Propionibacterium acnes biomimetics, prebiotics, probiotic and metabiotic compositions for treatment of skin conditions

Abstract

Disclosed are biomimetic substances, prebiotics, probiotic and metabiotic compositions, and methods of their use. The biomimetic substance, prebiotic, probiotic and metabiotic compositions may include a bacterium of the genus Propionibacterium acnes (C. acnes), a culture thereof, and / or a component thereof; and / or a substance that induces the growth or activity of C. acnes. The biomimetic substance, prebiotic, probiotic and metabiotic compositions may be used to prevent, ameliorate and / or treat such conditions, such as atopic dermatitis.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This patent application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 63 / 443,595, filed on February 6, 2023, and U.S. Provisional Application No. 63 / 443,796, filed on February 7, 2023, each of which is incorporated herein by reference in its entirety. Technical Field

[0003] The present disclosure generally relates to biomimetic, prebiotic, probiotic, and postbiotic compositions and methods of using the same. More specifically, the present disclosure 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 may be used to prevent, improve, and / or treat skin conditions such as atopic dermatitis. Background Art

[0004] The skin is the largest organ of the human body and is colonized by microorganisms from different environments. Colonization is driven by the ecology of the skin surface, which is highly variable depending on the local anatomical location, endogenous host factors, and exogenous environmental factors. Known microorganisms, including bacteria, fungi, and viruses, colonize the skin. When infants are exposed to the maternal microflora and other environmental microorganisms, the human skin and gastrointestinal ("GI") tract are colonized by a wide variety of microorganisms starting at birth. From the time of initial colonization, the human microbiome remains in a state of flux, with the composition of the resident microflora changing over time in response to intrinsic and extrinsic factors of the host.

[0005] Human skin is constantly undergoing self-renewal, and in this process, resident microbial cells are shed. Most microorganisms present on the skin are harmless to healthy individuals. Some microorganisms are considered commensal organisms and confer health benefits to the skin by, for example, secreting antimicrobial substances, preventing pathogen colonization, and influencing the host immune response. On the other hand, if the physical barrier of the skin has been compromised due to trauma or injury, commensal microorganisms may cause disease and infection.

[0006] Atopic dermatitis is one of the most common chronic diseases in the human population. Atopic dermatitis is characterized by a constellation of clinical signs, the most important of which are pruritus and eczematous lesions, which can be acute, subacute, or chronic. Atopic dermatitis usually begins around three months of age, but sometimes begins in the first few weeks of life, while the skin's physical barrier undergoes structural and functional maturation. Atopic dermatitis progresses with alternating periods of relapse and remission. Depending on the child and the severity of the condition, atopic dermatitis can last from several months to several years, and a significant percentage will persist into adulthood.

[0007] Atopic dermatitis is first and foremost a chronic inflammatory skin disease that combines skin barrier damage and skin inflammation. In the first sensitization phase, skin barrier defects allow 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, along with the direct activation of epidermal alarmins such as IL-33, IL-25, and TSLP, leads to the activation of a Th2 response, which results in the production of inflammatory cytokines such as IL-4, IL-5, and IL-13.

[0008] Bacterial or viral superinfection of the skin is the most common complication throughout the active phase of the disease. The skin of patients with atopic dermatitis is highly susceptible to secondary infections, which often become more extensive. For example, the bacterium Staphylococcus aureus is a major cause of skin infections. It often colonizes the skin of patients with atopic dermatitis, whereas it only exists transiently on healthy skin. The bacterium then secretes virulence factors that further degrade barrier function, exacerbating the disease and contributing to its chronicity. Furthermore, S. aureus is often found in patients with atopic dermatitis, including in homogeneous biofilms that are resistant to host defenses and treatments.

[0009] There are currently several treatment options, with varying degrees of success. For example, "probiotics" are live microorganisms (usually bacteria) that, when used, typically provide health benefits by improving or restoring the microbiome. "Postbiotics" are soluble factors (metabolites or byproducts) 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. In in vitro studies, colloidal oatmeal compositions have been found to increase the growth of C. acnes. In infants at risk of developing atopic dermatitis, the use of emollients was associated with increased abundance and a trend toward higher bacterial diversity compared to not using emollients. Some studies have shown that the microbial abundance of baby baths and lotions is significantly greater than that of baths alone. Both the cleansing and cleansing and emollient regimens were well tolerated; throughout each regimen, the skin pH remained slightly acidic; a gentle baby bath + lotion routine helped improve microbial abundance, which can promote overall skin barrier health by providing a suitable environment for healthy skin microorganisms to thrive. Early initiation of daily use of specialized emollients up to 2 months of age has been shown to reduce the incidence of AD in high-risk infants between zero and one year of age.

[0010] However, there remains a long felt need for effective treatments to enhance the health of an individual's skin. The present disclosure provides compositions and methods for addressing this need. Summary of the Invention

[0011] This summary is provided in a simplified form to introduce some concepts that are further described in the detailed description below. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to aid in determining the scope of the claimed subject matter. Various examples of the present disclosure provide systems and methods as described herein.

[0012] The present disclosure includes methods of preventing, ameliorating, and / or treating a skin condition in a subject comprising administering to the subject Propionibacterium acnes (C. acnes), cultures thereof, and / or components thereof.

[0013] In one example, the present disclosure also includes a composition for preventing, improving, and / or treating a skin condition in a subject, wherein the composition comprises Propionibacterium acnes (C. acnes), a culture thereof, and / or a component thereof, and a pharmaceutically and / or cosmetically acceptable carrier.

[0014] 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 conditioning agent, a preservative, a sunscreen, a fragrance, and a combination of two or more thereof.

[0015] In some examples, the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid wash, soap bar, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

[0016] The present disclosure also relates to the use of Propionibacterium acnes (C. acnes), cultures thereof, and / or components thereof in cosmetic compositions, food compositions, or pharmaceutical compositions.

[0017] In some examples, the composition is a cosmetic composition or a pharmaceutical composition that can be used as a skin external preparation and can be applied directly to the affected area. For example, the composition can be prepared into various forms, such as ointments, creams, lotions, etc.

[0018] In some examples, the pharmaceutical composition can be absorbed in vivo by oral or parenteral administration, for example, it can be administered in non-limiting forms such as powder, granules, capsules, injections, and the like.

[0019] The cosmetic composition or pharmaceutical composition may be provided in various forms without departing from the scope of the present invention. Various examples are possible.

[0020] In some examples, the cosmetic composition can inhibit or improve atopic dermatitis, other inflammatory skin diseases, or dry skin conditions.

[0021] 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, alopecia with folliculitis, deep impetigo, mastitis, folliculitis, etc.

[0022] Other technical features may be apparent to those skilled in the art from the following drawings, embodiments and claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 is a graph showing the effects of different concentrations of pure culture medium and conditioned culture medium on normal human epidermal keratinocytes (NHEK) after 24 hours of treatment using a viability test (MTT);

[0024] Figure 2 is a graph showing the effects of different concentrations of pure culture medium and conditioned culture medium on NHEK after 6 days of treatment using a viability test (MTT);

[0025] Figure 3 is a diagram showing the steps taken to prepare and collect samples for transcriptomic analysis;

[0026] Figure 4Ais a graph showing gene set enrichment analysis (ie, genes up-regulated and genes down-regulated) of 5% RCM C. acnes conditioned broth;

[0027] Figure 4B is a graph showing gene set enrichment analysis of 10% RCM C. acnes conditioned medium;

[0028] Figure 4C is a graph showing gene set enrichment analysis of 20% RCM C. acnes conditioned broth;

[0029] Figure 5 is a graph showing the effects of untreated control, 10 ug / ml adiponectin, and different concentrations of C. acnes conditioned medium on total lipids in NHEKs after 6 days of treatment;

[0030] Figure 6A are fluorescence microscopy images showing the effects of untreated controls after 6 days;

[0031] Figure 6B is a fluorescence microscopy image showing the effect of 10 ug / ml adiponectin on total lipids of NHEK after 6 days;

[0032] Figure 6C are fluorescence microscopy images showing the effect of 0.1% C. acnes conditioned medium on total lipids in NHEKs after 6 days;

[0033] Figure 6D are fluorescence microscopy images showing the effect of 0.5% C. acnes conditioned medium on total lipids in NHEKs after 6 days;

[0034] Figure 6E are fluorescence microscopy images showing the effect of 1.0% C. acnes conditioned medium on total lipids in NHEKs after 6 days;

[0035] Figure 7 is a graph showing the effects of untreated control, different concentrations of broth (non-conditioned C. acnes medium), different concentrations of C. acnes conditioned medium, and 10 ug / ml of adiponectin on total lipids in NHEKs after 1 day of treatment;

[0036] Figure 8A are fluorescence microscopy images showing the effects of untreated controls after one day;

[0037] Figure 8B are fluorescence microscopy images showing the effect of 5% broth on total lipids of NHEK after 1 day of treatment;

[0038] Figure 8Care fluorescence microscopy images showing the effect of 10% broth on total lipids of NHEK after 1 day of treatment;

[0039] Figure 8D are fluorescence microscopy images showing the effect of 5% C. acnes conditioned medium on total lipids of NHEKs after 1 day of treatment;

[0040] Figure 8E are fluorescence microscopy images showing the effect of 10% C. acnes conditioned medium on total lipids of NHEKs after 1 day of treatment;

[0041] Figure 8F is a fluorescence microscopy image showing the effect of 10 ug / ml adiponectin on total lipids of NHEK after 1 day of treatment;

[0042] Figure 9 Shown are principal component analysis (PCA) scores for lipidomic analysis of NHEK samples collected under various test conditions;

[0043] Figure 10 shows principal component analysis (PCA) scores for lipidomic analysis of NHEK samples collected at different time points after exposure to various test conditions; and

[0044] Figure 11 is a table showing lipid classes from lipidomic analysis of NHEK samples showing statistically significant differences between exposure to C. acnes conditioned media and untreated controls (for samples collected on days 2 and 3). DETAILED DESCRIPTION

[0045] Hereinafter, the present disclosure will be described by the following examples and the like to more specifically describe the present disclosure. 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 interpreted as being limited to the following examples. In order to facilitate a specific understanding of the present disclosure, the examples of the present disclosure are exemplarily provided.

[0046] Various embodiments and examples will be described in detail with reference to the accompanying drawings. Wherever possible, the same reference numerals will be used throughout the drawings to refer to the same or similar components. References made throughout this disclosure to specific examples and embodiments are provided for illustrative purposes only and are not intended to limit all examples unless otherwise indicated.

[0047] As used herein, unless the context clearly indicates otherwise, the singular forms "a", "an" and "the" include plural references. Thus, for example, reference to "a reagent" includes one or more such different reagents, and reference to "the method" includes reference to the same steps and methods known to those of ordinary skill in the art that can modify or replace the methods described herein. Unless otherwise indicated, the term "at least" before a series of elements should be understood to refer to each element in the series. Those skilled in the art will recognize or will be able to determine multiple equivalents of the specific examples disclosed herein using only routine experiments. Such equivalents are intended to be encompassed by the present disclosure.

[0048] 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.

[0049] As used herein, the term "and / or" includes the meaning of "and," "or," and "all or any other combination of elements connected by the terms." A "biomimetic substance" is (1) a substance synthesized by artificial means; and (2) a natural substance that mimics a 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 care formulations. Di Lorenzo et al., Biomimetic endorphin for wrinkle lifting in a daily cosmetic remedy, Dermatol Res Skin Care. 2022; 6(2): 106, discloses biomimetic peptides for cosmetic use. U.S. Patent No. 6,544,401 to Henceforth Hibernia, Inc. discloses biomimetic aqueous solutions and their use in health and beauty products.

[0050] Throughout this specification and the claims that follow, unless the context requires otherwise, the word "comprise" and variations such as "include" and "comprising" will be understood to imply the inclusion of a stated 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. When used herein, the term "comprise" may be replaced with the term "contains" or "includes," or sometimes as used herein, with the term "having."

[0051] "Conditioned medium" is medium containing biologically active components, including metabolites, obtained from previously cultured cells or tissues that have released substances into the medium that affect certain cellular functions (eg, growth, lysis).

[0052] The “culture” includes (1) a total culture medium containing a strain, a strain extract, its metabolites, additional nutrients, etc., which is obtained by culturing the strain in a culture medium capable of supplying nutrients for a certain period of time so that the strain can grow and survive, and (2) a solution in which the strain is eliminated after culturing the strain. The culture of the composition of the present disclosure can use a culture medium that can be easily selected by those skilled in the art among the culture media for microbial culture according to the purpose, and preferably, it can use a culture medium for Propionibacterium culture, and more preferably, it can use RCM (Reinforced Clostridium Medium) medium, TSB (Tryptic soy broth) or BHI (Brain Heart Infusion) medium, but is not limited to the above culture media.

[0053] "Diffusible mediators" are agents released locally or carried in the blood or interstitial fluids that may participate in initiating, maintaining, or exacerbating biological processes.

[0054] "Gene Set Enrichment Analysis" (GSEA) is a computational method that determines whether a priori defined gene sets show statistically significant consistent differences between two biological states.

[0055] The "MTT assay" is a colorimetric assay used to assess cellular metabolic activity. Under defined conditions, NAD(P)H-dependent cellular oxidoreductases can reflect the number of viable cells present. These enzymes are able to 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. It has also been found that MTT is reduced to formazan in lipid cell structures without the involvement of obvious oxidoreductases.

[0056] Principal Component Analysis (PCA) is a technique used to reduce the dimensionality of large datasets to improve interpretability.

[0057] Example

[0058] In clinical studies, the present inventors found that Propionibacterium acnes (C. acnes) was 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), 469-479, 2021). To test the existence of a causal relationship that could explain this observation, it was hypothesized that C. acnes stimulates lipid production in keratinocytes through diffusible mediators. To test this hypothesis, three supplementation types of experiments were performed, which involved treating human keratinocytes with C. acnes conditioned medium at non-cytotoxic concentrations. Transcriptomic analysis of the treated keratinocytes was performed to test whether genes related to lipid metabolism were upregulated, fluorescence assays using lipid staining were performed to observe whether there was intracellular lipid accumulation, and lipidomic analysis of the treated keratinocytes was performed to test whether there were dose- and time-dependent effects.

[0059] First, a cytotoxicity test was performed. C. acnes (ATCC 6919) was cultured in RCM broth, Biomerieux (Craponne, France) at a concentration of 2.03 × 10 9 CFU were cultured. After centrifugation and filtration of the RCM broth to eliminate viable bacteria, the "conditioned medium = conditioned broth" frozen at -80°C was separated for further testing on normal human epidermal keratinocytes (NHEK). Viability tests were performed on NHEK to determine the non-cytotoxic concentration.

[0060] Transcriptomic analysis was then performed. For example, MTT assays 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 concentration tested, while the correct concentration for C. acnes-conditioned broth depended on the duration of treatment. The cytotoxic effects observed with conditioned broth demonstrated that C. acnes releases virulence factors.

[0061] The NHEK of differentiation is treated with RCM broth (non-conditioned medium) and C.acnes conditioned medium (conditioned medium) at a concentration of 0, 5%, 10% and 20% for 1 day. Experiment is carried out using a replicate experiment / condition. After rinsing with PBS, harvest NHEK, use 0.05% trypsin to separate cells at 37°C, and add 10% calf serum in DMEM for trypsin neutralization (Lonza, Verviers Belgium, for all reagents). The cells are centrifuged, the supernatant is removed, and replaced with the RLT buffer (Qiagen, Courtaboeuf France) supplemented with 1% β-mercaptoethanol (Sigma-Aldrich, St Quentin Fallavier, France). RNA is extracted using Qiacube HT extractor and its specific reagent and protocol (Qiagen, Courtaboeuf, France). RNA aliquots are sent to Genex (Longjumeau, France) for transcriptomic analysis. It was observed that, independently of the concentration of the conditioned medium, genes involved in DNA replication were downregulated, ie the cells reduced their turnover, and genes involved in lipid production were upregulated.

[0062] Fluorescence assays were then used to assess lipid accumulation. Specifically, NHEKs were treated with conditioned medium at concentrations of 0.1%, 0.5%, 1%, and 2% for 6 days, based on the results of transcriptomic analysis. Adiponectin (Sigma, St Quentin Fallavier, France), 10 μg / ml, known to induce lipid production in cell culture, was used as a positive control. To quantify and visualize total lipids after 6 days of treatment, AdipoRed was used. TM The cells were treated with AdipoRed ELISA reagent (Lonza, Verviers, Belgium). TM The assay reagent is a lipophilic reagent that emits fluorescence (excitation: 485 nm, emission: 572 nm). Fluorescence intensity is proportional to lipid concentration and can be measured using a spectrophotometer (Envision, Perlin Elmer, Villebon-sur-Yvette, France). Images are acquired at a magnification of x 20 using a fluorescence microscope (Axio Imager, ZEISS, Rueil Malmaison France).

[0063] Adiponectin induced an increase in fluorescence signal (+25%) after 6 days of treatment, which validated the test. Conditioned medium tested at 0.1% (non-toxic concentration) also showed an increased fluorescence signal (+29%) compared to untreated controls. Fluorescence microscopy images also showed that treatment with 0.1% and 0.5% conditioned medium increased intracellular fluorescence on day 6 compared to untreated controls. The experiment was repeated, increasing the concentration of conditioned medium to 5% and 10% and reducing the treatment time to 1 day. 5% and 10% non-conditioned medium were also tested as negative controls, and adiponectin (10 μg / ml) was used as a positive control.

[0064] Compared to the untreated control, the fluorescence intensity values ​​measured by spectrophotometer increased significantly by +181% and +206% for 5% and 10% conditioned medium, respectively. 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.

[0065] Lipidomics analysis was used to further understand the types of lipids produced by keratinocytes treated with C. acnes conditioned medium, as well as to investigate whether there were dose-dependent and time-dependent effects. NHEKs were treated with RCM (non-conditioned) broth and 0%, 5% and 10% C. acnes conditioned medium (3 replicates / condition) for 1 day. Adiponectin at 10 μg / ml was used as a positive reference. Keratinocytes were dissociated using PBS (rinsing), trypsin (cell separation) and DMEM supplemented with 10% calf serum (trypsin neutralization). After centrifugation, the supernatant was removed and PBS was added to obtain a suspension of 3000 cells / μl.

[0066] 300 μl of these suspensions were sent to Lipotype GmbH (Dresden, Germany) for lipid analysis. Principal component analysis (PCA) scores based on lipid class showed clustering of the tested conditions, and cells treated with only broth changed their lipid profiles compared to untreated controls. Cells treated with conditioned broth had significantly different lipid profiles compared to cells that were untreated or not treated with conditioned broth. At higher concentrations, the distance from the untreated cluster was greater, indicating a dose-dependent effect.

[0067] In another experiment, NHEK were treated with RCM (non-conditioned) broth and 0% and 10% C. acnes conditioned broth (3 replicates / 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 described above. Following the same procedure for lipidomic analysis, in the PCA plot, it can be seen that the lipid profile shifted away from the untreated control in a time-dependent manner.

[0068] The lipid classes induced in keratinocytes were further examined by conditioned medium treatment. The results are summarized in e.g. Figure 11 In the table shown, the ten most significant lipid species are shown. Specifically, comparisons were made between i) day 2 conditioned medium and day 2 untreated controls, and ii) day 3 conditioned medium and day 3 untreated controls.

[0069] As shown herein, it was concluded that treatment of normal human epidermal keratinocytes with C. acnes-conditioned medium produced interesting and unexpected results relative to untreated controls. These results included upregulation of genes involved in lipid metabolism, increased fluorescence values ​​indicating enhanced lipid production, confirmation of intracellular lipid accumulation by fluorescence microscopy images, dose-dependent effects in lipid composition analysis, and time-dependent effects in lipid composition analysis. Thus, these results demonstrate that C. acnes stimulates lipid production in human keratinocytes via a diffusible mediator.

[0070] Any suitable carrier can be used in one or more compositions described herein. In some examples, 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, without undue toxicity, incompatibility, instability, irritation, allergic response, and the like. A safe and effective amount of the carrier is from about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 98% to about 85%, 90%, 95%, 98%, 99%, 99.1%, 99.5%, or 99.9% by weight of the composition.

[0071] The carrier can exist in a wide variety of forms. For example, carriers in the form of emulsions, including but not limited to oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone emulsions, can be used herein. These emulsions can cover a wide range of viscosities, for example, from about 100 cps to about 200,000 cps using a Brookfield RVT viscometer.

[0072] Examples of suitable cosmetically acceptable carriers include cosmetically acceptable solvents and materials suitable for cosmetic solutions, suspensions, lotions, creams, serums, essences, gels, toners, sticks, sprays, ointments, liquid washes and bars, shampoos, hair conditioners, pastes, foams, mousses, powders, shaving creams, wipes, patches, strips, super patches, microneedle patches, bandages, hydrogels, film-forming products, facial and skin masks, foundations, drops, etc. These product types may contain 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, and the like.

[0073] The following are non-limiting examples of carriers. Other carriers can be formulated by one of ordinary skill in the art. In one example, the carrier comprises water. In another example, the carrier may further comprise one or more aqueous solvents or organic solvents. Examples of organic solvents include, but are not limited to, dimethyl isosorbide; isopropyl myristate; surfactants of cationic, anionic, and nonionic nature; vegetable oils; mineral oils; waxes; gums; synthetic and natural gelling agents; alkanols; glycols; and polyols. Examples of glycols include, but are not limited to, glycerol, propylene glycol, butylene glycol, pentanediol, hexylene glycol, polyethylene glycol, polypropylene glycol, diethylene glycol, triethylene glycol, octanediol, glycerol, butylene glycol, and hexanetriol, and copolymers or mixtures thereof. Examples of alkanols include, but are not limited to, alkanols 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 isopropyl alcohol and ethanol. The example of polyol includes but is not limited to polyols with about 2 carbon atoms to about 15 carbon atoms (for example, about 2 carbon atoms to about 10 carbon atoms), such as propylene glycol. Based on the gross weight of the carrier, the organic solvent can be present in the carrier in an amount of about 1% to about 99.99% (for example, about 20% to about 50%). Based on the gross weight of the carrier, water can be present in the carrier (before use) in an amount of about 5% to about 95% (for example, about 50% to about 90%). The solution can include any suitable amount of solvent, including about 40% to about 99.99%. Some solutions contain 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 99% solvent.

[0074] Lotions can be prepared from such solutions. In addition to the solvent, the lotion typically comprises at least one emollient. The lotion can comprise from about 1% to about 20% (e.g., from about 5% to about 10%) of the emollient and from about 50% to about 90% (e.g., from about 60% to about 80%) of water.

[0075] Another type of product that can be formulated from a solution is a cream. Creams typically contain from about 5% to about 50% (e.g., from about 10% to about 20%) of an emollient and from about 45% to about 85% (e.g., from about 50% to about 75%) of water.

[0076] Another type of product that can also be formulated from a solution is an ointment. Ointments can contain animal, vegetable, or synthetic oils or a simple base of semisolid hydrocarbons. Ointments can contain from about 2% to about 10% of an emollient and from about 0.1% to about 2% of a thickener.

[0077] The compositions useful in the present disclosure can also be formulated as emulsions. If the carrier is an emulsion, about 1% to about 10% (e.g., about 2% to about 5%) of the carrier comprises an emulsifier. The emulsifier can be nonionic, anionic, or cationic.

[0078] Lotions and creams can be formulated as emulsions. Typically such lotions contain 0.5% to about 5% emulsifier, while such creams will typically contain about 1% to about 20% (e.g., about 5% to about 10%) of an emollient; about 20% to about 80% (e.g., 30% to about 70%) of water; and about 1% to about 10% (e.g., about 2% to about 5%) of an emulsifier.

[0079] Oil-in-water and water-in-oil single-phase emulsion skin care formulations (such as lotions and creams) are well known in the art and can be used in the present disclosure. Multiphase emulsion compositions (such as water-in-oil-in-water or oil-in-water-in-oil) can also be used in the present disclosure. Generally speaking, such single or multiphase emulsions contain water, an emollient, and an emulsifier as the main ingredients.

[0080] The compositions of the present disclosure may also be formulated as gels (e.g., aqueous gels, alcohol gels, alcohol / hydrogels, or oleogels, using suitable gelling agents). Suitable gelling agents for aqueous and / or alcohol gels include, but are not limited to, natural gums, acrylic acid and acrylate polymers and copolymers, and cellulose derivatives (e.g., hydroxymethyl cellulose and hydroxypropyl cellulose). 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 5% by weight of such gelling agents.

[0081] The compositions of the present disclosure may also be formulated into solid formulations (e.g., wax-based sticks, soap bar compositions, powders, or wipes). The compositions of the present disclosure may also be combined with solid, semi-solid, or dissolvable substrates (e.g., wipes, masks, pads, gloves, or strips).

[0082] Other additives

[0083] The compositions of the present disclosure may also include any of a variety of additional cosmetic active agents. Examples of suitable additional active agents include: skin lightening agents, darkening agents, additional anti-aging agents, tropoelastin promoters, collagen promoters, anti-acne agents, oil-control agents, antimicrobial agents (such as anti-yeast agents, antifungals, and antibacterial agents), anti-inflammatory agents, antiparasitic agents, topical analgesics, sunscreens, light protectants, antioxidants, keratolytics, detergents / surfactants, moisturizers, nutrients, vitamins, energy enhancers, antiperspirants, astringents, deodorants, depilatories, hair growth enhancers, hair growth retarders, curing agents, hydrating agents, synergists, anti-sclerosis agents, skin conditioning agents, anti-cellulite agents, odor control agents such as odor masking agents or pH regulators, etc.

[0084] Examples of various suitable additional cosmetically acceptable actives include hydroxy acids; benzoyl peroxide; D-panthenol; UV filters such as, but not limited to, avobenzone (Parsol 1789), disodium phenyldibenzimidazole tetrasulfonate (Neo Heliopan AP), diethylaminohydroxybenzoyl hexyl benzoate (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), triethanolamine salicylate, bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), dibenzophenone 1–12, dihydroxybenzone, drometrizole trialkoxyethane (Mexoryl XL), diethylhexyl butamido triazone (UvasorbHEB), octocrylene, oxybenzone (Eusolex 4360), sulisophenone, methylene dibenzotriazole tetramethylbutylphenol (Tinosorb M), titanium dioxide, zinc oxide; carotenoids; free radical scavengers; spin traps; retinoids and vitamin A precursors, such as retinol / retinoic acid and retinyl palmitate; ceramides; polyunsaturated fatty acids; essential fatty acids; enzymes; enzyme inhibitors; minerals; hormones, such as estrogens; steroids, for example, hydrocortisone; 2-dimethylaminoethanol; copper salts such as copper chloride; copper-containing peptides, such as Cu:Gly-His-Lys, coenzyme Q10; amino acids, such as proline; vitamins; lactobionic acid; acetyl-CoA; niacin; riboflavin; thiamine; ribose; electron transport proteins, such as NADH and FADH2; and other plant extracts, such as oat, aloe, agrimony, soy, shiitake mushroom extracts, and their derivatives and mixtures.

[0085] If present, any additional cosmetic active agent can be present in the composition in any suitable amount, for example, from about 0.0001% to about 20%, for example from about 0.001% to about 10%, such as from about 0.01% to about 5%, by weight of the composition. In some examples, the amount is from 0.1% to 5%, and in other examples, from 1% to 2%.

[0086] The compositions of the present disclosure may contain 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" commercially available from Sigma-Aldrich, St. Louis, Missouri), tetrahydrocurcumin (such as tetrahydrocurcumin CG commercially available from Sabinsa Corporation, Piscataway, NJ), extracts and materials obtained from: Phellodendronamurense cortex extract (PCE), non-denatured soy (Glycine max), feverfew (Tanacetum parthenium), ginger (Zingiber officinale), Ginkgo biloba, madecassoside (a component of Centella asiatica extract), Cotinus coggygria, butterbur extract (Petasites truncatula), and safflower extract (Safflower oil). hybridus), goji berry (Lycium barbarum), milk thistle extract (Silybum marianum), honeysuckle (Lonicerajaponica), Peruvian balsam (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), Lifenol (hops: Humulus lupulus) extract, Bugrane P (Ononis spinosa), licorice chalcone (ingredient of licorice: Glycyrrhiza inflate extract), Symrelief (bisabolol and ginger extract), combinations of two or more thereof, and the like.

[0087] In one example, the anti-inflammatory agent is resorcinol. Particularly suitable substituted resorcinols include 4-hexylresorcinol and 4-octylresorcinol, particularly 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).

[0088] By "extract of feverfew" is meant an extract of the plant "feverfew," such as may be prepared 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." A particularly suitable feverfew extract is commercially available from Integrated Botanical Technologies, Inc. (Ossining, NY) at approximately 20% active feverfew.

[0089] Many other substances may also be present in the compositions of the present disclosure. In one or more examples, the composition comprises one or more topical ingredients selected from the group consisting of surfactants, chelating agents, emollients, humectants, conditioning agents, preservatives, sunscreens, fragrances, and the like.

Claims

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

2. The method of claim 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.

6. The method of claim 5, wherein the postbiotic composition is prepared by collecting the supernatant from the centrifugation of the C. acnes microorganism.

7. The method of claim 1, wherein the composition further comprises at least one of a biomimetic substance of C. acnes, a culture of C. acnes, or a component thereof.

8. The method of claim 7, wherein the biomimetic substance produces a diffusible medium responsible for inducing lipid production by keratinocytes.

9. The method according to claim 1, wherein: The composition further comprises a prebiotic for at least one of preventing, improving or treating a skin condition of the subject, and The prebiotic induces at least one of the growth or activity of C. acnes.

10. The method of claim 9, wherein the prebiotic enhances the effect of C. acnes on lipid production by keratinocytes.

11. A composition for at least one of preventing, improving, or treating a skin condition of a subject, the composition comprising: at least one of Propionibacterium acnes (C. acnes), a culture of C. acnes, or a component thereof; and Pharmaceutically and / or cosmetically acceptable carrier.

12. The composition of claim 1, further comprising a material selected from the group consisting of surfactants, chelating agents, emollients, moisturizers, conditioners, preservatives, sunscreens, fragrances, 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 wash, soap bar, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

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