New skin care composition

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 a combination of live bacteria of at least one strain of Propionibacterium acnes (C.acnes) and an emollient, wherein the emollient specifically supports the viability of the bacteria during storage and / or their ability to replicate after application to the skin. Preferably, the cosmetic or therapeutic skin care composition comprises bacteria of at least one strain of Propionibacterium acnes selected from D1, A5, C1, C3, H1, H2, H3, K1, K2, K4, K6, K8, K9, L1 and F4. The present invention also provides a method for treating or preventing acne by applying the skin care composition of the present invention to a skin area 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 acne.

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 a combination of live bacteria of at least one strain of Propionibacterium acnes (C.acnes) and an emollient, wherein the emollient specifically supports the viability of the strain during storage and / or their ability to replicate after application to the skin. Preferably, the cosmetic or therapeutic skin care composition comprises bacteria of at least one strain of Propionibacterium acnes selected from D1, A5, C1, C3, H1, H2, H3, K1, K2, K4, K6, K8, K9, L1 and F4. The present invention also provides a method for treating or preventing acne by applying the skin care composition of the present invention to a skin area 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 acne. Background Art

[0002] Acne vulgaris is a widespread, long-term skin condition that affects more than 600 million people worldwide. Acne is most common among teenagers, although it affects people of all ages. It is usually caused by a combination of sebaceous gland hyperplasia, excessive sebum production, and impaired keratinization. As a result, hair follicles become clogged with oil and dead skin cells, leading to pimples and oily skin (Pschyrembel, Klinisches 258.ed., Walter de Gruyter-Verlag, Berlin, 1998). The affected skin areas are colonized by bacteria which may additionally cause inflammation. Acne primarily affects skin areas with a large number of sebaceous glands, especially the face, upper chest and back. The occurrence of acne may lead to emotional distress and psychiatric problems, such as reduced self-esteem and depression.

[0003] Oily skin is a transitional state between healthy skin and acne-prone skin. In oily skin, the sebaceous glands of the skin produce excessive sebum, which then serves as an ideal nutrient for many bacteria and yeasts including the different species of anaerobic gram-positive bacteria Propionibacterium acnes (formerly known as Propionibacterium acnes) and Pityrosporum yeast. These microorganisms decompose sebum into glycerol and fatty acids, thereby further inducing the production of sebum in the sebaceous glands and destroying the follicle walls in the skin. This leads to the formation of skin inflammation and acne, pustules, nodules and cysts, which usually form scars when healing, thereby permanently affecting the optical appearance of the subject's skin (W. Umbach [Ed.], Kosmetik, Entwicklung, Herstellung und Anwendung kosmetischer Mittel, 2. Edition Thieme Verlag, Stuttgart, 1995).

[0004] There appear to be many different factors that contribute to the development of acne, including genetics, hormonal status, stress, and diet. In addition, the anaerobic bacterial species Propionibacterium acnes (formerly Propionibacterium acnes) is thought to play an important role in the development of acne, as these bacteria are often found in high numbers in patients with moderate or severe inflammatory acne. However, the underlying mechanisms are not fully understood.

[0005] At present, the standard treatment of acne usually includes topical application of antibiotics including erythromycin, clindamycin, metronidazole, sulfacetamide, doxycycline or minocycline to reduce the number of bacteria, particularly Propionibacterium acnes. However, some of these antibiotics show considerable side effects, making their use inconvenient for patients. In addition, the use of antibiotics to treat acne is accompanied by a high recurrence rate, which is due to the fact that a small amount of Propionibacterium acnes survives and resumes growth after the termination of antibiotic treatment. Therefore, there is a demand for a new method for treating or preventing acne that is substantially free of side effects and provides a lasting effect.

[0006] In more recent treatments, acne is thought to be the result of aberrations in the human skin microbiome caused by specific strains of Propionibacterium acnes (Holmes, 2013; Lomholt and Kilian. 2010). Researchers have only recently begun to study the skin microbiome (Belkaid and Segre, 2014; Oh et al., 2014). Although the skin is colonized by a large number of harmless or even beneficial microorganisms (Grice and Segre, 2011), alterations in the microbiome can cause diseases such as acne (Bek-Thomsen et al., 2008; Holmes, 2013; Kong et al., 2012; Fitz-Gibbon et al., 2013). This aberration may be caused by specific subpopulations of the skin bacteria Propionibacterium acnes (Lomholt and Kilian, 2010). Therefore, it has been suggested that the skin microbiome should be modulated in an attempt to restore a healthy microbiome. For example, WO 2016 / 172196 A1 discloses a method for treating acne in a subject, the method comprising first administering a disinfectant or an antibiotic to the subject's skin, followed by administering a composition comprising one or more live strains of Propionibacterium acnes. Similarly, WO 2018 / 073651 A1 discloses a composition for treating acne, comprising two or more strains of Propionibacterium acnes, including Propionibacterium acnes strains C3 and / or K8. Summary of the invention

[0007] In a first aspect, the present invention relates to a skin care composition for topical administration to the skin, comprising:

[0008] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes (C. acnes); and

[0009] (b) an emollient selected from the group consisting of dicaprylyl carbonate, ethylhexyl cocoate, and mixtures thereof.

[0010] In certain embodiments, the skin care composition comprises dicaprylyl carbonate as an emollient. In certain embodiments, dicaprylyl carbonate is present in the skin care composition in an amount of 0.05 to 25.0% (w / w). In certain embodiments, dicaprylyl carbonate is present in the skin care composition in an amount of 7.5 to 10.0% (w / w).

[0011] In certain embodiments, the skin care composition comprises ethylhexyl cocoate as an emollient. In certain embodiments, ethylhexyl cocoate is present in the skin care composition in an amount of 0.05 to 25.0% (w / w). In certain embodiments, ethylhexyl cocoate is present in the skin care composition in an amount of 7.5 to 10.0% (w / w).

[0012] In certain embodiments, the skin care composition comprises a mixture of dicaprylyl carbonate and ethylhexyl cocoate as an emollient.

[0013] In certain embodiments, the skin care composition comprises equal amounts of dicaprylyl carbonate and ethylhexyl cocoate.

[0014] In certain embodiments, the total amount of emollient in the composition does not exceed 20.0% (w / w).

[0015] In certain embodiments, the skin care composition does not include any other emollients other than dicaprylyl carbonate and / or ethylhexyl cocoate.

[0016] In certain embodiments, the skin care composition further comprises a thickener selected from the group consisting of Chondruscrispus extract, hydroxypropyl starch phosphate, and mixtures thereof.

[0017] In certain embodiments, the skin care composition further comprises a filler selected from the group consisting of distarch phosphate, tapioca starch, and mixtures thereof.

[0018] In certain embodiments, the skin care composition further comprises an antioxidant selected from the group consisting of tocopherol, tocopherol acetate, and mixtures thereof.

[0019] In certain embodiments, the skin care composition further comprises a preservative selected from the group consisting of ethanol, phenoxyethanol, caprylyl glycol, methylpropanediol, and mixtures thereof.

[0020] In certain embodiments, the skin care composition further comprises PEG-40 hydrogenated castor oil as a solubilizer.

[0021] In certain embodiments, the skin care composition further comprises citric acid / citrate buffer as a pH adjusting agent.

[0022] In certain embodiments, the skin care composition comprises at least one strain of Propionibacterium acnes selected from single locus sequence typing (SLST) D1, A5, C1, C3, H1, H2, H3, K1, K2, K4, K6, K8, K9, L1 and F4 strains. In certain embodiments, the skin care composition comprises at least one freeze-dried or spray-dried live bacteria of Propionibacterium acnes SLST C3 strain. In certain embodiments, the skin care composition comprises at least one freeze-dried or spray-dried live bacteria of Propionibacterium acnes SLST K8 strain. In certain embodiments, the skin care composition comprises at least one Propionibacterium acnes SLST C3 strain and at least one freeze-dried or spray-dried live bacteria of Propionibacterium acnes SLST K8 strain.

[0023] In certain embodiments, the skin care composition further comprises at least one freeze-dried or spray-dried live bacteria of a SLST A5 strain of Propionibacterium acnes. In certain embodiments, the skin care composition further comprises at least one freeze-dried or spray-dried live bacteria of a SLST F4 strain of Propionibacterium acnes.

[0024] In certain embodiments, the concentration of each P. acnes strain is at least 0.5% (w / v) of the skin care composition. In certain embodiments, the at least one P. acnes SLST C3 type strain and the at least one P. acnes SLST K8 type strain have approximately equal concentrations in the composition. In certain embodiments, the at least one P. acnes SLST C3 type strain is present in the composition at a higher concentration than the at least one P. acnes SLST K8 type strain. In other embodiments, the at least one P. acnes SLST K8 type strain is present in the composition at a higher concentration than the at least one P. acnes SLST C3 type strain.

[0025] In certain embodiments, each strain of Propionibacterium acnes in the composition is present at 10 4 -10 11 Colony forming units / ml (CFU / ml), preferably 10 7 -10 10 In some embodiments, the total amount of bacteria in the composition is 10 4 -10 11 CFU / ml, preferably 10 7 -10 10 CFU / ml.

[0026] In certain embodiments, the skin care composition takes the form of a gel, cream, ointment, or lotion.

[0027] In a second aspect, the present invention relates to a method for improving the appearance of a subject's skin and / or regulating sebum production by a subject's skin cells and / or maintaining healthy skin of a subject, the method comprising topically administering the skin care composition of the present invention. In certain embodiments, the subject is a human.

[0028] In a third aspect, the present invention relates to a method of treating or preventing a condition selected from acne, oily skin, progressive macular hypopigmentation, dandruff, atopic eczema, atopic dermatitis and rosacea in a subject, the method comprising topically administering a skin care composition of the present invention. In certain embodiments, the subject is a human. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 Shown are the compositions of prototype formulations 1-15 used in reactivation experiments using freeze-dried bacteria.

[0030] Figure 2 Shown are the results of experiments analyzing the reactivation of freeze-dried bacteria from prototype formulations 1-11.

[0031] Figure 3 Shown are the results of experiments analyzing the reactivation of freeze-dried bacteria from prototype formulations 12-15.

[0032] Figure 4 The compositions of additional prototype formulations 1-11 used in reactivation experiments using freeze-dried bacteria are shown.

[0033] Figure 5 Shown are the results of experiments analyzing the reactivation of freeze-dried bacteria from the additional prototype formulations 1-11.

[0034] Figure 6 Shown are the results of experiments analyzing the reactivation of freeze-dried bacteria from comparative formulations V1-V10.

[0035] Figure 7 Shown are the compositions of comparative formulations V1-V10 used in reactivation experiments using freeze-dried bacteria. DETAILED DESCRIPTION

[0036] Although these methods and compositions provide new and highly effective microbiome modulation to improve or eliminate the symptoms of acne, it has been found that providing live bacteria in cosmetic skin care compositions is associated with significant problems. For example, some components commonly used in commercial skin care products interfere with the viability of bacteria. When these compounds are combined with freeze-dried or spray-dried bacteria into a composition, they may interfere with the viability of the bacteria or negatively affect the growth rate of the bacteria after application to the skin. Therefore, there is a need for new skin care products that are formulated in a manner compatible with the use of freeze-dried or spray-dried bacteria and do not inhibit the growth of these bacteria after the product is applied to the skin.

[0037] It has now surprisingly been found that the viability of freeze-dried or spray-dried bacteria, in particular bacterial strains of the species Propionibacterium acnes, in skin care compositions during storage and their ability to grow after application to the skin can be preserved or significantly improved by excipients added to the final skin care product formulation. The present invention is based on the identification of a group of excipients for skin care compositions that do not significantly interfere with or can improve the reactivation of bacterial viability and growth. These compounds have been found to be highly compatible with the administration of bacteria, in particular bacterial strains of the species Propionibacterium acnes.

[0038] Thus, in a first aspect, the present invention relates to a skin care composition for topical administration to the skin, said composition comprising, consisting essentially of or consisting of:

[0039] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes; and

[0040] (b) an emollient selected from the group consisting of dicaprylyl carbonate, ethylhexyl cocoate, and mixtures thereof.

[0041] In the context of the present invention, freeze-dried or spray-dried live bacteria are used in the skin care composition. This means that live bacteria are subjected to a drying process, which 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, for example human skin, the metabolism of the bacteria is reactivated, causing them to resume growth. They multiply on the skin surface and replace pathogenic bacterial strains, thereby restoring a diverse, healthy and balanced skin microbiome.

[0042] In one embodiment, the live P. acnes bacteria are in spray-dried form. The principle of spray drying is based on the dispersion of a solution into fine droplets, which are introduced into a stream of hot air. The solvent evaporates from the substrate droplets, leaving a mass of dry product. Standard spray drying equipment can be used, such as the Mini Spray Dryer B-290 from Büchi Labortechnik GmbH (Essen, Germany) or the Mobile Minor from GEA (Berlin, Germany). TM Spray dryer.

[0043] In one embodiment, the live P. acnes bacteria are in freeze-dried or lyophilized form. Freeze-drying or lyophilization is a process that involves freezing a product, reducing the pressure and heating to allow the frozen water in the material to sublime. A variety of different methods can be used to freeze the product. For example, freezing can be achieved using a standard refrigerator or a freezer bath. Cooling the product to below its triple point ensures that sublimation occurs after heating. 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, approximately 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 freeze drying equipment from GEA (Berlin, Germany). TM apparatus, Gamma 2-20 freeze dryer LCM-1 from Christ (Osterode am Harz, Germany) or ChristMartin from Fisher Scientific GmbH (Schwerte, Germany) TM Alpha 1-2 freeze dryer.

[0044] The one or more excipients that do not interfere with the reactivation of the viability and growth of the freeze-dried or spray-dried live bacteria are selected from emollients, thickeners, fillers, antioxidants, preservatives, solubilizers and pH adjusters. Suitable members of each of these compound groups are discussed below.

[0045] Emollients

[0046] According to the present invention, the skin care composition comprises an emollient in combination with the freeze-dried or spray-dried live bacteria of at least one Propionibacterium acnes strain. When used herein, an emollient is a compound that moisturizes and / or softens the skin. Emollients reduce the roughness, cracking and / or stimulation of the skin by penetrating into the deeper layers of the skin. Emollients commonly used in skin care products include vegetable oils such as sesame oil, coconut oil, olive oil, almond oil, macadamia oil, cottonseed oil or peanut oil, silicone oils such as dimethylpolysiloxane and cyclomethicone, fatty acids and fatty alcohol ethers.

[0047] According to the present invention, the skin care composition comprising freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes comprises an emollient selected from dicaprylyl carbonate, ethylhexyl cocoate and mixtures thereof. In a preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes and dicaprylyl carbonate as an emollient. In another preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes and ethylhexyl cocoate as an emollient. In yet another preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes and both dicaprylyl carbonate and ethylhexyl cocoate as emollients. Particularly preferably, the skin care composition does not comprise any other emollient other than dicaprylyl carbonate and / or ethylhexyl cocoate.

[0048] When dicaprylyl carbonate is used as an emollient, it is preferably used in an amount of 0.05 to 25.0% (w / w), more preferably 2.0 to 20.0% (w / w), more preferably 5.0 to 10.0% (w / w) or 7.5 to 10.0% (w / w) in the final skin care composition. In other words, the amount of dicaprylyl carbonate in the skin care composition of the present invention may be at least 0.05% (w / w), at least 0.1% (w / w), at least 0.25% (w / w), at least 0.5% (w / w), at least 0.75% (w / w), at least 1.0% (w / w), at least 1.25% (w / w), at least 1.5% (w / w), at least 1.75% (w / w), at least 2.0% (w / w), at least 2.5% (w / w), at least 3.0% (w / w), at least 4.0% (w / w), at least 5.0% (w / w), at least 6.0% (w / w), at least 7.0% (w / w), at least 8.0% (w / w) or at least 9.0% (w / w).

[0049] When ethylhexyl cocoate is used as an emollient, it is preferably used in the final skin care composition in an amount of 0.05 to 25.0% (w / w), more preferably 1.0 to 10.0% (w / w), more preferably 5.0 to 10.0% (w / w) or 7.5 to 10.0% (w / w). In other words, the amount of ethylhexyl cocoate in the skin care composition of the present invention may be at least 0.05% (w / w), at least 0.1% (w / w), at least 0.25% (w / w), at least 0.5% (w / w), at least 0.75% (w / w), at least 1.0% (w / w), at least 1.25% (w / w), at least 1.5% (w / w), at least 1.75% (w / w), at least 2.0% (w / w), at least 2.5% (w / w), at least 3.0% (w / w), at least 4.0% (w / w), at least 5.0% (w / w), at least 6.0% (w / w), at least 7.0% (w / w), at least 8.0% (w / w) or at least 9.0% (w / w).

[0050] When dicaprylyl carbonate and ethylhexyl cocoate are used as emollients in combination with each other, preferably the total amount of emollient is at least 0.05% (w / w), but not more than 20.0% (w / w), more preferably not more than 15.0% (w / w) or 10.0% (w / w). In addition, in this embodiment, preferably dicaprylyl carbonate and ethylhexyl cocoate are used in equal amounts, such as 2.0% (w / w) dicaprylyl carbonate combined with 2.0% (w / w) ethylhexyl cocoate, or 5.0% (w / w) dicaprylyl carbonate combined with 5.0% (w / w) ethylhexyl cocoate.

[0051] Thickener

[0052] Preferably, the skin care composition further comprises a thickener. A thickener is a compound that increases the viscosity of a cosmetic or pharmaceutical formulation. A thickener is typically a polymer that absorbs water and swells, thereby making the composition more viscous. Commonly used thickeners in skin care products include soy gum, xanthan gum, gelatin, carnauba wax, and stearic acid.

[0053] According to a preferred aspect of the invention, the skin care composition comprising freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes and an emollient as defined above comprises a thickener selected from Chondrus crispus extract, hydroxypropyl starch phosphate and mixtures thereof. In a preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above and Chondrus crispus extract as a thickener. In another preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above and hydroxypropyl starch phosphate as a thickener.

[0054] When Chondrus crispus extract is used as the thickening compound in the composition of the present invention, it is preferably used in an amount of 0.05 to 7.5% (w / w), more preferably 0.1 to 5.0% (w / w), more preferably 0.2 to 4.0% (w / w), 0.2 to 2.0% (w / w) or 0.2 to 1.5% (w / w) in the final skin care composition. In other words, the amount of Chondrus crispus extract in the skin care composition of the present invention may be at least 0.05% (w / w), at least 0.1% (w / w), at least 0.25% (w / w), at least 0.5% (w / w), at least 0.75% (w / w), at least 1.0% (w / w), at least 1.25% (w / w), at least 1.5% (w / w), at least 1.75% (w / w), at least 2.0% (w / w), at least 2.5% (w / w), at least 3.0% (w / w), at least 4.0% (w / w) or at least 5.0% (w / w).

[0055] When hydroxypropyl starch phosphate is used as a thickener, it is preferably used in the final skin care composition in an amount of 0.05 to 10.0% (w / w), more preferably 0.1 to 10.0% (w / w), more preferably 0.5 to 7.5% (w / w), 1.0 to 5.0% (w / w) or 1.0 to 2.0% (w / w). In other words, the amount of hydroxypropyl starch phosphate in the skin care composition of the present invention may be at least 0.05% (w / w), at least 0.1% (w / w), at least 0.25% (w / w), at least 0.5% (w / w), at least 0.75% (w / w), at least 1.0% (w / w), at least 1.25% (w / w), at least 1.5% (w / w) or at least 1.75% (w / w).

[0056] It should be understood that the skin care composition of the present invention may also contain a combination of Chondrus crispus extract and hydroxypropyl starch phosphate as a thickener. When Chondrus crispus extract and hydroxypropyl starch phosphate are used in combination with each other as thickeners, preferably the total amount of thickener is at least 0.05% (w / w), but not more than 10.0% (w / w), more preferably not more than 5.0% (w / w). Moreover, in this embodiment, preferably the two thickeners are used in equal amounts, for example 2.0% (w / w) Chondrus crispus extract and 2.0% (w / w) hydroxypropyl starch phosphate.

[0057] pH Adjusters

[0058] In another preferred embodiment, the skin care composition of the present invention further comprises a pH regulator. Since the composition of the present invention is used on human skin, it preferably has a neutral or slightly acidic pH to make it compatible with the acidic environment of the skin. The composition may have a pH in the range of about 2.5 to about 7.5, preferably about 4.0 to about 7.0, more preferably about 6.0 to about 7.0. Although the acidic pH in cosmetic preparations is usually achieved by adding acids such as formic acid, acetic acid, butyric acid, valeric acid, hexanoic acid, heptanoic acid or octanoic acid, it has been found that these acids may impair the ability of bacteria in the composition to grow and replicate after administration to the skin. According to the present invention, the pH regulator is preferably a citric acid / citrate buffer.

[0059] Therefore, in another preferred case, the skin care composition comprising at least one live freeze-dried or spray-dried bacteria of a strain of Propionibacterium acnes and an emollient as defined above further comprises a citric acid / citrate buffer, for example a citric acid / sodium citrate buffer as a pH regulator. In a preferred embodiment, the skin care composition comprises at least one live freeze-dried or spray-dried bacteria of a strain of Propionibacterium acnes, an emollient as defined above and a buffer consisting of citric acid and sodium citrate. Particularly preferably, the skin care composition does not comprise any other pH regulator other than citric acid / citrate.

[0060] When citric acid is used as a pH adjuster, it is preferably used in an amount of 0.01 to 1.5% (w / w), more preferably 0.01 to 0.25% (w / w), even more preferably 0.01 to 0.1% (w / w) in the final skin care composition. In other words, the amount of citric acid in the skin care composition of the present invention may be at least 0.01% (w / w), at least 0.02% (w / w), at least 0.03% (w / w), at least 0.04% (w / w), at least 0.05% (w / w), at least 0.06% (w / w), at least 0.07% (w / w), at least 0.08% (w / w), at least 0.09% (w / w) or at least 0.1% (w / w).

[0061] When sodium citrate is used as a pH adjuster, it is preferably used in an amount of 0.01 to 1.5% (w / w), more preferably 0.05 to 1.0% (w / w), more preferably 0.05 to 0.5% (w / w) or 0.1 to 0.2% (w / w) in the final skin care composition. In other words, the amount of sodium citrate in the skin care composition of the present invention may be at least 0.01% (w / w), at least 0.02% (w / w), at least 0.03% (w / w), at least 0.04% (w / w), at least 0.05% (w / w), at least 0.06% (w / w), at least 0.07% (w / w), at least 0.08% (w / w), at least 0.09% (w / w), at least 0.1% (w / w), 0.11% (w / w), 0.12% (w / w), 0.13% (w / w), 0.14% (w / w), 0.15% (w / w), 0.16% (w / w), 0.17% (w / w), 0.18% (w / w), 0.19% (w / w), 0.20% (w / w), 0.21% (w / w), 0.22% (w / w), 0.23% (w / w), 0.24% (w / w), 0.25% (w / w), 0.26% (w / w), 0.27% (w / w), 0.28% (w / w), 0.29% (w / w), 0.30% (w / w), 0.31% (w / w), 0.32% (w / w), 0.33% (w / w), 0.34% (w / w), 0.13% (w / w), 0.14% (w / w), 0.15% (w / w), 0.16% (w / w), 0.17% (w / w), 0.18% (w / w), 0.19% (w / w), 0.2% (w / w), at least 0.3% (w / w), at least 0.4% (w / w), at least 0.5% (w / w), at least 0.6% (w / w), at least 0.7% (w / w), at least 0.8% (w / w), at least 0.9% (w / w) or at least 1.0%.

[0062] When citric acid and sodium citrate are used in combination with each other as pH adjusters, preferably the total amount of the pH adjuster in the final skin care composition does not exceed 0.3% (w / w). In addition, in this embodiment, preferably citric acid and sodium citrate are used in a ratio of 1:2, such as 0.05% (w / w) citric acid and 0.10% (w / w) sodium citrate, or 0.1% (w / w) citric acid combined with 0.2% (w / w) sodium citrate.

[0063] Particularly preferably, citric acid and citrate salts are used in the skin care compositions of the present invention in an amount to ensure that the pH of the total composition is between 5.0 and 7.0.

[0064] Fillers

[0065] In another preferred embodiment, the skin care composition further comprises a filler. When used herein, a filler is a compound that helps make the skin care composition more homogeneous by being evenly dispersed in the composition. Fillers are used to improve the sensory properties of the skin. Depending on the filler material, the final product may impart a silky, dry, smooth or powdery skin feel.

[0066] According to another preferred aspect of the invention, the skin care composition comprising freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes and an emollient as defined above comprises a filler selected from distarch phosphate, tapioca starch and mixtures thereof. In a preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above and distarch phosphate as a filler. In another preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above and tapioca starch as a filler. In yet another preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above and both distarch phosphate and tapioca starch as fillers. Preferably, the skin care composition does not comprise any other filler other than distarch phosphate and / or tapioca starch.

[0067] When distarch phosphate is used as a filler, it is preferably used in the final skin care composition in an amount of 0.05 to 5.0% (w / w), more preferably 1.0 to 5.0% (w / w), more preferably 2.0 to 5.0% (w / w) or 2.0 to 3.0% (w / w). In other words, the amount of distarch phosphate in the skin care composition of the present invention may be at least 0.05% (w / w), at least 0.1% (w / w), at least 0.25% (w / w), at least 0.5% (w / w), at least 0.75% (w / w), at least 1.0% (w / w), at least 1.25% (w / w), at least 1.5% (w / w), at least 1.75% (w / w), at least 2.0% (w / w), at least 2.5% (w / w), at least 3.0% (w / w) or at least 4.0% (w / w). The same amounts apply when using tapioca starch as a filler.

[0068] When distarch phosphate and tapioca starch are used as fillers in combination with each other, preferably the total amount of the filler is at least 0.05% (w / w), but not more than 5.0% (w / w), more preferably not more than 3.0% (w / w). In addition, in this embodiment, preferably distarch phosphate and tapioca starch are used in equal amounts, such as 2.5% (w / w) distarch phosphate combined with 2.5% (w / w) tapioca starch, or 1.0% (w / w) distarch phosphate combined with 1.0% (w / w) tapioca starch.

[0069] Solubilizer

[0070] In another preferred embodiment, the skin care composition further comprises a solubilizer. When 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 perfume oils and other hydrophobic substances such as vitamins feasible in aqueous skin care compositions. It was found herein that polyethylene glycol (PEG)-40 hydrogenated castor oil did not interfere with the viability and replication of the freeze-dried or spray-dried bacteria.

[0071] Thus, in a preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above and PEG-40 hydrogenated castor oil. In an even more preferred embodiment, PEG-40 hydrogenated castor oil is the only solubilizer contained in the composition.

[0072] When PEG-40 hydrogenated castor oil is used as a solubilizer, it is preferably used in an amount of 0.01 to 2.5% (w / w), more preferably 0.05 to 1.5% (w / w), more preferably 0.5 to 1.0% (w / w) in the final skin care composition. In other words, the amount of PEG-40 hydrogenated castor oil in the skin care composition of the present invention may be at least 0.01% (w / w), at least 0.05% (w / w), at least 0.1% (w / w), at least 0.2% (w / w), at least 0.3% (w / w), at least 0.4% (w / w), at least 0.5% (w / w), at least 0.6% (w / w), at least 0.7% (w / w), at least 0.8% (w / w), at least 0.9% (w / w) or at least 1.0% (w / w).

[0073] Antioxidants

[0074] In another preferred embodiment, the skin care composition further comprises an antioxidant. These compounds are generally added to cosmetic 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 and butylated hydroxyanisole, as well as plant-derived polyphenols, flavonoids, flavanols, stilbenes and terpenes.

[0075] In a preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above, and an antioxidant selected from tocopherol, tocopherol acetate, and mixtures thereof. In a preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above, and tocopherol as an antioxidant. In another preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above, and tocopherol acetate as an antioxidant. In yet another preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above, and both tocopherol and tocopherol acetate as antioxidants. Particularly preferably, the skin care composition does not comprise any other antioxidant other than tocopherol and / or tocopherol acetate.

[0076] When tocopherol, tocopherol acetate or a mixture thereof is used as an antioxidant, they can be added to the freeze-dried or spray-dried live bacteria in a freeze-dried or spray-dried form. For example, if the composition of the present invention is provided in a form that requires the bacteria to be mixed with a cosmetic or pharmaceutical preparation before use, the freeze-dried or spray-dried antioxidant can be added to the freeze-dried or spray-dried bacteria and stored until reconstituted with the cosmetic or pharmaceutical preparation before use. When tocopherol, tocopherol acetate or a mixture thereof is used in a dry form, dried vitamin C can also be added.

[0077] When tocopherol is used as an antioxidant, it is preferably used in an amount of 0.01 to 2.0% (w / w), more preferably 0.05 to 1.5% (w / w), more preferably 0.1 to 1.0% (w / w) in the final skin care composition. In other words, the amount of tocopherol in the skin care composition of the present invention may be at least 0.01% (w / w), at least 0.025% (w / w), at least 0.05% (w / w), at least 0.075% (w / w), at least 0.1% (w / w), at least 0.2% (w / w), at least 0.3% (w / w), at least 0.4% (w / w), at least 0.5% (w / w), at least 0.6% (w / w), at least 0.7% (w / w), at least 0.8% (w / w), at least 0.9% (w / w) or at least 1.0% (w / w). When tocopherol acetate is used as an antioxidant, the same amounts apply.

[0078] When tocopherol and tocopherol acetate are used as antioxidants in combination with each other, preferably the total amount of antioxidant is at least 0.01% (w / w), but not more than 2.0% (w / w). In addition, in this embodiment, preferably tocopherol and tocopherol acetate are used in equal amounts, such as 0.25% (w / w) tocopherol combined with 0.25% (w / w) tocopherol acetate, or 0.5% (w / w) tocopherol combined with 0.5% (w / w) tocopherol acetate.

[0079] preservative

[0080] In another preferred embodiment, the skin care composition further comprises a preservative. As used herein, a preservative is a compound added to a cosmetic preparation to prevent microbial spoilage of the preparation by inhibiting the growth of unwanted bacteria and yeast. Common preservatives in cosmetic preparations include benzyl alcohol, salicylic acid, and sorbic acid.

[0081] In a preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above and a preservative selected from ethanol, phenoxyethanol, caprylyl glycol, methylpropanediol and mixtures thereof. These preservatives are surprisingly tolerated to a certain extent by strains of Propionibacterium acnes, while being effective against other bacteria that may contaminate the composition.

[0082] In a preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above, and ethanol as a preservative. In another preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above, and phenoxyethanol as a preservative. In yet another preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above, and caprylyl glycol as a preservative. In yet another preferred embodiment, the skin care composition comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient as defined above, and methylpropanediol as a preservative.

[0083] In addition, the skin care composition of the present invention may contain more than one preservative, such as two or more of the above preservatives. For example, the composition may contain a combination of ethanol and phenoxyethanol as a preservative. Alternatively, the composition may contain a combination of ethanol and octanediol as a preservative. Alternatively, the composition may contain a combination of ethanol and methylpropanediol as a preservative. The composition may also contain a combination of phenoxyethanol and octanediol as a preservative or a combination of phenoxyethanol and methylpropanediol as a preservative. The composition may also contain a combination of octanediol and methylpropanediol as a preservative.

[0084] The best results were obtained using a combination of phenoxyethanol, caprylyl glycol and methylpropanediol in protecting the skin care composition of the present invention from spoilage by other bacteria or fungi while maintaining the viability of the freeze-dried or spray-dried live bacteria of Propionibacterium acnes in the composition. Thus, in certain preferred embodiments, the skin care composition of the present invention comprises freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, an emollient and a combination of phenoxyethanol, caprylyl glycol and methylpropanediol.

[0085] When ethanol is used as a preservative, it is preferably used in the final skin care composition in an amount of 0.5 to 20.0% (w / w), more preferably 8.0 to 15.0% (w / w), more preferably 5.0 to 15.0% (w / w). In other words, the amount of ethanol in the skin care composition of the present invention may be at least 0.5% (w / w), at least 1.0% (w / w), at least 2.0% (w / w), at least 3.0% (w / w), at least 4.0% (w / w), at least 5.0% (w / w), at least 6.0% (w / w), at least 7.0% (w / w), at least 8.0% (w / w), at least 9.0% (w / w) or at least 10.0% (w / w).

[0086] When phenoxyethanol is used as a preservative, it is preferably used in an amount of 0.05 to 0.5% (w / w), more preferably 0.1 to 0.25% (w / w), more preferably 0.1 to 0.2% (w / w) in the final skin care composition. In other words, the amount of phenoxyethanol in the skin care composition of the present invention may be at least 0.05% (w / w), at least 0.075% (w / w), at least 0.1% (w / w), at least 0.15% (w / w), at least 0.2% (w / w) or at least 0.25% (w / w). When caprylyl glycol is used as a preservative, the same amounts apply.

[0087] When methylpropanediol is used as a preservative, it is preferably used in an amount of 0.05 to 5.0% (w / w), more preferably 0.5 to 2.5% (w / w), more preferably 1.0 to 1.5% (w / w) in the final skin care composition. In other words, the amount of methylpropanediol in the skin care composition of the present invention may be at least 0.5% (w / w), at least 1.0% (w / w), at least 2.0% (w / w), at least 3.0% (w / w) or at least 4.0% (w / w) or at least 5.0% (w / w).

[0088] When two or more of the above preservatives are used in combination with each other, preferably the total amount of preservatives does not exceed 5.0% (w / w) when a combination of phenoxyethanol and caprylyl glycol is used. Specifically, when a combination of caprylyl glycol, phenoxyethanol and methylpropanediol is used, these compounds are preferably used in a ratio of 1:2:20, for example 0.05% (w / w) caprylyl glycol, 0.1% (w / w) phenoxyethanol and 1.0% (w / w) methylpropanediol, or 0.1% (w / w) caprylyl glycol, 0.2% (w / w) phenoxyethanol and 2.0% (w / w) methylpropanediol.

[0089] The above preservatives can be used in combination with other preservatives, in particular short-chain fatty acids such as formic acid, propionic acid or isobutyric acid. In addition, the composition of the present invention can also contain lactic acid as an additional preservative.

[0090] Other cosmetic excipients

[0091] The skin care compositions described herein may include, in addition to the above-mentioned components, known excipients including perfumes, pigments, colorants, dyes, waxes, sequestering agents, moisturizers, surfactants, lubricants, stabilizers, sunscreens, emulsifiers, drugs, antibacterial agents, chelating agents, protectants, viscosity enhancers, vitamins, panthenol, ubiquinone Q10, hyaluronic acid, or any combination thereof.

[0092] Bacterial strains

[0093] The skin care composition of the present invention comprises freeze-dried or spray-dried live bacteria of at least one strain of the Propionibacterium acnes species. However, preferably the skin care composition comprises two or more strains of the Propionibacterium acnes species. For example, the skin care composition may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more strains of Propionibacterium acnes. In certain embodiments, the skin care composition comprises 2, 3, 4 or 5 different strains of Propionibacterium acnes. It has been reported that the reactivation and growth of certain Propionibacterium acnes strains are significantly supported when grown in a mixture of strains compared to when grown alone. For example, the SLST K8 type strain grows slowly alone, but grows significantly faster when grown in a mixture of strains. Therefore, according to the present invention, the composition preferably comprises two or more strains of Propionibacterium acnes.

[0094] The bacterial species Propionibacterium acnes (C. acnes) was previously known as Propionibacterium acnes (P. acnes). The species was taxonomically reclassified in 2016 based on biochemical and genomic studies. P. acnes is a Gram-positive anaerobic rod-shaped bacterium known to be involved in the development of acne and other pathological conditions. P. acnes strains occur on the skin of most people. P. acnes strains can be pathogenic or non-pathogenic. When used herein, a "pathogenic" P. acnes strain is a strain associated with acne. Assays for the identification and selection of pathogenic and non-pathogenic P. acnes strains are described in WO 2018 / 073651.

[0095] It has been shown that P. acnes comprises several different major phylogenetic groups classified as types I, II and III, wherein the major type I clade is further divided into subclades referred to as types IA, IB and IC (Lomholt and Kilian, 2010). Subclade IA is further subdivided into IA1 and IA2 (McDowell et al., 2012). Preferably, at least one strain of the species of P. acnes is a non-pathogenic strain of P. acnes. Genetic analysis of P. acnes strains has shown that strains that are non-pathogenic and not associated with acne are primarily members of (i) clade I subclade IA2, (ii) clade I subclade IB and (iii) clade II.

[0096] Thus, in one embodiment of the present invention, at least one strain of the Propionibacterium acnes species belongs to any of the subclades IA2, IB of clade I or to clade II. In one embodiment, at least one strain of the Propionibacterium acnes species belongs to subclade IA2. In another embodiment, at least one strain of the Propionibacterium acnes species belongs to subclade IB. In yet another embodiment, at least one strain of the Propionibacterium acnes species belongs to clade II. If more than one strain is used in the skin care composition of the present invention, strains from different clades or subclades are preferably mixed with each other. For example, in one embodiment, the skin care composition comprises at least one strain from subclade IA2 and at least one strain from subclade IB. In another embodiment, the skin care composition comprises at least one strain from subclade IA2 and at least one strain from clade II. In yet another embodiment, the skin care composition comprises at least one strain from subclade IB and at least one strain from clade II.

[0097] In other embodiments, the skin care composition of the present invention may include a mixture of P. acnes strains, including one or more clade I strains and one or more clade II strains. Although, as noted above, clade II strains may be less pathogenic than clade I strains, these strains may also grow more slowly than clade I strains and are less likely to be able to colonize the skin on their own. Therefore, in certain embodiments, it may be advantageous for the skin care composition to include a strain mixture that includes both clade I and clade II strains, allowing for improved colonization of the skin by clade II strains.

[0098] Non-limiting examples of non-pathogenic strains of Propionibacterium acnes include, but are not limited to, SLST D1, A5, C1, C3, H1, H2, H3, K1, K2, K4, K6, K8, K9, L1 and F4 strains. Particularly preferably, the skin care composition of the present invention comprises at least one SLST C3 strain and / or at least one SLST K8 strain. In one embodiment, the skin care composition of the present invention comprises at least one SLST C3 strain, more preferably two or more SLST C3 strains, such as 2, 3, 4, 5, 6, 7, 8, 9 or 10 SLST C3 strains. In another embodiment, the skin care composition of the present invention comprises at least one SLST K8 strain, more preferably two or more SLST K8 strains, such as 2, 3, 4, 5, 6, 7, 8, 9 or 10 SLST K8 strains. In yet another embodiment, the skin care composition of the present invention comprises a combination of at least one SLST C3 strain and at least one SLST K8 strain. In yet another embodiment, the skin care composition of the present invention comprises a combination of two or more SLST C3 type strains and at least one SLST K8 type strain. In yet another embodiment, the skin care composition of the present invention comprises a combination of at least one SLST C3 type strain and two or more SLST K8 type strains. In yet another embodiment, the skin care composition of the present invention comprises a combination of two or more SLST C3 type strains and two or more SLST K8 type strains. In certain embodiments, the one or more SLST C3 type strains and the one or more SLST K8 type strains have approximately equal concentrations in the composition. In other embodiments, the one or more SLST C3 type strains have a higher concentration than the one or more SLST K8 type strains in the composition. In other embodiments, the one or more SLST C3 type strains have a lower concentration than the one or more SLST K8 type strains in the composition.

[0099] In a particularly preferred embodiment, the skin care composition of the present invention comprises a SLST C3 type strain deposited under the Budapest Treaty by S-Biomedic NV (Turnhoutsweg 30, 2340 Beerse, Belgium) at the Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures (Inhoffenstr. 7B, D-38124 Braunschweig, Germany) on October 19, 2017 with the registration number DSM 32667. In another particularly preferred embodiment, the skin care composition of the present invention comprises a SLST K8 type strain deposited under the Budapest Treaty by S-Biomedic NV (Turnhoutsweg 30, 2340 Beerse, Belgium) at the Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures (Inhoffenstr. 7B, D-38124 Braunschweig, Germany) on October 19, 2017 under the accession number DSM 32668. In yet another preferred embodiment, the skin care composition of the present invention comprises both SLST C3 type strain DSM 32667 and SLST K8 type strain DSM 32668. In another embodiment, the skin care composition comprising at least one SLST C3 type strain and at least one SLST K8 type strain additionally comprises at least one SLST A5 type strain and / or at least one SLST F4 type strain. Thus, in one embodiment, the composition comprises at least one SLST C3 type strain, at least one SLST K8 type strain, and at least one SLST A5 type strain. In another embodiment, the composition comprises at least one SLST C3 type strain, at least one SLST K8 type strain, and at least one SLST F4 type strain. In yet another embodiment, the composition comprises at least one SLST C3 type strain, at least one SLST K8 type strain, at least one SLST A5 type strain, and at least one SLST F4 type strain.

[0100] The strain names referred to herein are based on the single locus sequence typing (SLST) protocol described in Scholz et al., 2014, using the locus PPA2385 as the SLST target sequence. The sequences of the PPA2385 locus of the different strains identified by Scholz are listed herein as SEQ ID NOs: 1-76. Thus, a "SLST C3 type" strain is a strain that contains in its genome a PPA2385 locus sequence that is 100% identical to the sequence depicted in SEQ ID NO: 27. Similarly, a "SLST K8 type" strain is a strain that contains in its genome a PPA2385 locus sequence that is 100% identical to the sequence depicted in SEQ ID NO: 64. The SLST protocol is also described in more detail in WO 2018 / 073651. Sequence identification of the PPA2385 locus can be performed by PCR amplification and DNA sequencing as described in WO 2018 / 073651, using the nucleotide primer set set forth in SEQ ID NOs: 77-82. Based on the information presented herein and in WO 2018 / 073651, one of ordinary skill in the art will understand how P. acnes strains can be identified and classified.

[0101] The composition of the present invention may comprise both pathogenic strains and non-pathogenic strains of P. acnes. However, in a preferred embodiment of the present invention, the skin care composition comprises only non-pathogenic strains of P. acnes. Particularly preferably, the skin care composition of the present invention does not comprise ribotype 6 (RT6) strains of P. acnes. The ribotype classification system is based on the differences in the 16S rDNA sequence between different strains of P. acnes. The ribotype system is explained in, for example, Fitz-Gibbon et al., 2013. Furthermore, particularly preferably, the skin care composition of the present invention does not comprise phenotype III strains of P. acnes.

[0102] Strains of Propionibacterium acnes are generally able to produce the signaling molecule trans-10, cis-12 linoleic acid from the precursor molecule linoleic acid naturally present in sebum (Rosson et al., 2004). Trans-10, cis-12 linoleic acid is believed to stimulate sebum production and secretion, which is important for the skin colonization of Propionibacterium acnes. In this way, trans-10, cis-12 linoleic acid promotes the onset of acne (Downing et al., 1986; Letawe et al., 1998). Depending on the skin of the object, reducing or increasing sebum production may be advantageous. For example, reducing sebum production in the skin of an object suffering from acne or oily skin may be useful. On the contrary, increasing sebum production in the skin of an object suffering from dry skin may be useful.

[0103] Thus, in one embodiment, one or more strains of Propionibacterium acnes included in the skin care compositions of the present invention are selected based on their ability to produce trans-10, cis-12 linoleic acid. In a preferred embodiment, strains that are selected to produce low levels of trans-10, cis-12 linoleic acid are included in the skin care compositions of the present invention for use in combating acne or oily skin. Without wishing to be limited by theory, it is believed that these strains reduce sebum production, which is useful for preventing or alleviating the symptoms of acne or oily skin. SLST C3, C1, F4, A5, K1, K2, K8 and L1 strains produce only small amounts of trans-10, cis-12 linoleic acid. In another preferred embodiment, strains that are selected to produce high levels of trans-10, cis-12 linoleic acid are included in the skin care compositions of the present invention for use in combating dry skin. Without wishing to be limited by theory, it is believed that these strains increase sebum production, which is useful for preventing or alleviating the symptoms of dry skin. SLST A1 strains produce large amounts of trans-10, cis-12 linoleic acid.

[0104] In one embodiment, one or more strains of Propionibacterium acnes included in the skin care composition of the present invention are isolated from the skin microbiome of a donor subject. The subject may not have acne or oily skin, or may have mild, moderate or severe acne. In another embodiment, the strain isolated from the skin microbiome of the donor subject is a non-pathogenic strain.

[0105] The skin care composition of the present invention may also include one or more genetically modified Propionibacterium acnes strains. In another embodiment, the skin care composition comprises a combination of one or more genetically modified Propionibacterium acnes strains and one or more naturally occurring Propionibacterium acnes strains. The genetically modified strains are preferably modified to produce lower or higher amounts of trans-10, cis-12 linoleic acid. The production of trans-10, cis-12 linoleic acid can be detected as described in U.S. Patent 6,743,609 or by other well-known methods such as FAME (fatty acid methyl esters) or gas chromatography. In certain other embodiments, the skin care composition of the present invention comprises only naturally occurring Propionibacterium acnes strains, i.e., only Propionibacterium acnes strains that have not been genetically modified by humans.

[0106] Particularly preferably, the at least one Propionibacterium acnes strain is present in an amount of 1.0×10 4 -1.0x10 11 Colony forming units (CFU) / ml, more preferably 1.0x10 5 -1.0x10 10 CFU / ml, even more preferably 1.0x10 7 -1.0x10 10 CFU / ml or 1.0x108 -1.0x10 9 CFU / ml is present in the composition. For example, the at least one strain of Propionibacterium acnes may be present in an amount of at least 1.0 x 10 5 CFU / ml, preferably at least 1.0x10 6 CFU / ml, more preferably at least 1.0x10 7 CFU / ml is at least 1.0x10 8 CFU / ml, at least 1.0x10 9 CFU / ml or at least 1.0x10 10 CFU / ml. Particularly preferably, the at least one strain of Propionibacterium acnes is present in the skin care composition in an amount of at least 1.0 x 10 10 CFU / ml, 2.0x10 10 CFU / ml, 3.0x10 10 CFU / ml, 4.0x10 10 CFU / ml, 5.0x10 10 CFU / ml, 6.0x10 10 CFU / ml, 7.0x10 10 CFU / ml, 8.0x10 10 CFU / ml or 9.0x10 10 An amount of CFU / ml is present in the skin care composition.

[0107] In certain embodiments, each strain of Propionibacterium acnes present in the composition is present at 1.0 x 10 4 -1.0x10 11 CFU / ml, more preferably 1.0x10 5 -1.0x10 10 CFU / ml, even more preferably 1.0x10 7 -1.0x10 10 CFU / ml or 1.0x10 8 -1.0x10 9 CFU / ml. For example, each P. acnes strain may be present in an amount of at least 1.0 x 10 5 CFU / ml, preferably at least 1.0x10 6 CFU / ml, more preferably at least 1.0x10 7 CFU / ml is at least 1.0x10 8 CFU / ml, at least 1.0x10 9 CFU / ml or at least 1.0x10 10CFU / ml is present in the skin care composition. Particularly preferably, each Propionibacterium acnes strain is present in an amount of at least 1.0 x 10 10 CFU / ml, 2.0x10 10 CFU / ml, 3.0x10 10 CFU / ml, 4.0x10 10 CFU / ml, 5.0x10 10 CFU / ml, 6.0x10 10 CFU / ml, 7.0x10 10 CFU / ml, 8.0x10 10 CFU / ml or 9.0x10 10 CFU / ml is present in the skin care composition. For example, if the skin care composition of the present invention comprises a SLST C3 type strain and a SLSTK8 type strain, each of these strains may be present in an amount of 1.0x10 4 -1.0x10 11 CFU / ml, for example 1.0x10 10 CFU / ml, 2.0x10 10 CFU / ml, 3.0x10 10 CFU / ml, 4.0x10 10 CFU / ml, 5.0x10 10 CFU / ml, 6.0x10 10 CFU / ml, 7.0x10 10 CFU / ml, 8.0x10 10 CFU / ml or 9.0x10 10 The amount of CFU / ml is present.

[0108] In certain embodiments, the total amount of freeze-dried or spray-dried bacteria in the composition is 1.0 x 10 4 -1.0x10 11 CFU / ml, more preferably 1.0x10 5 -1.0x10 10 CFU / ml, even more preferably 1.0x10 7 -1.0x10 10 CFU / ml or 1.0x10 8 -1.0x10 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 1.0x10 6 CFU / ml, more preferably at least 1.0x10 7 CFU / ml is at least 1.0x108 CFU / ml, at least 1.0x10 9 CFU / ml or at least 1.0x10 10 CFU / ml skin care composition. Particularly preferably, the bacteria are present in said composition in an amount of at least 1.0 x 10 10 CFU / ml, 2.0x10 10 CFU / ml, 3.0x10 10 CFU / ml, 4.0x10 10 CFU / ml, 5.0x10 10 CFU / ml, 6.0x10 10 CFU / ml, 7.0x10 10 CFU / ml, 8.0x10 10 CFU / ml or 9.0x10 10 The amount of CFU / ml of skin care composition is present in said composition. One of ordinary skill in the art can readily determine the amount of bacteria in a freeze-dried or spray-dried composition.

[0109] Preferred composition

[0110] The above components described as suitable for use in the skin care composition of the present invention can be combined with each other without limitation. Thus, in addition to the freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes and the emollient, the skin care composition of the present invention may also include at least one excipient selected from thickeners, fillers, antioxidants, preservatives, solubilizers and pH adjusters, wherein the one or more excipients do not interfere with the reactivation of the viability and growth of the freeze-dried or spray-dried live bacteria. Particularly preferred skin care compositions encompassed by the present disclosure are described below.

[0111] A preferred skin care composition comprises

[0112] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes; and

[0113] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate.

[0114] Another preferred skin care composition comprises

[0115] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes; and

[0116] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate.

[0117] A preferred skin care composition comprises

[0118] (a) freeze-dried or spray-dried live bacteria of at least one Propionibacterium acnes strain selected from SLST D1, A5, C1, C3, H1, H2, H3, K1, K2, K4, K6, K8, K9, L1 and F4 type strains; and

[0119] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate.

[0120] Another preferred skin care composition comprises

[0121] (a) freeze-dried or spray-dried live bacteria of at least one Propionibacterium acnes strain selected from SLST D1, A5, C1, C3, H1, H2, H3, K1, K2, K4, K6, K8, K9, L1 and F4 type strains; and

[0122] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate.

[0123] A preferred skin care composition comprises

[0124] (a) freeze-dried or spray-dried live bacteria of at least one Propionibacterium acnes SLST C3 type strain and at least one Propionibacterium acnes SLST K8 type strain; and

[0125] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate.

[0126] Another preferred skin care composition comprises

[0127] (a) freeze-dried or spray-dried live bacteria of at least one Propionibacterium acnes SLST C3 type strain and at least one Propionibacterium acnes SLST K8 type strain; and

[0128] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate.

[0129] Another preferred skin care composition comprises

[0130] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0131] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate; and

[0132] (c) 0.05 to 7.5% (w / w) of Chondrus crispus extract, preferably 0.2 or 1.5% (w / w) of Chondrus crispus extract.

[0133] Another preferred skin care composition comprises

[0134] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0135] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate; and

[0136] (c) 0.05 to 7.5% (w / w) of Chondrus crispus extract, preferably 0.2 or 1.5% (w / w) of Chondrus crispus extract.

[0137] Another preferred skin care composition comprises

[0138] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0139] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate; and

[0140] (c) 0.05 to 10.0% (w / w) hydroxypropyl starch phosphate, preferably 2.0 to 4.0% (w / w) hydroxypropyl starch phosphate.

[0141] Another preferred skin care composition comprises

[0142] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0143] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate; and

[0144] (c) 0.05 to 10.0% (w / w) hydroxypropyl starch phosphate, preferably 2.0 to 4.0% (w / w) hydroxypropyl starch phosphate.

[0145] Another preferred skin care composition comprises

[0146] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0147] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate; and

[0148] (c) a citric acid / citrate buffer that provides the composition with a pH of about 4.0 to about 7.0.

[0149] Another preferred skin care composition comprises

[0150] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0151] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate; and

[0152] (c) a citric acid / citrate buffer that provides the composition with a pH of about 4.0 to about 7.0.

[0153] Another preferred skin care composition comprises

[0154] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0155] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate; and

[0156] (c) 0.05 to 5.0% (w / w) distarch phosphate, preferably 2.0 to 3.0% (w / w) distarch phosphate.

[0157] Another preferred skin care composition comprises

[0158] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0159] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate; and

[0160] (c) 0.05 to 5.0% (w / w) distarch phosphate, preferably 2.0 to 3.0% (w / w) distarch phosphate.

[0161] Another preferred skin care composition comprises

[0162] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0163] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate; and

[0164] (c) 0.05 to 5.0% (w / w) tapioca starch, preferably 2.0 to 3.0% (w / w) tapioca starch.

[0165] Another preferred skin care composition comprises

[0166] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0167] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate; and

[0168] (c) 0.05 to 5.0% (w / w) tapioca starch, preferably 2.0 to 3.0% (w / w) tapioca starch.

[0169] Another preferred skin care composition comprises

[0170] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0171] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate; and

[0172] (c) 0.01 to 2.5% (w / w) PEG-40 hydrogenated castor oil, preferably 0.5 to 1.0% (w / w) PEG-40 hydrogenated castor oil.

[0173] Another preferred skin care composition comprises

[0174] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0175] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate; and

[0176] (c) 0.01 to 2.5% (w / w) PEG-40 hydrogenated castor oil, preferably 0.5 to 1.0% (w / w) PEG-40 hydrogenated castor oil.

[0177] Another preferred skin care composition comprises

[0178] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0179] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate; and

[0180] (c) 0.01 to 2.0% (w / w) tocopherol, preferably 0.1 to 1.0% (w / w) tocopherol.

[0181] Another preferred skin care composition comprises

[0182] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0183] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate; and

[0184] (c) 0.01 to 2.0% (w / w) tocopherol, preferably 0.1 to 1.0% (w / w) tocopherol.

[0185] Another preferred skin care composition comprises

[0186] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0187] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate; and

[0188] (c) 0.01 to 2.0% (w / w) tocopherol acetate, preferably 0.1 to 1.0% (w / w) tocopherol acetate.

[0189] Another preferred skin care composition comprises

[0190] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0191] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate; and

[0192] (c) 0.01 to 2.0% (w / w) tocopherol acetate, preferably 0.1 to 1.0% (w / w) tocopherol acetate.

[0193] Another preferred skin care composition comprises

[0194] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0195] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate; and

[0196] (c) 0.5 to 20.0% (w / w) ethanol, preferably 8.0 to 15.0% (w / w) ethanol.

[0197] Another preferred skin care composition comprises

[0198] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0199] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate; and

[0200] (c) 0.5 to 20.0% (w / w) ethanol, preferably 8.0 to 15.0% (w / w) ethanol.

[0201] Another preferred skin care composition comprises

[0202] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0203] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate; and

[0204] (c) 0.05 to 0.5% (w / w) phenoxyethanol, preferably 0.1 to 0.2% (w / w) phenoxyethanol.

[0205] Another preferred skin care composition comprises

[0206] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0207] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate; and

[0208] (c) 0.05 to 0.5% (w / w) phenoxyethanol, preferably 0.1 to 0.2% (w / w) phenoxyethanol.

[0209] Another preferred skin care composition comprises

[0210] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0211] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate; and

[0212] (c) 0.05 to 0.5% (w / w) caprylyl glycol, preferably 0.1 to 0.2% (w / w) caprylyl glycol.

[0213] Another preferred skin care composition comprises

[0214] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0215] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate; and

[0216] (c) 0.05 to 0.5% (w / w) caprylyl glycol, preferably 0.1 to 0.2% (w / w) caprylyl glycol.

[0217] Another preferred skin care composition comprises

[0218] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0219] (b) 0.05 to 25.0% (w / w) dicaprylyl carbonate, preferably 7.5 to 10.0% (w / w) dicaprylyl carbonate; and

[0220] (c) 0.05 to 5.0% (w / w) methylpropylene glycol, preferably 1.0 to 5.0% (w / w) methylpropylene glycol.

[0221] Another preferred skin care composition comprises

[0222] (a) freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes, preferably freeze-dried or spray-dried live bacteria of at least one strain of Propionibacterium acnes SLST C3 type and at least one strain of Propionibacterium acnes SLST K8 type;

[0223] (b) 0.05 to 25.0% (w / w) ethylhexyl cocoate, preferably 7.5 to 10.0% (w / w) ethylhexyl cocoate; and

[0224] (c) 0.05 to 5.0% (w / w) methylpropylene glycol, preferably 1.0 to 5.0% (w / w) methylpropylene glycol.

[0225] Cosmetic and therapeutic uses

[0226] The skin care composition described above can be used to modulate the skin microbiome, in particular for maintaining healthy skin, e.g., skin without acne. Compositions comprising at least one live bacterial strain of Propionibacterium acnes can help the skin to reverse a diseased microbiome state to a healthy microbiome state. In a preferred embodiment, the skin care composition is used to prevent acne formation or to treat acne. In another preferred embodiment, the skin care composition is used to prevent acne recurrence in a subject who has received standard acne treatment. Particularly preferably, the subject is a human.

[0227] In one aspect, the present invention provides a skin care composition as described above, which is used in a method for improving the appearance of the skin of a subject and / or regulating (e.g., increasing or decreasing) the sebum production of the skin cells of the subject and / or maintaining the healthy skin of the subject, e.g., skin without acne. In another aspect, the present invention relates to the use of a skin care composition as described above, which is used to improve the appearance of the skin of a subject and / or regulate (e.g., increasing or decreasing) the sebum production of the skin cells of the subject and / or maintaining the healthy skin of the subject, e.g., skin without acne. In one aspect, the present invention provides a skin care composition as described above, which is used in a method for treating or preventing a condition selected from acne, oily skin, progressive macular hypopigmentation, dandruff, atopic eczema, atopic dermatitis, and rosacea in a subject. Particularly preferably, the subject is a human being.

[0228] Also provided are methods of treating the skin of a subject by administering a skin care composition as described above. These methods may be cosmetic or therapeutic methods. In one aspect, a method of improving the appearance of a subject's skin and / or regulating sebum production in a subject's skin cells and / or maintaining healthy skin of a subject is provided, the method comprising topically administering a skin care composition as described above. In another aspect, the present invention provides a method of treating or preventing a condition selected from acne, oily skin, progressive macular hypopigmentation, dandruff, atopic eczema, atopic dermatitis and rosacea in a subject, the method comprising topically administering a skin care composition as described above. Particularly preferably, the subject is a human being.

[0229] When the composition is applied to the skin, the amount of the composition applied to the skin is preferably between 0.5 g and 2.0 g, more preferably between 0.5 g and 1.0 g. In other words, the amount of the composition may correspond to at least 1.0 x 10 5 CFU, at least 1.0x10 6 CFU, at least 1.0x10 7 CFU, at least 1.5x10 7 CFU, at least 2.0x10 7 CFU or at least 2.5x10 7 CFU.

[0230] Ready-to-use compositions and kits

[0231] The skin care composition of the present invention can be provided as a ready-to-use composition suitable for direct topical administration to the skin. Such compositions can be provided in different forms, including but not limited to the form of gels, creams, lotions, ointments, pastes, soft pastes, suspensions, solutions, salves, waxes, milks, emulsions, etc. In such compositions, the freeze-dried or spray-dried live bacteria are present in a mixture with other cosmetic or pharmaceutical excipients described elsewhere herein, such as emollients, fillers, etc. After these compositions are applied to the skin, the dried bacteria are reactivated on the skin of the object to which the product is applied. The growth of the reactivated bacteria from the skin care composition will positively affect the microbial flora on the skin of the object.

[0232] 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 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, at least 15 weeks, at least 16 weeks, at least 17 weeks, at least 18 weeks, at least 19 weeks, at least 20 weeks, at least 21 weeks, at least 22 weeks, at least 23 weeks, at least 24 weeks, at least 25 weeks, at least 26 weeks, at least 27 weeks, at least 28 weeks, at least 29 weeks, at least 30 weeks or more than 30 weeks. In other words, such compositions are preferably stable at room temperature for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months or more than 6 months. When used in this article, if the reduction of the number of colony forming units present in the composition after storage is less than 3log reduction, preferably less than 2log reduction, more preferably less than 1log reduction, then the composition is considered to be stable. In other words, a composition is considered stable if the number of colony forming units present in the composition after storage decreases less than 1000-fold, preferably less than 100-fold, more preferably less than 10-fold relative to the number of colony forming units in the composition before storage.

[0233] The skin care composition of the present invention can also be provided as a kit, wherein the freeze-dried or spray-dried bacteria are spatially separated from other components such as cosmetic or therapeutic components. For example, the kit can take the form of a package with two spatially separated compartments, wherein the first compartment contains the freeze-dried or spray-dried bacteria and the second compartment contains a cosmetic preparation such as an aqueous cosmetic preparation. Before use, the contents of the two compartments are mixed with each other by, for example, a consumer or a patient to provide a homogeneous skin care composition, which is then applied to the skin. The kit assembly has the advantage 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 assembly, in an advantageous case, the weight ratio of the bacteria in the first compartment to the cosmetic preparation in the second compartment, particularly the aqueous cosmetic preparation, 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 mixing the contents of the two compartments, the skin care composition preferably contains 1-10% by weight of freeze-dried or spray-dried bacteria and 99-90% by weight of a cosmetic preparation, such as an aqueous cosmetic preparation. According to the present invention, the kit of parts may be provided in, for example, Lyo- Dual compartment syringe, V- In a dual compartment system described in Dual Compartment Kapur or WO2018077598 A1. In another preferred embodiment, the freeze-dried or spray-dried bacteria in the first compartment can be suspended in lipids or oils. This will greatly facilitate packaging and filling. In addition, the surrounding lipids or oils 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.

[0234] In one embodiment, the skin care composition of the present invention is an aqueous formulation such as a gel. Aqueous formulations as used 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.

[0235] When used in the context of a method or composition, the term "comprising" means that in addition to the method steps or components presented, 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 an additional component. Similarly, a method "comprising" steps (a) and (b) may also include (c) as an additional 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 not mentioned 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 contain 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 contain 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 enumerated method steps or components, or more preferably may consist of the enumerated method steps or components. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0236] literature

[0237] Bek-Thomsen, M., Lomholt, HB and Kilian, M. (2008). Acne is not associated with yet-uncultured bacteria. J. Clin. Microbiol. 46, 3355-3360.

[0238] Belkaid, Y. and Segre, JA (2014). Dialogue between skin microbiota and immunity. Science 346, 954-959.

[0239] Downing, DT, Stewart, ME, Wertz, PW and Strauss, JS (1986), Essential fatty acids and acne, J. Am. Acad. Dermatol. 14, 221-225.

[0240] Fitz-Gibbon, S., Tomida, S., Chiu, B.-H., Nguyen, L., Du, C., Liu, M., Elashoff, D., Erfe, M. C., Loncaric, A., Kim, J., et al. (2013). Propionibacterium acnes strain populations in the humanskin microbiome associated with acne. J. Invest. Dermatol. 133, 2152-2160.

[0241] Grice, EA and Segre, JA (2011). The skin microbiome. Nat. Rev. Microbiol. 9, 244-253.

[0242] Holmes, AD. (2013), Potential role of microorganisms in the pathogenesis of rosacea, J. Am. Acad. Dermatol. 69, 1025-1032.

[0243] Kong, HH, Oh, J., Deming, C., Conlan, S., Grice, EA, Beatson, MA, Nomicos, E., Polley, EC, Komarow, HD, Murray, PR, et al. (2012). Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 22, 850-859.

[0244] Letawe, C., Boone, M. and Piérard, GE, (1998), Digital image analysis of the effect of topically applied linoleic acid on acne microcomedones, Clin. Exp. Dermatol. 23, 56-58.

[0245] Lomholt, HB and Kilian, M., (2010), Population Genetic Analysis of Propionibacterium acnesIdentifies a Subpopulation and Epidemic Clones Associated with Acne, PLoS ONE 5.

[0246] McDowell, A., Barnard, E., Nagy, I., Gao, A., Tomida, S., Li, H., Eady, A., Cove, J., Nord, C.E., and Patrick, S. (2012). An Expanded Multilocus Sequence Typing Scheme for Propioni-bacterium acnes: Investigation of “Pathogenic”, “Commensal” and Antibiotic Resistant Strains. PLoS ONE 7, e41480.

[0247] Oh, J., Byrd, AL, Deming, C., Conlan, S., NISC Comparative Sequencing Program, Kong, HH and Segre, JA, (2014), Biogeography and individuality shape function in the human skin metagenome, Nature 514, 59-64.

[0248] Rosson, RA, Grund, AD, Deng, M.-D. and Sanchez-Riera, F., (2004), Linoleate isomerase.

[0249] Scholz,CFP,Jensen,A.,Lomholt,HB, H. and Kilian, M., (2014), A Novel High-Resolution Single Locus Sequence Typing Scheme for Mixed Populations of Propionibacterium acnes In Vivo, PLoS ONE 9, e104199.

[0250] Example

[0251] The present invention is further illustrated by the following examples, which should not be construed as further limiting. The entire contents of all references (including literature references, authorized patents, published patent applications, and co-pending patent applications) cited throughout this application are expressly incorporated herein by reference.

[0252] Example 1: Evaluation of Minimum Inhibitory Concentration (MIC)

[0253] In microbiology, MIC is the lowest concentration of a chemical that prevents visible growth of bacteria. The MIC value obtained depends on both the microorganism and the test compound. MIC is determined by preparing a series of concentrations of the test compound in vitro, incubating the solution with a separate batch of cultured bacteria, and measuring the results using agar dilution or broth microdilution. For experiments using Propionibacterium acnes strains C3 and K8, a culture medium containing yeast extract, soy peptone and dextrose was used. MIC is determined by turbidity.

[0254] A total of 125 cosmetic excipients were tested for compatibility with Propionibacterium acnes strains C3 and K8. Hydrophilic compounds were tested in the form of 96-well plate liquid broth, poorly soluble compounds were pre-dissolved in DMSO before dilution in liquid broth, and hydrophobic or solid compounds were tested in agar well diffusion test assays. Different dilutions of the test excipients in culture medium were prepared in Falcon tubes and then dispensed into deep well plates using a multichannel dispenser. Each well received 1.2 ml and was subsequently inoculated with 120 μl of a P. acnes bacterial suspension (strains C3 and K8). 200 μl was transferred from the deep well plate to each well of a transparent 96-well parallel plate. The remainder was discarded. The plates were then incubated anaerobically at 37°C for 3 days. After incubation, the test plates were visually inspected and the wells were scored for growth inhibition or complete growth inhibition to determine the minimum inhibitory concentration.

[0255] result:

[0256] It has been found that the compatibility of standard excipients to bacterial strains varies widely. Only a few excipients resulted in no inhibition or significant inhibition. The following table lists these excipients and their compatibility values ​​to P. acnes strains C3 and K8. The compatibility values ​​represent the MIC values ​​of the listed ingredients when using the P. acnes strains tested. At this concentration [% w / vol], the test compound starts to interfere with the growth of the test strain. The compound can be used in the formulation at a concentration below this concentration.

[0257] The results obtained from the MIC testing are depicted in Table 1 below.

[0258]

[0259] Example 2: Reactivation assay of freeze-dried bacteria in prototype formulations

[0260] A set of 15 prototype formulations was designed based on the results from the MIC tests to test the efficient reactivation of freeze-dried P. acnes bacteria. For this purpose, freeze-dried powders of P. acnes strains K8 and C3 were produced and mixed with the other ingredients shown below. The ingredients are listed in % (w / w). The formulations were provided in two pre-mixed compositions A and B, which were finally mixed with each other. The following formulations were manufactured:

[0261] Preparation 1

[0262]

[0263]

[0264] Preparation 2

[0265]

[0266] Preparation 3

[0267]

[0268] Preparation 4

[0269]

[0270] Preparation 5

[0271]

[0272] Preparation 6

[0273]

[0274]

[0275] Preparation 7

[0276]

[0277] Preparation 8

[0278]

[0279]

[0280] Preparation 9

[0281]

[0282] Preparation 10

[0283]

[0284] Preparation 11

[0285]

[0286]

[0287] Preparation 12

[0288]

[0289] Preparation 13

[0290]

[0291]

[0292] Preparation 14

[0293]

[0294] Preparation 15

[0295]

[0296] The formulations are depicted in tabular form in Figure 1 For formulations 1-11, the CFU target value was 1x10 7 For formulations 12-15, the CFU target was 1x10 6 . CFU counts were performed directly after mixing the formulations to assess the effect of the prototype formulation on bacterial recovery and subsequent stability rates. Briefly, formulation component A (lyophilisate / oil suspension) and formulation component B (hydrogel / aqueous solution) were mixed together and vortexed thoroughly. Aliquots were taken immediately after mixing and transferred to 0.9% NaCl. Further dilutions were plated on COST agar plates and incubated anaerobically at 37°C for 5 days.

[0297] result :

[0298] The results are depicted in Figure 2 and 3 As can be seen, all formulations 1-15 showed acceptable reactivation of freeze-dried bacteria. The ingredients had no negative impact on bacterial reactivation.

[0299] Example 3: Reactivation assay of freeze-dried bacteria in prototype formulations

[0300] Another set of 11 prototype formulations with higher concentrations of excipients of the invention were prepared similar to the formulations tested in Example 2. The effects of the formulations on the reactivation of freeze-dried P. acnes bacteria were tested as described in Example 2. As a control, formulations containing the lyophilisate and a small amount of excipients were prepared. The following formulations were manufactured:

[0301] Comparison

[0302]

[0303]

[0304] Preparation 1

[0305]

[0306] Preparation 2

[0307]

[0308]

[0309] Preparation 3

[0310]

[0311] Preparation 4

[0312]

[0313]

[0314] Preparation 5

[0315]

[0316] Preparation 6

[0317]

[0318]

[0319] Preparation 7

[0320]

[0321] Preparation 8

[0322]

[0323]

[0324] Preparation 9

[0325]

[0326] Preparation 10

[0327]

[0328]

[0329] Preparation 11

[0330]

[0331] The formulations are depicted in tabular form in Figure 4 Medium. For all preparations, the CFU target value was 1x10 9 CFU counts were performed as described in Example 2 immediately and 1 hour after mixing the formulations.

[0332] result :

[0333] The results are depicted in Figure 5 As can be seen, all formulations 1-11 showed acceptable reactivation of freeze-dried bacteria. Even at the high concentrations used in this experiment, the ingredients had no negative impact on the reactivation of the bacteria.

[0334] Example 4: Comparative reactivation assay

[0335] To compare the excipients identified herein as being particularly useful for compositions containing lyophilized or spray-dried live bacteria with other excipients having the same or similar functions, comparative formulations V-1 to V-10 were prepared and tested for their effects on bacterial reactivation as described in Example 2. As a positive control, formulations containing lyophilisates that were found to have no negative effects on bacterial reactivation were used. The following formulations were made for comparison:

[0336] Comparison

[0337]

[0338] Preparation V-1

[0339]

[0340]

[0341] Preparation V-2

[0342]

[0343] Preparation V-3

[0344]

[0345]

[0346] Preparation V-4

[0347]

[0348] Preparation V-5

[0349]

[0350]

[0351] Preparation V-6

[0352]

[0353] Preparation V-7

[0354]

[0355]

[0356] Preparation V-8

[0357]

[0358] Preparation V-9

[0359]

[0360]

[0361] Preparation V-10

[0362]

[0363] The formulations are depicted in tabular form in Figure 7 Medium. For all preparations, the CFU target value was 1x10 9 CFU counts were performed as described above in Example 2 immediately after mixing the formulations and also after 1 hour or 6 hours, respectively.

[0364] result :

[0365] The results are depicted in Figure 6 As can be seen, formulations V-1 to V-10 had a significant negative effect on the reactivation of the bacteria. This confirms that a large number of excipients commonly used in cosmetic formulations negatively interfere with the viability or reactivation of the freeze-dried bacteria used in this study. Sequence Listing <110> S-Biomedic NV Beiersdorf AG <120> New skin care composition <130> P 108454 <160> 82 <170> PatentIn version 3.5 <210> 1 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 1 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 2 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 2 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgattctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaatat gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 3 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 3 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatgg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa taactcgatc cacccctgcc cattacatgg gtacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 4 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 4 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatgg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 5 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 5 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgccggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 6 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 6 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atat 484 <210> 7 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 7 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgccatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgattctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaatat gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 8 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 8 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg cctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 9 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 9 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgccggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 ctgtcatcat gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 10 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 10 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgccggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc tacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 11 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 11 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgccggg aaacagcacc aggaagcccg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 12 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 12 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgccggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atattccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 13 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 13 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctgg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 14 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 14 gttgcacacc agggggtcaa cttggcgttt tcagttcaaa attgattcaa actaacagtt ccatgccggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 15 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 15 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgccggg aaacagtacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 16 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 16 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgccggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gatccctatt gtcgccctta ttagggcaag cggtgccagt agcagaatat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 17 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 17 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccggt agcagaatat gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 18 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 18 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gccacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 19 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 19 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc gacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 20 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 20 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt ttcgccctta ttagggcaag cggtgccagt agcagaatat gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 21 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 21 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgccggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacaatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 22 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 22 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgccggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctggtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 23 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 23 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatctc ctttctagtc aacccaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgattctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaatat gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 24 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 24 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcag caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 25 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 25 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 26 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 26 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccat gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 27 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 27 gttgcacacc agggggtcaa cttggcgtcc ttagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 28 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 28 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatctgc atag 484 <210> 29 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 29 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaaactcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccgcc 240 ctgtcatcac gaagaccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac ttgaggatac agtcgtccat cacgcccacc tacataccca ttacatcagc atag 484 <210> 30 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 30 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaaactcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaac gccgcgatat atgttccgcc 240 ctgtcatcac gaagaccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac ttgaggatac agtcgtccat cacgcccacc tacataccca ttacatcagc atag 484 <210> 31 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 31 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaaactcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctaccttg tcagacccag gacgatgggt gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccgcc 240 ctgtcatcac gaagaccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac ttgaggatac agtcgtccat cacgcccacc tacataccca ttacatcagc atag 484 <210> 32 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 32 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgatttaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacctca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgagaatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 33 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 33 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgatttaa actaacagtt ccatgtcggg aaacagcacc agaaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacctca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 34 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 34 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgatttaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacctca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 35 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 35 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgatttaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacctca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catgaaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 36 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 36 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgatttaa actaacagtt tcatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacctca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 37 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 37 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgatttaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat tccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacctca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 38 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 38 gttgcacacc aggggtcaa cttggcgtcc tcagttcaaa attgatttaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacctca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 39 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 39 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgatttaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcgcctca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 40 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 40 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa atagatttaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacctca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 41 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 41 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tatatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 ctgtcatcac gaacgccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgattctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaatat gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 42 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 42 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tatatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 ctgtcatcac gaacgccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgattctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaatat gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacaccagc atag 484 <210> 43 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 43 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tatatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 ctgtcatcac gaacgccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgattctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaatat gtcacctaaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 44 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 44 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 ctgtcatcac gaacgccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 45 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 45 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 ctgtcatcac gaacgccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgcta gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaatat gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 46 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 46 gttacacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 ctgtcatcac gaacgccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 47 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 47 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tatatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 ctgtcatcac gaacgccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgattctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaatat gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat caagcccgcc tacataccca ttacatcagc atag 484 <210> 48 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 48 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcgga aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 ctgtcatcac gaacgccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 49 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 49 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 ctgtcatcac gaacgccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cgatgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 50 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 50 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacacccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 ctgtcatcac gaacgccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 51 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 51 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg cctttcattg cgagaaacat cttacttatg tacatttcta agctatagcg tctacccttg tcagacccag gacgatgggt 180 gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 ctgtcatcac gaacgccacc acaatcgatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatac tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 52 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 52 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatatcg tctacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 53 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 53 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatatcg tctacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctca ttagggcaag cggtgccagt together gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 54 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 54 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatatcg tccacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 55 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 55 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agctatatcg tctacccttg tcagacccgg gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 56 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 56 gttgcacacc agggggtcaa cttggcgtcc tcagttcaaa attgattcaa actaacagtt ccatgtcggg aaacagcacc aggaagctcg tgacatatcg tctttcattg cgagaaacat cttacttatg tacatttcta agccatatcg tctacccttg tcagacccag gacgatggat gtcacatccc ctttctagtc aacctaagag aggaggaat gccgcgatat atgttccacc 240 300. ctgtcatcac gaaggccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcaa caactcgatc cacccctgcc cattacatgg gtaacatatc catggaggtt cgatgtatat tcgaggatac agtcgtccat cacgcccgcc tacataccca ttacatcagc atag 484 <210> 57 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 57 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg tgacatatcg tctttcattg cgagaaacat cttacttata cacatttcta agctatattg tctacccctg tcagacccag gacgatgggt gtcatatccc ctttccagtc aacctaagaa gggaggaaat gccgcgatat atgttccgcc 300. ctgtcatcat gaatgccacc acaatctatc ccggaacagc cgtacttcac ccaccatgcc ccgatgctgg attcctattg tcgcccttat tagagcaagc ggtgccagca gcagaatatt tcacctcagc aactcgatcc gctcctgccc attacatggg taacatatcc atggaggtac 420 gatgtatgca tcgaggatgc agtcgtcc tatgcccgcc tacataccca ttccatcagc atag 484 <210> 58 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 58 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attggttcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg tgacatatcg tctttcattg cgagaaacat cttacttata cacatttcta agctatattg tctacccctg tcagacccag gacgatgggt gtcatatccc ctttccagtc aacctaagaa gggaggaaat gccgcgatat atgttccgcc 300. ctgtcatcat gaatgccacc acaatctatc ccggaacagc cgtacttcac ccaccatgcc ccgatgctgg attcctattg tcgcccttat tagagcaagc ggtgccagca gcagaatatt tcacctcagc aactcgatcc gctcctgccc attacatggg taacatatcc atggaggtac 420 gatgtatgca tcgaggatgc agtcgtcc tatgcccgcc tacataccca ttccatcagc atag 484 <210> 59 <211> 483 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 59 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg tgacatatcg tctttcattg cgagaaacat cttacttata cacatttcta agctatatgt ctacccctgt cagacccagg acgatgggtg 180 tcatatcccc tttccagtca acctaagaag ggaggaatg ccgcgatata tgttccgccc 240 tgtcatcatg aatgccacca caatctatcc cggaacagcc gtacttcacc caccatgccc cgatgctgga ttcctattgt cgcccttatt agagcaagcg gtgccagcag cagaatattt cacctcagca actcgatccg ctcctgccca ttacatgggt aacatatcca tggaggtacg 420 atgtatgcat cgaggatgca gtcgtctact atgcccgcct acatacccat tccatcagca 480 tag 483 <210> 60 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 60 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg taacatatcg tctttcattg cgagaaacat cttacttata cacatttcta agctatattg tctacccctg tcagacccag gacgatgggt gtcatatccc ctttccagtc aacctaagaa gggaggaaat gccgcgatat atgttccgcc 300. ctgtcatcat gaatgccacc acaatctatc ccggaacagc cgtacttcac ccaccatgcc ccgatgctgg attcctattg tcgcccttat tagagcaagc ggtgccagca gcagaatatt tcacctcagc aactcgatcc gctcctgccc attacatggg taacatatcc atggaggtac 420 gatgtatgca tcgaggatgc agtcgtcc tatgcccgcc tacataccca ttccatcagc atag 484 <210> 61 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 61 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg tgacatatcg tctttcattg cgagaaacat cttacttata cacatttcta agctatattg tctacccctg tcagacccag gacgatgggt gtcatatccc ctttccagtc aacctaagaa gggaggaaat gccgcgatat atgttccgcc 300. ctgtcatcat gaatgccacc acaatctatc ccggaacagc cgtacttcac ccaccatgcc tcgatgctgg attcctattg tcgcccttat taggcaagc ggtgccagca gcagaatatt tcacctcagc aactcgatcc gctcctgccc attacatggg taacatatcc atggaggtac 420 gatgtatgca tcgaggatgc agtcgtcc tatgcccgcc tacataccca ttccatcagc atag 484 <210> 62 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 62 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg tgacatatcg tctttcattg cgagaaacat cttatttata cacatttcta agctatattg tctacccctg tcagacccag gacgatgggt gtcatatccc ctttccagtc aacctaagaa gggaggaaat gccgcgatat atgttccgcc 300. ctgtcatcat gaatgccacc acaatctatc ccggaacagc cgtacttcac ccaccatgcc ccgatgctgg attcctattg tcgcccttat tagagcaagc ggtgccagca gcagaatatt tcacctcagc aactcgatcc gctcctgccc attacatggg taacatatcc atggaggtac 420 gatgtatgca tcgaggatgc agtcgtcc tatgcccgcc tacataccca ttccatcagc atag 484 <210> 63 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 63 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg tgacatatcg tctttcattg cgagaaacat cttacttata cacatttcta agctatattg tctacccctg tcagacccag gacgatgggt gtcatatccc ctttccagtc aacctaaga ggaggaat gccgcgatat atgttccgcc 300. ctgtcatcat gaatgccacc acaatctatc ccggaacagc cgtacttcac ccaccatgcc ccgatgctgg attcctattg tcgcccttat tagagcaagc ggtgccagca gcagaatatt tcacctcagc aactcgatcc gctcctgccc attacatggt taacatatcc atggaggtac 420 gatgtatgca tcgaggatgc agtcgtcc tatgcccgcc tacataccca ttccatcagc atag 484 <210> 64 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 64 attgcacacc agggggtcaa cttggtgtcc tcagttcaaa attggttcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg tgacatatcg tctttcattg cgagaaacat cttacttata cacatttcta agctatattg tctacccctg tcagacccag gacgatgggt gtcatatccc ctttccagtc aacctaagaa gggaggaaat gccgcgatat atgttccgcc 300. ctgtcatcat gaatgccacc acaatctatc ccggaacagc cgtacttcac ccaccatgcc ccgatgctgg attcctattg tcgcccttat tagagcaagc ggtgccagca gcagaatatt tcacctcagc aactcgatcc gctcctgccc attacatggg taacatatcc atggaggtac 420 gatgtatgca tcgaggatgc agtcgtcc tatgcccgcc tacataccca ttccatcagc atag 484 <210> 65 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 65 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attggttcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg tgacatatcg tctttcattg cgagaaacat cttacttata cacatttcta agctatattg tctacccctg tcagacccag gacgatgggt gtcatatccc ctttccagtc aacctaagaa gggaggaaat gccgcgatat atgttccgcc 300. ctgtcatcat gaatgccacc acaatctatc ccggaacagc cgtacttcac ccaccatgcc ccgatgctgg attcctatgg tcgcccttat taggcaagc ggtgccagca gcagaatatt tcacctcagc aactcgatcc gctcctgccc attacatggg taacatatcc atggaggtac 420 gatgtatgca tcgaggatgc agtcgtcc tatgcccgcc tacataccca ttccatcagc atag 484 <210> 66 <211> 483 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 66 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg tgacatatca tctttcattg cgagaaacat cttacttata cacatttcta agctatatgt ctacccctgt cagacccagg acgatgggtg 180 tcatatcccc tttccagtca acctaagaag ggaggaatg ccgcgatata tgttccgccc 240 tgtcatcatg aatgccacca caatctatcc cggaacagcc gtacttcacc caccatgccc cgatgctgga ttcctattgt cgcccttatt agagcaagcg gtgccagcag cagaatattt cacctcagca actcgatccg ctcctgccca ttacatgggt aacatatcca tggaggtacg 420 atgtatgcat cgaggatgca gtcgtctact atgcccgcct acatacccat tccatcagca 480 tag 483 <210> 67 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 67 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attggttcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg tgacatgtcg tctttcattg cgagaaacat cttacttata cacatttcta agctatattg tctacccctg tcagacccag gacgatgggt gtcatatccc ctttccagtc aacctaagaa gggaggaaat gccgcgatat atgttccgcc 300. ctgtcatcat gaatgccacc acaatctatc ccggaacagc cgtacttcac ccaccatgcc ccgatgctgg attcctattg tcgcccttat tagagcaagc ggtgccagca gcagaatatt tcacctcagc aactcgatcc gctcctgccc attacatggg taacatatcc atggaggtac 420 gatgtatgca tcgaggatgc agtcgtcc tatgcccgcc tacataccca ttccatcagc atag 484 <210> 68 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 68 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attggttcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg tgacatatcg tctttcattg cgagaaacat cttacttata cacatttcta agctatactg tctacccctg tcagacccag gacgatgggt gtcatatccc ctttccagtc aacctaagaa gggaggaaat gccgcgatat atgttccgcc 300. ctgtcatcat gaatgccacc acaatctatc ccggaacagc cgtacttcac ccaccatgcc ccgatgctgg attcctattg tcgcccttat tagagcaagc ggtgccagca gcagaatatt tcacctcagc aactcgatcc gctcctgccc attacatggg taacatatcc atggaggtac 420 gatgtatgca tcgaggatgc agtcgtcc tatgcccgcc tacataccca ttccatcagc atag 484 <210> 69 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 69 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attggttcaa actaacggtt ccgtgtcggg aaacagcacc agaaaacttg tgacatatcg tctttcattg cgagaaacat cttacttata cacatttcta agctatattg tctacccctg tcagacccag gacgatgggt gtcatatccc ctttccagtc aacctaagaa gggaggaaat gccgcgatat atgttccgcc 300. ctgtcatcat gaatgccacc acaatctatc ccggaacagc cgtacttcac ccaccatgcc ccgatgctgg attcctattg tcgcccttat tagagcaagc ggtgccagca gcagaatatt tcacctcagc aactcgatcc gctcctgccc attacatggg taacatatcc atggaggtac 420 gatgtatgca tcgaggatgc agtcgtcc tatgcccgcc tacataccca ttccatcagc atag 484 <210> 70 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 70 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attggttcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactca tgacatatcg tctttcattg cgagaaacat cttacttata cacatttcta agctatattg tctacccctg tcagacccag gacgatgggt gtcatatccc ctttccagtc aacctaagaa gggaggaaat gccgcgatat atgttccgcc 300. ctgtcatcat gaatgccacc acaatctatc ccggaacagc cgtacttcac ccaccatgcc ccgatgctgg attcctattg tcgcccttat tagagcaagc ggtgccagca gcagaatatt tcacctcagc aactcgatcc gctcctgccc attacatggg taacatatcc atggaggtac 420 gatgtatgca tcgaggatgc agtcgtcc tatgcccgcc tacataccca ttccatcagc atag 484 <210> 71 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 71 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtatcggg aaacagcacc agaaaactcg ggacatatcg tctttcattg cgagaaaaat cttacttatg cgcatttcta agctatagcg tctacccttg tcagacccag gacgatgagt gtcacatccc ctttccagtc aacctaagag aggaggaat gccgcgatat atgctccgcc 240 300. ctgtcatcac gaaagccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcag caactcgatc cgcccctgcc cattacatgg gtaacatatc catggaggtt 420 cgatgtatac tcgaggatac agtcgcccat cacgccagcc tacataccca ttacatcagc atag 484 <210> 72 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 72 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtatcggg aaacagcacc agaaaactcg ggacatatcg tctttcattg cgagaaaaat cttacttatg cgcatttcta agctatagcg tctacccttg ccagacccag gacgatgagt gtcacatccc ctttccagtc aacctaagag aggaggaat gccgcgatat atgctccgcc 240 300. ctgtcatcac gaaagccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcag caactcgatc cgcccctgcc cattacatgg gtaacatatc catggaggtt 420 cgatgtatac tcgaggatac agtcgcccat cacgccagcc tacataccca ttacatcagc atag 484 <210> 73 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 73 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtatcggg aaacagcacc agaaaactcg ggacatatcg tctttcattg cgagaaaaat cttacttatg cgcatttcta agctatatcg tctacccttg ccagacccag gacgatgagt gtcacatccc ctttccagtc aacctaagag aggaggaat gccgcgatat atgctccgcc 240 300. ctgtcatcac gaaagccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcag caactcgatc cgcccctgcc cattacatgg gtaacatatc catggaggtt 420 cgatgtatac tcgaggatac agtcgcccat cacgccagcc tacataccca ttacatcagc atag 484 <210> 74 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 74 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg ggacatatcg tctttcattg cgagaaaaat cttacttatg cgcatttcta agctatagcg tctacccttg tcagacccag gacgatgagt gtcacatccc ctttccagtc aacctaagag aggaggaat gccgcgatat atgctccgcc 240 300. ctgtcatcac gaaagccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcag caactcgatc cgcccctgcc cattacatgg ttaacatatc catggaggtt cgatgtatac tcgaggatac agtcgcccat cacgccagcc tacataccca ttacatcagc atag 484 <210> 75 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 75 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtgtcggg aaacagcacc agaaaactcg ggacatatcg tctttcattg cgagaaaaat cttacttatg cgcatttcta agctatagcg tctacccttg tcagacccag gacgatgagt gtcacatccc ctttccagtc aacctaagag aggaggaat gccgcgatat atgctccgcc 240 300. ctgtcatcac gaaagccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaat 360 gtcacctcag caactcgatc cgcccctgcc cattacatgg gtaacatatc catggaggtt 420 cgatgtatac tcgaggatac agtcgcccat cacgccagcc tacataccca ttacatcagc atag 484 <210> 76 <211> 484 <212> DNA <213> Anti-inflammatory drug(Propionibacterium acnes) <400> 76 gttgcacacc agggggtcaa cttggtgtcc tcagttcaaa attgattcaa actaacggtt ccgtatcggg aaacagcacc agaaaactcg ggacatatcg tctttcattg cgagaaaaat cttacttatg cgcatttcta agctatagcg tctacccttg tcagacccag gacgatgagt gtcacatccc ctttccagtc aacctaagag aggaggaat gccgcgatat atgctccgcc 240 ctgtcatcac gaaagccacc acaatctatc ccagaacagc cggcacttca ctcacgatgc 300 cccgatgctg gattcctatt gtcgccctta ttagggcaag cggtgccagt agcagaatat 360 gtcacctcag caactcgatc cgcccccgcc cattacatgg gtaacatatc catggaggtt 420 cgatgtatac tcgaggatac agtcgcccat cacgccagcc tacataccca ttacatcagc 480 atag 484 <210> 77 <211> twenty one <212> DNA <213> Artificial sequence <220> <223> Synthetic polynucleotides <400> 77 cagcggcgct gctagaact t 21 <210> 78 <211> 20 <212> DNA <213> Artificial sequence <220> <223> Synthetic polynucleotides <400> 78 ccggctggca aatgaggcat 20 <210> 79 <211> 54 <212> DNA <213> Artificial sequence <220> <223> Synthetic polynucleotides <400> 79 tcgtcggcag cgtcagatgt gtataagaga cagcagcggc gctgctaaga actt 54 <210> 80 <211> 54 <212> DNA <213> Artificial sequence <220> <223> Synthetic polynucleotides <400> 80 gtctcgtggg ctcggagatg tgtataagag acagccggct ggcaaatgag gcat 54 <210> 81 <211> 54 <212> DNA <213> Artificial sequence <220> <223> Synthetic polynucleotides <400> 81 tcgtcggcag cgtcagatgt gtataagaga cagcagcggc gctgctaaga actt 54 <210> 82 <211> 54 <212> DNA <213> Artificial sequence <220> <223> Synthetic polynucleotides <400> 82 gtctcgtggg ctcggagatg tgtataagag acagccggct ggcaaatgag gcat 54

Claims

1. A skin care composition for topical administration to the skin, comprising: (a) freeze-dried or spray-dried live bacteria of at least one SLST C3 strain of Propionibacterium acnes and / or at least one SLST K8 strain of Propionibacterium acnes, wherein each Propionibacterium acnes strain in the composition is present in an amount of 10 4 -10 11 CFU / ml; and (b) an emollient selected from dicaprylyl carbonate, ethylhexyl cocoate and mixtures thereof, wherein the dicaprylyl carbonate and / or the ethylhexyl cocoate are present in the skin care composition in an amount of 7.5 to 10.0% (w / w).

2. The skin care composition of claim 1, wherein the emollient is dicaprylyl carbonate.

3. The skin care composition of claim 1, wherein the emollient is ethylhexyl cocoate.

4. The skin care composition of claim 1, wherein the emollient is a mixture of dicaprylyl carbonate and ethylhexyl cocoate.

5. The skin care composition according to claim 4, wherein dicaprylyl carbonate and ethylhexyl cocoate are present in equal amounts.

6. A skin care composition according to claim 4, wherein the total amount of emollient in the composition does not exceed 20.0% (w / w).

7. A skin care composition according to any one of claims 1 to 6, wherein the composition does not comprise any other emollients than dicaprylyl carbonate and / or ethylhexyl cocoate.

8. The skin care composition according to any one of claims 1 to 6, wherein the composition further comprises a thickener selected from the group consisting of Chondrus crispus extract, hydroxypropyl starch phosphate, and mixtures thereof.

9. The skin care composition according to any one of claims 1 to 6, wherein the composition further comprises a filler selected from the group consisting of distarch phosphate, tapioca starch, and mixtures thereof.

10. The skin care composition according to any one of claims 1 to 6, wherein the composition further comprises an antioxidant selected from the group consisting of tocopherol, tocopherol acetate, and mixtures thereof.

11. The skin care composition according to any one of claims 1 to 6, wherein the composition further comprises a preservative selected from the group consisting of ethanol, phenoxyethanol, caprylyl glycol, methylpropanediol, and mixtures thereof.

12. The skin care composition according to any one of claims 1 to 6, wherein the composition further comprises PEG-40 hydrogenated castor oil as a solubilizer.

13. The skin care composition according to any one of claims 1 to 6, wherein the composition further comprises citric acid / citrate buffer as a pH adjusting agent.

14. The skin care composition according to any one of claims 1 to 6, wherein the composition further comprises at least one freeze-dried or spray-dried live bacteria of the Propionibacterium acnes SLST A5 strain.

15. The skin care composition according to any one of claims 1 to 6, wherein the composition further comprises at least one freeze-dried or spray-dried live bacteria of the Propionibacterium acnes SLST F4 type strain.

16. The skin care composition according to any one of claims 1 to 6, wherein the concentration of each P. acnes strain is at least 0.5% (w / v) of the skin care composition.

17. The skin care composition according to claim 1, wherein the at least one P. acnes SLST C3 type strain and the at least one P. acnes SLST K8 type strain are present in equal concentrations in the composition.

18. The skin care composition of claim 1, wherein the at least one P. acnes SLST C3 type strain is present in the composition at a higher concentration than the at least one P. acnes SLST K8 type strain, or wherein the at least one P. acnes SLST K8 type strain is present in the composition at a higher concentration than the at least one P. acnes SLST C3 type strain.

19. The skin care composition according to any one of claims 1 to 6, wherein each strain of Propionibacterium acnes in the composition is present in an amount of 10 7 -10 10 The amount of CFU / ml is present.

20. The skin care composition according to any one of claims 1 to 6, wherein the total amount of bacteria in the composition is 10 4 -10 11 CFU / ml.

21. The skin care composition according to any one of claims 1 to 6, wherein the total amount of bacteria in the composition is 10 7 -10 10 CFU / ml.

22. A skin care composition according to any one of claims 1 to 6, wherein the composition is in the form of a gel, cream, ointment or lotion.

23. The skin care composition of any one of claims 1-6, wherein the composition is for use in a method of improving the appearance of a subject's skin and / or regulating sebum production by a subject's skin cells and / or maintaining healthy skin in a subject.

24. The skin care composition of any one of claims 1-6, wherein the composition is for use in a method of treating or preventing a condition selected from acne, oily skin, progressive macular hypopigmentation, dandruff, atopic eczema, atopic dermatitis, and rosacea in a subject.

25. Use of the skin care composition according to any one of claims 1 to 22 for the preparation of a medicament for improving the appearance of a subject's skin and / or regulating sebum production in a subject's skin cells and / or maintaining healthy skin in a subject.

26. Use of the skin care composition according to any one of claims 1 to 22 in the preparation of a medicament for treating or preventing a condition selected from acne, oily skin, progressive macular hypopigmentation, dandruff, atopic eczema, atopic dermatitis and rosacea in a subject.

27. The skin care composition of claim 23, wherein the subject is a human.

28. The skin care composition of claim 24, wherein the subject is a human.

29. The use according to claim 25 or 26, wherein the subject is a human.

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