Novel skin care composition for treating atopic dermatitis

Abstract

The present invention relates generally to the field of skin care. More specifically, the present invention relates to a cosmetic or therapeutic skin care composition comprising at least one bacterial strain of the genus Staphylococcus selected from the group consisting of Staphylococcus epidermidis HAC26 and Staphylococcus warneri HAA333, which promotes skin health, or a culture supernatant of any one of these bacterial strains, and to a cosmetic or therapeutic skin care composition comprising at least one bacterial strain of the genus Staphylococcus selected from the group consisting of Staphylococcus epidermidis HAC26 and Staphylococcus warneri HAA333. The invention also provides a method of treating or preventing atopic dermatitis and / or rosacea by applying the skin care composition of the invention to an area of skin in need of treatment. The invention also relates to the use of the skin care composition of the invention for the treatment or prevention of atopic dermatitis and / or rosacea.

Description

[0001] The present invention relates generally to the field of skin care. More specifically, the present invention relates to a cosmetic or therapeutic skin care composition comprising at least one Staphylococcus strain selected from Staphylococcus epidermidis HAC26 and Staphylococcus warneri HAA333 that promotes skin health or a culture supernatant of any of these strains. The present invention also provides a method for treating or preventing atopic dermatitis and / or rosacea by applying the skin care composition of the present invention to an area of ​​skin in need of treatment. The present invention also relates to the use of the skin care composition of the present invention for treating or preventing atopic dermatitis and / or rosacea. Background Art

[0002] Atopic dermatitis, also known as atopic eczema or neurodermatitis, is a complex, multifactorial, chronic, relapsing inflammatory disorder of the skin. It is the result of an interaction of genetic and environmental factors as well as immune and structural disorders of the skin. The incidence of atopic dermatitis has increased dramatically in industrialized countries. Today, approximately 15-20% of children and 1-3% of adults worldwide are affected by the disease, placing a heavy burden on health care systems.

[0003] One of the hallmarks of atopic dermatitis is dysfunction of the skin barrier. Although an intact skin barrier protects the organism from water loss and prevents the penetration of harmful substances such as irritants, allergens and microorganisms, increased water loss is observed in the extremely dry skin that accompanies atopic dermatitis. It has been found that in patients with atopic dermatitis, the permeability barrier of the skin becomes leaky during the course of the disease, allowing allergens and microorganisms to penetrate it and enter the skin, thereby causing infection (Silverberg and Silverberg, 2015).

[0004] The barrier permeability function of the skin is mainly located in the epidermis. The epidermis of the skin consists of several layers that act as a barrier to prevent water loss and protect the body from foreign substances such as microorganisms and allergens. Filaggrin (FLAG), a protein that binds to keratin fibers in epithelial cells, has been found to play an important role in the skin barrier function. In the epidermis, FLG protein binds to other proteins and lipids to form a strong barrier that prevents microorganisms and allergens from entering deeper skin layers and minimizes transepidermal water loss (Sandilands et al., 2009). Mutations in the gene encoding this protein have been shown to be a major risk factor for atopic dermatitis (Sicherer and Leung, 2009; Ring et al., 2012; Brown and Irvine, 2008; Scharschmidt TC et al., 2009).

[0005] It has been hypothesized that downregulation of FLG may render the skin more susceptible to immune dysregulation, thereby further exacerbating the skin condition and exacerbating atopic dermatitis. The immune dysregulation that occurs during atopic dermatitis is characterized by a complex series of alterations involving interactions between antigen-presenting cells with IgE, T-cell activation, mast cell degranulation, keratinocytes, eosinophils, and a combination of immediate and cellular immune responses. Inflammatory dendritic epidermal cells constitute a unique population of dendritic cells that are predominantly present in atopic dermatitis and can induce a Th2 / Th1 allostatic switch, contributing to the chronic phase of atopic dermatitis (Miraglia del Giudice et al., 2006).

[0006] Furthermore, the microbiome of patients with atopic dermatitis has been reported to differ significantly from that of healthy subjects. It appears that part of the resident bacterial commensal flora is replaced by transient pathogenic species, particularly Staphylococcus aureus species. These species can colonize the skin and contribute to a worsening of the skin’s appearance. For example, S. aureus species, if present in excess, can lead to dry skin, eczema, or oily skin, all of which promote the development of atopic dermatitis. On skin already affected by atopic dermatitis, S. aureus species can significantly exacerbate adverse symptoms such as skin inflammation and itching.

[0007] Topical corticosteroids and calcineurin inhibitors have been the mainstay of treatment for atopic dermatitis over the past few decades. Potent corticosteroids are used only at the beginning of intensive treatment, as they promote a decrease in epidermal lipid formation and skin atrophy. On the other hand, calcineurin inhibitors, such as pimecrolimus, help restore the skin barrier. In cases where the skin is overcolonized with bacteria or fungi, infection-suppressing ointments are used. In cases of overcolonization with Staphylococcus aureus, antibiotics such as fusidic acid are often used. However, fusidic acid can cause serious side effects, such as liver damage and jaundice. In addition, pathogenic strains have developed resistance to fusidic acid (Dobie and Gray, 2004).

[0008] In view of the above, there is a considerable need for new treatment methods that are not accompanied by the above disadvantages. In particular, the new treatment methods should be highly effective, well tolerated, not prone to drug resistance and without side effects. The present invention is based on the discovery that naturally occurring Staphylococcus strains can be isolated that have high antimicrobial activity against Staphylococcus aureus (S. aureus) strains. Therefore, these strains are particularly useful as active agents for preventing or reducing the number of Staphylococcus aureus (S. aureus) cells on the skin of a subject, preferably a human subject. When applied to the skin in the form of a skin care composition, the Staphylococcus strains of the present invention can colonize the skin flora and can effectively eradicate Staphylococcus aureus (S. aureus) strains or reduce their abundance. Summary of the invention

[0009] In a first aspect, the present invention relates to a skin care composition for topical application to the skin comprising:

[0010] (a) Staphylococcus epidermidis strain HAC26 deposited with DSMZ under the accession number DSM 34117, and / or

[0011] (b) Staphylococcus warneri strain HAA333 deposited at DSMZ under the accession number DSM 34118,

[0012] Or a culture supernatant obtained from any of these strains. If a culture supernatant is used, the supernatant is preferably sterile filtered before being added to the skin care composition.

[0013] In one embodiment, the Staphylococcus epidermidis strain is present in the composition in a freeze-dried or spray-dried form. The Staphylococcus epidermidis strain is preferably present in a 10 4 -10 11 CFU / ml, preferably 10 7 -10 10 CFU / ml. The S. epidermidis strain may be present in the composition in an amount of at least 0.5% (w / v) of the skin care composition.

[0014] In another embodiment, the S. warneri strain is present in the composition in a freeze-dried or spray-dried form. The S. warneri strain is preferably present in a 10 4 -1011 CFU / ml, preferably 10 7 -10 10 CFU / ml. The S. warneri strain may be present in the composition in an amount of at least 0.5% (w / v) of the skin care composition.

[0015] In a particularly preferred embodiment, the skin care composition of the present invention comprises

[0016] (a) The amount is 10 4 -10 11 CFU / ml, preferably 10 7 -10 10 CFU / ml of Staphylococcus epidermidis strain HAC26, and / or

[0017] (b) The amount is 10 4 -10 11 CFU / ml, preferably 10 7 -10 10 CFU / ml of Staphylococcus warneri (S. warneri) strain HAA333.

[0018] In the composition, the two Staphylococcus strains are preferably present in approximately equal concentrations, ie the concentrations differ from each other by no more than 5% (w / v).

[0019] In one embodiment, the skin care composition further comprises one or more excipients, wherein the one or more excipients preferably include emollients, fillers, thickeners, solubilizers, antioxidants, preservatives, pH adjusters, binders, buffers, colorants, humectants, exfoliants, preservatives, plant extracts, essential oils or fragrances.

[0020] The skin care composition is preferably formulated as a gel, cream, ointment or lotion.

[0021] In a second aspect, the invention relates to a skin care composition for use in a method of treating atopic dermatitis and / or rosacea in a subject, reducing the number of Staphylococcus aureus (S. aureus) cells on the skin of a subject, and / or treating a skin infection in a subject.

[0022] In a third aspect, the present invention relates to the S. epidermidis strain HAC26 deposited at DSMZ under the accession number DSM 34117 or a culture supernatant obtained therefrom and the S. warneri strain HAA333 deposited at DSMZ under the accession number DSM 34118 or a culture supernatant obtained therefrom. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The results of skin moisture measurement at the location where coagulase-negative Staphylococcus was isolated are shown. The skin moisture data of the back, cheek, forearm and forehead skin of the test subjects are shown ( p ≤ 0.05, p ≤ 0.01, p ≤ 0.001, p ≤ 0.0001, unpaired Wilcoxon test).

[0024] Figure 2 The results of sebum content measurement at the location where coagulase-negative Staphylococci were isolated are shown. The sebum content data of the back, cheek, forearm and forehead skin of the test subjects are shown ( p ≤ 0.05, p ≤ 0.01, p ≤ 0.001, p ≤ 0.0001, unpaired Wilcoxon test).

[0025] Figure 3 Results of cell count measurements at locations where coagulase-negative Staphylococci were isolated are shown. Results of cell count measurements in CFU / cm2 of the back, cheek, forearm, and forehead skin of the test subjects are shown. 2 Cell count results based on the skin surface ( p ≤ 0.05, p ≤ 0.01, p ≤ 0.001, p ≤ 0.0001, unpaired Wilcoxon test).

[0026] Figure 4 Shown are the antimicrobial properties of S. epidermidis strain HAC26 and S. warneri strain HAA333 against S. aureus DSM799 as determined in a lawn plate test.

[0027] Figure 5Shown are the results of viability testing of S. epidermidis strain HAC26 and S. warneri strain HAA333 stored in freeze-dried form for up to 4 months in Formulations 1A and 1B described in Example 4 below. DETAILED DESCRIPTION

[0028] The present invention provides novel Staphylococcus strains isolated from natural environments, which show significant activity against Staphylococcus aureus strains, especially Staphylococcus aureus strains that appear on the skin with atopic dermatitis and rosacea. Specifically, the present invention provides Staphylococcus epidermidis strain HAC26 deposited in DSMZ on December 14, 2021 and obtained the deposit number DSM 34117 and Staphylococcus warneri strain HAA333 deposited in DSMZ on December 14, 2021 and obtained the deposit number DSM 34118. The present invention also relates to the culture supernatant of any of these strains.

[0029] Due to their ability to control and reduce the abundance of Staphylococcus aureus (S. aureus) strains on human skin, these strains or culture supernatants obtained from these strains can be used as active ingredients in cosmetic and pharmaceutical skin care compositions topically applied to skin containing an excess of one or more Staphylococcus aureus (S. aureus) strains. The activity of the strains of the present invention is based on the production and secretion of antibacterial compounds that are active against Staphylococcus aureus (S. aureus) strains. When these antibacterial compounds are secreted into the surrounding culture medium, the culture supernatant obtained from the strain can also be used. The culture supernatant used herein is a fraction of the cell culture medium used to culture the cells and in which the compounds secreted from the cultured cells are accumulated.

[0030] In the context of the present invention, S. epidermidis strain HAC26 or S. warneri strain HAA333 is considered active against S. aureus strains if it is active in the lawn assay described below. Cultures of S. epidermidis strain HAC26 or S. warneri strain HAA333 are prepared and incubated in CASO broth at 37°C overnight until the OD is 0. 600Then, 15 µl of the overnight culture was pipetted onto lawn plates of the corresponding S. aureus strain containing at least 4x10 5 CFU / plate. The S. epidermidis strain is active against the S. aureus strain if a zone of inhibition appears around the application site after incubation of the plates at 37°C for 24 hours.

[0031] Therefore, the present invention also provides a skin care composition for topical application to the skin, comprising:

[0032] (a) Staphylococcus epidermidis strain HAC26 deposited with DSMZ under the accession number DSM 34117, and / or

[0033] (b) Staphylococcus warneri strain HAA333 deposited with DSMZ under the accession number DSM 34118, and / or

[0034] (c) A culture supernatant obtained from any one of the above strains.

[0035] The S. epidermidis strain and / or the S. warneri strain may be present in the composition of the invention in a freeze-dried or spray-dried form. This means that the live bacteria have undergone a drying process that maintains their viability but minimizes their metabolic processes. In freeze-dried or spray-dried form, the bacteria can be stored for months or even years. Once they are applied to the skin, such as human skin, the metabolism of the bacteria is reactivated, thereby resuming growth. They multiply on the skin surface and replace pathogenic bacterial strains, thereby restoring a diverse, healthy and balanced skin microbiome.

[0036] In one embodiment, the S. epidermidis strain and / or the S. warneri strain are present in a spray-dried form. The principle of spray drying is based on dispersing a solution into fine droplets, which are then introduced into a stream of hot air. The solvent evaporates from the matrix droplets, leaving a dry product mass. Standard spray drying equipment can be used, such as a small spray dryer B-290 from Büchi Labortechnik GmbH (Essen, Germany) or a Mobile Minor™ spray dryer from GEA (Berlin, Germany). In another embodiment, the S. epidermidis strain and / or the S. warneri strain are present in a freeze-dried or lyophilized form. Freeze drying or lyophilization is a process that includes freezing a product, reducing pressure, and heating to allow the frozen water in the material to sublime. Various methods can be used to freeze the product. For example, freezing can be achieved by using a standard freezer or freezing bath. The product is cooled to below its triple point to ensure that sublimation occurs after heating. In order to prevent the formation of large crystals that could damage the structure of the product to be dried, freezing is performed rapidly. When the frozen water sublimates, about 95% of the water in the product is removed. Most materials can be dried to a residual moisture of 1-5%. Standard freeze drying equipment can be used, such as the Lyovac™ equipment from GEA (Berlin, Germany), the Gamma 2-20 freeze dryer LCM-1 from Christ (Osterode am Harz, Germany), or the Christ Martin™ Alpha 1-2 freeze dryer from FisherScientific GmbH (Schwerte, Germany).

[0037] Preferably, the Staphylococcus epidermidis (S. epidermidis) strain HAC26 is 1.0 x 10 4 -1.0 x 10 11 Colony forming units (CFU) / ml, more preferably 1.0 x 10 5 -1.0 x 10 10 CFU / ml, even more preferably 1.0 x10 7 -1.0 x 10 10 CFU / ml or 1.0 x 10 8 -1.0 x 10 9CFU / ml. For example, the S. epidermidis strain HAC26 may be present in the composition in an amount of at least 1.0 x 10 5 CFU / ml, preferably at least 1.0 x 10 6 CFU / ml, more preferably at least 1.0 x 10 7 CFU / ml, e.g. at least 1.0 x 10 8 CFU / ml, at least 1.0x 10 9 CFU / ml or at least 1.0 x 10 10 CFU / ml skin care composition. Particularly preferably, the Staphylococcus epidermidis (S. epidermidis) strain HAC26 is present in an amount of at least 1.0 x 10 10 CFU / ml, 2.0 x 10 10 CFU / ml, 3.0x 10 10 CFU / ml, 4.0 x 10 10 CFU / ml, 5.0 x 10 10 CFU / ml, 6.0 x 10 10 CFU / ml, 7.0 x 10 10 CFU / ml, 8.0 x 10 10 CFU / ml or 9.0 x 10 10 CFU / ml skin care composition.

[0038] In other words, the skin care composition of the present invention comprises at least 0.5% (w / v) of the S. epidermidis strain HAC26, measured by the total volume of the skin care composition. More preferably, the skin care composition of the present invention comprises at least 0.75% (w / v), at least 1.0% (w / v), at least 1.25% (w / v), at least 1.5% (w / v), at least 1.75% (w / v), at least 2.0% (w / v), at least 2.25% (w / v) or at least 2.5% (w / v) of the S. epidermidis strain HAC26, measured by the total volume of the skin care composition.

[0039] Likewise, preferably, the Staphylococcus warneri (S. warneri) strain HAA333 is 1.0 x 10 4 -1.0 x10 11 CFU / ml, more preferably 1.0 x 10 5 -1.0 x 10 10CFU / ml, even more preferably 1.0 x 10 7 -1.0 x 10 10 CFU / ml or 1.0 x 10 8 -1.0 x 10 9 CFU / ml. For example, the S. warneri strain HAA333 may be present in the composition in an amount of at least 1.0 x 10 5 CFU / m, preferably at least 1.0 x 10 6 CFU / ml, more preferably at least 1.0 x 10 7 CFU / ml, e.g. at least 1.0 x 10 8 CFU / ml, at least 1.0 x 10 9 CFU / ml or at least 1.0 x 10 10 CFU / ml skin care composition. Particularly preferably, the Staphylococcus warneri (S. warneri) strain HAA333 is present in an amount of at least 1.0 x 10 10 CFU / ml, 2.0 x 10 10 CFU / ml, 3.0 x 10 10 CFU / ml, 4.0 x 10 10 CFU / ml, 5.0 x 10 10 CFU / ml, 6.0 x 10 10 CFU / ml, 7.0 x 10 10 CFU / ml, 8.0 x10 10 CFU / ml or 9.0 x 10 10 CFU / ml skin care composition.

[0040] In other words, the skin care composition comprises at least 0.5% (w / v) of the Staphylococcus warneri (S. warneri) strain HAA333, based on the total volume of the skin care composition. More preferably, the skin care composition of the present invention comprises at least 0.75% (w / v), at least 1.0% (w / v), at least 1.25% (w / v), at least 1.5% (w / v), at least 1.75% (w / v), at least 2.0% (w / v), at least 2.25% (w / v) or at least 2.5% (w / v) of the Staphylococcus warneri (S. warneri) strain HAA333, based on the total volume of the skin care composition.

[0041] When both the S. epidermidis strain HAC26 and the S. warneri strain HAA333 are used in combination in the same skin care composition, each of the two strains is preferably present at 1.0 x 10 4 -1.0 x 10 11 CFU / ml, more preferably 1.0 x 10 5 -1.0 x 10 10 CFU / ml, even more preferably 1.0 x 10 7 -1.0 x 10 10 CFU / ml or 1.0 x 10 8 -1.0 x 10 9 CFU / ml. For example, each of the strains may be present in the composition at a concentration of at least 1.0 x 10 5 CFU / ml, preferably at least 1.0 x 10 6 CFU / ml, more preferably at least 1.0 x 10 7 CFU / ml, e.g. at least 1.0 x 10 8 CFU / ml, at least 1.0 x 10 9 CFU / ml or at least 1.0x 10 10 CFU / ml skin care composition. Particularly preferably, each of the strains is present in an amount of at least 1.0 x10 10 CFU / ml, 2.0 x 10 10 CFU / ml, 3.0 x 10 10 CFU / ml, 4.0 x 10 10 CFU / ml, 5.0 x 10 10 CFU / ml, 6.0 x 10 10 CFU / ml, 7.0 x 10 10 CFU / ml, 8.0 x 10 10 CFU / ml or 9.0 x 10 10 CFU / ml skin care composition.

[0042] In some embodiments, the total amount of freeze-dried or spray-dried bacteria in the composition is 1.0 x 10 4 -1.0 x 10 11 CFU / ml, more preferably 1.0 x 10 5 -1.0 x 10 10 CFU / ml, even more preferably 1.0 x 107 -1.0x 10 10 CFU / ml or 1.0 x 10 8 -1.0 x 10 9 CFU / ml. For example, the bacteria may be present in a total of at least 1.0 x 10 5 CFU / ml, preferably at least 1.0 x 10 6 CFU / ml, more preferably at least 1.0 x 10 7 CFU / ml, e.g. at least 1.0 x10 8 CFU / ml, at least 1.0 x 10 9 CFU / ml or at least 1.0 x 10 10 CFU / ml skin care composition. Particularly preferably, the bacteria are present in the composition in an amount of at least 1.0 x 10 10 CFU / ml, 2.0 x 10 10 CFU / ml, 3.0 x 10 10 CFU / ml, 4.0 x 10 10 CFU / ml, 5.0 x 10 10 CFU / ml, 6.0 x 10 10 CFU / ml, 7.0 x10 10 CFU / ml, 8.0 x 10 10 CFU / ml or 9.0 x 10 10 The amount of CFU / ml of skin care composition is present in said composition. One of ordinary skill in the art will be able to readily determine the amount of bacteria in a lyophilized or spray-dried composition.

[0043] When both S. epidermidis strain HAC26 and S. warneri strain HAA333 are used in combination in the same skin care composition, it is particularly preferred that both strains are present in the composition in approximately equal concentrations, ie the cell numbers differ from each other by no more than 10%.

[0044] In one embodiment, the culture supernatant of the culture of one or more strains of the present invention is added to the skin care composition of the present invention. Preferably, the culture supernatant is sterile filtered before being added to the skin care composition. For example, the culture supernatant can be sterile filtered by centrifuging an overnight culture at 8000 g for 10 min and then filtering the supernatant with a filter having a pore size of 0.2 μm.

[0045] The skin care composition of the present invention is formulated for topical application, which means that the composition is provided in a form that allows the consumer to distribute the composition after application to the skin. The skin care composition of the present invention can be formulated as a liquid, ointment, cream, scrub, lotion, paste, gel, hydrogel, foam or powder. However, it is preferably formulated as a gel, cream, ointment or lotion. The skin care composition can be formulated to be packaged in a pump dispenser that allows the liquid to be sprayed onto the skin area to be treated. The skin care composition of the present invention can also be incorporated into a patch applied to the skin.

[0046] The composition of the present invention may optionally include one or more excipients commonly used in cosmetic or pharmaceutical skin care products. For example, such excipients are described in detail in, for example, the International Cosmetic Ingredient Dictionary and Handbook, 16th edition (2016). For example, the one or more excipients may include emollients, exfoliants, moisturizers, pH adjusters, thickeners, solubilizers, antioxidants, preservatives, fillers, binders, buffers, colorants, essential oils, pigments, sunscreens, antimicrobial agents, chelating agents, vitamins, panthenol, ubiquinone Q10, hyaluronic acid, or any combination thereof.

[0047] For example, the skin care composition of the present invention may include an emollient. An emollient used herein is a compound that moisturizes and / or softens the skin. Emollients generally reduce the roughness, cracking and / or irritation of the skin by penetrating into the deeper layers of the skin. Emollients suitable for the skin care composition of the present invention include, but are not limited to, olive oil, palm oil, soybean oil, sesame oil, rapeseed oil, evening primrose oil, sunflower seed oil, avocado oil, olive oil, coconut oil, castor oil, safflower seed oil, myristyl lactate, isopropyl myristate, polyethylene glycol, isopropyl palmitate, isopropyl stearate, isobutyl palmitate, isocetyl stearate or cetyl alcohol. Preferably, the emollient is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 10% (w / w), preferably 0.1 to 10.0% (w / w), more preferably 1.0 to 10.0% (w / w), based on the gross weight of the composition. In another embodiment, the emollient is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 5.0% (w / w), preferably 0.1 to 5.0% (w / w), more preferably 1.0 to 5.0% (w / w), based on the total weight of the composition. The skin care composition of the present invention may also contain more than one emollient. In this case, the above amounts preferably refer to the total amount of emollients in the composition.

[0048] The skin care composition of the present invention may also contain an exfoliating compound. Exfoliating compounds are solids that provide a granular texture to the composition. When rubbed on the skin, these compounds eliminate old skin cells and enhance skin renewal. Exfoliating compounds that can be used in the composition of the present invention include, but are not limited to, urea, alpha-hydroxy acids and beta-hydroxy acids and their esters, anhydrides and salts. Suitable hydroxy acids include, for example, urea, glycolic acid, lactic acid, malic acid, mandelic acid, tartaric acid, citric acid, 2-hydroxyalkanoic acid, salicylic acid and its derivatives. The use of urea is particularly preferred because it also has additional hydration and enhances the absorption of other cosmetic ingredients. Preferably, the exfoliating compound is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 10% (w / w), preferably 0.1 to 10.0% (w / w), more preferably 1.0 to 10.0% (w / w), based on the total weight of the composition. In another embodiment, the exfoliating compound is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 5.0% (w / w), preferably 0.1 to 5.0% (w / w), more preferably 1.0 to 5.0% (w / w), based on the total weight of the composition. The skin care composition of the present invention may also contain more than one exfoliating compound. In this case, the above amount preferably refers to the total amount of exfoliating compounds in the composition.

[0049] The skin care composition of the present invention may also contain a moisturizer for improving the moisture content of the skin. Moisturizers suitable for the composition of the present invention include, but are not limited to, glycerol, polyethylene glycol ethers of glycerol, amino acids such as proline and arginine, sugars and sugar alcohols such as glucose, mannose, trehalose and polyglycerol sorbitol, 1,3-butylene glycol, propylene glycol, diglycerol, glycerol monopropoxylate, glycogen, sodium hyaluronate, sodium polyaspartate, sodium polyglutamate, sorbitol polyether 20, sorbitol polyether 6 and hydrogenated starch hydrolyzate. Preferably, the moisturizer is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 10% (w / w), preferably 0.1 to 10.0% (w / w), more preferably 1.0 to 10.0% (w / w), based on the total weight of the composition. In another embodiment, the moisturizer is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 5.0% (w / w), preferably 0.1 to 5.0% (w / w), more preferably 1.0 to 5.0% (w / w), based on the total weight of the composition. The skin care composition of the present invention may also contain more than one moisturizer. In this case, the above amount preferably refers to the total amount of moisturizer in the composition.

[0050] In a preferred embodiment, the skin care composition of the present invention comprises a compound that acts as a pH regulator. Since the composition of the present invention is used on human skin, it generally has a slightly acidic pH, making it more compatible with the acidic environment of the skin. The composition may have a pH in the range of about 2.5 to about 6.5, preferably about 4.0 to about 6.0, more preferably about 5.0 to about 6.0 or about 5.5 to about 6.0. The acidic pH may be achieved by adding an acid (e.g., a carboxylic acid such as an α-hydroxy acid) to the skin care composition of the present invention. There is no particular restriction on the nature of the acid that can be used in the composition of the present invention. Suitable acids include formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, heptanoic acid, caprylic acid, etc. In a particularly preferred embodiment, the composition comprises lactic acid as a pH regulator. Lactic acid is particularly useful for application to human skin because it is also secreted by skin flora to form a protective acidic environment on the surface of human skin. Preferably, the pH adjuster is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 10% (w / w), preferably 0.1 to 10.0% (w / w), more preferably 1.0 to 10.0% (w / w), based on the total weight of the composition. In another embodiment, the pH adjuster is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 5.0% (w / w), preferably 0.1 to 5.0% (w / w), more preferably 1.0 to 5.0% (w / w), based on the total weight of the composition. The skin care composition of the present invention may also contain more than one pH adjuster. In this case, the above amount preferably refers to the total amount of pH adjusters in the composition.

[0051] In a preferred embodiment, the skin care composition of the present invention comprises a thickener. A thickener is a compound that increases the viscosity of a cosmetic or pharmaceutical preparation. Thickeners are typically polymers that swell when exposed to water, thereby making the composition more viscous. Thickeners suitable for use in the skin care composition of the present invention include, but are not limited to, soy gum, xanthan gum, gelatin, carnauba wax, stearic acid, C. crispus extract, hydroxypropyl starch phosphate, and mixtures thereof. Preferably, the thickener is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 10% (w / w), preferably 0.1 to 10.0% (w / w), and more preferably 1.0 to 10.0% (w / w), based on the total weight of the composition. In another embodiment, the thickener is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 5.0% (w / w), preferably 0.1 to 5.0% (w / w), more preferably 1.0 to 5.0% (w / w), based on the total weight of the composition. The skin care composition of the present invention may also contain more than one thickener. In this case, the above amount preferably refers to the total amount of thickener in the composition.

[0052] In a preferred embodiment, the skin care composition of the present invention comprises a solubilizer. As used herein, a solubilizer is a compound that aids in the dissolution of hydrophobic substances in aqueous and alcoholic formulations. For example, a solubilizer can make the dissolution of aromatic oils and other hydrophobic substances (e.g., vitamins) in aqueous skin care compositions feasible. Suitable solubilizers for use in the skin care composition of the present invention include, but are not limited to, pentaerythritol tetraisostearate, polyglyceryl-4 caprate, polyglyceryl-3 cocoate, polyglyceryl-10 caprylate, and different poloxamers, such as poloxamer 188, 234, 235, 238, and 338. Preferably, the solubilizer is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 10% (w / w), preferably 0.1 to 10.0% (w / w), more preferably 1.0 to 10.0% (w / w), based on the total weight of the composition. In another embodiment, the solubilizer is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 5.0% (w / w), preferably 0.1 to 5.0% (w / w), more preferably 1.0 to 5.0% (w / w), based on the total weight of the composition. The skin care composition of the present invention may also contain more than one solubilizer. In this case, the above amount preferably refers to the total amount of solubilizer in the composition.

[0053] In a preferred embodiment, the skin care composition of the present invention comprises an antioxidant. These compounds are usually added to cosmetic or pharmaceutical preparations to prevent oxidation reactions catalyzed by oxygen free radicals, which would otherwise lead to the decomposition of ingredients such as proteins, sugars and lipids in the composition. Antioxidants commonly used in cosmetic products include chemicals such as butylated hydroxytoluene, butylated hydroxyanisole, tocopherol, tocopherol acetate and polyphenols, flavonoids, flavanols, stilbenes and terpenes of plant origin. Preferably, the antioxidant is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 10% (w / w), preferably 0.1 to 10.0% (w / w), more preferably 1.0 to 10.0% (w / w), based on the total weight of the composition. In another embodiment, the antioxidant is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 5.0% (w / w), preferably 0.1 to 5.0% (w / w), more preferably 1.0 to 5.0% (w / w), based on the total weight of the composition. The skin care composition of the present invention may also contain more than one antioxidant. In this case, the above amount preferably refers to the total amount of antioxidants in the composition.

[0054] In a preferred embodiment, the skin care composition of the present invention comprises a preservative. As used herein, a preservative is a compound added to a cosmetic or pharmaceutical preparation to prevent microbial spoilage of the preparation by inhibiting the growth of undesirable bacteria and yeasts. Preservatives commonly used in cosmetic preparations include benzyl alcohol, ethanol, phenoxyethanol, caprylyl glycol, salicylic acid, and sorbic acid, among others. Preferably, the preservative is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 10% (w / w), preferably 0.1 to 10.0% (w / w), and more preferably 1.0 to 10.0% (w / w), based on the total weight of the composition. In another embodiment, the preservative is present in the skin care composition of the present invention in an amount of 0.05% (w / w) to 5.0% (w / w), preferably 0.1 to 5.0% (w / w), and more preferably 1.0 to 5.0% (w / w), based on the total weight of the composition. The skin care composition of the present invention may also comprise more than one preservative. In this case, the above amounts preferably refer to the total amount of preservative in the composition.

[0055] Unless otherwise specifically stated, all percentages used herein are by weight of the skin care composition. Unless otherwise stated, all ratios are by weight.

[0056] The novel strains of the present invention, as well as the culture supernatants obtained from any of these strains, and skin care compositions comprising one or more of the strains or their culture supernatants can be used to modulate the skin microbiome, in particular to reduce the number of Staphylococcus aureus (S. aureus) cells on the skin of a subject. Therefore, the strains, culture supernatants and skin care compositions of the present invention are particularly useful for treating Staphylococcus aureus (S. aureus) skin infections and skin diseases characterized by an excess of Staphylococcus aureus (S. aureus) cells on the skin, such as atopic dermatitis and / or rosacea.

[0057] Therefore, in a preferred aspect, the present invention relates to S. epidermidis strain HAC26 or S. warneri strain HAA333 or a supernatant obtained from any of these strains or a combination of these strains or their culture supernatants or a skin care composition described above comprising one or more of these strains or their culture supernatants, for use in a method for reducing the number of S. aureus cells on the skin of a subject. The present invention also relates to the use of S. epidermidis strain HAC26 or S. warneri strain HAA333 or a supernatant obtained from any of these strains or a combination of these strains or their culture supernatants or a skin care composition described above, for reducing the number of S. aureus cells on the skin of a subject. The present invention also relates to a method for reducing the number of Staphylococcus aureus (S. aureus) cells on the skin of a subject, the method comprising applying to the skin of a subject in need thereof Staphylococcus epidermidis (S. epidermidis) strain HAC26 or Staphylococcus warneri (S. warneri) strain HAA333 or a supernatant obtained from any of these strains or a combination of these strains or their culture supernatants or a skin care composition as described above. Particularly preferably, the subject to be treated is a human being.

[0058] In another preferred aspect, the present invention relates to Staphylococcus epidermidis strain HAC26 or Staphylococcus warneri strain HAA333 or a culture supernatant obtained from any of these strains or a combination of these strains or their culture supernatants or a skin care composition described above comprising one or more of these strains or their culture supernatants, which is used in a method for treating Staphylococcus aureus (S. aureus) infection of the subject's skin. The present invention also relates to the use of Staphylococcus epidermidis strain HAC26 or Staphylococcus warneri strain HAA333 or a supernatant obtained from any of these strains or a combination of these strains or their culture supernatants or a skin care composition described above, which is used to treat Staphylococcus aureus (S. aureus) infection of the subject's skin. The present invention also relates to a method for treating a Staphylococcus aureus (S. aureus) infection of the skin of a subject, the method comprising applying to the skin of a subject in need thereof Staphylococcus epidermidis (S. epidermidis) strain HAC26 or Staphylococcus warneri (S. warneri) strain HAA333 or a supernatant obtained from any of these strains or a combination of these strains or their culture supernatants or a skin care composition as described above. Particularly preferably, the subject to be treated is a human being.

[0059] In another preferred aspect, the present invention relates to Staphylococcus epidermidis strain HAC26 or Staphylococcus warneri strain HAA333 or a supernatant obtained from any of these strains or a combination of these strains or their culture supernatants or a skin care composition described above comprising one or more of these strains or their culture supernatants, which is used in a method for treating atopic dermatitis and / or rosacea in a subject. The present invention also relates to the use of Staphylococcus epidermidis strain HAC26 or Staphylococcus warneri strain HAA333 or a supernatant obtained from any of these strains or a combination of these strains or their culture supernatants or a skin care composition described above, which is used to treat atopic dermatitis and / or rosacea in a subject. The present invention also relates to a method for treating atopic dermatitis and / or rosacea in a subject, the method comprising applying to the skin of a subject in need thereof Staphylococcus epidermidis strain HAC26 or Staphylococcus warneri strain HAA333 or a supernatant obtained from any of these strains or a combination of these strains or their culture supernatants or a skin care composition as described above. Particularly preferably, the subject to be treated is a human being.

[0060] The skin to be treated can include the skin of the face and body, such as the skin of the neck, chest, back, arms, hands, legs or thighs. According to a preferred embodiment, the skin treated with the composition of the present invention is facial skin. According to another preferred embodiment, the skin treated with the composition of the present invention is body skin.

[0061] The skin care composition can be applied to the skin area in need of treatment, such as the face or body, at least once a day, twice a day or even more frequently if necessary. When applied twice a day, the first and second applications are preferably separated by at least 6 hours, preferably 8 hours. Typically, the cosmetic composition is applied once in the morning and once in the evening. The composition of the present invention can be used for a long time without any adverse side effects. For example, the treatment duration can be at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 6 weeks, at least 12 weeks, at least 24 weeks or longer. In some embodiments, the treatment will extend for several months, such as 4 months, 6 months, 8 months, 12 months, 18 months or 24 months.

[0062] The skin care compositions of the present invention can be provided as ready-to-use compositions that allow for direct topical application to the skin. In such compositions, the lyophilized or spray-dried live bacteria will be present in admixture with other cosmetic or pharmaceutical excipients described elsewhere herein, such as emollients, fillers, etc. Upon application of these compositions to the skin, the dried bacteria will be reactivated on the skin of the subject to whom the product is applied. The growth of the bacteria reactivated from the skin care composition will have a positive impact on the microbial flora on the subject's skin.

[0063] These ready-to-use compositions are preferably stable at room temperature for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 14 weeks, at least 16 weeks, at least 18 weeks, at least 20 weeks, at least 22 weeks, at least 24 weeks, at least 26 weeks, at least 28 weeks or at least 30 weeks or more. When used herein, a composition is considered stable if the reduction in the number of CFUs present in the composition after storage is less than 3 log reductions, preferably less than 2 log reductions, more preferably less than 1 log reduction. In other words, a composition is considered stable if the number of CFUs present in the composition after storage is less than 1000-fold, preferably less than 100-fold, more preferably less than 10-fold relative to the number of CFUs in the composition before storage.

[0064] The skin care composition of the present invention can be optionally provided as a kit of parts, wherein the freeze-dried or spray-dried bacteria are spatially separated from other components (e.g., cosmetic or therapeutic components). For example, the kit of parts can take the form of a package with two spatially separated chambers, wherein the first chamber contains the freeze-dried or spray-dried bacteria and the second chamber contains a cosmetic preparation, such as an aqueous cosmetic preparation. Before use, the contents of the two chambers are mixed with each other by, for example, a consumer or a patient to provide a uniform skin care composition, which is then applied to the skin. The advantage of the kit of parts assembly is that the bacteria can be kept in a freeze-dried or spray-dried form before use, which is accompanied by a particularly high storage stability of the composition. In the kit of parts assembly, it is advantageous if the weight ratio of the bacteria in the first chamber to the cosmetic preparation (particularly aqueous cosmetic preparation) in the second chamber is 1:10 to 1:100, such as 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90 or 1:100. After the contents of the two chambers are mixed, the skin care composition preferably contains 1-10% by weight of the freeze-dried or spray-dried bacteria and 99-90% by weight of the cosmetic preparation, such as an aqueous cosmetic preparation. According to the present invention, the kit of parts can be provided in, for example, a Lyo-Ject® dual-chamber syringe, a V-LK® dual-chamber carpuel or a dual-chamber system. In another preferred embodiment, the freeze-dried or spray-dried bacteria in the first chamber can be suspended in a lipid or oil. This will greatly facilitate packaging and filling. In addition, the surrounding lipid or oil will protect the bacteria from premature rehydration. Preferably, the bacteria are suspended in ethylhexyl cocoate or dicaprylyl carbonate. The weight ratio of the bacteria to the oil or lipid is preferably between 1:1 and 1:2.

[0065] In one embodiment, the skin care composition of the present invention is an aqueous formulation, such as a gel. Aqueous formulations referred to herein encompass aqueous solutions as well as aqueous dispersions. In one embodiment, the skin care composition is an oil-in-water emulsion. If the skin care composition contains an oil phase, such as when an oil-in-water emulsion is used, preferably the oil phase contains triglycerides and / or octyldodecanol. In addition, the oil phase may contain one or more oils selected from lecithin, olive oil, sunflower oil, jojoba oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, castor oil, wheat germ oil, grape seed oil, safflower oil, evening primrose oil, macadamia oil, etc.

[0066] When used in the context of a method or composition, the term "comprising" means that in addition to the stated method steps or components, there may be other method steps or composition components. The use of the term "comprising" means inclusion rather than limitation. For example, a composition "comprising" components A+B may also include C as another component. Similarly, a method "comprising" steps (a) and (b) may also include (c) as another method step. In contrast, when used in the context of a method or composition, the term "consisting of" means that the method or composition does not include any other method steps or composition components that are not listed in the description of the corresponding composition or method. For example, a composition consisting of components A+B is limited to these two components and does not include any other components other than A and B. Similarly, a method consisting of steps (a) and (b) is a two-step method and does not include any other method steps other than (a) and (b). However, it should be understood that any method or composition described herein as "comprising" certain method steps or components may preferably consist essentially of the method steps or components recited, or more preferably consist of the method steps or components recited. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0067] Example

[0068] The following examples describe certain preferred embodiments of the present invention. It should be noted, however, that the present invention is not limited to such embodiments.

[0069] Example 1 : Sample acquisition and processing

[0070] As previously described (Ahle et al., 2020), swab samples were collected from the forehead, cheeks, back, and forearm skin of 30 volunteers (females, n = 14; males, n = 16) aged 22-43 years. Briefly, 25 cm of the forehead, cheeks, back, and forearm skin were swabbed with cotton swabs. 2 and 50 cm on the skin of the forearm 2The cotton swabs were pre-moistened in an aqueous sampling buffer containing disodium phosphate (12.49 g / L, Merck), potassium dihydrogen phosphate (0.63 g / L, Merck), and 1% Triton X-100 (Sigma) in the area of ​​​​the skin. The swabs were vigorously shaken in a test tube containing 2 mL of sampling buffer and then removed. The samples were stored at -20°C before DNA extraction. Skin water content and sebum content were measured using a Corneometer (Courage + Khazaka electronic) and a Sebumeter (Courage + Khazaka electronic), respectively. None of the volunteers had a history of skin diseases and had not received topical medications or antibiotics in the past six months. Written informed consent was obtained from all volunteers, and the study was approved by the International Medical & Dental Ethics Commission GmbH (IMDEC) of Freiburg (study number 67885).

[0071] The swab samples were diluted in 0.9% NaCl solution (back, cheek, forehead skin samples: 1:10 and 1:1000; forehead skin samples; 1:1 and 1:100). Culture was performed by plating on Columbia agar containing 5% sheep blood; the agar plates were incubated at 37°C for 24 h. CFU counts were determined using an automated colony counter (IUL). Up to five colonies similar to Staphylococcus were randomly picked from each plate based on colony size and color, and pure cultures were obtained by subculturing on the same agar. Each of the 572 isolates obtained was assigned to the species level by MALDI-TOF mass spectrometry.

[0072] Prior to DNA extraction, skin swab samples were centrifuged (8.000 g, 30 min at 4°C), and the supernatant was discarded. The precipitate was lysed using lysostaphin (0.05 mg / mL, Sigma) and lysozyme (9.5 mg / mL, Sigma). DNA was extracted using the DNeasy PowerSoil kit (QIAGEN) following the manufacturer's instructions. DNA concentration was measured with the Qubit dsDNA HS assay (ThermoFisher Scientific) using a Qubit fluorometer.

[0073] result: A total of 572 bacterial isolates were obtained by selective culture, of which 557 were identified as coagulase-negative staphylococci (CoNS) by MALDI-TOF mass spectrometry. In all skin sites, the majority of isolates were identified as S. epidermidis (n=374, 67.2%), followed by Staphylococcus hominis (n=86, 15.4%). S. epidermidis strains dominated the forehead, cheek, and back skin sites, followed by Staphylococcus capitis strains (relative abundances of 74.5% and 11.7%, respectively), while a larger number of S. hominis and Staphylococcus haemolyticus strains were isolated from the forearm skin site (relative abundances of 38.7% and 7.3%, respectively). The skin on the back and forehead has the highest water content (skin hydration) compared to the skin on the cheeks and forearms ( Figure 1 The forehead site showed the highest sebum content and number of Staphylococci per square centimeter (CFU), whereas the forearm skin site had particularly low sebum and Staphylococcus counts ( Figure 2 and 3 ).

[0074] Example 2 Antagonism plate assay

[0075] All 557 CoNS isolates were screened for antimicrobial properties against the indicator strain Staphylococcus aureus (S. aureus) DSM799 to identify bioactive Staphylococcal isolates. Therefore, bacterial lawn plates were prepared. Liquid cultures of Staphylococcus aureus (S. aureus) were prepared in CASO broth. For Staphylococci, the liquid culture was adjusted to an optical density of OD600nm = 0.002. 6 mL of the adjusted culture was pipetted onto rectangular tryptone soy agar (TSA) plates and evenly distributed. For round TSA plates, 3 mL of bacterial suspension was used. After 30 seconds, excess liquid was removed and the plates were dried for 4 h. The plates were stored at 4 °C for up to three weeks.

[0076] The isolates were cultured in 1 mL CASO broth in a 96-well deep-well plate with shaking at 37°C for 20 h. The 96-well deep-well plate was centrifuged at 2000 rpm for 5 min, 500 µL of supernatant was removed, and the pellet was resuspended in the remaining liquid. The concentrated bacterial culture was transferred to a 96-well U-bottom plate. The bacterial culture and supernatant were transferred to a rectangular lawn plate using a replica stamp. After drying for 4 h, the plates were incubated at 37°C for 24 h. The inhibition zone visible around the Staphylococcus colonies was considered to have antimicrobial activity. Staphylococcus strains that showed antimicrobial properties were validated in triplicate.

[0077] result : 4% (22 / 557) of the tested Staphylococcus isolates were observed to show activity against S. aureus. Of these 22 strains, S. epidermidis strain HAC26 and S. warneri strain HAA333 were found to have the highest antimicrobial activity against S. aureus. The results of the lawn plate assay for strains HAC26 and HAA333 are shown in Figure 4 Both test strains showed visible inhibition zones around strain colonies and S. aureus cell lawns compared to the control strain S. epidermidis ATCC 12228. In addition, inhibition of S. aureus could be observed when supernatants of the test strains were used.

[0078] Example 3 : Preparation of skin care compositions

[0079] Staphylococcus epidermidis strain HAC26 and Staphylococcus warneri strain HAA333 were incorporated into skin care compositions. To this end, lyophilized powders of Staphylococcus epidermidis HAC26 and Staphylococcus warneri HAA333 were prepared and mixed with the other ingredients shown below. The ingredients are listed in % (w / w).

[0080]

[0081] CFU= 10 10 / g

[0082] Example 4 : Preparation of two-component skin care compositions

[0083] Staphylococcus epidermidis strain HAC26 and Staphylococcus warneri strain HAA333 were incorporated into a two-component skin care composition. To this end, lyophilized powders of Staphylococcus epidermidis HAC26 and Staphylococcus warneri HAA333 were prepared and mixed with the other ingredients shown below. The ingredients are listed in % (w / w).

[0084]

[0085] CFU= 10 10 / g

[0086]

[0087] The survival rate of lyophilized strains formulated as Formulation 1A and Formulation 1B as shown in the table above was tested. Figure 5 As shown in , it was found that the strain was still viable even after 4 months of storage.

[0088] Then, just before applying the product, 25.96% of the bacteria-containing composition 1A or 1B was mixed with 74.04% of the carrier composition 2. The test product was applied once a day for 4 consecutive days to the 25 cm area on the palmar forearm of 12 volunteers. 2 The application rate was 2.12 mg test product / cm², 1 10 6 CFU / cm². A total of 53 mg of test product / 25 cm² was applied. Swab samples were obtained before application (baseline) and 24 h after the last application (day 5). DNA was extracted from the swab samples and analyzed for Staphylococcal composition by tuf sequencing as previously described (Ahle et al., 2021) with strain-specific primers and probes.

[0089] result : On the 5th day after applying the product consisting of formulations 1A and 2 in the above table to the skin, the HAC26 strain of Staphylococcus epidermidis could be specifically detected. Similarly, on the 5th day after applying the product consisting of formulations 1B and 2 in the above table to the skin, the HAA333 strain of Staphylococcus warneri could be specifically detected.

[0090] literature

[0091] Ahle CM et al., Staphylococcus saccharolyticus: An Overlooked Human Skin Colonizer, Microorganisms 2020, 8.

[0092] Ahle CM et al., Comparison of three amplicon sequencing approaches to determine taphylococcal populations on human skin, BMC Microbiol, 2021, 21(1):221.

[0093] Brown SJ, Irvine AD. Atopic eczema and the filaggrin story. Semin Cutan Med Surg. 2008; 27(2): 128-137.

[0094] Dobie D and Gray J. Fusidic acid resistance in Staphylococcus aureus. Arch Dis Child 2004; 89: 74–77.

[0095] Miraglia del Giudice et al., Immune dysregulation inatopic dermatitis, Allergy Asthma Proc, 2006; 27(6): 451-5.

[0096] Ring J et al. European Dermatology Forum (EDF); European Academy of Dermatology and Venereology (EADV); European Federation of Allergy (EFA); European Task Force on Atopic Dermatitis (ETFAD); European Society of Pediatric Dermatology (ESPD); Global Allergy and Asthma European Network (GA2LEN). Guidelines for treatment of atopic eczema (atopic dermatitis) part I. J Eur Acad Dermatol Venereol. 2012; 26(8):1045-1060.

[0097] Sandilands A et al. Filaggrin in the frontline: role in skin barrier function disease. J Cell Sci. 2009; 122(pt 9): 1285-1294.

[0098] Scharschmidt TC et al. Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens. J Allergy Clin Immunol. 2009; 124(3): 496-506,506.e1-e6.

[0099] Sicherer SC, Leung DY. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2008. J Allergy Clin Immunol. 2009; 123(2): 319-327.

[0100] Silverberg NB, Silverberg JI. Inside out or outside in: does atopic dermatitis disrupt barrier function or does disruption of barrier function trigger atopic dermatitis?. Cutis. 2015;96(6):359-361.

[0101]

[0102]

Claims

1. A skin care composition for topical application to the skin, comprising: (a) Staphylococcus epidermidis strain HAC26 deposited at DSMZ under the accession number DSM 34117, (b) Staphylococcus warneri strain HAA333 deposited with DSMZ under the accession number DSM 34118, and / or (c) A culture supernatant obtained from any of the strains described in (a) to (b).

2. The skin care composition according to claim 1, wherein the Staphylococcus epidermidis strain is present in the composition in a freeze-dried or spray-dried form.

3. A skin care composition according to claim 1 or 2, wherein the amount of the Staphylococcus epidermidis strain present in the composition is (a) 10 4 -10 11 CFU / ml, preferably 10 7 -10 10 CFU / ml of the skin care composition, and / or (b) at least 0.5% (w / v) of the skin care composition.

4. The skin care composition according to any one of claims 1 to 3, wherein the Staphylococcus warneri strain is present in the composition in a freeze-dried or spray-dried form.

5. The skin care composition according to claim 1 or 3, wherein the Staphylococcus warneri strain is present in the composition in an amount of (a) 10 4 -10 11 CFU / ml, preferably 10 7 -10 10 CFU / ml, or (b) at least 0.5% (w / v) of the skin care composition.

6. A skin care composition according to any one of claims 1 to 5, wherein the composition comprises (a) The amount is 10 4 -10 11 CFU / ml of Staphylococcus epidermidis strain HAC26, and (b) The amount is 10 4 -10 11 CFU / ml of Staphylococcus warneri strain HAA333.

7. The skin care composition according to any one of claims 1 to 6, wherein the composition further comprises one or more excipients.

8. The skin care composition of claim 7, wherein the one or more excipients comprise an emollient, a filler, a thickener, a solubilizer, an antioxidant, a preservative, a pH adjuster, a binder, a buffer, a colorant, a humectant, an exfoliant, a preservative, a plant extract, an essential oil, or a fragrance.

9. A skin care composition according to any one of claims 1 to 8, wherein the composition is in the form of a gel, cream, ointment or lotion.

10. A Staphylococcus epidermidis strain HAC26 deposited at DSMZ under the accession number DSM 34117, or a culture supernatant obtained from said strain.

11. A Staphylococcus warneri strain HAA333 deposited at DSMZ under the accession number DSM 34118 or a culture supernatant obtained from said strain.

12. A skin care composition according to any one of claims 1 to 9 or a bacterial strain or culture supernatant according to any one of claims 10 to 11 for use in a method of treating atopic dermatitis and / or rosacea in a subject.

13. A skin care composition according to any one of claims 1 to 19 or a bacterial strain or culture supernatant according to any one of claims 10 to 11 for use in a method of reducing the number of Staphylococcus aureus cells on the skin of a subject.

14. A skin care composition according to any one of claims 1 to 19 or a bacterial strain or culture supernatant according to any one of claims 10 to 11 for use in a method of treating a skin infection in a subject.

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