 wt.%, about 0.00001 wt.% to about 1 wt.%, about 0.5 wt.%, about 0.00001 wt.% to about 0.1 wt.%, about 0.00001 wt.% to about 0.05 wt.%, about 0.00001 wt.% to about 0.01 wt.%, about 0.00001 wt.% to about 0.005 wt.%, about 0.00001 wt.% to about 0.001 wt.%, about 0.00001 wt.% to about 0.0005 wt.%, about 0.00001 wt.% to about 0.0001 wt.%, about 0.0001 wt.% to about 1 wt.%, about 0.0001 wt.% to about 0.5 wt.%, about 0.0001 wt.% to about 0.1 wt.%, about 0.0001 wt.% to about 0.05 wt.%, about 0.0001 wt.% to about 0.01 wt.%, about 0.0001 wt.% to about0.005 wt.%, about 0.0001 wt.% to about 0.001 wt.%, about 0.001 wt.% to about 1 wt.%, about 0.001 wt.% to about 0.5 wt.%, about 0.001 wt.% to about 0.1 wt.%, about 0.001 wt.% to about 0.05 wt.%, about 0.001 wt.% to about 0.01 wt.%, about 0.01 wt.% to about 1 wt.%, about 0.01 wt.% to about 0.5 wt.%, about 0.01 wt.% to about 0.1 wt.%, or any range or value therein between.

[0083] In some embodiments, the polylysine dendrimer and the one or more plant extracts are present in amounts effective to exhibit synergistic reduction of inflammation when applied to the skin of a subject. As used herein, the term “synergy” or “synergistic” refers to an effect exhibited by the activity of two or more ingredients that is greater than the effect expected by adding the activity of the two or more ingredients (z.e., an additive effect).Antioxidants

[0084] UV irradiation induces oxidative stress, which is detrimental to cellular functions and can negatively affect cell survival. Antioxidants can alleviate these oxidative processes by acting against the formation or propagation of reactive oxygen species, which will improve cellular function and survival.

[0085] In some embodiments, anti-inflammatory topical compositions according to the present disclosure comprise one or more antioxidants. The one or more antioxidants may include any compound or compounds known to act as a preservative. In some embodiments, the one or more antioxidants comprise(s) tocopherol, tocopheryl acetate, hydroxyacetophenone, butylated hydroxyanisole (BHA), resveratrol, Oryza sativa (rice) bran water, Curcuma longa (turmeric) rhizome extract (e.g., in active solution with butylene glycol and / or water), caprylic / capric triglyceride, Laminaria ochroleuca extract, ginkgo biloba leaf extract (e.g., in active solution with water and / or glycerin), Ocimum sanctum (holy basil) leaf extract (e.g., in active solution with butylene glycol and / or water), Silybum marianum (milk thistle) fruit extract (e.g., in active solution with butylene glycol and / or water), ascorbyl palmitate, phloretin, Theobroma cacao (cocoa) seed extract (e.g., in active solution with water and / or butylene glycol), carnosine, Olea Europaea (olive) leaf extract (e.g., in active solution with water), grapefruit seed extract, Camellia sinensis (tea plant) leaf extract (e.g., in active solution with water, sodium benzoate, and / or sodium salicylate; or inactive solution with caprylic / capric triglyceride), Camellia Japonica flower extract (e.g., in active solution with propanediol and / or water), gluconolactone, Carthamus tinctorius (safflower) seed oil, lecithin (phosphatidylcholine), silybin (silibinin), maltodextrin, Rubus fruticosus (blackberry) leaf extract, acetyl zingerone, bakuchiol, Vitreoscilla ferment, squalene, or a combination thereof. In any embodiment, the one or more antioxidants may be provided in an active solution with a carrier (e.g., water, butylene glycol, glycerin, caprylic / capric triglyceride, etc.). In some embodiments, the one or more antioxidants comprise(s) tocopherol, tocopheryl acetate, or a combination thereof. In some embodiments, the one or more antioxidants comprise(s) tocopherol. In some embodiments, the one or more antioxidants comprise(s) tocopheryl acetate.

[0086] In some embodiments, the one or more antioxidants may be present, individually or collectively, at a concentration by weight, relative to the total weight of the composition, of at least about 0.00001 wt.%, at least about 0.00002 wt.%, at least about 0.00003 wt.%, at least about 0.00004 wt.%, at least about 0.00005 wt.%, at least about 0.00006 wt.%, at least about 0.00007 wt.%, at least about 0.00008 wt.%, at least about 0.00009 wt.%, at least about 0.0001 wt.%, at least about 0.0002 wt.%, at least about 0.0003 wt.%, at least about 0.0004 wt.%, at least about 0.0005 wt.%, at least about 0.0006 wt.%, at least about 0.0007 wt.%, at least about 0.0008 wt.%, at least about 0.001 wt.%, at least about 0.002 wt.%, at least about 0.003 wt.%, at least about 0.004 wt.%, at least about 0.005 wt.%, at least about 0.006 wt.%, at least about 0.007 wt.%, at least about 0.008 wt.%, at least about 0.009 wt.%, at least about 0.01 wt.%, at least about 0.02 wt.%, at least about 0.03 wt.%, at least about 0.04 wt.%, at least about 0.05 wt.%, at least about 0.06 wt.%, at least about 0.07 wt.%, at least about 0.08 wt.%, at least about 0.09 wt.%, at least about 0.1 wt.%, at least about 0.2 wt.%, at least about 0.3 wt.%, at least about 0.4 wt.%, at least about 0.5 wt.%, at least about 0.6 wt.%, at least about 0.7 wt.%, at least about 0.8 wt.%, at least about 0.9 wt.%, at least about 1.0 wt.%, at least about 1.2 wt.%, at least about 1.5 wt.%, at least about 1.8 wt.%, at least about 2.0 wt.%, at least about 2.5 wt.%, at least about 3.0 wt.%, at least about 3.5 wt.%, at least about 4.0 wt.%, at least about 4.5 wt.%, at least about 5.0 wt.%, at least about 5.5 wt.%, at least about 6.0 wt.%, at least about 6.5 wt.%, at least about 7.0 wt.%, at least about 7.5 wt.%, at least about 8.0 wt.%, at least about 8.5 wt.%, at least about 9.0 wt.%, at least about 9.5 wt.%, at least about 10 wt.%, or any range or value therein between.

[0087] In some embodiments, the one or more antioxidants may be present, individually or collectively, at a concentration by weight, relative to the total weight of the composition, of no greater than about 10.0 wt.%, no greater than about 9.5 wt.%, no greater than about 9.0 wt.%, no greater than about 8.5 wt.%, no greater than about 8.0 wt.%, no greater than about 7.5 wt.%, no greater than about 7.0 wt.%, no greater than about 6.5 wt.%, no greater than about 6.0 wt.%, no greater than about 5.5 wt.%, no greater than about 5.0 wt.%, no greater than about 4.5 wt.%, no greater than about 4.0 wt.%, no greater than about 3.5 wt.%, no greater than about 3.0 wt.%, no greater than about 2.5 wt.%, no greater than about 2.0 wt.%, no greater than about 1.5 wt.%, no greater than about 1.0 wt.%, no greater than about 0.9 wt.%, no greater than about 0.8 wt.%, no greater than about 0.7 wt.%, no greater than about 0.6 wt.%, no greater than about 0.5 wt.%, no greater than about 0.4 wt.%, no greater than about 0.3 wt.%, no greater than about 0.2 wt.%, no greater than about 0.1 wt.%, no greater than about 0.09 wt.%, no greater than about 0.08 wt.%, no greater than about 0.07 wt.%, no greater than about 0.06 wt.%, no greater than about 0.05 wt.%, no greater than about 0.04 wt.%, no greater than about 0.03 wt.%, no greater than about 0.02 wt.%, no greater than about 0.01 wt.%, no greater than about 0.009 wt.%, no greater than about 0.008 wt.%, no greater than about 0.007 wt.%, no greater than about 0.006 wt.%, no greater than about 0.005 wt.%, no greater than about 0.004 wt.%, no greater than about 0.003 wt.%, no greater than about 0.002 wt.%, no greater than about 0.001 wt.%, no greater than about 0.0009 wt.%, no greater than about 0.0008 wt.%, no greater than about 0.0007 wt.%, no greater than about 0.0006 wt.%, no greater than about 0.0005 wt.%, no greater than about 0.0004 wt.%, no greater than about 0.0003 wt.%, no greater than about 0.0002 wt.%, no greater than about 0.0001 wt.%, no greater than about 0.00009 wt.%, no greater than about 0.00008 wt.%, no greater than about 0.00007 wt.%, no greater than about 0.00006 wt.%, no greater than about 0.00005 wt.%, or any range or value therein between.

[0088] In some embodiments, the one or more antioxidants may be present, individually or collectively, at a concentration by weight, relative to the total weight of the composition, of about 0.00001 wt.%, about 0.00002 wt.%, about 0.00005 wt.%, about 0.00008 wt.%, about 0.0001 wt.%, about 0.0002 wt.%, about 0.0005 wt.%, about 0.0008 wt.%, about 0.001 wt.%, about 0.002 wt.%, about 0.005 wt.%, about 0.008 wt.%, about 0.01 wt.%, about 0.02 wt.%, about 0.05 wt.%, about 0.08 wt.%, about 0.1 wt.%, about 0.2 wt.%, about 0.5 wt.%, about 0.8wt.%, about 1.0 wt.%, about 1.2 wt.%, about 1.5 wt.%, about 1.8 wt.%, about 2.0 wt.%, about 2.2 wt.%, about 2.5 wt.%, about 2.8 wt.%, about 3.0 wt.%, about 3.2 wt.%, about 3.5 wt.%, about 3.8 wt.%, about 4.0 wt.%, about 4.2 wt.%, about 4.5 wt.%, about 4.8 wt.%, about 5.0 wt.%, about 5.5 wt.%, about 6.0 wt.%, about 6.5 wt.%, about 7.0 wt.%, about 7.5 wt.%, about 8.0 wt.%, about 8.5 wt.%, about 9.0 wt.%, about 9.5 wt.%, about 10.0 wt.%, or any range or value therein between.

[0089] In some embodiments, the one or more antioxidants is present in the composition, individually or collectively, at a concentration by weight, relative to the total weight of the composition, of 0.00001 wt.% to about 10 wt.%, about 0.0001 wt.% to about 10 wt.%, about 0.001 wt.% to about 10 wt.%, about 0.01 wt.% to about 10 wt.%, about 0.1 wt.% to about 10 wt.%, about 1 wt.% to about 10 wt.%, about 0.00001 wt.% to about 1 wt.%, about 0.0001 wt.% to about 1 wt.%, about 0.001 wt.% to about 1 wt.%, about 0.01 wt.% to about 1 wt.%, about 0.1 wt.% to about 1 wt.%, about 0.00001 wt.% to about 0.1 wt.%, about 0.0001 wt.% to about 0.1 wt.%, about 0.001 wt.% to about 0.1 wt.%, about 0.01 wt.% to about 0.1 wt.%, about 0.01 wt.% to about 10 wt. %, about 0.01 wt.% to about 1 wt.%, about 0.01 wt.% to about 0.1 wt.%, about 0.1 wt.% to about 10 wt.%, about 0.1 wt.% to about 1 wt.%, or any range or value therein between, such as about 0.00002 wt.% to about 10 wt.%, about 0.00002 wt.% to about 5.4 wt.%, about 0.0002 wt.% to about 1 wt.%, about 0.00005 wt.% to about 5 wt.%, or any other range or value therein.Gelling Agents

[0090] In some embodiments, an anti-inflammatory topical composition according to the present disclosure comprises one or more gelling agents (also known as suspending agents or thickening agents). By way of non-limiting example, the one or more gelling agents may comprise ready -for-use mixtures e.g., Polyacrylate- 13 / Polyisobutene / Polysorbate 20 sold by Seppic under the name SEPIPLUS 400®, or the Ammonium Acrylate / Acrylamide Copolymer / Polyisobutene / Polysorbate 20 mixture sold by Seppic under the name SEPIPLUS 265®, or Aery 1 ami de / S odium Acryloyldimethyl Taurate Copolymer / Isohexadecane / Polysorbate 80 sold by Seppic under the name SIMULGEL™ 600); acrylic acid polymers (e.g., Acrylates / C10-30 Alkyl Acrylate Crosspolymer);carbomers (e.g, ULTREZ 20®, ULTREZ 10®, CARBOPOL 1382®, CARBOPOL ETD2020NF® or AQUA SF1® sold by Lubrizol); polysaccharides (e.g, xanthan gum (such as XANTURAL 180® sold by Kelco), gellan gum (e.g., KELCOGEL® by Kelco), sclerotium gum (e.g, AMIGEL® by Alban Muller Industrie), guar gum and its derivatives (such as hydroxypropyl guar gum sold under the name JAGUAR HP- 105® by Rhodia), cationic guar gums, pullulan, cellulose and cellulose derivatives (such as microcrystalline cellulose and sodium carboxymethyl cellulose, e.g, sold under the name BLANOSE CMC 7H4XF® by Hercules, hydroxypropylmethyl cellulose, e.g., sold under the name of METHOCEL E4M® Premium by Dow Chemical, hydroxy ethyl cellulose, e.g., sold under the name of NATROSOL HHX 250® by Aquaion, methyl cellulose, carboxymethyl cellulose); magnesium aluminum silicates (e.g., VEEGUM K®, VEEGUM Plus®, or VEEGUM Ultra® sold by Vanderbilt); bentonite; modified starches (e.g., modified potato starch sold under the name of STRUCTURE SOLANACE®); carrageenans (e.g., the K, X, P and co families, such as the VISCARIN® and GELCARIN® products sold by IMCD); polyvinyl alcohols (PVAs) (e.g., Polyvinyl Alcohol 40-88® sold by Merck); polyvinylpyrrolidones; carboxyvinyl polymers; acrylic acid / ethyl acrylate copolymers (e.g., CARBOPOLS®); polyacrylic acid polymers; polymethyacrylic acid polymers; polyvinyl acetate polymers, polyvinylchloride polymers; polyvinylidene chloride polymers; mixtures of polyethylene glycol and polyethylene glycol stearate or distearate; oleogels (e.g., trihydroxystearin or aluminim magnesium hydroxy stearate); non-ionic polymers; and any combination of the above.

[0091] In some embodiments, the one or more gelling agents may be present at a concentration, individually or collectively, relative to the total weight of the composition, of at least about 0.1 wt.%, at least about 0.2 wt.%, at least about 0.3 wt.%, at least about 0.4 wt.%, at least about 0.5 wt.%, at least about 0.6 wt.%, at least about 0.7 wt.%, at least about 0.8 wt.%, at least about 0.9 wt.%, at least about 1.0 wt.%, at least about 1.2 wt.%, at least about 1.5 wt.%, at least about 1.8 wt.%, at least about 2.0 wt.%, at least about 2.2 wt.%, at least about 2.5 wt.%, at least about 2.8 wt.%, at least about 3.0 wt.%, at least about 3.2 wt.%, at least about 3.5 wt.%, at least about 3.8 wt.%, at least about 4.0 wt.%, at least about 4.2 wt.%, at least about 4.5 wt.%, at least about 4.8 wt.%, at least about 5.0 wt.%, at least about5.5 wt.%, at least about 6.0 wt.%, at least about 6.5 wt.%, at least about 7.0 wt.%, at least about 7.5 wt.%, at least about 8.0 wt.%, at least about 8.5 wt.%, at least about 9.0 wt.%, at least about 9.5 wt.%, at least about 10.0 wt.%, or any range or value therein between.

[0092] In some embodiments, the one or more gelling agents may be present at a concentration, individually or collectively, relative to the total weight of the composition, of no greater than about 10.0 wt.%, no greater than about 9.5 wt.%, no greater than about 9.0 wt.%, no greater than about 8.5 wt.%, no greater than about 8.0 wt.%, no greater than about7.5 wt.%, no greater than about 7.0 wt.%, no greater than about 6.5 wt.%, no greater than about 6.0 wt.%, no greater than about 5.5 wt.%, no greater than about 5.0 wt.%, no greater than about 4.5 wt.%, no greater than about 4.0 wt.%, no greater than about 3.5 wt.%, no greater than about 3.0 wt.%, or any range or value therein between.

[0093] In some embodiments, the one or more gelling agents may be present at a concentration, individually or collectively, relative to the total weight of the composition, of about 0.1 wt.%, about 0.2 wt.%, about 0.3 wt.%, about 0.4 wt.%, about 0.5 wt.%, about 0.6 wt.%, about 0.7 wt.%, about 0.8 wt.%, about 0.9 wt.%, about 1.0 wt.%, about 1.2 wt.%, about1.5 wt.%, about 1.8 wt.%, about 2.0 wt.%, about 2.2 wt.%, about 2.5 wt.%, about 2.8 wt.%, about 3.0 wt.%, about 3.2 wt.%, about 3.5 wt.%, about 3.8 wt.%, about 4.0 wt.%, about 4.2 wt.%, about 4.5 wt.%, about 4.8 wt.%, about 5.0 wt.%, about 5.5 wt.%, about 6.0 wt.%, about6.5 wt.%, about 7.0 wt.%, about 7.5 wt.%, about 8.0 wt.%, about 8.5 wt.%, about 9.0 wt.%, about 9.5 wt.%, about 10.0 wt.%, or any range or value therein.

[0094] In some embodiments, the one or more gelling agents may be present at a concentration, individually or collectively, relative to the total weight of the composition, of about 0.1 wt.% to about 10 wt.%, about 0.1 wt.% to about 5 wt.%, about 0.1 wt.% to about 4 wt.%, about 0.1 wt.% to about 3 wt.%, about 0.1 wt.% to about 2 wt.%, about 0.1 wt.% to about 1 wt.%, 0.1 wt.% to about 0.5 wt.%, about 0.5 wt.% to about 10 wt.%, about 0.5 wt.% to about 5 wt.%, about 0.5 wt.% to about 4 wt.%, about 0.5 wt.% to about 3 wt.%, about 0.5 wt.% to about 2 wt.%, about 0.5 wt.% to about 1 wt.%, about 1 wt.% to about 10 wt.%, about 1 wt.% to about 5 wt.%, about 1 wt.% to about 4 wt.%, about 1 wt.% to about 3 wt.%, about 1 wt.% to about 2 wt.%, about 2 wt.% to about 10 wt.%, about 2 wt.% to about 5 wt.%, about3 wt.% to about 10 wt.%, about 3 wt.% to about 5 wt.%, about 5 wt.% to about 10 wt.%, or any range or value therein.Humectants and / or Emollients

[0095] In some embodiments, an anti-inflammatory topical composition according to the present disclosure comprises one or more humectants and / or emollients. By way of nonlimiting example, in some embodiments, the one or more humectants and / or emollients may comprise polyols, such as polyols having from 2 to 20 carbon atoms, including glycerol (glycerin); glycol derivatives (e.g., propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, dipropylene glycol, diethylene glycol, caprylyl glycol); and mixtures thereof. In some embodiments, the humectants and / or emollients may comprise glycerin sorbitol; sugars (e.g., glucose, lactose, etc.); alkoxylated glucose derivatives; glucose ethers; panthenols (e.g., D-panthenol, DL-panthenol); polyethylene glycols (PEGs); urea; sodium hyaluronate; caprylyl glycol; pantolactone; caprylic / capric triglyceride; coco- caprylate / caprate; pantolactone; squalane; soluble chitosan; hexanetriol; amino acids (e.g., serine, citrulline, arginine, asparagine or alanine); alpha-hydroxy acids; salicylic acid; or combinations thereof.

[0096] In some embodiments, the one or more humectants and / or emollients may be present at a concentration, individually or collectively, relative to the total weight of the composition, of at least about 0.1 wt.%, at least about 0.2 wt.%, at least about 0.3 wt.%, at least about 0.4 wt.%, at least about 0.5 wt.%, at least about 0.6 wt.%, at least about 0.7 wt.%, at least about 0.8 wt.%, at least about 0.9 wt.%, at least about 1.0 wt.%, at least about 1.2 wt.%, at least about 1.5 wt.%, at least about 1.8 wt.%, at least about 2.0 wt.%, at least about 2.5 wt.%, at least about 3.0 wt.%, at least about 3.5 wt.%, at least about 4.0 wt.%, at least about 4.5 wt.%, at least about 5.0 wt.%, at least about 5.5 wt.%, at least about 6.0 wt.%, at least about 6.5 wt.%, at least about 7.0 wt.%, at least about 7.5 wt.%, at least about 8.0 wt.%, at least about 8.5 wt.%, at least about 9.0 wt.%, at least about 9.5 wt.%, at least about 10 wt.%, or any range or value therein between.

[0097] In some embodiments, the one or more humectants and / or emollients may be present at a concentration, individually or collectively, relative to the total weight of the composition,of no greater than about 10.0 wt.%, no greater than about 9.5 wt.%, no greater than about 9.0 wt.%, no greater than about 8.5 wt.%, no greater than about 8.0 wt.%, no greater than about 7.5 wt.%, no greater than about 7.0 wt.%, no greater than about 6.5 wt.%, no greater than about 6.0 wt.%, no greater than about 5.5 wt.%, no greater than about 5.0 wt.%, no greater than about 4.5 wt.%, no greater than about 4.0 wt.%, no greater than about 3.5 wt.%, no greater than about 3.0 wt.%, or any range or value therein between.

[0098] In some embodiments, the one or more humectants and / or emollients may be present at a concentration, individually or collectively, relative to the total weight of the composition, of about 0.1 wt.%, about 0.2 wt.%, about 0.5 wt.%, about 0.8 wt.%, about 1.0 wt.%, about 1.2 wt.%, about 1.5 wt.%, about 1.8 wt.%, about 2.0 wt.%, about 2.2 wt.%, about 2.5 wt.%, about 2.8 wt.%, about 3.0 wt.%, about 3.2 wt.%, about 3.5 wt.%, about 3.8 wt.%, about 4.0 wt.%, about 4.2 wt.%, about 4.5 wt.%, about 4.8 wt.%, about 5.0 wt.%, about 5.5 wt.%, about 6.0 wt.%, about 6.5 wt.%, about 7.0 wt.%, about 7.5 wt.%, about 8.0 wt.%, about 8.5 wt.%, about 9.0 wt.%, about 9.5 wt.%, about 10.0 wt.%, or any range or value therein between.

[0099] In some embodiments, the one or more humectants and / or emollients may be present at a concentration, individually or collectively, relative to the total weight of the composition, of about 0.1 wt.% to about 10.0 wt.%, about 0.1 wt.% to about 8 wt.%, about 0.1 wt.% to about 5 wt.%, about 0.1 to about 4 wt.%, about 0.1 wt.% to about 3 wt.%, about 0.1 wt.% to about 2 wt.%, about 0.1 to about 1 wt.%, about 0.1 wt.% to about 5 wt.%, about 0.1 wt.% to about 10 wt.%, about 0.5 wt.% to about 10.0 wt.%, about 0.5 wt.% to about 8 wt.%, about 0.5 wt.% to about 5 wt.%, about 0.5 to about 4 wt.%, about 0.5 wt.% to about 3 wt.%, about 0.5 wt.% to about 2 wt.%, about 0.5 to about 1 wt.%, about 0.5 wt.% to about 5 wt.%, about 0.5 wt.% to about 10 wt.%, about 1 wt.% to about 10 wt.%, about 1 wt.% to about 8 wt.%, about 1 wt.% to about 5 wt.%, about 1 wt.% to about 4 wt.%, about 1 wt.% to about 3 wt.%, about 1 wt.% to about 2 wt.%, about 3 wt.% to about 10 wt.%, about 3 wt.% to about 8 wt.%, about 3 wt.% to about 5 wt.%, about 5 wt.% to about 10 wt.%, about 5 wt.% to about 8 wt.%, or any range or value therein.Oils

[0100] In some embodiments, an anti-inflammatory topical composition according to the present disclosure comprises one or more oils. In some embodiments (e.g., when the composition is in the form of an emulsion such as an oil-in-water or water-in-oil emulsion), the composition comprises an oily phase comprising one or more oils. By way of nonlimiting example, the one or more oils may comprise vegetable oils, mineral oils, animal oils, or synthetic waxes, oils or butters, and mixtures thereof. In some embodiments, the oils may comprise: one or more mineral oils (e.g., PRIMOL 352®, MARCOL 82®, and MARCOL 152® sold by Esso); one or more vegetable oils (e.g., almond oil, sweet almond oil, palm oil, soybean oil, sesame oil, sunflower oil, olive oil, etc.); one or more animal oils or substitutes of vegetable origin (e.g., lanolin, squalene or fish oil and derivatives thereof, such as perhydrosqualene, e.g., sold as SOPHIDERM® by Sophim); one or more synthetic oils (e.g., cetearyl isononanoate, such as CETIOL SN PH® by Cognis France, isononyl isononanoate, such as DUB ININ® sold by Stearinerie Dubois, diisopropyl adipate, such as CRODAMOL DA® by Croda, isopropyl palmitate, such as CRODAMOL IPP® by Croda, caprylic / capric triglyceride, such as MIGLYOL 812® sold by Univar, hydrogenated polyisobutene, such as PARLEAM ® products by Rossow); one or more silicone oils (e.g., dimethicone, such as Q7- 9120 Silicone Fluid®, with a viscosity of 20 cSt to 12 500 cSt, by Dow Coming, cyclomethicone, such as ST-Cyclomethicone 5NF®, by Dow Corning, or DC 9045 Elastomer Blend®, by Dow Corning); or any combination thereof. In any embodiment, the exemplary oils of the present disclosure may be considered emollients.

[0101] In some embodiments, the one or more oils be present at a concentration, individually or collectively, relative to the total weight of the composition, of at least about 0.5 wt.%, at least about 0.6 wt.%, at least about 0.7 wt.%, at least about 0.8 wt.%, at least about 0.9 wt.%, at least about 1.0 wt.%, at least about 1.2 wt.%, at least about 1.5 wt.%, at least about 1.8 wt.%, at least about 2.0 wt.%, at least about 2.5 wt.%, at least about 3.0 wt.%, at least about 3.5 wt.%, at least about 4.0 wt.%, at least about 4.5 wt.%, at least about 5.0 wt.%, at least about 5.5 wt.%, at least about 6.0 wt.%, at least about 6.5 wt.%, at least about 7.0 wt.%, at least about 7.5 wt.%, at least about 8.0 wt.%, at least about 8.5 wt.%, at least about 9.0 wt.%,at least about 9.5 wt.%, at least about 10 wt.%, at least about 15 wt.%, and up to or including about 20%, or any range or value therein between.

[0102] In some embodiments, the one or more oils may be present at a concentration, individually or collectively, relative to the total weight of the composition, of no greater than about 10.0 wt.%, no greater than about 9.5 wt.%, no greater than about 9.0 wt.%, no greater than about 8.5 wt.%, no greater than about 8.0 wt.%, no greater than about 7.5 wt.%, no greater than about 7.0 wt.%, no greater than about 6.5 wt.%, no greater than about 6.0 wt.%, no greater than about 5.5 wt.%, no greater than about 5.0 wt.%, no greater than about 4.5 wt.%, no greater than about 4.0 wt.%, no greater than about 3.5 wt.%, no greater than about 3.0 wt.%, or any range or value therein between.

[0103] In some embodiments, the one or more oils may be present at a concentration, individually or collectively, relative to the total weight of the composition, of about 0.5 wt.%, about 0.8 wt.%, about 1.0 wt.%, about 1.2 wt.%, about 1.5 wt.%, about 1.8 wt.%, about 2.0 wt.%, about 2.2 wt.%, about 2.5 wt.%, about 2.8 wt.%, about 3.0 wt.%, about 3.2 wt.%, about 3.5 wt.%, about 3.8 wt.%, about 4.0 wt.%, about 4.2 wt.%, about 4.5 wt.%, about 4.8 wt.%, about 5.0 wt.%, about 5.5 wt.%, about 6.0 wt.%, about 6.5 wt.%, about 7.0 wt.%, about 7.5 wt.%, about 8.0 wt.%, about 8.5 wt.%, about 9.0 wt.%, about 9.5 wt.%, about 10.0 wt.%, or any range or value therein between.

[0104] In some embodiments, the one or more oils may be present at a concentration, individually or collectively, relative to the total weight of the composition, of about 0.5 wt.% to about 10.0 wt.%, about 0.5 wt.% to about 8 wt.%, about 0.5 wt.% to about 5 wt.%, about 0.5 wt.% to about 4 wt.%, about 0.5 wt.% to about 3 wt.%, about 0.5 wt.% to about 2 wt.%, about 0.5 to about 1 wt.%, about 1 wt.% to about 10 wt.%, about 1 wt.% to about 8 wt.%, about 1 wt.% to about 5 wt.%, about 1 wt.% to about 4 wt.%, about 1 wt.% to about 3 wt.%, about 1 wt.% to about 2 wt.%, about 3 wt.% to about 10 wt.%, about 3 wt.% to about 8 wt.%, about 3 wt.% to about 5 wt.%, about 5 wt.% to about 10 wt.%, about 5 wt.% to about 8 wt.%, or any range or value therein.Sebum-Regulating Agents

[0105] In some embodiments, an anti-inflammatory topical composition according to the present disclosure comprises one or more sebum-regulating agents. In some embodiments, the one or more sebum-regulating agents comprises zinc gluconate, isopropylcarbonate benzoyl peroxide, clascoterone, isotretinoin, salicylic acid, sulfur, one or more clays (e.g., kaolin, bentonite, hectorite, perlite, ghassoul (rhassoul), etc.), silica, Enantia chlorantha bark extract, one or more starches, or a combination thereof. In some embodiments, the sebumregulating agent is zinc gluconate.

[0106] In some embodiments, the one or more sebum-regulating agents may be present at a concentration, individually or collectively, relative to the total weight of the composition, of at least about 0.1 wt.%, at least about 0.2 wt.%, at least about 0.3 wt.%, at least about 0.4 wt.%, at least about 0.5 wt.%, at least about 0.6 wt.%, at least about 0.7 wt.%, at least about 0.8 wt.%, at least about 0.9 wt.%, at least about 1.0 wt.%, at least about 1.2 wt.%, at least about 1.5 wt.%, at least about 1.8 wt.%, at least about 2.0 wt.%, at least about 2.2 wt.%, at least about 2.5 wt.%, at least about 2.8 wt.%, at least about 3.0 wt.%, at least about 3.2 wt.%, at least about 3.5 wt.%, at least about 3.8 wt.%, at least about 4.0 wt.%, at least about 4.2 wt.%, at least about 4.5 wt.%, at least about 4.8 wt.%, at least about 5.0 wt.%, at least about 5.5 wt.%, at least about 6.0 wt.%, at least about 6.5 wt.%, at least about 7.0 wt.%, at least about 7.5 wt.%, at least about 8.0 wt.%, at least about 8.5 wt.%, at least about 9.0 wt.%, at least about 9.5 wt.%, at least about 10.0 wt.%, or any range or value therein between.

[0107] In some embodiments, the one or more sebum-regulating agents may be present at a concentration, individually or collectively, relative to the total weight of the composition, of no greater than about 10.0 wt.%, no greater than about 9.5 wt.%, no greater than about 9.0 wt.%, no greater than about 8.5 wt.%, no greater than about 8.0 wt.%, no greater than about 7.5 wt.%, no greater than about 7.0 wt.%, no greater than about 6.5 wt.%, no greater than about 6.0 wt.%, no greater than about 5.5 wt.%, no greater than about 5.0 wt.%, no greater than about 4.5 wt.%, no greater than about 4.0 wt.%, no greater than about 3.5 wt.%, no greater than about 3.0 wt.%, or any range or value therein between.

[0108] In some embodiments, the one or more sebum-regulating agents may be present at a concentration, individually or collectively, relative to the total weight of the composition, of about 0.1 wt.%, about 0.2 wt.%, about 0.3 wt.%, about 0.4 wt.%, about 0.5 wt.%, about 0.6 wt.%, about 0.7 wt.%, about 0.8 wt.%, about 0.9 wt.%, about 1.0 wt.%, about 1.2 wt.%, about1.5 wt.%, about 1.8 wt.%, about 2.0 wt.%, about 2.2 wt.%, about 2.5 wt.%, about 2.8 wt.%, about 3.0 wt.%, about 3.2 wt.%, about 3.5 wt.%, about 3.8 wt.%, about 4.0 wt.%, about 4.2 wt.%, about 4.5 wt.%, about 4.8 wt.%, about 5.0 wt.%, about 5.5 wt.%, about 6.0 wt.%, about6.5 wt.%, about 7.0 wt.%, about 7.5 wt.%, about 8.0 wt.%, about 8.5 wt.%, about 9.0 wt.%, about 9.5 wt.%, about 10.0 wt.%, or any range or value therein.

[0109] In some embodiments, the one or more sebum-regulating agents may be present at a concentration, individually or collectively, relative to the total weight of the composition, of about 0.1 wt.% to about 10 wt.%, about 0.1 wt.% to about 5 wt.%, about 0.1 wt.% to about 4 wt.%, about 0.1 wt.% to about 3 wt.%, about 0.1 wt.% to about 2 wt.%, about 0.1 wt.% to about 1 wt.%, 0.1 wt.% to about 0.5 wt.%, about 0.5 wt.% to about 10 wt.%, about 0.5 wt.% to about 5 wt.%, about 0.5 wt.% to about 4 wt.%, about 0.5 wt.% to about 3 wt.%, about 0.5 wt.% to about 2 wt.%, about 0.5 wt.% to about 1 wt.%, about 1 wt.% to about 10 wt.%, about 1 wt.% to about 5 wt.%, about 1 wt.% to about 4 wt.%, about 1 wt.% to about 3 wt.%, about 1 wt.% to about 2 wt.%, about 2 wt.% to about 10 wt.%, about 2 wt.% to about 5 wt.%, about 3 wt.% to about 10 wt.%, about 3 wt.% to about 5 wt.%, about 5 wt.% to about 10 wt.%, or any range or value therein.Water

[0110] The anti-inflammatory topical composition according to the present disclosure may comprise water at a concentration by weight, relative to the total weight of the composition, of about 0 wt.% to about 98 wt.%, about 5 wt.% to about 95 wt.%, about 10 wt.% to about 90 wt.%, or about 15 wt.% to about 85 wt.%. In some embodiments, the water is present at a concentration by weight, relative to the total weight of the composition, of about 0 wt.%, about 1 wt.%, about 2 wt.%, about 3 wt.%, about 4 wt.%, about 5 wt.%, about 6 wt.%, about 7 wt.%, about 8 wt.%, about 9 wt.%, about 10 wt.%, about 12 wt.%, about 15 wt.%, about 18 wt.%, about 20 wt.%, about 22 wt.%, about 25 wt.%, about 30 wt.%, about 35 wt.%, about 40wt.%, about 45 wt.%, about 50 wt.%, about 55 wt.%, about 60 wt.%, about 65 wt.%, about 70 wt.%, about 75 wt.%, about 80 wt.%, about 81 wt.%, about 82 wt.%, about 83 wt.%, about 84 wt.%, about 85 wt.%, about 86 wt.%, about 87 wt.%, about 88 wt.%, about 89 wt.%, about 90 wt.%, about 91 wt.%, about 92 wt.%, about 93 wt.%, about 94 wt.%, about 95 wt.%, about 96 wt.%, about 97 wt.%, about 98 wt.%, about 99 wt.%, or any range or value therein between.Other Additives[OHl] The anti-inflammatory topical compositions according to the present disclosure may comprise a broad range of optional ingredients or additives. The CTFA International Cosmetic Ingredient Dictionary, Fifteenth Edition, 2014, which is incorporated by reference herein in its entirety, describes a wide variety of non-limiting cosmetic and pharmaceutical ingredients commonly used in the skin care industry, which are suitable for use in the antiinflammatory topical compositions of the present disclosure. Non-limiting examples of genera of such ingredients include: abrasives, anti-acne agents, anticaking agents (e.g., silica, distarch phosphate, etc.), binders, biological additives, bulking agents, chelating agents (e.g., disodium EDTA), chemical additives; colorants; cosmetic astringents, cosmetic biocides, denaturants, drug astringents, emulsifiers, external analgesics, film formers, fragrance components, opacifying agents, plasticizers, preservatives, propellants, reducing agents, skin bleaching agents, skin-conditioning agents, skin protectants, solvents (e.g., ethanol, 1,2- hexanediol, etc.), foam boosters, hydrotropes, solubilizing agents, suspending agents (nonsurfactant), sunscreen agents, ultraviolet light absorbers, and viscosity increasing agents (aqueous and nonaqueous), solubilizing agents, sequestrants, and keratolytics, and any combination thereof.Composition Forms

[0112] An anti-inflammatory topical composition according to the present disclosure may be in any galenical form that ensures the composition is stable, non-irritating to the skin, nondrying to the skin, and / or pleasant and easy to apply. In some embodiments, the antiinflammatory topical composition may be an emulsion (e.g., oil-in water emulsion or water- in-oil emulsion), a gel, a cream, a cream-gel, a solution, suspension, lotion, milk, ointment, salve, foam (e.g., aerosol or self-foaming composition), balm, paste, or sachet. In someembodiments, the anti-inflammatory topical composition is an emulsion. In some embodiments, the anti-inflammatory topical composition is a gel. In some embodiments, the anti-inflammatory topical composition is a cream. In some embodiments, the antiinflammatory topical composition is a galenical form suitable for a pump dispenser. In some embodiments, the anti-inflammatory composition is formulated for leave-on (as opposed to “rinse-off ’) application.Composition pH

[0113] An anti-inflammatory topical composition according to the present disclosure may have any suitable pH for ensuring chemical and physical stability of the composition and any active ingredients contained therein, non-irritation to the skin, and prevention of dry skin. In some embodiments, an anti-inflammatory topical composition according to the present disclosure has a pH of between about 3.0 and about 9.0, between about 3.0 and about 8.5, between about 3.0 and about 8.0, between about 3.0 and about 7.5, between about 3.0 and about 7.0, between about 3.0 and about 6.5, between about 3.0 and about 6.0, between about 3.5 and about 9.0, between about 3.5 and about 8.5, between about 3.5 and about 8.0, between about 3.5 and about 7.5, between about 3.5 and about 7.0, between about 3.5 and about 6.5, between about 4.0 and about 9.0, between about 4.0 and about 8.5, between about 4.0 and about 8.0, between about 4.0 and about 7.5, between about 4.0 and about 7.0, between about 4.5 and about 9.0, between about 4.5 and about 8.5, between about 4.5 and about 8.0, between about 4.5 and about 7.5, between about 4.5 and about 7.0, between about 5.0 and about 9.0, between about 5.0 and about 8.5, between about 5.0 and about 8.0, between about 5.0 and about 7.5, between about 5.5 and about 9.0, between about 5.5 and about 8.5, between about 5.5 and about 8.0, between about 6.0 and 9.0, or any range or value therein.

[0114] In some embodiments, an anti-inflammatory topical composition according to the present application may have a pH of about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.9, about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5.0, about 5.1 about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0,about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, about 8.0, about 8.1, about 8.2, about 8.3, about 8.4, about 8.5, about 8.6, about 8.7, about 8.8, about 8.9, about 9.0, or any range or value therein between. pH Adjusting Agents

[0115] In some embodiments, an anti-inflammatory topical composition may include one or more pH adjusting agents suitable for adjusting the pH of the composition to be in any of the ranges discussed above. In some embodiments, the pH adjusting agent may comprise one or more suitable mineral acids (e.g., hydrochloric acid, nitric acid, phosphoric acid, phosphorous acid, sulfuric acid, etc.), carboxylic acids (e.g., citric acid, glycolic acid, lactic acid, maleic acid, malic acid, succinic acid, glutaric acid, benzoic acid, malonic acid, salicylic acid, gluconic acid, etc.), polymeric acids (e.g., straight-chain poly(acrylic) acid and its copolymers, such as maleic-acrylic, sulfonic-acrylic, and styrene-acrylic copolymers), crosslinked polyacrylic acids, poly(methacrylic) acids, carageenic acid, alginic acid, etc.), and any combination thereof.

[0116] The pH may be raised or made more alkaline by addition of any suitable alkaline pH adjusting agent (e.g., sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, etc.). In some embodiments, the one or more pH adjusting agents may comprise: ammonia; mono-, di-, and tri-alkyl amines (e.g., trimethylamine); mono-, di-, and tri-alkanolamines (e.g., monoethanolamine, diethanolamine, triethanolamine, isopropanolamine, diisopropanolamine, and triisopropanolamine); alkali metal and alkaline earth metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, lithium hydroxide, etc.); alkali metal and alkaline earth metal silicates; and other pH adjusters (e.g., aminomethylpropanol (AMP-95), tetrahydroxypropylethylenediamine, ETHOMEEN® C-25 (PEG- 15 cocoamine), etc.).

[0117] In some embodiments, the one or more pH adjusting agents comprises a buffering agent. A buffering agent is a chemical compound that is or compounds that are added to a solution to allow that solution to resist changes in pH as a result of either dilution or small additions of acids or bases. Effective buffer systems employ solutions which contain largeand approximately equal concentrations of a conjugate acid-base pair (or buffering agents). A buffering agent employed herein may be any such chemical compound(s) which is pharmaceutically acceptable, including but not limited to salts (conjugates acids and / or bases) of phosphates and citrates. In some aspects, the buffering agent comprises phosphate buffered saline (PBS) or an alternative phosphate buffer.Methods of Treatment

[0118] In another aspect, the present disclosure relates to a method of treating an inflammatory skin disorder, the method comprising administering to the skin of a subject an effective amount of the anti-inflammatory topical composition disclosed herein. In some embodiments, the inflammatory skin disorder is acne (e.g., acne vulgaris, comedonic acne, polymorphic acne, acne rosacea, nodulocystic acne, acne conglobata, senile acne, solar acne, drug acne, or occupational acne). In some embodiments, the inflammatory skin disorder is acne. In some embodiments, the inflammatory skin disorder is acne vulgaris.

[0119] In another aspect, the present disclosure relates to a method of preventing or reducing skin inflammation, the method comprising administering to the skin of a subject an effective amount of the composition of the anti-inflammatory topical composition disclosed herein.

[0120] In another aspect, the present disclosure relates to a method of improving skin clarity, the method comprising administering to the skin of a subject an effective amount of the antiinflammatory topical composition disclosed herein.

[0121] In another aspect, the present disclosure relates to a method of reducing the release of inflammatory compounds in the skin of a human subject, the method comprising administering to the skin of a subject an effective amount of the anti-inflammatory topical composition disclosed herein. For example, in some embodiments, the inflammatory compound is IL-8, IL-6, TNF-a, PGE-2, or a combination thereof. In some embodiments, the inflammatory compound is IL-8.

[0122] In another aspect, the present disclosure relates to a method of reducing the degree of oxidative degradation of skin-bound squalene in the skin of a subject, the method comprising administering to the skin of the subject an effective amount of the anti-inflammatory topicalcomposition disclosed herein. In some embodiments, reducing the degree of oxidative degradation of skin-bound squalene comprises reducing the ratio of squalene monohydroperoxide to squalene in the skin. In some embodiments, a reduced degree of oxidative degradation of skin-bound squalene is observed after 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 weeks of administering the topical composition to the skin once weekly, once every 5 days, once every 4 days, once every 3 days, once every 2 days, once daily, twice daily, 3 times daily, 4 times daily, 5 times daily, or more.

[0123] Squalene is known to play a role in reducing free radical oxidative damage to skin and is one of the primary components (-13% of sebum). Skin-bound squalene is thought to function in the skin to quench singlet oxygen, thereby protecting human skin from lipid peroxidation upon exposure to UV light or other sources of oxidative damage. Thus, a reduction in the degree of oxidative reduction of skin-bound squalene to squalene monohydroperoxide may protect the skin from oxidative damage or reduce the degree of oxidative damage to skin upon exposure to UV light or other sources of oxidative damage. (See, e.g., Z.-R. Huang et al., Biological and Pharmacological Activities of Squalene and Related Compounds: Potential Uses in Cosmetic Dermatology, 14 MOLECULES 540 (2009).) Thus, in another aspect, the present disclosure relates to a method of preventing or reducing oxidative damage to skin, comprising administering to the skin of a subject an effective amount of the anti-inflammatory topical composition disclosed herein.

[0124] In some embodiments, the administration is at least once daily, at least twice daily, or at least 3, 4, 5, 6, 7, 8, 9, or 10 times daily. In some embodiments, the administration is at least once weekly, at least twice weekly, or at least 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, or 100 times weekly. In some embodiments, the administration is twice daily.

[0125] In some embodiments, the anti-inflammatory topical composition is effective to reduce or prevent inflammation when applied to the skin of a subject by reducing release of an inflammatory compound (e.g., IL-8) by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%,relative to the amount of the inflammatory compound (e.g, IL-8) released in skin to which the composition is not applied.EXAMPLESExample 1. Preparation of Anti-Inflammatory Compositions

[0126] Exemplary anti-inflammatory topical compositions were prepared as shown in Table 1 (Examples 1-4).

[0127] The compositions were prepared according to the following general procedure. In a first annex tank, a gellifying phase was prepared by pre-mixing gelling agents and glycerin until a smooth paste was obtained. In a second annex tank, an oily phase was prepared by pre-mixing antioxidants, humectants / emollients, squalane, and fragrance.

[0128] In the main tank, an aqueous phase was prepared by first adding water, which was stirred and heated to 40°C. With stirring, disodium EDTA, zinc gluconate, niacinamide, antioxidants (e.g., hydroxyacetophenone) , solvents (e.g., caprylyl glycol and 1,2- hexanediol), panthenol, polylysine dendrimer (e.g., DENDRICLEAR™), additional gelling agents, and the gellifying phase, were added and stirred until completely dispersed. Heating was then turned off to the main tank, and the mixture was allowed to cool to 25°C. The oily phase was then added to the main tank under high propeller stirring and was homogenized to ensure formation of an emulsion. Lastly, distarch phosphate was slowly added to the emulsion in the main tank and was mixed until completely dispersed.Table 1. Exemplary Anti-Inflammatory Topical CompositionsExample 2. Anti-Inflammatory Activity of Active Ingredients

[0129] Referring to FIG. 1, to test the anti-inflammatory activity of active ingredients, IL-8 release induced by IL-lb exposure was compared for keratinocytes pre-incubated in media containing test compounds or combinations thereof, versus control. Keratinocytes were seeded in 96-well plates and incubated in culture medium for 24 hours. The medium was then replaced by culture medium containing the test compounds (individually or in combination),a control medium not containing the test compounds, or a medium containing the reference compound (IKK Inhibitor X, 10 pM), and the cells were pre-incubated for 24 hours. After pre-incubation, the medium was replaced by culture medium containing the inducer (IL-lb tested at 10 ng / ml) and containing or not (control) the test compounds (individually or in combination), or the reference. The cells were then incubated for 48 hours. In parallel, a nonstimulated control was performed. Following incubation with the inducer, the amount of IL-8 released from the cells was measured by ELISA. All experiments were performed in triplicate.

[0130] Referring to FIG. 2, IL-8 release was measured for keratinocytes pre-incubated in two different concentrations of DENDRICLEAR™ (concentration 1 = 0.123 vol.%; concentration 2 = 0.37 vol.%, expressed as v / v dilution from manufacturer’s solution) and niacinamide (concentration 1 = 0.367 mg / ml; concentration 2 = 1.1 mg / ml), individually and in combination. Concentration 2 indicates the highest concentration of each active without inducing any observed cytotoxicity. Non-treated cells were resting keratinocytes not treated with IL-lb. Injured cells were treated with IL-lb and showed a significant release of IL-8 (1693 pg / ml).

[0131] By comparison, DENDRICLEAR™ showed reduction in IL-8 release for both concentrations 1 and 2, while niacinamide reduced the IL-8 release at concentration 2, but not concentration 1. Moreover, the combination of DENDRICLEAR™ and niacinamide showed significant synergy in reducing IL-8 release at concentration 1, while the combination at concentration 2 showed at least significant additivity. The results indicate synergistic antiinflammatory activity for DENDRICLEAR™ and niacinamide.

[0132] Referring now to FIGs. 3-7, to test the anti-inflammatory activity of various plant extracts in combination with DENDRICLEAR™, IL-8 release was measured for keratinocytes pre-incubated in two different concentrations of various plant extracts, individually and in combination with two different concentrations of DENDRICLEAR™ (concentration 1 = 0.123 vol.%; concentration 2 = 0.37 vol.%, expressed as v / v dilution from manufacturer’s solution).

[0133] Referring to FIG. 3, aloe vera extract was tested by adding aloe leaf juice (200X dilution from manufacturer’s solution) at concentration 1 (0.041 mg / ml of the 200X dilution) and concentration 2 (0.123 mg / ml of the 200X dilution). As shown in FIG. 3, aloe vera extract reduced the IL-8 release at concentration 2, but not at concentration 1. Moreover, the combination of DENDRICLEAR™ and aloe vera extract showed synergistic reduction in IL- 8 release at concentration 1, while the combination at concentration 2 showed at least additivity, if not synergy. The results indicate synergistic anti-inflammatory activity for DENDRICLEAR™ and aloe vera extract.

[0134] Referring to FIG. 4, the anti-inflammatory activity of edelweiss extract was tested by adding edelweiss to the cell culture medium at concentration 1 (0.014 vol.% dilution from manufacturer’s solution) and concentration 2 (0.041 vol.% dilution from manufacturer’s solution). As shown in FIG. 4, edelweiss extract reduced the IL-8 release at concentration 1 and concentration 2, though to a lesser extent than DENDRICLEAR™ at each concentration. Moreover, the combination of DENDRICLEAR™ and edelweiss extract showed additive reduction in IL-8 release at concentration 1, while the combination at concentration 2 showed a synergistic reduction. The results indicate synergistic anti-inflammatory activity for DENDRICLEAR™ and edelweiss extract.

[0135] Referring to FIG. 5, the anti-inflammatory activity of scutaline (Exsymol from Unipex) was tested by adding scutaline to cell culture medium at concentration 1 (0.005 vol.% dilution from manufacturer’s solution) and concentration 2 (0.014 vol.% dilution from manufacturer’s solution). Scutaline reduced the IL-8 release at concentration 1 and concentration 2, though to a lesser extent than DENDRICLEAR™ at each concentration. Moreover, the combination of DENDRICLEAR™ and scutaline showed at least significant additive reduction (and perhaps synergistic reduction) in IL-8 release at concentration 1, and concentration 2. The results indicate possible synergistic anti-inflammatory activity for DENDRICLEAR™ and scutaline.

[0136] Referring to FIG. 6, the anti-inflammatory activity of quercetin (95%, Nutraceuticals) was tested by addition to the cell culture medium at concentration 1 (0.367 pg / ml) and concentration 2 (1.1 pg / ml). As shown in FIG. 6, quercetin reduced the IL-8 release atconcentration 1 and concentration 2, on par with the reduction observed for DENDRICLEAR™ alone at each concentration. Moreover, the combination of DENDRICLEAR™ and quercetin showed at least significant additive reduction in IL-8 release at concentration 2, while there was no additivity or synergy observed at concentration 1. The results indicate additive anti-inflammatory activity for DENDRICLEAR™ and quercetin.

[0137] Referring to FIG. 7, the anti-inflammatory activity of lycopene (>98% from tomato) was tested by addition to the cell culture medium at concentration 1 (3.33 pg / ml) and concentration 2 (lOpg / ml). As shown in FIG. 7, lycopene reduced the IL-8 release at concentration 1, on par with the reduction observed for DENDRICLEAR™ alone. At concentration 2, lycopene alone increased the IL-8 released. Moreover, the combination of DENDRICLEAR™ and lycopene at concentration 1 showed additive reduction in IL-8 release, while the combination showed antagonism at concentration 2. The results indicate additive anti-inflammatory activity for DENDRICLEAR™ and lycopene at concentration 1.

[0138] The anti-inflammatory activity of combinations of DENDRICLEAR™ with various actives is summarized in Table 2 below. Combinations of DENDRICLEAR™ with AquaROX® (rosemary extract), vitamin E acetate, marigold extract (lutein, 20%), and sodium ascorbyl phosphate showed no additivity or antagonism at high and low concentrations (data not shown in figures).Table 2. IL-8 Reduction Activity for DENDRICLEAR™ Combined with VariousActives

[0139] Example 3. Anti-Oxidative Activity

[0140] Referring to FIG. 8, to test the oxidative activity of DENDRICLEAR™ in combination with various antioxidants, skin keratinocytes (NHEK) were seeded in 96-well plates and incubated in culture media containing the test compounds (individually or in combination), a control medium not containing the test compounds, or a medium containing the reference compound (BHA, 100 pM), and the cells were pre-incubated for 24 hours.After 24 hours, a fluorescent probe (C-l 1 5 -aminofluorescein, 1 pM) was added to the culture media, and the cells were incubated in the presence of the fluorescent probe for 45 minutes. After 45 minutes, the culture media were irradiated (UVB, 300 mJ / cm2+ UVA, 2200 J / cm2). After irradiation, the culture media were allowed to incubate for an additional 30 minutes before fluorescence was measured using flow cytometry. In parallel, a non-irradiated control was performed. All experimental conditions were performed in triplicate.

[0141] Referring to FIG. 9, DENDRICLEAR™ was observed to have a pro-oxidative effect after UV irradiation and is known to reduce cellular membrane fluidity, consistent with pro-oxidative behavior against lipids in the cellular membrane. Lysine is also known to be susceptible to UV oxidation. Thus, it would be advantageous to identify antioxidants that address the pro-oxidative effect of DENDRICLEAR™ to allow formulation of compositions that have an anti-inflammatory effect without showing pro-oxidative behavior.

[0142] As shown in FIG. 10, the oxidative activity (measured as a reduction in fluorescence versus control) shows that tocopheryl acetate has significant anti -oxi dative activity at the highest concentration tested (0.033 wt.% + 0.37 wt.% DENDRICLEAR™), but not at the lowest concentration tested (0.011 wt.% + 0.123 wt.% DENDRICLEAR™). Thus, antiinflammatory compositions comprising DENDRICLEAR™ may be improved in terms of oxidative degradation by addition of an antioxidant, such as tocopherol or tocopheryl acetate.Example 4. Clinical Study

[0143] An exploratory study was conducted to assess the efficacy, skin tolerability, and product acceptance of a topical composition according to the present disclosure (the “test product”; see Table 1). For this study, 44 male and female subjects from 12 to 60 years of age with normal to oily and acne-prone skin (at least 2 inflammatory lesions within the test area, which included the face) were enrolled, of whom 40 were analyzed. A pea size amount of the test product was applied twice daily (once in the morning and once in the evening) by the subjects at home, according to normal use conditions. The first application was done at the study center under the guidance of a study technician.

[0144] To evaluate the skin tolerability of the test product, an objective and subjective dermatological assessment of pre-defined skin / discomfort parameters was completed at the beginning of the study, as well as after 4 and 8 weeks of test product application. Additionally, inflammatory and non-inflammatory lesions were counted by a dermatologist.

[0145] In sub-panels, the effect of the test product on the sebum production of the skin, as well as confocal microscopic measurements and assessments of the skin microbiome, biomarkers, and skin lipids were completed at the beginning and end of the use period.Reduction in Inflammatory Lesions

[0146] The dermatologist counted the incidences of inflammatory lesions (papules and pustules) and non-inflammatory lesions (whiteheads and blackheads) on the subjects’ skin before the first application of the test product on day 1 (baseline, “BL”), as well as after 4 and 8 weeks of application, on days 28 and 57, respectively.

[0147] As shown in Table 3, after 8 weeks of application with the test product, the counts of observed inflammatory lesions were significantly decreased after eight weeks of application compared to both pre-application and four-week observations. Counts of inflammatory lesions significantly decreased on D57 compared to both baseline and D28 observations. No significant differences were observed upon comparing D28 observations to baseline.Table 3. Counts of Inflammatory Lesions

[0148] FIG. 11 shows side-by-side front view images of an exemplary mean case of a subject at baseline and day 57, showing a reduction in the number of inflammatory lesions, with 9 inflammatory lesions at baseline and 0 inflammatory lesions at day 57.

[0149] Meanwhile, after 4 weeks of application with the test product, the counts of observed non-inflammatory lesions, as determined by the dermatologist, were significantly decreased on D28 compared to baseline. Mean counts were also decreased on D57 compared to baseline. The results are shown in Table 4.Table 4. Counts of Non-Inflammatory LesionsDermatological Skin Assessment

[0150] At days 1, 28, and 57, a dermatological evaluation of predefined skin parameters was performed. The objective skin status in the test area (e.g., skin shininess, skin brightness, skin redness) was evaluated according to the following scale:• Skin shininess: 0= not shiny, 9= very shiny• Skin brightness: 0= not luminous skin, 9= very luminous skin• Skin redness: 0= no redness, 9= strong rednessScores were directly entered into a PC system with an appropriate computer program.

[0151] As shown in Table 5, skin shininess was significantly reduced after 4 and 8 weeks of test product application compared to baseline. Comparing the post-application assessment times, skin shininess was significantly lower after 4 weeks of application compared to the observations made during the 8 week assessment.Table 5. Skin Shininess Mean Values

[0152] As shown in Table 6, skin redness was significantly reduced after 4 and 8 weeks of test product application compared to baseline. No significant differences in skin redness were observed upon comparing the post-application assessment times.Table 6. Skin Redness Mean Values

[0153] As shown in Table 7, skin brightness remained consistent with baseline levels after 4 weeks of test product application, but was significantly reduced after 8 weeks of test product application compared to both baseline and D28 observations.Table 7. Skin Brightness Mean Values

[0154] Additionally, at the above mentioned assessment times, the dermatologist assessed the objective skin status (e.g., dryness, scaling), according to the following scale:• 0 = None• 0.5 = Very slight• 1 = Slight• 2 = Moderate• 3 = StrongScores were directly entered into a PC system with an appropriate computer program. The results are summarized in Table 8.Table 8. Counts of Scores for Objective Dermatological Evaluation of Dryness and Scaling

[0155] The overall number of subjects displaying cases of dryness was continuously reduced over the course of the test period, with the lowest number of cases occurring on day 57. Similarly, cases of scaling were reduced at both post-application assessment times compared to baseline. No cases of edema, fissures, vesicles or weeping were observed at any assessment time.

[0156] The subjects also completed a subjective dermatological evaluation at the same assessment times as the dermatologist objective evaluations discussed above. Reductions in the number of reported cases were observed for all assessed subjective discomfort parameters, although reports of a feeling of dryness and itching were notably decreased after four and eight weeks of test product application. The data is summarized in Table 9, which presents the counts of scores for subjective dermatological evaluation by the subjects themselves.Table 9. Counts of Scores for Subjective Dermatological Evaluation

[0157] Reports of a feeling of dryness were decreased by the largest amount after 4 and 8 weeks of test product application, however all subjective parameters were reduced regarding the overall number of cases reported by the subjects. None of the subjective discomforts were reported as “strong” in severity. In sum, reductions in the numbers of reported cases were observed for all assessed subjective discomfort parameters, although reports of a feeling of dryness and itching were notably decreased after 4 and 8 weeks of test product application.

[0158] Overall, the subjects tolerated the test product very well, and no adverse reactions were recorded. Therefore, in accordance with the dermatologists observations of objective skin parameters and lack of adverse reactions, the skin tolerability of the test product can be assumed to be very good..Squalene Monohydroperoxide / Squalene Ratio Analysis

[0159] Swab samples from subjects within a sub group were analyzed for the ratio of squalene monohydroperoxide to squalene (SQOOH / SQ) by liquid chromatography-mass spectroscopy (LC / MS). The analysis took place before the first application of the test product on day 1, as well as at the end of the use period on day 57, after 8 weeks of test product application.

[0160] Table 10 presents the mean values and standard deviations for SQOOH / SQ (ng / pg), as well as a comparison of assessment times on raw data by paired t-test.Table 10. Ratio of Squalene Monohydroperoxide to Squalene at BL and D57

[0161] As shown in Table 10, the ratio SQOOH / SQ surprisingly was significantly reduced after 8 weeks of test product application compared to baseline observations.Inflammatory Marker Prostaglandin E2 Analysis

[0162] Swab samples from subjects within a sub group were analyzed for the content of the inflammatory marker Prostaglandin E2 (PGE2) by ELISA / EIA measurements. The analysis took place before the first application of the test product on day 1, as well as at the end of the use period on D57, after 8 weeks of test product application.

[0163] Table 11 presents the mean values and standard deviations for Prostaglandin E2 (PGE2) content (ng / mg), as well as a comparison of assessment times on raw data by paired t-test.Table 11. PGE2 Concentration (BL and D57)

[0164] As shown in Table 11, the presence of the inflammatory marker PGE2 within the swab samples was significantly reduced after 8 weeks of test product application, compared to baseline observations.

[0165] While the foregoing terms are believed to be well understood by one of ordinary skill in the art, the following definitions are set forth to facilitate explanation of the presently disclosed subject matter.

[0166] The term “a” or “an” may refer to one or more of that entity, i.e. can refer to plural referents. As such, the terms “a” or “an”, “one or more” and “at least one” are used interchangeably herein. In addition, reference to “an element” by the indefinite article “a” or “an” does not exclude the possibility that more than one of the elements is present, unless the context clearly requires that there is one and only one of the elements.

[0167] Reference throughout this specification to “one embodiment”, “an embodiment”, “one aspect”, or “an aspect” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics can be combined in any suitable manner in one or more embodiments.

[0168] As used herein, the terms “about” or “approximately” when preceding a numerical value indicates the value plus or minus a range of 10% of the value.

[0169] As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges disclosed herein also encompass anyand all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like, include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 cells refers to groups having 1, 2, or 3 cells. Similarly, a group having 1-5 cells refers to groups having 1, 2, 3, 4, or 5 cells, and so forth.

[0170] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the present application and relevant art and should not be interpreted in an idealized or overly formal sense unless expressly so defined herein. While not explicitly defined below, such terms should be interpreted according to their common meaning.

[0171] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0172] Unless the context indicates otherwise, it is specifically intended that the various features of the invention described herein can be used in any combination. Moreover, the disclosure also contemplates that in some embodiments, any feature or combination of features set forth herein can be excluded or omitted. To illustrate, if the specification states that a complex comprises components A, B and C, it is specifically intended that any of A, B or C, or a combination thereof, can be omitted and disclaimed singularly or in any combination.

[0173] Unless explicitly indicated otherwise, all specified embodiments, features, and terms intend to include both the recited embodiment, feature, or term and equivalents thereof.

[0174] All patents, patent applications, provisional applications, and publications referred to or cited herein are incorporated by reference in their entirety, including all figures and tables, to the extent they are not inconsistent with the explicit teachings of this specification.

[0175] Reference will now be made in detail to some specific embodiments contemplated by the present disclosure. While various embodiments are described herein, it will be understood that it is not intended to limit the present technology to the described embodiments. On the contrary, it is intended to cover alternatives, modifications, and equivalents as may be included within the spirit and scope of the technology as defined by the appended claims.ENUMERATED EMBODIMENTS1. A topical composition for reducing skin inflammation, the composition comprising: a polylysine dendrimer; niacinamide, and an antioxidant.2. The topical composition of embodiment 1, wherein the polylysine dendrimer comprises unconjugated poly-L-lysine dendrimer.3. The composition of embodiment 1 or embodiment 2, wherein the antioxidant comprises tocopheryl acetate, tocopherol, or a combination thereof.4. The composition of embodiment 3, wherein the tocopheryl acetate is present at a concentration of about 0.00002 wt.% to about 5.4 wt.%, relative to the total weight of the composition.5. The composition of embodiment 3, wherein the tocopheryl acetate is present at a concentration of about 0.01 wt.% to about 1.5 wt.%, relative to the total weight of the composition.6. The composition of any one of embodiments 3-5, wherein the tocopherol is present at a concentration of about 0.00002 wt % to about 5.4 wt %, relative to the total weight of the composition.7. The composition of any one of embodiments 3-6, wherein the tocopherol is present at a concentration of about 0.01 wt.% to about 1.5 wt.%, relative to the total weight of the composition.8. The composition of any one of embodiments 1-7, wherein the niacinamide is present at a concentration of about 0.0001 wt.% to about 3 wt.%, relative to the total weight of the composition.9. The composition of any one of embodiments 1-8, wherein the niacinamide is present at a concentration of about 0.01 wt.% to about 1.5 wt.%, relative to the total weight of the composition.10. The composition of any one of embodiments 1-9, wherein the polylysine dendrimer is present at a concentration of about 0.1 ppm to about 100 ppm, relative to the total weight of the composition.11. The composition of any one of embodiments 1-10, wherein the polylysine dendrimer is present at a concentration of about 0.5 ppm to about 10 ppm, relative to the total weight of the composition.12. The composition of any one of embodiments 1-11, wherein the polylysine dendrimer is present at a concentration of about 1 ppm to about 5 ppm, relative to the total weight of the composition.13. The composition of any one of embodiments 1-12, further comprising gelling agents at a concentration of 0.5 wt.% to 5 wt.%, relative to the total weight of the composition.14. The composition of any one of embodiments 1-13, further comprising D-panthenol at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.15. The composition of any one of embodiments 1-14, further comprising a sebum regulating agent wherein the sebum regulating agent is one or more selected from zinc gluconate, isopropyl carb onate benzoyl peroxide, clascoterone, isotretinoin, salicylic acid, sulfur, one or more clays, silica, Enantia chlorantha bark extract, one or more starches, or a combination thereof.16. The composition of any one of embodiments 1-15, wherein the sebum regulating agent is zinc gluconate at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.17. The composition of any one of embodiments 1-16, further comprising glycerin at a concentration of 0.5 wt.% to 5 wt.%, relative to the total weight of the composition.18. The composition of any one of embodiments 1-17, further comprising at least one selected from the group consisting of: aloe vera extract, edelweiss, and scutaline.19. The composition of any one of embodiments 1-18, further comprising squalene at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.20. The composition of any one of embodiments 1-19, wherein: the polylysine dendrimer is present at a concentration of 0.1 ppm to about 100 ppm, relative to the total weight of the composition; and the niacinamide is present at a concentration of 1 wt.% to 5 wt.%, relative to the total weight of the composition; the antioxidant is tocopherol or tocopheryl acetate, or a combination thereof, present at a concentration of 00002 wt % to 5.4 wt %; and one or more humectants or emollients.21. The composition of any one of embodiments 1-20, wherein the composition is formulated as a gel, emulsion, or cream.22. The composition of any one of embodiments 1-21, wherein the composition is formulated for leave-on topical application.23. The composition of any one of embodiments 1-22, wherein the composition is effective to reduce or prevent inflammation when applied to the skin of a subject by reducing IL-8 release by at least about 20%, relative to the amount of IL-8 released in skin to which the composition is not applied.24. The composition of any one of embodiments 1-23, wherein the polylysine dendrimer and the niacinamide are present in amounts effective to exhibit synergistic reduction of inflammation when applied to the skin of a subject.25. A topical composition for reducing skin inflammation, the composition comprising: a polylysine dendrimer; and at least one selected from the group consisting of: aloe vera extract, edelweiss, and scutaline.26. The topical composition of embodiment 25, wherein the polylysine dendrimer comprises unconjugated poly-L-lysine dendrimer.27. The composition of embodiment 25 or embodiment 26, wherein the polylysine dendrimer is present at a concentration of about 0.1 ppm to about 100 ppm, relative to the total weight of the composition.28. The composition of any one of embodiments 25-27, wherein the polylysine dendrimer is present at a concentration of about 0.5 ppm to about 10 ppm, relative to the total weight of the composition.29. The composition of any one of embodiments 25-28, wherein the polylysine dendrimer is present at a concentration of about 1 ppm to about 5 ppm, relative to the total weight of the composition.30. The composition of any one of embodiments 25-29, further comprising an antioxidant.31. The composition of embodiment 30, wherein the antioxidant comprises tocopheryl acetate, tocopherol, or a combination thereof.32. The composition of embodiment 31, wherein the tocopheryl acetate is present at a concentration of about 0.00002 wt.% to about 5.4 wt.%, relative to the total weight of the composition.33. The composition of embodiment 31 or embodiment 32, wherein the tocopheryl acetate is present at a concentration of about 0.01 wt.% to about 1.5 wt.%, relative to the total weight of the composition.34. The composition of any one of embodiments 31-33, wherein the tocopherol is present at a concentration of about 0.00002 wt % to about 5.4 wt %, relative to the total weight of the composition.35. The composition of any one of embodiments 31-34, wherein the tocopherol is present at a concentration of about 0.01 wt.% to about 1.5 wt.%, relative to the total weight of the composition.36. The composition of any one of embodiments 25-35, further comprising niacinamide, wherein the niacinamide is present at a concentration of about 0.0001 wt.% to about 3 wt.%, relative to the total weight of the composition.37. The composition of any one of embodiments 25-36, wherein the niacinamide is present at a concentration of from 0.5 wt.% to 5 wt.%, relative to the total weight of the composition.38. The composition of any one of embodiments 25-37, further comprising gelling agents at a concentration of 0.5 wt.% to 5 wt.%, relative to the total weight of the composition.39. The composition of any one of embodiments 25-38, further comprising D-panthenol at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.40. The composition of any one of embodiments 25-39, further comprising a sebum regulating agent wherein the sebum regulating agent is one or more selected from zinc gluconate, isopropylcarbonate benzoyl peroxide, clascoterone, isotretinoin, salicylic acid, sulfur, one or more clays, silica, Enantia chlorantha bark extract, one or more starches, or a combination thereof.41. The composition of embodiment 40, wherein the sebum regulating agent is zinc gluconate at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.42. The composition of any one of embodiments 25-41, further comprising glycerin at a concentration of 0.5 wt.% to 5 wt.%, relative to the total weight of the composition.43. The composition of any one of embodiments 25-42, further comprising squalene at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.44. The composition of any one of embodiments 25-43, wherein: the polylysine dendrimer is present at a concentration of about 0.1 ppm to about 100 ppm, relative to the total weight of the composition; and the aloe vera extract, edelweiss, or scutaline is present at a concentration of 0.00001 wt.% to 1 wt.%, relative to the total weight of the composition.45. The composition of any one of embodiments 25-44, wherein the composition is formulated as a gel, emulsion, or cream.46. The composition of any one of embodiments 25-45, wherein the composition is formulated for leave-on topical application.47. The composition of any one of embodiments 25-46, wherein the composition is effective to reduce or prevent inflammation when applied to the skin of a subject by reducing IL-8 release by at least about 20%, relative to the amount of IL-8 released in skin to which the composition is not applied.48. The composition of any one of embodiments 25-47, wherein the polylysine dendrimer and the aloe vera extract, edelweiss, and / or scutaline are present in amounts effective to exhibit synergistic reduction of inflammation when applied to the skin of a subject.49. A method of treating an inflammatory skin disorder, the method comprising administering to the skin of a subject an effective amount of the composition of any one of embodiments 1-48.50. The method of embodiment 49, wherein the administration is twice daily.51. The method of embodiment 49 or embodiment 50, wherein the inflammatory skin disorder is acne.52. A method of preventing or reducing skin inflammation, the method comprising administering to the skin of a subject an effective amount of the composition of any one of embodiments 1-48.53. The method of embodiment 52, wherein the administration is twice daily.54. A method of improving skin clarity, the method comprising administering to the skin of a subject an effective amount of the composition of any one of embodiments 1-48.55. The method of embodiment 54, wherein the administration is twice daily.56. A method of reducing IL-8 release in skin, the method comprising administering to the skin of a subject an effective amount of the composition of any one of embodiments 1-48.57. The method of embodiment 56, wherein the administration is twice daily.58. A method of reducing oxidative degradation of skin-bound squalene, the method comprising administering to the skin of a subject an effective amount of the composition of any one of embodiments 1-48.59. The method of embodiment 58, wherein the administration is twice daily.60. A method of reducing a ratio of squalene monohydroperoxide to squalene in skin, the method comprising administering to the skin of a subject an effective amount of the composition of any one of embodiments 1-48.61. The method of embodiment 60, wherein the administration is twice daily.62. A method of preventing or reducing oxidative damage to skin, the method comprising administering to the skin of a subject an effective amount of the composition of any one of embodiments 1-48.63. The method of embodiment 62, wherein the administration is twice daily.64. A method of reducing PGE2 expression in skin, the method comprising administering to the skin of a subject an effective amount of the composition of any one of embodiments 1-48.65. The method of embodiment 64, wherein the administration is twice daily.66. Use of a composition according to any one of embodiments 1-48 in treating an inflammatory skin disorder, preventing or reducing skin inflammation, improving skin clarity, reducing inflammation in skin, reducing IL-8 release in skin, reducing oxidative degradation of skin-bound squalene, reducing a ratio of squalene monohydroperoxide to squalene in skin, or preventing or reducing oxidative damage to skin.67. The use according to embodiment 66, wherein the inflammatory skin disorder is acne.68. A composition according to any one of embodiments 1-48, for use in treating an inflammatory skin disorder, preventing or reducing skin inflammation, improving skin clarity, reducing inflammation in skin, reducing IL-8 release in skin, reducing oxidative degradation of skin-bound squalene, reducing a ratio of squalene monohydroperoxide to squalene in skin, or preventing or reducing oxidative damage to skin.69. The composition for use according to embodiment 68, wherein the inflammatory skin disorder is acne.70. Use of a composition according to any one of embodiments 1-48 in the manufacture of a medicament for treating an inflammatory skin disorder, preventing or reducing skin inflammation, improving skin clarity, reducing inflammation in skin, reducing IL-8 release in skin, reducing oxidative degradation of skin-bound squalene, reducing a ratio of squalene monohydroperoxide to squalene in skin, or preventing or reducing oxidative damage to skin.71. The use according to embodiment 70, wherein the inflammatory skin disorder is acne.

Claims

WHAT IS CLAIMED IS:

1. A topical composition for reducing skin inflammation, the composition comprising: a polylysine dendrimer; niacinamide, and an antioxidant selected from the group consisting of tocopheryl acetate, tocopherol, or a combination thereof.

2. The topical composition of claim 1, wherein the polylysine dendrimer comprises unconjugated poly -L-ly sine dendrimer.

3. The composition of claim 1 or claim 2, wherein the tocopheryl acetate or tocopherol is present at a concentration of about 0.00002 wt.% to about 5.4 wt.%, preferably about 0.01 wt.% to about 1.5 wt.%, relative to the total weight of the composition.

4. The composition of any one of claims 1-3, wherein the niacinamide is present at a concentration of about 0.0001 wt.% to about 3 wt.%, preferably about 0.01 wt.% to about 1.5 wt.%, relative to the total weight of the composition.

5. The composition of any one of claims 1-4, wherein the poly lysine dendrimer is present at a concentration of about 0.1 ppm to about 100 ppm, preferably about 0.5 ppm to about 10 ppm, more preferably about 1 ppm to about 5 ppm, relative to the total weight of the composition.

6. The composition of any one of claims 1-5, further comprising gelling agents at a concentration of about 0.5 wt.% to about 5 wt.%, relative to the total weight of the composition.

7. The composition of any one of claims 1-6, further comprising D-panthenol at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.

8. The composition of any one of claims 1-7, further comprising a sebum regulating agent wherein the sebum regulating agent is one or more selected from zinc gluconate, isopropylcarbonate benzoyl peroxide, clascoterone, isotretinoin, salicylic acid, sulfur, one or more clays, silica, Enantia chlorantha bark extract, one or more starches, or a combination thereof.

9. The composition of any one of claims 1-8, further comprising glycerin at a concentration of 0.5 wt.% to 5 wt.%, relative to the total weight of the composition.

10. The composition of any one of claims 1-9, further comprising at least one selected from the group consisting of: aloe vera extract, edelweiss, and scutaline.

11. The composition of any one of claims 1-10, further comprising squalene at a concentration of 0.1 wt.% to 5 wt.%, relative to the total weight of the composition.

12. The composition of any one of claims 1-11, formulated as a gel, emulsion, or cream.

13. The composition of any one of claims 1-12, wherein the poly lysine dendrimer and the niacinamide are present in amounts effective to exhibit synergistic reduction of inflammation when applied to the skin of a subject.

14. The composition of any one of claims 1-13, for use in treating an inflammatory skin disorder, preventing or reducing skin inflammation, improving skin clarity, reducing inflammation in skin, reducing IL- 8 release in skin, reducing oxidative degradation of skinbound squalene, reducing a ratio of squalene monohydroperoxide to squalene in skin, or preventing or reducing oxidative damage to skin.

15. The composition for use according to claim 14, wherein the inflammatory skin disorder is acne.

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