Probiotic bacterial compositions for inhibiting fungal growth - Patents.com

Abstract

The present invention relates to a composition comprising one or more isolated probiotic bacterial strains, two or more active substances of one or more isolated probiotic bacterial strains, or a combination of one or more isolated probiotic bacterial strains and two or more active substances of one or more isolated probiotic bacterial strains, and an acceptable carrier, wherein the one or more isolated probiotic bacterial strains and / or the two or more active substances of the one or more isolated probiotic bacterial strains are capable of inhibiting fungal growth.

Description

[Technical field]

[0001] The present invention relates to antimicrobial compositions comprising active materials derived from microorganisms. More particularly, the present invention relates to compositions comprising probiotic bacteria or postbiotic fractions produced by probiotic bacteria that are effective in inhibiting fungal growth, such as the growth of Malassezia furfur, and treating Seborrheic Dermatitis (SD). [Background technology]

[0002] Seborrheic dermatitis is a histopathological eczematous skin disease characterized by poorly demarcated, scaly, erythematous patches with yellowish, greasy scales. "Dandruff" is a milder form of this condition localized to the scalp. The disease may involve any one, some, or all of the following sites: scalp, eyebrows, glabella, sinuses, and chin folds, ears and postauricular grooves, presternal interscapular region, pubic region, and intergluteal folds.

[0003] Corticosteroids, including tar, sulfur, or antibiotics, may provide temporary control in some cases, but in many cases the condition is chronic and reverts once treatment is terminated. Current therapy consists of topical and systemic antimicrobials, corticosteroids, and topical tar. The infectious organisms associated with these skin conditions can spread to other skin areas and may even be contagious to other people, resulting in alterations of the natural skin microflora causing a dysfunctional microflora that further exacerbates the disease. The therapy consists of topical and systemic antibiotics and antimicrobials. Conventional treatments for seborrheic dermatitis have a significant effect on the scalp, and in particular on the microflora, so a less irritating treatment is needed, and the dysfunctional microflora associated with seborrheic dermatitis is re-established.

[0004] Seborrheic dermatitis corresponds to excessive and visible scalp scaling due to the excessively rapid proliferation of epidermal cells and their abnormal maturation.Various factors can induce this condition, such as excessive hair treatment, extreme weather conditions, irritability, diet, fatigue, or pollution.However, seborrheic dermatitis, especially its continuous recurrence, is most commonly caused by disturbance of the scalp microflora, more specifically by excessive colonization by fungi belonging to the family of yeasts of the genus Malassezia, which naturally occur on the scalp.

[0005] Malassezia colonize the skin of various mammals, domestic animals and birds. These lipophilic yeasts live in the stratum corneum of human and animal skin because this layer is rich in lipids. For reasons currently unknown, these yeasts can change their saprophytic state and penetrate the stratum corneum as pathogens.

[0006] One form of seborrheic dermatitis is neonatal capitis in infants. Babies with neonatal capitis have slightly red, scaly or crusty yellow patches on their scalp. This can also start on the face or diaper area and spread to other parts of the body.

[0007] Malassezia also infects the skin of animals and is common in dermatitis in horses, cattle, sheep, dogs and cats. Malassezia is normally found on the skin, but its abnormal overgrowth can cause dermatitis, or inflammation of the skin, ears, mouth and body orifices.

[0008] Seborrheic dermatitis, including the milder form often referred to as dandruff, affects up to 50 percent of the world's population, affects both men and women, and generally has a negative psychosocial impact. Dandruff is both aesthetically unpleasant (due to the visible presence of dead skin flakes) and unpleasant due to the personal discomfort felt by the individual (especially the itching). Therefore, sufferers who are more or less faced with this problem wish to get rid of it efficiently and permanently.

[0009] Despite many commercially available remedies, scalp treatments and shampoos, seborrheic dermatitis remains a challenging condition, with many patients not responding to several attempted treatments, making treatment often unpredictable and difficult.

[0010] Many anti-dandruff treatments have been developed with the main aim of eradicating Malassezia yeast from the scalp.Therefore, the activity of today's anti-dandruff actives, such as zinc pyrithione, piroctone olamine, climbazole, ketoconazole, or selenium disulfide, is mainly based on their fungicidal properties.Recently, other formulations have been described that use natural-based alternatives, such as the anti-dandruff composition based on ellagic acid and at least one essential oil described in US Pat. No. 5,399,431 or the hydrolyzable tannin-concentrated active material from Punica granatum described in US Pat. No. 5,499,431. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] WO 2011 / 138450 Specification [Patent Document 2] French Patent No. 2908045 Summary of the Invention [Problem to be solved by the invention]

[0012] Notwithstanding the above, there remains a need for new effective natural solutions for inhibiting fungal growth and / or treating or preventing mycoses and / or treating or preventing dandruff that do not cause skin irritation and that facilitate the re-establishment of a balanced natural scalp microflora. [Means for solving the problem]

[0013] The present invention is premised on the recognition that various combinations of anti-dandruff actives derived from probiotic microorganisms are formulated in compositions for topical use, particularly for seborrheic dermatitis (SD), which further comprise a microbial-derived active material, more particularly a composition comprising probiotic bacteria or a postbiotic fraction produced by a probiotic microorganism that is effective in inhibiting fungi having a genus from the family Malasseziaceae, such as Malassezia furfur, and treating seborrheic dermatitis.

[0014] An aspect of the present invention relates to a composition comprising one or more isolated probiotic bacterial strains, two or more active substances of the one or more isolated probiotic bacterial strains, or a combination of one or more isolated probiotic bacterial strains and two or more active substances of the one or more isolated probiotic bacterial strains, and an acceptable carrier, wherein the one or more isolated probiotic bacterial strains and / or the two or more active substances of the one or more isolated probiotic bacterial strains are capable of inhibiting fungal growth.

[0015] A further aspect of the invention relates to an anti-dandruff composition comprising (or consisting essentially of) a combination of at least two anti-dandruff actives derived from probiotic microorganisms, the anti-dandruff actives being present in the anti-dandruff composition in an amount effective to treat or prevent dandruff.

[0016] A further aspect of the invention relates to the use in the prevention and / or treatment of fungal diseases in humans or animals.

[0017] The present invention also seeks to provide compounds in hair care formulations that can provide anti-fungal properties, such as anti-dandruff properties, that are comparable or improved compared to existing anti-dandruff agents.

[0018] An embodiment of the present invention relates to a topical hair care composition comprising a composition according to the present invention in combination with a shampoo matrix having a pH of less than 6.5 comprising at least one cleansing surfactant selected from the group consisting of anionic surfactants, nonionic surfactants, amphoteric surfactants, or combinations thereof.

[0019] Aspects of the present invention relate to leave-on compositions for treating fungal diseases.

[0020] The present invention also seeks to provide compounds as anti-dandruff agents, and formulations containing said compounds, for use in reducing dandruff on human skin.

[0021] According to another embodiment of the present invention, there is provided an anti-dandruff hair care composition suitable for treating dandruff for Malassezia furfur.

[0022] The compositions of the present invention may comprise one or more isolated probiotic bacterial strains and / or two or more actives of the one or more isolated probiotic bacterial strains, such as anti-dandruff actives, and an acceptable carrier, and have a pH of less than 6.5.

[0023] It was surprising to determine the synergistic effect between antifungal effect, for example antidandruff active, and the pH of the composition.Without being bound by theory, it is believed that this synergistic effect is identified as at least two different mechanisms and observed for both live probiotic microorganisms and any fraction derived therefrom that also contains antifungal effect, particularly antidandruff active.Therefore, synergistic effect can be observed between the antibacterial activity of active on inhibiting fungus, which can be a genus from the Malasseziaceae family, for example Malassezia furfur, and also between the pH of the antidandruff composition and the ability of natural microflora to re-establish after treatment, thereby allowing mild antifungal treatment, such as mild antidandruff treatment, with longer and more sustained effect compared to conventional treatments that do not repair or promote the repair of the dysfunctional microflora remaining on the scalp after antibacterial treatment.

[0024] As a further advantage of the present invention, the probiotic treatment did not cause any irritation to the human or animal body or to the skin or scalp.

[0025] According to yet another embodiment of the present invention, there is provided a method of treating a dandruff condition associated with the proliferation of yeast of the genus Malassezia on the scalp of a subject, the method comprising applying to the scalp of the subject an effective amount of an anti-dandruff composition, the effective amount of the anti-dandruff composition inhibiting the proliferation of yeast of the genus Malassezia on the scalp. [Brief description of the drawings]

[0026]

[0027] The present invention will now be described in more detail. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] Detailed Description of the Invention The present invention may relate to compositions, uses of said compositions and methods for use to inhibit fungal growth and prevent or treat scalp conditions associated with a dysfunctional microflora. The compositions, such as anti-dandruff compositions, may comprise functional probiotic bacteria and / or metabolites obtained by fermentation of probiotic bacteria.

[0029] Anti-dandruff compositions, particularly shampoos, have been well known and have been available commercially for many years. Many anti-dandruff actives have been used commercially, such as ketoconazole, zinc pyrithione, piroctone olamine, octopirox, salicylic acid, selenium sulfide, coal tar and azelaic acid.

[0030] These types of actives may preferably be active compounds that generally function as antibacterial / fungal agents and are effective against certain species and strains of fungi, yeasts and / or bacteria, and are particularly effective against fungi and / or yeasts. For example, the yeast-like fungus Malassezia lives on the scalp of most adults, but in some people, it can irritate the scalp and cause more skin cells to grow. Malassezia yeast is part of the normal microflora, but under certain conditions, it can cause superficial skin infections. These excess skin cells die and fall off, appearing white and flaky on hair and clothing. Thus, materials active against Malassezia, especially the Malassezia furfur species, can reduce the severity of dandruff.

[0031] Preferably, the one or more active substances of the one or more probiotic bacterial strains (preferably isolated probiotic bacterial strains) may be provided in an amount effective to inhibit fungal growth.

[0032] These shampoos and other topical antifungal preparations are often combined with cortisone drugs to control inflammation and reduce pain and itching.However, the use of these molecules may not produce satisfactory results, and in some cases, these compounds show inherent and undesirable cytotoxicity and damage to microflora.

[0033] There is a continuing need for improved anti-dandruff actives and end-use products containing anti-dandruff actives that are non-irritating to the skin and do not adversely affect the scalp microflora.

[0034] The present invention can provide effective inhibition, treatment or prevention when applied topically and does not adversely affect the native microflora.

[0035] A preferred embodiment of the present invention relates to a composition comprising one or more isolated probiotic bacterial strains, two or more active substances of one or more isolated probiotic bacterial strains, or a combination of one or more isolated probiotic bacterial strains and two or more active substances of one or more isolated probiotic bacterial strains, and an acceptable carrier, wherein the one or more isolated probiotic bacterial strains and / or the two or more active substances of the one or more isolated probiotic bacterial strains are capable of inhibiting fungal growth.

[0036] Preferably, the fungus having fungal growth ability may be a fungus of a genus selected from the family Malasseziaceae. Preferably, the genus from the family Malasseziaceae may be Malassezia.

[0037] A further preferred embodiment of the present invention relates to a composition (e.g. an anti-dandruff composition) comprising an effective amount of a probiotic microorganism or a fraction of a probiotic microorganism capable of producing an active substance (e.g. an anti-dandruff active substance), wherein the fraction comprises the active substance.

[0038] According to another aspect of the present invention there is provided a method of providing anti-fungal efficacy, particularly anti-dandruff efficacy, comprising the steps of: (i) wetting the hair with water; (ii) applying an effective amount of a composition according to the invention comprising a probiotic microorganism or a fraction thereof; (iii) rinsing the composition from the hair using water; and (iv) optionally repeating steps (ii) and (iii); A method is provided, comprising:

[0039] According to another aspect of the present invention, there is provided a method of providing anti-fungal efficacy comprising the step of applying a leave-on composition to skin, epithelia, nails, mouth, including the skin of the scalp, feet, vagina, genitals and ears.

[0040] According to another aspect of the present invention there is provided a method of killing or slowing the growth of fungi, particularly fungi from the family Malasseziaceae, such as Malassezia spp., comprising the step of contacting the fungi, such as Malassezia spp., with a composition comprising an active material derived from a probiotic microorganism according to the present invention.

[0041] As used herein, the terms "for example," "for instance," "such as," or "including" are meant to introduce examples that further clarify a more general subject matter. Unless otherwise specified, these examples are provided only as an aid in understanding the applications presented in this disclosure and are not meant to be limiting in any way.

[0042] The term "antifungal composition" relates to a composition according to the invention which is capable of inhibiting fungal growth, treating or preventing fungal infections, for example treating or preventing mycoses and / or dandruff in humans or animals.

[0043] Furthermore, the anti-dandruff effect is also a major effect described in the present invention, and the composition according to the present invention also exhibits a strong anti-mycosis effect.

[0044] Fungal growth can lead to the occurrence of dandruff and / or mycoses in mammals. It is believed that by limiting, reducing or terminating fungal growth, the occurrence of dandruff and / or mycoses can be prevented, avoided or limited.

[0045] Preferably, the composition according to the invention may be an anti-dandruff composition and / or an anti-fungal composition.

[0046] The term "anti-dandruff composition" refers to providing a preventative and / or therapeutic benefit to the scalp, including preventing and / or reducing excessive dandruff formation and / or visually unappealing excessively formed dandruff.

[0047] The term "active agent" may relate to a compound active against fungal growth for the treatment and / or prevention of mycoses in humans or animals. The active agent may preferably comprise a bacteriocin, an organic acid, cell wall material, or a combination thereof.

[0048] The present invention relates to antifungal compositions, particularly antidandruff compositions, and methods of using the compositions to treat or inhibit antifungal growth, such as for treating or inhibiting dandruff. The compositions of the present invention may be useful for application to keratinous tissue or scalp surfaces and may contain an effective amount of a combination of actives that inhibit, reduce or eliminate symptoms resulting from the growth of Malassezia furfur, such as dandruff symptoms. The compositions of the present invention may be in a wide variety of product forms, including, but not limited to, solutions, suspensions, lotions, creams, gels, ointments, oils, emulsions, sprays, aerosols, shampoos, hair conditioners, pastes, foams, powders, mousses, wipes, strips, patches, hydrogels, film-forming products, and the like. The composition form may be derived from the particular dermatologically acceptable carrier selected.

[0049] In embodiments of the invention, the anti-dandruff composition may include a composition applied to the hair and / or the skin beneath the hair, and the anti-dandruff composition may comprise (or consist essentially of) at least one of various combinations of probiotic-derived actives and dermatologically acceptable carriers, which combinations are effective to inhibit Malassezia furfur and treat dandruff.

[0050] An active agent can refer to a single compound or a composition containing two or more compounds that have the ability to inhibit the growth of fungi, such as Malassezia furfur, when present in the composition in an effective amount.

[0051] As used herein, the term "effective amount" means an amount of a compound or a composition comprising two or more compounds sufficient to reduce or inhibit the growth of fungi, particularly Malassezia furfur, reduce or inhibit the visible and / or physical effects of fungal infection, mycosis or dandruff caused by fungal growth, such as the growth of Malassezia furfur, or reduce or inhibit scalp pruritus by a statistically significant amount.

[0052] As used herein, the term "topical application" means applying or spreading the compositions of the present invention onto the surface of the hair, skin (eg, scalp).

[0053] As used herein, the term "acceptable carrier" means a carrier suitable for internal (e.g., oral or rectal ingestion) or external (topical) use that is not associated with undue toxicity, incompatibility, instability, allergic reaction, discomfort, and the like.

[0054] As used herein, the term "dermatologically acceptable" means that the composition or components thereof so described are suitable for use in contact with mammalian keratinous or skin tissue without undue toxicity, incompatibility, instability, allergic response, and the like.

[0055] According to an embodiment of the present invention, the composition, for example the antidandruff composition, comprises (or essentially consists of) an effective amount of a combination of at least two active substances selected from the group of organic acids.In a further preferred embodiment, the organic acid is selected from the group consisting of lactic acid, citric acid, acetic acid, malic acid, tartaric acid, 3-phenyllactic acid, 3-hydroxyphenyllactic acid, 4-hydroxyphenyllactic acid, propionic acid and succinic acid, salicylic acid, azelaic acid, indole-3-lactic acid, indole-3-acetic acid, 2-hydroxybutyric acid, 2-hydroxyisocaproic acid, 3-(R)-hydroxydecanoic acid, 3-hydroxy-5-cic dodecanoic acid, 3-(R)-hydroxydodecanoic acid, 3-(R)-hydroxytetradecanoic acid, glycolic acid and N-acetylaspartic acid.

[0056] In an embodiment of the present invention, the composition may comprise live probiotic microorganisms. In a further embodiment of the present invention, the active substance present in the composition may be in the form of live probiotic microorganisms. Preferably, the live probiotic microorganisms may inhibit fungal growth, for example, may inhibit Malassezia furfur. Preferably, inhibition of Malassezia furfur may be obtained when the composition may be topically applied to the scalp or dandruff-affected areas of the skin.

[0057] As used herein, the term "viable" or "living" refers to a microorganism that is not dead and capable of having an active metabolism.

[0058] The term "microbiota" as used herein refers to the commensal, symbiotic and pathogenic microbial communities found in and on all multicellular organisms. Microbiota include bacteria, archaea, protists, fungi, yeasts, viruses and phages.

[0059] As used herein, the term "dysfunction of the microbiota" refers to a state in which the microbiota functions incorrectly or is completely prevented from functioning.Unless otherwise stated, the dysfunction of the microbiota in the context of the present invention includes the overgrowth or increased growth of pathogenic microorganisms, which results in a dysfunctional microbiota.One example of a dysfunctional microbiota is the increase of Malassezia furfur, which leads to fungal infections or seborrheic dermatitis such as dandruff.

[0060] In an embodiment of the present invention, the fungal infection may be mycosis or seborrheic dermatitis. Preferably, the seborrheic dermatitis may be dandruff.

[0061] As used herein, the term "probiotic microorganisms" refers to live microorganisms intended to have a health benefit when consumed or applied to a host. Examples of suitable probiotic microorganisms include yeasts such as Saccharomyces, Debaromyces, Candida, Pichia and Torulopsis, molds such as Aspergillus, Rhizopus, Mucor and Penicillium and Torulopsis, and species of the genera Bifidobacterium, Bacteroides, Clostridium, Fusobacterium, Melissococcus, Propionibacterium, Streptococcus, Enterococcus, Lactococcus, Staphylococcus, Peptostrepococcus, Bacillus, Pediococcus, Micrococcus, Leuconostoc, Weissella, Ae Examples include bacteria of the genus rococcus, genus Oenococcus, genus Cutibacterium, genus Lacticaseibacillus, genus Levilactobacillus, genus Lactiplantibacillus, and genus Lactobacillus.

[0062] The most commonly used probiotics are lactic acid bacteria strains (LAB). The term "lactic acid bacteria" includes species from the families Lactobacillaceae, Aerococcaceae, Bifidobacteriaceae, Carnobacteriaceae, Enterococcaceae, Leuconostocaceae and Streptococcaceae. They are considered non-pathogenic and are commonly used as probiotic bacteria to improve gastrointestinal flora and in the treatment of gastrointestinal symptoms. The present invention relates to the topical application of probiotics, characterized in that the probiotics produce antidandruff active substances.

[0063] The microorganism may preferably be a lactic acid bacterium. The microorganism may more preferably be a member of the genus Lactobacillus, Lactiplantbacillus, Holzapfelia, Amylolactobacillus, Bombilactobacillus, Companilactobacillus, Lapidilactobacillus, Agrilactobacillus, Schleiferilactobacillus, Loigolactobacillus, Lacticaseibacillus, Latilactobacillus, Dellaglioa, Liquorilactobacillus, Ligilactobacillus, Furfurilactobacillus, Paucilactobacillus Genus, Limosilactobacillus, Fructilactobacillus, Acetilactobacillus, Apilactobacillus, Levilactobacillus, Secundilactobacillus, Lentilactobacillus, Leuconostoc, Bifidobacterium Pediococcus, Lactococcus, Streptococcus, Aerococcus, Carnobacterium, Enterococcus, Oenococcus, Sporolactobacillus, Tetragenococcus, Vagococcus, and Weissella.

[0064] Preferred microorganisms may be bacteria in particular. Probiotic bacteria are preferably Lactococcus lactis, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, Lactobacillus helveticus, Lactobacillus jensenii, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus amylovorus, Lactobacillus amylolyticus, Lactobacillus alimentarius, Lactobacillus aviaries, Lactobacillus delbrueckii, Lactobacillus diolivorans, Lactobacillus farciminis, Lactobacillus gallinarum, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus hilgardii, Lactobacillus kefiranofaciens, Lactobacillus kefiri, Lactobacillus mucosae, Lactobacillus panis, Lactiplantibacillus paraplantarum, Lactobacillus pontis, Latilactobacillus sakei, Lactobacillus salivarius, Lactobacillus sanfraciscensis, Lacticaseibacillus paracasei, Lactobacillus pentosus, Lactobacillus cellobiosus, Lactobacillus collinoides, Lactobacillus coryniformis, Lactobacillus curvatus, Levilactobacillus brevis, Lactobacillus buchneri, Lactobacillusfructivorans, Lactobacillus hilgardii, Lactobacillus fermentum, Lactobacillus reuteri, Lactobacillus ingluviei, Weissella viridescens, Bifidobacterium bifidum, Bifidobacterium adolescentis, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium animalis, Carnobacterium divergens, Corynebacterium glutamicum, Leuconostoc citreum, Leuconostoc lactis, Leuconostoc mesenteroides, Leuconostoc pseudomesenteroides, Oenococcus oeni, Pasteuria nishizawae, Pediococcus acidilactici, Pediococcus dextrinicus, Pediococcus parvulus, Pediococcus pentosaceus, Probionibacterium freudenreichii, Probionibacterium acidipropioni, Enterococcus faecium, Enterococcus faecalis, Streptococcus thermophilus, Bacillus amyloliquefaciens, Bacillus atrophaeus, Bacillus clausii, Bacillus coagulans, Bacillus flexus, Bacillus fusiformis, Bacillus lentus, Bacillus licheniformis, Bacillus mega-terium、Bacillus mojavensis、Bacillus pumilus、Bacillus smithii、Bacillus subtilis、Bacillus vallismortis、Geobacillus stearother-mophilus。

[0065] In a preferred embodiment of the present invention, the composition comprises Lactiplantibacillus plantarum LB356R (DSM 33094), Lactiplantibacillus plantarum LB244R (DSM 32996), Weissella viridescens LB10G (DSM 32906), Lacticaseibacillus paracasei LB113R (DSM 32907), Lacticaseibacillus paracasei LB116R (DSM 32908), Levilactobacillus brevis LB152G (DSM 32995), Lacticaseibacillus paracasei LB28R (DSM 32994), Enterococcus faecium LB276R (DSM 32997), Leuconostoc mesenteriodes LB349R (DSM 33093), Lactiplantibacillus plantarum LB316R (DSM 33091), Lactiplantibacillus plantarum LB312R (DSM 33098), Pediococcus pentosaceus LB606R(DSM 33730)、Lactiplantibacillus plantarum LB679R(DSM 33731)、Lactobacillus crispatus LB714R(DSM 33732)Lactobacillus gasseri LB905R(DSM 34094)、Lactobacillus crispatus LB912R(DSM 34095)、Lactobacillus jensenii LB918R(DSM 34096)、Lactobacillus crispatus LB919R(DSM 34097)、Lacticeibacillus paracasei subsp.and / or any combination thereof, or mutant strains thereof, and / or cells and / or cell lysates and / or soluble metabolites of any one of these probiotic strains. The probiotic comprises at least one strain selected from the group consisting of Lactobacillus subtilis LB555R (DSM 34249), Lactiplantibacillus plantarum LB681R (DSM 34250); and / or any combination thereof, or mutant strains thereof, and / or cells and / or cell lysates and / or soluble metabolites of any one of these probiotic strains.

[0066] Microbial numbers are measured as Colony Forming Units (CFU) per ml or per gram.

[0067] The microorganisms according to the invention may preferably be in isolated or purified form, the term "isolated" meaning in particular that the lactic acid bacteria are derived from their culture medium, including for example their natural culture medium. The terms "isolated" or "purified" may not be limited to absolute purity. The terms "isolated" and "purified" may be used interchangeably.

[0068] In an embodiment of the present invention, the probiotic strains may be used as live isolated microorganisms in a stabilized form. Suitable methods for stabilization are known to those skilled in the art and include freeze-drying or freeze-drying with different cryoprotectants.

[0069] In a further embodiment of the invention the strain may be used as a live isolate.

[0070] Preferably, the strain can be used as a live isolate. Preferably, the strain can be used as a live isolate stabilized strain. Even more preferably, the strain can be used as a live isolate stabilized by freeze-drying. Even more preferably, the strain can be used as a live isolate stabilized by freeze-drying and containing a cryoprotectant.

[0071] In a preferred embodiment of the present invention, the probiotic strain is a Gram-positive bacterium.

[0072] The active ingredients are Lactiplantibacillus plantarum LB356R(DSM 33094) and Lactiplantibacillus plantarum LB244R(DSM). 32996)、Weissella viridescens LB10G(DSM 32906)、Lacticaseibacillus paracasei LB113R(DSM 32907)、Lacticaseibacillus paracasei LB116R(DSM 32908)、Levilactobacillus brevis LB152G(DSM). 32995)、Lacticaseibacillus paracasei LB28R(DSM 32994)、Enterococcus faecium LB276R(DSM 32997)、Leuconostoc mesenteriodes LB349R(DSM 33093)、Lactiplantibacillus plantarum LB316R(DSM 33091)、Lactiplantibacillus plantarum LB312R(DSM 33098)、Pediococcus pentosaceus LB606R(DSM 33730)、Lactiplantibacillus plantarum LB679R(DSM 33731) Lactobacillus crispatus LB714R(DSM 33732)Lactobacillus gasseri LB905R(DSM 34094)、Lactobacillus crispatus LB912R(DSM 34095)、Lactobacillus jensenii LB918R(DSM 34096)、Lactobacillus crispatus LB919R(DSM 34097)、Lacticaseibacillus paracasei subsp.paracasei LB555R(DSM 34249)、Lactiplantibacillus plantarum LB681R(DSM). 34250) This is a 100% free range.

[0073] The term "postbiotic" refers to compounds, metabolic products, or cellular material secreted or released from probiotic microorganisms that provide a health benefit when applied to a host. Postbiotic compositions are characterized as having a health benefit without the presence of viable microorganisms.

[0074] The term "postbiotic fraction of a probiotic microorganism" as used herein discloses a fermentation composition of a probiotic microorganism that is substantially free of viable microorganisms. The composition may contain cellular material, including dead cells.

[0075] In an embodiment of the invention the composition may have a pH value of less than pH 8.0, such as less than pH 7.5 (e.g. less than pH 7.0), for example less than pH 6.5 (e.g. less than pH 6.0), such as less than pH 5.5 (e.g. less than pH 5.0), for example less than pH 4.75 (e.g. less than pH 4.5), such as less than pH 4.25 (e.g. less than pH 4.0), for example less than pH 3.75 (e.g. less than pH 3.5), such as less than pH 3.25.

[0076] The preferred pH of the composition is between pH 2.5 and pH 7, more preferably between pH 3 and pH 6.5, and even more preferably between pH 3.5 and pH 5.5. The low pH of the composition resulting from the acids produced by the probiotic microorganisms causes acidification of the skin surface with an elevated pH when applied to the scalp. A healthy scalp has a pH of about 4.5, and the metabolites produced by the probiotic microorganisms help maintain a healthy pH of the skin as another beneficial effect.

[0077] In an embodiment of the present invention, the at least two active substances may be produced by the metabolism of an isolated live probiotic bacterial strain.

[0078] In a further embodiment of the present invention, the at least two active substances may be produced by a single isolated probiotic bacterial strain.

[0079] Preferably, the active agent may be selected from a bacteriocin, an organic acid, a cell wall material, or a combination thereof.

[0080] In one preferred embodiment of the invention, the active ingredient which is an organic acid is present in the protonated form of the acid and the pH is equal to or below the pKa of the acid.

[0081] The present invention is based on the discovery that some species of lactic acid bacteria produce bacteriocins in the supernatant in amounts effective to inhibit the growth of Malassezia even when the lactic acid bacteria are no longer present.

[0082] In one embodiment of the present invention, the preferred microorganism is an isolated wild-type lactic acid bacterium.

[0083] In one embodiment the preferred bacteriocin used in the present invention is produced by a probiotic bacterium, in a further preferred embodiment the bacteriocin is produced by a lactic acid bacterium, in a further preferred embodiment the bacteriocin is produced by one of the following bacteria: Lactiplantibacillus plantarum LB356R (DSM 33094), Lactiplantibacillus plantarum LB244R (DSM 32996), Weissella viridescens LB10G (DSM 32906), Lacticaseibacillus paracasei LB113R (DSM 32907), Lacticaseibacillus paracasei LB116R (DSM 32908), Levilactobacillus brevis LB152G (DSM 32995), Lacticaseibacillus paracasei LB28R (DSM 32994), Enterococcus faecium LB276R(DSM 32997), Leuconostoc mesenteriodes LB349R(DSM 33093), Lactiplantibacillus plantarum LB316R(DSM 33091), Lactiplantibacillus plantarum LB312R(DSM 33098), Pediococcus pentosaceus LB606R (DSM 33730), Lactiplantibacillus plantarum LB679R (DSM 33731), Lactobacillus crispatus LB714R (DSM 33732), Lactobacillus gasseri LB905R (DSM 34094), Lactobacillus crispatus LB912R(DSM 34095), Lactobacillus jensenii LB918R (DSM 34096), Lactobacillus crispatus LB919R (DSM 34097), Lacticaseibacillus paracasei subsp.paracasei LB555R (DSM 34249), Lactiplantibacillus plantarum LB681R (DSM 34250); and / or any combination thereof.

[0084] Bacteriocins are preferably used in the compositions of the invention in an amount of 1 to 1 million arbitrary units (AU) of the bacteriocin, the AU being defined as 5 microliters of the highest dilution of culture supernatant that results in a clear zone of growth inhibition by a lawn of the indicator strain on an agar plate.

[0085] In an embodiment of the invention, the active agent may be a bacteriocin.

[0086] The term "bacteriocin" refers to antimicrobial peptides or proteins produced by bacteria that are active against microorganisms but do not harm the producing bacteria. For the purposes of the present invention, bacterocins or sources of bacterocins generally include antimicrobial agents suitable for use in cosmetic or pharmaceutical formulations. Particularly preferred antimicrobial agents include "antibiotics" (i.e., polypeptides containing lanthionine and beta-methyllanthionine). Non-limiting examples of such antibiotics are nisin, e.g., nisin A or nisin Z, or nisin analogs or related lanthionine-containing peptides, e.g., pediocin, lactocin, lactacin (e.g., lacticin A, lacticin B, lactacin F), camocin, enterocin, plantarcin, subtilin, epidermin, cinnamycin, duramycin, ancovenin, Pep5, etc. (individually or in any combination thereof).Other bacterocins useful in the present invention include, for example, lactococcin (e.g., lactococcin A, lactococcin B, lactococcin M), leucocoin, helvetican, acidophilucin, caseicin, lacticin J46, lacticin 481, lacticin 3147, salivarcin A, salivarcin A2, salivarcin A3, salivarcin A4, BHT-Aa, BHT Ab, salivarcin A5, salivarcin B, streptin, salivarcin Al, streptin, streptococcin A-FF22, mutacin BNY266, mutacin 1140, mutacin K8, mutacin II, smbAB, bovicin HJ50, bovicin HC5, macedocin, leucocin C, sakacin 5X, enterocin CRL35 / mundticin, avicin A, mundticin I, enterocin HF, bavaricin A, ubericin A, leucocin A, mesentericin Y105, sakacin G, carbacin (c urvacin A / sakacin A, lactocin 5, cytolysin, enterocin A, divercin V41, divercin M35, bavaricin, coagulin, pediocin PA-1, munditicin, piscicocin CS526, piscicocin 126 / Vla, sakacin, Pcarnobacteriocin BM1, enterocin P, piscicoin Vlb, penocin A, bacteriocin 31, bacteriocin RC714, hiracin JM79, bacteriocin T8, enterocin SE-K4, carnobacteriocin B2, and plantaricin.

[0087] The term "plantaricin" refers to a bacteriocin derived from Lactiplantibacillus plantarum, and the main types of plantaricin include plantaricin A, plantaricin E, plantaricin F, plantaricin J, plantaricin K, plantaricin C, plantaricin D, plantaricin W, plantaricin T and plantaricin S. As well as other plantaricins such as plantaricin 35d, plantaricin MG, plantaricin 423, plantaricin 154, plantaricin 149, plantaricin 163, plantaricin LC74, plantaricin K25, plantaricin ST31, plantaricin SA6. In particular, broad spectrum plantaricins, such as Plantaricin F, Plantaricin DL3, Plantaricin ZJ008, Plantaricin MG, Plantaricin Q7, Plantaricin KL-1Y, Plantaricin 163, Plantaricin 154.

[0088] Thus, an embodiment of the present invention relates to a composition comprising a probiotic microorganism producing at least one active substance, wherein the active substance comprises (consists essentially of) a bacteriocin.

[0089] In yet another embodiment of the invention, at least two different bacteriocins may be produced by the probiotic microorganism.

[0090] The compositions of the present invention include probiotic microorganisms capable of producing actives, such as anti-dandruff actives, or postbiotic fractions from probiotic organisms, where the actives are maintained in the postbiotic composition.

[0091] In an embodiment of the invention, the active agent may include an organic acid or a combination of one or more organic acids with one or more baseriocins.

[0092] The organic acid is preferably used in the postbiotic composition at a total weight concentration of about 0.1 to 20%, e.g., 1 to 5% lactic acid or acetic acid by weight. The organic acid is preferably selected from the group consisting of lactic acid, citric acid, acetic acid, malic acid, tartaric acid, phenyllactic acid, 3-hydroxyphenyllactic acid, 4-hydroxyphenyllactic acid, propionic acid and succinic acid, salicylic acid, azelaic acid, indole-3-lactic acid, indole-3-acetic acid, 2-hydroxybutyric acid, 2-hydroxyisocaproic acid, 3-(R)-hydroxydecanoic acid, 3-hydroxy-5-thiocyanodecanoic acid, 3-(R)-hydroxydodecanoic acid, 3-(R)-hydroxytetradecanoic acid, glycolic acid, and N-acetylaspartic acid is preferably used in the postbiotic composition at a concentration of 0.1 to 10% (w / w). As mentioned above, the active part of the composition comprises (or essentially consists of) a combination of at least two active substances derived from probiotic microorganisms or applied in the form of live probiotic microorganisms capable of producing at least two active substances.

[0093] In an embodiment of the invention, the active substance may be produced by probiotic bacteria and the active substance may be selected from lactic acid, citric acid, acetic acid, malic acid, tartaric acid, 3-phenyllactic acid, 3-hydroxyphenyllactic acid, 4-hydroxyphenyllactic acid, propionic acid and succinic acid, salicylic acid, azelaic acid, indole-3-lactic acid, indole-3-acetic acid, 2-hydroxybutyric acid, 2-hydroxyisocaproic acid, 3-(R)-hydroxydecanoic acid, 3-hydroxy-5-thiocyanoic acid, 3-(R)-hydroxydodecanoic acid, 3-(R)-hydroxytetradecanoic acid, glycolic acid, and N-acetylaspartic acid.

[0094] The active substance may be produced on the scalp by probiotic bacteria and may be selected from 2-hydroxyisocaproic acid, phenyllactic acid, salicylic acid, acetylsalicylic acid, indole-3-lactic acid, gallic acid, azelaic acid, 2-hydroxybutyric acid, N-acetylaspartic acid, succinic acid and lactic acid.

[0095] In an embodiment of the invention, the composition may comprise at least one of the following combinations of active substances: bacteriocin and / or phenyllactic acid and / or salicylic acid and / or lactic acid and / or 2-hydroxyisocaproic acid and / or azelaic acid and / or succinic acid and / or indole-3-lactic acid and / or 2-hydroxybutyric acid and / or N-acetylaspartic acid and / or indole-3-acetic acid and / or gallic acid.

[0096] In another embodiment of the invention, the active substance may comprise a combination of at least two different bacteriocins produced by a probiotic microorganism or isolated in a fraction from the fermentation of a probiotic microorganism, the probiotic microorganism not being genetically modified to produce the bacteriocin.

[0097] The present invention may be suitable for use directly as a scalp care product or for formulation into a scalp care product in a therapeutic or scalp care composition for the prevention or treatment of a scalp condition or for regulating a dysfunctional microbiota.

[0098] During growth, the probiotic microorganisms of the present invention can produce a yield of functional metabolites, such as actives, e.g., anti-dandruff actives, sufficient to provide functional benefits such as broad spectrum antibacterial activity, anti-inflammatory activity, exfoliation, moisturizing effects and / or firmness of the feet, nails and scalp. Without wishing to be bound by theory, it is believed that the benefits may be provided by activation of fibrillin and collagen synthesis.

[0099] Moreover, it was surprising to determine a synergistic effect between the active substances or metabolites present in the composition and the pH of the composition, which allows the functional concentration of each active substance to be lower than that required for the purified active substance.

[0100] For example, azelaic acid may be used at high concentrations. In an embodiment of the present invention, the concentration of azelaic acid may be 2-20% (w / w) using azelaic acid in a composition containing multiple active substances or metabolites that all contribute to a synergistic functional effect, thereby significantly reducing the concentration during use and also reducing side effects and any toxicity or irritation that may be observed while using these compounds at high concentrations of more than 2% (w / w).

[0101] The present invention relates to a composition comprising an active substance produced by the growth of a probiotic microorganism. The composition may be administered for internal or external use. External use may be, for example, topical application to the scalp, feet, and / or nails as a live microorganism, or may be applied as a postbiotic composition comprising the active substance.

[0102] The present invention may relate to compositions comprising anti-dandruff actives produced by the growth of probiotic microorganisms and applied topically to the scalp as viable microorganisms or as postbiotic compositions comprising anti-dandruff actives.

[0103] In an embodiment of the invention, the composition comprises a probiotic microorganism capable of producing a bacteriocin and at least one organic acid as active substances.

[0104] In another embodiment of the invention, the composition comprises a probiotic microorganism capable of producing plantarcin and at least one organic acid as active substances.

[0105] Preferably, the composition comprises at least two different bacteriocins as active agents.

[0106] The compositions of the present invention may include probiotic microorganisms capable of producing active substances.

[0107] The compositions of the present invention may include an acceptable carrier, and for topical compositions, the acceptable carrier may be a dermatologically acceptable carrier (sometimes referred to as a "carrier") for providing the active agent. A suitable carrier may be selected to obtain the desired product form. Additionally, the solubility or dispersibility of the ingredients may determine the form and characteristics of the carrier. In one embodiment, the carrier may be present at a level of about 30 weight percent to about 99 weight percent, about 40 weight percent to about 98 weight percent, about 50 weight percent to about 96 weight percent, or alternatively about 60 weight percent to about 95 weight percent of the composition. The weight percentages are based on the weight of the entire composition.

[0108] The carrier may be in a wide variety of forms. Non-limiting examples include simple solutions (e.g., aqueous, organic solvent, or oil-based), emulsions, and solid forms (e.g., gels, powders, sticks, flowable solids, or amorphous materials). In certain embodiments, the carrier is an aqueous carrier that may include water or natural plant juices such as Aloe Vera water. In certain embodiments, the carrier may be in the form of an emulsion. Emulsions can generally be classified as having a continuous aqueous phase (e.g., oil-in-water and water-in-oil-in-water) or a continuous oil phase (e.g., water-in-oil and oil-in-water-in-oil). The oil phase of the present invention may include natural oils, vegetable oils, silicone oils, non-silicone oils such as hydrocarbon oils, esters, ethers, and mixtures thereof.

[0109] In the case of emulsions, the aqueous phase may include water, such as demineralized water or distilled water. Other acceptable carriers that may be used in the aqueous carrier include, but are not limited to, alcohols or ether compounds, such as ethanol, glycerol, dipropylene glycol, propylene glycol, butylene glycol, 1,4-butanediol, 3-allyloxy-1,2-propanediol, dipropylene glycol n-butyl ether, 1,2-hexanediol, dimethyl isosorbide, ethanol, 1,3-butanediol, 1,3-propanediol, 2,2'-thiodiethanol, and 1,6-hexanediol, or combinations thereof.

[0110] In one embodiment of the invention, the carrier and active agent can be separated into two compartments and the contents of the two compartments can then be mixed into one composition immediately prior to administration, such as by topical application.

[0111] For example, a bottle comprising a carrier and a cap having a compartment containing lyophilized viable probiotic microorganisms which can be released from the cap compartment into the carrier prior to administration.

[0112] The compositions of the present invention may have a pH in the range of about 3.0 to about 6.5, which may be measured by making a direct pH measurement using a standard hydrogen electrode on the composition at 25° C. Thus, the pH of the composition may be within the range of about 3 to about 6, more preferably within the range of 3.5 to 5.5.

[0113] A preferred embodiment of the present invention is a composition having a pH of less than 6.5, such as an anti-dandruff composition, more preferably a composition having a pH of less than 6, more preferably a composition having a pH of less than 5.5, more preferably a composition having a pH of less than 5.2.

[0114] In embodiments of the present invention, the compositions may be formulated as a soap, a shampoo, an emulsion; an oil; a paste; a powder; a talc; a lotion; a foam; a gel; an ointment; a suspension; a mist; or a liquid; or a tablet.

[0115] In a further embodiment of the present invention, the compositions of the present invention may be prepared in typical formulations for topical application, preferably in the form of solutions, dispersions, emulsions, powders, talcum, encapsulations, spheres, sponges, solid dosage forms, foams, and other delivery mechanisms.

[0116] Compositions of embodiments of the present invention include hair tonics, leave-on hair products such as scalp serums, conditioners, treatment and styling products, rinse-off hair products such as conditioners, shampoos, and treatment products, and any other form that can be applied to the scalp or skin.

[0117] The compositions according to the invention may be leave-on or rinse-off compositions depending on the desired application.

[0118] In one preferred embodiment of the present invention, the composition may be an anti-dandruff composition, preferably a leave-on scalp treatment.

[0119] In another preferred embodiment of the present invention, the composition may be a shampoo.

[0120] In a further embodiment of the present invention, the composition may be a nail composition. In addition to the above description of the composition formulations, the nail composition may be a nail varnish, nail cream, nail oil, nail emulsion, nail gel, ointment, and the like.

[0121] The nail composition may be suitable for removing, limiting, treating or preventing a fungal infection, such as mycosis or onychomycosis on the nails of a human or animal.

[0122] In a further embodiment of the present invention, the composition may be a foot composition. In addition to the above description of the composition formulations, the foot composition may preferably be a foot cream, foot oil, foot emulsion, foot ointment, and the like.

[0123] The foot composition may be suitable for eliminating, limiting, treating or preventing fungal infections such as mycosis or pediculosis, athlete's foot on the feet of humans or animals.

[0124] Other components of the composition Thus, the compositions of the present invention may also include other common hair ingredients. The CTFA Cosmetic Ingredient Handbook, Tenth Edition (published by the Cosmetic, Toiletry, and Fragrance Association, Inc. (now called The Personal Care Products Council), Washington, DC) (2004) describes a wide variety of non-limiting materials that can be added to the compositions herein. Examples of these ingredient classes include, but are not limited to, abrasives, absorbents, fragrances, pigments, coloring / colorants, essential oils, skin sensates, astringents, anti-acne agents, anti-caking agents, anti-foaming agents, antibacterial agents, antioxidants, binders, biological additives, buffers, bulking agents, chelating agents, film formers, opacifiers, pH adjusters, propellants, reducing agents, sequestering agents, rheology modifiers, conditioning agents, emulsifiers, and surfactants. According to embodiments, the anti-dandruff composition may be formulated as a hair care composition, such as a shampoo, a hair conditioner, or a shampoo-conditioner combination, further comprising one or more of the following ingredients: (i) surfactants (anionic, amphoteric / zwitterionic, nonionic), (ii) conditioning agents, (iii) emulsifiers, (iv) opacifying agents, (v) thickening agents, and (vi) buffering agents.

[0125] Surfactants Thus, in one embodiment, the compositions of the present invention may be formulated as hair care compositions with a shampoo matrix comprising at least one cleansing surfactant selected from the group consisting of anionic surfactants, nonionic surfactants, amphoteric surfactants, or combinations thereof.

[0126] The hair care compositions of the present invention may include detersive surfactants which provide cleaning performance to the composition. The concentration of the cleansing surfactant component in a composition, such as a hair care composition, should be sufficient to provide the desired cleaning and lathering performance, and generally ranges from about 2 weight percent to about 50 weight percent, about 5 weight percent to about 40 weight percent, about 8 weight percent to about 35 weight percent, or about 10 weight percent to about 30 weight percent. Thus, a composition, such as a hair care composition, may contain, for example, about 5 weight percent, about 10 weight percent, about 12 weight percent, about 15 weight percent, about 17 weight percent, about 18 weight percent, about 20 weight percent, about 25 weight percent, about 30 weight percent, or an amount ranging between any two of the foregoing. The weight percent is based on the weight of the entire composition.

[0127] Exemplary anionic surfactants for use in the compositions include ammonium lauryl sulfate, ammonium laureth sulfate, triethylamine lauryl sulfate, triethylamine laureth sulfate, triethanolamine lauryl sulfate, triethanolamine laureth sulfate, monoethanolamine lauryl sulfate, monoethanolamine laureth sulfate, diethanolamine lauryl sulfate, diethanolamine laureth sulfate, lauric monoglyceride sodium sulfate, sodium lauryl sulfate, sodium laureth sulfate, potassium lauryl sulfate, potassium laureth sulfate, sodium lauryl sarcosinate, sodium lauro ... sarcosinate), lauryl sarcosine, cocoyl sarcosine, ammonium cocoyl sulfate, ammonium lauroyl sulfate, sodium cocoyl sulfate, sodium lauroyl sulfate, potassium cocoyl sulfate, potassium lauryl sulfate, triethanolamine lauryl sulfate, triethanolamine lauryl sulfate, monoethanolamine cocoyl sulfate, monoethanolamine lauryl sulfate, sodium tridecylbenzenesulfonate, sodium dodecylbenzenesulfonate, sodium cocoyl isethionate, and combinations thereof. In a further embodiment of the invention, the anionic surfactant is sodium lauryl sulfate, sodium laureth sulfate, or combinations thereof.

[0128] Suitable amphoteric / zwitterionic surfactants for use in the compositions herein may include, for example, those known for use in hair care or other personal care cleansing. The concentration of such surfactants may range from about 0.5 weight percent to about 20 weight percent, and from about 1 weight percent to about 10 weight percent. An example is betaine, and further non-limiting examples of suitable zwitterionic or amphoteric surfactants are described in U.S. Pat. Nos. 5,104,646 and 5,106,609, which are incorporated herein by reference in their entireties.

[0129] Amphoteric cleansing surfactants suitable for use in the compositions may include surfactants broadly described as derivatives of aliphatic secondary and tertiary amines, where the aliphatic group may be straight or branched chain, one of the aliphatic substituents contains from about 8 to about 18 carbon atoms, and contains at least one anionic group, such as carboxy, sulfonate, sulfate, phosphate, or phosphonate. Zwitterionic cleansing surfactants suitable for use in the hair care compositions include surfactants broadly described as derivatives of aliphatic quaternary ammonium, phosphonium, and sulfonium compounds, where the aliphatic group may be straight or branched chain, one of the aliphatic substituents contains from about 8 to about 18 carbon atoms, and one contains an anionic group, such as carboxy, sulfonate, sulfate, phosphate, or phosphonate. Exemplary amphoteric and / or zwitterionic detersive surfactants for use in the present compositions include cocoamphoacetate, cocoamphodiacetate, lauroamphoacetate, lauroamphodiacetate, cocamidopropyl betaine, cocamidopropyl hydroxysultaine, and mixtures thereof.

[0130] Nonionic surfactants may be added to some compositions, particularly shampoo compositions.

[0131] The compositions according to the invention, such as shampoo compositions, may contain non-ionic surfactants, which may include compounds produced by condensation of an essentially hydrophilic alkylene oxide group with an organic hydrophobic compound, which may be aliphatic or alkylaromatic in nature.

[0132] Non-limiting examples of nonionic surfactants for use, for example, in shampoo compositions, may include: (1) polyethylene oxide condensates of alkylphenols, such as condensation products of alkylphenols having an alkyl group containing from about 6 to about 20 carbon atoms in either a linear or branched arrangement with ethylene oxide, the ethylene oxide being present in an amount equivalent to from about 10 to about 60 moles of ethylene oxide per mole of alkylphenol; (2) those derived from the condensation of ethylene oxide with a product resulting from the reaction of propylene oxide with an ethylenediamine product; (3) condensation products of aliphatic alcohols having from about 8 to about 18 carbon atoms in either a linear or branched arrangement with ethylene oxide, such as coconut alcohol ethylene oxide condensates having from about 10 to about 30 moles of ethylene oxide per mole of coconut alcohol, the coconut alcohol fraction having from about 10 to about 14 carbon atoms; (4) those of the formula [R 1 R 2 R 3 N0], 1 contains an alkyl, alkenyl, or monohydroxyalkyl group of from about 8 to about 18 carbon atoms, from 0 to about 10 ethylene oxide moieties, and from 0 to about 1 glyceryl moiety; R 2 and R 3contains from about 1 to about 3 carbon atoms and 0 to about 1 hydroxy group, e.g., methyl, ethyl, propyl, hydroxyethyl, or hydroxypropyl groups; (5) the formula [RR'R"P(R)0], where R contains an alkyl, alkenyl, or monohydroxyalkyl group ranging in chain length from about 8 to about 18 carbon atoms, 0 to about 10 ethylene oxide moieties, and 0 to 1 glyceryl moiety, and R' and R" are each an alkyl or monohydroxyalkyl group containing from about 1 to about 3 carbon atoms; (6) long chain dialkyl groups containing one short chain alkyl or hydroxyalkyl group of 1 to about 3 carbon atoms (usually methyl) and one long chain hydrophobic chain containing an alkyl, alkenyl, hydroxyalkyl, or ketoalkyl group containing from about 8 to about 20 carbon atoms, 0 to about 10 ethylene oxide moieties, and 0 to 1 glyceryl moiety. sulfoxides; (7) alkyl polysaccharide (APS) surfactants (e.g., alkyl polyglycosides), examples of which are described in U.S. Pat. No. 4,565,647, which is incorporated herein by reference in its entirety and discloses APS surfactants having a hydrophobic group having from about 6 to about 30 carbon atoms and a polysaccharide (e.g., polyglycoside) as the hydrophilic group, optionally with a polyalkylene oxide group connecting the hydrophobic and hydrophilic portions. The alkyl group (i.e., the hydrophobic portion) can be saturated or unsaturated, branched or unbranched, and unsubstituted or substituted (e.g., with hydroxy or cyclic rings); and (8) alkyl groups of the general formula RO(CH2CH2) n H), and polyoxyethylene alkyl ethers having the general formula R(0)0CH2CH(0H)CH2(0CH2CH2) n 0H), where n is 1 to about 200, preferably about 20 to about 100, and R is an alkyl having from about 8 to about 22 carbon atoms.

[0133] Certain nonionic surfactants can also function as foam stabilizers, viscosity control agents, or conditioning agents. When included, the composition may contain about 0.5 weight percent to about 5.0 weight percent of nonionic surfactants, or about 0.75 weight percent to about 2.0 weight percent. Non-limiting examples of other anionic, amphoteric / zwitterionic, nonionic, or optional additional surfactants suitable for use in the composition are described in U.S. Patent Nos. 3,929,678, 2,658,072, 2,438,091, and 2,528,378, which are incorporated herein by reference in their entirety.

[0134] Conditioning Agent In one embodiment of the present invention, the composition may include one or more conditioning agents. Conditioning agents include materials used to impart specific conditioning benefits to human or animal hair, nails, and / or skin. Conditioning agents useful in the compositions of the present invention typically include water-insoluble, water-dispersible, non-volatile liquids that form emulsified liquid particles. Conditioning agents suitable for use in the composition may be conditioning agents generally characterized as silicones (e.g., silicone oils, cationic silicones, silicone gums, high refractive silicones, and silicone resins), organic conditioning oils (e.g., hydrocarbon oils, polyolefins, and fatty esters), or combinations thereof, or conditioning agents that form liquid particles dispersed in an aqueous surfactant matrix. In embodiments, the one or more conditioning agents are present in an amount of from about 0.01 weight percent to about 10 weight percent, from about 0.1 weight percent to about 8 weight percent, and from about 0.2 weight percent to about 4 weight percent of the total composition weight.

[0135] emulsifier Various anionic emulsifiers may be used in the compositions of the present invention, particularly shampoo compositions, described below. Anionic emulsifiers include, by way of example and not limitation, alkyl sulfates, alkyl ether sulfates, alkyl isothionates, alkyl carboxylates, alkyl sulfosuccinates, alkyl succinamates, alkyl ether sulfates ... succinamates), alkyl sulfate salts such as sodium dodecyl sulfate, alkyl sarcosinates, alkyl derivatives of protein hydrolysates, acylaspartates, alkyl ether or alkyl ether or alkylaryl ether phosphate esters, sodium dodecyl sulfate, phospholipids or lecithins, or soaps, sodium stearate, potassium stearate or ammonium stearate, oleates or palmitates, alkylarylsulfonates such as sodium dodecylbenzenesulfonate, sodium dialkylsulfosuccinate, dioctyl sulfosuccinate, sodium dilauryl sulfosuccinate, poly(styrenesulfonic acid) sodium salt, isobutylene-maleic anhydride copolymer, gum arabic, sodium alginate, carboxymethylcellulose, cellulose sulfate and pectin, poly(styrenesulfonate), isobutylene-maleic anhydride acid copolymers, gum arabic, carrageenan, sodium alginate, pectinic acid, tragacanth gum, almond gum and agar; semi-synthetic polymers such as carboxymethylcellulose, cellulose sulfate, methylcellulose sulfate, carboxymethylstarch, starch phosphate, lignosulfonic acid; and synthetic polymers such as maleic anhydride copolymers (including their hydrolysates), polyacrylic acid, polymethacrylic acid, acrylate-butyl acrylate copolymers or crotonic acid homopolymers and copolymers, vinylbenzenesulfonic acid or 2-acrylamido-2-methylpropanesulfonic acid homopolymers and copolymers, and partial amides or partial esters of such polymers and copolymers, carboxyl-, sulfonate- and phosphate-modified polyvinyl alcohols, phosphated or sulfated tristyrylphenol ethoxylates.

[0136] Additionally, anionic emulsifiers having acrylate functionality may also be used in the compositions of the present invention, such as in the shampoo compositions of the present invention. Anionic emulsifiers useful herein include, but are not limited to, poly(meth)acrylic acid; copolymers of (meth)acrylic acid and its (meth)acrylates with Cl-22 alkyl, C1-C8 alkyl, butyl; copolymers of (meth)acrylic acid and (meth)acrylamide; carboxyvinyl polymers; acrylate copolymers such as acrylates / C10-30 alkyl acrylate crosspolymer, acrylic acid / vinyl ester copolymer / acrylates / vinyl isodecanoate crosspolymer, acrylates / palmeto-25 acrylate copolymer, acrylates / steareth-20 itaconate copolymer, and acrylates / cereth-20 itaconate copolymer; polystyrene sulfonate, copolymers of methacrylic acid and acrylamidomethylpropane sulfonic acid, and copolymers of acrylic acid and acrylamidomethylpropane sulfonic acid; carboxymethylcellulose; carboxyguar; copolymers of ethylene and maleic acid; and acrylate silicone polymers. In embodiments, the emulsifier, when present, ranges from about 0.01 weight percent to about 5 weight percent, or from about 0.1 weight percent to about 4 weight percent, or from about 0.1 weight percent to about 3 weight percent of the total composition, where weight percent is based on the weight of the total composition.

[0137] Carbomers can be used in hydrogels at low concentrations for liquid gels and at higher concentrations for solid gels.

[0138] Optional Opacifier Some compositions of the present invention may be provided as opacifying formulations by incorporating materials therein to achieve a cosmetically attractive pearl-like appearance known as pearlescence. Opacifying or pearlescent materials may include, but are not limited to, titanium dioxide coated mica, iron oxide coated mica, ethylene glycol monostearate, ethylene glycol distearate, polyethylene glycol distearate, bismuth oxychloride coated mica, myristyl myristate, guanine, glitters (polyester or metallic), and mixtures thereof. Other pearlescent materials may be found in U.S. Pat. Nos. 4,654,207 and 5,019,376, which are incorporated herein by reference. In embodiments, the concentration of the opacifying agent, if present, ranges from about 0.01 weight percent to about 5 weight percent of the total, or from about 0.1 weight percent to about 3 weight percent, or from about 0.1 weight percent to about 2 weight percent. Weight percent is based on the weight of the total composition.

[0139] Thickener Thickeners or rheology modifiers include acrylamide / ammonium acrylate copolymer (and) polyisobutene (and) polysorbate 20; acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80; acrylates copolymer; acrylates / beheneth-25 methacrylate copolymer; acrylates / C10-C30 alkyl acrylate crosspolymer; acrylates / steareth-20 itaconate copolymer; ammonium polyacrylate / isohexadecane / PEG-40 castor oil; Cl2-16 alkyl PEG-2 hydroxypropyl hydroxyethyl ethylcellulose (HM-EHEC); carbomer; cross-linked polyvinylpyrrolidone (PVP); dibenzylidene sorbitol; hydroxyethyl ethylcellulose (EHEC); hydroxypropyl methylcellulose (HPMC); hydroxypropyl methylcellulose (HPMC); hydroxypropyl cellulose (HPC); methylcellulose (MC); methylhydroxyethylcellulose (MEHEC); PEG-1 50 / Decyl Alcohol / SMDI Copolymer;PEG-1 50 / Stearyl Alcohol / SMDI Copolymer;Polyacrylamide / C 13-14 Isoparaffin / Laureth-7;Polyacrylate 13 / Polyisobutene / Polysorbate 20;Polyacrylate Crosspolymer-6;Polyamide-3;Polyquatium-37 (and) Hydrogenated Polydecene (and) Trideceth-6;Polyurethane-39;Sodium Acrylate / Acryloyldimethyltaurate / Dimethylacrylamide;Crosspolymer (and)Isohexadecane (and)Polysorbate 60;Sodium Polyacrylate, and combinations thereof. In one embodiment, the concentration of the rheology modifier, if present, ranges from about 0.01 weight percent to about 7 weight percent, or from about 0.1 weight percent to about 5 weight percent, or from about 0.2 weight percent to about 4 weight percent of the total composition. The weight percent is based on the weight of the total composition.

[0140] buffer solution The compositions of the present invention may have a pH in the range of about 3.0 to about 6.5 and may be stabilized by the presence of a buffer system. Suitable buffers may be prepared using a weak acid or weak base system using, for example, citric acid, phosphoric acid, phthalic acid, acetic acid, lactic acid, glycine or mixtures thereof. In either case, adequate buffering capacity is obtained by adjusting the final pH of the composition to within the above pH range. This may be done using an acid (e.g., HCl, citric acid) or a base (e.g., NaOH, sodium citrate) as necessary. The amount of buffering agent used in the present compositions may depend on the particular acid selected, but is generally about 0.1 weight percent to about 10 weight percent, preferably about 0.2 weight percent to about 5 weight percent. Weight percentages are based on the weight of the entire composition.

[0141] Additional agents, such as benefit agents, may also be included in the compositions of the present invention. The benefit agents may include materials selected from the group consisting of prebiotics, fragrances, brighteners, enzymes, sensates (cooling or warming), attractants, preservatives, dyes, pigments, bleaching agents, and mixtures thereof.

[0142] It should be further understood that the inventive combinations of natural actives disclosed herein may also be used in combination with secondary scalp benefit actives, such as soluble and / or insoluble secondary actives. Such secondary active substances include azoles such as ketoconazole, econazole, climbazole and elubiol; keratolytic agents such as salicylic acid; and zinc-containing layered (ZLM) materials, pyridinethione antidandruff particles, e.g. zinc pyrithione, coal tar, sulfur, charcoal, whitfield ointment, castellani paint, aluminum chloride, gentian violet, octopirox (piroctone olamine), ciclopirox olamine, undecylenic acid and its metal salts, potassium permanganate, selenium sulfide, sodium thiosulfate, propylene glycol, urea preparations, griseofulvin, 8-hydroxyquinolinic trioquinol, thiobendazole, thiocarbamates, haloprogins, polyenes, hydroxypyridones, morpholines, benzylamines, allylamines (such as terbinafine), Sensiva SC-50, Elestab Examples of secondary benefit agents include, but are not limited to, HP-100, azelaic acid, lyticase, iodopropynyl butylcarbamate (IPBC), isothiazalinones such as octylisothiazarinone, other natural oils, extracts, or compounds such as bitter orange oil, tea tree oil, clove leaf oil, coriander, palmarosa, berberine, thyme red, cinnamon oil, cinnamaldehyde, citronellic acid, hinokitol, ictyl pale, and combinations thereof. In embodiments, the concentration of the secondary benefit agent may range from about 0.01 weight percent to about 5 weight percent, or from about 0.1 weight percent to about 3 weight percent, or from about 0.1 weight percent to about 2 weight percent of the total composition. The weight percentages are based on the weight of the total composition. In alternative embodiments of the present invention, the inventive combination of natural actives disclosed herein may also be free of any of the secondary actives listed above.

[0143] Preferably, at least one prebiotic compound can be included as an additional agent, i.e., as another component, in the composition of the present invention.In a very broad concept, prebiotics are all compounds that can be metabolized by probiotics.Preferably, prebiotics are not digested or are hardly digested by mammals.Prebiotics are well known in the art, and there is no particular limitation on prebiotics itself when used in the present invention.

[0144] Preferably, the at least one prebiotic product in the composition may be selected from the following compounds and compositions: non-digestible carbohydrates, beta-glucans, mannan-oligosaccharides, inulin, oligofructose, human milk oligosaccharides (HMO), galactooligosaccharides (GOS), lactulose, lactosucrose, galactotriose, fructo-oligosaccharides (FOS), cellobiose, cellodextrin, cyclodextrin, maltitol, lactitol, glycosylsucrose. Mannan oligosaccharides and / or inulin may be preferred.

[0145] HMOs may include lacto-N-tetraose, lacto-N-fucopentaose, lacto-N-triose, 3'-sialyllactose, lacto-N-neofucopentaose, sialic acid, L-fucose, 2-fucosyllactose, 6'-sialyllactose, lacto-N-neotetraose and 3-fucosyllactose.

[0146] D-fucose and L-fucose may be suitable and may strengthen the skin's natural defenses, stimulate the epidermal immune defenses and / or prevent and / or treat skin autoimmune diseases. In a preferred embodiment of the invention, the composition comprises D- and / or L-fucose.

[0147] In a preferred embodiment of the present invention, the composition further comprises L-fucose at a concentration of 10 mM to 500 mM in the composition.

[0148] The compositions of the present invention can generally be prepared by conventional methods known in the art, such as preparing shampoo compositions, creams, oils, emulsions, and the like. Such methods typically include mixing the ingredients in one or more steps to a relatively homogeneous state, with or without heating, cooling, application of vacuum, and the like. The compositions can be prepared to optimize the stability (physical stability, chemical stability, photostability) and / or delivery of the actives. This optimization can include appropriate pH and the elimination of materials that may complex or react with the active(s) and thus adversely affect stability or delivery.

[0149] The composition may be a single phase or a single product, or the composition may be separate phases or separate products. When two products are used, they may be used together simultaneously or sequentially. Sequential use may occur over a short period of time, such as immediately after use of one product, or over the course of several hours or days.

[0150] In one embodiment of the present invention, the composition comprises 10 3 From 10 13 A leave-on composition comprising live probiotic bacteria at a concentration of colony forming bacteria units. More specifically, the leave-on composition comprises live probiotic bacteria at a concentration of 10 per gram. 4 ~10 10 Compositions containing colony forming units of bacteria, more specifically 10 per gram 5 ~10 9 A composition comprising colony forming units of bacteria.

[0151] In one embodiment of the invention, the composition has at least 10 3 A leave-on composition comprising live probiotic bacteria at a concentration of colony forming bacteria units. More specifically, at least 10 per gram. 4 Compositions containing colony forming units of bacteria, more particularly at least 10 per gram 5 Compositions containing colony forming units of bacteria, more particularly at least 10 per gram 6Compositions containing colony forming units of bacteria, more particularly at least 10 per gram 7 A composition comprising colony forming units of bacteria.

[0152] In one embodiment of the invention, the composition comprises a postbiotic fraction of an active, such as an anti-dandruff active or an anti-fungal active.

[0153] Use of the composition of the present invention as an anti-dandruff composition: According to an embodiment of the present invention, a method is provided for treating a subject with dandruff and / or for preventing or inhibiting the onset of dandruff symptoms associated with the proliferation of yeast of the genus Malassezia on the scalp of a subject. The method comprises contacting the scalp or keratinous tissue of the subject with an effective amount of the anti-dandruff composition of the present invention. The anti-dandruff composition may be massaged onto the scalp and should remain in contact with the scalp or keratinous tissue of the subject for a period of at least 15 seconds or more. Depending on the formulation, the anti-dandruff composition may be a leave-in or may be rinsed off.

[0154] Thus, in another embodiment, the method comprises topically applying an anti-dandruff composition comprising an effective amount of an anti-dandruff active to an area of ​​the subject's skin where inhibition of Malassezia is necessary or desired, where the anti-dandruff active is left in contact with the area as a leave-on composition or for a period of 15 seconds or more and then washed off. In yet another embodiment, the method comprises applying the composition according to a regimen comprising (a) cleansing the scalp to form a cleansed scalp, and (b) topically applying the anti-dandruff composition to the cleansed scalp.

[0155] Use of the composition of the present invention as an anti-fungal composition: According to an embodiment of the present invention, there is provided a method for treating a subject having a fungal infection on the nails or feet and / or for preventing or inhibiting the onset of fungal symptoms associated with the growth of Malassezia on the nails and / or feet of a subject. The method comprises contacting the nails and / or feet of a subject with an effective amount of the anti-fungal composition of the present invention. The anti-fungal composition may be massaged into the nails and / or feet and should remain in contact with the nails and / or feet of the subject for a period of at least 15 seconds or more. Depending on the formulation, the anti-fungal composition may be a leave-in or a wash-off.

[0156] Thus, in another embodiment, the method comprises topically applying an anti-fungal composition comprising an effective amount of an anti-fungal active to an area of ​​the subject's nails and / or feet where inhibition of fungus is necessary or desired, either as a leave-on composition or the anti-fungal active remains in contact with the area for a period of 15 seconds or more and then washed off. In yet another embodiment, the method comprises applying the composition according to a regimen comprising (a) washing the nails or feet to form a washed scalp, and (b) topically applying the anti-fungal composition to the washed nails or feet.

[0157] According to the present invention, a fungal infection may include dandruff and / or mycosis. A mycosis may relate to any disease caused by a fungus and may affect different parts of the body, in particular the feet, ears, hands and / or nails of the human or animal body.

[0158] A preferred embodiment of the invention relates to a composition according to the invention for use in the prevention and / or treatment of fungal diseases in humans or animals.

[0159] Preferably, the prevention and / or treatment of fungal diseases and / or dandruff in humans or animals may include the prevention and / or treatment of conditions associated with the proliferation of yeasts of the genus Malassezia on the scalp, hands, ears, feet, nails or skin of a subject.

[0160] In a further embodiment of the invention, the composition comprises one or more probiotic bacterial strains (preferably isolated probiotic bacterial strains) and / or active substances of one or more probiotic bacterial strains (preferably isolated probiotic bacterial strains) for use in the prevention and / or treatment of a fungal disease in a human or animal.

[0161] The prevention and / or treatment of mycoses in humans or animals may be the prevention and / or treatment of: - a dandruff condition associated with the proliferation of yeasts of the genus Malassezia on the scalp or skin of humans or animals; or - in humans or animals, fungal nail infections associated with the growth of fungi or yeasts, e.g. Tinea unguium or Trichophyton spp. on the nail; or

[0162] In an embodiment of the invention, the composition comprises nucleic acids and / or nucleotides.

[0163] In a further embodiment of the invention the composition is free of plant and / or fibrous material.Preferably the fibrous material is a plant fibrous material.

[0164] Preferably, the content of fibre material in the composition is less than 5% (w / w), such as less than 4% (w / w), for example less than 3% (w / w), such as less than 2% (w / w), for example less than 1% (w / w), such as less than 0.5 (w / w), for example less than 0.1% (w / w), such as 0%, relative to the total composition.

[0165] In an embodiment of the invention the composition comprises two or more active substances (the particular active substances may be as described above) of one or more isolated probiotic bacterial strains, such as three or more (e.g. four or more), such as five or more (e.g. four or more), such as ten or more (e.g. fifteen or more), such as twenty or more (e.g. twenty-five or more).

[0166] The subject according to the present invention may be a mammal selected from a human, a dog, a cat, a horse, a cow or a sheep.

[0167] The compositions of the present invention may be used daily, weekly, or in various regimes. The compositions may be used more than once a day, such as at night and in the morning. The compositions may be used after washing the hair (even on wet or dry hair), or after washing the body, feet, or nails, which may mean using the composition more than once a day on a particular day, or using it only a few times a week. The compositions may be used three times a day, twice a day, once a day, six times a week, five times a week, four times a week, three times a week, two times a week, or once a week. In some embodiments, the anti-dandruff composition is used 4, 5, 6, or 7 times a week.

[0168] According to another embodiment, the composition may be applied at least once a day for at least about one week, or at least twice a day for at least about one week.

[0169] According to another embodiment, the composition can be applied at least once a day for at least about 4 weeks, or at least twice a day for at least about 4 weeks. According to another embodiment, the composition can be applied at least once a day for at least about 8 weeks. The composition can be used by men and women. The composition can be used by mammals of any age, including newborns, infants, babies and children.

[0170] In an embodiment of the present invention, the composition may be an anti-dandruff composition. Preferably, the anti-dandruff composition may be used for the prevention or treatment of neonatal scalp dermatitis.

[0171] In another embodiment of the invention, the composition may be applied to the skin, fur, oral cavity, genital area, ears and / or body orifices of humans or animals.

[0172] Preferably, the composition according to the invention may be applied topically to the animal, in a further preferred embodiment, the animal may be selected from dogs, cats, cows, bovines, sheep, goats, horses and birds.

[0173] The present invention may relate to compositions (such as anti-dandruff compositions and / or anti-fungal compositions) comprising probiotic microorganisms capable of producing active substances when applied topically to infected areas such as the scalp, hands, skin, ears, feet and / or nails.

[0174] The present invention may relate to anti-dandruff compositions comprising probiotic microorganisms capable of producing anti-dandruff actives when applied topically to the scalp.

[0175] Preferably, the composition comprises at least two anti-dandruff actives produced by probiotic microorganisms selected from bacteriocin, lactic acid, acetic acid, succinic acid, azelaic acid, salicylic acid, indole-3-lactic acid, indole-3-acetic acid, 2-hydroxybutyric acid, N-acetyltryptophan, glycolic acid, N-acetylglutamine and N-acetylaspartic acid.

[0176] A composition for treating dandruff and / or fungal conditions, comprising at least 10 3 A composition comprising viable probiotic microorganisms in a concentration of colony forming units, the probiotic microorganisms being capable of producing anti-dandruff and / or anti-fungal active substances.

[0177] A composition for treating dandruff and / or fungal diseases having a pH of less than 6.5, the composition comprising at least 10 3 A composition comprising viable probiotic microorganisms in a concentration of colony forming units, the probiotic microorganisms being capable of producing anti-dandruff and / or anti-fungal active substances.

[0178] A composition comprising a live bacteriocin-producing probiotic microorganism, wherein the same microorganism produces at least two of the following metabolic products: succinic acid, azelaic acid, salicylic acid, 2-hydroxyisocaproic acid, indole-3-lactic acid, indole-3-acetic acid, 2-hydroxybutyric acid, N-acetyltryptophan, glycolic acid, N-acetyl-glutamine, and N-acetylaspartic acid.

[0179] A composition comprising a postbiotic fraction derived from lactic acid bacteria capable of producing at least two of the following anti-dandruff and / or anti-fungal actives: succinic acid, azelaic acid, salicylic acid, 2-hydroxyisocaproic acid, indole-3-lactic acid, indole-3-acetic acid, 2-hydroxybutyric acid, N-acetyltryptophan, glycolic acid, N-acetylglutamine or N-acetylaspartic acid.

[0180] An anti-dandruff and / or anti-fungal composition comprising indole-3-lactic acid, wherein the indole-3-lactic acid is produced by lactic acid bacteria.

[0181] 1. An anti-dandruff and / or anti-fungal composition comprising salicylic acid, wherein the salicylic acid is produced by lactic acid bacteria.

[0182] 1. An anti-dandruff and / or anti-fungal composition comprising gluconic acid, wherein the gluconic acid is produced by lactic acid bacteria.

[0183] An anti-dandruff and / or anti-fungal composition comprising phenyllactic acid, wherein the phenyllactic acid is produced by lactic acid bacteria.

[0184] 1. An anti-dandruff and / or anti-fungal composition comprising 2-hydroxyisocaproic acid, wherein the 2-hydroxyisocaproic acid is produced by lactic acid bacteria.

[0185] 1. An anti-dandruff and / or anti-fungal composition comprising 2-hydroxy-butyric acid, wherein the 2-hydroxy-butyric acid is produced by lactic acid bacteria.

[0186] An anti-dandruff and / or anti-fungal disease composition comprising N-acetylaspartic acid, wherein the N-acetylaspartic acid is produced by lactic acid bacteria.

[0187] 1. An anti-dandruff and / or anti-fungal composition comprising azelaic acid, wherein the azelaic acid is produced by lactic acid bacteria.

[0188] 1. An anti-dandruff and / or anti-fungal composition comprising succinic acid, wherein the succinic acid is produced by lactic acid bacteria.

[0189] 1. An anti-dandruff and / or anti-fungal composition comprising indole 3-acetic acid, wherein the indole 3-acetic acid is produced by lactic acid bacteria.

[0190] An anti-dandruff and / or anti-fungal composition comprising 3-phenyllactic acid, wherein the 3-phenyllactic acid is produced by lactic acid bacteria.

[0191] 1. An anti-dandruff and / or anti-fungal disease composition comprising N-acetylglutamine, wherein the N-acetylglutamine is produced by lactic acid bacteria.

[0192] An anti-dandruff and / or anti-fungal composition comprising 2-hydroxyisocaproic acid and salicylic acid produced by lactic acid bacteria.

[0193] An anti-dandruff and / or anti-fungal composition according to any one of the compositions above, said composition comprising at least one bacteriocin.

[0194] An anti-dandruff and / or anti-fungal composition comprising a bacteriocin, salicylic acid, indole-3-lactic acid and 3-phenyllactic acid.

[0195] An anti-dandruff and / or anti-fungal composition comprising a bacteriocin, 2-hydroxyisocaproic acid, salicylic acid, indole-3-lactic acid, 2-hydroxybutyric acid and N-acetylaspartic acid.

[0196] An anti-dandruff and / or anti-fungal composition according to any of the compositions above, wherein the composition is produced by an isolated lactic acid bacterium.

[0197] An anti-dandruff and / or anti-fungal composition according to any of the above compositions further comprising at least one antibacterial bacterial metabolite selected from the group comprising hydrogen peroxide, 3-phenyllactic acid, 3-hydroxyphenyllactic acid, 4-hydroxyphenyllactic acid, 2-hydroxyisocaproic acid, 3-hydroxypropanaldehyde, 1,2-propanediol, 1,3-propanediol, succinic acid, ethanol, acetic acid, carbonic acid, propanoic acid, butyric acid, cyclic dipeptides, cyclo(L-Phe-L-Pro), cyclo(L-Traps-4-OH-L-Pro), 3-(R)-hydroxydecanoic acid, 3-hydroxy-5-thiocyanododecanoic acid, 3-(R)-hydroxydodecanoic acid, and 3-(R)-hydroxytetradecanoic acid.

[0198] Probiotic microorganisms include Lactiplantibacillus plantarum LB356R (DSM 33094), Lactiplantibacillus plantarum LB244R (DSM 32996), Weissella viridescens LB10G (DSM 32906), Lacticaseibacillus paracasei LB113R (DSM 32907), Lacticaseibacillus paracasei LB116R(DSM 32908), Levilactobacillus brevis LB152G(DSM 32995), Lacticaseibacillus paracasei LB28R(DSM 32994), Enterococcus faecium LB276R(DSM 32997), Leuconostoc mesenteriodes LB349R(DSM 33093), Lactiplantibacillus plantarum LB316R (DSM 33091), Lactiplantibacillus plantarum LB312R (DSM 33098), Pediococcus pentosaceus LB606R (DSM 33730), Lactiplantibacillus plantarum LB679R (DSM 33731), Lactobacillus crispatus LB714R (DSM 33732), Lactobacillus gasseri LB905R (DSM 34094), Lactobacillus crispatus LB912R (DSM 34095), Lactobacillus jensenii LB918R (DSM 34096), Lactobacillus crispatus LB919R(DSM 34097), Lacticaseibacillus paracasei subsp. paracasei LB555R (DSM 34249), Lactiplantibacillus plantarum LB681R (DSM 34250); and / or any combination thereof.

[0199] Deposit of biomaterials The lactic acid bacteria according to the present invention include in particular microorganisms or analogues, fragments, derivatives, ferments, lysates, mutants or combinations thereof selected from the group comprising: -Microorganisms deposited at the German Collection for Microorganisms and Cell Cultures on May 5, 2022: Lactiplantibacillus plantarum LB681R (DSM 34250) and Lacticaseibacillus paracasei subsp. paracasei LB555R (DSM 34249); - Microorganisms deposited at the German Collection for Microorganisms and Cell Cultures on December 14, 2020: Lactobacillus crispatus LB714R (DSM 33732), Pediococcus pentosaceus LB606R (DSM 33730), and / or Lactiplantibacillus plantarum LB679R (DSM 33731); - Microorganisms deposited on November 25, 2021: Lactobacillus crispatus LB919R (DSM 34097), Lactobacillus crispatus LB912R (DSM 34095), Lactobacillus gasseri LB905R (DSM 34094), and / or Lactobacillus jensenii LB918R (DSM 34096); - the microorganisms deposited at the German Collection for Microorganisms and Cell Cultures on April 10, 2019: Lactobacillus plantarum LB356R (DSM 33094), Leuconostoc mesenteriodes LB349R (DSM 33093), Lacticaseibacillus paracasei LB316R (DSM 33091) and / or Lactiplantibacillus plantarum LB312R (DSM 33098); - the microorganisms deposited at the German Collection for Microorganisms and Cell Cultures on December 13, 2018: Lactobacillus plantarum LB244R (DSM 32996), Enterococcus faecium LB276R (DSM 32997), Levilactobacillus brevis LB152G (DSM 32995), and / or Lacticaseibacillus paracasei LB28R (DSM 32994), and / or - Microorganisms deposited at the German Collection for Microorganisms and Cell Cultures on August 28, 2018: Lactobacillus plantarum LB116R (DSM 32908), Lacticaseibacillus paracasei LB113R (DSM 32907) and / or Weissella viridescens LB10G (DSM 32906).

[0200] All patent and non-patent literature cited in this application is hereby incorporated by reference in its entirety.

[0201] The invention is described in further detail in the following non-limiting examples. EXAMPLES

[0202] Example 1: Malassezia furfur with CCUG number 59937 was delivered by the "Culture Collection University Gothenburg". The strain was isolated from a 15-year-old girl suffering from human tinea versicolor. M. furfur 59937 was inoculated into potato dextrose broth (Sigma) and incubated for 5 days at 30°C. After incubation, the culture was streaked onto potato dextrose agar (Sigma) plates with a cotton swab to generate a lawn. The streaked agar plates were spotted with 20 μL of 48-h cultures of Lactiplantibacillus plantarum LB244R® (DSM 32996), Lactiplantibacillus plantarum LB356R® (DSM 33094) and Pediococcus pentosaceus LB606R® (DSM 33730). The plates were incubated for 5 days at 30° C. After incubation, the plates were visually inspected: a zone of inhibition of +1 cm in the M. furfur lawn could be observed around all spots of lactic acid bacteria.

[0203] Example 2. Various formulations Anti-dandruff shampoo composition:

[0204] Shampoo Formulation A11 component: Water 65% (w / w) After antibiotic administration (Lactobio Lactiplantibacillus LB356R® fermentation lysate) containing 15% (w / w)-95 to 98% (w / w) moisture (10 7 ~10 10 (equivalent to cell concentration in cells / ml) Lauroyl / myristoyl methyl glucamide 7% (w / w) Decyl glucoside 2% (w / w) Betaine 2% (w / w) Sodium cocoyl isethionate 1% (w / w) Glycerin 1% (w / w) Cocamide mipa 1% (w / w) Hydrogenated coconut acid 1% (w / w) Sorbic acid 1% (w / w) Sodium isethionate 1% (w / w) Sodium phytate 1% (w / w) Ethanol 1% (w / w) Sodium benzoate 0.5% (w / w) Potassium sorbate 0.5% (w / w) Adjust pH to 4.5

[0205] All ingredients except the probiotic microorganisms are heated until melted, cooled with stirring, and the probiotic microorganisms are added as a postbiotic solution when the shampoo has cooled to 20°C.

[0206] Shampoo formulation A12: component: Water 39% (w / w) Postbiotics (Lactiplantibacillus plantarum LB356R (registered trademark) fermentation lysate) 14% (w / w) - containing 95 to 98% (w / w) moisture (10 7 ~10 10 (equivalent to cell concentration in cells / ml) Sodium Laureth Sulfate 13% (w / w) Disodium Cocoamphodiacetate 8% (w / w) PEG-200 Hydrogenated Glyceryl Palmitate 5% (w / w) Polysorbate 20 5% (w / w) Hexylene glycol 2% (w / w) Disodium ricinoleamide MEA 2% (w / w) Sulfosuccinate 2% (w / w) Sodium benzoate 1% (w / w) Polysorbate 21 1% (w / w) Sodium methylparaben 1% (w / w) Polyquaternium-10 1% (w / w) PEG-7 Glyceryl Cocoate, Menthol 1% (w / w) Ethylparaben 1% (w / w) Propylene glycol 1% (w / w) Butylphenyl methylpropional 1% (w / w) Benzyl alcohol 1% (w / w) Sodium hydroxide 1% (w / w) Adjust pH to 3.7

[0207] All ingredients except the probiotic microorganisms are heated until melted, cooled with stirring, and the probiotic microorganisms are added as a postbiotic solution when the shampoo has cooled to 20°C.

[0208] Shampoo Formulation A13 component: Water 21% (w / w) Sodium coco sulfate 20% (w / w) Cocoglucoside 20% (w / w) Glycerin 12% (w / w) Sodium cocoyl isethionate 6% (w / w) Lauryl glucoside 5% (w / w) Stearyl citrate 4% (w / w) vitis vinifera (grape / raisin) seed oil 4% (w / w) Citric acid 3% (w / w) Lactiplantibacillus plantarum LB244R (registered trademark) 3% (w / w) (9 × 10 10 CFU / g concentration of lyophilized powder) Panthenol (vitamin B5) 0.5% (w / w) Glyceryl oleate 0.5% (w / w) Inulin 0.5% (w / w) Potassium sorbate 0.5% (w / w)

[0209] All ingredients except the probiotic microorganisms are heated until melted, cooled with stirring, the pH adjusted to 5.0 and the probiotic microorganisms added when the shampoo has cooled to 20°C.

[0210] Shampoo Formulation A14 component: Water 40% (w / w) Sodium C14-16 olefin sulfonate 18% (w / w) Cocamidopropyl betaine 8% (w / w) Sodium chloride 4% (w / w) Cocamidopropyl betaine 4% (w / w) Cocos Nucifera (Coconut) Oil 5% PPG-2 Hydroxyethyl Coco / Isostearamide 2% Acrylates Copolymer 2% Inulin 2% Lactiplantibacillus plantarum LB356R (registered trademark) 2% (w / w) (2 × 10 10 CFU / g concentration of lyophilized powder) Hydrolyzed Milk Protein 2% Egg white 2% Amodimethicone 1% Sodium cocoyl isethionate 1% Glycol distearate 1% Laureth-4 1% Polyquaternium-6 1% Polyquaternium-10 1% Trideceth-12 1% Cetrimonium chloride 0.5% Guar Hydroxypropyltrimonium Chloride 0.5% PEG-120 methyl glucose dioleate 0.5% Disodium EDTA 0.4% Diazolidinyl urea 0.1%

[0211] The lyophilized probiotic microorganisms are encapsulated in dual-chamber plastic caps containing 2 g of lyophilized material (AccuRec kit biphasic caps obtained from Bormioli Pharma, Italy).

[0212] All ingredients except the probiotic microorganisms are heated until melted, the pH is measured to 4.8, cooled with stirring, the composition is filled into 100 ml bottles, and the cap containing the probiotic microorganisms is placed in a separate compartment and closed. Before use, the microorganisms are released from the cap into the bottle and shaken thoroughly.

[0213] Dry Shampoo Loose Powder, Leave-In Formula B11 Zea Mays starch 46% (w / w) Aluminum starch octenyl succinate 38% (w / w) Kaolin 10% (w / w) Cyclodextrin 5% (w / w) Lactiplantibacillus plantarum LB356R (registered trademark) 1% (w / w) (2 × 10 10 CFU / g concentration of lyophilized powder)

[0214] The lyophilized viable probiotic microorganisms are mixed with the cyclodextrin and then mixed with the remaining ingredients at room temperature.

[0215] The anti-dandruff composition is sprayed or dusted onto the scalp as a leave-on composition.

[0216] Dry Shampoo Loose Powder, Leave-In Formula B12 Talc 97% (w / w) Lactiplantibacillus plantarum LB356R (registered trademark) 2% (w / w) (2 × 10 10 CFU / g concentration of lyophilized powder) Inulin 1% (w / w)

[0217] Lyophilized viable probiotic microorganisms are gently blended with talc at room temperature.

[0218] The anti-dandruff composition is sprayed or dusted onto the scalp as a leave-on composition.

[0219] Dry Shampoo Loose Powder, Leave-In Formula B13 Cornstarch 90% (w / w) Talc 9% (w / w) Pediococcus pentosaceus LB606R (registered trademark) 1% (w / w) (9 × 10 9 CFU / g concentration of lyophilized powder)

[0220] The lyophilized live probiotic microorganisms are gently blended with the cornstarch and talc at room temperature.

[0221] The anti-dandruff composition is sprayed or dusted onto the scalp as a leave-on composition.

[0222] Dry Shampoo Loose Powder, Leave-In Formula B14 Potato starch 40% (w / w) Cornstarch 37% (w / w) Kaolin 10% 8w / w) Talc 9% (w / w) Cyclodextrin 4% (w / w) Pediococcus pentosaceus LB606R (registered trademark) 1% (w / w) (9 × 10 9 CFU / g concentration of lyophilized powder)

[0223] The lyophilized live probiotic microorganisms are gently blended with the other ingredients at room temperature.

[0224] The anti-dandruff composition is sprayed or dusted onto the scalp as a leave-on composition.

[0225] Hair Lins Sleeve Ingredient C11 Water 70% (w / w) Apple cider vinegar 10% (w / w) Cetrimonium chloride 5% (w / w) Glycerin 3% (w / w) Hydrolyzed vegetable protein 1% (w / w) PG-propyl silanetriol 1% (w / w) Argania Spinosa Kernel Oil 1% (w / w) Aloe Barbadensis leaf juice 1% (w / w) Macadamia Ternifolia seed oil 1% (w / w) Quaternium-96 1% (w / w) Polyquaternium-55 1% (w / w) Dipropylene glycol 1% (w / w) Propylene glycol 1% (w / w) Diazolidinyl urea 1% (w / w) Iodopropynyl butylcarbamate 1% (w / w) Pediococcus pentosaceus LB606R (registered trademark) 1% (w / w) (9 × 10 9 CFU / g concentration of lyophilized powder)

[0226] The lyophilized probiotic microorganisms are encapsulated in dual-chamber plastic caps containing 2 g of lyophilized material (AccuRec kit biphasic caps obtained from Bormioli Pharma, Italy).

[0227] All ingredients except the probiotic microorganisms are heated until melted, the pH is measured to 4.5, cooled with stirring, the composition is filled into 100 ml bottles, and the cap containing the probiotic microorganisms is placed in a separate compartment and closed. Before use, the microorganisms are released from the cap into the bottle and shaken thoroughly.

[0228] Hair Lins Sleeve Ingredient C12 Water 70% (w / w) Apple cider vinegar 10% (w / w) Glycerin (3% w / w) Rapeseedamidopropyl Ethyldimonium Ethosulfate 1% (w / w) Polyacrylamidopropyltrimonium Chloride 1% (w / w) Hydrolyzed vegetable protein PG-propylsilanetriol 1% (w / w) Argania Spinosa Kernel Oil 1% (w / w) Aloe Barbadensis leaf juice 1% (w / w) Macadamia Ternifolia seed oil 1% (w / w) Quaternium-96 1% (w / w) Polyquaternium-55 1% (w / w) Dipropylene glycol 1% (w / w) Propanediol 1% (w / w) Propylene glycol 1% (w / w) Diazolidinyl urea 1% (w / w) Tetrasodium Glutamate Diacetate 1% (w / w) Iodopropynyl butylcarbamate 1% (w / w) Pediococcus pentosus LB606R (registered trademark) 2% (w / w) (9 × 10 9 CFU / g concentration of lyophilized powder) Lactiplantibacillus plantarum LB356R (registered trademark) 1% (w / w) (2 × 10 10 CFU / g concentration of lyophilized powder)

[0229] The lyophilized probiotic microorganisms are encapsulated in dual-chamber plastic caps containing 2 g of lyophilized material (AccuRec kit biphasic caps obtained from Bormioli Pharma, Italy).

[0230] All ingredients except the probiotic microorganisms are heated until melted, the solution as a homogeneous solution (pH is measured at 4.4) is cooled while stirring, the composition is filled into 100 ml bottles, and the cap containing the probiotic microorganisms is placed in a separate compartment and closed. Before use, the microorganisms are released from the cap into the bottle and shaken thoroughly.

[0231] Hair Lins Sleeve Ingredient C13 Water 70% (w / w) Lactiplantibacillus plantarum LB356R® fermentation lysate (15% w / w) - containing 95-98% (w / w) moisture (10 7 ~10 10 (equivalent to cell concentration in cells / ml) Glycerin (3% w / w) Rapeseed amidopropyl ethyldimonium ethosulfate 1% (w / w) Polyacrylamidopropyltrimonium Chloride 1% (w / w) Argania Spinosa Kernel Oil 1% (w / w) Aloe Barbadensis leaf juice 1% (w / w) Macadamia Ternifolia seed oil 1% (w / w) Quaternium-96 1% (w / w) Polyquaternium-55 1% (w / w) Dipropylene glycol 1% (w / w) Propanediol 1% (w / w) Propylene glycol 1% (w / w) Diazolidinyl urea 1% (w / w) Tetrasodium Glutamate Diacetate 1% (w / w)

[0232] Gentle heating was applied until all ingredients were solubilized. After the composition was cooled to room temperature, L. plantarum LB356R® fermentation lysate was added. The pH was measured to be 4.4.

[0233] Hair Lins Sleeve Ingredient C14 Helianthus annuus seed oil Ricinus communis seed oil Pediococcus pentosaceus LB606R 1%(w / w)(9×10 9 CFU / g concentration of lyophilized powder) Lactiplantibacillus plantarum LB356R (registered trademark) 2% (w / w) (2 × 10 10 CFU / g concentration of lyophilized powder) Tocopherol (Vit E) Hair Lins Sleeve Ingredient C15 Helianthus annuus seed oil 75%(w / w) Ricinus communis seed oil 22%(w / w) Lactiplantibacillus plantarum LB356R (registered trademark) 2% (w / w) (2 × 10 10 CFU / g concentration of lyophilized powder) Tocopherol (Vit E) (1% w / w)

[0234] Formulations C13 and C14 were mixed at room temperature without heating the components.

[0235] The powder composition is useful not only as a dry shampoo, but also for scalp treatment, skin treatment, and diaper rash.

[0236] Topical leave-on formulation C16 Helianthus annuus seed oil 55%(w / w) Ricinus communis seed oil 42%(w / w) Lactiplantibacillus plantarum LB356R (registered trademark) 2% (w / w) (2 × 10 10 CFU / g concentration of lyophilized powder) Tocopherol (Vit E) (1% w / w)

[0237] Mix all ingredients at room temperature.

[0238] Topical leave-on formulation C17 Water 83.8% (w / w) Pediococcus pentosaceus LB606R® fermentation lysate (15% w / w) - containing 95-98% (w / w) moisture (10 7 ~10 10 (equivalent to cell concentration in cells / ml) Betaine 1% (w / w) Carbomer 0.2% (w / w)

[0239] The water, betaine and carbomer are mixed until a clear solution is obtained, the pH is adjusted to pH 4.7 and the fermentation lysate is added.

[0240] Example 3 Metabolomics was performed on three different lactic acid bacteria: Lactiplantibacillus plantarum LB356R (DSM 33094), Lactiplantibacillus plantarum LB244R (DSM 32996) and Pediococcus pentosaceus LB606R (DSM 33730).

[0241] Microorganisms were grown in MRS medium at 30° C. for 24 h. Supernatants were analyzed by semi-polar metabolite method. Sample analysis was performed by MS-Omics (Vedbaek, Denmark) as follows.

[0242] Samples were diluted 10-fold with 10 mM ammonium formate containing 0.1% formic acid.

[0243] LC-MS method The analysis was performed using a UPLC system (Vanquish, Thermo Fisher Scientific) coupled to a high-resolution quadrupole-orbitrap mass spectrometer (Q Exactive™ HF Hybrid Quadrupole-Orbitrap, Thermo Fisher Scientific). An electrospray ionization interface was used as the ionization source. The analysis was performed in negative and positive ionization mode. QC samples were analyzed in MS / MS mode for compound identification. UPLC was performed using a slightly modified version of the protocol described by Catalin et al. (UPLC / MS Monitoring of Water-Soluble Vitamin B in Cell Culture Media in Minutes, Water Application note 2011,720004042en).

[0244] Data Processing Data were processed using Compound Discoverer 3.1 (ThermoFisher Scientific) and TraceFinder 4.1 (ThermoFisher Scientific).

[0245] compound extraction Since a compound often gives rise to signals in more than one mass trace (e.g., due to naturally occurring C13 isotopes, adducts, and / or fragments), a compound is almost always represented by more than one feature with the same retention time but different mass. Compound extraction performed by Compound Discoverer consists of four steps: 1) First, extract features from the raw data. 2) Feature detection is performed, followed by grouping of features that belong to the same compound. 3) This additional information (e.g., isotopic pattern) is then used along with the accurate mass to determine the molecular formula. 4) All the information collected about each compound is then used in the following identification step.

[0246] The analysis was performed using a Thermo Scientific Vanquish LC coupled to a Thermo Q Exactive HF MS. An electrospray ionization interface was used as the ionization source. The analysis was performed in negative and positive ionization modes. UPLC was performed using a slightly modified version of the protocol described by Catalin et al. (UPLC / MS Monitoring of Water-Soluble B Vitamins in Cell Culture Media in Minutes, Water Application note 2011,720004042en). Peak areas were extracted using Compound Discoverer 3.1 (Thermo Scientific). Compound identification was performed at four levels: Level 1: identification by retention time (compared to in-house authentic standards), accurate mass (tolerated deviation 3 ppm), and MS / MS spectrum; Level 2a: identification by retention time (compared to in-house authentic standards), accurate mass (tolerated deviation 3 ppm). Level 2b: identification by exact mass (allowed deviation of 3 ppm) and MS / MS spectrum, Level 3: identification by exact mass only (allowed deviation of 3 ppm).

[0247] A total of 1606 compounds were detected in the samples, of which 271 were annotated at level 3, 103 at level 2b, 113 at level 2a, and 60 at level 1.

[0248] Lactic acid, acetic acid, succinic acid, azelaic acid, salicylic acid, indole-3-lactic acid, indole-3-acetic acid, 2-hydroxybutyric acid, 2-hydroxyisocaproic acid and N-acetylaspartic acid were all annotated at level 1 with significant abundance for the strains.

[0249] Organic acids were at concentrations above 3% (w / w) for all fermentations.

[0250] Example 4: Dandruff evaluation test Twelve people with dandruff evaluated composition C14 for two weeks.

[0251] The leave-in composition was massaged into the affected areas of the scalp once daily for 14 days. The composition was left on for at least 8 hours before any washing.

[0252] The subjects were asked to self-assess the dandruff compared to the dandruff before the treatment started. Dandruff was rated according to the following scores:

[0253]

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[0254] All test subjects observed a significant reduction in dandruff.

[0255] Example 5: Composition B12 was evaluated for the treatment of Malassezia infected skin in the outer ear of an Irish Soft Coated Wheaten Terrier (dog age 11 years). The ear was gently washed with saline and powdered composition B12 was sprinkled on the ear and gently massaged into the infected area of ​​the outer ear twice daily. A significant effect of treatment was already observed after 2 days, with a reduction in redness, moldy odor and ear skin irritation. After 7 days, treatment was reduced to once a day. After 2 weeks, the infection in the outer ear was gone.

[0256] Example 6: The effect of pH on the activity of the active substances was determined using the spot on lawn method as described in Example 1. Lactiplantibacillus plantarum LB244R® (DSM 32996), Lactiplantibacillus plantarum LB356R® (DSM 33094) and Pediococcus pentosaceus LB606R® (DSM 33730) were each grown in MRS medium at 30°C for 48 hours and the supernatant from each culture was separated by centrifugation and filtered to produce cell-free supernatants.

[0257] The supernatants were adjusted with 1M NaOH and 1M HCl to the following pH values, respectively: 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8. Phosphate buffers at each pH value were used as controls for pH effects.

[0258] Malassezia growth was measured as zone of inhibition using the spot-on-lawn method.

[0259] All three supernatants were able to inhibit the growth of Malassezia at a pH below about 6.6.

[0260] Example 7: Inhibition of M. furfur DSMZ 6170, M. restricta CBS 7877 and M. lobose CBS 7874 Inhibition was assessed using a spot-on-lawn method modified from Zhang P.et al.(2015) Inter-strain interactions between bacteria isolated from vacuum-packaged refrigerated beef.Appl Environ Microbiol 81:2753-2761.doi:10.1128 / AEM.03933-14 and Arena,MPet al.(2016) Use of Lactobacillus plantarum Strains as a Bio-Control Strategy against Food-Borne Pathogenic Microorganisms.Frontiers in Microbiology 7(APR):1-10.doi:10.3389 / fmicb.2016.00464.

[0261] The target strain Malassezia furfur DSMZ 6170 was obtained from the Leibniz Institute DSMZ. The target strains M. globosa CBS 7874 and M. restricta CBS 7877 were obtained from the Westerdijk fungal biodiversity institute CBS. The target strains were grown in modified Leeming Notmann (mLN) (ATCC medium No. 2737 Leeming&Notman agar Modified) agar and a single colony was inoculated into 10 mL of mLN broth. The target strain culture was used to create a lawn and dried. The bacterial strains isolated from Example 1 were cultured from storage in 10 mL of MRS broth. Overnight cultures of LAB were then spotted onto the plates and incubated. M. furfur was grown for approximately 10 days at 30°C, M. restricta was grown for approximately 14 days at 30°C, and M. globosa was grown for approximately 14 days at 33°C. The zone of inhibition was measured in millimeters from the edge of the LAB colony to the beginning of visible Malassezia growth (clearing zone). All plates were technically duplicated and repeated separately.

[0262] The LAB were screened against M. furfur DSMZ 6170, of which 84 showed moderate inhibition and 18 showed high inhibition. Two strains were selected from the 18 strains and subsequently tested using the spot-on-lawn method against M. restricta CBS 7877 and M. globosa CBS 7874. All four strains were able to inhibit M. restricta CBS 7877 and M. globosa CBS 7874.

[0263] [Table 1]

[0264] Example 8: Trichophyton spp. spots in agar assay

[0265] Antifungal activity against Trichophyton spp. was determined as described in Example 7.

[0266] Trichophyton rubrum CBS 189.69 a nail isolate was obtained from the Westerdijk Fungal Biodiversity Institute department of the Royal Netherlands Academy of Arts and Sciences.

[0267] Trichophyton rubrum CBS 392.58 (neotype of Epidermophyton rubrum Castell) skin (foot) isolate was obtained from the Westerdijk Fungal Biodiversity Institute department of the Royal Netherlands Academy of Arts and Sciences.

[0268] Trichophyton spp. were grown on Sabouraud maltose agar at 24°C for 2-3 weeks.

[0269] [Table 2]

[0270] Example 9: Inhibition by cell-free supernatant solution Growth of Malassezia spp. (three strains described in Example 7) with and without cell-free supernatant (CFS) of LAB from Example 2 was monitored using an oCelloScope (BioSense Solutions ApS, Denmark).

[0271] Five to ten milliliters of LAB cell culture were centrifuged (2,700 × g, 10 min) and sterile filtered using a 0.2 μm syringe filter. Samples were taken from the LAB cultures after 24 to 72 h.

[0272] Culture 1:2 dilutions were prepared from 10 mL of Malassezia spp. From each of these dilutions, 100 μL was mixed with 100 μL of CFS or its dilutions in 96-well microtiter plates using 100, 75, 50, 25, 10 and 0% CFS. The volume was adjusted using MRS broth. As a positive control for inhibition, Malassezia spp. were treated with fluconazole (64 μg / mL). All challenge assays were performed technically in triplicate and repeated separately. Plates were incubated at 37°C in an oCelloScope. Raw images were taken every 2.5 hours for up to 48 hours and growth curves were plotted in Excel and calculated as the average of triplicates.

[0273] After the experiment, the plates were visually inspected and the raw images were visually inspected. Images were analyzed using UniExplorer PC software.

[0274] The results are shown in Figures 1-3 and show that cell-free supernatants obtained from three isolates (LB555R, LB681R, and LB606R) using a composition comprising (i) Lacticaseibacillus paracasei subsp. paracasei LB555R deposited under accession number DSM 34249, (ii) Lactiplantibacillus plantarum, LB681R deposited under accession number DSM 34250, and (iii) Pediococcus pentosaceus LB606R (DSM 33730) inhibited the growth of Malassezia furfur DSM 6170 (Figure 1), M. restricta CBS 7877 (Figure 2) and M. globosa CBS 7877 (Figure 3) in comparison to a composition containing the antifungal compound fluconazole (at a concentration of 64 µg / ml) and in comparison to an untreated fungal solution. We demonstrated potent and significant inhibition of 7874 (Figure 3).

[0275] Three hit strains were identified in the screen as capable of growing lactic acid bacteria and inhibiting fungal growth of at least two pathogenic fungi, with growth inhibition significantly better than that observed for the known antifungal antibiotic fluconazole.

[0276] Example 10: Analysis of short chain fatty acid (SCFA) production Sample analysis was performed as follows: Cell-free supernatants from the four strains (LB555R; LB681R; LB606R; and LB244R) grown in MRS medium for 24 hours at 37°C were acidified using hydrochloric acid and deuterium-labeled internal standards added. Analysis was performed using a highly polar column (Zebron™ ZB-FFAP, GC Cap). The column 30 m x 0.25 mm x 0.25 μm was installed in a GC (7890B, Agilent) coupled to a quadrupole detector (5977B, Agilent). The system was controlled by a ChemStation (Agilent). The raw data were converted to netCDF format using Chemstation (Agilent), after which the data were imported and processed in Matlab R2014b (Mathworks, Inc.) using PARADISe software described by Johnsen et.al (DOI: 10.1016 / j.chroma.2017.04.052). The SCFA method is a GC-MS method that specifically targets short-chain fatty acids using highly polar columns and standards. The concentration of short-chain fatty acids (acetic acid) in the supernatant of each strain was determined.

[0277]

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[0278] Example 11: Various topical formulations for skin and nails

[0279] Loose powder, leave-on formula component: Oryza sative (rice) starch 49% (w / w) Tapioca starch 49% (w / w) Lacticaseibacillus paracasei subsp.paracasei LB555R 2%(w / w)(9×10 9 (lyophilized powder with a concentration of CFU / g)

[0280] Loose powder, leave-on formula component: Zea mays (corn) starch 49% (w / w) Tapioca starch 49% (w / w) Lactiplantibacillus plantarum LB830R (registered trademark) 2% (w / w) (8x10 9 CFU / g concentration of lyophilized powder)

[0281] Topical liquid ointment component: Water 90% (w / w) Fermentation lysate / postbiotics (Lactiplantibacillus plantarum, LB681R) 10% (w / w)

[0282] Topical Oil Formulations: component: Jojoba oil 48% (w / w) Sunflower oil 48% (w / w) Lactiplantibacillus plantarum LB681R (registered trademark) 1% (w / w) (5x10 9 CFU / g concentration of lyophilized powder) Lacticaseibacillus paracasei subsp.paracasei LB555R 1%(w / w)(9×10 9 (lyophilized powder with a concentration of CFU / g) Inulin (FOS) 1% (w / w) Tocopherol 1% (w / w)

[0283] Example 12. Well diffusion assay Overnight cultures of LAB were prepared. LAB were grown in MRS broth and fungi were grown as described in the above example for spots on lawns. Wells were made in the plate and 50 μL of LAB culture was transferred to the wells. After incubation until fungal growth was visible, the inhibition zones around the wells were examined.

[0284] [Table 3]

[0285] References U.S. Pat. No. 4,654,207 U.S. Patent No. 5,019,376 U.S. Patent No. 3,929,678 U.S. Patent No. 2,658,072 U.S. Patent No. 2,438,091 U.S. Patent No. 2,528,378 U.S. Patent No. 5,104,646 U.S. Patent No. 5,106,609 International Publication No. 2011 / 138450 French Patent No. 2908045 U.S. Patent No. 4,565,647 The CTFA Cosmetic Ingredient Handbook (2004)

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Claims

1. one or more isolated probiotic bacterial strains, two or more active substances of said one or more isolated probiotic bacterial strains, or a combination of one or more isolated probiotic bacterial strains with two or more active substances of said one or more isolated probiotic bacterial strains, an acceptable carrier; Including, A composition, wherein said one or more isolated probiotic bacterial strains and / or two or more active substances of said one or more isolated probiotic bacterial strains are capable of inhibiting fungal growth.

2. The composition of claim 1 , wherein the composition comprises nucleic acids and / or nucleotides.

3. The composition of claim 1 , wherein the composition is free of plant and / or fibrous materials.

4. 2. The composition of claim 1, wherein the composition has a pH value of less than pH 8.0, such as less than pH 7.5 (e.g. less than pH 7.0), for example less than pH 6.5 (e.g. less than pH 6.0), for example less than pH 5.5 (e.g. less than pH 5.0), for example less than pH 4.5 (e.g. less than pH 4.0), for example less than pH 3.5 (e.g. less than pH 2.0), for example less than pH 1.5 (e.g. less than pH 1.0).

5. 10. The composition of claim 1, wherein the at least two active substances are produced by the metabolism of the isolated live probiotic bacterial strain.

6. 10. The composition of claim 1, wherein the at least two active substances are produced by a single isolated strain of probiotic bacteria.

7. 10. The composition of claim 1, wherein the active agent is selected from a bacteriocin, an organic acid, a cell wall material, or a combination thereof.

8. 10. The composition of claim 1 for use in the prevention and / or treatment of fungal diseases and / or dandruff in humans or animals.

9. 9. The composition of claim 8, wherein the prevention and / or treatment of fungal diseases and / or dandruff in humans or animals is the prevention and / or treatment of conditions associated with the proliferation of yeasts of the genus Malassezia on the scalp, hands, ears, feet, nails or skin of a subject.

10. 10. A topical hair care composition comprising the composition of claim 1 in combination with a shampoo matrix having a pH of less than 6.5 comprising at least one cleansing surfactant selected from the group consisting of anionic surfactants, nonionic surfactants, amphoteric surfactants, or combinations thereof.

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