A novel cosmetic composition

Abstract

The present invention relates to a composition comprising salicylic acid and a Lactobacillus rye ferment wherein the Lactobacillus rye ferment comprises at least five bacterial strains Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus helveticus, Levilactobacillus brevis, Lactobacillus paracasei subsp. paracasei, and Limosilactobacillus pontis.

Description

[0001] A NOVEL COSMETIC COMPOSITION

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a composition, particularly an anti-blemish composition, more particularly an acne composition method of preparing the same and use of the composition on skin, particularly as cosmetic treatment against acne. In particular, the composition comprises salicylic acid.

[0004] BACKGROUND OF THE INVENTION

[0005] Acne is an inflammatory disorder of the skin, which has sebaceous (oil) glands that connect to hair follicles, which contain fine hair. When the hair, sebum, and keratinocytes stick together inside the pore, acne occurs. This prevents the keratinocytes from shedding and keeps the sebum from reaching the surface of the skin. The mixture of oil and cells allows bacteria that normally live on the skin to grow in the plugged follicles and cause inflammation (i.e. acne).

[0006] There are several anti-acne medications that exists. One commonly used effective form of anti-acne treatment is salicylic acid.

[0007] Salicylic acid has long been a cornerstone in the cosmetic treatment of acne due to its ability to penetrate the lipid layers of the skin and facilitate the exfoliation of dead cells, thereby preventing pore clogging and reducing inflammation. Its keratolytic properties make it an effective component in combating the multifactorial nature of acne. However, the quest for enhanced efficacy often leads to the association of salicylic acid with other compounds, such as benzoyl peroxide, which is known for its potent antibacterial action against acne-causing bacteria.

[0008] While the combination of salicylic acid and benzoyl peroxide can offer a multi-pronged approach to acne management, it is not without its drawbacks. Benzoyl peroxide, for instance, can be overly harsh on the skin, leading to irritation, dryness, and disruption of the skin's natural barrier. These adverse effects can be particularly problematic, as they may exacerbate the very issues that acne treatments aim to resolve, presenting a significant challenge for cosmetic formulators.

[0009] Considering these concerns, the cosmetic industry is actively seeking alternative strategies that can potentiate the effects of salicylic acid without disturbing the delicate balance of the skin's microbiome. Accordingly, there is still a need in the art for a cosmetic formulation comprising salicylic acid that is not only effective in treatment of acne but also in reducing the side effects of salicylic acid.

[0010] BRIEF DESCRIPTION OF FIGURES

[0011] Figure 1 is a graph showing reduction in non-inflammatory lesions in the presence of Formulation 4, results indicated by % change in lesion counts, vs. Baseline. (++) p value >0.05. Figure 2 is a graph showing reduction in inflammatory lesions in the presence of Formulation 4. Results are expressed in change in lesions vs. baseline. *p value <0.05, **p value <0.01 , ***p value <0.001 , # p value <0.05 vs. vehicle.

[0012] Figure 3 is a colour parameter evolution over time (Week12-T0). Results are indicated as % of change. *p value <0.05, **p value <0.01 , ***p value <0.001 , # p value <0.05 vs. salicylic acid.

[0013] DESCRIPTION OF THE INVENTION

[0014] The present invention solves the problems above by providing a means of improving acne treatment using a composition comprising salicylic acid in combination with fermentation-derived products. In particular, the composition according to any aspect of the present invention displays reduced side effects known to be present with use of salicylic acid alone.

[0015] According to a first aspect of the present invention, there is provided a composition comprising Salicylic acid and a Lactobacillus rye ferment comprising at least two bacterial strains from the family Lactobacillus sp. The Lactobacillus rye ferment, a well-known bioactive compound, produced through the fermentation process, has been shown to work synergistically with salicylic acid. By harnessing the natural processes of fermentation, the composition according to any aspect of the present invention, provides acne treatments that are not only effective but also gentler on the skin, thereby offering a more holistic approach to acne management that aligns with the evolving demands of consumers for products that support the overall health of their skin.

[0016] Further, an advantage of the composition according to any aspect of the present invention is the synergistic effect of the Lactobacillus rye ferment in combination with salicylic acid, clinically proven, with Salicylic acid as a monographed ingredient, its dosage is defined by the monograph and limited also due to its side effects on very sensitive acne skin, a synergistic ingredient as such which would boost Salicylic acid’s efficacy on acne skin, addressing acne skin conditions from different mode of actions and working mechanisms is leveraging the consumer perception for the finished formulation and effect on their skin.

[0017] In particular, the composition according to any aspect of the present invention comprises at least two active ingredients- salicylic acid and Lactobacillus rye ferment. Both components are equally considered as active ingredients and work synergistically, enhancing the effectiveness of each component against acne.

[0018] Salicylic acid is an important over the counter monograph active ingredient for acne skin, and it is proven to be one of the more effective ingredients used in compositions for treatment against acne skin conditions. In particular, salicylic acid is a molecule known to have bactericidal properties against pathogenic strains of C. acnes. Accordingly, the presence of salicylic acid in the composition according to any aspect of the present invention, ensures that the composition according to any aspect of the present invention is not only effective in treatment of acne but will also be already established for being an effective treatment against acne.

[0019] In particular, the presence of Lactobacillus rye ferment in the composition according to any aspect of the present invention not only enhances the effectiveness of salicylic acid but also reduces the side effects of salicylic acid that are present when salicylic acid is used individually against acne, for example skin irritation. On top of the side effects such as skin irritation that accompanies the use of salicylic acid, the achievable efficacy of salicylic acid is also known to vary with the type of acne skin condition and it has to be limited in its dosage according to monograph. The presence of the Lactobacillus rye ferment in the composition according to any aspect of the present invention, keeps all these negative aspects of salicylic acid use in check, making the use of the composition according to any aspect of the present invention especially attractive for skin consumers, particularly due to their skin sensitivity. The composition according to any aspect of the present invention which is based on multiple strains of different lactobacillus species, and salicylic acid has also been clinical proven to be effective in skin care. The presence of the Lactobacillus rye ferment in the composition according to any aspect of the present invention also avoids the need of any other means of reducing the negative effects of salicylic acid. For example, there is no need for encapsulation or the like for reducing the side effects of salicylic acid because of the presence of Lactobacillus rye ferment in the composition according to any aspect of the present invention. Further, the Lactobacillus rye ferment has other benefits such as it enhances the skin's natural defence mechanisms, resurfaces the skin through enhanced cell renewal and promotes the growth of a diversity of a beneficial skin bacteria

[0020] The Lactobacillus rye ferment in the composition according to any aspect of the present invention is a paraprobiotic (Lactobacillus / Rye flour ferment), offering probiotic benefits, which is a multi-strain fermentation-based lactobacillus ferment, for which organic rye flour is used as feedstock. In particular, the bacteria present in the Lactobacillus rye ferment is from the Lactobacillus species. More in particular, the bacteria is selected from the group consisting of at least Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus helveticus, Levilactobacillus brevis, Lactobacillus paracasei subsp. paracasei and Limosilactobacillus pontis. Even more in particular, there may be at least two strains of bacteria from the Lactobacillus species. In particular, at least three, four or five strains of bacteria from the Lactobacillus species is present in the Lactobacillus rye ferment according to any aspect of the present invention. In one example, the Lactobacillus rye ferment comprises at least five strains of Lactobacillus species - Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus helveticus, Levilactobacillus brevis, Lactobacillus paracasei subsp. paracasei and Limosilactobacillus pontis.

[0021] Metabolic profiling of the Lactobacillus rye ferment in the composition according to any aspect of the present invention revealed a diverse array of over 600 metabolites, highlighting the product's rich content in amino acids, lipids, and vitamins, which may contribute lead to a beneficial effect on skin hyperpigmentation, redness reduction, and sebum production regulation. Notably, the upregulation of specific lipids, such as lysophospholipids and galactolipids, suggests potential roles in skin barrier function, moisturization, and anti-inflammatory responses. Additionally, the increased levels of fatty acids and endocannabinoids in the Lactobacillus rye ferment indicate a multifaceted approach to skin health, promoting wound healing and reducing inflammation. Furthermore, significant alterations in amino acid metabolism found in Lactobacillus rye ferment has implications for skin hydration and elasticity, as well as the potential for anti-aging effects through the modulation of nucleotide metabolism. The presence of key cofactors and vitamins, particularly nicotinamide in the Lactobacillus rye ferment, reinforces the product's role in improving skin tone and reducing hyperpigmentation. Lactobacillus rye ferment in the composition according to any aspect of the present invention is therefore a promising formulation for addressing acne-related skin concerns.

[0022] The Lactobacillus rye ferment in the composition according to any aspect of the present invention may further comprise at least one yeast strain. In particular, the yeast strain is Saccharomyces cerevisiae.

[0023] In particular, the Lactobacillus rye ferment is obtainable by fermenting the Lactobacillus strains in the presence of rye meal. More in particular, fermentation takes please under conditions as specified in DE 29923627 and in WO 03 / 053376. A preferred compound for use in the present invention is Woresana® serum, a water-based, slightly viscous, transparent solution. Woresana® is a registered trademark of Woresan GmbH.

[0024] The composition according to any aspect of the present invention comprises a concentration of at least about 0.5 wt.-% -15 wt. -% Lactobacillus rye ferment of the total composition. More in particular, the weight concentration of Lactobacillus rye ferment is 0.5-14, 0.5-13, 0.5-12, 0.5-11 , 0.5-10, 0.5-9, 0.5-8, 0.5-7, 0.5-6, 0.5-5, 1-15, 1-14, 1-13, 1-12, 1-11 , 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 2-15, 2-14, 2-13, 2-12, 2-11 , 2-10, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 3-15, 3-14, 3-13, 3-12, 3-11 , 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 4-15, 4-14, 4- 13, 4-12, 4-11 , 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-15, 5-14, 5-13, 5-12, 5-11 , 5-10, 5-9, 5-8, 5-7, or 5-6 wt. -% of the total composition according to any aspect of the present invention. Even more in particular, the concentration of Lactobacillus rye ferment is 1 wt.-% -10 wt.-% or 1-5 wt.-% of the total composition. In one example, the concentration of Lactobacillus rye ferment is about 1 , 2, 3, 4, 5, 6, 7, 8, 9 or 10 wt. -% of the total composition according to any aspect of the present invention.

[0025] The composition according to any aspect of the present invention comprises a maximum concentration of salicylic acid of about 2 wt.-% of the total composition. In particular, the concentration of salicylic acid may be about 2, 1 .9, 1 .8, 1 .7, 1 .6, 1 .5, 1 .4, 1 .3, 1 .2, 1 .1 , 1 .0, 0.9, 0.8, 0.7, 0.6 or 0.5 wt.-% of the total composition. The composition according to any aspect of the present invention comprises salicylic acid in a concentration of 0.1-2 wt.-% of the total composition. The concentration of salicylic acid may be 0.1-1 .5, 0.1-1 , 0.2- 2, 0.2-1 .5, 0.2-1 , 0.3- 2, 0.3-1 .5, 0.3-1 , 0.4- 2, 0.4-1 .5, 0.4-1 , 0.5- 2, 0.5-1 .5, 0.5-1 , 1-2 wt.-% of the total composition.

[0026] The weight of the ingredients in the composition according to any aspect of the present invention may be measured using any method known in the art. In particular, the concentration of the components of the composition according to any aspect of the present invention may be measured using any method known in the art, for example LC-MS / MS. In one example, the composition according to any aspect of the present invention comprises no preservative at all. This makes the composition especially attractive due to the flexibility it provides for formulators for finished product design, as they can add any preservative they want for the finished product, and the fact that it is free of preservation related regulatory concerns.

[0027] In particular, any suitable preservative may be added to the composition according to any aspect of the present invention based on the customers’ preference for their formulation in view of special requirements based on their products due to its physio-chemical properties, instabilities with certain raw materials and / or incompatibilities with the packaging used for the formulation. In this example, the composition according to any aspect of the present invention may undergo a short pasteurization to prevent the composition from going bad. In particular, the composition according to any aspect of the present invention may undergo a short pasteurization at 80°C for at least 10 minutes.

[0028] The composition according to any aspect of the present invention further comprises at least one preservative. As used herein, the term “preservative” refers to a substance which inhibits the development of microorganisms in the composition. Examples of preservatives suitable for the composition according to any aspect of the present invention are phenoxyethanol; a mixture of caprylyl glycol, glyceryl caprylate, glycerin, and phenylpropanol; a mixture of benzyl alcohol, glyceryl caprylate, and glyceryl undecylenate; a mixture of 2,2-hexanediol and caprylyl glycol; a mixture of phenethyl alcohol, and ethylhexylglycerin; a mixture of pentylene glycol, caprylyl glycol, and ethylhexylglycerin, 1 ,2- pentanediol, 1 ,2-hexanediol, 1 ,2-heptanediol, 1 ,2-octanediol, sodium benzoate, potassium sorbate and mixtures thereof. In particular, the composition is so versatile that any preservative may be effectively used without compromising the effectiveness of the active ingredients. In one example, the preservative used in the composition according to any aspect of the present invention may be Sodium benzoate in combination with Potassium Sorbate. In another example, the preservative used in the composition according to any aspect of the present invention may be Pentylene glycol.

[0029] The composition according to any aspect of the present invention is a cosmetical formulation. In one example, the composition may further comprise Glyceryl Stearate Citrate, Cetearyl Alcohol, Xanthan Gum, Octyldodecanol, Capric Triglyceride, Phenoxyethanol, water and the like.

[0030] In particular, glyceryl stearate citrate is an emulsifier derived from glycerin and stearic acid, which helps to form stable oil-in-water emulsions. It is present in the composition according to any aspect of the present invention in an amount ranging from about 1 % to about 5% by weight of the total composition.

[0031] Cetearyl alcohol is a fatty alcohol that acts as a co-emulsifier, thickener, and stabilizer. It is present in the composition according to any aspect of the present invention in an amount ranging from about 0.5% to about 3% by weight of the total composition.

[0032] Capric triglyceride is derived from coconut oil and glycerin, this ingredient acts as an emollient and provides a lightweight, non-greasy skin feel. It is present in the composition according to any aspect of the present invention in an amount ranging from about 2% to about 10% by weight of the total composition.

[0033] Octyldodecanol is a fatty alcohol that serves as an emollient, providing a smooth and soft skin feel. It is present in the composition according to any aspect of the present invention in an amount ranging from about 1 % to about 5% by weight of the total composition.

[0034] Water serves as the solvent for the composition according to any aspect of the present invention. Water is present in an amount ranging from about 50% to about 90% by weight of the total composition.

[0035] Xanthan Gum is a polysaccharide that acts as a thickening agent and stabilizer to enhance the texture and stability of the composition. It is present in the composition according to any aspect of the present invention in an amount ranging from about 0.1 % to about 1 % by weight of the total composition.

[0036] Phenoxyethanol is a preservative that helps to prevent microbial growth and extend the shelf life of the composition. It is present in the composition according to any aspect of the present invention in an amount ranging from about 0.5% to about 1 % by weight of the total composition.

[0037] In particular, the cosmetic formulation may further comprise at least one cosmetic agent and / or dermatologically acceptable carrier that may act as a dilutant, dispersant or carrier for the active ingredients. The carrier may comprise materials commonly employed in skin care products such as water, liquid or solid emollients, surfactants silicone oils, emulsifiers, waxes, consistency enhancers, moisturizing agents, solvents, antioxidants, emollients, humectants, thickeners / viscosity modifiers, powders, propellants and a mixture thereof.

[0038] As used herein, the term “surfactant” is a substance which decreases the surface tension of a composition with respect to the same composition in the absence of said component and furthermore facilitates the uniform distribution of the composition when it is used. Examples of surfactants suitable for the capsules according to any aspect of the present invention are lauryl isoquinolinium bromide and isopropyl alcohol, polysorbate 20, steareth-2 (polyethylene glycol ether (2 units) and stearyl alcohol), oleth-2 (polyethylene glycol ether (2 units) and oleyl alcohol), PEG-8 caprylic / capric glycerides (ethoxylated with 8 units of polyethylene glycol), sodium cocoamphoacetate, coconut oil esters - polyglycerol 6, almond oil esters- PEG-8, ammonium cocosulfate and avocado oil esters PEG-11 , and mixtures thereof.

[0039] As used herein, the term “moisturizing agent” refers to a substance which increases the water content of the skin or hair and helps to keep it soft. Examples of moisturizing agents suitable for the capsules according to any aspect of the present invention are vitis vinifera seed oil, ceramide, glucosylceramide, grape oil esters - PEG-8, glyceryl esters - cocoa butter, shea butter cetyl esters, shea butter glyceride, lauryl cocoate, and mixtures thereof. As used herein, the term “antioxidant” refers to a substance which inhibits or reduces reactions promoted by oxygen, thereby preventing oxidation and rancidity. Examples of antioxidants suitable for the capsules according to any aspect of the present invention are tocopherol, sodium tocopheryl phosphate, 3-glyceryl ascorbate, acetylcysteine, aloe vera plant extract, ascorbic acid, ascorbyl dipalmitate, ascorbic acid polypeptide, acetyl trihexylcitrate, ascorbyl linoleate, 2-acetylhydroquinone, apo-lactoferrin, ascorbyl glucoside, ascorbyl lactoside, and mixtures thereof.

[0040] As used herein, the term “emollient” refers to a substance which softens the skin. Examples of emollients suitable for the caosules according to any aspect of the present invention are apo-lactoferrin, acacia dealbata flower wax, acetylarginine, acetylproline, acetylhydroxyproline, acetylated glycol stearate, algae extract, almond oil esters and propylene glycol, aminopropyltocopheryl phosphate, 1 ,2,6-hexanetriol, and mixtures thereof.

[0041] As used herein, the term “humectant” refers to a substance which retains humidity. Examples of humectants suitable for the capsules according to any aspect of the present invention are 3-glyceryl ascorbate, acetylcyclodextrin, propanediol, algae extract, 2,3-butanediol, 3-ethylhexylglyceryl ascorbate, 3-laurylglycery I ascorbate, and capryl 3-glyceryl ascorbate.

[0042] As used herein, the term “viscosity modifier” refers to a substance which increases the viscosity of a composition, particularly an aqueous composition. Examples of viscosity modifiers suitable for the capsules according to any aspect of the present invention are carbomer, sodium carbomer, dextran sulfate sodium, carboxymethyl chitosan, propanediol, carboxymethyl dextran, steareth-30, steareth-40, steareth-50, sodium poly polynaphthalene sulfonate, croscarmelose, sodium glycereth-polyphosphate, and mixtures thereof.

[0043] In particular, the carrier may form from 80% to 99.999%, more particularly from 90% to 99.99% and most particularly from 99.98 to 98% by weight of the composition, and can, in the absence of other cosmetic adjuncts, form the balance of the composition.

[0044] The cosmetical formulation may be an aqueous solution, water-in-oil (w / o) emulsion, oil-in-water (o / w) emulsion, a dispersion of lipids, an aqueous, water-alcohol, oil or oil-alcohol gel, a solid stick, a wet-wipe or an aerosol.

[0045] If the carrier itself is an (w / o) or (o / w) emulsion, it preferably contains 5 to 50 % of an oil phase and 47 to 94.95 % water, with respect to the weight of the whole formulation or composition according to any aspect of the present invention.

[0046] Typical guideline formulations are publicly available and can be obtained by the manufacturers of either the raw materials or the active ingredients, (e.g.: Kosmetik-Jahrbuch, B. Ziolkowsky, Verlag fur Chemische Industrie, Germany). The cosmetic formulations or compositions according to any aspect of the present invention show an anti-acne effect.

[0047] In one example, the composition according to any aspect of the present invention may further include a beta-hydroxy acid known for its exfoliating properties, which can help to unclog pores and reduce the appearance of acne. Beta-hydroxy acid may be present in the composition in an amount ranging from about 0.5% to about 2% by weight of the total composition. According to another aspect of the present invention, there is provided a method of preparing a composition comprising salicylic acid and a Lactobacillus rye ferment, the method comprising a step of: mixing salicylic acid and a Lactobacillus rye ferment comprising at least two bacterial strains from the family Lactobacillus sp. that is obtainable by fermenting the Lactobacillus strains in the presence of rye meal.

[0048] In particular, a preservative is also added to the composition according to any aspect of the present invention. Examples of preservatives suitable for the composition according to any aspect of the present invention are phenoxyethanol; a mixture of caprylyl glycol, glyceryl caprylate, glycerin, and phenylpropanol; a mixture of benzyl alcohol, glyceryl caprylate, and glyceryl undecylenate; a mixture of

[0049] 2.2-hexanediol and caprylyl glycol; a mixture of phenethyl alcohol, and ethylhexylglycerin; a mixture of pentylene glycol, caprylyl glycol, and ethylhexylglycerin, 1 ,2-pentanediol, 1 ,2-hexanediol, 1 ,2-heptanediol,

[0050] 1 .2-octanediol, sodium benzoate, potassium sorbate and mixtures thereof.

[0051] According to a further aspect of the present invention, there is provided a use of the composition according to any aspect of the present invention in skin care, particularly, specialized cosmetics related to dermatology or derma-cosmetics, blemished skin, particularly for over the counter products.

[0052] According to a further aspect of the present invention, there is provided a use of the composition according to any aspect of the present invention in scalp care, particularly, for treatment of dandruff.

[0053] According to another aspect of the present invention, there is provided a use of a composition according to any aspect of the present invention for cosmetic treatment of blemished skin, preferably acne.

[0054] According to a further aspect of the present invention, there is provided a composition comprising a compound according to any aspect of the present invention and at least one cosmetically acceptable excipient and / or adjuvant.

[0055] The term excipients or adjuvants also relate to carriers. Such pharmaceutical excipients, adjuvants or carriers can be liquids, such as water, oils or surfactants, including those of petroleum, animal, plant or synthetic origin, such as for example and in a non-limiting sense peanut oil, soybean oil, mineral oil, sesame oil, castor oils, polysorbates, sorbitan esters, ether sulfates, sulfates, betaines, glucosides, maltosides, fatty alcohols, nonoxinols, poloxamers, polyoxyethylenes, polyethylene glycols, dextrose, glycerol and the like. “Remington's Pharmaceutical Sciences” by E. W. Martin describes diluents, adjuvants or excipients as suitable carriers.

[0056] The skin care formulation can be an aqueous solution, water-in-oil (w / o) emulsion, oil-in-water (o / w) emulsion, a dispersion of lipids, an aqueous, water-alcohol, oil or oil-alcohol gel, a solid stick, a wet-wipe or an aerosol. In particular, the composition according to any aspect of the present invention is in an oil- in-water (O / W) cosmetic matrix. In particular, the composition according to any aspect of the present invention has a low amount of fatty raw materials. The composition according to any aspect of the present invention may comprise a carrier. In particular, the carrier may form from 80% to 99.999%, more preferably from 90% to 99.99% and most preferably from 99.98 to 98% by weight of the composition, and can, in the absence of other cosmetic adjuncts, form the balance of the composition. If the carrier itself is an (w / o) or (o / w) emulsion, it preferably contains 5 to 50 % of an oil phase and 47 to 94.95 % water, with respect to the weight of the whole formulation.

[0057] Typical guideline formulations are publicaly available and can be obtained by the manufacturers of either the raw materials or the active ingredients, (e.g.: Kosmetik-Jahrbuch, B. Ziolkowsky, Verlag fur Chemische Industrie, Germany). The cosmetic formulations of the present invention show an anti-acne effect.

[0058] In particular, the composition according to any aspect of the present invention is used topically. More in particular, the composition according to any aspect of the present invention is used for topical application on facial skin. Facial skin has a very different build-up of components compared to for instance the skin on the sole of a foot sole or hand which is covered with callus (i.e. layers of dead skin cells), having a very different, non-comparable penetration profile. Also, the skin of the face is more sensitive, is always in view and exposed to the environment. Accordingly, the composition according to any aspect of the present invention is especially suitable for use on facial skin, particularly, facial blemished skin, more particularly skin with acne.

[0059] According to a further aspect of the present invention, there is provided a non-therapeutical use of the composition according any aspect of the present invention for maintaining and / or establishing and / or restoring a healthy state of the skin microbiome. In particular, the healthy state of the skin microbiome is determined using the Shannon diversity index. More in particular, the healthy state of the skin microbiome is determined by the richness and / or diversity of microorganisms in the human skin. In one example, Grice EA, et al., Genome Res. 2008 Jul;18(7): 1043-50 provides an explanation of healthy state of skin microbiome or microbiota.

[0060] In particular, it was observed in an in vitro model that the composition according to any aspect of the present invention could modulate the skin microbiome (i.e. changes in microbiome composition and richness) and an in vivo study confirmed that the composition according to any aspect of the present invention was especially effective against acne of bacterial origin, particularly inflammatory acne lesions, and the presence of both ingredients- salicylic acid and a Lactobacillus rye ferment were more effective in treatment than used individually. Also, it was observed that the combination had a statistically significant reduction of PIE (Post Inflammatory Erythema), 27% superior improvement over just the salicylic acid alone. Further, the composition according to any aspect of the present invention is also capable of reducing lesions, improving skin evenness and has brightening effects.

[0061] According to yet another aspect of the present invention, there is provided a non-therapeutical use of the composition according any aspect of the present invention for treatment of blemished skin, preferably acne. According to another aspect of the present invention, there is provided non-therapeutical use of the composition according any aspect of the present invention for treatment of dandruff.

[0062] Unless stated otherwise, all percentages (%) given are percentages by mass.

[0063] The examples adduced hereinafter describe the present invention by way of example, without any intention that the invention, the scope of application of which is apparent from the entirety of the description and the claims, be restricted to the embodiments specified in the examples.

[0064] EXAMPLES

[0065] Example 1 :

[0066] Preparation of Formulations

[0067] Four different formulations were tested.

[0068] Formulation 1 (vehicle):

[0069] Formulation 2 (vehicle + salicylic acid): Formulation 3 (vehicle + lactobacillus rye ferment):

[0070] Formulation 4 (vehicle + lactobacillus rye ferment + salicylic acid):

[0071] Preparation Method:

[0072] The formulations were prepared by first heating the water phase and the oil phase separately. The oil phase included glyceryl stearate citrate, cetearyl alcohol, capric triglyceride, and octyldodecanol. Once both phases reached the desired temperature (usually around 70-80°C), they were combined with continuous stirring. The xanthan gum was dispersed in the water phase before combining with the oil phase to ensure a homogenous mixture. After the emulsion was formed and cooled to below 40°C, temperature-sensitive ingredients such as phenoxyethanol, salicylic acid, and lactobacillus ferment were added under gentle stirring. The final composition was then homogenized and packaged under aseptic conditions.

[0073] Example 2:

[0074] In vivo study: a safety in use and efficacy evaluation of a facial acne product on Example 1.

[0075] Details of Study

[0076] Time period: 12 weeks Test product and application instructions: Facial acne products from Example 1 , subjects will apply the randomized assigned acne product twice daily after washing to the face with defined facial cleanser.

[0077] 3 formulations tested: o Vehicle + Salicylic acid formulation o Vehicle + ferment formulation (ferment / rye ferment) o Vehicle + ferment + salicylic acid formulation o Vehicle alone

[0078] Design:

[0079] Number of participants: 80, 20 subjects per formulation

[0080] Studied population: Healthy male and female subjects 16-45 years of age of all Fitzpatrick skin types with mild to moderate acne consisting of 5-20 inflammatory lesions and no nodules / cysts.

[0081] Subjects applied the assigned study product morning and evening following washing a cleanser. The dermatologist investigator assessed the face using global acne assessment (IGA) based on the following 5 point ordinal scale: 0=clear, 1 =almost clear, 2=mild, 3=moderate, and 4=severe. In addition, the dermatologist investigator performed an inflammatory and noninflammatory lesion count. The dermatologist investigator also assessed the following skin parameters: dryness, lack of tactile smoothness, lack of visual smoothness, lack of softness, lack of luminosity, post-inflammatory hyperpigmentation (PIH), and post-inflammatory erythema (PIE). All assessments were made on a 5- point ordinal scale (0=none, 1 =minimal, 2=mild, 3=moderate, 4=severe). Finally, the dermatologist investigator assessed the tolerability in terms of peeling, dryness, redness, and swelling on a 5- point ordinal scale (0=none, 1 =minimal, 2=mild, 3=moderate, & 4=severe).

[0082] The subjects also assessed the regimen efficacy in terms of: dryness, lack of tactile smoothness, lack of visual smoothness, lack of softness, lack of luminosity, brown spots at healed acne lesions (PIH), and red spots at healed acne lesions (PIE). The subjects also assessed tolerability in terms of itching, burning, redness, and swelling. All assessments were made on a 5-point ordinal scale (0=none, 1 =minimal, 2=mild, 3=moderate, & 4=severe).

[0083] Subject Microbiome Swabbing: subjects were swabbed from a target site on the face at baseline and week 12. Skin microbiome analysis, was carried out on the samples using Shotgun metagenomics techniques.

[0084] All subjects were also photographed (front face, right face, left face) with the Canfield VISIA CR using Standard 1 lighting at baseline and week 12.

[0085] The assessment was carried out every 4 weeks (i.e. weeks 4, 8, and 12 from the start of the study).

[0086] Statistical methods: Along with descriptive statistics, investigator and subject ordinal efficacy and tolerability and IGA nonparametric data were analysed using the Wilcoxon signed rank test. Numerical acne lesion counts (inflammatory and non-inflammatory) were assessed using a Student t test.

[0087] Microbiome statistical analysis was performed by the processing laboratory. Change was considered to be significant at a p value of less than or equal to 0.05.

[0088] It was observed in an in vitro model that Formulation 4 from Example 1 , modulated the skin microbiome and the in vivo study performed confirmed that Formulation 4 was effective against acne of bacterial origin. Salicylic acid, a molecule known to have bactericidal properties against pathogenic strains of C. acnes, was used as a positive control (Formulation 2). The in vivo study showed that for noninflammatory acne, Formulation 4 had the same behaviour against these type of lesions in terms of efficacy. On the other hand, Formulation 2 was observed to be effective against inflammatory acne lesions, however, Formulation 4 was observed to be more effective due to the combinatorial effect of both the active ingredients. Also, it was observed that the combination (i.e. Formulation 4) had a statistically significant reduction of PIE (Post Inflammatory Erythema), 27% superior improvement over just the salicylic acid alone.

[0089] The results are provided in Figure 1 . At 12 weeks, Formulation 4 showed a decrease in non-inflammatory lesion count that is close to statistical significance (p=0.057 and 0.052) vs. vehicle. At all time-points, no statistically significant difference in decrease of non-inflammatory lesion count between Formulation 4. Formulation 3 demonstrated comparable efficacy to salicylic acid in reducing non-inflammatory acne lesions, highlighting its potential as a viable alternative in acne treatment regimens.

[0090] After 12 weeks, combination of vehicle, SA and ferment formulation (i.e. Formulation 4) showed a statistically significant decrease in inflammatory lesion count vs vehicle and vs ferment formulation alone. Combination of ferment formulation and Salicylic acid showed a rapid reduction (after 4 weeks) in inflammatory lesion count vs. salicylic acid alone with statistical tendency (p=0.077).These results suggest that combination of ferment formulation and Salicylic Acid shows better efficacy than ferment formulation alone. It also suggests that the combination acts much more rapidly than Salicylic acid alone in reducing the number of inflammatory acne lesions. Notably, the combination of ferment formulation and Salicylic Acid led to a remarkable 50% reduction in lesion counts compared to baseline within just 4 weeks of treatment. This rapid improvement underscores the synergistic effects of ferment formulation, as it markedly outperformed the results achieved with Salicylic Acid alone, which required a longer duration of 12 weeks to achieve similar reductions in inflammatory lesions. This enhanced performance may offer patients a more effective and time-efficient option for achieving clearer skin, ultimately improving treatment adherence and satisfaction.

[0091] Standard images captured on VISIA (Front, Left and Right view) captured at DO and D84 were analysed for changes in skin color tone and homogeneity by a third party (Newtone technologies) in a blinded manner. The skin parameters analyzed included skin lightness (L*), redness (a*), yellowness (b*), pigmentation degree (ITA°), skin whiteness (IWA°Newtone), and homogeneity (H76) after repeated applications of these products. The analysis included rigorous image quality control, color registration, and statistical evaluations to ensure data integrity. The color calibration process was crucial, as it ensured that all images were in the same color space, with a single calibration performed for all images. The results are shown in Figure 3. All four products demonstrated a statistically significant increase in skin brightness parameters (L* and ITA°, IWA° Newtone), with combination of ferment formulation and Salicylic acid demonstrating maximum improvement. Combination of ferment formulation and Salicylic acid showed a statistically significant improvement vs. Salicylic acid alone for all skin brightness parameters (L* and ITA°, IWA° Newtone). ferment formulation alone as well as combination of ferment formulation and Salicylic acid showed a statistically significant reduction in skin redness vs. baseline. Taken together, these results suggest that a combination of ferment formulation and Salicylic acid can provide a skin brightening effect as well as reduce skin redness resulting in a brighter and healthier looking skin.

[0092] In addition, a study of the microbiota of the panelists was carried out, using shotgun metagenome sequencing, and analyzed by diversity measures and LEfSe, a method for microbiome biomarker discovery and explanation. Metagenomics revealed minor changes in microbiome composition and richness, compared to the control group, as well as bacterial and fungal discriminatory taxa across treatment groups and timepoints. In particular, it was observed that Formulation 4 from Example 1 had a slightly positive effect on microbiome richness (median number of taxa, summarized by the Shannon diversity index) compared to other formulations.

[0093] Additionally, a metabolic study of Formulation 4 was carried out using ultrahigh performance liquid chromatography - Tandem mass spectrometry (UPLC-MS / MS) where more than 600 different metabolites were found and supported with the microbiome and the alignment with clinical studies, it was proven that the broad spectrum of metabolites enabled by this special multi-strain fermentation of lactobacillus, helped anti-inflammation, skin microbiome related Mode of Actions (MOAs) for such ferment, in conjunction with the MOAs for Salicylic acid on acne skin.

[0094] Example 3:

[0095] The ferment formulation used in in Examples 1 and 2 (ferment / rye ferment) is a multi-strain fermentation product, meaning that different microorganisms have been used to ferment rye flour, a comparative study was conducted to observe the metabolic differences between single-strain and multi-strain products. For this purpose, the complete consortium of microorganisms was used to ferment the rye flour, while the microorganisms were also fermented separately, including: Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus helveticus, Levilactobacillus brevis, Lactobacillus paracasei subsp. paracasei, Limosilactobacillus pontis, and Saccharomyces cerevisiae. For each of the products generated from the fermentation, three different fermentations (batches) were carried out to serve as biological replicates and control the reproducibility of the data between batches, and a metabolomic study was conducted to examine the differences in the metabolic profile of each. Additionally, three technical replicates were performed for each of the biological replicates to ensure reproducibility.

Claims

CLAIMS1 . A composition comprising salicylic acid and a Lactobacillus rye ferment, wherein the Lactobacillus rye ferment comprises at least five bacterial strains Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus helveticus, Levilactobacillus brevis, Lactobacillus paracasei subsp. paracasei, and Limosilactobacillus pontis2. The composition according to either claim 1 , wherein the Lactobacillus rye ferment is obtainable by fermenting the Lactobacillus strains in the presence of rye meal.

3. The composition according to either claim 1 or 2, wherein the Lactobacillus rye ferment is 1 wt.-% -10 wt. -% of the total composition.

4. The composition according to any one of the preceding claims, wherein the salicylic acid concentration is a maximum of 0.5-2 wt.-% of the total composition.

5. The composition according to any one of the preceding claims, wherein the composition further comprises at least one preservative.

6. The composition according to any one of the preceding claims, wherein the composition is a cosmetical formulation.

7. The composition according to any one of the preceding claims for use in cosmetic treatment of skin and / or sculp, preferably blemished skin or dandruff, more preferably skin acne.

8. A method of preparing a composition comprising Salicylic acid and a Lactobacillus rye ferment, the method comprising a step of: mixing salicylic acid and a Lactobacillus rye ferment, wherein the Lactobacillus rye ferment comprises at least five bacterial strains Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus helveticus, Levilactobacillus brevis, Lactobacillus paracasei subsp. paracasei, and Limosilactobacillus pontis that is obtainable by fermenting the Lactobacillus strains in the presence of rye meal.

9. The method according to claim 8, wherein a further preservative is added.

10. Use of the composition according to any one of the claims 1 to 7 in skin care.11 . Use of the composition according to any one of the claims 1 to 7 for cosmetic treatment of blemished skin, preferably skin acne.

12. Use of either claim 10 or 11 , wherein the composition is used topically.

13. A non-therapeutical use of the composition according any one of the claims 1 to 7 for maintaining and / or establishing and / or restoring a healthy state of the skin microbiome.

14. A non-therapeutical use of the composition according any one of the claims 1 to 7 for cosmetic treatment of blemished skin, preferably acne.

Images