Propionibacterium acnes biomimetic, prebiotic, probiotic, and postbiotic compositions for the treatment of skin conditions

Abstract

Biomimetic, prebiotic, probiotic, and postbiotic compositions, and methods of using them, are disclosed. The biomimetic, prebiotic, probiotic, and postbiotic compositions may include bacteria of the genus C. acnes, cultures thereof, and / or components thereof, and / or substances that induce the growth or activity of C. acnes. The biomimetic, prebiotic, probiotic, and postbiotic compositions can be used to prevent, ameliorate, and / or treat conditions such as atopic dermatitis.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 63 / 443,595, filed February 6, 2023, and U.S. Provisional Patent Application No. 63 / 443,796, filed February 7, 2023, the disclosures of each of which are incorporated herein by reference in their entireties.

[0002] FIELD OF THE INVENTION The present disclosure generally relates to biomimetic, prebiotic, probiotic, and postbiotic compositions and methods of using the same. More specifically, the present invention relates to biomimetic, prebiotic, probiotic, and postbiotic compositions that may include bacteria of the species Cutibacterium acnes (C. acnes), cultures thereof, and / or components thereof. The biomimetic, prebiotic, probiotic, and postbiotic compositions can be used to prevent, improve, and / or treat skin conditions, such as atopic dermatitis. [Background technology]

[0003] Skin is the largest organ of the human body colonized by a diverse group of microorganisms. Colonization is driven by the skin surface ecosystem, which can vary greatly depending on anatomical location, intrinsic host factors, and extrinsic environmental factors. Microorganisms, including bacteria, fungi, and viruses, are known to colonize the skin. Human skin and the gastrointestinal (GI) tract are colonized by a wide variety of microorganisms from birth, when infants are exposed to maternal microbiota and other environmental microorganisms. From the time of initial colonization, the human microbiome remains in a state of flux, with the composition of the resident microbiota changing over time depending on factors present within and external to the host.

[0004] Human skin continuously renews itself, shedding resident microbial cells in the process. Most microorganisms found on the skin are harmless to healthy individuals. Some are considered mutualistic organisms, conferring health benefits to the skin by, for example, secreting antimicrobial substances, preventing pathogen colonization, and influencing the host immune response. However, commensal microorganisms can cause disease and infection when the skin's physical barrier is compromised by trauma or injury.

[0005] Atopic dermatitis is one of the chronic diseases with the highest population prevalence. It is characterized by a series of clinical signs, the most important of which are pruritus and eczema lesions, which can be acute, subacute, or chronic. Atopic dermatitis typically begins around 3 months of age, but sometimes as early as several weeks after birth, during which time the skin's physical barrier undergoes structural and functional maturation. Atopic dermatitis progresses with alternating periods of remission and remission. Depending on the child and the severity of the condition, atopic dermatitis can last from several months to several years, while a significant proportion persist into adulthood.

[0006] Atopic dermatitis is primarily a chronic inflammatory skin disease that combines skin barrier dysfunction and skin inflammation. In the first sensitization phase, a defect in the skin barrier allows allergens to penetrate the skin. Allergens that penetrate the upper layers of the epidermis are processed (internalized) by epidermal Langerhans cells and dermal dendritic cells. Langerhans cells are antigen-presenting cells that can capture skin antigens, prepare them, and present them to T lymphocytes. This presentation leads to the activation of Th2 responses, along with the direct activation of epidermal alarmins such as IL-33, IL-25, and TSLP, resulting in the production of proinflammatory cytokines such as IL-4, IL-5, and IL-13.

[0007] The most common complication during the entire active phase of the disease is bacterial or viral skin superinfection. The skin of patients with atopic dermatitis is prone to secondary infections, which then tend to spread more widely. For example, Staphylococcus aureus is a major cause of skin infections. It commonly colonizes the skin of patients with atopic dermatitis but only temporarily exists on healthy skin. The bacteria then secrete virulence factors that further compromise barrier function, exacerbate the disease, and contribute to its chronicity. Furthermore, Staphylococcus aureus is commonly found in patients with atopic dermatitis, including in the form of a homogeneous biofilm, which is resistant to host defenses and treatment.

[0008] Currently, several treatment options exist with varying degrees of success. For example, "probiotics" are live microorganisms (typically bacteria) that generally provide health benefits by improving or restoring the microflora upon use. "Postbiotics" are soluble factors (metabolites or by-products) secreted by bacteria or released after bacterial lysis that provide physiological benefits to the host. "Prebiotics" are substances that selectively induce the growth or activity of beneficial microorganisms. Colloidal oat compositions have been found to increase the growth of C. acnes in in vitro studies. In infants at risk for developing atopic dermatitis, the use of emollients correlates with a tendency toward greater bacterial species richness and diversity compared with the absence of emollients. Several studies have shown that the use of infant detergents and lotions results in significantly richer microbial species than detergent alone. Both cleansing-only regimens and cleansing and emollient regimens are well tolerated. Skin pH remains slightly acidic throughout each regimen. A gentle baby cleanser and lotion routine can help improve microbial species richness and contribute to overall skin barrier health by providing an appropriate environment for healthy skin microorganisms to thrive. The incidence of atopic dermatitis in high-risk infants during the first year of life has been shown to be reduced by early initiation of daily use of a dedicated emollient by 2 months of age. Summary of the Invention [Problem to be solved by the invention]

[0009] However, there is a long-felt need for effective treatments to promote skin health in individuals. The present disclosure provides compositions and methods to meet that need. [Means for solving the problem]

[0010] This Summary is provided to introduce a selection of concepts in a concise form that are further described below in the Detailed Description. This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter. Various examples of the present disclosure provide systems and methods described herein.

[0011] The present invention includes a method for preventing, improving and / or treating a skin condition in a subject, the method comprising administering to the subject C. acnes, a culture thereof and / or a component thereof.

[0012] In one example, the present disclosure also includes a composition for use in preventing, improving, and / or treating a skin condition in a subject, the composition comprising C. acnes, a culture thereof, and / or components thereof, and a pharmaceutically and / or cosmetically acceptable carrier.

[0013] In some examples, the composition further comprises a material selected from the group consisting of a surfactant, a chelating agent, an emollient, a moisturizer, a conditioner, a preservative, an opacifier, a fragrance, and combinations of two or more thereof.

[0014] In some examples, the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid wash, bar soap, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

[0015] The present invention also relates to the use of C. acnes, its cultures and / or its components in cosmetic, food or pharmaceutical compositions.

[0016] In some examples, the composition is a cosmetic or pharmaceutical composition that can be used as a topical skin preparation and applied directly to the affected area. For example, the composition can be prepared in various forms such as an ointment, cream, emulsion, etc.

[0017] In some examples, the pharmaceutical composition may be absorbed into the body by oral or parenteral administration, and may be administered in forms such as, but not limited to, powders, granules, capsules, and injections.

[0018] A variety of forms of the cosmetic or pharmaceutical composition may be provided without departing from the scope of the present invention.

[0019] In some examples, the cosmetic composition may inhibit or improve atopic dermatitis, other inflammatory skin diseases, or dry skin conditions.

[0020] Examples of inflammatory skin diseases include atopic dermatitis, acne, inflammatory keratosis, psoriasis, staphylococcal scalded skin syndrome, contact dermatitis, bacterial dermatitis, impetigo, secondary infection of eczema, folliculitis alopecia, eczema, mastitis, and folliculitis.

[0021] Other technical features will be readily apparent to those skilled in the art from the following figures, descriptions, and claims. [Brief explanation of the drawings]

[0022] [Figure 1] 1 is a graph showing the effect of various concentrations of pure and conditioned media on normal human epidermal keratinocytes (NHEK) using a viability test (MTT) 24 hours after treatment. [Figure 2] 1 is a graph showing the effect of various concentrations of pure and conditioned media on NHEKs using a viability test (MTT) after 6 days of treatment. [Figure 3]FIG. 1 illustrates the steps taken to prepare and collect samples for transcriptome analysis. [Figure 4A] FIG. 1 is a graph showing gene set enrichment analysis, i.e., up-regulated and down-regulated genes, for 5% RCM C. acnes conditioned broth. [Figure 4B] 10 is a graph showing gene set enrichment analysis for 10% RCM C. acnes conditioned medium. [Figure 4C] 1 is a graph showing gene set enrichment analysis for 20% RCM C. acnes conditioned broth. [Figure 5] 1 is a graph showing the effect of untreated control, 10 μg / mL adiponectin, and various concentrations of C. acnes conditioned medium on NHEK total lipids after 6 days of treatment. [Figure 6A] Fluorescence microscopy images showing the effect of untreated controls after 6 days. [Figure 6B] Fluorescence microscopy images showing the effect of 10 ug / mL adiponectin on NHEK total lipids after 6 days of treatment. [Figure 6C] Fluorescence microscopy images showing the effect of 0.1% C. acnes conditioned medium on NHEK total lipids after 6 days of treatment. [Figure 6D] Fluorescence microscopy images showing the effect of 0.5% C. acnes conditioned medium on NHEK total lipids after 6 days of treatment. [Figure 6E] Fluorescence microscopy images showing the effect of 1.0% C. acnes conditioned medium on NHEK total lipids after 6 days of treatment. [Figure 7] 1 is a graph showing the effect of untreated control, various concentrations of broth (unconditioned C. acnes medium), various concentrations of C. acnes conditioned medium, and 10 μg / mL adiponectin on NHEK total lipids after 1 day of treatment. [Figure 8A] Fluorescence microscopy images showing the effect of untreated controls after 1 day. [Figure 8B]Fluorescence microscopy images showing the effect of 5% broth on NHEK total lipids after 1 day of treatment. [Figure 8C] Fluorescence microscopy images showing the effect of 10% broth on NHEK total lipids after 1 day of treatment. [Figure 8D] Fluorescence microscopy images showing the effect of 5% C. acnes conditioned medium on NHEK total lipids after 1 day of treatment. [Figure 8E] Fluorescence microscopy images showing the effect of 10% C. acnes conditioned medium on NHEK total lipids after 1 day of treatment. [Figure 8F] Fluorescence microscopy images showing the effect of 10 ug / mL adiponectin on NHEK total lipids after 1 day of treatment. [Figure 9] Principal Component Analysis (PCA) scores of lipidomic analysis of NHEK samples collected after various test conditions are shown. [Figure 10] Principal component analysis (PCA) scores of lipidomic analysis of NHEK samples collected at different time points after exposure to various test conditions are shown. [Figure 11] 1 is a table showing lipid classes from lipidomic analysis of NHEK samples that showed statistically significant differences between exposure to C. acnes conditioned medium and untreated control (for samples collected on days 2 and 3). DETAILED DESCRIPTION OF THE INVENTION

[0023] Hereinafter, in order to more specifically explain the present disclosure, the following examples will be given. However, the examples according to the present disclosure can be modified into various other forms, and the scope of the present disclosure should not be construed as being limited to the examples described below. The examples of the present disclosure are provided as examples to facilitate a specific understanding of the present disclosure.

[0024] Various embodiments and examples will now be described in detail with reference to the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts. References made throughout this disclosure to specific examples and embodiments are provided for illustrative purposes only and are not meant to limit all examples unless otherwise indicated.

[0025] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a reagent" includes one or more of such different reagents, and reference to "the method" includes reference to equivalent steps and methods known to those of skill in the art that may modify or substitute for the method described herein. Unless otherwise indicated, the term "at least" preceding a series of elements should be understood to refer to every element in the series. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the present disclosure described herein. Such equivalents are intended to be encompassed by the present disclosure.

[0026] As used herein, the term "about" or "approximately" means within 20%, preferably within 15%, more preferably within 10%, preferably within 5%, and preferably within 1% of a given value or range.

[0027] The term "and / or," whenever used herein, includes "and," "or," and "all or any other combination of the elements connected by this term." A "biomimetic" is a substance that (1) is synthesized by artificial means and (2) mimics a natural substance with known biological function. Ahmadi et al., "Supramolecular architecture of a multi-component biomimetic lipid barrier formulation," Journal of Colloid and Interface Science, Vol. 587, April 2021, pp. 597-612, discloses a multi-component lipid / surfactant formulation that can be used in "biomimetic" skin applications. Di Lorenzo et al., "Biomimetic endorphin for wrinkle lifting in a daily cosmetic remedy," Dermatol Res Skin Care, 2022;6(2):106, discloses a biomimetic peptide for cosmetic applications. US Patent No. 6,544,401 to Henceforth Hibernia, Inc. discloses biomimetic aqueous solutions and their use in health and beauty products.

[0028] Throughout this specification and the claims that follow, unless the context otherwise requires, the word "comprise" and variations such as "comprises" and "comprising" will be understood to mean the inclusion of a specified integer or step or group of integers or steps, but not the exclusion of any other integer or step or group of integers or steps. As used herein, the term "comprising" can be replaced with the terms "containing" or "including," or, as sometimes used herein, can also be replaced with the term "having."

[0029] "Conditioned medium" is a medium containing biologically active components, including metabolites, obtained from cells or tissues that have previously been cultured and have released substances into the medium that affect specific cell functions (e.g., proliferation, lysis).

[0030] The term "culture" includes (1) a whole medium containing a bacterial strain, a bacterial extract, its metabolic products, additional nutrients, etc., obtained by culturing the bacterial strain for a certain period of time in a medium capable of supplying nutrients so that the bacterial strain can grow and survive, and (2) a solution from which the bacterial strain has been removed after culturing. For culturing the composition of the present invention, a medium used for culturing microorganisms can be easily selected and used by those skilled in the art according to the purpose. Preferably, a medium used for culturing bacteria of the genus Cutibacterium can be used, and more preferably, Reinforced Clostridium Medium (RCM), Tryptic soy broth (TSB), or Brain Heart Infusion (BHI) can be used, but is not limited to these.

[0031] A "diffusible mediator" is an agent locally released or carried in blood or tissue fluids that may be involved in the initiation, perpetuation, or exacerbation of a biological process.

[0032] "Gene Set Enrichment Analysis" (GSEA) is a computational method that determines whether a predefined set of genes shows statistically significant concordant differences between two biological states.

[0033] The "MTT assay" is a colorimetric assay for assessing cellular metabolic activity. NAD(P)H-dependent cellular oxidoreductase enzymes can reflect the number of viable cells present under defined conditions. These enzymes can reduce the tetrazolium dye MTT, chemically 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, to its insoluble formazan, which has a purple color. Furthermore, reduction of MTT to formazan in lipid cellular structures was found without the apparent involvement of oxidoreductases.

[0034] Principal component analysis (PCA) is a method for reducing the dimensionality of large datasets to improve their interpretability. [Example]

[0035] In clinical studies, we found that the presence of Propionibacterium acnes (C. acnes) positively correlated with enriched lipid signaling pathways (PF Roux, T Oddos, and G Stamatas, "Deciphering the Role of Skin Surface Microbiome in Skin Health: An Integrative Multiomics Approach Reveals Three Distinct Metabolite-Microbe Clusters," J Invest Dermatol, 142(2), pp. 469-479, 2021). To test the existence of a causal relationship that could explain this observation, we hypothesized that C. acnes stimulated lipid production in keratinocytes via a diffusible mediator. To test this hypothesis, we performed three complementary experiments on human keratinocytes treated with non-cytotoxic concentrations of C. acnes-conditioned medium. Transcriptome analysis of treated keratinocytes was performed to test whether genes related to lipid metabolism were upregulated, a fluorescent assay using lipid staining was performed to observe whether there was intracellular lipid accumulation, and lipidome analysis of treated keratinocytes was performed to test whether there was a dose- and time-dependent effect.

[0036] First, a cytotoxicity test was performed. C. acnes (ATCC 6919) was cultured at 2.03 × 10 in RCM broth from Biomerieux (Craponne, France). 9 CFU were cultured. After centrifugation and filtration of the RCM broth to remove viable cells, the "conditioned medium" was frozen at -80°C and isolated for further testing in normal human epidermal keratinocytes (NHEK). Viability studies were performed on NHEK to determine non-cytotoxic concentrations.

[0037] Transcriptome analysis was then performed. For example, MTT tests were performed to estimate the non-cytotoxic concentrations of RCM broth and C. acnes conditioned broth. RCM broth alone was well tolerated regardless of the test concentration, but the correct concentration of C. acnes conditioned medium depended on the duration of treatment. The cytotoxic effect observed in the conditioned broth demonstrated that C. acnes releases virulence factors.

[0038] Differentiated NHEKs were treated with 0%, 5%, 10%, and 20% RCM broth (unconditioned medium) and C. acnes conditioned broth (conditioned medium) for one day. Experiments were performed with one replicate per condition. Cells were treated with 0.05% trypsin at 37°C to detach cells. 10% fetal bovine serum in DMEM (Lonza, Verviers, Belgium) was added for trypsin neutralization, and NHEKs were harvested after rinsing with PBS. Cells were centrifuged, and the supernatant was removed and replaced with RLT buffer (Qiagen, Courtaboeuf, France) supplemented with 1% β-mercaptoethanol (Sigma-Aldrich, St. Quentin Fallavier, France). RNA was extracted using a Qiacube HT extractor and its specific reagents and protocol (Qiagen, Courtaboeuf, France). RNA aliquots were sent to Genex (Longjumeau, France) for transcriptome analysis. It was observed that, independent of the concentration of conditioned medium, genes involved in DNA replication were downregulated, i.e., the cells reduced their turnover, and genes involved in lipid production were upregulated.

[0039] Lipid accumulation was then assessed using a fluorescence assay. Specifically, according to the results of the transcriptome analysis, NHEKs were treated with conditioned medium at concentrations of 0.1%, 0.5%, 1%, and 2% for 6 days. Adiponectin (10 μg / mL, Sigma, St. Quentin Fallavier, France), which has been shown to induce lipid production in cell culture, was used as a positive control. To quantify and visualize total lipids after 6 days of treatment, cells were treated with AdipoRed™ Assay Reagent (Lonza, Verviers, Belgium), a lipophilic reagent that fluoresces (excitation: 485 nm, emission: 572 nm). The intensity of fluorescence is proportional to lipid concentration and can be measured using a spectrophotometer (Envision, Perlin Elmer, Villebon-sur-Yvette, France). Images were acquired at 20x magnification using a fluorescence microscope (Axio Imager, ZEISS, Rueil Malmaison, France).

[0040] Adiponectin induced an increase in the fluorescent signal (+25%) after 6 days of treatment, validating the study. Conditioned medium tested at 0.1% (a non-toxic concentration) also showed an increase in the fluorescent signal (+29%) compared to the untreated control. Fluorescence microscopy images also showed that treatment with 0.1% and 0.5% conditioned medium increased intracellular fluorescence on day 6 compared to the untreated control. This experiment was repeated by increasing the concentration of conditioned medium to 5% and 10% and shortening the treatment time to 1 day. 5% and 10% unconditioned medium were also tested as negative controls, and adiponectin (10 μg / mL) was tested as a positive control.

[0041] For 5% and 10% conditioned medium, fluorescence intensity values ​​measured by a spectrophotometer dramatically increased by +181% and +206%, respectively, compared to the untreated control. Non-conditioned medium did not induce any increase in fluorescence. Adiponectin induced a 250% increase in fluorescence, validating the test. Fluorescence microscopy images of these test conditions on day 1 confirmed the increase in fluorescence induced by the conditioned medium.

[0042] Lipidome analysis was used to further understand the lipid classes produced by keratinocytes treated with C. acnes-conditioned medium and to investigate whether dose- and time-dependent effects existed. NHEKs were treated with RCM (unconditioned) broth and C. acnes-conditioned broth at 0%, 5%, and 10% (three replicates per condition) for 1 day. Adiponectin at 10 μg / mL was used as a positive reference. Keratinocytes were dissociated using PBS (rinse), trypsin (cell detachment), and the addition of DMEM supplemented with 10% fetal bovine serum (trypsin neutralization). After centrifugation, the supernatant was removed, and PBS was added to obtain a suspension of 3000 cells / μL.

[0043] 300 μl of these suspensions were sent to Lipotype GmbH (Dresden, Germany) for lipid analysis. Principal component analysis (PCA) scores based on lipid species showed clustering of the tested conditions and also showed that cells treated with broth alone shifted their lipid profile compared to untreated controls. Cells treated with conditioned broth had significantly different lipid profiles compared to untreated or unconditioned broth-treated cells. The distance from the untreated cluster was greater at higher concentrations, indicating a dose-dependent effect.

[0044] In another experiment, NHEKs were treated with RCM (unconditioned) broth and C. acnes-conditioned broth at 0% and 10% (3 replicates per condition). Adiponectin at 10 μg / mL was used as a positive reference. Cells were harvested on days 2 and 3 using the same protocol as above. After lipidomic analysis using the same procedure, the PCA plot showed a time-dependent shift in the lipid profile away from the untreated control.

[0045] The lipid classes induced in keratinocytes were further investigated by conditioned medium treatment. The results are summarized in the table shown in Figure 11, which lists the 10 most significant lipid species. In particular, comparisons were made between i) conditioned medium on day 2 versus the untreated control on day 2, and ii) conditioned medium on day 3 versus the untreated control on day 3.

[0046] We conclude that, as shown herein, treatment of normal human epidermal keratinocytes with C. acnes-conditioned medium produced interesting and unexpected results compared with untreated controls. These results included upregulation of genes involved in lipid metabolism, increased fluorescence indicative of enhanced lipid production, confirmation of intracellular lipid accumulation by fluorescence microscopy, and dose- and time-dependent effects on lipid composition analysis. Therefore, these results demonstrate that C. acnes stimulates lipid production in human keratinocytes via a diffusible mediator.

[0047] Any suitable carrier can be used in one or more of the compositions described herein. In some embodiments, the carrier is a cosmetically acceptable carrier. As will be appreciated by those skilled in the art, a cosmetically acceptable carrier includes a carrier suitable for use in contact with the body, particularly the skin, that is free from undue toxicity, incompatibility, instability, irritation, allergic reaction, etc. A safe and effective amount of carrier is from about 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 98% by weight to about 85, 90, 95, 98, 99, 99.1, 99.5, or 99.9% by weight of the composition.

[0048] The carrier may be in a wide variety of forms. For example, but not limited to, carriers in the form of emulsions such as oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone are useful herein. These emulsions may cover a wide range of viscosities, for example, from about 100 cP to about 200,000 cP using a Brookfield RVT viscometer.

[0049] Examples of suitable cosmetically acceptable carriers include cosmetically acceptable solvents and materials for cosmetic solutions, suspensions, lotions, creams, serums, essences, gels, toners, sticks, sprays, ointments, liquid cleansers and bars, shampoos, hair conditioners, pastes, foams, mousses, powders, shaving creams, wipes, patches, strips, powered patches, microneedle patches, bandages, hydrogels, film-forming products, facial and skin masks, makeup, liquid drops, etc. These product types can comprise several types of cosmetically acceptable carriers, including, but not limited to, solutions, suspensions, emulsions such as microemulsions and nanoemulsions, gels, solids, liposomes, other encapsulation technologies, etc.

[0050] The following are non-limiting examples of carriers. Other carriers can be formulated by those skilled in the art. In one embodiment, the carrier comprises water. In further embodiments, the carrier may further comprise one or more aqueous or organic solvents. Examples of organic solvents include, but are not limited to, dimethyl isosorbide; isopropyl myristate; cationic, anionic, and nonionic surfactants; vegetable oils; mineral oils; waxes; gums; synthetic and natural gelling agents; alkanols; glycols, and polyols. Examples of glycols include, but are not limited to, glycerin, propylene glycol, butylene glycol, pentalene glycol, hexylene glycol, polyethylene glycol, polypropylene glycol, diethylene glycol, triethylene glycol, capryl glycol, glycerol, butanediol, and hexanetriol, as well as copolymers or mixtures thereof. Examples of alkanols include, but are not limited to, those having from about 2 carbon atoms to about 12 carbon atoms (e.g., from about 2 carbon atoms to about 4 carbon atoms), such as isopropanol and ethanol. Examples of polyols include, but are not limited to, those having from about 2 carbon atoms to about 15 carbon atoms (e.g., from about 2 carbon atoms to about 10 carbon atoms), such as propylene glycol. The organic solvent may be present in the carrier in an amount of from about 1 percent to about 99.99 percent (e.g., from about 20 percent to about 50 percent) based on the total weight of the carrier. Water may be present in the carrier (prior to use) in an amount of from about 5 percent to about 95 percent (e.g., from about 50 percent to about 90 percent) based on the total weight of the carrier. Solutions can contain any suitable amount of solvent, including from about 40 to about 99.99%. Some solutions contain from about 50 to about 99.9%, about 60 to about 99%, about 70 to about 99%, about 80 to about 99%, or about 90 to about 99% solvent.

[0051] A lotion can be made from such a solution. The lotion typically contains at least one emollient in addition to the solvent. The lotion can contain about 1% to about 20% (e.g., about 5% to about 10%) of the emollient and about 50% to about 90% (e.g., about 60% to about 80%) of water.

[0052] Another type of product that can be formulated from a solution is a cream, which typically contains about 5% to about 50% (e.g., about 10% to about 20%) emollient and about 45% to about 85% (e.g., about 50% to about 75%) water.

[0053] Yet another type of product that can be formulated from a solution is an ointment. Ointments can contain a simple base of animal, vegetable, or synthetic oils, or a semi-solid 10-carbon hydrocarbon. Ointments can contain from about 2% to about 10% of an emollient and from about 0.1% to about 2% of a thickening agent.

[0054] The compositions useful in the present invention can also be formulated as emulsions. When the carrier is an emulsion, about 1% to about 10% (e.g., about 2% to about 5%) of the carrier contains an emulsifier. The emulsifier may be nonionic, anionic, or cationic.

[0055] Lotions and creams can be formulated as emulsions. Such lotions typically contain 0.5% to about 5% emulsifier, and such creams typically contain about 1% to about 20% (e.g., about 5% to about 10%) emollient, about 20% to about 80% (e.g., about 30% to about 70%) water, and about 1% to about 10% (e.g., about 2% to about 5%) emulsifier.

[0056] Single-phase emulsion skin preparations, such as lotions and creams, of the oil-in-water and water-in-oil types, are well known in the art and are useful in the present disclosure.Multiple-phase emulsion compositions, such as water-in-oil-in-water or oil-in-water-in-oil types, are also useful in the present disclosure.In general, such single-phase or multi-phase emulsions contain water, emollients, and emulsifiers as essential ingredients.

[0057] The compositions of the present disclosure can also be formulated as gels (e.g., aqueous, alcohol, alcohol / water, or oil gels using a suitable gelling agent). Suitable gelling agents for aqueous and / or alcoholic gels include, but are not limited to, natural gums, acrylic acid and acrylate polymers and copolymers, and cellulose derivatives (e.g., hydroxymethylcellulose and hydroxypropylcellulose). Suitable gelling agents for oils (such as mineral oil) include, but are not limited to, hydrogenated butylene / ethylene / styrene copolymers and hydrogenated ethylene / propylene / styrene copolymers. Such gels typically contain from about 0.1% to about 5% by weight of such gelling agents.

[0058] The compositions of the present disclosure can also be formulated into solid preparations (e.g., wax-based sticks, soap bars, powders, or wipes). The compositions of the present disclosure may be combined with solid, semi-solid, or soluble substrates (e.g., wipes, masks, pads, gloves, or strips).

[0059] Other additives The compositions of the present invention may further comprise any of a variety of additional cosmetic active agents. Examples of suitable additional active agents include skin lightening agents, tanning agents, additional anti-aging agents, tropoelastin promoters, collagen promoters, anti-acne agents, sheen adjusting agents, antimicrobial agents (e.g., anti-yeast, anti-fungal, and anti-bacterial agents), anti-inflammatory agents, anti-parasitic agents, topical analgesics, sunscreens, photoprotective agents, antioxidants, keratolytic agents, detergents / surfactants, moisturizers, nutrients, vitamins, energy enhancers, antiperspirants, astringents, deodorants, hair removal agents, hair growth strengthening agents, hair growth retarding agents, stabilizers, hydration enhancers, efficacy enhancers, anti-callus agents, skin conditioning agents, anti-cellulite agents, malodor counteractants (e.g., malodor masking agents), or pH modifiers.

[0060] Examples of various suitable additional cosmetically acceptable actives include: hydroxy acids, benzoyl peroxide, D-panthenol; avobenzone (Parsol 1789), bisdisulizole disodium (Neo Heliopan AP), diethylaminohydroxybenzoyl hexylbenzoate (Uvinul A Plus), ecamsule (Mexoryl SX), methyl anthranilate, 4-aminobenzoic acid (PABA), cinoxate, ethylhexyl triazone (Uvinul T150), homosalate, 4-methylbenzylidene camphor (Parsol 5000), octyl methoxycinnamate (Octinoxate), octyl salicylate (Octisalate), padimate O (Escalol 507), phenylbenzimidazole sulfonic acid (Ensulizole), polysilicone-15 (Parsol SLX), trolamine salicylate, bemotrizinol (Tinosorb S), Benzophenone 1-12, Dioxybenzone, Drometrizole Trisiloxane (Mexoryl XL), Iscotrizinol (Uvasorb HEB), Octocrylene, Oxybenzone (Eusolex 4360), Sulisobenzone, Bisoctrizole (Tinosorb M), titanium dioxide, zinc oxide, and other UV filters, such as, but not limited to, carotenoids, free radical scavengers, spin traps, retinoids and retinoid precursors (e.g., retinol, retinoic acid, and retinyl palmitate), ceramides, polyunsaturated fatty acids, essential fatty acids, enzymes, enzyme inhibitors, minerals, hormones (e.g., estrogen), steroids (e.g., hydrocortisone), 2-dimethylaminoethanol, copper salts (e.g., copper chloride), copper-containing peptides such as Cu: Gly-His-Lys, Coenzyme Q10, amino acids (e.g., proline), vitamins, lactobionic acid, acetyl-coenzyme A, niacin, riboflavin, thiamine, ribose, electron transporters (e.g., NADH and FADH2), and other plant extracts (e.g., extracts of oat, aloe vera, feverfew, soy, and shiitake mushroom), and derivatives and mixtures thereof.

[0061] If present, any additional cosmetic active agent may be present in the composition in any suitable amount, such as from about 0.0001% to about 20% by weight of the composition, such as from about 0.001% to about 10% by weight, such as from about 0.01% to about 5% by weight, in some embodiments from 0.1% to 5%, and in other embodiments from 1% to 2%.

[0062] The compositions of the present disclosure may also include a cosmetically effective amount of one or more additional anti-inflammatory compounds. Examples of suitable anti-inflammatory agents include substituted resorcinols, (E)-3-(4-methylphenylsulfonyl)-2-propenenitrile (such as "Bay 11-7082" available from Sigma-Aldrich, St. Louis, Missouri), tetrahydrocurcuminoids (such as Tetrahydrocurcuminoid CG available from Sabinsa Corporation, Piscataway, NJ), extracts and materials derived from: Phellodendron amurense bark extract (PCE), unmodified soybean (Glycine max), feverfew (Tanacetum parthenium), ginger (Zingiber officinale), ginkgo biloba, madecassoside (a component of Centella asiatica extract), Cotinus coggygria, butterbur extract (Petasites hybridus), wolfberry (Lycium barbarum), milk thistle extract (Silybum marianum), honeysuckle (Lonicera japonica), Peruvian basalum (Myroxylon pereirae), sage (Salvia officinalis), cranberry extract (Vaccinium oxycoccos), amaranth oil (Amaranthus cruentus), pomegranate (Punica granatum), yerba mate (Ilex paraguariensis leaf extract), white lily flower extract (Lilium candidum), olive leaf extract (Olea europaea), phloretin (apple extract), oat flour (Aveena sativa), leifenol (hops: Humulus lupulus) extract, bouglan P (Ononis spinosa), licochalcone (a component of licorice: Glycyrrhiza inflate extract), Symrelief (bisabolol and ginger extract), and combinations of two or more thereof.

[0063] In one embodiment, the anti-inflammatory agent is resorcinol. Particularly suitable substituted resorcinols include 4-hexylresorcinol and 4-octylresorcinol, especially 4-hexylresorcinol. 4-Hexylresorcinol is commercially available as "SYNOVEA HR" from Sytheon (Lincoln Park, NJ). 4-Octylresorcinol is commercially available from City Chemical LLC (West Haven, Connecticut).

[0064] "Feverfew extract" refers to an extract of the plant "Tanacetum parthenium," which may be produced according to the details set forth in U.S. Patent No. 7,537,791, entitled "PARTHENOLIDE-FREE BIOACTIVE INGREDIENTS FROM FEVERFEW (TANACETUM PARTHENIUM) AND PROCESSES FOR THEIR PRODUCTION." One particularly suitable feverfew extract is commercially available from Integrated Botanical Technologies (Ossining, NY) as approximately 20% active feverfew.

[0065] A variety of other materials may also be present in the compositions of the present disclosure. In one or more embodiments, the composition comprises one or more topical ingredients selected from the group consisting of surfactants, chelating agents, emollients, moisturizers, conditioners, preservatives, opacifiers, fragrances, and the like.

[0066] [Embodiment] (1) A method comprising at least one of preventing, ameliorating, or treating a skin condition in a subject, administering to the subject a composition comprising at least one of C. acnes, a culture of C. acnes, or a component thereof. A method comprising: (2) The method of embodiment 1, wherein the composition is a pharmaceutical composition. (3) The method of claim 1, wherein the composition is a cosmetic composition. (4) The method of claim 1, wherein the skin condition is atopic dermatitis. (5) The method of claim 1, wherein the composition is a postbiotic composition derived from a liquid fermentation medium of the C. acnes microorganism.

[0067] (6) The method of embodiment 5, wherein the postbiotic composition is prepared by collecting the supernatant from centrifugation of the C. acnes microorganisms. (7) The method of embodiment 1, wherein the composition further comprises at least one of a C. acnes biomimetic, a C. acnes culture, or a component thereof. (8) The method of embodiment 7, wherein the biomimetic produces a diffusible mediator involved in the induction of lipid production by keratinocytes. (9) The composition further comprises a prebiotic for use in at least one of preventing, ameliorating, or treating the skin condition in the subject; The prebiotic induces at least one of the growth and activity of C. acnes. 3. The method of embodiment 1. (10) The method of embodiment 9, wherein the prebiotic enhances the effect of C. acnes on lipid production by keratinocytes.

[0068] (11) A composition for use in at least one of preventing, improving, or treating a skin condition in a subject, comprising: At least one of C. acnes, a culture of C. acnes, or a component thereof; a pharmaceutically and / or cosmetically acceptable carrier; A composition comprising: (12) The composition of embodiment 1, further comprising a material selected from the group consisting of a surfactant, a chelating agent, an emollient, a moisturizer, a conditioner, a preservative, an opacifier, a fragrance, and combinations of two or more thereof. 13. The composition of claim 1, wherein the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid cleanser, bar soap, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

Claims

1. 1. A composition for use in at least one of preventing, ameliorating, or treating a skin condition in a subject, comprising: at least one of C. acnes, a culture of C. acnes, or a component thereof; a pharmaceutically and / or cosmetically acceptable carrier; A composition comprising:

2. 10. The composition of claim 1, further comprising a material selected from the group consisting of surfactants, chelating agents, emollients, moisturizers, conditioners, preservatives, opacifiers, fragrances, and combinations of two or more thereof.

3. 10. The composition of claim 1, wherein the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid cleanser, bar soap, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

4. 1. A method comprising at least one of preventing, ameliorating, or treating a skin condition in a subject, comprising: administering to the subject a composition comprising at least one of C. acnes, a culture of C. acnes, or a component thereof. A method comprising:

5. The method of claim 4 , wherein the composition is a pharmaceutical composition.

6. The method of claim 4, wherein the composition is a cosmetic composition.

7. 5. The method of claim 4, wherein the skin condition is atopic dermatitis.

8. 5. The method of claim 4, wherein the composition is a postbiotic composition derived from a liquid fermentation medium of the C. acnes microorganism.

9. 10. The method of claim 8, wherein the postbiotic composition is prepared by collecting the supernatant from centrifugation of the C. acnes microorganisms.

10. 5. The method of claim 4, wherein the composition further comprises at least one of a C. acnes biomimetic, a C. acnes culture, or a component thereof.

11. The method of claim 10, wherein the biomimetic produces a diffusible mediator involved in the induction of lipid production by keratinocytes.

12. the composition further comprises a prebiotic for use in at least one of preventing, ameliorating, or treating the skin condition in the subject; The prebiotic induces at least one of the growth or activity of C. acnes. The method of claim 4.

13. 13. The method of claim 12, wherein the prebiotic enhances the effect of C. acnes on lipid production by keratinocytes.

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